WorldWideScience

Sample records for climate molecular insights

  1. Surviving historical Patagonian landscapes and climate: molecular insights from Galaxias maculatus

    Directory of Open Access Journals (Sweden)

    Carrea Cecilia

    2010-03-01

    Full Text Available Abstract Background The dynamic geological and climatic histories of temperate South America have played important roles in shaping the contemporary distributions and genetic diversity of endemic freshwater species. We use mitochondria and nuclear sequence variation to investigate the consequences of mountain barriers and Quaternary glacial cycles for patterns of genetic diversity in the diadromous fish Galaxias maculatus in Patagonia (~300 individuals from 36 locations. Results Contemporary populations of G. maculatus, east and west of the Andes in Patagonia, represent a single monophyletic lineage comprising several well supported groups. Mantel tests using control region data revealed a strong positive relationship when geographic distance was modeled according to a scenario of marine dispersal. (r = 0.69, P = 0.055. By contrast, direct distance between regions was poorly correlated with genetic distance (r = -0.05, P = 0.463. Hierarchical AMOVAs using mtDNA revealed that pooling samples according to historical (pre-LGM oceanic drainage (Pacific vs. Atlantic explained approximately four times more variance than pooling them into present-day drainage (15.6% vs. 3.7%. Further post-hoc AMOVA tests revealed additional genetic structure between populations east and west of the Chilean Coastal Cordillera (coastal vs. interior. Overall female effective population size appears to have remained relatively constant until roughly 0.5 Ma when population size rapidly increased several orders of magnitude [100× (60×-190×] to reach contemporary levels. Maximum likelihood analysis of nuclear alleles revealed a poorly supported gene tree which was paraphyletic with respect to mitochondrial-defined haplogroups. Conclusions First diversifying in the central/north-west region of Patagonia, G. maculatus extended its range into Argentina via the southern coastal regions that join the Pacific and Atlantic oceans. More recent gene flow between northern

  2. Vitamin D and Adipogenesis: New Molecular Insights

    Science.gov (United States)

    The focus of the current review is to highlight some new insights into the molecular mechanism by which vitamin D, a potentially nutritionally modulated factor, influences adipogenesis. Recent studies, predominantly using the mouse 3T3-L1 pre-adipocyte cell culture model, have shown that the role of...

  3. Extinction risks from climate change: macroecological and historical insights

    OpenAIRE

    Jansson, Roland

    2009-01-01

    Human-induced climate change may threaten a large proportion of Earth's biota, but the uncertainties involved in projecting the future geographical distributions of species make quantitative predictions of extinction risk difficult to make. I discuss how insight from recent advances in macroecology and knowledge about species responses to past climate change can help predict extinction risks more accurately.

  4. Climatic change and climate policy. Insight in choices for the Dutch Parliament (Second Chamber)

    International Nuclear Information System (INIS)

    The aim of the study on the title subject is to provide information and insight to the Dutch parliament (Second Chamber) (1) in the state of the art with regard to climate science and international climate policy; (2) in different policy options and possible incentives; (3) in the macro-economical, societal, and environmental cost and benefit of those policy options; and (4) in the dilemmas with regard to environment, economy and other societal developments, being the consequence of climatic change and climate policy

  5. Local Business Climate in Ghana – Insights for Policy Direction

    Directory of Open Access Journals (Sweden)

    Mavis Serwah Benneh Mensah

    2012-01-01

    Full Text Available This study provides insights for enhancing the business climate in Ghana. The primary objective of the studywas to identify the most relevant binding constraint(s on the activities of micro, small and medium-sizedenterprises (MSMEs in the manufacturing sector of Sunyani Municipality and Berekum District of Ghana.Accordingly, a survey of 85 manufacturing MSMEs was conducted. In spite of energy crisis in Ghana at the timeof research, the most relevant binding constraints to the enterprises surveyed were poor access to technologyincluding technological support services, and poor access to market (which will be discussed in subsequentpaper. The findings contradict policy focus on addressing governance and regulatory bottlenecks, andinadequate physical infrastructure. This underscores the importance of local business climate surveys in additionto national surveys in establishing the right policy focus for enhancing the business climate of localities within acountry.

  6. Combining Global Climate Model Outputs and Insights from Downscaling for Australian Climate Projections

    Science.gov (United States)

    Grose, M. R.; Timbal, B.; Katzfey, J. J.; Moise, A. F.; Eksrtrom, M.; Whetton, P.

    2013-12-01

    Dynamical and statistical downscaling of global climate model (GCM) outputs has the potential to provide valuable insights when making regional climate projections. It may reveal regional detail in the projected climate change signal through higher resolution and accounting for local influences such as topography and coastlines. However, climate change adaptation research and planning desires a coherent view of possible future climate that accounts for the various sources of uncertainty and at a relevant spatial scale. This means there is value in combining the most useful insights from all available downscaling with a more comprehensive set of designed global climate model (GCM) projections (e.g. the CMIP5 archive), and this is done for the next set of national climate projections products in Australia. There are several practical considerations in this process that affect the process, primarily because downscaling is done using various disparate methods for a limited set of models and scenarios. There is no objective framework to combine different sets of ad hoc downscaling simulations with a set of GCMs, so some degree of expert judgment is used. We emphasize cases where there is the most apparent ';added value' and report these insights in complement, and in some cases in preference to, GCM projections. Confidence in such insights first requires understanding of what input data is used from the host model, what biases are reduced and what new biases are potentially introduced. We then seek an understanding of how the climate change signal differs from that of the host model, and an attribution of the cause of this difference. Several case studies within Australia are discussed.

  7. NEW INSIGHTS INTO MOLECULAR TARGETS FOR DEPRESSION

    Directory of Open Access Journals (Sweden)

    Mehta Hiren R

    2011-12-01

    Full Text Available Major depressive disorder is a heritable neuropsychiatric syndrome characterized by relatively subtle cellular and molecular alterations localized to a complex network of neural substrates. Various forms of psychotherapy, pharmacotherapy, and electroconvulsive therapy (ECT are currently the most commonly used antidepressant treatments. Despite adequate care with currently available treatments, up to 70% of depressed patients have residual symptoms, and, even with more aggressive therapies, 20% or more may show only a limited response. The need for newer compounds to treat depression is still an ever growing concern due to the enormous societal and famifications of depression. This review covers all the monoaminergic (SSRI/5-HT1A antagonists, SSRI/5-HT2C antagonists, SSRI/alpha-2 adrenergic antagonists, triple reuptake inhibitors, dopamine agonists,targeting GABA and beyond monoaminergic strategies including corticotropin-releasing factor (CRF-1 receptor antagonists, Inhibition of glucocorticoid function, substance P (Nk-1 antagonists, MCH1 receptor antagonists, Gal3 receptor antagonists, arginine vasopressin as the potential novel targets for depression.. However, To be the most successful novel target it shouldn’t only demonstrate preclinical antidepressant like effects, but also target the unmet clinical needs and lead to long-term disease modification.

  8. Helicases as molecular motors: An insight

    Science.gov (United States)

    Tuteja, Narendra; Tuteja, Renu

    2006-12-01

    Helicases are one of the smallest motors of biological system, which harness the chemical free energy of ATP hydrolysis to catalyze the opening of energetically stable duplex nucleic acids and thereby are involved in almost all aspect of nucleic acid metabolism including replication, repair, recombination, transcription, translation, and ribosome biogenesis. Basically, they break the hydrogen bonding between the duplex helix and translocate unidirectionally along the bound strand. Mostly all the helicases contain some conserved signature motifs, which act as an engine to power the unwinding. After the discovery of the first prokaryotic DNA helicase from Escherichia coli bacteria in 1976 and the first eukaryotic one from the lily plant in 1978, many more (>100) have been isolated. All the helicases share some common properties, including nucleic acid binding, NTP hydrolysis and unwinding of the duplex. Many helicases have been crystallized and their structures have revealed an underlying common structural fold for their function. The defects in helicases gene have also been reported to be responsible for variety of human genetic disorders, which can lead to cancer, premature aging or mental retardation. Recently, a new role of a helicase in abiotic stress signaling in plant has been discovered. Overall, helicases act as essential molecular tools for cellular machinery and help in maintaining the integrity of genome. Here an overview of helicases has been covered which includes history, biochemical assay, properties, classification, role in human disease and mechanism of unwinding and translocation.

  9. Molecular dynamics insights into human aquaporin 2 water channel.

    Science.gov (United States)

    Binesh, A R; Kamali, R

    2015-12-01

    In this study, the first molecular dynamics simulation of the human aquaporin 2 is performed and for a better understanding of the aquaporin 2 permeability performance, the characteristics of water transport in this protein channel and key biophysical parameters of AQP2 tetramer including osmotic and diffusive permeability constants and the pore radius are investigated. For this purpose, recently recovered high resolution X-ray crystal structure of` the human aquaporin 2 is used to perform twenty nanosecond molecular dynamics simulation of fully hydrated tetramer of this protein embedded in a lipid bilayer. The resulting water permeability characteristics of this protein channel showed that the water permeability of the human AQP2 is in a mean range in comparison with other human aquaporins family. Finally, the results reported in this research demonstrate that molecular dynamics simulation of human AQP2 provided useful insights into the mechanisms of water permeation and urine concentration in the human kidney. PMID:26489820

  10. Factoring the car-climate challenge: Insights and implications

    International Nuclear Information System (INIS)

    Three approaches commonly are identified for controlling automobile greenhouse gas (GHG) emissions: reducing travel demand, improving vehicle efficiency and using alternatively (non-petroleum) fueled vehicles (AFVs). Similarly, sector emissions are factored by travel distance, vehicle fuel intensity and fuel GHG (“carbon”) intensity. Analyzing these factors using US and China data reveals that for a broad range of conditions, stringent GHG emissions limits for the auto sector imply limits of comparable stringency for fuel carbon intensity. However, carbon intensity is a modeled representation of complex energy supply and use systems rather than a measurable property of fuels themselves. Carefully examining the locations and magnitudes of fuel-related emissions indicates that the proper policy focus is on the sectors that supply fuel rather than the choice of fuels in the auto sector. Therefore, beyond fundamental R and D, policies to commercialize AFVs are not necessarily required for climate protection at present. In addition to managing travel demand and improving vehicle efficiency, the implied policy priority is limiting net GHG impacts in the energy and other natural resource sectors that supply fuels. Future work is needed to develop GHG management protocols for liquid fuel supply systems involving fungible commodities and dynamic global supply chains. - Highlights: • Factor analysis offers insights about ways to reduce automotive GHG emissions. • Improving vehicle efficiency and reducing travel demand remain important. • Reducing net GHG impacts in energy sectors that supply motor fuels is also a priority. • Commercialization of alternatively fueled vehicles is not necessarily required at present

  11. Insights from past millennia into climatic impacts on human health and survival

    OpenAIRE

    Anthony J McMichael

    2012-01-01

    Climate change poses threats to human health, safety, and survival via weather extremes and climatic impacts on food yields, fresh water, infectious diseases, conflict, and displacement. Paradoxically, these risks to health are neither widely nor fully recognized. Historical experiences of diverse societies experiencing climatic changes, spanning multicentury to single-year duration, provide insights into population health vulnerability—even though most climatic changes were considerably less...

  12. Molecular responses to xenoestrogens: Mechanistic insights from toxicogenomics

    International Nuclear Information System (INIS)

    The xenoestrogen group of endocrine disruptors has the potential to cause reproductive and developmental effects through stimulation or disruption of sex steroid nuclear receptor signalling pathways. A more detailed understanding of the ways in which xenoestrogens interact with biological systems at the molecular level will provide a mechanistic basis for improved safety assessment. The recent sequencing of mammalian genomes has driven the development of toxicogenomic technologies, including microarray based gene expression profiling, which allow the expression levels of thousands of genes to be measured simultaneously. Since the cellular responses to xenoestrogens are predominantly mediated by estrogen receptors, which function as ligand-activated transcription factors to regulate gene expression, the application of toxicogenomics has great potential for providing insights into the molecular mechanisms of xenoestrogen action. A major challenge in applying toxicogenomics to the field of endocrine disruption is the need to define how xenoestrogen-induced changes in gene expression relate to conventional physiological and toxicological endpoints. Gene Ontology Mapping, Pathway Mapping and Phenotypic Anchoring of xenoestrogen-induced gene expression changes to cellular pathways and processes represent key steps in defining these relationships. Mechanistic insights into how xenoestrogens target specific genes and into the functional significance of xenoestrogen-induced alterations in gene expression can be further enhanced by combining transcript profiling with transgenic animal models or cell-based systems in which the estrogen receptor signalling pathways have been modified experimentally. This review illustrates how these toxicogenomic approaches are providing an unprecedented amount of mechanistic information on the molecular responses to xenoestrogens and how they are likely to impact on hazard and risk assessment

  13. Managing U.S. climate risk through mitigation: Insights from the American Climate Prospectus

    Science.gov (United States)

    Kopp, R. E., III; Hsiang, S. M.; Houser, T.; Larsen, K.; Rasmussen, D. M., Jr.; Jina, A.; Rising, J.; Delgado, M.; Mohan, S.; Muir-Wood, R.; Wilson, P. S.

    2014-12-01

    The American Climate Prospectus (ACP), the technical analysis underlying the Risky Business project, quantitatively assessed the economic risks posed to the United States by six categories of climate change impacts: crop yield, energy demand, coastal storm damage, criminal activity, labor productivity, and mortality [1]. At a national level, measured by impact on gross domestic product, increased mortality and decreased labor productivity pose the large risks, followed by increased energy demand and coastal damages. Changes in crop yield and crime have smaller impacts. The ACP was not intended to conduct a benefit-cost analysis of climate change mitigation. It assessed the economic consequences of future impacts on an economy with a structure equivalent to that of the current economy, not accounting for socio-economic development and adaptation, and did not assess the cost of mitigation. One of its primary goals was to inform adaptation decisions that are conventionally considered 'endogenous' in economic analyses of climate change. Nonetheless, its results provide insight into the potential of mitigation to manage climate risk. Differences between RCP 8.5 (moderately-high business-as-usual emissions), RCP 4.5 (moderate mitigation) and RCP 2.6 (extremely strong mitigation) are not apparent until mid-century and become significant only late in the century. For all impacts except coastal damages, mitigation significantly reduces uncertainty in late-century impact estimates. Nationally, mitigation significantly and monotonically reduces median projected labor productivity losses and violent crime. Switching from RCP 8.5 to RCP 4.5 also significantly reduces median projections of mortality and energy demand, but the domestic value to the U.S. of further mitigation to RCP 2.6 is less clear. The marginal benefits decline in part because some regions of the country (especially the Northwest) may experience increased crop yields, reduced mortality, and reduced energy

  14. Molecular insights into the terminal energy acceptor in cyanobacterial phycobilisome.

    Science.gov (United States)

    Gao, Xiang; Wei, Tian-Di; Zhang, Nan; Xie, Bin-Bin; Su, Hai-Nan; Zhang, Xi-Ying; Chen, Xiu-Lan; Zhou, Bai-Cheng; Wang, Zhi-Xin; Wu, Jia-Wei; Zhang, Yu-Zhong

    2012-09-01

    The linker protein L(CM) (ApcE) is postulated as the major component of the phycobilisome terminal energy acceptor (TEA) transferring excitation energy from the phycobilisome to photosystem II. L(CM) is the only phycobilin-attached linker protein in the cyanobacterial phycobilisome through auto-chromophorylation. However, the underlying mechanism for the auto-chromophorylation of L(CM) and the detailed molecular architecture of TEA is still unclear. Here, we demonstrate that the N-terminal phycobiliprotein-like domain of L(CM) (Pfam00502, LP502) can specifically recognize phycocyanobilin (PCB) by itself. Biochemical assays indicated that PCB binds into the same pocket in LP502 as that in the allophycocyanin α-subunit and that Ser152 and Asp155 play a vital role in LP502 auto-chromophorylation. By carefully conducting computational simulations, we arrived at a rational model of the PCB-LP502 complex structure that was supported by extensive mutational studies. In the PCB-LP502 complex, PCB binds into a deep pocket of LP502 with a distorted conformation, and Ser152 and Asp155 form several hydrogen bonds to PCB fixing the PCB Ring A and Ring D. Finally, based on our results, the dipoles and dipole-dipole interactions in TEA are analysed and a molecular structure for TEA is proposed, which gives new insights into the energy transformation mechanism of cyanobacterial phycobilisome. PMID:22758351

  15. Molecular insight into conformational transmission of human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shan-Yan [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Liu, Fu-Feng, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn; Dong, Xiao-Yan; Sun, Yan, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China)

    2013-12-14

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  16. Molecular insight into conformational transmission of human P-glycoprotein

    Science.gov (United States)

    Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

    2013-12-01

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  17. Molecular Determinants of Magnesium Homeostasis: Insights from Human Disease

    Science.gov (United States)

    Alexander, R. Todd; Hoenderop, Joost G.; Bindels, René J.

    2016-01-01

    The past decade has witnessed multiple advances in our understanding of magnesium (Mg2+) homeostasis. The discovery that mutations in claudin-16/paracellin-1 or claudin-19 are responsible for familial hypomagnesemia with hypercalciuria and nephrocalcinosis provided insight into the molecular mechanisms governing paracellular transport of Mg2+. Our understanding of the transcellular movement of Mg2+ was similarly enhanced by the realization that defects in transient receptor potential melastatin 6 (TRPM6) cause hypomagnesemia with secondary hypocalcemia. This channel regulates the apical entry of Mg2+ into epithelia. In so doing, TRPM6 alters whole-body Mg2+ homeostasis by controlling urinary excretion. Consequently, investigation into the regulation of TRPM6 has increased. Acid-base status, 17β estradiol, and the immunosuppressive agents FK506 and cyclosporine affect plasma Mg2+ levels by altering TRPM6 expression. A mutation in epithelial growth factor is responsible for isolated autosomal recessive hypomagnesemia, and epithelial growth factor activates TRPM6. A defect in the γ-subunit of the Na,K-ATPase causes isolated dominant hypomagnesemia by altering TRPM6 activity through a decrease in the driving force for apical Mg2+ influx. We anticipate that the next decade will provide further detail into the control of the gatekeeper TRPM6 and, therefore, overall whole-body Mg2+ balance. PMID:18562569

  18. Molecular Sociology: Further Insights from Biological and Environmental Aspects

    Directory of Open Access Journals (Sweden)

    Ahed Jumah Mahmoud Al-Khatib

    2015-11-01

    Full Text Available The present study expanded our previous study in which features of molecular sociology were mentioned. In this study, we added the microbial dimensions in which it is thought that religiosity may be impacted by microbes that manipulate brains to create better conditions for their existence. This hypothesis is called “biomeme hypothesis”. We talked about other environmental impacts on human behaviors through three studies in which exposure to lead caused violent behaviors ending with arresting in prisons. By conclusion, the present study has expanded our horizon about interferences on various levels including biological and environmental impacts with our behaviors. Although we are convinced that behavior is a very diverse and complex phenomenon and cannot be understood within certain frame as either biologically or environmentally, but further new insights are possible to participate in better understanding of human behaviors. Many behaviors have their roots in religion, and we showed how religious rituals may be affected by some microbes that make to form a microenvironment within the host for microbial benefits.

  19. New Molecular Insights of Insulin in Diabetic Cardiomyopathy

    Science.gov (United States)

    Westermeier, Francisco; Riquelme, Jaime A.; Pavez, Mario; Garrido, Valeria; Díaz, Ariel; Verdejo, Hugo E.; Castro, Pablo F.; García, Lorena; Lavandero, Sergio

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a highly prevalent disease worldwide. Cardiovascular disorders generated as a consequence of T2DM are a major cause of death related to this disease. Diabetic cardiomyopathy (DCM) is characterized by the morphological, functional and metabolic changes in the heart produced as a complication of T2DM. This cardiac disorder is characterized by constant high blood glucose and lipids levels which eventually generate oxidative stress, defective calcium handling, altered mitochondrial function, inflammation and fibrosis. In this context, insulin is of paramount importance for cardiac contractility, growth and metabolism and therefore, an impaired insulin signaling plays a critical role in the DCM development. However, the exact pathophysiological mechanisms leading to DCM are still a matter of study. Despite the numerous questions raised in the study of DCM, there have also been important findings, such as the role of micro-RNAs (miRNAs), which can not only have the potential of being important biomarkers, but also therapeutic targets. Furthermore, exosomes also arise as an interesting variable to consider, since they represent an important inter-cellular communication mechanism and therefore, they may explain many aspects of the pathophysiology of DCM and their study may lead to the development of therapeutic agents capable of improving insulin signaling. In addition, adenosine and adenosine receptors (ARs) may also play an important role in DCM. Moreover, the possible cross-talk between insulin and ARs may provide new strategies to reverse its defective signaling in the diabetic heart. This review focuses on DCM, the role of insulin in this pathology and the discussion of new molecular insights which may help to understand its underlying mechanisms and generate possible new therapeutic strategies. PMID:27148064

  20. Emerging insights into the molecular and cellular basis of glioblastoma

    Science.gov (United States)

    Dunn, Gavin P.; Rinne, Mikael L.; Wykosky, Jill; Genovese, Giannicola; Quayle, Steven N.; Dunn, Ian F.; Agarwalla, Pankaj K.; Chheda, Milan G.; Campos, Benito; Wang, Alan; Brennan, Cameron; Ligon, Keith L.; Furnari, Frank; Cavenee, Webster K.; Depinho, Ronald A.; Chin, Lynda; Hahn, William C.

    2012-01-01

    Glioblastoma is both the most common and lethal primary malignant brain tumor. Extensive multiplatform genomic characterization has provided a higher-resolution picture of the molecular alterations underlying this disease. These studies provide the emerging view that “glioblastoma” represents several histologically similar yet molecularly heterogeneous diseases, which influences taxonomic classification systems, prognosis, and therapeutic decisions. PMID:22508724

  1. Molecular Electronics: Insight from First-Principles Transport Simulations

    DEFF Research Database (Denmark)

    Paulsson, Magnus; Frederiksen, Thomas; Brandbyge, Mads

    2010-01-01

    Conduction properties of nanoscale contacts can be studied using first-principles simulations. Such calculations give insight into details behind the conductance that is not readily available in experiments. For example, we may learn how the bonding conditions of a molecule to the electrodes affe...

  2. Estimating the limits of adaptation from historical behaviour: Insights from the American Climate Prospectus

    Science.gov (United States)

    Jina, A.; Hsiang, S. M.; Kopp, R. E., III; Rasmussen, D.; Rising, J.

    2014-12-01

    The American Climate Prospectus (ACP), the technical analysis underlying the Risky Business project, quantitatively assessed the climate risks posed to the United States' economy in a number of economic sectors [1]. The main analysis presents projections of climate impacts with an assumption of "no adaptation". Yet, historically, when the climate imposed an economic cost upon society, adaptive responses were taken to minimise these costs. These adaptive behaviours, both autonomous and planned, can be expected to occur as climate impacts increase in the future. To understand the extent to which adaptation might decrease some of the worst impacts of climate change, we empirically estimate adaptive responses. We do this in three sectors considered in the analysis - crop yield, crime, and mortality - and estimate adaptive capacity in two steps. First, looking at changes in climate impacts through time, we identify a historical rate of adaptation. Second, spatial differences in climate impacts are then used to stratify regions into more adapted or less adapted based on climate averages. As these averages change across counties in the US, we allow each to become more adapted at the rate identified in step one. We are then able to estimate the residual damages, assuming that only the historical adaptive behaviours have taken place (fig 1). Importantly, we are unable to estimate any costs associated with these adaptations, nor are we able to estimate more novel (for example, new technological discoveries) or more disruptive (for example, migration) adaptive behaviours. However, an important insight is that historical adaptive behaviours may not be capable of reducing the worst impacts of climate change. The persistence of impacts in even the most exposed areas indicates that there are non-trivial costs associated with adaptation that will need to be met from other sources or through novel behavioural changes. References: [1] T. Houser et al. (2014), American Climate

  3. The PICS Climate Insights 101 Courses: A Visual Approach to Learning About Climate Science, Mitigation and Adaptation

    Science.gov (United States)

    Pedersen, T. F.; Zwiers, F. W.; Breen, C.; Murdock, T. Q.

    2014-12-01

    The Pacific Institute for Climate Solutions (PICS) has now made available online three free, peer-reviewed, unique animated short courses in a series entitled "Climate Insights 101" that respectively address basic climate science, carbon-emissions mitigation approaches and opportunities, and adaptation. The courses are suitable for students of all ages, and use professionally narrated animations designed to hold a viewer's attention. Multiple issues are covered, including complex concerns like the construction of general circulation models, carbon pricing schemes in various countries, and adaptation approaches in the face of extreme weather events. Clips will be shown in the presentation. The first course (Climate Science Basics) has now been seen by over two hundred thousand individuals in over 80 countries, despite being offered in English only. Each course takes about two hours to work through, and in recognizing that that duration might pose an attention barrier to some students, PICS selected a number of short clips from the climate-science course and posted them as independent snippets on YouTube. A companion series of YouTube videos entitled, "Clear The Air", was created to confront the major global-warming denier myths. But a major challenge remains: despite numerous efforts to promote the availability of the free courses and the shorter YouTube pieces, they have yet to become widely known. Strategies to overcome that constraint will be discussed.

  4. Molecular insights into the causes of male infertility

    Indian Academy of Sciences (India)

    Polani B Seshagiri

    2001-11-01

    Infertility is a reproductive health problem that affects many couples in the human population. About 13–18% of couple suffers from it and approximately one-half of all cases can be traced to either partner. Regardless of whether it is primary or secondary infertility, affected couples suffer from enormous emotional and psychological trauma and it can constitute a major life crisis in the social context. Many cases of idiopathic infertility have a genetic or molecular basis. The knowledge of the molecular genetics of male infertility is developing rapidly, new ``spermatogenic genes” are being discovered and molecular diagnostic approaches (DNA chips) established. This will immensely help diagnostic and therapeutic approaches to alleviate human infertility. The present review provides an overview of the causes of human infertility, particularly the molecular basis of male infertility and its implications for clinical practice.

  5. Clinical and molecular insights into primary pediatric liver cancer

    OpenAIRE

    Weeda, V.B.

    2016-01-01

    This thesis aims to give insight into the clinical status quo of primary pediatric liver tumors and investigate signaling pathways that may be of importance for liver tumorigenesis. The most recent series of the International Childhood Liver Tumors Strategy Group (SIOPEL) of hepatocellular carcinoma (HCC) and its distinct variant fibrolamellar hepatocellular carcinoma (FL-HCC) are discussed. For both tumors, complete resection is at present the only curative option. FL-HCC does not have a bet...

  6. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    Directory of Open Access Journals (Sweden)

    Marko Zivcec

    2016-04-01

    Full Text Available Crimean-Congo hemorrhagic fever virus (CCHFV is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  7. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus.

    Science.gov (United States)

    Zivcec, Marko; Scholte, Florine E M; Spiropoulou, Christina F; Spengler, Jessica R; Bergeron, Éric

    2016-01-01

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research. PMID:27110812

  8. Increased genome sampling reveals novel insights into vertebrate molecular evolution

    OpenAIRE

    Doherty, Aoife

    2012-01-01

    In this thesis, increased vertebrate genome sampling and recent methodological advancements were combined to address three distinct questions pertaining to vertebrate molecular evolution. Gene duplicability is the tendency to retain multiple gene copies after a duplication event. Various factors correlate with gene duplicability, such as protein function and timing of expression during development. The position of a gene’s encoded product in the protein-protein interaction n...

  9. Molecular Insight into Gut Microbiota and Rheumatoid Arthritis

    OpenAIRE

    Xiaohao Wu; Bing He; Jin Liu; Hui Feng; Yinghui Ma; Defang Li; Baosheng Guo; Chao Liang; Lei Dang; Luyao Wang; Jing Tian; Hailong Zhu; Lianbo Xiao; Cheng Lu; Aiping Lu

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, ...

  10. Interaction of peptides with cell membranes: insights from molecular modeling

    International Nuclear Information System (INIS)

    The investigation of the interaction of peptides with cell membranes is the focus of active research. It can enhance the understanding of basic membrane functions such as membrane transport, fusion, and signaling processes, and it may shed light on potential applications of peptides in biomedicine. In this review, we will present current advances in computational studies on the interaction of different types of peptides with the cell membrane. Depending on the properties of the peptide, membrane, and external environment, the peptide–membrane interaction shows a variety of different forms. Here, on the basis of recent computational progress, we will discuss how different peptides could initiate membrane pores, translocate across the membrane, induce membrane endocytosis, produce membrane curvature, form fibrils on the membrane surface, as well as interact with functional membrane proteins. Finally, we will present a conclusion summarizing recent progress and providing some specific insights into future developments in this field. (topical review)

  11. From quantifying historical LULCC impacts to optimizing land management for climate mitigation: Insights from climate modelling

    Science.gov (United States)

    Davin, E.; Lejeune, Q.; Seneviratne, S. I.

    2015-12-01

    Human activities have profoundly transformed the land surface through land use/land cover change (LULCC). The consequence of this transformation is twofold: First, the conversion from natural to anthropogenic systems exert a direct forcing on climate (through both biogeochemical and biogeophysical processes); Second the transformed ecosystems may modify land-atmosphere feedback mechanisms thus modulating the response to climate change or to specific weather events. The first point will be illustrated by reviewing recent modelling results, including LUCID and CMIP5 model intercomparisons, to shed some light on the relative importance of LULCC versus other climate forcings. Given the importance of LULCC impacts at the regional scale, some recent efforts to improve the representation of land processes in regional climate models [1] as well as a regional assessment of the impact of amazonian deforestation [2] will be presented. The second point will be discussed through two examples. First, the fact that LULCC may modulate certain modes of variability will be illustrated based on model experiments highlighting the regional interplay between ENSO variability and amazonian deforestation. Second, we will show that peak temperatures during heat waves can be strongly influenced locally by the type of land cover or land management practices. In particular no-till farming, by increasing surface albedo, can lead to a substantial attenuation of hot temperatures during heat waves, in part due to a more efficient radiative cooling effect during cloud-free conditions [3]. References:[1] Davin, E.L. and S.I. Seneviratne (2012), Role of land surface processes and diffuse/direct radiation partitioning in simulating the European climate, Biogeosciences, 9, 1695-1707, doi:10.5194/bg-9-1695-2012.[2] Lejeune, Q., E.L. Davin, B. Guillod and S.I. Seneviratne (2015), Influence of Amazonian deforestation on the future evolution of regional surface fluxes, circulation, surface temperature and

  12. Buckling of microtubules: An insight by molecular and continuum mechanics

    International Nuclear Information System (INIS)

    The molecular structural mechanics method has been extended to investigate the buckling of microtubules (MTs) with various configurations. The results indicate that for relative short MTs the shear deformation effect, rather than the nonlocal effect, is mainly responsible for the limitation of their widely used Euler beam description and the observed length-dependence of their bending stiffness. In addition, the configuration effect of MTs is also studied and considered as an explanation for the large scattering of the critical buckling force and bending stiffness observed in existing experiments. This configuration effect is also found to mainly originate from the geometry of the MTs and is mainly determined by the protofilament number.

  13. Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics Simulations.

    Science.gov (United States)

    Liao, Chenyi; Esai Selvan, Myvizhi; Zhao, Jun; Slimovitch, Jonathan L; Schneebeli, Severin T; Shelley, Mee; Shelley, John C; Li, Jianing

    2015-08-20

    Melittin is a natural peptide that aggregates in aqueous solutions with paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is known about the molecular mechanisms of melittin aggregation in solution, we simulated its self-aggregation process under various conditions. After confirming the stability of a melittin tetramer in solution, we observed—for the first time in atomistic detail—that four separated melittin monomers aggregate into a tetramer. Our simulated dependence of melittin aggregation on peptide concentration, temperature, and ionic strength is in good agreement with prior experiments. We propose that melittin mainly self-aggregates via a mechanism involving the sequential addition of monomers, which is supported by both qualitative and quantitative evidence obtained from unbiased and metadynamics simulations. Moreover, by combining computer simulations and a theory of the electrical double layer, we provide evidence to suggest why melittin aggregation in solution likely stops at the tetramer, rather than forming higher-order oligomers. Overall, our study not only explains prior experimental results at the molecular level but also provides quantitative mechanistic information that may guide the engineering of melittin for higher efficacy and safety. PMID:26208115

  14. Insights into the molecular genetics of Kabuki syndrome

    Directory of Open Access Journals (Sweden)

    Adam MP

    2015-02-01

    Full Text Available Margaret P Adam Department of Pediatrics, Division of Genetic Medicine, University of Washington School of Medicine, Seattle, WA, USA Abstract: Kabuki syndrome (KS is a well-recognized multiple congenital anomaly/intellectual disability syndrome characterized by distinctive facial features, congenital heart defects, skeletal anomalies, persistent fingertip pads, postnatal growth retardation, and cognitive impairment to varying degrees. To date, mutations or deletions in two genes (KMT2D and KDM6A have been identified to cause the majority of cases of KS. Both genes are involved in histone modification and epigenetic regulation of gene expression in early embryogenesis. In this report, we review the clinical features and management of patients with KS, explore the proposed protein interactions and the molecular pathway that may lead to features of KS, and discuss how knowledge of the molecular mechanisms has the potential to inform further disease gene discovery and targeted treatment of the condition. Keywords: Kabuki syndrome, Kabuki make-up syndrome, KMT2D, KDM6A, histone modification

  15. Insights of asphaltene aggregation mechanism from molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    Jennifer De León

    2015-01-01

    Full Text Available Se estudió el proceso de agregación de asfaltenos utilizando té cnicas de dinámica molecular. Se utilizaron cuatro estructuras diferentes. Las primeras tres moléculas tienen una estructura continental, con núcleos aromáticos condensador, mientras que la cuarta pose e una estructura tipo archipiélago, con pequeños grupos de anillos ar omáticos conectados con cadenas saturadas. Las moléculas fueron construidas de manera atomística, en la cual cada átomo se desc ribe individualmente. Se calcula ron las fuerzas de interacción a 300 K y 200 atm; las fuerzas de Van der W aals y las interacciones elect rostáticas fueron evaluadas separadamente. Se calculó el paráme tro de solubilidad para las cuatro molécu las. Se encontró que las inte racciones de Van der Waals asoc iadas a los anillos aromáticos y las fuerzas electrostáticas ocasionadas princ ipalmente por la presencia de heteroátomos como oxígeno, azufr e y nitrógeno, son igualmente r elevantes en la agregación de moléculas de asfalteno. Para todas las molé culas se encontró que los sistemas de asfaltenos tienen menor e nergía en estado de agregación que en estado monomérico. Para las estruct uras continentales, la presencia de largas cadenas obstruye el proceso de formación de agregados. Para las estructuras tipo archipiélago, la flexibilidad de las moléculas facilita la agregación con ot ras estructuras. La presencia de heteroátomos ocasiona una fuerza repulsiva que dificulta la agregación. El volumen molecular y la energía de c ohesión también son sensibles a la confi guración geométrica y la compos ición de las especies, lo cual afecta el parámetro de solubilidad.

  16. New insights into molecular targets for urinary incontinence

    Directory of Open Access Journals (Sweden)

    Poonia Manoj

    2010-01-01

    Full Text Available Urinary incontinence (UI is a disease affecting quality of life of 200 million patients worldwide. It is characterized by involuntary loss of urine. The factors involved are cystitis, detrusor hyperreflexia, spinal injury, benign prostatic hyperplasia, etc. The surge in the number of reviews on this subject indicates the amount of research devoted to this field. The prevalence is increasing at an alarming rate but unfortunately, only a few medications are currently available for this condition. There are peripheral as well as central targets including cholinergic, vanilloid, prostaglandin, kinin, calcium channel, cannabinoid, serotonin, and GABA-receptors, which act by different mechanisms to treat different types of incontinence. Drugs acting on the central nervous system (CNS increase urinary bladder capacity, volume, or pressure threshold for micturition reflex activation while peripherally acting drugs decrease the amplitude of micturition contraction and residual volume. Anticholinergic drugs specifically M3 receptor antagonists are the first choice but have frequent side effects such as dry mouth, CNS disturbances, etc. Therefore, there is a need to understand the biochemical pathways that control urinary dysfunction to determine the potential to which they can be exploited in the treatment of this condition. This article reviews the central and peripheral molecular targets and the potential therapeutic approaches to the treatment of UI.

  17. Mechanics at the molecular scale: Insight into the physical mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Neucheva, Olga A.; Temirov, Ruslan; Tautz, Stefan [Institut fuer Bio- und Nanosysteme (IBN-3) and JARA - Fundamental of Future Information Technology, Forschungszentrum Juelich, 52425 Juelich (Germany)

    2010-07-01

    The manipulation of atoms and molecules is one of the problems under investigation in a surface science. The first successful attempt to transfer an atom from a surface with use of a scanning tunneling microscope has been realized by Eigler et al. An interest to understand the underlying physical mechanism from both experimental and theoretical points of view has led to investigations of many systems which can be used as atomic and molecular switches. In our work the behaviour of a single PTCDA molecule on Ag(111) has been investigated with a LT-STM. Two level fluctuations of the conductance of the junction have been observed within a narrow range of the tip heights and bias voltages. The bistability is related to reversible switching of one of the carboxylic oxygen atoms between the surface and the STM-tip. The current passing through the junction induces vibrations of the molecule leading to weakening and breaking of a chemical bond with the surface and establishing a new one with the tip and vice versa. The switching frequency strongly depends on the bias voltages and tip heights, following a non-linear dependence on the current.

  18. Response of germinating barley seeds to Fusarium graminearum: The first molecular insight into Fusarium seedling blight

    DEFF Research Database (Denmark)

    Yang, Fen; Svensson, Birte; Finnie, Christine

    2011-01-01

    Fusarium seedling blight in cereals can result in significant reductions in plant establishment but has not received much attention. The disease often starts during seed germination due to sowing of the seeds infected by Fusarium spp. including Fusarium graminearum. In order to gain the first...... provides the first molecular insight into Fusarium seedling blight....

  19. Molecular insights into seed dispersal mutualisms driving plant population recruitment

    Science.gov (United States)

    García, Cristina; Grivet, Delphine

    2011-11-01

    Most plant species require mutualistic interactions with animals to fulfil their demographic cycle. In this regard frugivory (i.e., the intake of fruits by animals) enhances natural regeneration by mobilizing a large amount of seeds from source trees to deposition sites across the landscape. By doing so, frugivores move propagules, and the genotypes they harbour creating the spatial, ecological, and genetic environment under which subsequent recruitment proceeds. Recruitment patterns can be envisioned as the result of two density- and distance-dependent processes: seed dispersal and seed/seedling survival (the Janzen-Connell model). Population genetic studies add another layer of complexity for understanding the fate of dispersed propagules: the genetic relatedness among neighbouring seeds within a seed clump, a major outcome of frugivore activity, modifies their chances of germinating and surviving. Yet, we virtually ignore how the spatial distribution of maternal progenies and recruitment patterns relate with each other in frugivore-generated seed rains. Here we focus on the critical role of frugivore-mediated seed dispersal in shaping the spatial distribution of maternal progenies in the seed rain. We first examine which genetic mechanisms underlying recruitment are influenced by the spatial distribution of maternal progenies. Next, we examine those studies depicting the spatial distribution of maternal progenies in a frugivore-generated seed rain. In doing so, we briefly review the most suitable analytical approaches applied to track the contribution of fruiting trees to the seed rain based on molecular data. Then we look more specifically at the role of distinct frugivore guilds in determining maternal genetic correlations and their expected consequences for recruitment patterns. Finally we posit some general conclusions and suggest future research directions that would provide a more comprehensive understanding of the ecological and evolutionary consequences

  20. Molecular signatures of ovarian diseases: Insights from network medicine perspective.

    Science.gov (United States)

    Kori, Medi; Gov, Esra; Arga, Kazim Yalcin

    2016-08-01

    Dysfunctions and disorders in the ovary lead to a host of diseases including ovarian cancer, ovarian endometriosis, and polycystic ovarian syndrome (PCOS). Understanding the molecular mechanisms behind ovarian diseases is a great challenge. In the present study, we performed a meta-analysis of transcriptome data for ovarian cancer, ovarian endometriosis, and PCOS, and integrated the information gained from statistical analysis with genome-scale biological networks (protein-protein interaction, transcriptional regulatory, and metabolic). Comparative and integrative analyses yielded reporter biomolecules (genes, proteins, metabolites, transcription factors, and micro-RNAs), and unique or common signatures at protein, metabolism, and transcription regulation levels, which might be beneficial to uncovering the underlying biological mechanisms behind the diseases. These signatures were mostly associated with formation or initiation of cancer development, and pointed out the potential tendency of PCOS and endometriosis to tumorigenesis. Molecules and pathways related to MAPK signaling, cell cycle, and apoptosis were the mutual determinants in the pathogenesis of all three diseases. To our knowledge, this is the first report that screens these diseases from a network medicine perspective. This study provides signatures which could be considered as potential therapeutic targets and/or as medical prognostic biomarkers in further experimental and clinical studies. Abbreviations DAVID: Database for Annotation, Visualization and Integrated Discovery; DEGs: differentially expressed genes; GEO: Gene Expression Omnibus; KEGG: Kyoto Encyclopedia of Genes and Genomes; LIMMA: Linear Models for Microarray Data; MBRole: Metabolite Biological Role; miRNA: micro-RNA; PCOS: polycystic ovarian syndrome; PPI: protein-protein interaction; RMA: Robust Multi-Array Average; TF: transcription factor. PMID:27341345

  1. Molecular Ecological Insights into Neotropical Bird–Tick Interactions

    Science.gov (United States)

    Esser, Helen J.; Loaiza, Jose R.; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds’ role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually–sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical–Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically–identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly–discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the

  2. Climate change induced transformations of agricultural systems: insights from a global model

    International Nuclear Information System (INIS)

    Climate change might impact crop yields considerably and anticipated transformations of agricultural systems are needed in the coming decades to sustain affordable food provision. However, decision-making on transformational shifts in agricultural systems is plagued by uncertainties concerning the nature and geography of climate change, its impacts, and adequate responses. Locking agricultural systems into inadequate transformations costly to adjust is a significant risk and this acts as an incentive to delay action. It is crucial to gain insight into how much transformation is required from agricultural systems, how robust such strategies are, and how we can defuse the associated challenge for decision-making. While implementing a definition related to large changes in resource use into a global impact assessment modelling framework, we find transformational adaptations to be required of agricultural systems in most regions by 2050s in order to cope with climate change. However, these transformations widely differ across climate change scenarios: uncertainties in large-scale development of irrigation span in all continents from 2030s on, and affect two-thirds of regions by 2050s. Meanwhile, significant but uncertain reduction of major agricultural areas affects the Northern Hemisphere’s temperate latitudes, while increases to non-agricultural zones could be large but uncertain in one-third of regions. To help reducing the associated challenge for decision-making, we propose a methodology exploring which, when, where and why transformations could be required and uncertain, by means of scenario analysis. (letter)

  3. New insights into the properties of contrail cirrus and their impact on climate from airborne experiments

    Science.gov (United States)

    Voigt, Christiane; Schumann, Ulrich; Minikin, Andreas; Schlager, Hans; Anderson, Bruce

    2016-04-01

    Current growth rates in aviation demand a profound scientific data base of contrail cirrus properties in order to accurately assess their climate impact. In particular, the differentiation of contrail cirrus in natural cirrus fields is challenging. Direct observations of contrail cirrus throughout their life cycle are scarce and therefore limit our understanding of the climate effects from contrail cirrus. Here, we give new insights into the growth, life-cycle and climate impact from contrail cirrus based on results from suite of aircraft experiments. NASA's ACCESSII mission focused on the detection of aircraft emissions and initial contrail stages. Nascent contrails were detected at cruise altitudes at 100 m distance to the engine exit. Contrail growth to 10-min contrail age was investigated during DLR's CONCERT campaigns. Finally, the objective of the ML-CIRRUS experiment was to study the life cycle and climate impact of contrail cirrus. The contrail measurements are related to previous observations and discussed in the context of recent developments in contrail modeling. Highlights include the quantification of the effects of aircraft type on contrail microphysics, the analysis of ice particle shapes and the quantitative distinction of contrail cirrus and natural cirrus.

  4. Polymer Nanocomposites: Insights from Theory and Molecular Simulations

    Science.gov (United States)

    Pani, Rakhee

    Advantages of polymer nanocomposites have attracted great industrial attention due to their multifunctionality and innovative technological properties. Addition of small amount of nanoparticle (nanospheres, nanotubes, nanorods, nanoplatelets, or sheets) to polymer matrix cause dramatic improvement in structural and functional properties, which is difficult to attain from those of individual components. The interaction between polymer and nanoparticle create bulk materials dominated by solid state physics at the nanoscale. Furthermore, morphology of nanocomposites depends on structural arrangements of nanoparticles. Thus, for achievement of optimized functionality like electrical, optical, mechanical and thermal properties control over the dispersion of the nanoparticle is essential. However, properties of polymer nanocomposites depend on morphology control and nature of interfacial interactions. In order to control the morphology it is necessary to understand how the processing conditions, shape and size of nanoparticle influence the structure of composite. Molecular simulations can help us to predict the parameters that control the structural changes and we could design polymer nanocomposite entailing their end-use. In this work, we addressed the following research questions: (1) the dependence of nanoparticle ligand corona structure on solvent quality and (2) the role of interfacial energy and interactions on the dispersion of molecules and nanoparticles. Specifically, this research assessed the effect of solvent interactions on the structure of nanoparticles on the example of redox core encapsulating dendrimer and ligand functionalized gold nanoparticles, role of chemical interaction on solubility of glucose in ionic liquids, diffusion of fullerene nanoparticles in polymer matrix and influence of solubility parameters on the compatibility of gold nanoparticles with diblock copolymers. Computational methods allow quantifying the structure and flexibility of the

  5. A Social Identity Analysis of Climate Change and Environmental Attitudes and Behaviors: Insights and Opportunities.

    Science.gov (United States)

    Fielding, Kelly S; Hornsey, Matthew J

    2016-01-01

    Environmental challenges are often marked by an intergroup dimension. Political conservatives and progressives are divided on their beliefs about climate change, farmers come into conflict with scientists and environmentalists over water allocation or species protection, and communities oppose big business and mining companies that threaten their local environment. These intergroup tensions are reminders of the powerful influence social contexts and group memberships can have on attitudes, beliefs, and actions relating to climate change and the environment more broadly. In this paper, we use social identity theory to help describe and explain these processes. We review literature showing, how conceiving of oneself in terms of a particular social identity influences our environmental attitudes and behaviors, how relations between groups can impact on environmental outcomes, and how the content of social identities can direct group members to act in more or less pro-environmental ways. We discuss the similarities and differences between the social identity approach to these phenomena and related theories, such as cultural cognition theory, the theory of planned behavior, and value-belief-norm theory. Importantly, we also advance social-identity based strategies to foster more sustainable environmental attitudes and behaviors. Although this theoretical approach can provide important insights and potential solutions, more research is needed to build the empirical base, especially in relation to testing social identity solutions. PMID:26903924

  6. A Social Identity Analysis of Climate Change and Environmental Attitudes and Behaviors: Insights and Opportunities

    Science.gov (United States)

    Fielding, Kelly S.; Hornsey, Matthew J.

    2016-01-01

    Environmental challenges are often marked by an intergroup dimension. Political conservatives and progressives are divided on their beliefs about climate change, farmers come into conflict with scientists and environmentalists over water allocation or species protection, and communities oppose big business and mining companies that threaten their local environment. These intergroup tensions are reminders of the powerful influence social contexts and group memberships can have on attitudes, beliefs, and actions relating to climate change and the environment more broadly. In this paper, we use social identity theory to help describe and explain these processes. We review literature showing, how conceiving of oneself in terms of a particular social identity influences our environmental attitudes and behaviors, how relations between groups can impact on environmental outcomes, and how the content of social identities can direct group members to act in more or less pro-environmental ways. We discuss the similarities and differences between the social identity approach to these phenomena and related theories, such as cultural cognition theory, the theory of planned behavior, and value-belief-norm theory. Importantly, we also advance social-identity based strategies to foster more sustainable environmental attitudes and behaviors. Although this theoretical approach can provide important insights and potential solutions, more research is needed to build the empirical base, especially in relation to testing social identity solutions. PMID:26903924

  7. Molecular genetics and genomics generate new insights into invertebrate pest invasions

    OpenAIRE

    Kirk, Heather; Dorn, Silvia; Mazzi, Dominique

    2013-01-01

    Invertebrate pest invasions and outbreaks are associated with high social, economic, and ecological costs, and their significance will intensify with an increasing pressure on agricultural productivity as a result of human population growth and climate change. New molecular genetic and genomic techniques are available and accessible, but have been grossly underutilized in studies of invertebrate pest invasions, despite that they are useful tools for applied pest management and for understandi...

  8. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    International Nuclear Information System (INIS)

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum

  9. Application of molecular simulations: Insight into liquid bridging and jetting phenomena

    Directory of Open Access Journals (Sweden)

    I. Nezbeda

    2015-03-01

    Full Text Available Molecular dynamics simulations have been performed on pure liquid water, aqueous solutions of sodium chloride, and polymer solutions exposed to a strong external electric field with the goal to gain molecular insight into the structural response to the field. Several simulation methodologies have been used to elucidate the molecular mechanisms of the processes leading to the formation of liquid bridges and jets (in the production of nanofibers. It is shown that in the established nanoscale structures, the molecules form a chain with their dipole moments oriented parallel to the applied field throughout the entire sample volume. The presence of ions may disturb this structure leading to its ultimate disintegration into droplets; the concentration dependence of the threshold field required to stabilize a liquid column has been determined. Conformational changes of the polymer in the jetting process have also been observed.

  10. Sustainable management for rangelands in a variable climate: evidence and insights from northern Australia.

    Science.gov (United States)

    O'Reagain, P J; Scanlan, J C

    2013-03-01

    Inter-annual rainfall variability is a major challenge to sustainable and productive grazing management on rangelands. In Australia, rainfall variability is particularly pronounced and failure to manage appropriately leads to major economic loss and environmental degradation. Recommended strategies to manage sustainably include stocking at long-term carrying capacity (LTCC) or varying stock numbers with forage availability. These strategies are conceptually simple but difficult to implement, given the scale and spatial heterogeneity of grazing properties and the uncertainty of the climate. This paper presents learnings and insights from northern Australia gained from research and modelling on managing for rainfall variability. A method to objectively estimate LTCC in large, heterogeneous paddocks is discussed, and guidelines and tools to tactically adjust stocking rates are presented. The possible use of seasonal climate forecasts (SCF) in management is also considered. Results from a 13-year grazing trial in Queensland show that constant stocking at LTCC was far more profitable and largely maintained land condition compared with heavy stocking (HSR). Variable stocking (VAR) with or without the use of SCF was marginally more profitable, but income variability was greater and land condition poorer than constant stocking at LTCC. Two commercial scale trials in the Northern Territory with breeder cows highlighted the practical difficulties of variable stocking and provided evidence that heavier pasture utilisation rates depress reproductive performance. Simulation modelling across a range of regions in northern Australia also showed a decline in resource condition and profitability under heavy stocking rates. Modelling further suggested that the relative value of variable v. constant stocking depends on stocking rate and land condition. Importantly, variable stocking may possibly allow slightly higher stocking rates without pasture degradation. Enterprise

  11. Alluvial fan response to climatic change: Insights from numerical modeling (Invited)

    Science.gov (United States)

    Pelletier, J. D.

    2009-12-01

    Alluvial fans in the western U.S. exhibit a regionally correlative sequence of Plio-Quaternary deposits. Cosmogenic and U-series dating has greatly improved the age control on these deposits and their associated terraces and generally strengthened the case for aggradation during humid-to-arid transitions. Still, the linkages between climate change, upland basin response, and alluvial fan response are not well constrained. Fans may fill and cut as a result of autogenetic processes/internal adjustments, changes in regional temperature (which controls snowmelt-induced flooding), changes in the frequency-size distribution of rainfall events, and/or changes in upslope vegetation. Here I describe the results of a numerical modeling study designed to better constrain the relationships between different end-member forcing mechanisms and the geologic record of alluvial fan deposits and terraces. The model solves the evolution of the fan topography using Exner's equation (conservation of mass) coupled with a nonlinear, threshold-controlled transport relation for sand and gravel. Bank retreat is modeled using an advection equation with a rate proportional to bank shear stress. I begin by considering the building of a fan under conditions of constant water and sediment supply. This simple system exhibits all of the complexity of fans developed under experimental conditions, and it provides insights into the mechanisms that control avulsions and it provides a baseline estimate for the within-fan relief that can result from autogenetic processes. Relationships between the magnitude and period of variations in the sediment-to-water ratio and the geomorphic response of fans are then discussed. I also consider the response of a coupled drainage basin-fan system to changes in climate, including the hydrologic and vegetation response of upland hillslopes. Fans can aggrade or incise in response to the same climatic event depending on the relief of the upstream drainage basin, which

  12. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    International Nuclear Information System (INIS)

    Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder

  13. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    Energy Technology Data Exchange (ETDEWEB)

    Sidhu, Navdeep S. [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Schreiber, Kathrin [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany); Pröpper, Kevin [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Becker, Stefan [Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen (Germany); Usón, Isabel [Instituto de Biologia Molecular de Barcelona (IBMB–CSIC), Barcelona Science Park, Baldiri Reixach 15, 08028 Barcelona (Spain); Institucio Catalana de Recerca i Estudis Avancats (ICREA), (Spain); Sheldrick, George M. [University of Göttingen, Tammannstrasse 4, 37077 Göttingen (Germany); Gärtner, Jutta; Krätzner, Ralph, E-mail: rkraetz@gwdg.de; Steinfeld, Robert, E-mail: rkraetz@gwdg.de [University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen (Germany)

    2014-05-01

    Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.

  14. Molecular self-assembly on two-dimensional atomic crystals: insights from molecular dynamics simulations.

    Science.gov (United States)

    Zhao, Yinghe; Wu, Qisheng; Chen, Qian; Wang, Jinlan

    2015-11-19

    van der Waals (vdW) epitaxy of ultrathin organic films on two-dimensional (2D) atomic crystals has become a sovereign area because of their unique advantages in organic electronic devices. However, the dynamic mechanism of the self-assembly remains elusive. Here, we visualize the nanoscale self-assembly of organic molecules on graphene and boron nitride monolayer from a disordered state to a 2D lattice via molecular dynamics simulation for the first time. It is revealed that the assembly toward 2D ordered structures is essentially the minimization of the molecule-molecule interaction, that is, the vdW interaction in nonpolar systems and the vdW and Coulomb interactions in polar systems that are the decisive factors for the formation of the 2D ordering. The role of the substrate is mainly governing the array orientation of the adsorbates. The mechanisms unveiled here are generally applicable to a broad class of organic thin films via vdW epitaxy. PMID:26523464

  15. Insight into the molecular switch mechanism of human Rab5a from molecular dynamics simulations

    International Nuclear Information System (INIS)

    Rab5a is currently a most interesting target because it is responsible for regulating the early endosome fusion in endocytosis and possibly the budding process. We utilized longtime-scale molecular dynamics simulations to investigate the internal motion of the wild-type Rab5a and its A30P mutant. It was observed that, after binding with GTP, the global flexibility of the two proteins is increasing, while the local flexibility in their sensitive sites (P-loop, switch I and II regions) is decreasing. Also, the mutation of Ala30 to Pro30 can cause notable flexibility variations in the sensitive sites. However, this kind of variations is dramatically reduced after binding with GTP. Such a remarkable feature is mainly caused by the water network rearrangements in the sensitive sites. These findings might be of use for revealing the profound mechanism of the displacements of Rab5a switch regions, as well as the mechanism of the GDP dissociation and GTP association.

  16. Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

    Science.gov (United States)

    Sidhu, Navdeep S.; Schreiber, Kathrin; Pröpper, Kevin; Becker, Stefan; Usón, Isabel; Sheldrick, George M.; Gärtner, Jutta; Krätzner, Ralph; Steinfeld, Robert

    2014-01-01

    Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However, the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder. PMID:24816101

  17. Estimating evapotranspiration under warmer climates: Insights from a semiarid riparian system

    Science.gov (United States)

    This paper presents an approach to quantify evapotranspiration under changing climates, using field observations, theoretical evaporation models and meteorological predictions from global climate models. We analyzed evaporation and meteorological data from three riparian sites located in a semiarid ...

  18. Crystal Structures of Human and Staphylococcus aureus Pyruvate Carboxylase and Molecular Insights into the Carboxyltransfer Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Xiang,S.; Tong, L.

    2008-01-01

    Pyruvate carboxylase (PC) catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes. PC contains the biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) domains. We report here the crystal structures at 2.8-Angstroms resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC. A conserved tetrameric association is observed for both enzymes, and our structural and mutagenesis studies reveal a previously uncharacterized domain, the PC tetramerization (PT) domain, which is important for oligomerization. A BCCP domain is located in the active site of the CT domain, providing the first molecular insights into how biotin participates in the carboxyltransfer reaction. There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli.

  19. Human metapneumovirus: insights from a ten-year molecular and epidemiological analysis in Germany.

    Directory of Open Access Journals (Sweden)

    Janine Reiche

    Full Text Available Human metapneumovirus (HMPV is a cause of respiratory tract illness at all ages. In this study the epidemiological and molecular diversity among patients of different ages was investigated. Between 2000-2001 and 2009-2010, HMPV was detected in 3% (138/4,549 of samples from outpatients with influenza-like illness with a new, sensitive real-time RT-PCR assay. Several hundred (797 clinical specimens from hospitalized children below the age of 4 years with acute respiratory illness were investigated and HMPV was detected in 11.9% of them. Investigation of outpatients revealed that HMPV infections occurred in individuals of all ages but were most prevalent in children (0-4 years and the elderly (>60 years. The most present clinical features of HMPV infections were cough, bronchitis, fever/shivers and pneumonia. About two thirds of HMPV-positive samples were detected in February and March throughout the study period. Molecular characterization of HMPV revealed a complex cyclic pattern of group dominance where HMPV subgroup A and B viruses predominated in general for three consecutive seasons. German HMPV represented all genetic lineages including A1, A2, B1, B2, sub-clusters A2a and A2b. For Germany, not only time-dependent circulation of lineages and sub-clusters was observed but also co-circulation of two or three predominant lineages. Two newly emerging amino acid substitutions (positions 223 and 280 of lineage B2 were detected in seven German HMPV sequences. Our study gives new insights into the molecular epidemiology of HMPV in in- and outpatients over a time period of 10 years for the first time. It is one of only few long-term surveillance studies in Europe, and allows comparative molecular analyses of HMPV circulating worldwide.

  20. A multi-layered governance framework for incorporating social science insights into adapting to the health impacts of climate change

    Directory of Open Access Journals (Sweden)

    Kathryn J. Bowen

    2013-09-01

    Full Text Available Background: Addressing climate change and its associated effects is a multi-dimensional and ongoing challenge. This includes recognizing that climate change will affect the health and wellbeing of all populations over short and longer terms, albeit in varied ways and intensities. That recognition has drawn attention to the need to take adaptive actions to lessen adverse impacts over the next few decades from unavoidable climate change, particularly in developing country settings. A range of sectors is responsible for appropriate adaptive policies and measures to address the health risks of climate change, including health services, water and sanitation, trade, agriculture, disaster management, and development. Objectives: To broaden the framing of governance and decision-making processes by using innovative methods and assessments to illustrate the multi-sectoral nature of health-related adaptation to climate change. This is a shift from sector-specific to multi-level systems encompassing sectors and actors, across temporal and spatial scales. Design: A review and synthesis of the current knowledge in the areas of health and climate change adaptation governance and decision-making processes. Results: A novel framework is presented that incorporates social science insights into the formulation and implementation of adaptation activities and policies to lessen the health risks posed by climate change. Conclusion: Clarification of the roles that different sectors, organizations, and individuals occupy in relation to the development of health-related adaptation strategies will facilitate the inclusion of health and wellbeing within multi-sector adaptation policies, thereby strengthening the overall set of responses to minimize the adverse health effects of climate change.

  1. Molecular Insights into Aqueous NaCl Electrolytes Confined within Vertically-oriented Graphenes.

    Science.gov (United States)

    Bo, Zheng; Yang, Huachao; Zhang, Shuo; Yang, Jinyuan; Yan, Jianhua; Cen, Kefa

    2015-01-01

    Vertically-oriented graphenes (VGs) are promising active materials for electric double layer capacitors (EDLCs) due to their unique morphological and structural features. This study, for the first time, reports the molecular dynamics (MD) simulations on aqueous NaCl electrolytes confined within VG channels with different surface charge densities and channel widths. Simulation results show that the accessibility of ions and the structure of EDLCs are determined by the ion type/size, surface charging, and VG channel width. For relatively narrow VG channels with the same width, the threshold charge density (to compensate the energy penalty for shedding hydration shell) and the dehydration rate of Cl(-) ions are larger than those of Na(+) ions. To achieve the highest ion concentration coefficient, the effective VG channel width should be between the crystal and hydration diameters of the ions. The results are further quantified and elucidated by calculating the electrolyte density profiles. The molecular insights obtained in the current work are useful in guiding the design and fabrication of VGs for advancing their EDLC applications. PMID:26424365

  2. Molecular and evolutionary insights into the structural organization of cation chloride cotransporters

    Directory of Open Access Journals (Sweden)

    Anna-Maria Hartmann

    2015-01-01

    Full Text Available Cation chloride cotransporters (CCC play an essential role for neuronal chloride homeostasis. KCC2 is the principal Cl--extruder, whereas NKCC1 is the major Cl--uptake mechanism in many neurons. As a consequence, the action of the inhibitory neurotransmitters GABA and glycine strongly depend on the activity of these two transporters. Knowledge of the mechanisms involved in ion transport and regulation is thus of great importance to better understand normal and disturbed brain function. Although no overall 3-dimensional crystal structures are yet available, recent molecular and phylogenetic studies and modeling have provided new and exciting insights into structure-function relationships of cation chloride cotransporters. Here, we will summarize our current knowledge of the gross structural organization of the proteins, their functional domains, ion binding and translocation sites, and the established role of individual amino acids. A major focus will be laid on the delineation of shared and distinct organizational principles between KCC2 and NKCC1. Exploiting the richness of recently generated genome data across the tree of life, we will also explore the molecular evolution of these features.

  3. Communicating Climate Change in the Agricultural Sector: Insights from Surveys and Interviews with Agricultural Advisors in the Midwestern United States

    Science.gov (United States)

    Prokopy, L. S.; Carlton, S.; Dunn, M.

    2014-12-01

    Understanding U.S. agricultural stakeholder views about the existence of climate change and what influences these views is central to developing communication in support of adaptation and mitigation. It has been postulated in the literature that extreme weather events can shape people's climate change beliefs and adaptation attitudes. In this presentation, we use data from pre- and post-extreme event surveys and interviews to examine the effects of the 2012 Midwestern US drought on agricultural advisors' climate change beliefs, adaptation attitudes, and risk perceptions. We found that neither climate change beliefs nor attitudes toward adaptation changed significantly as a result of the drought. Risk perceptions did change, however, with advisors becoming more concerned about risks from drought and pests and less concerned about risks related to flooding and ponding. Qualitative interviews revealed that while advisors readily accept the occurrence of extreme weather as a risk, the irregularity and unpredictability of extreme events for specific localities limits day-to-day consideration in respect to prescribed management advice. Instead, advisors' attention is directed towards planning for short-term changes encompassing weather, pests, and the market, as well as planning for long-term trends related to water availability. These findings provide important insights for communicating climate change in this critical sector while illustrating the importance of social science research in planning and executing communication campaigns.

  4. An insight into the isolation, enumeration and molecular detection of Listeria monocytogenes in food

    Directory of Open Access Journals (Sweden)

    Jodi Woan-Fei Law

    2015-11-01

    Full Text Available Listeria monocytogenes, a foodborne pathogen that can cause listeriosis through the consumption of food contaminated with this pathogen. The ability of L. monocytogenes to survive in extreme conditions and cause food contaminations have become a major concern. Hence, routine microbiological food testing is necessary to prevent food contamination and outbreaks of foodborne illness. This review provides insight into the methods for cultural detection, enumeration and molecular identification of L. monocytogenes in various food samples. There are a number of enrichment and plating media that can be used for the isolation of L. monocytogenes from food samples. Enrichment media such as buffered Listeria Enrichment Broth (BLEB, Fraser broth and University of Vermont Medium (UVM Listeria enrichment broth are recommended by regulatory agencies such as FDA-BAM, USDA-FSIS and ISO. Many plating media are available for the isolation of L. monocytogenes, for instance, PALCAM, Oxford and other chromogenic media. Besides, reference methods like FDA-BAM, ISO 11290 method and USDA-FSIS method are usually applied for the cultural detection or enumeration of L. monocytogenes. MPN technique is applied for the enumeration of L. monocytogenes in the case of low level contamination. Molecular methods including polymerase chain reaction (PCR, multiplex polymerase chain reaction (mPCR, real-time/quantitative polymerase chain reaction (qPCR, nucleic acid sequence-based amplification (NASBA, loop-mediated isothermal amplification (LAMP, DNA microarray and Next Generation Sequencing (NGS technology for the detection and identification of L. monocytogenes are discussed in this review. Overall, molecular methods are rapid, sensitive, specific, time- and labour-saving. In future, there are chances for the development of new techniques for the detection and identification of foodborne with improved features.

  5. Molecular fossils in modern genomes provide physiological and geochemical insights to the ancient earth (Invited)

    Science.gov (United States)

    Dupont, C.; Caetano-Anolles, G.

    2010-12-01

    The genomes of extant organisms are ultimately derived from ancient life, thus theoretically contain insight to ancient physiology, ecology, and environments. In particular, metalloenzymes may be particularly insightful. The fundamental chemistry of trace elements dictates the molecular speciation and reactivity both within cells and the environment at large. Using protein structure and comparative genomics, we elucidate several major influences this chemistry has had upon biology. All of life exhibits the same proteome size-dependent scaling for the number of metal-binding proteins within a proteome. This fundamental evolutionary constant shows that the selection of one element occurs at the exclusion of another, with the eschewal of Fe for Zn and Ca being a defining feature of eukaryotic pro- teomes. Early life lacked both the structures required to control intracellular metal concentrations and the metal-binding proteins that catalyze electron transport and redox transformations. The development of protein structures for metal homeostasis coincided with the emergence of metal-specific structures, which predomi- nantly bound metals abundant in the Archean ocean. Potentially, this promoted the diversification of emerging lineages of Archaea and Bacteria through the establishment of biogeochemical cycles. In contrast, structures binding Cu and Zn evolved much later, pro- viding further evidence that environmental availability influenced the selection of the elements. The late evolving Zn-binding proteins are fundamental to eukaryotic cellular biology, and Zn bioavailabil- ity may have been a limiting factor in eukaryotic evolution. The results presented here provide an evolutionary timeline based on genomic characteristics, and key hypotheses can be tested by alternative geochemical methods.

  6. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    Energy Technology Data Exchange (ETDEWEB)

    Wyrick, Jonathan; Bartels, Ludwig, E-mail: ludwig.bartels@ucr.edu [Pierce Hall, University of California-Riverside, Riverside, California 92521 (United States); Einstein, T. L. [Department of Physics and Condensed Matter Theory Center, University of Maryland, College Park, Maryland 20742-4111 (United States)

    2015-03-14

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species’ diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

  7. Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

    International Nuclear Information System (INIS)

    We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species’ diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system

  8. Migration out of 1930s Rural Eastern Oklahoma: Insights for Climate Change Research

    Science.gov (United States)

    McLeman, Robert

    2006-01-01

    The question of how communities and individuals adapt to changing climatic conditions is of pressing concern to scientists and policymakers in light of the growing evidence that human activity has modified the Earth's climate. A number of authors have suggested that widespread changes in human settlement and migration patterns may occur in…

  9. Stimuli for municipal responses to climate adaptation: insights from Philadelphia – an early adapter

    NARCIS (Netherlands)

    Uittenbroek, C.J.; Janssen-Jansen, Leonie; Runhaar, H.A.C.

    2016-01-01

    An in-depth understanding of these stimuli is currently lacking in literature as most research has focussed on overcoming barriers to climate adaptation. The aim of this paper is to identify stimuli for municipal responses to climate adaptation and examine how they influence the governance approach

  10. Climate Change Adaptation Strategy in the Food Industry—Insights from Product Carbon and Water Footprints

    Directory of Open Access Journals (Sweden)

    Bradley Ridoutt

    2016-05-01

    Full Text Available Climate change adds an additional layer of complexity that needs to be considered in business strategy. For firms in the food industry, many of the important climate impacts are not directly related to food processing so a value chain approach to adaptation is recommended. However, there is a general lack of operational tools to support this. In this study, carbon and water footprints were conducted at a low-precision screening level in three case studies in Australia: Smith’s potato chips, OneHarvest Calypso™ mango and selected Treasury Wine Estates products. The approach was cost-effective when compared to high-definition studies intended to support environmental labels and declarations, yet provided useful identification of physical, financial, regulatory and reputational hotspots related to climate change. A combination of diagnostic footprinting, downscaled climate projection and semi-quantitative value chain analysis is proposed as a practical and relevant toolkit to inform climate adaptation strategies.

  11. Informing energy and climate policies using energy systems models insights from scenario analysis increasing the evidence base

    CERN Document Server

    Giannakidis, George; Ó Gallachóir, Brian; Tosato, GianCarlo

    2015-01-01

    This book highlights how energy-system models are used to underpin and support energy and climate mitigation policy decisions at national, multi-country and global levels. It brings together, for the first time in one volume, a range of methodological approaches and case studies of good modeling practice on a national and international scale from the IEA-ETSAP energy technology initiative. It provides insights for the reader into the rich and varied applications of energy-system models and the underlying methodologies and policy questions they can address. The book demonstrates how these mode

  12. Can Payments for Ecosystem Services Contribute to Adaptation to Climate Change? Insights from a Watershed in Kenya

    Directory of Open Access Journals (Sweden)

    Isabel van de Sand

    2014-03-01

    Full Text Available Climate change presents new challenges for the management of social-ecological systems and the ecosystem services they provide. Although the instrument of payments for ecosystem services (PES has emerged as a promising tool to safeguard or enhance the provision of ecosystem services (ES, little attention has been paid to the potential role of PES in climate change adaptation. As an external stressor climate change has an impact on the social-ecological system in which PES takes place, including the various actors taking part in the PES scheme. Following a short description of the conceptual link between PES and adaptation to climate change, we provide practical insights into the relationship between PES and adaptation to climate change by presenting results from a case study of a rural watershed in Kenya. Drawing upon the results of a participatory vulnerability assessment among potential ecosystem service providers in Sasumua watershed north of Nairobi, we show that PES can play a role in enhancing adaptation to climate change by influencing certain elements of adaptive capacity and incentivizing adaptation measures. In addition, trade-offs and synergies between proposed measures under PES and adaptation to climate change are identified. Results show that although it may not be possible to establish PES schemes based on water utilities as the sole source of financing, embedding PES in a wider adaptation framework creates an opportunity for the development of watershed PES schemes in Africa and ensures their sustainability. We conclude that there is a need to embed PES in a wider institutional framework and that extra financial resources are needed to foster greater integration between PES and adaptation to climate change. This can be achieved through scaling up PES by bringing in other buyers and additional ecosystem services. PES can achieve important coadaptation benefits, but for more effective adaptation outcomes it needs to be combined

  13. New Insights into the Molecular Basis of Kidney Governing Bone Theory

    Institute of Scientific and Technical Information of China (English)

    Dong-feng Zhao; Yong-jian Zhao; Cheng-long Wang; Yan-ping Yang; Yong-jun Wang

    2015-01-01

    Kidney governing bone theory plays an important role in treating bone metabolic disease such as osteoporosis, and many tonifying kidney prescriptions/herbs are widely used in Traditional Chinese Medicine (TCM). However, the exact biological basis of kidney governing bone theory in the context of new advances in biology is still not fully established. In this paper, the content of kidney governing bone theory in biology has been fully demonstrated from different aspects. We first propose that bone and kidney mutually affect each other in pathology and physiology, particularly through homeostasis of calcium, phosphorus and fibroblast growth factor-23(FGF-23). Next, we identify that tonifying kidney prescriptions/herbs exert bone protective effects, thus treating osteoporosis by regulating bone formation and bone resorption. Furthermore, the exact molecular mechanisms of tonifying kidney prescriptions, herbs and their effective components in treating osteoporosis have been systematically reviewed. Finally, we come into the conclusion that kidney regulating bone mineral homeostasis, bone protective effects of tonifying kidney herbs and regulatory effects on bone homeostasis are all the manifestations of kidney governing bone theory. Therefore, the new insights into kidney governing bone theory in biology will promote the development of clinical practices, and drugs discovery in treating osteoporosis.

  14. Prolactin and teleost ionocytes: new insights into cellular and molecular targets of prolactin in vertebrate epithelia

    Science.gov (United States)

    Breves, Jason P.; McCormick, Stephen D.; Karlstrom, Rolf O.

    2014-01-01

    The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that a conserved function for prolactin across vertebrates is the regulation of ion and water transport in a variety of tissues including those responsible for whole-organism ion homeostasis. In teleost fishes, prolactin was identified as the “freshwater-adapting hormone”, promoting ion-conserving and water-secreting processes by acting on the gill, kidney, gut and urinary bladder. In mammals, prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia, with dysfunction linked to hypogonadism, infertility, and metabolic disorders. Until recently, our understanding of the cellular mechanisms of prolactin action in fishes has been hampered by a paucity of molecular tools to define and study ionocytes, specialized cells that control active ion transport across branchial and epidermal epithelia. Here we review work in teleost models indicating that prolactin regulates ion balance through action on ion transporters, tight-junction proteins, and water channels in ionocytes, and discuss recent advances in our understanding of ionocyte function in the genetically and embryonically accessible zebrafish (Danio rerio). Given the high degree of evolutionary conservation in endocrine and osmoregulatory systems, these studies in teleost models are contributing novel mechanistic insight into how prolactin participates in the development, function, and dysfunction of osmoregulatory systems across the vertebrate lineage.

  15. UV Photodissociation of Proline-containing Peptide Ions: Insights from Molecular Dynamics

    Science.gov (United States)

    Girod, Marion; Sanader, Zeljka; Vojkovic, Marin; Antoine, Rodolphe; MacAleese, Luke; Lemoine, Jérôme; Bonacic-Koutecky, Vlasta; Dugourd, Philippe

    2015-03-01

    UV photodissociation of proline-containing peptide ions leads to unusual product ions. In this paper, we report laser-induced dissociation of a series of proline-containing peptides at 213 nm. We observe specific fragmentation pathways corresponding to the formation of (y-2), (a + 2) and (b + 2) fragment ions. This was not observed at 266 nm or for peptides which do not contain proline residues. In order to obtain insights into the fragmentation dynamics at 213 nm, a small peptide (RPK for arginine-proline-lysine) was studied both theoretically and experimentally. Calculations of absorption spectra and non-adiabatic molecular dynamics (MD) were made. Second and third excited singlet states, S2 and S3, lie close to 213 nm. Non-adiabatic MD simulation starting from S2 and S3 shows that these transitions are followed by C-C and C-N bond activation close to the proline residue. After this first relaxation step, consecutive rearrangements and proton transfers are required to produce unusual (y-2), (a + 2) and (b + 2) fragment ions. These fragmentation mechanisms were confirmed by H/D exchange experiments.

  16. Atractaspis aterrima toxins: the first insight into the molecular evolution of venom in side-stabbers.

    Science.gov (United States)

    Terrat, Yves; Sunagar, Kartik; Fry, Bryan G; Jackson, Timothy N W; Scheib, Holger; Fourmy, Rudy; Verdenaud, Marion; Blanchet, Guillaume; Antunes, Agostinho; Ducancel, Frederic

    2013-11-01

    Although snake venoms have been the subject of intense research, primarily because of their tremendous potential as a bioresource for design and development of therapeutic compounds, some specific groups of snakes, such as the genus Atractaspis, have been completely neglected. To date only limited number of toxins, such as sarafotoxins have been well characterized from this lineage. In order to investigate the molecular diversity of venom from Atractaspis aterrima-the slender burrowing asp, we utilized a high-throughput transcriptomic approach completed with an original bioinformatics analysis pipeline. Surprisingly, we found that Sarafotoxins do not constitute the major ingredient of the transcriptomic cocktail; rather a large number of previously well-characterized snake venom-components were identified. Notably, we recovered a large diversity of three-finger toxins (3FTxs), which were found to have evolved under the significant influence of positive selection. From the normalized and non-normalized transcriptome libraries, we were able to evaluate the relative abundance of the different toxin groups, uncover rare transcripts, and gain new insight into the transcriptomic machinery. In addition to previously characterized toxin families, we were able to detect numerous highly-transcribed compounds that possess all the key features of venom-components and may constitute new classes of toxins. PMID:24169588

  17. New insights on Arctic Quaternary climate variability from palaeo-records and numerical modelling

    OpenAIRE

    Jakobsson, Martin; Long, A; Ingólfsson, Ó.; Kjaer, K. H.; Spielhagen, R. F.

    2010-01-01

    Terrestrial and marine geological archives in the Arctic contain information on environmental change through Quaternary interglacial–glacial cycles. The Arctic Palaeoclimate and its Extremes (APEX) scientific network aims to better understand the magnitude and frequency of past Arctic climate variability, with focus on the “extreme” versus the “normal” conditions of the climate system. One important motivation for studying the amplitude of past natural environmental changes in the Arctic is t...

  18. Global Deliberative Democracy and Climate Change: Insights from World Wide Views on Global Warming in Australia

    OpenAIRE

    Chris Riedy; Jade Herriman

    2011-01-01

    On 26 September 2009, approximately 4,000 citizens in 38 countries participated in World Wide Views on Global Warming (WWViews). WWViews was an ambitious first attempt to convene a deliberative mini-public at a global scale, giving people from around the world an opportunity to deliberate on international climate policy and to make recommendations to the decision-makers meeting at the United Nations Climate Change Conference in Copenhagen (COP-15) in December 2009. In this paper, we examine t...

  19. The Psychology of Climate Change Communication - Insights from the Center for Research on Environmental Decisions (CRED) (Invited)

    Science.gov (United States)

    Marx, S.

    2010-12-01

    social goals in favor or self interest; early involvement of stakeholders through participatory processes can help identify key concerns and information needs which can then be addressed in a tailored approach; taking advantage of default effects can make it easier for people to choose environmentally and socially beneficial options. Using research into the reactions of groups as disparate as African farmers and conservative U.S. voters, we offer insights on how scientists, educators, journalists and others can effectively connect with wider audiences. The communication principles presented in this talk can be applied beyond climate change and to science communication in general.

  20. Parasite zoonoses and climate change: molecular tools for tracking shifting boundaries.

    Science.gov (United States)

    Polley, Lydden; Thompson, R C Andrew

    2009-06-01

    For human, domestic animal and wildlife health, key effects of directional climate change include the risk of the altered occurrence of infectious diseases. Many parasite zoonoses have high potential for vulnerability to the new climate, in part because their free-living life-cycle stages and ectothermic hosts are directly exposed to climatic conditions. For these zoonoses, climate change can shift boundaries for ecosystem components and processes integral to parasite transmission and persistence, and these shifts can impact host health. Vulnerable boundaries include those for spatial distributions, host-parasite assemblages, demographic rates, life-cycle phenologies, associations within ecosystems, virulence, and patterns of infection and disease. This review describes these boundary shifts and how molecular techniques can be applied to defining the new boundaries. PMID:19428303

  1. Topographic Evolution and Climate Aridification during Continental Collision: Insights from Computer Simulations

    Science.gov (United States)

    2015-01-01

    How do the feedbacks between tectonics, sediment transport and climate work to shape the topographic evolution of the Earth? This question has been widely addressed via numerical models constrained with thermochronological and geomorphological data at scales ranging from local to orogenic. Here we present a novel numerical model that aims at reproducing the interaction between these processes at the continental scale. For this purpose, we combine in a single computer program: 1) a thin-sheet viscous model of continental deformation; 2) a stream-power surface-transport approach; 3) flexural isostasy allowing for the formation of large sedimentary foreland basins; and 4) an orographic precipitation model that reproduces basic climatic effects such as continentality and rain shadow. We quantify the feedbacks between these processes in a synthetic scenario inspired by the India-Asia collision and the growth of the Tibetan Plateau. We identify a feedback between erosion and crustal thickening leading locally to a basins and ranges seems insensitive to climatic factors, despite these do have important, sometimes counterintuitive effects on the amount of sediments trapped within the continent. The dry climatic conditions that naturally develop in the interior of the continent, for example, trigger large intra-continental sediment trapping at basins similar to the Tarim Basin because they determine its endorheic/exorheic drainage. These complex climatic-drainage-tectonic interactions make the development of steady-state topography at the continental scale unlikely. PMID:26244662

  2. Small islands, valuable insights: systems of customary resource use and resilience to climate change in the Pacific

    Directory of Open Access Journals (Sweden)

    Heather L. McMillen

    2014-12-01

    Full Text Available Understanding how social-ecological systems are and can be resilient to climate change is one of the world's most crucial problems today. It requires knowledge at local and global scales, the integration of natural and social sciences, and a focus on biocultural diversity. Small Pacific Islands and the knowledge-practice-belief systems of their peoples have a long history of resilience to environmental variability and unpredictability, including in areas with marginal habitats and with periodic, severe disturbance (e.g., drought, flood, storms, and tsunami. We review the state of research on these knowledge systems as it pertains to resilience and adaptation, and we highlight critical research needs to address the interrelated areas of: (1 local-scale expertise and observations of change with regard to weather, life-history cycles, and ecological processes; (2 customary resource management institutions and practices (i.e., with agroforests and the nearshore marine environment; and (3 the roles of leaders, social institutions, and social networks in the context of disturbance and change. We conclude that these knowledge systems can contribute high-resolution observations, benchmark data, and insights into practices that enhance resilience and adaptive capacity in integrated terrestrial and marine systems. Community-based and participatory approaches can complement and ground-truth climate models and direct culturally appropriate resource management, research, and adaptation measures. Although most islands in the Pacific are small, their knowledge systems include valuable insights on seasonal cycles, ecological processes, and the management of biocultural diversity that are relevant at a broad scale for understanding resilience and adaptability to the social-ecological effects of climate change.

  3. Facilitating climate change adaptation through communication: Insights from the development of a visualization tool

    DEFF Research Database (Denmark)

    Glaas, Erik; Ballantyne, Anne Gammelgaard; Neset, Tina;

    2015-01-01

    capacity among Nordic homeowners. Based on the results from continuous user-testing and focus group interviews we outline lessons learned and key aspects to consider in the design of tools for communicating complex issues such as climate change effects and adaptive response measures.......Climate change communication on anticipated impacts and adaptive responses is frequently presented as an effective means to facilitate implementation of adaptation to mitigate risks to residential buildings. However, it requires that communication is developed in a way that resonates with the...... context of the target audience, provides intelligible information and addresses perceived barriers to adaptation. In this paper we reflect upon criteria for useful climate change communication gained over a three year development process of a web-based tool - VisAdaptTM – aimed at increasing the adaptive...

  4. Topographic Evolution and Climate Aridification during Continental Collision: Insights from Computer Simulations.

    Science.gov (United States)

    Garcia-Castellanos, Daniel; Jiménez-Munt, Ivone

    2015-01-01

    How do the feedbacks between tectonics, sediment transport and climate work to shape the topographic evolution of the Earth? This question has been widely addressed via numerical models constrained with thermochronological and geomorphological data at scales ranging from local to orogenic. Here we present a novel numerical model that aims at reproducing the interaction between these processes at the continental scale. For this purpose, we combine in a single computer program: 1) a thin-sheet viscous model of continental deformation; 2) a stream-power surface-transport approach; 3) flexural isostasy allowing for the formation of large sedimentary foreland basins; and 4) an orographic precipitation model that reproduces basic climatic effects such as continentality and rain shadow. We quantify the feedbacks between these processes in a synthetic scenario inspired by the India-Asia collision and the growth of the Tibetan Plateau. We identify a feedback between erosion and crustal thickening leading locally to a <50% increase in deformation rates in places where orographic precipitation is concentrated. This climatically-enhanced deformation takes place preferentially at the upwind flank of the growing plateau, specially at the corners of the indenter (syntaxes). We hypothesize that this may provide clues for better understanding the mechanisms underlying the intriguing tectonic aneurisms documented in the Himalayas. At the continental scale, however, the overall distribution of topographic basins and ranges seems insensitive to climatic factors, despite these do have important, sometimes counterintuitive effects on the amount of sediments trapped within the continent. The dry climatic conditions that naturally develop in the interior of the continent, for example, trigger large intra-continental sediment trapping at basins similar to the Tarim Basin because they determine its endorheic/exorheic drainage. These complex climatic-drainage-tectonic interactions make the

  5. Topographic Evolution and Climate Aridification during Continental Collision: Insights from Computer Simulations.

    Directory of Open Access Journals (Sweden)

    Daniel Garcia-Castellanos

    Full Text Available How do the feedbacks between tectonics, sediment transport and climate work to shape the topographic evolution of the Earth? This question has been widely addressed via numerical models constrained with thermochronological and geomorphological data at scales ranging from local to orogenic. Here we present a novel numerical model that aims at reproducing the interaction between these processes at the continental scale. For this purpose, we combine in a single computer program: 1 a thin-sheet viscous model of continental deformation; 2 a stream-power surface-transport approach; 3 flexural isostasy allowing for the formation of large sedimentary foreland basins; and 4 an orographic precipitation model that reproduces basic climatic effects such as continentality and rain shadow. We quantify the feedbacks between these processes in a synthetic scenario inspired by the India-Asia collision and the growth of the Tibetan Plateau. We identify a feedback between erosion and crustal thickening leading locally to a <50% increase in deformation rates in places where orographic precipitation is concentrated. This climatically-enhanced deformation takes place preferentially at the upwind flank of the growing plateau, specially at the corners of the indenter (syntaxes. We hypothesize that this may provide clues for better understanding the mechanisms underlying the intriguing tectonic aneurisms documented in the Himalayas. At the continental scale, however, the overall distribution of topographic basins and ranges seems insensitive to climatic factors, despite these do have important, sometimes counterintuitive effects on the amount of sediments trapped within the continent. The dry climatic conditions that naturally develop in the interior of the continent, for example, trigger large intra-continental sediment trapping at basins similar to the Tarim Basin because they determine its endorheic/exorheic drainage. These complex climatic

  6. Global Deliberative Democracy and Climate Change: Insights from World Wide Views on Global Warming in Australia

    Directory of Open Access Journals (Sweden)

    Chris Riedy

    2011-12-01

    Full Text Available On 26 September 2009, approximately 4,000 citizens in 38 countries participated in World Wide Views on Global Warming (WWViews. WWViews was an ambitious first attempt to convene a deliberative mini-public at a global scale, giving people from around the world an opportunity to deliberate on international climate policy and to make recommendations to the decision-makers meeting at the United Nations Climate Change Conference in Copenhagen (COP-15 in December 2009. In this paper, we examine the role that deliberative mini-publics can play in facilitating the emergence of a global deliberative system for climate change response. We pursue this intent through a reflective evaluation of the Australian component of the World Wide Views on Global Warming project (WWViews. Our evaluation of WWViews is mixed. The Australian event was delivered with integrity and feedback from Australian participants was almost universally positive. Globally, WWViews demonstrated that it is feasible to convene a global mini-public to deliberate on issues of global relevance, such as climate change. On the other hand, the contribution of WWViews towards the emergence of a global deliberative system for climate change response was limited and it achieved little influence on global climate change policy. We identify lessons for future global mini-publics, including the need to prioritise the quality of deliberation and provide flexibility to respond to cultural and political contexts in different parts of the world. Future global mini-publics may be more influential if they seek to represent discourse diversity in addition to demographic profiles, use designs that maximise the potential for transmission from public to empowered space, run over longer time periods to build momentum for change and experiment with ways of bringing global citizens together in a single process instead of discrete national events.

  7. Structural and molecular insights into novel surface-exposed mucus adhesins from Lactobacillus reuteri human strains.

    Science.gov (United States)

    Etzold, Sabrina; MacKenzie, Donald A; Jeffers, Faye; Walshaw, John; Roos, Stefan; Hemmings, Andrew M; Juge, Nathalie

    2014-05-01

    The mucus layer covering the gastrointestinal tract is the first point of contact of the intestinal microbiota with the host. Cell surface macromolecules are critical for adherence of commensal bacteria to mucus but structural information is scarce. Here we report the first molecular and structural characterization of a novel cell-surface protein, Lar_0958 from Lactobacillus reuteri JCM 1112(T) , mediating adhesion of L. reuteri human strains to mucus. Lar_0958 is a modular protein of 133 kDa containing six repeat domains, an N-terminal signal sequence and a C-terminal anchoring motif (LPXTG). Lar_0958 homologues are expressed on the cell-surface of L. reuteri human strains, as shown by flow-cytometry and immunogold microscopy. Adhesion of human L. reuteri strains to mucus in vitro was significantly reduced in the presence of an anti-Lar_0958 antibody and Lar_0958 contribution to adhesion was further confirmed using a L. reuteri ATCC PTA 6475 lar_0958 KO mutant (6475-KO). The X-ray crystal structure of a single Lar_0958 repeat, determined at 1.5 Å resolution, revealed a divergent immunoglobulin (Ig)-like β-sandwich fold, sharing structural homology with the Ig-like inter-repeat domain of internalins of the food borne pathogen Listeria monocytogenes. These findings provide unique structural insights into cell-surface protein repeats involved in adhesion of Gram-positive bacteria to the intestine. PMID:24593252

  8. New insights into the molecular mechanisms of biomembrane structural changes and interactions by optical biosensor technology.

    Science.gov (United States)

    Lee, Tzong-Hsien; Hirst, Daniel J; Aguilar, Marie-Isabel

    2015-09-01

    Biomolecular-membrane interactions play a critical role in the regulation of many important biological processes such as protein trafficking, cellular signalling and ion channel formation. Peptide/protein-membrane interactions can also destabilise and damage the membrane which can lead to cell death. Characterisation of the molecular details of these binding-mediated membrane destabilisation processes is therefore central to understanding cellular events such as antimicrobial action, membrane-mediated amyloid aggregation, and apoptotic protein induced mitochondrial membrane permeabilisation. Optical biosensors have provided a unique approach to characterising membrane interactions allowing quantitation of binding events and new insight into the kinetic mechanism of these interactions. One of the most commonly used optical biosensor technologies is surface plasmon resonance (SPR) and there have been an increasing number of studies reporting the use of this technique for investigating biophysical analysis of membrane-mediated events. More recently, a number of new optical biosensors based on waveguide techniques have been developed, allowing membrane structure changes to be measured simultaneously with mass binding measurements. These techniques include dual polarisation interferometry (DPI), plasmon waveguide resonance spectroscopy (PWR) and optical waveguide light mode spectroscopy (OWLS). These techniques have expanded the application of optical biosensors to allow the analysis of membrane structure changes during peptide and protein binding. This review provides a theoretical and practical overview of the application of biosensor technology with a specific focus on DPI, PWR and OWLS to study biomembrane-mediated events and the mechanism of biomembrane disruption. This article is part of a Special Issue entitled: Lipid-protein interactions. PMID:26009270

  9. Reconciling collaborative action research with existing institutions: insights from Dutch and German climate knowledge programmes

    NARCIS (Netherlands)

    Termeer, C.J.A.M.; Buuren, van A.; Knieling, J.; Gottschick, M.

    2015-01-01

    Researchers and policymakers increasingly aim to set up collaborative research programmes to address the challenges of adaptation to climate change. This does not only apply for technical knowledge, but for governance knowledge also. Both the Netherlands and Germany have set up large scale collabora

  10. Planning for climate change in small islands: insights from national hurricane preparedness in the Cayman Islands

    International Nuclear Information System (INIS)

    This paper examines contemporary national scale responses to tropical storm risk in a small island in the Caribbean to derive lessons for adapting to climate change. There is little empirical evidence to guide national planners on how to adapt to climate change, and less still on how to build on past adaptation experiences. The paper investigates the construction of institutional resilience and the process of adaptation to tropical storm risk by the Cayman Islands' Government from 1988 to 2002. It explains the roles of persuasion, exposure and collective action as key components in developing the ability to buffer external disturbance using models of institutional economics and social resilience concepts. The study finds that self-efficacy, strong local and international support networks, combined with a willingness to act collectively and to learn from mistakes appear to have increased the resilience of the Cayman Islands' Government to tropical storm risk. The lessons learned from building resilience to storm risk can contribute to the creation of national level adaptive capacity to climate change, but climate change has to be prioritised before these lessons can be transferred. (author)

  11. Insights from the molecular characterization of mercury stress proteins identified by proteomics in E.coli nissle 1917

    OpenAIRE

    Seshapani, Panthangi; Rayalu, Daddam Jayasimha; Kumar, Vadde Kiran; Sekhar, Kathera Chandra; Kumari, Jasti Pramoda

    2013-01-01

    Differently expressed proteins in probiotic Escherichia coli nissle 1917 under mercury stress identified by using a proteomic approach. We applied to separate proteins by using two-dimensional gel electrophoresis and proteins were identified using MALDI-TOF-MS using PMF, by mascot database search using the NCBI database. we identified six proteins after exposure to mercury stress with respect to different functional classes. It is useful to understand the molecular insights into mercury stres...

  12. Characterization of hairless (Hr) and FGF5 genes provides insights into the molecular basis of hair loss in cetaceans

    OpenAIRE

    Chen, Zhuo; Wang, Zhengfei; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2013-01-01

    Background Hair is one of the main distinguishing characteristics of mammals and it has many important biological functions. Cetaceans originated from terrestrial mammals and they have evolved a series of adaptations to aquatic environments, which are of evolutionary significance. However, the molecular mechanisms underlying their aquatic adaptations have not been well explored. This study provided insights into the evolution of hair loss during the transition from land to water by investigat...

  13. Climate, history and neutrality as drivers of mammal beta diversity in Europe: insights from multiscale deconstruction

    DEFF Research Database (Denmark)

    Svenning, J.-C.; Fløjgaard, Camilla; Baselga, Andrés

    2011-01-01

    regional (250 000 km2) scales. 3. We found continental-scale mammal beta diversity to be mainly caused by spatial turnover (99·9%), with only a small contribution (0·1%) from nestedness. 4. Current climate emerged as an important driver of beta diversity, given the strong continental-scale turnover......1. Environmental sorting, historical factors and neutral dynamics may all drive beta diversity (change in species composition across space), but their relative importance remains unresolved. In the case of European mammals, key potential drivers of large-scale beta diversity include current climate...... novel analytical framework to deconstruct beta diversity of non-volant mammals in Europe (138 species) into its turnover (change in species composition because of species replacements) and nestedness components (change in species composition because of species richness differences) at continental and...

  14. Enhanced insights into late Quaternary African hydroclimate dynamics using a water-isotope enabled climate model

    Science.gov (United States)

    Singarayer, Joy; Holloway, Max

    2016-04-01

    The climate of intertropical Africa is strongly governed by the dynamics of the tropical rainbelt, which is often associated with the Intertropical Convergence Zone (ITCZ). On millennial time-scales the primary drivers of variation in the rainbelt include orbital configuration changes to insolation seasonality and high-latitude forcing (e.g. Heinrich events). The spatial pattern of precipitation variability in tropical and subtropical Africa over the late Quaternary is complex and has long been debated. Stable water isotopes from inland lakes and off-shore ocean core records have provided longitudinal records, variously interpreted as changes to precipitation intensity or changes to moisture source location due to atmospheric circulation changes (or a combination of several factors). In this preliminary study we have used a global climate model, HadCM3, in which water isotopes are interactively coupled to produce snapshots at 1000-year intervals covering the last deglaciation (21kyr to pre-industrial). In conjunction with a comparison to available palaeodata, this enables us to better elucidate the connections between precipitation and other climate factors with changes to the water isotope signature, as well as how this varies regionally and through time.

  15. Role of Livelihood Capital in Reducing Climatic Vulnerability: Insights of Australian Wheat from 1990–2010

    Science.gov (United States)

    Huai, Jianjun

    2016-01-01

    In many agricultural countries, development of rural livelihood through increasing capital is a major regional policy to adapt to climate change. However, the role of livelihood capital in reducing climatic vulnerability is uncertain. This study assesses vulnerability and identifies the effects of common capital indicators on it, using Australian wheat as an example. We calculate exposure (a climate index) and sensitivity (a wheat failure index) to measure vulnerability and classify the resilient and sensitive cases, and express adaptive capacity through financial, human, natural, physical, and social capital indicators for 12 regions in the Australian wheat–sheep production zone from 1991–2010. We identify relationships between 12 indicators of five types of capital and vulnerability with t-tests and six logistic models considering the capital indicator itself, its first-order lag and its square as dependent variables to test the hypothesis that a high level of each capital metric results in low vulnerability. Through differing adaptive capacities between resilient and sensitive groups, we found that only four of the 12 (e.g., the access to finance, cash income level, total crop gross revenues, and family share of farm income) relate to vulnerability, which challenges the hypothesis that increasing capital reduces vulnerability. We conclude that further empirical reexaminations are required to test the relationships between capital measures and vulnerability under the sustainable livelihood framework (SLF). PMID:27022910

  16. Structure and Dynamics of Glycosphingolipids in Lipid Bilayers: Insights from Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Ronak Y. Patel

    2011-01-01

    Full Text Available Glycolipids are important constituents of biological membranes, and understanding their structure and dynamics in lipid bilayers provides insights into their physiological and pathological roles. Experimental techniques have provided details into their behavior at model and biological membranes; however, computer simulations are needed to gain atomic level insights. This paper summarizes the insights obtained from MD simulations into the conformational and orientational dynamics of glycosphingolipids and their exposure, hydration, and hydrogen-bonding interactions in membrane environment. The organization of glycosphingolipids in raft-like membranes and their modulation of lipid membrane structure are also reviewed.

  17. Insights into molecular properties of the human monocarboxylate transporter 8 by combining functional with structural information

    Directory of Open Access Journals (Sweden)

    Kleinau Gunnar

    2011-08-01

    Full Text Available Abstract Background The monocarboxylate transporter 8 (MCT8 is a member of the major facilitator superfamily (MFS and transports specificly iodothyronines. MCT8 mutations are the underlying cause of a syndrome of severe X-linked psychomotor retardation known as the Allan-Herndon-Dudley syndrome. This syndrome is characterized by abnormally high T3, low/normal T4 serum levels and slightly elevated serum TSH. To date, more than 25 pathogenic mutations in hMCT8 are known and they are valuable indicators of important regions for structural and functional MCT8 properties. Methods We designed a structural human MCT8 model and studied reported pathogenic missense mutations with focus on the estimation of those amino acid positions which are probably sensitive for substrate transport. Furthermore, assuming similarities between determinants of T3 binding observed in the published crystal structure of the thyroid hormone receptor beta occupied by its ligand T3 and the structural MCT8 model, we explore potential T3 binding sites in the MCT8 substrate channel cavity. Results We found that all known pathogenic missense mutations are located exclusively in the transmembrane helices and to a high degree at conserved residues among the MCT family. Furthermore, mutations either of or to prolines/glycines are located mainly at helices 9-12 and are expected to cause steric clashes or structural misfolding. In contrast, several other mutations are close to the potential substrate channel and affected amino acids are likely involved in the switching mechanism between different transporter conformations. Finally, three potential substrate binding sites are predicted for MCT8. Conclusions Naturally occurring mutations of MCT8 provide molecular insights into protein regions important for protein folding, substrate binding and the switching mechanism during substrate transport. Future studies guided by this information should help to clarify structure

  18. Late Oligocene to Late Miocene Antarctic Climate Reconstructions Using Molecular and Isotopic Biomarker Proxies

    Science.gov (United States)

    Duncan, B.; Mckay, R. M.; Bendle, J. A.; Naish, T.; Levy, R. H.; Ventura, G. T.; Moossen, H. M.; Krishnan, S.; Pagani, M.

    2015-12-01

    Major climate and environmental changes occurred during late Oligocene to the late Miocene when atmospheric CO2 ranged between 500 and 300ppm, indicating threshold response of Antarctic ice sheets and climate to relatively modest CO2 variations. This implies that the southern high latitudes are highly sensitive to feedbacks associated with changes in global ice sheet and sea-ice extent, as well as terrestrial and marine ecosystems. This study focuses on two key intervals during the evolution of the Antarctic Ice Sheet: (1) The Late Oligocene and the Oligocene/Miocene boundary, when the East Antarctic Ice Sheet expanded close to present day volume following an extended period of inferred warmth. (2) The Mid-Miocene Climate Optimum (MMCO ~17-15 Ma), a period of global warmth and moderately elevated CO2 (350->500 ppm) which was subsequently followed by rapid cooling at 14-13.5 Ma. Reconstructions of climate and ice sheet variability, and thus an understanding of the various feedbacks that occurred during these intervals, are hampered by a lack of temperature and hydroclimate proxy data from the southern high latitudes. We present proxy climate reconstructions using terrestrial and marine organic biomarkers that provide new insights into Antarctica's climate evolution, using Antarctic drill cores and outcrop samples from a range of depositional settings. Bacterial ether-lipids have been analysed to determine terrestrial mean annual temperatures and soil pH (via the methylation and cyclisation indexes of branched tetraethers - MBT and CBT, respectively). Tetraether-lipids of crenarchaeota found in marine sediments sampled from continental shelves around Antarctica have been used to derive sea surface temperatures using the TEX86 index. Compound specific stable isotopes on n-alkanes sourced from terrestrial plants have been analysed to investigate changes in the hydrological and carbon cycles.

  19. KZai 02 pollen record, an insight into West African monsoon fluctuations during the Last Climatic Cycle

    Science.gov (United States)

    Dalibard, M.; Popescu, S.; Maley, J.; Suc, J.

    2012-12-01

    Climate of the circum-Atlantic intertropical zone is driven by the ocean/atmosphere dynamics in response to variations of yearly insolation. These latitudes correspond to the convergence of the Hadley cells expressed on earth surface by intense trade winds and in lower troposphere by the African easterly jet making the edges of the intertropical zone relatively dry, while humidity is concentrated near the Equator. This phenomenon generates a precipitation front, known as the InterTropical Convergence Zone (ITCZ), the oscillations of which regulate the latitudinal vegetation distribution. Pollen record of core KZai 02 (Guinea Gulf) allows high resolution reconstruction of variations of past ecosystems over Central Africa during the Last Climatic Cycle. Plant taxa recorded in pollen analyses have been clustered according to their ecological requirements and African phytogeography. Fluctuations of these groups inform on precipitation intensity and their distribution during the last 130 ka. During Glacials, an open vegetation made of Cyperaceae marshes developed in the central Zaire/Congo Basin, surrounded by savannah on borders and afromontane forests on reliefs. Composition and distribution of vegetation indicate a decrease in monsoon activity and the strengthening of the precipitation front in the center of the basin. Interglacial phases are characterized by rain forest expansion over Central Africa in response to a precipitation enhancement associated with a northward shift of the rainfall front. Replacement of afromontane forest and marsh ecosystems by savannah then lowland pioneering, warm-temperate and rain forests characterized glacial/interglacial transitions. This succession suggests the increasing influence of at least two climatic parameters: the water availability and temperature and/or CO2 fluctuation. Spectral analysis applied to vegetation groups evidences the forcing of insolation, mainly driven by precession, on the West African monsoon system. Sub

  20. Quantitative analysis of oyster larval proteome provides new insights into the effects of multiple climate change stressors.

    Science.gov (United States)

    Dineshram, Ramadoss; Chandramouli, Kondethimmanahalli; Ko, Ginger Wai Kuen; Zhang, Huoming; Qian, Pei-Yuan; Ravasi, Timothy; Thiyagarajan, Vengatesen

    2016-06-01

    The metamorphosis of planktonic larvae of the Pacific oyster (Crassostrea gigas) underpins their complex life-history strategy by switching on the molecular machinery required for sessile life and building calcite shells. Metamorphosis becomes a survival bottleneck, which will be pressured by different anthropogenically induced climate change-related variables. Therefore, it is important to understand how metamorphosing larvae interact with emerging climate change stressors. To predict how larvae might be affected in a future ocean, we examined changes in the proteome of metamorphosing larvae under multiple stressors: decreased pH (pH 7.4), increased temperature (30 °C), and reduced salinity (15 psu). Quantitative protein expression profiling using iTRAQ-LC-MS/MS identified more than 1300 proteins. Decreased pH had a negative effect on metamorphosis by down-regulating several proteins involved in energy production, metabolism, and protein synthesis. However, warming switched on these down-regulated pathways at pH 7.4. Under multiple stressors, cell signaling, energy production, growth, and developmental pathways were up-regulated, although metamorphosis was still reduced. Despite the lack of lethal effects, significant physiological responses to both individual and interacting climate change related stressors were observed at proteome level. The metamorphosing larvae of the C. gigas population in the Yellow Sea appear to have adequate phenotypic plasticity at the proteome level to survive in future coastal oceans, but with developmental and physiological costs. PMID:26990129

  1. Vulnerability of the northern Mongolian steppe to climate change: insights from flower production and phenology.

    Science.gov (United States)

    Liancourt, Pierre; Spence, Laura A; Boldgiv, Bazartseren; Lkhagva, Ariuntsetseg; Helliker, Brent R; Casper, Brenda B; Petraitis, Peter S

    2012-04-01

    The semiarid, northern Mongolian steppe, which still supports pastoral nomads who have used the steppe for millennia, has experienced an average 1.7 degrees C temperature rise over the past 40 years. Continuing climate change is likely to affect flowering phenology and flower numbers with potentially important consequences for plant community composition, ecosystem services, and herder livelihoods. Over the growing seasons of 2009 and 2010, we examined flowering responses to climate manipulation using open-top passive warming chambers (OTCs) at two locations on a south-facing slope: one on the moister, cooler lower slope and the other on the drier, warmer upper slope, where a watering treatment was added in a factorial design with warming. Canonical analysis of principal coordinates (CAP) revealed that OTCs reduced flower production and delayed peak flowering in graminoids as a whole but only affected forbs on the upper slope, where peak flowering was also delayed. OTCs affected flowering phenology in seven of eight species, which were examined individually, either by altering the time of peak flowering and/or the onset and/or cessation of flowering, as revealed by survival analysis. In 2010, which was the drier year, OTCs reduced flower production in two grasses but increased production in an annual forb found only on the upper slope. The particular effects of OTCs on phenology, and whether they caused an extension or contraction of the flowering season, differed among species, and often depended on year, or slope, or watering treatment; however, a relatively strong pattern emerged for 2010 when four species showed a contraction of the flowering season in OTCs. Watering increased flower production in two species in 2010, but slope location more often affected flowering phenology than did watering. Our results show the importance of taking landscape-scale variation into account in climate change studies and also contrasted with those of several studies set in cold

  2. Molecular-Level Insights into Photocatalysis from Scanning Probe Microscopy Studies on TiO2(110)

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Michael A.; Lyubinetsky, Igor

    2013-06-12

    The field of heterogeneous photocatalysis has grown considerably in the decades since Fujishima and Honda's ground-breaking publications of photoelectrochemistry on TiO2. Numerous review articles continue to point to both progress made in the use of heterogeneous materials (such as TiO2) to perform photoconversion processes, and the many opportunities and challenges in heterogeneous photocatalysis research such as solar energy conversion and environmental remediation. The past decade has also seen an increase in the use of molecular-level approaches applied to model single crystal surfaces in an effort to obtain new insights into photocatalytic phenomena. In particular, scanning probe techniques (SPM) have enabled researchers to take a ‘nanoscale’ approach to photocatalysis that includes interrogation of the reactivities of specific sites and adsorbates on a model photocatalyst surface. The rutile TiO2(110) surface has become the prototypical oxide single crystal surface for fundamental studies of many interfacial phenomena. In particular, TiO2(110) has become an excellent model surface for probing photochemical and photocatalytic reactions at the molecular level. A variety of experimental approaches have emerged as being ideally suited for studying photochemical reactions on TiO2(110), including desorption-oriented approaches and electronic spectroscopies, but perhaps the most promising techniques for evaluating site-specific properties are those of SPM. In this review, we highlight the growing use of SPM techniques in providing molecular-level insights into surface photochemistry on the model photocatalyst surface of rutile TiO2(110). Our objective is to both illustrate the unique knowledge that scanning probe techniques have already provided the field of photocatalysis, and also to motivate a new generation of effort into the use of such approaches to obtain new insights into the molecular level details of photochemical events occurring at interfaces

  3. Climate control on ancestral population dynamics: insight from Patagonian fish phylogeography.

    Science.gov (United States)

    Ruzzante, Daniel E; Walde, Sandra J; Gosse, John C; Cussac, Victor E; Habit, Evelyn; Zemlak, Tyler S; Adams, Emily D M

    2008-05-01

    Changes in lake and stream habitats during the growth and retreat of Pleistocene glaciers repeatedly altered the spatial distributions and population sizes of the aquatic fauna of the southern Andes. Here, we use variation in mtDNA control region sequences to infer the temporal dynamics of two species of southern Andean fish during the past few million years. At least five important climate events were associated with major demographic changes: (i) the widespread glaciations of the mid-Pliocene (c. 3.5 Ma); (ii) the largest Patagonian glaciation (1.1 Ma); (iii) the coldest Pleistocene glaciation as indicated by stacked marine delta(18)O (c. 0.7 Ma); (iv) the last southern Patagonian glaciation to reach the Atlantic coast (180 ka); and (v) the last glacial maximum (LGM, 23-25,000 years ago). The colder-water inhabitant, Galaxias platei, underwent a strong bottleneck during the LGM and its haplotype diversity coalesces c. 0.7 Ma. In contrast, the more warm-adapted and widely distributed Percichthys trucha showed continuous growth through the last two glacial cycles but went through an important bottleneck c. 180,000 years ago, at which time populations east of the Andes may have been eliminated. Haplotype diversity of the most divergent P. trucha populations, found west of the Andes, coalesces c. 3.2 Ma. The demographic timelines obtained for the two species thus illustrate the continent-wide response of aquatic life in Patagonia to climate change during the Pleistocene, but also show how differing ecological traits and distributions led to distinctive responses. PMID:18363661

  4. Carbon nanotubes as nanodelivery systems an insight through molecular dynamics simulations

    CERN Document Server

    Lim, Melvin Choon Giap

    2013-01-01

    This book showcases the application of carbon nanotubes as nanodelivery systems for copper atoms, using molecular dynamics simulations as a means of investigation. The nanodelivery system of the carbon nanotube presents the possible usage of the carbon structure in many areas in the future. This book is comprehensive and informative, and serves as a guide for any reader who wishes to perform a molecular dynamics simulation of his own and to conduct an analytical study of a molecular system.

  5. Oldest isotopically characterized fish otoliths provide insight to Jurassic continental climate of Europe

    Science.gov (United States)

    Patterson, William P.

    1999-03-01

    Large, shallow, epeiric seas and adjacent lagoons such as those described herein likely played a significant role in moderating Jurassic coastal and continental climate. Jurassic (Bathonian) ocean surface temperatures in Scotland have been calculated from δ18O(CaCO3) values of a suite of the oldest well-preserved fish otoliths analyzed to date. Otolith δ18O values range from -4.7‰ to -1.9‰ (Vienna Peedee belemnite, VPDB), while δ13C(CaCO3) values vary from -5.4‰ to +1.5‰ (VPDB), representing the oldest stable isotopic record of paleodiet, paleoecology, and fish migration to date. Using a global ocean δ18O(H2O) value of -1.0‰ (Vienna standard mean ocean water, VSMOW) for an ice-free Jurassic, fish species that migrated from estuarine to open marine water record time-averaged temperatures of 23 °C. Estuarine fish, assuming a similar temperature, record variation in δ18O(H2O) values from -3.7‰ to -2.0‰ (VSMOW). That significant mixing of fresh water and seawater occurred in the Jurassic in Scotland is in general agreement with data presented by others (molluscan fauna, lithostratigraphy, paleogeography, and paleocirculation models). The δ18O values and temperatures derived in this study correspond to the meteorologic and hydrologic parameters of a mid-latitude maritime climate with low seasonality, a mean temperature of 23 °C, and abundant precipitation and humidity. The δ18O(H2O) values calculated from estuarine fish indicate that rainfall must have a δ18O(H2O) value lower than -3.7‰ (VSMOW). Values of δ18O and δ13C suggest an environment hydrologically similar to that observed in the Everglades of south Florida or the estuaries of south Texas, both notable fish nurseries today. However, sea-surface temperatures were lower than those of modern Florida or Texas as evidenced by reduced evaporative enrichment of δ18O(H2O) values.

  6. Insights from the Molecular Dynamics Simulation of Cellobiohydrolase Cel6A Molecular Structural Model from Aspergillus fumigatus NITDGPKA3.

    Science.gov (United States)

    Dodda, Subba Reddy; Sarkar, Nibedita; Aikat, Kaustav; Krishnaraj, Navanietha R; Bhattacharjee, Sanchari; Bagchi, Angshuman; Mukhopadhyay, Sudit S

    2016-01-01

    Global demand for bioethanol is increasing tremendously as it could help to replace the conventional fossil fuel and at the same time supporting the bioremediation of huge volume of cellulosic wastes generated from different sources. Ideal genetic engineering approaches are essential to improve the efficacy of the bioethanol production processes for real time applications. A locally isolated fungal strain Aspergillus fumigatus NITDGPKA3 was used in our laboratory for the hydrolysis of lignocellulose with good cellulolytic activity when compared with other contemporary fungal strains. An attempt is made to sequence the cellobiohydrolases (CBHs) of A. fumigatus NITDGPKA3, model its structure to predict its catalytic activity towards improving the protein by genetic engineering approaches. Herein, the structure of the sequenced Cellobiohydrolases (CBHs) of A. fumigatus NITDGPKA3, modelled by homology modelling and its validation is reported. Further the catalytic activity of the modelled CBH enzyme was assessed by molecular docking analysis. Phylogenetic analysis showed that CBH from A. fumigatus NITDGPKA3 belongs to the Glycohydro 6 (Cel6A) super family. Molecular modeling and molecular dynamics simulation suggest the structural and functional mechanism of the enzyme. The structures of both the cellulose binding (CBD) and catalytic domain (CD) have been compared with most widely studied CBH of Trichoderma reesei. The molecular docking with cellulose suggests that Gln 248, Pro 287, Val236, Asn284, and Ala288 are the main amino acids involved in the hydrolysis of the β, 1-4, glycosidic bonds of cellulose. PMID:27109185

  7. Monitoring of Odonata in Britain and possible insights into climate change

    Directory of Open Access Journals (Sweden)

    Adrian Parr

    2010-12-01

    Full Text Available The history of recording and monitoring of Odonata in Britain is briefly described. Results are then presented which suggest that the country’s Odonata fauna is currently in a period of flux, in a manner consistent with the actions of a high-level regulatory factor such as climate change. The ranges of many resident species are shifting. Leucorrhinia dubia has recently been lost from southern England, but many species are presently expanding their ranges to the north and west, some (such as Aeshna mixta and Anax imperator with considerable speed. In addition to these changes, a number of ‘southern’ species have started to appear in Britain for the very first time. These include Lestes barbarus, Erythromma viridulum (which has now become a locally-common resident in southeast England, Anax parthenope and Crocothemis erythraea. In addition to these distributional changes, some recent trends in flight times are also discussed. Evidence indicates that many species are now emerging significantly earlier than in the past, though trends relating to the end of the flight period are less clear cut.

  8. Insight into glacier climate interaction: reconstruction of the mass balance field using ice extent data

    Science.gov (United States)

    Visnjevic, Vjeran; Herman, Frédéric; Licul, Aleksandar

    2016-04-01

    With the end of the Last Glacial Maximum (LGM), about 20 000 years ago, ended the most recent long-lasting cold phase in Earth's history. We recently developed a model that describes large-scale erosion and its response to climate and dynamical changes with the application to the Alps for the LGM period. Here we will present an inverse approach we have recently developed to infer the LGM mass balance from known ice extent data, focusing on a glacier or ice cap. The ice flow model is developed using the shallow ice approximation and the developed codes are accelerated using GPUs capabilities. The mass balance field is the constrained variable defined by the balance rate β and the equilibrium line altitude (ELA), where c is the cutoff value: b = max(βṡ(S(z) - ELA), c) We show that such a mass balance can be constrained from the observed past ice extent and ice thickness. We are also investigating several different geostatistical methods to constrain spatially variable mass balance, and derive uncertainties on each of the mass balance parameters.

  9. Atomic-Scale Insight into Tautomeric Recognition, Separation, and Interconversion of Guanine Molecular Networks on Au(111).

    Science.gov (United States)

    Zhang, Chi; Xie, Lei; Wang, Likun; Kong, Huihui; Tan, Qinggang; Xu, Wei

    2015-09-16

    Although tautomerization may directly affect the chemical or biological properties of molecules, real-space investigation on the tautomeric behaviors of organic molecules in a larger area of molecular networks has been scarcely reported. In this paper, we choose guanine (G) molecule as a model system. From the interplay of high-resolution scanning tunneling microscopy (STM) imaging and density functional theory (DFT) calculations, we have successfully achieved the tautomeric recognition, separation, and interconversion of G molecular networks (formed by two tautomeric forms G/9H and G/7H) with the aid of NaCl on the Au(111) surface in ultrahigh vacuum (UHV) conditions. Our results may serve as a prototypical system to provide important insights into tautomerization related issues, which should be intriguing to biochemistry, pharmaceutics, and other related fields. PMID:26322860

  10. Climate impacts on human settlement and agricultural activities in northern Norway: new insights from biogeochemistry

    Science.gov (United States)

    D'anjou, R. M.; Bradley, R. S.; Balascio, N. L.; Finkelstein, D. B.

    2012-12-01

    Disentangling the effects of climate change and anthropogenic activities on the environment is a major challenge in paleoenvironmental research. Here, we used fecal sterols and other biogeochemical compounds in lake sediments from northern Norway to identify both natural and anthropogenic signals of environmental change during the late Holocene. The area was first occupied by humans and their grazing animals at ~2,250±75 cal yr BP. The arrival of humans is indicated by an abrupt increase in coprostanol (and its epimer epicoprostanol) in the sediments, and an associated increase in 5β-stigmastanol (and 5β-epistigmastanol), which resulted from human and animal feces washing into the lake. Human settlement was accompanied by an abrupt increase in landscape fires (indicated by the rise in pyrolytic polycyclic aromatic hydrocarbons, PAHs) and a decline in woodland (registered by a change in n-alkane chain lengths from leaf waxes), accelerating a process that began earlier in the Holocene. Human activity and associated landscape changes in the region over the last two millennia were mainly driven by summer temperatures, as indicated by independent tree-ring reconstructions, though there were periods when socio-economic factors played an equally important role. This is the first time that fecal sterols in lake sediments have been used to provide a record of human occupancy through time. This approach may be useful in many archeological studies, both to confirm the presence of humans and grazing animals, and to distinguish between anthropogenic and natural factors that have influenced the environment in the past.

  11. The microtubule-associated molecular pathways may be genetically disrupted in patients with Bipolar Disorder. Insights from the molecular cascades.

    Science.gov (United States)

    Drago, Antonio; Crisafulli, Concetta; Sidoti, Antonina; Calabrò, Marco; Serretti, Alessandro

    2016-01-15

    Bipolar Disorder is a severe disease characterized by pathological mood swings from major depressive episodes to manic ones and vice versa. The biological underpinnings of Bipolar Disorder have yet to be defined. As a consequence, pharmacological treatments are suboptimal. In the present paper we test the hypothesis that the molecular pathways involved with the direct targets of lithium, hold significantly more genetic variations associated with BD. A molecular pathway approach finds its rationale in the polygenic nature of the disease. The pathways were tested in a sample of ∼ 7,000 patients and controls. Data are available from the public NIMH database. The definition of the pathways was conducted according to the National Cancer Institute (http://pid.nci.nih.gov/). As a result, 3 out of the 18 tested pathways related to lithium action resisted the permutation analysis and were found to be associated with BD. These pathways were related to Reelin, Integrins and Aurora. A pool of genes selected from the ones linked with the above pathways was further investigated in order to identify the fine molecular mechanics shared by our significant pathways and also their link with lithium mechanism of action. The data obtained point out to a possible involvement of microtubule-related mechanics. PMID:26551401

  12. Climate- vs. Earthquake-induced Rock-Glacier Advances in the Tien Shan: Insights from Lichenometry

    Science.gov (United States)

    Rosenwinkel, Swenja; Landgraf, Angela; Korup, Oliver; Sorg, Annina

    2014-05-01

    that Tien Shan rock glaciers do not record a consistent palaeoclimatic signal. We discuss whether distinct peaks of comparable lichen sizes and associated distributions of surface velocities for a given rock-glacier lobe result from rapid climate-driven advances or high lateral material input provided by seismically-induced slope instability instead. We compare our field data to advance-rate estimates from ground surveys and remote sensing (1 to >10 m/a), and dendrogeomorphic constraints obtained from trees growing on the rock glaciers. We conclude by highlighting a number of constraints that may limit the use of lichenometry for dating rock-glacier advances, and scope for future research on seismic triggers.

  13. Molecular taxonomy provides new insights into anopheles species of the neotropical arribalzagia series.

    Directory of Open Access Journals (Sweden)

    Giovan F Gómez

    Full Text Available Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I (COI and nuclear internal transcribed spacer 2 (ITS2 sequences were used to evaluate initial identification and to investigate phylogenetic relationships of seven Anopheles morphospecies of the Arribalzagia Series from Colombia. Phylogenetic trees recovered highly supported clades for An. punctimaculas.s., An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l., An. mattogrossensis and An. peryassui. This study provides the first molecular confirmation of An. malefactorfrom Colombia and discovered conflicting patterns of divergence for the molecular markers among specimens from northeast and northern Colombia suggesting the presence of two previously unrecognized Molecular Operational Taxonomic Units (MOTUs. Furthermore, two highly differentiated An. apicimacula MOTUs previously found in Panama were detected. Overall, the combined molecular dataset facilitated the detection of known and new Colombian evolutionary lineages, and constitutes the baseline for future research on their bionomics, ecology and potential role as malaria vectors.

  14. How Dopamine Transporter Interacts with Dopamine: Insights from Molecular Modeling and Simulation

    OpenAIRE

    Huang, Xiaoqin; Zhan, Chang-Guo

    2007-01-01

    By performing homology modeling, molecular docking, and molecular dynamics simulations, we have developed three-dimensional (3D) structural models of both dopamine transporter and dopamine transporter-dopamine complex in the environment of lipid bilayer and solvent water. According to the simulated structure of dopamine transporter-dopamine complex, dopamine was orientated in a hydrophobic pocket at the midpoint of the membrane. The modeled 3D structures provide some detailed structural and m...

  15. Cellular and molecular mechanisms of negligible senescence: insight from the sea urchin

    OpenAIRE

    Bodnar, Andrea G.

    2014-01-01

    Sea urchins exhibit a very different life history from humans and short-lived model animals and therefore provide the opportunity to gain new insight into the complex process of aging. Sea urchins grow indeterminately, regenerate damaged appendages, and reproduce throughout their lifespan. Some species show no increase in mortality rate at advanced ages. Nevertheless, different species of sea urchins have very different reported lifespans ranging from 4 to more than 100 years, thus providing ...

  16. Molecular genetic insights into deuterostome evolution from the direct-developing hemichordate Saccoglossus kowalevskii

    OpenAIRE

    Lowe, Christopher J.

    2008-01-01

    Progress in developmental biology, phylogenomics and palaeontology over the past five years are all making major contributions to a long-enduring problem in comparative biology: the early origins of the deuterostome phyla. Recent advances in the developmental biology of hemichordates have given a unique insight into developmental similarities between this phylum and chordates. Transcriptional and signalling gene expression patterns between the two groups during the early development of the an...

  17. Molecular signature of hypersaline adaptation: insights from genome and proteome composition of halophilic prokaryotes

    OpenAIRE

    Paul, Sandip; Sumit K Bag; Das, Sabyasachi; Harvill, Eric T.; Dutta, Chitra

    2008-01-01

    Background Halophilic prokaryotes are adapted to thrive in extreme conditions of salinity. Identification and analysis of distinct macromolecular characteristics of halophiles provide insight into the factors responsible for their adaptation to high-salt environments. The current report presents an extensive and systematic comparative analysis of genome and proteome composition of halophilic and non-halophilic microorganisms, with a view to identify such macromolecular signatures of haloadapt...

  18. Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

    Science.gov (United States)

    Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

    2014-01-01

    Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green. PMID:24226412

  19. Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations.

    Science.gov (United States)

    Hedger, George; Sansom, Mark S P

    2016-10-01

    Lipid molecules are able to selectively interact with specific sites on integral membrane proteins, and modulate their structure and function. Identification and characterization of these sites are of importance for our understanding of the molecular basis of membrane protein function and stability, and may facilitate the design of lipid-like drug molecules. Molecular dynamics simulations provide a powerful tool for the identification of these sites, complementing advances in membrane protein structural biology and biophysics. We describe recent notable biomolecular simulation studies which have identified lipid interaction sites on a range of different membrane proteins. The sites identified in these simulation studies agree well with those identified by complementary experimental techniques. This demonstrates the power of the molecular dynamics approach in the prediction and characterization of lipid interaction sites on integral membrane proteins. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. PMID:26946244

  20. Molecular insight into amyloid oligomer destabilizing mechanism of flavonoid derivative 2-(4' benzyloxyphenyl)-3-hydroxy-chromen-4-one through docking and molecular dynamics simulations.

    Science.gov (United States)

    Kumar, Akhil; Srivastava, Swati; Tripathi, Shubhandra; Singh, Sandeep Kumar; Srikrishna, Saripella; Sharma, Ashok

    2016-06-01

    Aggregation of amyloid peptide (Aβ) has been shown to be directly related to progression of Alzheimer's disease (AD). Aβ is neurotoxic and its deposition and aggregation ultimately lead to cell death. In our previous work, we reported flavonoid derivative (compound 1) showing promising result in transgenic AD model of Drosophila. Compound 1 showed prevention of Aβ-induced neurotoxicity and neuroprotective efficacy in Drosophila system. However, mechanism of action of compound 1 and its effect on the amyloid is not known. We therefore performed molecular docking and atomistic, explicit-solvent molecular dynamics simulations to investigate the process of Aβ interaction, inhibition, and destabilizing mechanism. Results showed different preferred binding sites of compound 1 and good affinity toward the target. Through the course of 35 ns molecular dynamics simulation, conformations_5 of compound 1 intercalates into the hydrophobic core near the salt bridge and showed major structural changes as compared to other conformations. Compound 1 showed interference with the salt bridge and thus reducing the inter strand hydrogen bound network. This minimizes the side chain interaction between the chains A-B leading to disorder in oligomer. Contact map analysis of amino acid residues between chains A and B also showed lesser interaction with adjacent amino acids in the presence of compound 1 (conformations_5). The study provides an insight into how compound 1 interferes and disorders the Aβ peptide. These findings will further help to design better inhibitors for aggregation of the amyloid oligomer. PMID:26208790

  1. Gene expression profiles give insight into the molecular pathology of bone in primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Reppe, Sjur; Stilgren, Lis; Olstad, Ole K; Brixen, Kim; Nissen-Meyer, Lise Sofie; Gautvik, Kaare M; Abrahamsen, Bo

    2006-01-01

    Global gene expression profiling has been used to study the molecular mechanisms of increased bone remodeling caused by PHPT. This disease is a model for chronic over-stimulation of target organs by PTH due to an inappropriate overproduction of the hormone. Hyperactivity of osteoblasts and...... potential bearing on future treatment....

  2. Molecular dynamics insight to phase transition in n-alkanes with carbon nanofillers

    International Nuclear Information System (INIS)

    The present work aims to investigate the phase transition, dispersion and diffusion behavior of nanocomposites of carbon nanotube (CNT) and straight chain alkanes. These materials are potential candidates for organic phase change materials(PCMs) and have attracted flurry of research recently. Accurate experimental evaluation of the mass, thermal and transport properties of such composites is both difficult as well as economically taxing. Additionally it is crucial to understand the factors that results in modification or enhancement of their characteristic at atomic or molecular level. Classical molecular dynamics approach has been extended to elucidate the same. Bulk atomistic models have been generated and subjected to rigorous multistage equilibration. To reaffirm the approach, both canonical and constant-temperature, constant- pressure ensembles were employed to simulate the models under consideration. Explicit determination of kinetic, potential, non-bond and total energy assisted in understanding the enhanced thermal and transport property of the nanocomposites from molecular point of view. Crucial parameters including mean square displacement and simulated self diffusion coefficient precisely define the balance of the thermodynamic and hydrodynamic interactions. Radial distribution function also reflected the density variation, strength and mobility of the nanocomposites. It is expected that CNT functionalization could improve the dispersion within n-alkane matrix. This would further ameliorate the mass and thermal properties of the composite. Additionally, the determined density was in good agreement with experimental data. Thus, molecular dynamics can be utilized as a high throughput technique for theoretical investigation of nanocomposites PCMs

  3. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

    Science.gov (United States)

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  4. Chiral Room-Temperature Ionic Liquids: Insight from Molecular Dynamics Simulations

    Czech Academy of Sciences Publication Activity Database

    Lísal, Martin; Chval, Z.; Storch, Jan; Izák, Pavel; Aim, Karel

    - : -, 2013. s. 1. ISBN N. [International Conference on Properties and Phase Equilibria for Products and Process Design /13./. 26.05.2013-30.05.2013, Iguazu Falls] Institutional support: RVO:67985858 Keywords : RTIL * molecular dynamics * simulation Subject RIV: CF - Physical ; Theoretical Chemistry http://www.ppeppd2013.plapiqui.edu.ar/openconf.php

  5. Molecular dynamics insight to phase transition in n-alkanes with carbon nanofillers

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Monisha [School of Engineering, Indian Institute of Technology Mandi, Himachal Pradesh 175 001 (India); Vaish, Rahul, E-mail: rahul@iitmandi.ac.in [School of Engineering, Indian Institute of Technology Mandi, Himachal Pradesh 175 001 (India); Materials Research Centre, Indian Institute of Science, Bangalore 560 012 (India)

    2015-05-15

    The present work aims to investigate the phase transition, dispersion and diffusion behavior of nanocomposites of carbon nanotube (CNT) and straight chain alkanes. These materials are potential candidates for organic phase change materials(PCMs) and have attracted flurry of research recently. Accurate experimental evaluation of the mass, thermal and transport properties of such composites is both difficult as well as economically taxing. Additionally it is crucial to understand the factors that results in modification or enhancement of their characteristic at atomic or molecular level. Classical molecular dynamics approach has been extended to elucidate the same. Bulk atomistic models have been generated and subjected to rigorous multistage equilibration. To reaffirm the approach, both canonical and constant-temperature, constant- pressure ensembles were employed to simulate the models under consideration. Explicit determination of kinetic, potential, non-bond and total energy assisted in understanding the enhanced thermal and transport property of the nanocomposites from molecular point of view. Crucial parameters including mean square displacement and simulated self diffusion coefficient precisely define the balance of the thermodynamic and hydrodynamic interactions. Radial distribution function also reflected the density variation, strength and mobility of the nanocomposites. It is expected that CNT functionalization could improve the dispersion within n-alkane matrix. This would further ameliorate the mass and thermal properties of the composite. Additionally, the determined density was in good agreement with experimental data. Thus, molecular dynamics can be utilized as a high throughput technique for theoretical investigation of nanocomposites PCMs.

  6. Designing voltage-sensitive probes for neural imaging - Insight from molecular dynamics simulations

    Czech Academy of Sciences Publication Activity Database

    Bonhenry, Daniel; Melcr, Josef; Timr, Štěpán; Lazar, Josef; Jungwirth, Pavel

    2015-01-01

    Roč. 44, Suppl 1 (2015), S162. ISSN 0175-7571. [EBSA European Biophysics Congress /10./. 18.07.2015-22.07.2015, Dresden] Institutional support: RVO:61388963 Keywords : molecular dynamics simulations * voltage-sensitive probes Subject RIV: CF - Physical ; Theoretical Chemistry

  7. Structure and Function: Insights into Bioinorganic Systems from Molecular Mechanics Calculations

    Science.gov (United States)

    Marques, Helder M.; Egan, Timothy J.; de Villiers, Katherine A.

    The use of empirical force field methods for modeling important systems in bioinorganic chemistry, including the cobalt corrins (derivatives of vitamin B12) and the iron porphyrins, is described. Particular attention is given to the use of molecular dynamics and simulated annealing calculations in exploring the solution structures of corrin, and those of likely complexes between the ferriprotoporphyrin-IX and the arylmethanol antimalarials.

  8. Glioma-related edema: new insight into molecular mechanisms and their clinical implications

    Institute of Scientific and Technical Information of China (English)

    Zhi-Xiong Lin

    2013-01-01

    Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma.GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body.In terms of etiology,this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention,and different cell types contribute to distinct components of GRE.Peritumoral edema was previously believed to loosen glioma tissue,facilitating tumor-cell invasion;however,the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition.Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem.Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells,suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells.There are differences between pivotal molecular events and reactive molecular events in the development of GRE.Molecular therapy should target the former,as targeting reactive molecular events will produce undesired or even adverse results.At present,brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images.The effect of these models on peritumoral brain edema is unclear.Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE.Exploring clinical assessment methods,optimizing the existing control strategy of GRE,and simultaneously developing new treatments are essential.

  9. DNA molecular wire-based nanoelectronics: New insight and high frequency AC electrical characterization

    Science.gov (United States)

    Wibowo, Denni Ari

    While recent research in electron-transport mechanism on a double strands DNA seems to converge into a consensus, experiments in direct electrical measurements on a long DNA molecules still lead to a conflicting result. This research investigates experimentally the attachment of DNA molecular wire to high aspect ratio three-dimensional (3D) metal electrode and the effect of temperature to its AC electrical conductivity. The 3-D microelectrode was built on a silicone oxide substrate using patterned thick layers of negative tone photoresist covered by sputtered gold on the top surface. Attachment of lambda-DNA to the microelectrode was demonstrated using oligonucleotide-DNA phosphate backbone ligation and thiol-gold covalent bonding. Electrical characterizations based on I-V and AC impedance analysis of several repeatable data points of attachment with varying lambda-DNA concentration (500 ng/microL to 0.0625 ng/microL) showed measurable and significant conductivity of lambda-DNA molecular wires. Further study was carried out by measuring I-V and impedance while ramping up the temperature to reach complete denaturation (~1100C) resulting in no current transduction. Subsequent re-annealing of the DNA through incubation in TM buffer at annealing temperature (~900C) resulted in recovery of electrical conduction, providing a strong proof that DNA molecular wire is the one generate the electrical conductivity. lambda-DNA molecular wires reported to have differing impedance response at two temperature regions: impedance increases (conductivity decrease) between 40C -- 400C, and then decreases from 400C until DNA completely denatured (~1100C). The increase conductivity after 400C is an experimental support the long distance electron transport mechanism referred as "thermal hopping" mechanism. We believe that this research represents a significant departure from previous studies and makes unique contributions through (i) modification of DNA attachment methods has increase

  10. Coexistence of spinodal instability and thermal nucleation in thin-film rupture: Insights from molecular levels

    Science.gov (United States)

    Nguyen, Trung Dac; Fuentes-Cabrera, Miguel; Fowlkes, Jason D.; Rack, Philip D.

    2014-03-01

    Despite extensive investigation using hydrodynamic models and experiments over the past decades, there remain open questions regarding the origin of the initial rupture of thin liquid films. One of the reasons that makes it difficult to identify the rupture origin is the coexistence of two dewetting mechanisms, namely, thermal nucleation and spinodal instability, as observed in many experimental studies. Using a coarse-grained model and large-scale molecular dynamics simulations, we are able to characterize the very early stage of dewetting in nanometer-thick liquid-metal films wetting a solid substrate. We observe the features characteristic of both spinodal instability and thermal nucleation in the spontaneously dewetting films and show that these two macroscopic mechanisms share a common origin at molecular levels.

  11. Materials for organic photovoltaics: insights from detailed structural models and molecular simulations

    Directory of Open Access Journals (Sweden)

    Po Riccardo

    2012-10-01

    Full Text Available This paper contains a brief discussion of the role of detailed structural and computational studies, within the general field of organic photovoltaics. We review some of our recent work on poly(3-butylthiophene (P3BT and on [6,6]phenyl-C61-butyric acid methyl ester (PCBM. The first is a prototypical hole-transporting material, whose crystal forms I.’ and II were solved by us through the combined use of powder Xray diffraction, electron diffraction and molecular modelling. PCBM is a widely used fullerene derivative with electron-transporting properties. It has a rich polymorphism, which to date remains largely unexplored. Our molecular dynamics simulations have revealed interesting features of its solid-state organization, including that in the amorphous phase.

  12. Molecular Structure of Aggregated Amyloid-β: Insights from Solid-State Nuclear Magnetic Resonance.

    Science.gov (United States)

    Tycko, Robert

    2016-01-01

    Amyloid-β (Aβ) peptides aggregate to form polymorphic amyloid fibrils and a variety of intermediate assemblies, including oligomers and protofibrils, both in vitro and in human brain tissue. Since the beginning of the 21st century, considerable progress has been made to characterize the molecular structures of Aβ aggregates. Full molecular structural models based primarily on data from measurements using solid-state nuclear magnetic resonance (ssNMR) have been developed for several in vitro Aβ fibrils and one metastable protofibril. Partial structural characterization of other aggregation intermediates has been achieved. One full structural model for fibrils derived from brain tissue has also been reported. Future work is likely to focus on additional structures from brain tissue and on further clarification of nonfibrillar Aβ aggregates. PMID:27481836

  13. Molecular Insights into Aqueous NaCl Electrolytes Confined within Vertically-oriented Graphenes

    OpenAIRE

    Zheng Bo; Huachao Yang; Shuo Zhang; Jinyuan Yang; Jianhua Yan; Kefa Cen

    2015-01-01

    Vertically-oriented graphenes (VGs) are promising active materials for electric double layer capacitors (EDLCs) due to their unique morphological and structural features. This study, for the first time, reports the molecular dynamics (MD) simulations on aqueous NaCl electrolytes confined within VG channels with different surface charge densities and channel widths. Simulation results show that the accessibility of ions and the structure of EDLCs are determined by the ion type/size, surface ch...

  14. Mechanism for Cocaine Blocking the Transport of Dopamine: Insights from Molecular Modeling and Dynamics Simulations

    OpenAIRE

    Huang, Xiaoqin; Gu, Howard H.; Zhan, Chang-Guo

    2009-01-01

    Molecular modeling and dynamics simulations have been performed to study how cocaine inhibits dopamine transporter (DAT) for the transport of dopamine. The computationally determined DAT-ligand binding mode is totally different from previously proposed overlap binding mode in which cocaine- and dopamine-binding sites are the same (Beuming, T. et al. Nature Neurosci. 2008, 11, 780–789). The new cocaine-binding site does not overlap with, but close to, the dopamine-binding site. Analysis of all...

  15. Structural insights into the molecular ruler mechanism of the endoplasmic reticulum aminopeptidase ERAP1

    OpenAIRE

    Amit Gandhi; Damodharan Lakshminarasimhan; Yixin Sun; Hwai-Chen Guo

    2011-01-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an essential component of the immune system, because it trims peptide precursors and generates the N--restricted epitopes. To examine ERAP1's unique properties of length- and sequence-dependent processing of antigen precursors, we report a 2.3 Å resolution complex structure of the ERAP1 regulatory domain. Our study reveals a binding conformation of ERAP1 to the carboxyl terminus of a peptide, and thus provides direct evidence for the molecular...

  16. Mitochondrial DNA disease—molecular insights and potential routes to a cure

    OpenAIRE

    Russell, Oliver; Turnbull, Doug

    2014-01-01

    Mitochondrial DNA diseases are common neurological conditions caused by mutations in the mitochondrial genome or nuclear genes responsible for its maintenance. Current treatments for these disorders are focussed on the management of the symptoms, rather than the correction of biochemical defects caused by the mutation. This review focuses on the molecular effects of mutations, the symptoms they cause and current work focusing on the development of targeted treatments for mitochondrial DNA dis...

  17. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-01-01

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents. PMID:27147293

  18. Voltage-Gated Sodium Channels: Mechanistic Insights From Atomistic Molecular Dynamics Simulations.

    Science.gov (United States)

    Oakes, V; Furini, S; Domene, C

    2016-01-01

    The permeation of ions and other molecules across biological membranes is an inherent requirement of all cellular organisms. Ion channels, in particular, are responsible for the conduction of charged species, hence modulating the propagation of electrical signals. Despite the universal physiological implications of this property, the molecular functioning of ion channels remains ambiguous. The combination of atomistic structural data with computational methodologies, such as molecular dynamics (MD) simulations, is now considered routine to investigate structure-function relationships in biological systems. A fuller understanding of conduction, selectivity, and gating, therefore, is steadily emerging due to the applicability of these techniques to ion channels. However, because their structure is known at atomic resolution, studies have consistently been biased toward K(+) channels, thus the molecular determinants of ionic selectivity, activation, and drug blockage in Na(+) channels are often overlooked. The recent increase of available crystallographic data has eminently encouraged the investigation of voltage-gated sodium (NaV) channels via computational methods. Here, we present an overview of simulation studies that have contributed to our understanding of key principles that underlie ionic conduction and selectivity in Na(+) channels, in comparison to the K(+) channel analogs. PMID:27586285

  19. Stress-induced neutral lipid biosynthesis in microalgae - Molecular, cellular and physiological insights.

    Science.gov (United States)

    Zienkiewicz, Krzysztof; Du, Zhi-Yan; Ma, Wei; Vollheyde, Katharina; Benning, Christoph

    2016-09-01

    Photosynthetic microalgae have promise as biofuel feedstock. Under certain conditions, they produce substantial amounts of neutral lipids, mainly in the form of triacylglycerols (TAGs), which can be converted to fuels. Much of our current knowledge on the genetic and molecular basis of algal neutral lipid metabolism derives mainly from studies of plants, i.e. seed tissues, and to a lesser extent from direct studies of algal lipid metabolism. Thus, the knowledge of TAG synthesis and the cellular trafficking of TAG precursors in algal cells is to a large extent based on genome predictions, and most aspects of TAG metabolism have yet to be experimentally verified. The biofuel prospects of microalgae have raised the interest in mechanistic studies of algal TAG biosynthesis in recent years and resulted in an increasing number of publications on lipid metabolism in microalgae. In this review we summarize the current findings on genetic, molecular and physiological studies of TAG accumulation in microalgae. Special emphasis is on the functional analysis of key genes involved in TAG synthesis, molecular mechanisms of regulation of TAG biosynthesis, as well as on possible mechanisms of lipid droplet formation in microalgal cells. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:26883557

  20. Molecular dynamics simulations provide insights into the substrate specificity of FAOX family members.

    Science.gov (United States)

    Rigoldi, Federica; Spero, Ludovica; Dalle Vedove, Andrea; Redaelli, Alberto; Parisini, Emilio; Gautieri, Alfonso

    2016-07-19

    Enzymatic assays based on Fructosyl Amino Acid Oxidases (FAOX) represent a potential, rapid and economical strategy to measure glycated hemoglobin (HbA1c), which is in turn a reliable method to monitor the insurgence and the development of diabetes mellitus. However, the engineering of naturally occurring FAOX to specifically recognize fructosyl-valine (the glycated N-terminal residue of HbA1c) has been hindered by the paucity of information on the tridimensional structures and catalytic residues of the different FAOX that exist in nature, and in general on the molecular mechanisms that regulate specificity in this class of enzymes. In this study, we use molecular dynamics simulations and advanced modeling techniques to investigate five different relevant wild-type FAOX (Amadoriase I, Amadoriase II, PnFPOX, FPOX-E and N1-1-FAOD) in order to elucidate the molecular mechanisms that drive their specificity towards polar and nonpolar substrates. Specifically, we compare these five different FAOX in terms of overall folding, ligand entry tunnels, ligand binding residues and ligand binding energies. Our work will contribute to future enzyme structure modifications aimed at the rational design of novel biosensors for the monitoring of blood glucose levels. PMID:27327839

  1. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared – non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  2. Insights from the molecular characterization of mercury stress proteins identified by proteomics in E.coli nissle 1917.

    Science.gov (United States)

    Seshapani, Panthangi; Rayalu, Daddam Jayasimha; Kumar, Vadde Kiran; Sekhar, Kathera Chandra; Kumari, Jasti Pramoda

    2013-01-01

    Differently expressed proteins in probiotic Escherichia coli nissle 1917 under mercury stress identified by using a proteomic approach. We applied to separate proteins by using two-dimensional gel electrophoresis and proteins were identified using MALDI-TOF-MS using PMF, by mascot database search using the NCBI database. we identified six proteins after exposure to mercury stress with respect to different functional classes. It is useful to understand the molecular insights into mercury stress in probiotic E. coli. Next we describe a structure generated by homology modelling and functional domain identification; it is interesting to study the impact of stress on protein structures. MS characterization and computational methods together provide the opportunity to examine the impact of stress arising from mercury. The role of these proteins in metal tolerance and structure relation is discussed. To the best of our knowledge, proteomics of E. coli nissle 1917 overview of mercury stress has been reported for the first time. PMID:23847405

  3. New insights into the molecular epidemiology and population genetics of Schistosoma mansoni in Ugandan pre-school children and mothers.

    Directory of Open Access Journals (Sweden)

    Martha Betson

    Full Text Available Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1 gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes.

  4. New Insights into Fluvial Carbon Responses to Future Forest Management and Climate Change Obtained from Multi-Scale Modelling of Biogeochemical Processes

    Science.gov (United States)

    Oni, S. K.; Tiwari, T.; Futter, M. N.; Agren, A.; Teutschbein, C.; Ledesma, J.; Schelker, J.; Laudon, H.

    2014-12-01

    The boreal ecozone covers 2x107 km2 of the northern circumpolar region and includes 29% of the world's forests. The boreal consists of mosaic of forest/wetland landscape elements and stores about 500 Gt3 carbon (C) with a delicate sink-source C balance. Dissolved organic carbon (DOC) is the main form of C exported from boreal landscapes and is fundamental to global C cycling. This northern ecosystem is vulnerable to global climate change, and increasing demands for forest products threaten its surface water resources. So far, there have been no attempts to assess the combined impacts of climate change and forest management on the future DOC fluxes from boreal surface waters. While differences in model assumptions may have negligible effects on present day simulations, these differences could be amplified when projecting the future climate and land use change conditions. Here we use an ensemble of regional climate models and multi-scale models of biogeochemical processes to gain insights into uncertainties associated with climate change and forest management on C and runoff dynamics in boreal landscape. While there are significant uncertainties associated with model projections, our results show that climate change will be the main driver of long term DOC dynamics in meso- to large boreal catchments in the future. However, forestry intensifies hydrological processes and can lead to large DOC fluxes at the headwater scales.

  5. Mitochondrial DNA disease—molecular insights and potential routes to a cure

    Energy Technology Data Exchange (ETDEWEB)

    Russell, Oliver; Turnbull, Doug, E-mail: doug.turnbull@newcastle.ac.uk

    2014-07-01

    Mitochondrial DNA diseases are common neurological conditions caused by mutations in the mitochondrial genome or nuclear genes responsible for its maintenance. Current treatments for these disorders are focussed on the management of the symptoms, rather than the correction of biochemical defects caused by the mutation. This review focuses on the molecular effects of mutations, the symptoms they cause and current work focusing on the development of targeted treatments for mitochondrial DNA disease. - Highlights: • We discuss several common disease causing mtDNA mutations. • We highlight recent work linking pathogenicity to deletion size and heteroplasmy. • We discuss recent advances in the development of targeted mtDNA disease treatments.

  6. Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations

    Science.gov (United States)

    Lin, Xubo; Bai, Tingting; Zuo, Yi Y.; Gu, Ning

    2014-02-01

    Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs

  7. Insights into the structural stability of Bax from molecular dynamics simulations at high temperatures

    Science.gov (United States)

    Rosas-Trigueros, Jorge Luis; Correa-Basurto, José; Guadalupe Benítez-Cardoza, Claudia; Zamorano-Carrillo, Absalom

    2011-01-01

    Bax is a member of the Bcl-2 protein family that participates in mitochondrion-mediated apoptosis. In the early stages of the apoptotic pathway, this protein migrates from the cytosol to the outer mitochondrial membrane, where it is inserted and usually oligomerizes, making cytochrome c-compatible pores. Although several cellular and structural studies have been reported, a description of the stability of Bax at the molecular level remains elusive. This article reports molecular dynamics simulations of monomeric Bax at 300, 400, and 500 K, focusing on the most relevant structural changes and relating them to biological experimental results. Bax gradually loses its α-helices when it is submitted to high temperatures, yet it maintains its globular conformation. The resistance of Bax to adopt an extended conformation could be due to several interactions that were found to be responsible for maintaining the structural stability of this protein. Among these interactions, we found salt bridges, hydrophobic interactions, and hydrogen bonds. Remarkably, salt bridges were the most relevant to prevent the elongation of the structure. In addition, the analysis of our results suggests which conformational movements are implicated in the activation/oligomerization of Bax. This atomistic description might have important implications for understanding the functionality and stability of Bax in vitro as well as within the cellular environment. PMID:21936009

  8. Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies.

    Science.gov (United States)

    Karthikeyan, Subramani; Bharanidharan, Ganesan; Kesherwani, Manish; Mani, Karthik Ananth; Srinivasan, Narasimhan; Velmurugan, Devadasan; Aruna, Prakasarao; Ganesan, Singaravelu

    2016-06-01

    4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster's theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction. PMID:26368536

  9. Molecular insights into the boundary conditions in the Stokes-Einstein relation

    Science.gov (United States)

    Ishii, Yoshiki; Ohtori, Norikazu

    2016-05-01

    In order to mimic the Brownian particle in liquid, molecular dynamics calculations of dilute solutions of spherical fullerene molecules with various sizes in liquid Ar were performed. To establish the scaling equation for self-diffusion coefficient, D , of the fullerenes, the dependence of D was examined on the mass ratio of solute to solvent and on the energy-parameter ratio used in the Lennard-Jones potentials. The dependence on the energy-parameter ratio remains up to C540, whereas D rapidly becomes independent of the mass ratio with increasing mass of the solute. The product of the scaling equations obtained for the D of the solute and for shear viscosity, ηsv, for the solvent gives a relation which replaces the Stokes-Einstein relation based on the hydrodynamics. The present expression does not need both the boundary conditions and the hydrodynamic particle size, but instead the energy-parameter ratio, packing fraction of solvent, and bare size of solute. From the viewpoint of the tackiness at the boundary, the cage correlation function around the diffusing particle was examined; it was found that the decay time of the function depends mainly on the the energy-parameter ratio. Therefore, the energy-parameter ratio accounts for the main part of both the boundary conditions and the hydrodynamic particle size in the Stokes equation, which have so far been ill-defined in any molecular theories.

  10. Enhanced heme accessibility in horse heart mini-myoglobin: Insights from molecular modelling and reactivity studies.

    Science.gov (United States)

    Polticelli, Fabio; Zobnina, Veranika; Ciaccio, Chiara; de Sanctis, Giampiero; Ascenzi, Paolo; Coletta, Massimo

    2015-11-01

    Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure-function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the molecular model of mini-HHMb has been built and refined by molecular dynamics simulations, and analyzed in parallel with that of full length HHMb. Moreover, imidazole binding parameters of ferric mini-HHMb and HHMb have been determined. Furthermore, structural data of ferric mini-HHMb and HHMb have been correlated with the imidazole and previously determined azide binding properties. Present results indicate that, despite the extensive trimming, the heme-α-helices E-F substructure is essentially unaltered in mini-HHMb with respect to HHMb. However, the heme-Fe atom displays an enhanced accessibility in mini-HHMb, which may affect both ligand association and dissociation kinetics. PMID:26363214

  11. The peptide-receptive transition state of MHC-1 molecules: Insight from structure and molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Robinson H.; Mage, M.; Dolan, M.; Wang, R.; Boyd, L.; Revilleza, M.; Natarajan, K.; Myers, N.; Hansen, T.; Margulies, D.

    2012-05-01

    MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I-restricted CD8(+) T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 3(10) helix that flips from an exposed 'open' position in the PR transition state to a 'closed' position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46-53 of murine H-2L(d) MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.

  12. Inhibitory effects of daidzein and genistein on trypsin: Insights from spectroscopic and molecular docking studies.

    Science.gov (United States)

    Zeng, Hua-Jin; Wang, Ya-Ping; Yang, Ran; You, Jing; Qu, Ling-Bo

    2016-08-01

    In this work, the inhibitory effect of two isoflavonoids including daidzein and genistein on trypsin and their binding mechanism were determined by spectroscopic and molecular docking approaches. The results indicated that both daidzein and genistein reversibly inhibited trypsin in a competitive manner with IC50 values of 68.01×10(-6)molL(-1) and 64.70×10(-6)molL(-1) and Ki values of 62.12×10(-6)molL(-1) and 59.83×10(-6)molL(-1), respectively. They could spontaneously bind with trypsin mainly through hydrophobic force and electrostatic interactions with a single binding site. Analysis of circular dichrosim spectra and molecular docking revealed that both isoflavonoids bound directly into the catalytic cavity and the microenvironment and secondary structure of trypsin were changed in this process, which caused the inhibition of trypsin activity. All these experimental results and theoretical data in this work would be help in understanding the mechanism of inhibitory effects of daidzein and genistein against trypsin and the potential of isoflavonoid to relieve symptoms of pancreatitis. PMID:27109756

  13. Interaction of Tenebrio Molitor Antifreeze Protein with Ice Crystal: Insights from Molecular Dynamics Simulations.

    Science.gov (United States)

    Ramya, L; Ramakrishnan, Vigneshwar

    2016-07-01

    Antifreeze proteins (AFP) observed in cold-adapting organisms bind to ice crystals and prevent further ice growth. However, the molecular mechanism of AFP-ice binding and AFP-inhibited ice growth remains unclear. Here we report the interaction of the insect antifreeze protein (Tenebrio molitor, TmAFP) with ice crystal by molecular dynamics simulation studies. Two sets of simulations were carried out at 263 K by placing the protein near the primary prism plane (PP) and basal plane (BL) of the ice crystal. To delineate the effect of temperatures, both the PP and BL simulations were carried out at 253 K as well. The analyses revealed that the protein interacts strongly with the ice crystal in BL simulation than in PP simulation both at 263 K and 253 K. Further, it was observed that the interactions are primarily mediated through the interface waters. We also observed that as the temperature decreases, the interaction between the protein and the ice increases which can be attributed to the decreased flexibility and the increased structuring of the protein at low temperature. In essence, our study has shed light on the interaction mechanism between the TmAFP antifreeze protein and the ice crystal. PMID:27492241

  14. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    Science.gov (United States)

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets.

  15. Molecular underpinnings of prefrontal cortex development in rodents provide insights into the etiology of neurodevelopmental disorders.

    Science.gov (United States)

    Schubert, D; Martens, G J M; Kolk, S M

    2015-07-01

    The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcription factors, guidance cues and other regulatory molecules and requires the intricate and temporal orchestration of a number of developmental processes. Disturbance or failure of any of these processes causing neurodevelopmental abnormalities within the PFC may contribute to several of the cognitive deficits seen in patients with neurodevelopmental disorders. In this review, we elaborate on the specific processes underlying prefrontal development, such as induction and patterning of the prefrontal area, proliferation, migration and axonal guidance of medial prefrontal progenitors, and their eventual efferent and afferent connections. We furthermore integrate for the first time the available knowledge from genome-wide studies that have revealed genes linked to neurodevelopmental disorders with experimental molecular evidence in rodents. The integrated data suggest that the pathogenic variants in the neurodevelopmental disorder-associated genes induce prefrontal cytoarchitectonical impairments. This enhances our understanding of the molecular mechanisms of prefrontal (mis)development underlying the four major neurodevelopmental disorders in humans, that is, intellectual disability, autism spectrum disorders, attention deficit hyperactivity disorder and schizophrenia, and may thus provide clues for the development of novel therapies. PMID:25450230

  16. Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy.

    Science.gov (United States)

    Martínez-Aguilar, Juan; Clifton-Bligh, Roderick; Molloy, Mark P

    2016-01-01

    Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype. PMID:27025787

  17. Extending Molecular Signatures of Climatic and Environmental Change to the Mesozoic

    Science.gov (United States)

    Brassell, S. C.

    2007-12-01

    The distributions, abundances and isotopic compositions of molecular constituents in sediments depend on their source organisms and the combination of environmental and climatic parameters that constrain or control their biosynthesis. Many such relationships are well documented and understood, thereby providing proxies of proven utility in paleoclimatic reconstructions. Thus, the temperature dependence in the extent of unsaturation in alkenones derived from prymnesiophyte algae, and in the proportion of ring structures in glycerol dibiphytanyl glycerol tetraethers (GDGTs) synthesized by crenarchaeota enables determination of sea surface paleotemperatures from sedimentary records. This molecular approach presumes temporal uniformity in the controlling factors on biosynthesis of these lipids, and their survival in the geological record, notwithstanding the challenge of establishing ancient calibrations for such proxies. Thus, alkenone records from marine sediments document cooling at the Eocene/Oligocene boundary but cannot assess changes in ocean temperatures during the Cretaceous, unlike GDGTs, which record fluctuations in ocean temperatures during the Early Cretaceous, and even survive in Jurassic strata. Other molecular measures offer less precise, yet informative, indications of climate. For example, the occurrence of sterol ethers in Valanginian sediments from the mid-Pacific suggests some cooling at that time, since these compounds are only known to occur elsewhere in cold waters or upwelling systems. Molecular compositions can also attest to levels of oxygenation in marine systems. In particular, the occurrence of 13C-depleted isorenieratane indicates the presence of photosynthetic green sulfur bacteria, and therefore anoxic conditions, albeit perhaps short-lived. Intermittent occurrences of isorenieratane often alternate with the appearance of 2-methylhopanoids, which provide separate distinct evidence for variations in oxygenation, linked to circumstances

  18. Anticancer compound plumbagin and its molecular targets: a structural insight into the inhibitory mechanisms using computational approaches.

    Directory of Open Access Journals (Sweden)

    Mohammad S Jamal

    Full Text Available Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone is a naphthoquinone derivative from the roots of plant Plumbago zeylanica and belongs to one of the largest and diverse groups of plant metabolites. The anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin exerts inhibitory effects on multiple cancer-signaling proteins, however, the binding mode and the molecular interactions have not yet been elucidated for most of these protein targets. The present study is the first attempt to provide structural insights into the binding mode of plumbagin to five cancer signaling proteins viz. PI3Kγ, AKT1/PKBα, Bcl-2, NF-κB, and Stat3 using molecular docking and (unbinding simulation analysis. We validated plumbagin docking to these targets with previously known important residues. The study also identified and characterized various novel interacting residues of these targets which mediate the binding of plumbagin. Moreover, the exact modes of inhibition when multiple mode of inhibition existed was also shown. Results indicated that the engaging of these important interacting residues in plumbagin binding leads to inhibition of these cancer-signaling proteins which are key players in the pathogenesis of cancer and thereby ceases the progression of the disease.

  19. Structural and molecular basis of cellulase Cel48F by computational modeling: Insight into catalytic and product release mechanism.

    Science.gov (United States)

    Qian, Mengdan; Guan, Shanshan; Shan, Yaming; Zhang, Hao; Wang, Song

    2016-06-01

    As a processive cellulase, Cel48F from Clostridium cellulolyticum plays a crucial role in cellulose fiber degradation. It has been confirmed in experiment that residue Glu44 will greatly affect the catalytic activity but the mechanism is still unknown. In this study, conventional molecular dynamics, steered molecular dynamics and free energy calculation were integrated to simulate the hydrolysis and product release process to gain insights into the factors that influence catalytic activity. Analysis of simulation results indicated that Glu44 could maintain the proper conformation of its substrate to ensure successful cleavage reaction or serve as a base required in the inverting mechanism in hydrolysis. After hydrolysis is completed, residues Glu44, Asp494, Trp611 and Glu55 participate in hydrogen bond rearrangement during product releasing process. This rearrangement can reduce the sliding barrier and stimulate the product to move toward the exit in the initial release stage. Dependent on the rearrangement, the product moves toward the exit and is exposed to an increasing amount of solvent molecules, which makes solvent effect more and more notable. With the assistance of solvent interaction, product can get rid of the enzyme more easily. However, the subsequent release process remains uncertain because of the disordered motion of solvent molecules. This work provides theoretical data as a basis of cellulase modification or mutation. PMID:26993462

  20. Insight into a molecular interaction force supporting peptide backbones and its implication to protein loops and folding.

    Science.gov (United States)

    Du, Qi-Shi; Chen, Dong; Xie, Neng-Zhong; Huang, Ri-Bo; Chou, Kuo-Chen

    2015-09-01

    Although not being classified as the most fundamental protein structural elements like α-helices and β-strands, the loop segment may play considerable roles for protein stability, flexibility, and dynamic activity. Meanwhile, the protein loop is also quite elusive; i.e. its interactions with the other parts of protein as well as its own shape-maintaining forces have still remained as a puzzle or at least not quite clear yet. Here, we report a molecular force, the so-called polar hydrogen-π interaction (Hp-π), which may play an important role in supporting the backbones of protein loops. By conducting the potential energy surface scanning calculations on the quasi π-plane of peptide bond unit, we have observed the following intriguing phenomena: (1) when the polar hydrogen atom of a peptide unit is perpendicularly pointing to the π-plane of other peptide bond units, a remarkable Hp-π interaction occurs; (2) the interaction is distance and orientation dependent, acting in a broad space, and belonging to the 'point-to-plane' one. The molecular force reported here may provide useful interaction concepts and insights into better understanding the loop's unique stability and flexibility feature, as well as the driving force of the protein global folding. PMID:25375237

  1. Insights into the molecular phylogeny and historical biogeography of the white-clawed crayfish (Decapoda, Astacidae).

    Science.gov (United States)

    Jelić, Mišel; Klobučar, Göran I V; Grandjean, Frédéric; Puillandre, Nicolas; Franjević, Damjan; Futo, Momir; Amouret, Julien; Maguire, Ivana

    2016-10-01

    In this study, the evolutionary history of the white-clawed crayfish (WCC) was evaluated using large-scale datasets comprising >1350 specimens from the entire distribution range. Using species delimitation methods on mitochondrial DNA (mtDNA) sequences, we propose four primary species hypotheses for WCC. Sequences for several nuclear regions were screened but none showed significant variation within WCC. This result favours a single secondary species hypothesis and indicates the existence of a mito-nuclear discordance in WCC. Therefore, mtDNA groups were considered only as genetic units that carry information about ancient divergences within WCC and not as taxonomic units. The reconstruction of ancestral ranges and divergence time estimates were used to link the current genetic structure with paleogeographic processes. These results showed that the emergence of mtDNA groups in WCC could be related to the Messinian Salinity Crisis, the climate cooling during the Pliocene and Pleistocene, and (paleo)shifting of the Adriatic Sea coastline in the Padanovenezian Plain. The most recent common ancestor of the mtDNA groups most likely originated from Dalmatia (eastern Adriatic coast) as indicated by the reconstruction of ancestral ranges. This ecoregion, along with the Gulf of Venice Drainages, harbours a high genetic diversity and should be emphasised as an area of the highest conservation priority. PMID:27404041

  2. Optimizing Water Transport through Graphene-Based Membranes: Insights from Nonequilibrium Molecular Dynamics.

    Science.gov (United States)

    Muscatello, Jordan; Jaeger, Frederike; Matar, Omar K; Müller, Erich A

    2016-05-18

    Recent experimental results suggest that stacked layers of graphene oxide exhibit strong selective permeability to water. To construe this observation, the transport mechanism of water permeating through a membrane consisting of layered graphene sheets is investigated via nonequilibrium and equilibrium molecular dynamics simulations. The effect of sheet geometry is studied by changing the offset between the entrance and exit slits of the membrane. The simulation results reveal that the permeability is not solely dominated by entrance effects; the path traversed by water molecules has a considerable impact on the permeability. We show that contrary to speculation in the literature, water molecules do not pass through the membrane as a hydrogen-bonded chain; instead, they form well-mixed fluid regions confined between the graphene sheets. The results of the present work are used to provide guidelines for the development of graphene and graphene oxide membranes for desalination and solvent separation. PMID:27121070

  3. Molecular Insights into Carbon Nanotube Supercapacitors: Capacitance Independent of Voltage and Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Guang [Vanderbilt Univ., Nashville, TN (United States). Dept. of Chemical and Biomolecular Engineering; Li, Song [Vanderbilt Univ., Nashville, TN (United States). Dept. of Chemical and Biomolecular Engineering; Atchison, Jennifer S. [Leibniz Inst. for New Materials (INM), Saarbrücken (Germany); Presser, Volker [Leibniz Inst. for New Materials (INM), Saarbrücken (Germany); Cummings, Peter T. [Vanderbilt Univ., Nashville, TN (United States). Dept. of Chemical and Biomolecular Engineering; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Science

    2013-04-12

    Molecular dynamics (MD) simulations of supercapacitors with single-walled carbon nanotube (SWCNT) electrodes in room-temperature ionic liquids were performed to investigate the influences of the applied electrical potential, the radius/curvature of SWCNTs, and temperature on their capacitive behavior. It is found that (1) SWCNTs-based supercapacitors exhibit a near-flat capacitance–potential curve, (2) the capacitance increases as the tube radius decreases, and (3) the capacitance depends little on the temperature. We report the first MD study showing the influence of the electrode curvature on the capacitance–potential curve and negligible dependence of temperature on capacitance of tubular electrode. The latter is in good agreement with recent experimental findings and is attributed to the similarity of the electrical double layer (EDL) microstructure with temperature varying from 260 to 400 K. The electrode curvature effect is explained by the dominance of charge overscreening and increased ion density per unit area of electrode surface.

  4. Solid phase epitaxy amorphous silicon re-growth: some insight from empirical molecular dynamics simulation

    CERN Document Server

    Krzeminski, Christophe; 10.1140/epjb/e2011-10958-7

    2011-01-01

    The modelling of interface migration and the associated diffusion mechanisms at the nanoscale level is a challenging issue. For many technological applications ranging from nanoelectronic devices to solar cells, more knowledge of the mechanisms governing the migration of the silicon amorphous/crystalline interface and dopant diffusion during solid phase epitaxy is needed. In this work, silicon recrystallisation in the framework of solid phase epitaxy and the influence on orientation effects have been investigated at the atomic level using empirical molecular dynamics simulations. The morphology and the migration process of the interface has been observed to be highly dependent on the original inter-facial atomic structure. The [100] interface migration is a quasi-planar ideal process whereas the cases [110] and [111] are much more complex with a more diffuse interface. For [110], the interface migration corresponds to the formation and dissolution of nanofacets whereas for [111] a defective based bilayer reor...

  5. How are completely desolvated ions produced in electrospray ionization: insights from molecular dynamics simulations.

    Science.gov (United States)

    Daub, Christopher D; Cann, Natalie M

    2011-11-15

    We apply molecular dynamics (MD) simulations to study the final phase of electrospray ionization (ESI), where an ion loses all of its associated solvent molecules. By applying an electric field to a cluster of H(2)O molecules solvating an ion and including a surrounding gas of varying pressure, we demonstrate that collisions with the gas play a major role in removing this final layer of solvent. We make quantitative predictions of the critical velocity required for the cluster to start losing molecules via collisions with gas and propose that this should be important in real ESI experiments. Such collisions have heretofore not been explicitly considered in discussions of the ESI process. PMID:22017403

  6. Molecular Ecology of Hypersaline Microbial Mats: Current Insights and New Directions

    Directory of Open Access Journals (Sweden)

    Hon Lun Wong

    2016-01-01

    Full Text Available Microbial mats are unique geobiological ecosystems that form as a result of complex communities of microorganisms interacting with each other and their physical environment. Both the microorganisms present and the network of metabolic interactions govern ecosystem function therein. These systems are often found in a range of extreme environments, and those found in elevated salinity have been particularly well studied. The purpose of this review is to briefly describe the molecular ecology of select model hypersaline mat systems (Guerrero Negro, Shark Bay, S’Avall, and Kiritimati Atoll, and any potentially modulating effects caused by salinity to community structure. In addition, we discuss several emerging issues in the field (linking function to newly discovered phyla and microbial dark matter, which illustrate the changing paradigm that is seen as technology has rapidly advanced in the study of these extreme and evolutionally significant ecosystems.

  7. Water adsorption and proton conduction in metal-organic frameworks: Insights from molecular simulations

    Science.gov (United States)

    Paesani, Francesco

    2014-03-01

    Metal-organic frameworks (MOFs) are a relatively new class of porous materials that hold great potential for a wide range of applications in chemistry, materials science, and nanoengineering. Compared to other porous materials such as zeolites, MOF properties are highly tunable. In particular, it has been shown that both size and shape of the MOF pores can be rationally designed for specific applications. For example, the ability to modify the framework properties with respect to hydrophilicity/hydrophobicity and acidity/basicity can enable the direct control of proton conduction through carrier molecules adsorbed inside the pores. Here, I report on our current efforts aimed at providing a molecular-level characterization of water-mediated proton conduction through the MOF pores. Particular emphasis will be put on correlation between proton conduction and both structural and chemical properties of the frameworks as well as on the dynamical behavior of water confined in the MOF pores. NSF award number: DMR-130510

  8. Emerging molecular insights into the interaction between probiotics and the host intestinal mucosa.

    Science.gov (United States)

    Bron, Peter A; van Baarlen, Peter; Kleerebezem, Michiel

    2012-01-01

    Probiotic bacteria can modulate immune responses in the host gastrointestinal tract to promote health. The genomics era has provided novel opportunities for the discovery and characterization of bacterial probiotic effector molecules that elicit specific responses in the intestinal system. Furthermore, nutrigenomic analyses of the response to probiotics have unravelled the signalling and immune response pathways which are modulated by probiotic bacteria. Together, these genomic approaches and nutrigenomic analyses have identified several bacterial factors that are involved in modulation of the immune system and the mucosal barrier, and have revealed that a molecular 'bandwidth of human health' could represent a key determinant in an individual's physiological responsiveness to probiotics. These approaches may lead to improved stratification of consumers and to subpopulation-level probiotic supplementation to maintain or improve health, or to reduce the risk of disease. PMID:22101918

  9. Molecular mechanisms of D-cycloserine in facilitating fear extinction: insights from RNAseq.

    Science.gov (United States)

    Malan-Müller, Stefanie; Fairbairn, Lorren; Daniels, Willie M U; Dashti, Mahjoubeh Jalali Sefid; Oakeley, Edward J; Altorfer, Marc; Kidd, Martin; Seedat, Soraya; Gamieldien, Junaid; Hemmings, Sîan Megan Joanna

    2016-02-01

    D-cycloserine (DCS) has been shown to be effective in facilitating fear extinction in animal and human studies, however the precise mechanisms whereby the co-administration of DCS and behavioural fear extinction reduce fear are still unclear. This study investigated the molecular mechanisms of intrahippocampally administered D-cycloserine in facilitating fear extinction in a contextual fear conditioning animal model. Male Sprague Dawley rats (n = 120) were grouped into four experimental groups (n = 30) based on fear conditioning and intrahippocampal administration of either DCS or saline. The light/dark avoidance test was used to differentiate maladapted (MA) (anxious) from well-adapted (WA) (not anxious) subgroups. RNA extracted from the left dorsal hippocampus was used for RNA sequencing and gene expression data was compared between six fear-conditioned + saline MA (FEAR + SALINE MA) and six fear-conditioned + DCS WA (FEAR + DCS WA) animals. Of the 424 significantly downregulated and 25 significantly upregulated genes identified in the FEAR + DCS WA group compared to the FEAR + SALINE MA group, 121 downregulated and nine upregulated genes were predicted to be relevant to fear conditioning and anxiety and stress-related disorders. The majority of downregulated genes transcribed immune, proinflammatory and oxidative stress systems molecules. These molecules mediate neuroinflammation and cause neuronal damage. DCS also regulated genes involved in learning and memory processes, and genes associated with anxiety, stress-related disorders and co-occurring diseases (e.g., cardiovascular diseases, digestive system diseases and nervous system diseases). Identifying the molecular underpinnings of DCS-mediated fear extinction brings us closer to understanding the process of fear extinction. PMID:26400817

  10. Insights using a molecular approach into the life cycle of a tapeworm infecting great white sharks.

    Science.gov (United States)

    Randhawa, Haseeb S

    2011-04-01

    The great white shark Carcharodon carcharias Linnaeus, 1758 is a versatile and fierce predator (and responsible for many shark attacks on humans). This apex predator feeds on a wide range of organisms including teleosts, other elasmobranchs, cephalopods, pinnipeds, and cetaceans. Although much is known about its diet, no trophic links have been empirically identified as being involved in the transmission of its tapeworm parasites. Recently, the use of molecular tools combined with phylogenetics has proven useful to identify larval and immature stages of marine tapeworms; utilization of the technique has been increasing rapidly. However, the usefulness of this approach remains limited by the availability of molecular data. Here, I employed gene sequence data from the D2 region of the large subunit of ribosomal DNA to link adults of the tapeworm Clistobothrium carcharodoni Dailey and Vogelbein, 1990 (Cestoda: Tetraphyllidea) to larvae for which sequence data for this gene are available. The sequences from the adult tapeworms were genetically identical (0% sequence divergence) to those available on GenBank for "SP" 'small' Scolex pleuronectis recovered from the striped dolphin (Stenella coeruleoalba) and Risso's dolphin (Grampus griseus). This study is the first to provide empirical evidence linking the trophic interaction between great white sharks and cetaceans as a definitive route for the successful transmission of a tetraphyllidean tapeworm. Using the intensity of infection data from this shark and from cetaceans as proxies for the extent of predation, I estimate that this individual shark would have consumed between 9 to 83 G. griseus , fresh, dead, or both, in its lifetime. PMID:21506792

  11. Electrochemical double layer near polar reduced graphene oxide electrode: Insights from molecular dynamic study

    International Nuclear Information System (INIS)

    Graphical abstract: Display Omitted - Highlights: • We have investigated the electrochemical double layer capacity of polar reduced graphene oxide electrode with aqueous solution by using molecular dynamic simulation, which is rare in previous studies currently. • The dipole orientation of water molecules near the polar reduced graphene oxide electrode will strongly depend on the polarity of functional group on reduced graphene oxide surface. The polarization interaction also restricts the rotation response of water molecules and weakens their mobility near the charged electrode, resulting in the decrease of integral capacitance value of reduced graphene oxide with increasing of functional groups concentration. • To obtain the accurate partial charge distribution of decorated functional group and corresponding surface polarization of reduced graphene oxide electrode, Bader charge analysis based on density functional theory calculations is used. - Abstract: Reduced graphene oxide (rGO) has emerged as an attractive choice for electrochemical double layer capacitors. Based on the accurate atomic partial charge distribution determined by density functional theory calculations, the electrochemical double layer structural and capacitive properties at the rGO/NaCl aqueous electrolyte interface are studied using the molecular dynamic simulations. Due to the charge redistribution mainly around oxygen functional groups, rGO will form a strong polar surface. It will significantly change the arrangement of surrounding water molecules through a hydrogen bond like interaction. The change of dipole orientation of water will induce corresponding net charge redistribution, leading to a change of potential of zero charge of rGO electrode. The polarization interaction also restricts the orientation of electrolyte molecules and weakens their mobility, resulting in the decrease of integral capacitance value of rGO with increasing of functional groups concentration. This work

  12. Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells

    Directory of Open Access Journals (Sweden)

    Jonathan Laiño

    2016-08-01

    Full Text Available Researchers have demonstrated that lactic acid bacteria (LAB with immunomodulatory capabilities (immunobiotics exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS, that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals.

  13. Lessons from mammalian hibernators: molecular insights into striated muscle plasticity and remodeling.

    Science.gov (United States)

    Tessier, Shannon N; Storey, Kenneth B

    2016-05-01

    Striated muscle shows an amazing ability to adapt its structural apparatus based on contractile activity, loading conditions, fuel supply, or environmental factors. Studies with mammalian hibernators have identified a variety of molecular pathways which are strategically regulated and allow animals to endure multiple stresses associated with the hibernating season. Of particular interest is the observation that hibernators show little skeletal muscle atrophy despite the profound metabolic rate depression and mechanical unloading that they experience during long weeks of torpor. Additionally, the cardiac muscle of hibernators must adjust to low temperature and reduced perfusion, while the strength of contraction increases in order to pump cold, viscous blood. Consequently, hibernators hold a wealth of knowledge as it pertains to understanding the natural capacity of myocytes to alter structural, contractile and metabolic properties in response to environmental stimuli. The present review outlines the molecular and biochemical mechanisms which play a role in muscular atrophy, hypertrophy, and remodeling. In this capacity, four main networks are highlighted: (1) antioxidant defenses, (2) the regulation of structural, contractile and metabolic proteins, (3) ubiquitin proteosomal machinery, and (4) macroautophagy pathways. Subsequently, we discuss the role of transcription factors nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Myocyte enhancer factor 2 (MEF2), and Forkhead box (FOXO) and their associated posttranslational modifications as it pertains to regulating each of these networks. Finally, we propose that comparing and contrasting these concepts to data collected from model organisms able to withstand dramatic changes in muscular function without injury will allow researchers to delineate physiological versus pathological responses. PMID:26982616

  14. New insight on FGFR3-related chondrodysplasias molecular physiopathology revealed by human chondrocyte gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Laurent Schibler

    Full Text Available Endochondral ossification is the process by which the appendicular skeleton, facial bones, vertebrae and medial clavicles are formed and relies on the tight control of chondrocyte maturation. Fibroblast growth factor receptor (FGFR3 plays a role in bone development and maintenance and belongs to a family of proteins which differ in their ligand affinities and tissue distribution. Activating mutations of the FGFR3 gene lead to craniosynostosis and multiple types of skeletal dysplasia with varying degrees of severity: thanatophoric dysplasia (TD, achondroplasia and hypochondroplasia. Despite progress in the characterization of FGFR3-mediated regulation of cartilage development, many aspects remain unclear. The aim and the novelty of our study was to examine whole gene expression differences occurring in primary human chondrocytes isolated from normal cartilage or pathological cartilage from TD-affected fetuses, using Affymetrix technology. The phenotype of the primary cells was confirmed by the high expression of chondrocytic markers. Altered expression of genes associated with many cellular processes was observed, including cell growth and proliferation, cell cycle, cell adhesion, cell motility, metabolic pathways, signal transduction, cell cycle process and cell signaling. Most of the cell cycle process genes were down-regulated and consisted of genes involved in cell cycle progression, DNA biosynthesis, spindle dynamics and cytokinesis. About eight percent of all modulated genes were found to impact extracellular matrix (ECM structure and turnover, especially glycosaminoglycan (GAG and proteoglycan biosynthesis and sulfation. Altogether, the gene expression analyses provide new insight into the consequences of FGFR3 mutations in cell cycle regulation, onset of pre-hypertrophic differentiation and concomitant metabolism changes. Moreover, impaired motility and ECM properties may also provide clues about growth plate disorganization. These

  15. Molecular insights into the local anesthetic receptor within voltage-gated sodium channels using hydroxylated analogues of mexiletine

    Directory of Open Access Journals (Sweden)

    Jean-François eDesaphy

    2012-02-01

    Full Text Available We previously showed that the β-adrenoceptor modulators, clenbuterol and propranolol, directly blocked voltage-gated sodium channels, whereas salbutamol and nadolol did not (Desaphy et al., 2003, suggesting the presence of two hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for impeding sodium channel block. To verify such an hypothesis, we synthesized five new mexiletine analogues by adding one or two hydroxyl groups to the aryl moiety of the sodium channel blocker and tested these compounds on hNav1.4 channels expressed in HEK293 cells. Concentration-response relationships were constructed using an holding potential of -120 mV at 0.1 Hz (tonic block and 10 Hz (use-dependent block stimulation frequencies. The half-maximum inhibitory concentrations (IC50 were linearly correlated to drug lipophilicity: the less lipophilic the drug, minor was the block. The same compounds were also tested on F1586C and Y1593C hNav1.4 channel mutants, to gain further information on the molecular interactions of mexiletine with its receptor within the sodium channel pore. Alteration of tonic block suggests that the aryl moiety of mexiletine may interact either directly or indirectly with Phe1586 in the closed sodium channel to produce low-affinity binding block, and that this interaction depends on the electrostatic potential of the drug aromatic tail. Alteration of use-dependent block suggests that addition of hydroxyl groups to the aryl moiety may modify high-affinity binding of the drug ammine terminal to Phe1586 through cooperativity between the two pharmacophores, this effect being mainly related to drug lipophilicity. Mutation of Tyr1593 further impaired such cooperativity. In conclusion, these results confirm our former hypothesis showing that the presence of hydroxyl groups to the aryl moiety of mexiletine greatly reduced sodium channel block, and provide molecular insights into the intimate interaction of local anesthetics with

  16. The botulinum toxin as a therapeutic agent: molecular and pharmacological insights

    Directory of Open Access Journals (Sweden)

    Kukreja R

    2015-12-01

    Full Text Available Roshan Kukreja,1 Bal Ram Singh2 1Department of Chemistry and Biochemistry, University of Massachusetts, 2Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, USA Abstract: Botulinum neurotoxins (BoNTs, the most potent toxins known to mankind, are metalloproteases that act on nerve–muscle junctions to block exocytosis through a very specific and exclusive endopeptidase activity against soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins of presynaptic vesicle fusion machinery. This very ability of the toxins to produce flaccid muscle paralysis through chemical denervation has been put to good use, and these potentially lethal toxins have been licensed to treat an ever expanding list of medical disorders and more popularly in the field of esthetic medicine. In most cases, therapeutic BoNT preparations are high-molecular-weight protein complexes consisting of BoNT, complexing proteins, and excipients. There is at least one isolated BoNT, which is free of complexing proteins in the market (Xeomin®. Each commercially available BoNT formulation is unique, differing mainly in molecular size and composition of complexing proteins, biological activity, and antigenicity. BoNT serotype A is marketed as Botox®, Dysport®, and Xeomin®, while BoNT type B is commercially available as Myobloc®. Nerve terminal intoxication by BoNTs is completely reversible, and the duration of therapeutic effects of BoNTs varies for different serotypes. Depending on the target tissue, BoNTs can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. Therapeutic BoNTs exhibit a high safety and very limited adverse effects profile. Despite their established efficacy, the greatest concern with the use of therapeutic BoNTs is their propensity to elicit immunogenic reactions that might render the patient unresponsive to subsequent treatments, particularly in chronic

  17. New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.

    Directory of Open Access Journals (Sweden)

    Xinbo Zhang

    Full Text Available BACKGROUND: Bisbenzimides, or Hoechst 33258 (H258, and its derivative Hoechst 33342 (H342 are archetypal molecules for designing minor groove binders, and widely used as tools for staining DNA and analyzing side population cells. They are supravital DNA minor groove binders with AT selectivity. H342 and H258 share similar biological effects based on the similarity of their chemical structures, but also have their unique biological effects. For example, H342, but not H258, is a potent apoptotic inducer and both H342 and H258 can induce transgene overexpression in in vitro studies. However, the molecular mechanisms by which Hoechst dyes induce apoptosis and enhance transgene overexpression are unclear. METHODOLOGY/PRINCIPAL FINDINGS: To determine the molecular mechanisms underlying different biological effects between H342 and H258, microarray technique coupled with bioinformatics analyses and multiple other techniques has been utilized to detect differential global gene expression profiles, Hoechst dye-specific gene expression signatures, and changes in cell morphology and levels of apoptosis-associated proteins in malignant mesothelioma cells. H342-induced apoptosis occurs in a dose-dependent fashion and is associated with morphological changes, caspase-3 activation, cytochrome c mitochondrial translocation, and cleavage of apoptosis-associated proteins. The antagonistic effect of H258 on H342-induced apoptosis indicates a pharmacokinetic basis for the two dyes' different biological effects. Differential global gene expression profiles induced by H258 and H342 are accompanied by unique gene expression signatures determined by DNA microarray and bioinformatics software, indicating a genetic basis for their different biological effects. CONCLUSIONS/SIGNIFICANCE: A unique gene expression signature associated with H342-induced apoptosis provides a new avenue to predict and classify the therapeutic class of minor groove binders in the drug

  18. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2.

    Science.gov (United States)

    Rossor, Alexander M; Oates, Emily C; Salter, Hannah K; Liu, Yang; Murphy, Sinead M; Schule, Rebecca; Gonzalez, Michael A; Scoto, Mariacristina; Phadke, Rahul; Sewry, Caroline A; Houlden, Henry; Jordanova, Albena; Tournev, Iyailo; Chamova, Teodora; Litvinenko, Ivan; Zuchner, Stephan; Herrmann, David N; Blake, Julian; Sowden, Janet E; Acsadi, Gyuda; Rodriguez, Michael L; Menezes, Manoj P; Clarke, Nigel F; Auer Grumbach, Michaela; Bullock, Simon L; Muntoni, Francesco; Reilly, Mary M; North, Kathryn N

    2015-02-01

    Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without SMN1 mutations are subclassified according to phenotype. Spinal muscular atrophy, lower extremity-predominant, is characterized by lower limb muscle weakness and wasting, associated with reduced numbers of lumbar motor neurons and is caused by mutations in DYNC1H1, which encodes a microtubule motor protein in the dynein-dynactin complex and one of its cargo adaptors, BICD2. We have now identified 32 patients with BICD2 mutations from nine different families, providing detailed insights into the clinical phenotype and natural history of BICD2 disease. BICD2 spinal muscular atrophy, lower extremity predominant most commonly presents with delayed motor milestones and ankle contractures. Additional features at presentation include arthrogryposis and congenital dislocation of the hips. In all affected individuals, weakness and wasting is lower-limb predominant, and typically involves both proximal and distal muscle groups. There is no evidence of sensory nerve involvement. Upper motor neuron signs are a prominent feature in a subset of individuals, including one family with exclusively adult-onset upper motor neuron features, consistent with a diagnosis of hereditary spastic paraplegia. In all cohort members, lower motor neuron features were static or only slowly progressive, and the majority remained ambulant throughout life. Muscle MRI in six individuals showed a common pattern of muscle involvement with fat deposition in most thigh muscles, but sparing of the adductors and semitendinosus. Muscle pathology findings were highly variable and included pseudomyopathic features, neuropathic features, and minimal change. The six causative mutations, including one not previously reported, result in amino acid changes within all three coiled-coil domains of the BICD2 protein, and include a possible 'hot spot' mutation, p.Ser107Leu

  19. Molecular simulations of aromatase reveal new insights into the mechanism of ligand binding.

    Science.gov (United States)

    Park, Jiho; Czapla, Luke; Amaro, Rommie E

    2013-08-26

    CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model of the lipid bilayer and the transmembrane helix are performed. The dynamics of aromatase and the role of titration of an important amino acid residue involved in aromatization of androgens are investigated via two 250-ns long simulations. One simulation treats the protonated form of the catalytic aspartate 309, which appears more consistent with crystallographic data for the active site, while the simulation of the deprotonated form shows some notable conformational shifts. Ensemble-based computational solvent mapping experiments indicate possible novel druggable binding sites that could be utilized by next-generation inhibitors. In addition, the effects of protonation on the ligand positioning and channel dynamics are investigated using geometrical models that estimate the opening width of critical channels. Significant differences in channel dynamics between the protonated and deprotonated trajectories are exhibited, suggesting that the mechanism for substrate and product entry and the aromatization process may be coupled to a "locking" mechanism and channel opening. Our results may be particularly relevant in the design of novel drugs, which may be useful therapeutic treatments of cancers such as those of the breast and prostate. PMID:23927370

  20. Insight into Conformational Change for 14-3-3σ Protein by Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Guodong Hu

    2014-02-01

    Full Text Available 14-3-3σ is a member of a highly conserved family of 14-3-3 proteins that has a double-edged sword role in human cancers. Former reports have indicated that the 14-3-3 protein may be in an open or closed state. In this work, we found that the apo-14-3-3σ is in an open state compared with the phosphopeptide bound 14-3-3σ complex which is in a more closed state based on our 80 ns molecular dynamics (MD simulations. The interaction between the two monomers of 14-3-3σ in the open state is the same as that in the closed state. In both open and closed states, helices A to D, which are involved in dimerization, are stable. However, large differences are found in helices E and F. The hydrophobic contacts and hydrogen bonds between helices E and G in apo-14-3-3σ are different from those in the bound 14-3-3σ complex. The restrained and the mutated (Arg56 or Arg129 to alanine MD simulations indicate that the conformation of four residues (Lys49, Arg56, Arg129 and Tyr130 may play an important role to keep the 14-3-3σ protein in an open or closed state. These results would be useful to evaluate the 14-3-3σ protein structure-function relationship.

  1. Reproductive mode evolution in nematodes: insights from molecular phylogenies and recently discovered species.

    Science.gov (United States)

    Denver, D R; Clark, K A; Raboin, M J

    2011-11-01

    The Phylum Nematoda has long been known to contain a great diversity of species that vary in reproductive mode, though our understanding of the evolutionary origins, causes and consequences of nematode reproductive mode change have only recently started to mature. Here we bring together and analyze recent progress on reproductive mode evolution throughout the phylum, resulting from the application of molecular phylogenetic approaches and newly discovered nematode species. Reproductive mode variation is reviewed in multiple free-living, animal-parasitic and plant-parasitic nematode groups. Discussion ranges from the model nematode Caenorhabditis elegans and its close relatives, to the plant-parasitic nematodes of the Meloidogyne genus where there is extreme variation in reproductive mode between and even within species, to the vertebrate-parasitic genus Strongyloides and related genera where reproductive mode varies across generations (heterogony). Multiple evolutionary transitions from dioecous (obligately outcrossing) to hermaphroditism and parthenogenesis in the phylum are discussed, along with one case of an evolutionary transition from hermaphroditism to doioecy in the Oscheius genus. We consider the roles of underlying genetic mechanisms in promoting reproductive plasticity in this phylum, as well as the potential evolutionary forces promoting transitions in reproductive mode. PMID:21787872

  2. Molecular insights into chronotype and time-of-day effects on decision-making.

    Science.gov (United States)

    Ingram, Krista K; Ay, Ahmet; Kwon, Soo Bin; Woods, Kerri; Escobar, Sue; Gordon, Molly; Smith, Isaac H; Bearden, Neil; Filipowicz, Allan; Jain, Kriti

    2016-01-01

    Recent reports highlight that human decision-making is influenced by the time of day and whether one is a morning or evening person (i.e., chronotype). Here, we test whether these behavioral effects are associated with endogenous biological rhythms. We asked participants to complete two well-established decision-making tasks in the morning or evening: the matrix task (an ethical decision task) and the balloon analog risk task (BART; a risk-taking task), and we measured their chronotype in two ways. First, participants completed a self-report measure, the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ). Second, we measured the expression of two circadian clock-regulated genes-Per3 and Nr1d2-from peripheral clock cells in participants' hair follicle samples. Using a cosinor model, we estimated the phase of the peripheral clock and assigned RNA chronotypes to participants with advanced (larks) or delayed (owls) phases. The behavioral data were analyzed independently for self-reported (MEQ) and RNA-based chronotypes. We find that significant chronotype and/or time-of-day effects between larks and owls in decision-making tasks occur only in RNA-based chronotypes. Our results provide evidence that time-of-day effects on decision-making can be explained by phase differences in oscillating clock genes and suggest that variation in the molecular clockwork may influence inter-individual differences in decision-making behavior. PMID:27388366

  3. Insights into photodissociation dynamics of acetaldehyde from ab initio calculations and molecular dynamics simulations

    International Nuclear Information System (INIS)

    In the present paper we report a theoretical study on mechanistic photodissociation of acetaldehyde (CH3CHO). Stationary structures for H2 and CO eliminations in the ground state (S0) have been optimized with density functional theory method, which is followed by the intrinsic reaction coordinate and ab initio molecular dynamics calculations to confirm the elimination mechanism. Equilibrium geometries, transition states, and intersection structures for the C-C and C-H dissociations in excited states were determined by the complete-active-space self-consistent field (CASSCF) method. Based on the CASSCF optimized structures, the potential energy profiles for the dissociations were refined by performing the single-point calculations using the multireference configuration interaction method. Upon the low-energy irradiation of CH3CHO (265 nm1 C-C bond fission following intersystem crossing from the S1 state is the predominant channel and the minor channel, the ground-state elimination to CH4+CO after internal conversion (IC) from S1 to S0, could not be excluded. With the photon energy increasing, another pathway of IC, achieved via an S1/S0 intersection point resulting from the S1 C-C bond fission, becomes accessible and increases the yield of CH4+CO.

  4. Metabolism of triacylglycerols in Rhodococcus species: insights from physiology and molecular genetics

    Directory of Open Access Journals (Sweden)

    Martín A. Hernández

    2013-02-01

    Full Text Available Rhodococcus bacteria possess the ability to accumulate variable amounts of triacylglycerols (TAG during growth on diverse carbon sources. The evolution seems to have selected these microorganisms as specialists in the accumulation of TAG among bacteria, since their biochemistry is efficiently designed for the biosynthesis and mobilization of these lipids. Detailed research of rhodococcal TAG metabolism started only a few years ago; thus, the fundamental understanding of this process and its regulation remains to be clarified. However, some interesting advances in the basic knowledge on TAG metabolism in rhodococci have been made. Most studies have focused on the physiology of TAG biosynthesis and mobilization in rhodococci. Only recently, some advances in molecular biology and genetics on TAG metabolism occurred as a result of the increasing available genomic information and the development of new genetic tools for rhodococci. These studies have been focused principally on some enzymes of TAG biosynthesis, such as the wax esters/diacylglycerolacyltransferases (WS/DGAT and TAG granule-associated proteins. In this context, the most relevant achievements of basic research in the field have been summarized in this review article.

  5. Molecular insights into chronotype and time-of-day effects on decision-making

    Science.gov (United States)

    Ingram, Krista K; Ay, Ahmet; Kwon, Soo Bin; Woods, Kerri; Escobar, Sue; Gordon, Molly; Smith, Isaac H.; Bearden, Neil; Filipowicz, Allan; Jain, Kriti

    2016-01-01

    Recent reports highlight that human decision-making is influenced by the time of day and whether one is a morning or evening person (i.e., chronotype). Here, we test whether these behavioral effects are associated with endogenous biological rhythms. We asked participants to complete two well-established decision-making tasks in the morning or evening: the matrix task (an ethical decision task) and the balloon analog risk task (BART; a risk-taking task), and we measured their chronotype in two ways. First, participants completed a self-report measure, the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ). Second, we measured the expression of two circadian clock-regulated genes—Per3 and Nr1d2—from peripheral clock cells in participants’ hair follicle samples. Using a cosinor model, we estimated the phase of the peripheral clock and assigned RNA chronotypes to participants with advanced (larks) or delayed (owls) phases. The behavioral data were analyzed independently for self-reported (MEQ) and RNA-based chronotypes. We find that significant chronotype and/or time-of-day effects between larks and owls in decision-making tasks occur only in RNA-based chronotypes. Our results provide evidence that time-of-day effects on decision-making can be explained by phase differences in oscillating clock genes and suggest that variation in the molecular clockwork may influence inter-individual differences in decision-making behavior. PMID:27388366

  6. Molecular insights into diphenylalanine nanotube assembly: all-atom simulations of oligomerization.

    Science.gov (United States)

    Jeon, Joohyun; Mills, Carolyn E; Shell, M Scott

    2013-04-18

    Self-assembling peptides represent a growing class of inexpensive, environmentally benign, nanostructured materials. In particular, diphenylalanine (FF) self-assembles into nanotubes with remarkable strength and thermal stability that have found use in a wide variety of applications, including as sacrificial templates and scaffolds for structuring inorganic materials and as interfacial "nanoforests" for superhydrophobic surfaces and high-performance supercapacitors and biosensors. However, little is known about the assembly mechanisms of FF nanotubes or the forces underlying their stability. Here, we perform a variety of molecular dynamics simulations on both zwitterionic and capped (uncharged) versions of the FF peptide to understand the early stages of self-assembly. We compare these results to simulations of the proposed nanotube X-ray crystal structure. When comparing the zwitterionic and uncharged FF peptides, we find that, while electrostatic interactions steer the former into more ordered dimers and trimers, the hydrophobic side chain interactions play a strong role in determining the structures of larger oligomers. Simulations of the crystal structure fragment also suggest that the strongest interactions occur between side chains, not between the charged termini that form salt bridges. We conclude that the amphiphilic nature of FF is key to understanding its self-assembly, and that the early precursors to nanotube structures are likely to involve substantial hydrophobic clustering, rather than hexamer ring motifs as has been previously suggested. PMID:23521630

  7. Postcollision multifragmentation in fullerene-surface impact: Microscopic insights via molecular dynamics simulations

    Science.gov (United States)

    Bernstein, Victor; Kolodney, Eli

    2016-07-01

    Postcollision multifragmentation which we have recently observed experimentally in C60 - -surface impact is the phenomenon of a delayed multiparticle breakup of a highly collisionally vibrationally excited large molecule/cluster (the precursor species) into several polyatomic fragments, after leaving the surface. In this paper, we show that the molecular dynamics simulations of near-grazing C60 collisions with a gold surface at 300 eV impact energy (very similar to the experimental conditions) successfully reproduce the experimentally observed characteristics of the postcollision multifragmentation process. The calculated mass resolved kinetic energy distributions and the time dependent yield curves of the Cn fragments revealed a precursor mediated, velocity correlated, delayed fragmentation event along the outgoing trajectory, far away from the surface. Most of the large fragments (n ≥ 5) are formed within a time window of 2-20 ps after leaving the surface, corresponding to the vertical distances of 3-30 nm from the surface. Analysis of delay times and actual time duration for multifragmentation reveal that a large part can be described as simultaneous postcollision (delayed) multifragmentation events. The delayed nature of the event seems to be due to an early sequence of structural transformations of the precursor.

  8. Molecular Dynamics Simulation of HIV Fusion Inhibitor T-1249: Insights on Peptide-Lipid Interaction

    Directory of Open Access Journals (Sweden)

    A. M. T. Martins do Canto

    2012-01-01

    Full Text Available T-1249 is a peptide that inhibits the fusion of HIV envelope with the target cell membrane. Recent results indicate that T-1249, as in the case of related inhibitor peptide T-20 (enfuvirtide, interacts with membranes, more extensively in the bilayer liquid disordered phase than in the liquid ordered state, which could be linked to its effectiveness. Extensive molecular dynamics simulations (100 ns were carried out to investigate the interaction between T-1249 and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC and POPC/cholesterol (1 : 1. It was observed that T-1249 interacts to different extents with both membrane systems and that peptide interaction with the bilayer surface has a local effect on membrane structure. Formation of hydrogen bonding between certain peptide residues and several acceptor and donor groups in the bilayer molecules was observed. T-1249 showed higher extent of interaction with bilayers when compared to T-20. This is most notable in POPC/Chol membranes, owing to more peptide residues acting as H bond donors and acceptors between the peptide and the bilayer lipids, including H-bonds formed with cholesterol. This behavior is at variance with that of T-20, which forms no H bonds with cholesterol. This higher ability to interact with membranes is probably correlated with its higher inhibitory efficiency.

  9. New insights into the enigma of boron carbide inverse molecular behavior

    International Nuclear Information System (INIS)

    Equation of state and compression mechanism of nearly stoichiometric boron carbide B4C were investigated using diamond anvil cell single crystal synchrotron X-ray diffraction technique up to a maximum quasi-hydrostatic pressure of 74.0(1) GPa in neon pressure transmitting medium at ambient temperature. No signatures of structural phase transitions were observed on compression. Crystal structure refinements indicate that the icosahedral units are less compressible (13% volume reduction at 60 GPa) than the unit cell volume (18% volume reduction at 60 GPa), contrary to expectations based on the inverse molecular behavior hypothesis, but consistent with spectroscopic evidence and first principles calculations. The high-pressure crystallographic refinements reveal that the nature of the chemical bonds (two, versus three centered character) has marginal effect on the bond compressibility and the compression of the crystal is mainly governed by the force transfer between the rigid icosahedral structural units. - Graphical abstract: Single crystal measurements of equation of state and compression mechanism of B4C show that the icosahedral units are less compressibe than the unit cell volume, despite the threei-ceneterd nature of some icosahedral bonds. - Highlights: • Equation of state and compression mechanism of B4C were measured to 75 GPa. • No signatures of structural phase transitions were observed on compression. • Icosahedral units are less compressibe than the unit cell volume. • The nature of the chemical bonds has mariginal effect on the bond compressibility. • The compression is governed by force transfer between the rigid icosahedra

  10. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    International Nuclear Information System (INIS)

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC

  11. Merkel cell polyomavirus: molecular insights into the most recently discovered human tumour virus.

    Science.gov (United States)

    Stakaitytė, Gabrielė; Wood, Jennifer J; Knight, Laura M; Abdul-Sada, Hussein; Adzahar, Noor Suhana; Nwogu, Nnenna; Macdonald, Andrew; Whitehouse, Adrian

    2014-01-01

    A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC. PMID:24978434

  12. Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

    Directory of Open Access Journals (Sweden)

    Gabrielė Stakaitytė

    2014-06-01

    Full Text Available A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC, a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.

  13. Insights into surface–adsorbate interactions in corrosion inhibition processes at the molecular level

    International Nuclear Information System (INIS)

    Graphical abstract: The interaction of 2-((3-methylpyridine-2-imino)methyl)phenol (MPIMP) with the Fe(1 1 0) surface was clarified at the molecular level using density functional theory (DFT). Highlights: •2-((3-Methylpyridine-2-imino)methyl)phenol was tested as a corrosion inhibitor. •Its interaction with the surface was characterized using density functional theory. •Three stable adsorption configurations on Fe(1 1 0) surface were identified. -- Abstract: 2-((3-Methylpyridine-2-imino)methyl)phenol (MPIMP) was investigated as a potential corrosion inhibitor for mild steel in 0.5 M HCl solution using impedance spectroscopy (IS). Changes in impedance parameters indicated that adsorption of MPIMP occurred on the mild steel surface. Three stable adsorption configurations for MPIMP on the Fe(1 1 0) surface were identified as a result of geometry optimization starting from several adsorption geometries using density functional theory (DFT). Involvement of the delocalized π-electrons of the aromatic rings in the interaction provides extra stabilization to the flat adsorption configurations

  14. Effect of temperature on DNA double helix: An insight from molecular dynamics simulation

    Indian Academy of Sciences (India)

    Sangeeta Kundu; Sanchita Mukherjee; Dhananjay Bhattacharyya

    2012-07-01

    The three-dimensional structure of DNA contains various sequence-dependent structural information, which control many cellular processes in life, such as replication, transcription, DNA repair, etc. For the above functions, DNA double helices need to unwind or melt locally, which is different from terminal melting, as often seen in molecular dynamics (MD) simulations or even in many DNA crystal structures. We have carried out detailed MD simulations of DNA double helices of regular oligonucleotide fragments as well as in polymeric constructs with water and charge-neutralizing counter-ions at several different temperatures. We wanted to eliminate the end-effect or terminal melting propensity by employing MD simulation of DNA oligonucleotides in such a manner that gives rise to properties of polymeric DNA of infinite length. The polymeric construct is expected to allow us to see local melting at elevated temperatures. Comparative structural analysis of oligonucleotides and its corresponding virtual polymer at various temperatures ranging from 300 K to 400 K is discussed. The general behaviour, such as volume expansion coefficients of both the simulations show high similarity, indicating polymeric construct, does not give many artificial constraints. Local melting of a polymer, even at elevated temperature, may need a high nucleation energy that was not available in the short (7 ns) simulations. We expected to observe such nucleation followed by cooperative melting of the polymers in longer MD runs. Such simulations of different polymeric sequences would facilitate us to predict probable melting origins in a polymeric DNA.

  15. Interaction of amyloid inhibitor proteins with amyloid beta peptides: insight from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Payel Das

    Full Text Available Knowledge of the detailed mechanism by which proteins such as human αB- crystallin and human lysozyme inhibit amyloid beta (Aβ peptide aggregation is crucial for designing treatment for Alzheimer's disease. Thus, unconstrained, atomistic molecular dynamics simulations in explicit solvent have been performed to characterize the Aβ17-42 assembly in presence of the αB-crystallin core domain and of lysozyme. Simulations reveal that both inhibitor proteins compete with inter-peptide interaction by binding to the peptides during the early stage of aggregation, which is consistent with their inhibitory action reported in experiments. However, the Aβ binding dynamics appear different for each inhibitor. The binding between crystallin and the peptide monomer, dominated by electrostatics, is relatively weak and transient due to the heterogeneous amino acid distribution of the inhibitor surface. The crystallin-bound Aβ oligomers are relatively long-lived, as they form more extensive contact surface with the inhibitor protein. In contrast, a high local density of arginines from lysozyme allows strong binding with Aβ peptide monomers, resulting in stable complexes. Our findings not only illustrate, in atomic detail, how the amyloid inhibitory mechanism of human αB-crystallin, a natural chaperone, is different from that of human lysozyme, but also may aid de novo design of amyloid inhibitors.

  16. Can Payments for Ecosystem Services Contribute to Adaptation to Climate Change? Insights from a Watershed in Kenya

    OpenAIRE

    Isabel van de Sand; John K. Mwangi; Sara Namirembe

    2014-01-01

    Climate change presents new challenges for the management of social-ecological systems and the ecosystem services they provide. Although the instrument of payments for ecosystem services (PES) has emerged as a promising tool to safeguard or enhance the provision of ecosystem services (ES), little attention has been paid to the potential role of PES in climate change adaptation. As an external stressor climate change has an impact on the social-ecological system in which PES takes place, inclu...

  17. CAM and cell fate targeting: molecular and energetic insights into cell growth and differentiation.

    Science.gov (United States)

    Ventura, Carlo

    2005-09-01

    Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM) offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence-based CAM. PMID:16136206

  18. CAM and Cell Fate Targeting: Molecular and Energetic Insights into Cell Growth and Differentiation

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2005-01-01

    Full Text Available Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence–based CAM.

  19. Calcium induced regulation of skeletal troponin--computational insights from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Georgi Z Genchev

    Full Text Available The interaction between calcium and the regulatory site(s of striated muscle regulatory protein troponin switches on and off muscle contraction. In skeletal troponin binding of calcium to sites I and II of the TnC subunit results in a set of structural changes in the troponin complex, displaces tropomyosin along the actin filament and allows myosin-actin interaction to produce mechanical force. In this study, we used molecular dynamics simulations to characterize the calcium dependent dynamics of the fast skeletal troponin molecule and its TnC subunit in the calcium saturated and depleted states. We focused on the N-lobe and on describing the atomic level events that take place subsequent to removal of the calcium ion from the regulatory sites I and II. A main structural event - a closure of the A/B helix hydrophobic pocket results from the integrated effect of the following conformational changes: the breakage of H-bond interactions between the backbone nitrogen atoms of the residues at positions 2, 9 and sidechain oxygen atoms of the residue at position 12 (N(2-OE(12/N(9-OE(12 in sites I and II; expansion of sites I and II and increased site II N-terminal end-segment flexibility; strengthening of the β-sheet scaffold; and the subsequent re-packing of the N-lobe hydrophobic residues. Additionally, the calcium release allows the N-lobe to rotate relative to the rest of the Tn molecule. Based on the findings presented herein we propose a novel model of skeletal thin filament regulation.

  20. Insights into enzyme point mutation effect by molecular simulation: phenylethylamine oxidation catalyzed by monoamine oxidase A.

    Science.gov (United States)

    Oanca, Gabriel; Purg, Miha; Mavri, Janez; Shih, Jean C; Stare, Jernej

    2016-05-21

    The I335Y point mutation effect on the kinetics of phenylethylamine decomposition catalyzed by monoamine oxidase A was elucidated by means of molecular simulation. The established empirical valence bond methodology was used in conjunction with the free energy perturbation sampling technique and a classical force field representing the state of reactants and products. The methodology allows for the simulation of chemical reactions, in the present case the breaking of the α-C-H bond in a phenylethylamine substrate and the subsequent hydrogen transfer to the flavin cofactor, resulting in the formation of the N-H bond on flavin. The empirical parameters were calibrated against the experimental data for the simulated reaction in a wild type protein and then used for the calculation of the reaction free energy profile in the I335Y mutant. In very good agreement with the measured kinetic data, mutation increases the free energy barrier for the rate limiting step by slightly more than 1 kcal mol(-1) and consequently decreases the rate constant by about an order of magnitude. The magnitude of the computed effect slightly varies with simulation settings, but always remains in reasonable agreement with the experiment. Analysis of trajectories reveals a major change in the interaction between phenyl rings of the substrate and the neighboring Phe352 residue upon the I335Y mutation due to the increased local polarity, leading to an attenuated quadrupole interaction between the rings and destabilization of the transition state. Additionally, the increased local polarity in the mutant allows for a larger number of water molecules to be present near the active site, effectively shielding the catalytic effect of the enzyme and contributing to the increased barrier. PMID:27121693

  1. Way back for fructose and liver metabolism: bench side to molecular insights.

    Science.gov (United States)

    Rebollo, Alba; Roglans, Núria; Alegret, Marta; Laguna, Juan C

    2012-12-01

    The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy. The consumption of sugar-sweetened beverages is the main source of added sugars. Fructose, together with glucose, as a component of high fructose corn syrups or as a component of the sucrose molecule, is one of the main sweeteners present in this kind of beverages. Data from prospective and intervention studies clearly point to high fructose consumption, mainly in the form of sweetened beverages, as a risk factor for several metabolic diseases in humans. The incidence of hypertension, nonalcoholic fatty liver disease (NAFLD), dyslipidemia (mainly hypertriglyceridemia), insulin resistance, type 2 diabetes mellitus, obesity, and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose. Adolescent and young adults from low-income families are especially at risk. We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism. In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances, especially NAFLD, type 2 diabetes mellitus, and metabolic syndrome. We have explored recent data from observational and experimental human studies, as well as experimental data from animal and cell models. Finally, using information generated in our laboratory and others, we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form. PMID:23236229

  2. Heterogeneous behavior of metalloproteins toward metal ion binding and selectivity: insights from molecular dynamics studies.

    Science.gov (United States)

    Gogoi, Prerana; Chandravanshi, Monika; Mandal, Suraj Kumar; Srivastava, Ambuj; Kanaujia, Shankar Prasad

    2016-07-01

    About one-third of the existing proteins require metal ions as cofactors for their catalytic activities and structural complexities. While many of them bind only to a specific metal, others bind to multiple (different) metal ions. However, the exact mechanism of their metal preference has not been deduced to clarity. In this study, we used molecular dynamics (MD) simulations to investigate whether a cognate metal (bound to the structure) can be replaced with other similar metal ions. We have chosen seven different proteins (phospholipase A2, sucrose phosphatase, pyrazinamidase, cysteine dioxygenase (CDO), plastocyanin, monoclonal anti-CD4 antibody Q425, and synaptotagmin 1 C2B domain) bound to seven different divalent metal ions (Ca(2+), Mg(2+), Zn(2+), Fe(2+), Cu(2+), Ba(2+), and Sr(2+), respectively). In total, 49 MD simulations each of 50 ns were performed and each trajectory was analyzed independently. Results demonstrate that in some cases, cognate metal ions can be exchanged with similar metal ions. On the contrary, some proteins show binding affinity specifically to their cognate metal ions. Surprisingly, two proteins CDO and plastocyanin which are known to bind Fe(2+) and Cu(2+), respectively, do not exhibit binding affinity to any metal ion. Furthermore, the study reveals that in some cases, the active site topology remains rigid even without cognate metals, whereas, some require them for their active site stability. Thus, it will be interesting to experimentally verify the accuracy of these observations obtained computationally. Moreover, the study can help in designing novel active sites for proteins to sequester metal ions particularly of toxic nature. PMID:26248730

  3. Molecular insights into connective tissue growth factor action in rat pancreatic stellate cells.

    Science.gov (United States)

    Karger, Anna; Fitzner, Brit; Brock, Peter; Sparmann, Gisela; Emmrich, Jörg; Liebe, Stefan; Jaster, Robert

    2008-10-01

    Pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer, is mediated by activated pancreatic stellate cells (PSC). Connective tissue growth factor (CTGF) has been suggested to play a major role in fibrogenesis by enhancing PSC activation after binding to alpha5beta1 integrin. Here, we have focussed on molecular determinants of CTGF action. Inhibition of CTGF expression in PSC by siRNA was associated with decreased proliferation, while application of exogenous CTGF stimulated both cell growth and collagen synthesis. Real-time PCR studies revealed that CTGF target genes in PSC not only include mediators of matrix remodelling but also the proinflammatory cytokines interleukin (IL)-1beta and IL-6. CTGF stimulated binding of NF-kappaB to the IL-6 promoter, and siRNA targeting the NF-kappaB subunit RelA interfered with CTGF-induced IL-6 expression, implicating the NF-kappaB pathway in the mediation of the CTGF effect. In further studies, we have analyzed regulation of CTGF expression in PSC. Transforming growth factor-beta1, activin A and tumor necrosis factor-alpha enhanced expression of the CTGF gene, while interferon-gamma displayed the opposite effect. The region from -74 to -125 of the CTGF promoter was revealed to be critical for its activity in PSC as well as for the inhibitory effect of interferon-gamma. Taken together, our results indicate a tight control of CTGF expression in PSC at the transcriptional level. CTGF promotes fibrogenesis both directly by enhancing PSC proliferation and matrix protein synthesis, and indirectly through the release of proinflammatory cytokines that may accelerate the process of chronic inflammation. PMID:18639630

  4. Recent insights into the molecular pathogenesis of Crohn's disease: a review of emerging therapeutic targets.

    Science.gov (United States)

    Manuc, Teodora-Ecaterina M; Manuc, Mircea M; Diculescu, Mircea M

    2016-01-01

    Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD. Moreover, cellular therapy is another therapeutic approach under development, aimed for severe refractory CD. Other experimental treatments include intravenous immunoglobulins, exclusive enteral

  5. New insights into the enigma of boron carbide inverse molecular behavior

    Energy Technology Data Exchange (ETDEWEB)

    Dera, Przemyslaw, E-mail: pdera@hawaii.edu [Hawaii Institute of Geophysics and Planetology, School of Ocean and Earth Science and Technology, University of Hawaii at Manoa, 1680 East West Road, POST Building, Honolulu, HI 96822 (United States); Manghnani, Murli H.; Hushur, Anwar; Hu, Yi [Hawaii Institute of Geophysics and Planetology, School of Ocean and Earth Science and Technology, University of Hawaii at Manoa, 1680 East West Road, POST Building, Honolulu, HI 96822 (United States); Tkachev, Sergey [Center for Advanced Radiation Sources, The University of Chicago, Argonne National Laboratory, 9700 S. Cass Avenue, Building 434, Argonne, IL 60439 (United States)

    2014-07-01

    Equation of state and compression mechanism of nearly stoichiometric boron carbide B{sub 4}C were investigated using diamond anvil cell single crystal synchrotron X-ray diffraction technique up to a maximum quasi-hydrostatic pressure of 74.0(1) GPa in neon pressure transmitting medium at ambient temperature. No signatures of structural phase transitions were observed on compression. Crystal structure refinements indicate that the icosahedral units are less compressible (13% volume reduction at 60 GPa) than the unit cell volume (18% volume reduction at 60 GPa), contrary to expectations based on the inverse molecular behavior hypothesis, but consistent with spectroscopic evidence and first principles calculations. The high-pressure crystallographic refinements reveal that the nature of the chemical bonds (two, versus three centered character) has marginal effect on the bond compressibility and the compression of the crystal is mainly governed by the force transfer between the rigid icosahedral structural units. - Graphical abstract: Single crystal measurements of equation of state and compression mechanism of B{sub 4}C show that the icosahedral units are less compressibe than the unit cell volume, despite the threei-ceneterd nature of some icosahedral bonds. - Highlights: • Equation of state and compression mechanism of B{sub 4}C were measured to 75 GPa. • No signatures of structural phase transitions were observed on compression. • Icosahedral units are less compressibe than the unit cell volume. • The nature of the chemical bonds has mariginal effect on the bond compressibility. • The compression is governed by force transfer between the rigid icosahedra.

  6. Way back for fructose and liver metabolism: Bench side to molecular insights

    Institute of Scientific and Technical Information of China (English)

    Alba Rebollo; Núria Roglans; Marta Alegret; Juan C Laguna

    2012-01-01

    The World Health Organization recommends that the daily intake of added sugars should make up no more than 10% of total energy.The consumption of sugarsweetened beverages is the main source of added sugars.Fructose,together with glucose,as a component of high fructose corn syrups or as a component of the sucrose molecule,is one of the main sweeteners present in this kind of beverages.Data from prospective and intervention studies clearly point to high fructose consumption,mainly in the form of sweetened beverages,as a risk factor for several metabolic diseases in humans.The incidence of hypertension,nonalcoholic fatty liver disease (NAFLD),dyslipidemia (mainly hypertriglyceridemia),insulin resistance,type 2 diabetes mellitus,obesity,and the cluster of many of these pathologies in the form of metabolic syndrome is higher in human population segments that show high intake of fructose.Adolescent and young adults from lowincome families are especially at risk.We recently reviewed evidence from experimental animals and human data that confirms the deleterious effect of fructose on lipid and glucose metabolism.In this present review we update the information generated in the past 2 years about high consumption of fructose-enriched beverages and the occurrence of metabolic disturbances,especially NAFLD,type 2 diabetes mellitus,and metabolic syndrome.We have explored recent data from observational and experimental human studies,as well as experimental data from animal and cell models.Finally,using information generated in our laboratory and others,we provide a view of the molecular mechanisms that may be specifically involved in the development of liver lipid and glucose metabolic alterations after fructose consumption in liquid form.

  7. Molecular analysis of the anaerobic rumen fungus Orpinomyces - insights into an AT-rich genome.

    Science.gov (United States)

    Nicholson, Matthew J; Theodorou, Michael K; Brookman, Jayne L

    2005-01-01

    The anaerobic gut fungi occupy a unique niche in the intestinal tract of large herbivorous animals and are thought to act as primary colonizers of plant material during digestion. They are the only known obligately anaerobic fungi but molecular analysis of this group has been hampered by difficulties in their culture and manipulation, and by their extremely high A+T nucleotide content. This study begins to answer some of the fundamental questions about the structure and organization of the anaerobic gut fungal genome. Directed plasmid libraries using genomic DNA digested with highly or moderately rich AT-specific restriction enzymes (VspI and EcoRI) were prepared from a polycentric Orpinomyces isolate. Clones were sequenced from these libraries and the breadth of genomic inserts, both genic and intergenic, was characterized. Genes encoding numerous functions not previously characterized for these fungi were identified, including cytoskeletal, secretory pathway and transporter genes. A peptidase gene with no introns and having sequence similarity to a gene encoding a bacterial peptidase was also identified, extending the range of metabolic enzymes resulting from apparent trans-kingdom transfer from bacteria to fungi, as previously characterized largely for genes encoding plant-degrading enzymes. This paper presents the first thorough analysis of the genic, intergenic and rDNA regions of a variety of genomic segments from an anaerobic gut fungus and provides observations on rules governing intron boundaries, the codon biases observed with different types of genes, and the sequence of only the second anaerobic gut fungal promoter reported. Large numbers of retrotransposon sequences of different types were found and the authors speculate on the possible consequences of any such transposon activity in the genome. The coding sequences identified included several orphan gene sequences, including one with regions strongly suggestive of structural proteins such as collagens

  8. A promiscuous recognition mechanism between GPR17 and SDF-1: Molecular insights.

    Science.gov (United States)

    Parravicini, Chiara; Daniele, Simona; Palazzolo, Luca; Trincavelli, Maria Letizia; Martini, Claudia; Zaratin, Paola; Primi, Roberto; Coppolino, Giusy; Gianazza, Elisabetta; Abbracchio, Maria P; Eberini, Ivano

    2016-06-01

    Recent data and publications suggest a promiscuous behaviour for GPR17, a class-A GPCR operated by different classes of ligands, such as uracil nucleotides, cysteinyl-leukotrienes and oxysterols. This observation, together with the ability of several class-A GPCRs to form homo- and hetero-dimers, is likely to unveil new pathophysiological roles and novel emerging pharmacological properties for some of these GPCRs, including GPR17. This receptor shares structural, phylogenetic and functional properties with some chemokine receptors, CXCRs. Both GPR17 and CXCR2 are operated by oxysterols, and both GPR17 and CXCR ligands have been demonstrated to have a role in orchestrating inflammatory responses and oligodendrocyte precursor cell differentiation to myelinating cells in acute and chronic diseases of the central nervous system. Here, by combining in silico modelling data with in vitro validation in (i) a classical reference pharmacological assay for GPCR activity and (ii) a model of maturation of primary oligodendrocyte precursor cells, we demonstrate that GPR17 can be activated by SDF-1, a ligand of chemokine receptors CXCR4 and CXCR7, and investigate the underlying molecular recognition mechanism. We also demonstrate that cangrelor, a GPR17 orthosteric antagonist, can block the SDF-1-mediated activation of GPR17 in a concentration-dependent manner. The ability of GPR17 to respond to different classes of GPCR ligands suggests that this receptor modifies its function depending on the extracellular mileu changes occurring under specific pathophysiological conditions and advocates it as a strategic target for neurodegenerative diseases with an inflammatory/immune component. PMID:26971834

  9. Insights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSAR.

    Directory of Open Access Journals (Sweden)

    Luisa Quesada-Romero

    Full Text Available Many protein kinase (PK inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3β using docking experiments. We found that the orientations that these compounds adopt inside GSK3β binding site prioritize the formation of hydrogen bond (HB interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133, and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades. In addition, quantitative structure-activity relationship (QSAR models using CoMSIA methodology were constructed to explain the trend of the GSK3β inhibitory activities for the studied compounds. We found a model to explain the structure-activity relationship of non-cyclic maleimide (NCM derivatives (54 compounds. The best CoMSIA model (training set included 44 compounds included steric, hydrophobic, and HB donor fields and had a good Q(2 value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors.

  10. Ion equilibrium in Na-montmorillonite - Insights from molecular dynamics simulations

    International Nuclear Information System (INIS)

    Document available in extended abstract form only. Bentonite clay is proposed as buffer material in several concepts of High Level Radioactive Waste repositories, and a truthful description of ion diffusion in this material is of vital importance for any quantification of the chemical evolution of the repository near field. This study investigates the importance of ion equilibrium between montmorillonite interlayer space and an external solution for the diffusional behaviour of bentonite. We present molecular dynamics simulations of compacted montmorillonite with three hydration layers of water in the interlayer. The montmorillonite is contacted to a reservoir of NaCl solution as shown in Figure 1, and the calculations are performed at three different concentrations. Overall the calculations are performed in the canonical (NVT) ensemble but from the perspective of the interlayer the calculations are done in the grand canonical (μVT) ensemble. However, both the limited volume of the bulk solution and that of the interlayer poses problem for the simulations. A criterion, that must be fulfilled in order to obtain physically meaningful results, is derived using the Poisson-Boltzmann equation and standard Donnan theory. The validity of this criterion is tested in the simulations by choosing conditions where the criterion is either fulfilled or violated. The calculations show that excess salt, i.e., both anions and cations enter interlayer space to the extent predicted by Donnan equilibrium. Thus the excess salt concentration is reduced in the interlayer in comparison to the external electrolyte but not totally excluded. This draws attention to a misconception, often seen in the literature, stating that anions cannot enter interlayer space due to electrostatic repulsion forces. Taking into account that anions can and will enter the interlayer space a general theoretical framework for describing through-diffusion in montmorillonite is developed. By using a single pore

  11. Recent insights into the molecular pathogenesis of Crohn's disease: a review of emerging therapeutic targets

    Directory of Open Access Journals (Sweden)

    Manuc TE

    2016-03-01

    Full Text Available Teodora-Ecaterina M Manuc,1 Mircea M Manuc,2 Mircea M Diculescu2 1Fundeni Clinical Institute, 2University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania Abstract: Chronic inflammatory bowel diseases (IBDs are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD

  12. Influences of subtropical jet and Tibetan Plateau on precipitation pattern in Asia : Insights from regional climate modeling

    NARCIS (Netherlands)

    Sato, Tomonori

    2009-01-01

    Large topographic features, like the Tibetan Plateau (TP) and the Rocky Mountains, have significant impacts on Earth's climate. Numerical experiments were carried out using a regional climate model in order to study the sensitivity of rainfall distribution to the TP's thermal/dynamic effects and mer

  13. Structure based investigation on the binding interaction of transport proteins in leishmaniasis: insights from molecular simulation.

    Science.gov (United States)

    Singh, Shailza; Mandlik, Vineetha

    2015-05-01

    Leishmania major is the causative agent of cutaneous leishmaniasis which affects over 1 million people in 88 different countries. The incidence of this disease is on the rise due to the current problems associated with the present chemotherapeutics. In addition, Leishmania confronts resistance to the traditional drugs like sodium stibogluconate and newer repurposed drugs like miltefosine. ABC transporters are involved in the development of drug resistance. Miltefosine, the drug used for the treatment of leishmaniasis, is effluxed by P4 ATPase and ABC transporter, which is the prime focus of our study in this paper. P4 ATPase (MDR1) along with an unnamed protein (cdc50) translocates miltefosine from the outer to the inner leaflet by the process of flipping which is ATP driven. In contrast, miltefosine also escapes from the cells by an energy dependent mechanism that involves the ABC transporter protein (ABC). It is known that certain genes in the parasite amplify the portions of a gene which encodes ABC transporter and P4 ATPase involved in translocating phospholipids and hence resistance to miltefosine. We observed the ABC and P4 ATPase genes, 39 T-box elements were observed in the ABC transporter protein and three elements were observed in the P4 ATPase gene suggesting its role in transcription regulation. To the best of our knowledge, there are no structural and regulatory reports on these two proteins in L. major. Computational structural biology tools may aid in understanding the interaction of miltefosine with the P4-ATPase-cdc50 complex and the ABC transporter. This can be achieved by modeling the target protein structures, studying the dynamics associated with the different domains of the protein and later using activators and inhibitors to alter the functioning of the protein. Molecular dynamics simulation with a lipid bilayer is performed to investigate the conformational changes and structure-activity relationship. As transporters are difficult to model

  14. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Parvez; Chaturvedi, Sumit Kumar [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Anwar, Tamanna [Center of Bioinformatics Research and Technology, Aligarh 202002 (India); Siddiqi, Mohammad Khursheed; Ajmal, Mohd Rehan [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Badr, Gamal [Laboratory of Immunology & Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, 71516 Assiut (Egypt); Mahmoud, Mohamed H. [Food Science and Nutrition Department, National Research Center, Dokki, Cairo (Egypt); Deanship of Scientific Research, King Saud University, Riyadh (Saudi Arabia); Hasan Khan, Rizwan, E-mail: rizwanhkhan@hotmail.com [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India)

    2015-08-15

    Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×10{sup 3} M{sup −1}. The average binding distance between drug and Trp{sup 214} of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV–visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH=−26.01 kJ mol{sup −1} and TΔS=6.5 kJ mol{sup −1}) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations. - Highlights: • Comprehensive insight into the interaction of CBDA with HSA. • The interaction process is spontaneous and exothermic. • The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding. • CBDA binds at subdomain IB on HSA.

  15. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

    International Nuclear Information System (INIS)

    Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×103 M−1. The average binding distance between drug and Trp214 of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV–visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH=−26.01 kJ mol−1 and TΔS=6.5 kJ mol−1) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations. - Highlights: • Comprehensive insight into the interaction of CBDA with HSA. • The interaction process is spontaneous and exothermic. • The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding. • CBDA binds at subdomain IB on HSA

  16. Integrated Molecular and Microscopic Scale Insight into Morphology and Ion Dynamics in Ca2+-Mediated Natural Organic Matter Floccs

    Energy Technology Data Exchange (ETDEWEB)

    Bowers, Geoffrey M.; Argersinger, Haley E.; Reddy, Venkataswara; Johnson, Timothy A.; Arey, Bruce W.; Bowden, Mark E.; Kirkpatrick, Robert J.

    2015-08-06

    Combined X-ray diffraction (XRD), helium ion microscopy (HeIM), and Ca-43 nuclear magnetic resonance (NMR) results provide novel insight into the nano- and microstructure of flocculated NOM; the molecular-scale interaction among natural organic matter (NOM), dissolved Ca2+ ions, and water in NOM floccs; and the effects of pH and ionic strength on these characteristics. Suwannee River humic acid (HA), fulvic acid (FA), and NOM flocculated from Ca2+ bearing solutions share similar morphological characteristics on the 100 nm to micron scales, including micron-sized equant fragments and rounded, rough areas with features on the 100 nm scale. HeIM suggests that the NOM floccs are built from a fundamental spheroidal structure that is similar to 10 nm in diameter, in agreement with published AFM and small-angle X-ray scattering results. Calcium is incorporated into these floccs at 100% relative humidity in a wide range of disordered structural environments, with basic pH leading to shorter mean Ca-O distances and lower mean coordination numbers with respect to floccs formed under acidic conditions. The NMR results show that dynamical processes involving water and Ca2+ occurring at frequencies >10(4) Hz are important for hydrated OM floccs, in agreement with published molecular dynamics simulations of OM in solution. From the NMR results, we find evidence for two Ca2+ dynamic averaging mechanisms: one related to rapid exchange (>100 kHz) between surface proximity-restricted (those within 5 angstrom of a surface) and bulk solution environments when excess Ca2+ is present in the pore solution when pore water is unfrozen and a second consisting of intermediate scale (tens of kHz) site exchange among strongly sorbed inner-sphere sites when excess Ca2+ is absent and the carboxylic and phenolic functional groups of the NOM are deprotonated.

  17. Insights on the structural perturbations in human MTHFR Ala222Val mutant by protein modeling and molecular dynamics.

    Science.gov (United States)

    Abhinand, P A; Shaikh, Faraz; Bhakat, Soumendranath; Radadiya, Ashish; Bhaskar, L V K S; Shah, Anamik; Ragunath, P K

    2016-04-01

    Methylenetetrahydrofolate reductase (MTHFR) protein catalyzes the only biochemical reaction which produces methyltetrahydrofolate, the active form of folic acid essential for several molecular functions. The Ala222Val polymorphism of human MTHFR encodes a thermolabile protein associated with increased risk of neural tube defects and cardiovascular disease. Experimental studies have shown that the mutation does not affect the kinetic properties of MTHFR, but inactivates the protein by increasing flavin adenine dinucleotide (FAD) loss. The lack of completely solved crystal structure of MTHFR is an impediment in understanding the structural perturbations caused by the Ala222Val mutation; computational modeling provides a suitable alternative. The three-dimensional structure of human MTHFR protein was obtained through homology modeling, by taking the MTHFR structures from Escherichia coli and Thermus thermophilus as templates. Subsequently, the modeled structure was docked with FAD using Glide, which revealed a very good binding affinity, authenticated by a Glide XP score of -10.3983 (kcal mol(-1)). The MTHFR was mutated by changing Alanine 222 to Valine. The wild-type MTHFR-FAD complex and the Ala222Val mutant MTHFR-FAD complex were subjected to molecular dynamics simulation over 50 ns period. The average difference in backbone root mean square deviation (RMSD) between wild and mutant variant was found to be ~.11 Å. The greater degree of fluctuations in the mutant protein translates to increased conformational stability as a result of mutation. The FAD-binding ability of the mutant MTHFR was also found to be significantly lowered as a result of decreased protein grip caused by increased conformational flexibility. The study provides insights into the Ala222Val mutation of human MTHFR that induces major conformational changes in the tertiary structure, causing a significant reduction in the FAD-binding affinity. PMID:26273990

  18. Conduction and Reactivity in Heterogeneous-Molecular Catalysis: New Insights in Water Oxidation Catalysis by Phosphate Cobalt Oxide Films.

    Science.gov (United States)

    Costentin, Cyrille; Porter, Thomas R; Savéant, Jean-Michel

    2016-05-01

    Cyclic voltammetry of phosphate cobalt oxide (CoPi) films catalyzing O2-evolution from water oxidation as a function of scan rate, phosphate concentration and film thickness allowed for new insights into the coupling between charge transport and catalysis. At pH = 7 and low buffer concentrations, the film is insulating below 0.8 (V vs SHE) but becomes conductive above 0.9 (V vs SHE). Between 1.0 to 1.3 (V vs SHE), the mesoporous structure of the film gives rise to a large thickness-dependent capacitance. At higher buffer concentrations, two reversible proton-coupled redox couples appear over the capacitive response with 0.94 and 1.19 (V vs SHE) pH = 7 standard potentials. The latter is, at most, very weakly catalytic and not responsible for the large catalytic current observed at higher potentials. CV-response analysis showed that the amount of redox-active cobalt-species in the film is small, less than 10% of total. The catalytic process involves a further proton-coupled-electron-transfer and is so fast that it is controlled by diffusion of phosphate, the catalyst cofactor. CV-analysis with newly derived relationships led to a combination of the catalyst standard potential with the catalytic rate constant and a lower-limit estimation of these parameters. The large currents resulting from the fast catalytic reaction result in significant potential losses related to charge transport through the film. CoPi films appear to combine molecular catalysis with semiconductor-type charge transport. This mode of heterogeneous molecular catalysis is likely to occur in many other catalytic films. PMID:26981886

  19. Insights into the potential aggregation liabilities of the b12 Fab fragment via elevated temperature molecular dynamics.

    Science.gov (United States)

    Buck, Patrick M; Kumar, Sandeep; Singh, Satish K

    2013-03-01

    Aggregation is a common hurdle faced during the development of antibody therapeutics. In this study, we explore the potential aggregation liabilities of the Fab (fragment antigen-binding) from a human IgG1κ antibody via multiple elevated temperature molecular dynamic simulations, analogous to accelerated stability studies performed during formulation development. Deformation and solvent exposure changes in response to thermal stress were monitored for individual structural domains (V(H), V(L), C(H)1 and C(L)), their interfaces (V(H):V(L) and C(H)1:C(L)), edge beta-strands and sequence-predicted aggregation-prone regions (APRs). During simulations, domain interfaces deformed prior to the unfolding of individual domains. However, interfacial beta-strands retained their secondary structure and remained solvent protected longer than all other strands or loops. Thus, APRs located in interfacial beta-strands are effectively blocked from self-association. Structural deformations were also observed in complementarity-determining regions, edge beta-strands and adjoining framework beta-strands, which increased their solvent-accessible surface area and exposed APRs in these regions. From the analysis of these structural changes, two potential aggregation liabilities were identified in the V(H) domain of this Fab. Insights gained from this investigation should be useful in devising a rational structure-based strategy for the design and selection of antibody candidates with high potency and improved developability. PMID:23188804

  20. Insights into the Formation and Structures of Molecular Gels by Diimidazolium Salt Gelators in Ionic Liquids or "Normal" Solvents.

    Science.gov (United States)

    Rizzo, Carla; D'Anna, Francesca; Noto, Renato; Zhang, Mohan; Weiss, Richard G

    2016-08-01

    Insights are provided into the properties of molecular gels formed by diimidazolium salts both in "normal" solvents and ionic liquids. These materials can be interesting for applications in green and sustainable chemistry in which ionic liquids play a significant role, like catalysis and energy. In particular, two positional isomers of a diimidazolium cation have been examined with a wide range of anions for their ability to form gel phases. In particular, di-, tri-, and tetravalent anions bearing aliphatic or aromatic spacers were paired with the divalent cations. The properties of the organo- and ionogels formed have been analyzed by means of several different techniques, including calorimetry, rheology, resonance light scattering, UV/Vis absorption, polarizing optical microscopy, and powder X-ray diffraction measurements. The investigations performed enabled us to obtain a wide range of conductive materials characterized by a high thermal stability and a low corrosiveness of the gelator (organogels) or of both gelator and solvent (ionogels). The information gained should be useful in the broader quest to identify and promote their applications. PMID:27359108

  1. Paleodistributions and comparative molecular phylogeography of leafcutter ants (Atta spp. provide new insight into the origins of Amazonian diversity.

    Directory of Open Access Journals (Sweden)

    Scott E Solomon

    Full Text Available The evolutionary basis for high species diversity in tropical regions of the world remains unresolved. Much research has focused on the biogeography of speciation in the Amazon Basin, which harbors the greatest diversity of terrestrial life. The leading hypotheses on allopatric diversification of Amazonian taxa are the Pleistocene refugia, marine incursion, and riverine barrier hypotheses. Recent advances in the fields of phylogeography and species-distribution modeling permit a modern re-evaluation of these hypotheses. Our approach combines comparative, molecular phylogeographic analyses using mitochondrial DNA sequence data with paleodistribution modeling of species ranges at the last glacial maximum (LGM to test these hypotheses for three co-distributed species of leafcutter ants (Atta spp.. The cumulative results of all tests reject every prediction of the riverine barrier hypothesis, but are unable to reject several predictions of the Pleistocene refugia and marine incursion hypotheses. Coalescent dating analyses suggest that population structure formed recently (Pleistocene-Pliocene, but are unable to reject the possibility that Miocene events may be responsible for structuring populations in two of the three species examined. The available data therefore suggest that either marine incursions in the Miocene or climate changes during the Pleistocene--or both--have shaped the population structure of the three species examined. Our results also reconceptualize the traditional Pleistocene refugia hypothesis, and offer a novel framework for future research into the area.

  2. The Response of Stratospheric Water Vapor to a Changing Climate: Insights from In Situ Water Vapor Measurements

    OpenAIRE

    Sargent, Maryann Racine

    2012-01-01

    Stratospheric water vapor plays an important role in the Earth system, both through its role in stratospheric ozone destruction and as a greenhouse gas contributing to radiative forcing of the climate. Highly accurate water vapor measurements are critical to understanding how stratospheric water vapor concentrations will respond to a changing climate. However, the past disagreement among water vapor instruments on the order of 1 – 2 ppmv hinders understanding of the mechanisms which control s...

  3. Simple Indices Provide Insight to Climate Attributes Delineating the Geographic Range of Aedes albopictus (Diptera: Culicidae) Prior to Worldwide Invasion.

    Science.gov (United States)

    Mogi, Motoyoshi; Armbruster, Peter; Tuno, Nobuko; Campos, Raúl; Eritja, Roger

    2015-07-01

    Aedes albopictus (Skuse) has expanded its distribution worldwide during the past decades. Despite attempts to explain and predict its geographic occurrence, analyses of the distribution of Ae. albopictus in the context of broad climatic regions (biomes) has not been performed. We analyzed climate conditions at its distribution sites in the range before the worldwide invasions (from the easternmost Hawaii through westernmost Madagascar) by using thermal and aridity-humidity indices descriptive of major biomes. A significant advantage of this approach is that it uses simple indices clearly related to the population dynamics of Ae. albopictus. Although Ae. albopictus has been regarded as a forest species preferring humid climate, in areas with significant human habitation, the distribution sites extended from the perhumid, rain forest zone to the semiarid, steppe zone. This pattern was common from the tropics through the temperate zone. Across the distribution range, there was no seasonal discordance between temperature and precipitation; at sites where winter prevents Ae. albopictus reproduction (monthly means10°C) under the Asian summer monsoon. Absence of the species in northern and eastern coastal Australia and eastern coastal Africa was not attributable solely to climate conditions. However, Asia west of the summer monsoon range was climatically unsuitable because of low precipitation throughout the year or in warm months favorable to reproduction (concentration of precipitation in winter). We hypothesized that Ae. albopictus originated in continental Asia under the monsoon climate with distinct dry seasons and hot, wet summer, enabling rapid population growth. PMID:26335471

  4. Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate.

    Science.gov (United States)

    Ray, Adrian S; Yang, Zhenjun; Shi, Junxing; Hobbs, Ann; Schinazi, Raymond F; Chu, Chung K; Anderson, Karen S

    2002-04-23

    Abacavir (1592U89, or Ziagen) is a powerful and selective inhibitor of HIV-1 viral replication that has been approved by the FDA for treatment of acquired immunodeficiency syndrome. Abacavir is metabolized to the active compound carbovir triphosphate (CBVTP). This compound is a guanosine analogue containing a 2',3'-unsaturation in its planar carbocyclic deoxyribose ring that acts on HIV-1 reverse transcriptase (RT(WT)) as a molecular target, resulting in chain termination of DNA synthesis. A single amino acid change from methionine 184 to valine in HIV-1 RT (RT(M184V)) has been observed clinically in response to abacavir treatment. The ability of the natural substrate, dGTP, or CBVTP to be utilized during DNA- and RNA-directed polymerization by RT(WT) and RT(M184V) was defined by pre-steady-state kinetic parameters. In the case of RT(WT), CBVTP was found to be a surprisingly poor substrate relative to dGTP. In both DNA- and RNA-directed polymerization, a decrease in the efficiency of CBVTP utilization with respect to dGTP was found with RT(M184V), suggesting that this mutation confers resistance at the level of CBVMP incorporation. The relatively low incorporation efficiency for RT(WT) was unanticipated considering earlier studies showing that the triphosphate form of a thymidine nucleoside analogue containing a planar 2',3'-unsaturated ribose ring, D4TTP, was incorporated with high efficiency relative to the natural substrate, dTTP. The difference may be related to the isosteric replacement of oxygen in the deoxyribose ring with carbon. This hypothesis was tested by synthesizing and evaluating D4GTP (the planar 2',3'-unsaturated deoxyribose guanosine analogue that is complementary to D4TTP). In contrast to CBVTP, D4GTP was found to be an excellent substrate for RT(WT) and no resistance was conferred by the M184V mutation, thus providing novel insight into structure-activity relationships for nucleoside-based inhibitors. In this work, we illustrate how an

  5. Release of Native-like Gaseous Proteins from Electrospray Droplets via the Charged Residue Mechanism: Insights from Molecular Dynamics Simulations.

    Science.gov (United States)

    McAllister, Robert G; Metwally, Haidy; Sun, Yu; Konermann, Lars

    2015-10-01

    The mechanism whereby gaseous protein ions are released from charged solvent droplets during electrospray ionization (ESI) remains a matter of debate. Also, it is unclear to what extent electrosprayed proteins retain their solution structure. Molecular dynamics (MD) simulations offer insights into the temporal evolution of protein systems. Surprisingly, there have been no all-atom simulations of the protein ESI process to date. The current work closes this gap by investigating the behavior of protein-containing aqueous nanodroplets that carry excess positive charge. We focus on "native ESI", where proteins initially adopt their biologically active solution structures. ESI proceeds while the protein remains entrapped within the droplet. Protein release into the gas phase occurs upon solvent evaporation to dryness. Droplet shrinkage is accompanied by ejection of charge carriers (Na(+) for the conditions chosen here), keeping the droplet at ∼85% of the Rayleigh limit throughout its life cycle. Any remaining charge carriers bind to the protein as the final solvent molecules evaporate. The outcome of these events is largely independent of the initial protein charge and the mode of charge carrier binding. ESI charge states and collision cross sections of the MD structures agree with experimental data. Our results confirm the Rayleigh/charged residue model (CRM). Field emission of excess Na(+) plays an ancillary role by governing the net charge of the shrinking droplet. Models that envision protein ejection from the droplet are not supported. Most nascent CRM ions retain native-like conformations. For unfolded proteins ESI likely proceeds along routes that are different from the native state mechanism explored here. PMID:26325619

  6. Mutant analysis in Arabidopsis provides insight into the molecular mode of action of the auxinic herbicide dicamba.

    Directory of Open Access Journals (Sweden)

    Cynthia Gleason

    Full Text Available Herbicides that mimic the natural auxin indole-3-acetic acid are widely used in weed control. One common auxin-like herbicide is dicamba, but despite its wide use, plant gene responses to dicamba have never been extensively studied. To further understand dicamba's mode of action, we utilized Arabidopsis auxin-insensitive mutants and compared their sensitivity to dicamba and the widely-studied auxinic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D. The mutant axr4-2, which has disrupted auxin transport into cells, was resistant to 2,4-D but susceptible to dicamba. By comparing dicamba resistance in auxin signalling F-box receptor mutants (tir1-1, afb1, afb2, afb3, and afb5, only tir1-1 and afb5 were resistant to dicamba, and this resistance was additive in the double tir1-1/afb5 mutant. Interestingly, tir1-1 but not afb5 was resistant to 2,4-D. Whole genome analysis of dicamba-induced gene expression showed that 10 hours after application, dicamba stimulated many stress-responsive and signalling genes, including those involved in biosynthesis or signalling of auxin, ethylene, and abscisic acid (ABA, with TIR1 and AFB5 required for the dicamba-responsiveness of some genes. Research into dicamba-regulated gene expression and the selectivity of auxin receptors has provided molecular insight into dicamba-regulated signalling and could help in the development of novel herbicide resistance in crop plants.

  7. Functional and structural insights revealed by molecular dynamics simulations of an essential RNA editing ligase in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Rommie E Amaro

    Full Text Available RNA editing ligase 1 (TbREL1 is required for the survival of both the insect and bloodstream forms of Trypanosoma brucei, the parasite responsible for the devastating tropical disease African sleeping sickness. The type of RNA editing that TbREL1 is involved in is unique to the trypanosomes, and no close human homolog is known to exist. In addition, the high-resolution crystal structure revealed several unique features of the active site, making this enzyme a promising target for structure-based drug design. In this work, two 20 ns atomistic molecular dynamics (MD simulations are employed to investigate the dynamics of TbREL1, both with and without the ATP substrate present. The flexibility of the active site, dynamics of conserved residues and crystallized water molecules, and the interactions between TbREL1 and the ATP substrate are investigated and discussed in the context of TbREL1's function. Differences in local and global motion upon ATP binding suggest that two peripheral loops, unique to the trypanosomes, may be involved in interdomain signaling events. Notably, a significant structural rearrangement of the enzyme's active site occurs during the apo simulations, opening an additional cavity adjacent to the ATP binding site that could be exploited in the development of effective inhibitors directed against this protozoan parasite. Finally, ensemble averaged electrostatics calculations over the MD simulations reveal a novel putative RNA binding site, a discovery that has previously eluded scientists. Ultimately, we use the insights gained through the MD simulations to make several predictions and recommendations, which we anticipate will help direct future experimental studies and structure-based drug discovery efforts against this vital enzyme.

  8. Insight into the Li2CO3-K2CO3 eutectic mixture from classical molecular dynamics: Thermodynamics, structure, and dynamics

    Science.gov (United States)

    Corradini, Dario; Coudert, François-Xavier; Vuilleumier, Rodolphe

    2016-03-01

    We use molecular dynamics simulations to study the thermodynamics, structure, and dynamics of the Li2CO3-K2CO3 (62:38 mol. %) eutectic mixture. We present a new classical non-polarizable force field for this molten salt mixture, optimized using experimental and first principles molecular dynamics simulations data as reference. This simple force field allows efficient molecular simulations of phenomena at long time scales. We use this optimized force field to describe the behavior of the eutectic mixture in the 900-1100 K temperature range, at pressures between 0 and 5 GPa. After studying the equation of state in these thermodynamic conditions, we present molecular insight into the structure and dynamics of the melt. In particular, we present an analysis of the temperature and pressure dependence of the eutectic mixture's self-diffusion coefficients, viscosity, and ionic conductivity.

  9. Climate, people, fire and vegetation: new insights into vegetation dynamics in the Eastern Mediterranean since the 1st century AD

    Directory of Open Access Journals (Sweden)

    J. Bakker

    2012-08-01

    Full Text Available Anatolia forms a bridge between Europe, Africa and Asia and is influenced by all three continents in terms of climate, vegetation and human civilisation. Unfortunately, well dated palynological records focussing on the period from the end of the classical Roman period until subrecent times are rare for Anatolia and completely absent for southwest Turkey, resulting in a lacuna in knowledge concerning the interactions of climatic change, human impact, and environmental change in this important region. Two well dated palaeoecological records from the Western Taurus Mountains, Turkey, provide a first relatively detailed record of vegetation dynamics from late Roman times until the present in SW Turkey. Combining pollen, non-pollen palynomorphs, charcoal, sedimentological, archaeological data, and newly developed multivariate numerical analyses, allows for the disentangling of climatic and anthropogenic influences on vegetation change. Results show both the regional pollen signal as well as local soil sediment characteristics respond accurately to shifts in regional climatic conditions. Both climatic as well as anthropogenic change had a strong influence on vegetation dynamics and land use. A moist environmental trend during the late 3rd century caused an increase in marshes and wetlands in the moister valley floors, limiting possibilities for intensive crop cultivation at such locations. A mid 7th century shift to pastoralism coincided with a climatic deterioration as well as the start of Arab incursions into the region, the former driving the way in which the vegetation developed afterwards. Resurgence in agriculture was observed in the study during the mid 10th century AD, coinciding with the Medieval Climate Anomaly. An abrupt mid 12th century decrease in agriculture is linked to socio-political change, rather than the onset of the Little Ice Age. Similarly, gradual deforestation occurring from the 16th century onwards has been linked to changes

  10. Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: Insights into TCDD-induced endocrine disruption and reproductive toxicity

    OpenAIRE

    King Heiden, Tisha C.; Struble, Craig A.; Rise, Matthew L.; Hessner, Martin J; Hutz, Reinhold J.; Carvan, Michael J.

    2007-01-01

    TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD’s reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In-silico computational approaches were ...

  11. Anthropogenic and Climate Influences on Biogeochemical Dynamics and Molecular-Level Speciation of Soil Sulfur

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, D.; Lehmann, J; Kinyangi, J; Pell, A; Theis , J; Riha , S; Ngoze, S; Amelung, W; du Preez, C; et. al.

    2009-01-01

    The soil environment is a primary component of the global biogeochemical sulfur (S) cycle, acting as a source and sink of various S species and mediating oxidation state changes. However, ecological significance of the various S forms and the impacts of human intervention and climate on the amount and structural composition of these compounds are still poorly understood. We investigated the long-term influences of anthropogenically mediated transitions from natural to managed ecosystems on molecular-level speciation, biogeochemical dynamics, and the apparent temperature sensitivity of S moieties in temperate, subtropical, and tropical environments with mean annual temperature (MAT) ranging from 5C to 21C, using elemental analysis and X-ray absorption near-edge structure (XANES) spectroscopy. Land-use and land-cover changes led to the depletion of total soil S in all three ecoregions over a period of up to 103 years. The largest decline occurred from tropical forest agroecosystems (67% Kakamega and 76% Nandi, Kenya), compared to losses from temperate (36% at Lethbridge, Canada, and 40% at Pendleton, USA) and subtropical (48% at South Africa) grassland agroecosystems. The total S losses correlated significantly with MAT. Anthropogenic interventions profoundly altered the molecular-level composition and resulted in an apparent shift in oxidation states of organic S from native ecosystems composed primarily of S moieties in intermediate and highly reduced oxidation states toward managed agroecosystems dominated by organic S rich in strongly oxidized functionalities. The most prominent change occurred in thiols and sulfides, the proportion of which decreased by 46% (Lethbridge) and 57% (Pendleton) in temperate agroecosystems, by 46% in subtropical agroecosystems, and by 79% (Nandi) and 81% (Kakamega) in tropical agroecosystems. The proportion of organic S directly linked to O increased by 81%, 168%, 40%, 92%, and 85%, respectively. Among the various organic S

  12. Value of traditional oral narratives in building climate-change resilience: insights from rural communities in Fiji

    Directory of Open Access Journals (Sweden)

    Shaiza Z. Janif

    2016-06-01

    Full Text Available In the interests of improving engagement with Pacific Island communities to enable development of effective and sustainable adaptation strategies to climate change, we looked at how traditional oral narratives in rural/peripheral Fiji communities might be used to inform such strategies. Interviews were undertaken and observations made in 27 communities; because the custodians of traditional knowledge were targeted, most interviewees were 70-79 years old. The view that oral traditions, particularly those referring to environmental history and the observations/precursors of environmental change, were endangered was widespread and regretted. Interviewees' personal experiences of extreme events (natural disasters were commonplace but no narratives of historical (unwitnessed by interviewees events were found. In contrast, experiences of previous village relocations attributable (mainly to environmental change were recorded in five communities while awareness of environmentally driven migration was more common. Questions about climate change elicited views dominated by religious/fatalist beliefs but included some more pragmatic ones; the confusion of climate change with climate variability, which is part of traditional knowledge, was widespread. The erosion of traditional environmental knowledge in the survey communities over recent decades has been severe and is likely to continue apace, which will reduce community self-sufficiency and resilience. Ways of conserving such knowledge and incorporating it into adaptation planning for Pacific Island communities in rural/peripheral locations should be explored.

  13. Southern African continental climate since the late Pleistocene: Insights from biomarker analyses of Kalahari salt pan sediments

    Science.gov (United States)

    Belz, Lukas; Schüller, Irka; Wehrmann, Achim; Wilkes, Heinz

    2016-04-01

    The climate system of sub-tropical southern Africa is mainly controlled by large scale atmospheric and marine circulation processes and, therefore, very sensitive to global climate change. This underlines the importance of paleoenvironmental reconstructions in order to estimate regional implications of current global changes. However, the majority of studies on southern African paleoclimate are based on the investigation of marine sedimentary archives and past climate development especially in continental areas is still poorly understood. This emphasizes the necessity of continental proxy-data from this area. Proxy datasets from local geoarchives especially of the southwestern Kalahari region are still scarce. A main problem is the absence of conventional continental climatic archives, due to the lack of lacustrine systems. In this study we are exploring the utility of sediments from western Kalahari salt pans, i.e. local depressions which are flooded temporarily during rainfall events. An age model based on 14C dating of total organic carbon (TOC) shows evidence that sedimentation predominates over erosional processes with respect to pan formation. Besides the analyses of basic geochemical bulk parameters including TOC, δ13CTOC, total inorganic carbon, δ13CTIC, δ18OTIC, total nitrogen and δ15N, our paleo-climatic approach focuses on reconstruction of local vegetation assemblages to identify changes in the ecosystem. This is pursued using plant biomarkers, particularly leaf wax n-alkanes and n-alcohols and their stable carbon and hydrogen isotopic signatures. Results show prominent shifts in n-alkane and n-alkanol distributions and compound specific carbon isotope values, pointing to changes to a more grass dominated environment during Heinrich Stadial 1 (18.5-14.6 ka BP), while hydrogen isotope values suggest wetter phases during Holocene and LGM. This high variability indicates the local vulnerability to global change.

  14. Impacts of climate and humans on the vegetation in NW Turkey: palynological insights from Lake Iznik since the Last Glacial

    Directory of Open Access Journals (Sweden)

    A. Miebach

    2015-11-01

    Full Text Available The Marmara region in northwestern Turkey provides a unique opportunity for studying the vegetation history in response to climate changes and anthropogenic impacts because of its location between different climate and vegetation zones and its long settlement history. Geochemical and mineralogical investigations of the largest lake in the region, Lake Iznik, already registered climate related changes of the lake level and the lake mixing. However, a palynological investigation encompassing the Late Pleistocene to Middle Holocene was still missing. Here, we present the first pollen record of the last ca. 31 ka cal BP (calibrated kilo years before 1950 inferred from Lake Iznik sediments as an independent proxy for paleoecological reconstructions. Our study reveals that the vegetation in the Iznik area changed generally between steppe during glacial/stadial conditions, forest-steppe during interstadial conditions, and oak dominated mesic forest during interglacial conditions. Moreover, a pronounced succession of pioneer trees, cold temperate, warm temperate, and Mediterranean trees appeared since the Lateglacial. Rapid climate changes, which are reflected by vegetation changes, can be correlated with Dansgaard–Oeschger (DO events such as DO-4, DO-3, and DO-1, the Younger Dryas, and probably also the 8.2 event. Since the mid-Holocene, the vegetation was influenced by anthropogenic activities. During early settlement phases, the distinction between climate-induced and human-induced changes of the vegetation is challenging. Still, evidence for human activities consolidates since the Early Bronze Age (ca. 4.8 ka cal BP: cultivated trees, crops, and secondary human indicator taxa appeared, and forests got cleared. Subsequent fluctuations between extensive agricultural use and regeneration of the natural vegetation become apparent.

  15. Climate, people, fire and vegetation: new insights into vegetation dynamics in the Eastern Mediterranean since the 1st century AD

    Directory of Open Access Journals (Sweden)

    J. Bakker

    2013-01-01

    Full Text Available Anatolia forms a bridge between Europe, Africa and Asia and is influenced by all three continents in terms of climate, vegetation and human civilisation. Unfortunately, well-dated palynological records focussing on the period from the end of the classical Roman period until subrecent times are rare for Anatolia and completely absent for southwest Turkey, resulting in a lacuna in knowledge concerning the interactions of climatic change, human impact, and environmental change in this important region. Two well-dated palaeoecological records from the Western Taurus Mountains, Turkey, provide a first relatively detailed record of vegetation dynamics from late Roman times until the present in SW Turkey. Combining pollen, non-pollen palynomorphs, charcoal, sedimentological, archaeological data, and newly developed multivariate numerical analyses allows for the disentangling of climatic and anthropogenic influences on vegetation change. Results show changes in both the regional pollen signal as well as local soil sediment characteristics match shifts in regional climatic conditions. Both climatic as well as anthropogenic change had a strong influence on vegetation dynamics and land use. A moist environmental trend during the late-3rd century caused an increase in marshes and wetlands in the moister valley floors, limiting possibilities for intensive crop cultivation at such locations. A mid-7th century shift to pastoralism coincided with a climatic deterioration as well as the start of Arab incursions into the region, the former driving the way in which the vegetation developed afterwards. Resurgence in agriculture was observed in the study during the mid-10th century AD, coinciding with the Medieval Climate Anomaly. An abrupt mid-12th century decrease in agriculture is linked to socio-political change, rather than the onset of the Little Ice Age. Similarly, gradual deforestation occurring from the 16th century onwards has been linked to changes in

  16. Climate, people, fire and vegetation: new insights into vegetation dynamics in the Eastern Mediterranean since the 1st century AD

    Science.gov (United States)

    Bakker, J.; Paulissen, E.; Kaniewski, D.; Poblome, J.; De Laet, V.; Verstraeten, G.; Waelkens, M.

    2013-01-01

    Anatolia forms a bridge between Europe, Africa and Asia and is influenced by all three continents in terms of climate, vegetation and human civilisation. Unfortunately, well-dated palynological records focussing on the period from the end of the classical Roman period until subrecent times are rare for Anatolia and completely absent for southwest Turkey, resulting in a lacuna in knowledge concerning the interactions of climatic change, human impact, and environmental change in this important region. Two well-dated palaeoecological records from the Western Taurus Mountains, Turkey, provide a first relatively detailed record of vegetation dynamics from late Roman times until the present in SW Turkey. Combining pollen, non-pollen palynomorphs, charcoal, sedimentological, archaeological data, and newly developed multivariate numerical analyses allows for the disentangling of climatic and anthropogenic influences on vegetation change. Results show changes in both the regional pollen signal as well as local soil sediment characteristics match shifts in regional climatic conditions. Both climatic as well as anthropogenic change had a strong influence on vegetation dynamics and land use. A moist environmental trend during the late-3rd century caused an increase in marshes and wetlands in the moister valley floors, limiting possibilities for intensive crop cultivation at such locations. A mid-7th century shift to pastoralism coincided with a climatic deterioration as well as the start of Arab incursions into the region, the former driving the way in which the vegetation developed afterwards. Resurgence in agriculture was observed in the study during the mid-10th century AD, coinciding with the Medieval Climate Anomaly. An abrupt mid-12th century decrease in agriculture is linked to socio-political change, rather than the onset of the Little Ice Age. Similarly, gradual deforestation occurring from the 16th century onwards has been linked to changes in land use during Ottoman

  17. Importance of abiotic stress as a range-limit determinant for European plants: insights from species responses to climatic gradients

    DEFF Research Database (Denmark)

    Normand, Signe; Treier, Urs; Randin, Christophe; Vittoz, Pascal; Guisan, Antoine; Svenning, J.-C.

    2009-01-01

    Aim We examined whether species occurrences are primarily limited by physiological tolerance in the abiotically more stressful end of climatic gradients (the asymmetric abiotic stress limitation (AASL) hypothesis) and the geographical predictions of this hypothesis: abiotic stress mainly determin...... upper-latitudinal and upper-altitudinal species range limits, and the importance of abiotic stress for these range limits increases the further northwards and upwards a species occurs...

  18. Value of traditional oral narratives in building climate-change resilience: insights from rural communities in Fiji

    OpenAIRE

    Shaiza Z. Janif; NUNN, Patrick D.; Paul Geraghty; William Aalbersberg; Frank R. Thomas; Mereoni Camailakeba

    2016-01-01

    In the interests of improving engagement with Pacific Island communities to enable development of effective and sustainable adaptation strategies to climate change, we looked at how traditional oral narratives in rural/peripheral Fiji communities might be used to inform such strategies. Interviews were undertaken and observations made in 27 communities; because the custodians of traditional knowledge were targeted, most interviewees were 70-79 years old. The view that oral traditions, pa...

  19. Small islands, valuable insights: systems of customary resource use and resilience to climate change in the Pacific

    OpenAIRE

    Heather L. McMillen; Tamara Ticktin; Alan Friedlander; Stacy D Jupiter; Randolph Thaman; John Campbell; Joeli Veitayaki; Thomas Giambelluca; Salesa Nihmei; Etika Rupeni; Lucille Apis-Overhoff; William Aalbersberg; Dan F. Orcherton

    2014-01-01

    Understanding how social-ecological systems are and can be resilient to climate change is one of the world's most crucial problems today. It requires knowledge at local and global scales, the integration of natural and social sciences, and a focus on biocultural diversity. Small Pacific Islands and the knowledge-practice-belief systems of their peoples have a long history of resilience to environmental variability and unpredictability, including in areas with marginal habitats and with period...

  20. Decadal-to-centennial-scale climate variability: Insights into the rise and fall of the Great Salt Lake

    Science.gov (United States)

    Mann, Michael E.; Lall, Upmanu; Saltzman, Barry

    1995-01-01

    We demonstrate connections between decadal and secular global climatic variations, and historical variations in the volume of the Great Salt Lake. The decadal variations correspond to a low-frequency shifting of storm tracks which influence winter precipitation and explain nearly 18% of the interannual and longer-term variance in the record of monthly volume change. The secular trend accounts for a more modest approximately 1.5% of the variance.

  1. Insights into soil carbon dynamics across climatic and geologic gradients from time-series and fraction-specific radiocarbon analysis

    Science.gov (United States)

    van der Voort, Tessa Sophia; Hagedorn, Frank; Zell, Claudia; McIntyre, Cameron; Eglinton, Tim

    2016-04-01

    Understanding the interaction between soil organic matter (SOM) and climatic, geologic and ecological factors is essential for the understanding of potential susceptibility and vulnerability to climate and land use change. Radiocarbon constitutes a powerful tool for unraveling SOM dynamics and is increasingly used in studies of carbon turnover. The complex and inherently heterogeneous nature of SOM renders it challenging to assess the processes that govern SOM stability by solely looking at the bulk signature on a plot-scale level. This project combines bulk radiocarbon measurements on a regional-scale spanning wide climatic and geologic gradients with a more in-depth approach for a subset of locations. For this subset, time-series and carbon pool-specific radiocarbon data has been acquired for both topsoil and deeper soils. These well-studied sites are part of the Long-Term Forest Ecosystem Research (LWF) program of the Swiss Federal Institute for Forest, Snow and Landscape research (WSL). Statistical analysis was performed to examine relationships of radiocarbon signatures with variables such as temperature, precipitation and elevation. Bomb-curve modeling was applied determine carbon turnover using time-series data. Results indicate that (1) there is no significant correlation between Δ14C signature and environmental conditions except a weak positive correlation with mean annual temperature, (2) vertical gradients in Δ14C signatures in surface and deeper soils are highly similar despite covering disparate soil-types and climatic systems, and (3) radiocarbon signatures vary significantly between time-series samples and carbon pools. Overall, this study provides a uniquely comprehensive dataset that allows for a better understanding of links between carbon dynamics and environmental settings, as well as for pool-specific and long-term trends in carbon (de)stabilization.

  2. The Climate Potentials and Side-Effects of Large-Scale terrestrial CO2 Removal - Insights from Quantitative Model Assessments

    Science.gov (United States)

    Boysen, L.; Heck, V.; Lucht, W.; Gerten, D.

    2015-12-01

    Terrestrial carbon dioxide removal (tCDR) through dedicated biomass plantations is considered as one climate engineering (CE) option if implemented at large-scale. While the risks and costs are supposed to be small, the effectiveness depends strongly on spatial and temporal scales of implementation. Based on simulations with a dynamic global vegetation model (LPJmL) we comprehensively assess the effectiveness, biogeochemical side-effects and tradeoffs from an earth system-analytic perspective. We analyzed systematic land-use scenarios in which all, 25%, or 10% of natural and/or agricultural areas are converted to tCDR plantations including the assumption that biomass plantations are established once the 2°C target is crossed in a business-as-usual climate change trajectory. The resulting tCDR potentials in year 2100 include the net accumulated annual biomass harvests and changes in all land carbon pools. We find that only the most spatially excessive, and thus undesirable, scenario would be capable to restore the 2° target by 2100 under continuing high emissions (with a cooling of 3.02°C). Large-scale biomass plantations covering areas between 1.1 - 4.2 Gha would produce a climate reduction potential of 0.8 - 1.4°C. tCDR plantations at smaller scales do not build up enough biomass over this considered period and the potentials to achieve global warming reductions are substantially lowered to no more than 0.5-0.6°C. Finally, we demonstrate that the (non-economic) costs for the Earth system include negative impacts on the water cycle and on ecosystems, which are already under pressure due to both land use change and climate change. Overall, tCDR may lead to a further transgression of land- and water-related planetary boundaries while not being able to set back the crossing of the planetary boundary for climate change. tCDR could still be considered in the near-future mitigation portfolio if implemented on small scales on wisely chosen areas.

  3. Insights into regioselective metabolism of mefenamic acid by cytochrome P450 BM3 mutants through crystallography, docking, molecular dynamics, and free energy calculations

    DEFF Research Database (Denmark)

    Capoferri, Luigi; Leth, Rasmus; Ter Haar, Ernst; Mohanty, Arun K; Grootenhuis, Peter D J; Vottero, Eduardo; Commandeur, Jan M N; Vermeulen, Nico P E; Jørgensen, Flemming Steen; Olsen, Lars; Geerke, Daan P

    2016-01-01

    active-site mutations such as V87I were reported to invert regioselectivity in NSAID hydroxylation. In this work, we combine crystallography and molecular simulation to study the effect of single mutations on binding and regioselective metabolism of mefenamic acid by M11 mutants. The heme domain of the...... protein mutant M11 was expressed, purified, and crystallized, and its X-ray structure was used as template for modeling. A multistep approach was used that combines molecular docking, molecular dynamics (MD) simulation, and binding free-energy calculations to address protein flexibility. In this way...... mefenamic acid by M11 and its mutants by including protein flexibility and dynamics in free-energy computation. In addition, we could obtain structural insights into the change in regioselectivity of mefenamic acid hydroxylation due to single active-site mutations. Our findings confirm that use of MD and...

  4. The Pleistocene vermicular red earth in South China signaling the global climatic change: The molecular fossil record

    Institute of Scientific and Technical Information of China (English)

    XIE; Shucheng; (谢树成); YI; Yi; (易; 轶); LIU; Yuyan; (刘育燕); GU; Yansheng; (顾延生); MA; Zhenxing; (马振兴); LIN; Wenjiao; (林文姣); WANG; Xianyan; (王先彦); LIU; Gang; (刘; 刚); LIANG; Bin; (梁; 斌); ZHU; Zongmin; (朱宗敏)

    2003-01-01

    The trace molecular fossils identified in the Pleistocene vermicular red earth by using the gas chromatography-mass spectrometry (GC/MS) analysis include n-alkanes, n-alkanoic acids, n-alkanols and n-alkan-2-ones. The variations of the n-alkane parameters appear to bear significant climate information, in striking contrast to the oxygen-bearing molecules (n-alkanoic acids and n-alkanols) believed to be more easily reworked by post-depositional processes. Of importance in paleoclimate reconstruction are the ratios of C27/C31 n-alkane indicative of the replacement of woody plants by grassy vegetation, and C15-21/C22-33 n-alkane representative of the relative abundance between microorganisms and higher plants. The profile trends of the two n-alkane ratios are comparable to the marine oxygen isotope record among stages 4-20. These molecular fossil records implicate that the Pleistocene vermicular red earth widespread in South China was formed in coupling to the global climatic change and could be an important climate carrier.

  5. A molecular perspective on Late Quaternary climate and vegetation change in the Lake Tanganyika basin, East Africa

    Science.gov (United States)

    Tierney, Jessica E.; Russell, James M.; Huang, Yongsong

    2010-03-01

    Characterizing the nature of past hydrological change and its interactions with vegetation is fundamental to acquiring a better understanding of continental tropical climate dynamics. Here, we outline major shifts in the climate and ecosystem of tropical East Africa for the past 60,000 years (60 ka) by examining molecular records of hydrology, vegetation, and temperature from a sediment sequence from Lake Tanganyika. We demonstrate, via comparison with pollen spectra, that stable carbon isotopes measured on higher plant leaf waxes ( δ13C wax) are a reliable proxy for vegetation change. In addition we argue that the D/H ratio of higher plant leaf waxes ( δD wax) is a robust and independent indicator of past changes in aridity, and is not affected by regional vegetation change directly. Our paired, compound-specific isotope data show that shifts in vegetation lead major changes in hydrology in the Tanganyika basin at several major climate transitions during the past 60,000 years, suggesting that vegetation in the Tanganyika basin is not as sensitive to aridity as previous studies have suggested and that variations in carbon dioxide, temperature, and internal ecosystem dynamics are equally, if not more, important. We hypothesize that regional vegetation change may exert a positive feedback on regional hydrology, thus partially accounting for the abrupt threshold behavior evident in our paleohydrological data. Furthermore, we find that past changes in Tanganyika basin climate and ecology are closely linked to concentrations of atmospheric trace gases, highlighting the paramount influence of global climatic shifts upon regional tropical climate over glacial/interglacial timescales.

  6. Insights into the molecular level composition, sources, and formation mechanisms of dissolved organic matter in aerosols and precipitation

    Science.gov (United States)

    Altieri, Katye Elisabeth

    Atmospheric aerosols scatter and absorb light influencing the global radiation budget and climate, and are associated with adverse effects on human health. Precipitation is an important removal mechanism for atmospheric dissolved organic matter (DOM), and a potentially important input for receiving ecosystems. However, the sources, formation, and composition of atmospheric DOM in aerosols and precipitation are not well understood. This dissertation investigates the composition and formation mechanisms of secondary organic aerosol (SOA) formed through cloud processing reactions, elucidates the composition and sources of DOM in rainwater, and provides links connecting the two. Photochemical batch aqueous-phase reactions of organics with both biogenic and anthropogenic sources (i.e., methylglyoxal, pyruvic acid) and OH radical were performed to simulate cloud processing. The composition of products formed through cloud processing experiments and rainwater collected in New Jersey, USA was investigated using a combination of electrospray ionization mass spectrometry techniques, including ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry. This dissertation has resulted in the first evidence that oligomers form through cloud processing reactions, the first detailed chemical mechanism of aqueous phase oligomerization, the first identification of oligomers, organosulfates, and nitrooxy organosulfates in precipitation, and the first molecular level chemical characterization of organic nitrogen in precipitation. The formation of oligomers in SOA helps to explain the presence of large multifunctional compounds and humic like substances (HULIS) that dominate particulate organic mass. Oligomers have low vapor pressures and remain in the particle phase after cloud evaporation, enhancing SOA. The chemical properties of the oligomers suggest that they are less hygroscopic than the monomeric reaction products (i.e., organic acids). Their elemental

  7. A tale of two spartinas: Climatic, photobiological and isotopic insights on the fitness of non-indigenous versus native species

    Science.gov (United States)

    Duarte, B.; Baeta, A.; Rousseau-Gueutin, M.; Ainouche, M.; Marques, J. C.; Caçador, I.

    2015-12-01

    Salt marshes are facing a new threat: the invasion by non-indigenous species (NIS), Although its introduction time is not established yet, in 1999 Spartina versicolor was already identified as a NIS in the Mediterranean marshes, significantly spreading its area of colonization. Using the Mediterranean native Spartina maritima as a reference, the present research studied the ecophysiological fitness of this NIS in its new environment, as a tool to understand its potential invasiveness. It was found that Spartina versicolor had a stable photobiological pattern, with only minor fluctuations during an annual cycle, and lower efficiencies comparated to S. maritima. The NIS seems to be rather insensitive to the observed abiotic factors fluctuations (salinity and pH of the sediment), and thus contrasts with the native S. maritima, known to be salinity dependent with higher productivity values in higher salinity environments. Most of the differences observed between the photobiology of these species could be explained by their nitrogen nutrition (here evaluated by the δ15N stable isotope) and directly related with the Mediterranean climate. Enhanced by a higher N availability during winter, the primary production of S. maritima which lead to dilution of the foliar δ15N concentration in the newly formed biomass, similarly to what is observed along a rainfall gradient. On the other hand, S. versicolor showed an increased δ15N in its tissues along the annual rainfall gradient, probably due to a δ15N concentration effect during low biomass production periods (winter and autumn). Together with the photobiological traits, these isotopic data point out to a climatic misfit of S. versicolor to the Mediterranean climate compared to the native S. maritima. This appears to be the major constrain shaping the ecophysiological fitness of this NIS, its primary production and consequently, its spreading rate along the Mediterranean marshes.

  8. Response of lightning NOx emissions and ozone production to climate change: Insights from the Atmospheric Chemistry and Climate Model Intercomparison Project

    Science.gov (United States)

    Finney, D. L.; Doherty, R. M.; Wild, O.; Young, P. J.; Butler, A.

    2016-05-01

    Results from an ensemble of models are used to investigate the response of lightning nitrogen oxide emissions to climate change and the consequent impacts on ozone production. Most models generate lightning using a parameterization based on cloud top height. With this approach and a present-day global emission of 5 TgN, we estimate a linear response with respect to changes in global surface temperature of +0.44 ± 0.05 TgN K-1. However, two models using alternative approaches give +0.14 and -0.55 TgN K-1 suggesting that the simulated response is highly dependent on lightning parameterization. Lightning NOx is found to have an ozone production efficiency of 6.5 ± 4.7 times that of surface NOx sources. This wide range of efficiencies across models is partly due to the assumed vertical distribution of the lightning source and partly to the treatment of nonmethane volatile organic compound (NMVOC) chemistry. Careful consideration of the vertical distribution of emissions is needed, given its large influence on ozone production.

  9. The relationships between temperature changes and reproductive investment in a Mediterranean goby: Insights for the assessment of climate change effects

    Science.gov (United States)

    Zucchetta, M.; Cipolato, G.; Pranovi, F.; Antonetti, P.; Torricelli, P.; Franzoi, P.; Malavasi, S.

    2012-04-01

    The relationships between changes in water temperature and the timing and level of reproductive investment were investigated in an estuarine fish, inhabiting the Venice lagoon: the grass goby Zosterisessor ophiocephalus. A time series of the mean monthly values of gonado-somatic index was coupled with thermal profiles of lagoon water temperatures over 14 years, from 1997 to 2010. Results showed that the reproductive investment was positively affected by water temperature changes, both in terms of monthly thermal anomalies and cumulative degree days. A predictive model was also developed to assess the temporal shift of reproductive peaks as a response to inter-annual thermal fluctuations. This model allowed the detection of deviations from the median level, indicating that during warmer years, the reproductive peak tended to occur earlier than during colder years. The model is therefore proposed as a tool to predict anticipated consequences of climate change on fish phenology in transitional waters, regarding recurrent biological phenomena, such as reproduction and recruitment.

  10. Insights into Ocean Acidification During the Middle Eocene Climatic Optimum from Boron Isotopes at Southern Ocean Site 738

    Science.gov (United States)

    Moebius, I.; Hoenisch, B.; Friedrich, O.

    2015-12-01

    The Middle Eocene Climatic Optimum (MECO) is a ~650-kyr interval of global warming, with a brief ~50 ky long peak warming interval, and an abrupt termination. Deep sea and surface ocean temperature evolution across this interval are fairly well constrained, but thus far we have little understanding of the mechanisms responsible for the gradual warming and rapid recovery. Carbonate mass accumulation rates suggest a shoaling of the carbonate compensation depth, and studies on alkenones indicate increasing atmospheric CO2 levels during the MECO. This suggests an increase in surface ocean CO2, and consequently ocean acidification. However, the severity and timing of the proposed ocean acidification with respect to the onset, peak warming and the termination are currently not well resolved. The boron isotopic composition (δ11B) recorded in planktic foraminifer shells offers an opportunity to infer oceanic pH across this interval. We are working on a boron isotope reconstruction from Southern Ocean IODP site 738 and South Atlantic IODP site 1263, covering 42.0 to 38.5 Ma. These sites are characterized by good carbonate preservation and well-defined age models have been established. Additionally, ecology, nutrient content and bottom-water oxygenation have been shown to change significantly across the event towards a more eutrophic, periodically oxygen-depleted environment supporting different biological communities. We selected the planktic foraminifera species Acarinina spinuloinflata for this study because it is symbiont-bearing, suggesting a near-surface habitat and little vertical migration in the water column, and because of its abundance in the samples. δ11B data will be translated to surface ocean pH and atmospheric pCO2 will be approximated to refine knowledge about the carbon cycle during this time. Parallel analysis of two core sites will help to evaluate the tenacity of the data.

  11. Storm surges and climate change implications for tidal marshes: Insight from the San Francisco Bay Estuary, California, USA

    Science.gov (United States)

    Thorne, Karen M.; Buffington, Kevin J.; Swanson, Kathleen; Takekawa, John Y.

    2013-01-01

    Tidal marshes are dynamic ecosystems that are influenced by oceanic and freshwater processes and daily changes in sea level. Projected sea-level rise and changes in storm frequency and intensity will affect tidal marshes by altering suspended sediment supply, plant and wildlife communities, and the inundation duration and depth of the marsh platform. The objective of this research was to evaluate how regional weather conditions resulting in low-pressure storms changed tidal conditions locally within three tidal marshes. We hypothesized that regional storms will increase sea level heights locally, resulting in increased inundation of the tidal marsh platform and plant communities. Using site-level measurements of elevation, plant communities, and water levels, we present results from two storm events in 2010 and 2011 from the San Francisco Bay Estuary (SFBE), California, USA. The January 2010 storm had the lowest recorded sea level pressure in the last 30 years for this region. During the storm episodes, the duration of tidal marsh inundation was 1.8 and 3.1 times greater than average for that time of year in 2010 and 2011, respectively. At peak storm surges, over 65% in 2010 and 93% in 2011 of the plant community was under water. We also discuss the implications of these types of storms and projected sea-level rise on the structure and function of tidal marshes and how that may affect the hydrogeomorphic processes and marsh biotic communities. This type of information is useful to managers for incorporating local climate change into developing their monitoring, management, and adaptation strategies.

  12. Molecular, immunological, and biological characterization of Tityus serrulatus venom hyaluronidase: new insights into its role in envenomation.

    OpenAIRE

    Carolina Campolina Rebello Horta; Bárbara de Freitas Magalhães; Bárbara Bruna Ribeiro Oliveira-Mendes; Anderson Oliveira do Carmo; Clara Guerra Duarte; Liza Figueiredo Felicori; Ricardo Andrez Machado-de-Ávila; Carlos Chávez-Olórtegui; Evanguedes Kalapothakis

    2014-01-01

    BACKGROUND: Scorpionism is a public health problem in Brazil, and Tityus serrulatus (Ts) is primarily responsible for severe accidents. The main toxic components of Ts venom are low-molecular-weight neurotoxins; however, the venom also contains poorly characterized high-molecular-weight enzymes. Hyaluronidase is one such enzyme that has been poorly characterized. METHODS AND PRINCIPAL FINDINGS: We examined clones from a cDNA library of the Ts venom gland and described two novel isoforms of hy...

  13. Insights into mechanism of pyrido[2,3-d]pyrimidines as DYRK1A inhibitors based on molecular dynamic simulations.

    Science.gov (United States)

    Li, Jiao Jiao; Tian, Yue Li; Zhai, Hong Lin; Lv, Min; Zhang, Xiao Yun

    2016-08-01

    DYRK1A is characterized by the early development and regulation of neuronal proliferation, and its over expression gives rise to neurological abnormalities. As the promising DYRK1A inhibitors, the binding mechanism between DYRK1A and pyrido[2,3-d]pyrimidines derivatives at molecular level are still veiled. In this article, it was achieved to get the structural insights into pyrido[2,3-d]pyrimidines derivatives as DYRK1A inhibitors by means of comprehensive computational approaches involving molecular docking, molecular dynamics simulation, free energy calculation, and energy decomposition analysis. The calculated energy values were highly consistent with the experimental activities. Based on the individual energy terms analysis, the van der Waals interaction was the major leading force in the DYRK1A-ligand interaction. Lys188 was the important residue that formed the hydrogen bond, which improved the inhibitory activity. Furthermore, four novel inhibitors with higher predicted activity were designed based on the obtained findings and confirmed by molecular simulations. Our study is expected to provide significant drug design strategy for the development of more promising DYRK1A inhibitors. Proteins 2016; 84:1108-1123. © 2016 Wiley Periodicals, Inc. PMID:27119584

  14. Freshwater paths across the ocean: molecular phylogeny of the frog Ptychadena newtoni gives insights into amphibian colonization of oceanic islands

    OpenAIRE

    Measey, John G.; Vences, M.; Drewes, R. C.; Chiari, Y.; Melo, M.; Bourlès, Bernard

    2007-01-01

    Aim Amphibians are a model group for studies of the biogeographical origins of salt-intolerant taxa on oceanic islands. We used the Gulf of Guinea islands to explore the biogeographical origins of island endemism of one species of frog, and used this to gain insights into potential colonization mechanisms. Location Sao Tome and Principe, two of the four major islands in the Gulf of Guinea, West Africa, are truly oceanic and have an exceptionally high biodiversity. Methods Mitochondrial DNA is...

  15. VIP and PACAP. Recent insights into their functions/roles in physiology and disease from molecular and genetic studies

    Science.gov (United States)

    Moody, Terry W.; Ito, Tetsuhide; Osefo, Nuramy; Jensen, Robert T.

    2010-01-01

    Purpose of review VIP and PACAP as well as the three classes of G-protein-coupled receptors mediating their effects, are widely distributed in the CNS and peripheral tissues. These peptides are reported to have many effects in different tissues, which are physiological or pharmacological, and which receptor mediates which effect, has been difficult to determine, primarily due to lack of potent, stable, selective agonists/antagonists. Recently the use of animals with targeted knockout (KO) of the peptide or a specific receptor has provided important insights into the role of their role in normal physiology and disease states. Recent findings During the review period, considerable progress and insights has occurred in the understanding of the role of VIP/PACAP as well as their receptors in a number of different disorders/areas. Particularly, insights into their roles in energy metabolism, glucose regulation, various gastrointestinal processes including GI inflammatory conditions and motility and their role in the CNS as well as CNS diseases has greatly expanded. Summary PACAP/VIP as well as there three classes of receptors are important in many physiological/pathophysiological processes, some of which are identified in these studies using knockout animals. These studies may lead to new novel treatment approaches. Particularly important are their roles in glucose metabolism and on islets leading to possible novel approaches in diabetes; their novel anti-inflammatory, cytoprotective effects, their CNS neuroprotective effects, and their possible roles in diseases such as schizophrenia and chronic depression. PMID:21157320

  16. High molecular weight SOA formation during limonene ozonolysis: insights from ultrahigh-resolution FT-ICR mass spectrometry characterization

    Science.gov (United States)

    Kundu, S.; Fisseha, R.; Putman, A. L.; Rahn, T. A.; Mazzoleni, L. R.

    2012-06-01

    The detailed molecular composition of laboratory generated limonene ozonolysis secondary organic aerosol (SOA) was studied using ultrahigh-resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Approximately 1200 molecular formulas were identified in the SOA over the mass range of 140 to 850 Da. Four characteristic groups of high relative abundance species were observed; they indicate an array of accretion products that retain a large fraction of the limonene skeleton. The identified molecular formulas of each of the groups are related to one another by CH2, O and CH2O homologous series. The CH2 and O homologous series of the low molecular weight (MW) SOA (m/z 300) were found to constitute a significant number fraction of the identified SOA components. The formation of high MW compounds was evaluated by molecular formula trends, fragmentation analysis of select high MW compounds and a comprehensive reaction matrix including the identified low MW SOA, hydroperoxides and Criegee radicals as building blocks. Although the formation of high MW SOA may occur via a variety of radical and non-radical reaction channels, the combined approach indicates a greater importance of the non-condensation reactions over aldol and ester condensation reaction channels. Among these hemi-acetal reactions appear to be most dominant followed by hydroperoxide and Criegee reaction channels.

  17. Entanglements in P3HT and their influence on thin-film mechanical properties: Insights from molecular dynamics simulations

    KAUST Repository

    Tummala, Naga Rajesh

    2015-04-01

    Due to their inherent mechanical flexibility and stretchability, organic-based electronic devices have garnered a great deal of academic and industrial interest. Here, molecular-dynamics simulations are used to examine the molecular-scale details that govern the relationships among molecular weight, chain entanglement, persistence length, and the elastic characteristics of the widely studied π-conjugated polymer poly-(3-hexyl thiophene), P3HT. Oligomers containing at least 50 monomer units are required in the simulations to observe elastic behavior in P3HT, while much longer chains are required to ensure description of appropriate levels of entanglement: only when the molecular weight is greater than 50 kDa, that is, oligomers with approximately 400 monomer units, is truly entangled behavior observed. Interestingly, results from primitive path analysis of amorphous P3HT matches well with the observed onsets of inter-chain excitonic coherence with increased molecular weight. The simulations also indicate that the P3HT modulus saturates at 1.6 GPa for chain lengths of 50–100 monomers, a result that compares well with experimental results. This work highlights the care that needs to be taken to accurately model P3HT morphologies in relation to experimental measurements. © 2015 The Authors. Journal of Polymer Science Part B: Polymer Physics Published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015

  18. Symbiosis between hydra and chlorella: molecular phylogenetic analysis and experimental study provide insight into its origin and evolution.

    Science.gov (United States)

    Kawaida, Hitomi; Ohba, Kohki; Koutake, Yuhki; Shimizu, Hiroshi; Tachida, Hidenori; Kobayakawa, Yoshitaka

    2013-03-01

    Although many physiological studies have been reported on the symbiosis between hydra and green algae, very little information from a molecular phylogenetic aspect of symbiosis is available. In order to understand the origin and evolution of symbiosis between the two organisms, we compared the phylogenetic relationships among symbiotic green algae with the phylogenetic relationships among host hydra strains. To do so, we reconstructed molecular phylogenetic trees of several strains of symbiotic chlorella harbored in the endodermal epithelial cells of viridissima group hydra strains and investigated their congruence with the molecular phylogenetic trees of the host hydra strains. To examine the species specificity between the host and the symbiont with respect to the genetic distance, we also tried to introduce chlorella strains into two aposymbiotic strains of viridissima group hydra in which symbiotic chlorella had been eliminated in advance. We discussed the origin and history of symbiosis between hydra and green algae based on the analysis. PMID:23219706

  19. Pholcid spider molecular systematics revisited, with new insights into the biogeography and the evolution of the group

    DEFF Research Database (Denmark)

    Dimitrov, Dimitar Stefanov; Astrin, Jonas J.; Huber, Bernhard A.

    2013-01-01

    We analysed seven genetic markers sampled from 165 pholcids and 34 outgroups in order to test and improve the recently revised classification of the family. Our results are based on the largest and most comprehensive set of molecular data so far to study pholcid relationships. The data were analy...

  20. TRPV1 function is modulated by Cdk5-mediated phosphorylation: insights into the molecular mechanism of nociception.

    Science.gov (United States)

    Jendryke, Thomas; Prochazkova, Michaela; Hall, Bradford E; Nordmann, Grégory C; Schladt, Moritz; Milenkovic, Vladimir M; Kulkarni, Ashok B; Wetzel, Christian H

    2016-01-01

    TRPV1 is a polymodally activated cation channel acting as key receptor in nociceptive neurons. Its function is strongly affected by kinase-mediated phosphorylation leading to hyperalgesia and allodynia. We present behavioral and molecular data indicating that TRPV1 is strongly modulated by Cdk5-mediated phosphorylation at position threonine-407(mouse)/T406(rat). Increasing or decreasing Cdk5 activity in genetically engineered mice has severe consequences on TRPV1-mediated pain perception leading to altered capsaicin consumption and sensitivity to heat. To understand the molecular and structural/functional consequences of TRPV1 phosphorylation, we generated various rTRPV1T406 receptor variants to mimic phosphorylated or dephosphorylated receptor protein. We performed detailed functional characterization by means of electrophysiological whole-cell and single-channel recordings as well as Ca(2+)-imaging and challenged recombinant rTRPV1 receptors with capsaicin, low pH, or heat. We found that position T406 is critical for the function of TRPV1 by modulating ligand-sensitivity, activation, and desensitization kinetics as well as voltage-dependence. Based on high resolution structures of TRPV1, we discuss T406 being involved in the molecular transition pathway, its phosphorylation leading to a conformational change and influencing the gating of the receptor. Cdk5-mediated phosphorylation of T406 can be regarded as an important molecular switch modulating TRPV1-related behavior and pain sensitivity. PMID:26902776

  1. Molecular insights into DNA binding and anchoring by the Bacillus subtilis sporulation kinetochore-like RacA protein

    Science.gov (United States)

    Schumacher, Maria A.; Lee, Jeehyun; Zeng, Wenjie

    2016-01-01

    During Bacillus subtilis sporulation, segregating sister chromosomes are anchored to cell poles and the chromosome is remodeled into an elongated structure called the axial filament. Data indicate that a developmentally regulated protein called RacA is involved in these functions. To gain insight into how RacA performs these diverse processes we performed a battery of structural and biochemical analyses. These studies show that RacA contains an N-terminal winged-helix-turn-helix module connected by a disordered region to a predicted coiled-coil domain. Structures capture RacA binding the DNA using distinct protein–protein interfaces and employing adjustable DNA docking modes. This unique DNA binding mechanism indicates how RacA can both specifically recognize its GC-rich centromere and also non-specifically bind the DNA. Adjacent RacA molecules within the protein–DNA structure interact leading to DNA compaction, suggesting a mechanism for axial filament formation. We also show that the RacA C-domain coiled coil directly contacts the coiled coil region of the polar protein DivIVA, which anchors RacA and hence the chromosome to the pole. Thus, our combined data reveal unique DNA binding properties by RacA and provide insight into the DNA remodeling and polar anchorage functions of the protein. PMID:27085804

  2. Quaternary association in -prism I fold plant lectins: Insights from X-ray crystallography, modelling and molecular dynamics

    Indian Academy of Sciences (India)

    Alok Sharma; Mamannamana Vijayan

    2011-12-01

    Dimeric banana lectin and calsepa, tetrameric artocarpin and octameric heltuba are mannose-specific -prism I fold lectins of nearly the same tertiary structure. MD simulations on individual subunits and the oligomers provide insights into the changes in the structure brought about in the protomers on oligomerization, including swapping of the N-terminal stretch in one instance. The regions that undergo changes also tend to exhibit dynamic flexibility during MD simulations. The internal symmetries of individual oligomers are substantially retained during the calculations. Energy minimization and simulations were also carried out on models using all possible oligomers by employing the four different protomers. The unique dimerization pattern observed in calsepa could be traced to unique substitutions in a peptide stretch involved in dimerization. The impossibility of a specific mode of oligomerization involving a particular protomer is often expressed in terms of unacceptable steric contacts or dissociation of the oligomer during simulations. The calculations also led to a rationale for the observation of a heltuba tetramer in solution although the lectin exists as an octamer in the crystal, in addition to providing insights into relations among evolution, oligomerization and ligand binding.

  3. Climate adaption and post-fire restoration of a foundational perennial in cold desert: Insights from intraspecific variation in response to weather

    Science.gov (United States)

    Brabec, Martha M.; Germino, Matthew; Richardson, Bryce A.

    2016-01-01

    responses among subspecies/cytotypes were not as strong and did not relate to survival patterns. 5.Synthesis and applications. Low temperature responses are a key axis defining climate adaptation in young sagebrush seedlings and vary more with cytotype than with subspecies, which contrasts with the traditional emphases on (i) water limitations to explain establishment in these deserts, and (ii) subspecies in selecting restoration seedings. These important and novel insights on climate adaptation are critical for seed selection and parameterizing seed transfer zones, and were made possible by incorporating weather data with survival statistics. The survival/weather statistics used here could be applied to any restoration planting or seeding to help elucidate factors contributing to success and enable adaptive management.

  4. Surface grafted chitosan gels. Part I. Molecular insight into the formation of chitosan and poly(acrylic acid) multilayers

    DEFF Research Database (Denmark)

    Liu, Chao; Thormann, Esben; Claesson, Per M.;

    2014-01-01

    Composite polyelectrolyte multilayers of chitosan and low molecular weight poly(acrylic acid) (PAA) have been assembled by sequential adsorption as a first step toward building a surface anchored chitosan gel. Silane chemistry was used to graft the first chitosan layer to prevent film detachment...... and decomposition. The assembly process is characterized by nonlinear growth behavior, with different adsorption kinetics for chitosan and PAA. In situ analysis of the multilayer by means of surface sensitive total internal reflection Raman (TIRR) spectroscopy, combined with target factor analysis of...... steps. The higher molecular weight chitosan shows a similar behavior, although to a much lower extent. Our data demonstrate that the charged monomeric units of chitosan are mainly compensated by carboxylate ions from PAA. Furthermore, the morphology and mechanical properties of the multilayers were...

  5. Coexistence of spinodal instability and thermal nucleation in thin-film rupture:Insights from molecular levels

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Trung D [ORNL; Fuentes-Cabrera, Miguel A [ORNL; Fowlkes, Jason Davidson [ORNL; Rack, Philip D [ORNL

    2014-01-01

    Despite extensive investigation using hydrodynamic models and experiments over the past decades, there remain open questions regarding the origin of the initial rupture of thin liquid films. One of the reasons that makes it difficult to identify the rupture origin is the coexistence of two dewettingmechanisms, namely, thermal nucleation and spinodal instability, as observed in many experimental studies. Using a coarse-grained model and large-scale molecular dynamics simulations, we are able to characterize the very early stage of dewetting in nanometer-thick liquid-metal films wetting a solid substrate. We observe the features characteristic of both spinodal instability and thermal nucleation in the spontaneously dewetting films and show that these two macroscopic mechanisms share a common origin at molecular levels.

  6. Anticancer Compound Plumbagin and Its Molecular Targets: A Structural Insight into the Inhibitory Mechanisms Using Computational Approaches

    OpenAIRE

    Mohammad S Jamal; Shadma Parveen; Mohd A Beg; Mohd Suhail; Chaudhary, Adeel G. A.; Damanhouri, Ghazi A.; Abuzenadah, Adel M; Mohd Rehan

    2014-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a naphthoquinone derivative from the roots of plant Plumbago zeylanica and belongs to one of the largest and diverse groups of plant metabolites. The anticancer and antiproliferative activities of plumbagin have been observed in animal models as well as in cell cultures. Plumbagin exerts inhibitory effects on multiple cancer-signaling proteins, however, the binding mode and the molecular interactions have not yet been elucidated for most of...

  7. Intralacustrine speciation in coregonids: insight from molecular cytogenetic analysis of two sympatric ciscoes C.albula and C.fontanae

    Czech Academy of Sciences Publication Activity Database

    Symonová, Radka; Majtánová, Zuzana; Sember, Alexandr; Staaks, G.B.O.; Bohlen, Jörg; Freyhof, J.; Ráb, Petr

    Mondsee : Institute for Limnology , 2011. s. 63-63. [11th International Symposium on the Biology and Management of Coregonid Fishes. 26.09.2011-30.09.2011, Mondsee] R&D Projects: GA ČR GA523/08/0824; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z50450515 Keywords : C.albula * C.fontanae Subject RIV: EB - Genetics ; Molecular Biology http://www.oeaw.ac.at/limno/symcore.html

  8. Molecular methods for the detection of human papillomavirus infection: new insights into their role in diagnostics and epidemiological surveillance

    Directory of Open Access Journals (Sweden)

    Andrea Piana

    2009-06-01

    Full Text Available Human papillomaviruses (HPVs comprise more than 180 genotypes. HPV infection is mainly diagnosed by molecular methods. The aim of our study was to review the main molecular methods used to diagnose HPV infection, underscoring their characteristics. Several methods have been developed for molecular diagnosis of Papilloma infection, such as those based on PCR technique. Another commercial non-PCR based diagnostic method is Hybrid Capture test; it is the only commercially available HPV DNA detection test approved by the FDA. Several Authors have suggested that viral load and E6/E7 transcripts could be used as surrogate markers of persistent HPV infection, being more specific predictors of progressive disease than the simple presence of HPV DNA. Validating clinical sensitivity and specificity of each technique and improving the interpretation of the results are essential; consequently, there is a clear need for well characterized international quality control panels to compare the various diagnostic methods. HPV DNA testing could be useful both as a primary screening test, alone or in combination with a Pap smear, for the early detection of cervical cancer precursors, and as triage test to select women with minor cytological abnormalities who will need further follow-up and to predict possible treatment failure in women with diagnosed high-grade intraepithelial lesions who have undergone excisional therapy. In the next future surveillance for HPV infections, based on these molecular methods, could represent an important step for the development of primary and secondary prophylactic interventions, such as new vaccines targeted to genotypes who might replace those previously prevalent.

  9. Comparative proteome analysis of psychrophilic versus mesophilic bacterial species: Insights into the molecular basis of cold adaptation of proteins

    OpenAIRE

    Metpally, Raghu Prasad Rao; Reddy, Boojala Vijay B.

    2009-01-01

    Background Cold adapted or psychrophilic organisms grow at low temperatures, where most of other organisms cannot grow. This adaptation requires a vast array of sequence, structural and physiological adjustments. To understand the molecular basis of cold adaptation of proteins, we analyzed proteomes of psychrophilic and mesophilic bacterial species and compared the differences in amino acid composition and substitution patterns to investigate their likely association with growth temperatures....

  10. Molecular Signatures for the PVC Clade (Planctomycetes, Verrucomicrobia, Chlamydiae, and Lentisphaerae) of Bacteria Provide Insights into Their Evolutionary Relationships.

    Science.gov (United States)

    Gupta, Radhey S; Bhandari, Vaibhav; Naushad, Hafiz Sohail

    2012-01-01

    The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia, and Chlamydiae, along with the Lentisphaerae, Poribacteria, and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, six conserved signature indels (CSIs) in the proteins Cyt c oxidase, UvrD helicase, urease, and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase, and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia, and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae, and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms. PMID:23060863

  11. Molecular Signatures for the PVC Clade (Planctomycetes, Verrucomicrobia, Chlamydiae and Lentisphaerae of Bacteria Provide Insights into their Evolutionary Relationships

    Directory of Open Access Journals (Sweden)

    Radhey S. Gupta

    2012-09-01

    Full Text Available The PVC superphylum is an amalgamation of species from the phyla Planctomycetes, Verrucomicrobia and Chlamydiae, along with the Lentisphaerae, Poribacteria and two other candidate divisions. The diverse species of this superphylum lack any significant marker that differentiates them from other bacteria. Recently, genome sequences for 37 species covering all of the main PVC groups of bacteria have become available. We have used these sequences to construct a phylogenetic tree based upon concatenated sequences for 16 proteins and identify molecular signatures in protein sequences that are specific for the species from these phyla or those providing molecular links among them. Of the useful molecular markers identified in the present work, 6 conserved signature indels (CSIs in the proteins Cyt c oxidase, UvrD helicase, urease and a helicase-domain containing protein are specific for the species from the Verrucomicrobia phylum; three other CSIs in an ABC transporter protein, cobyrinic acid ac-diamide synthase and SpoVG protein are specific for the Planctomycetes species. Additionally, a 3 aa insert in the RpoB protein is uniquely present in all sequenced Chlamydiae, Verrucomicrobia and Lentisphaerae species, providing evidence for the shared ancestry of the species from these three phyla. Lastly, we have also identified a conserved protein of unknown function that is exclusively found in all sequenced species from the phyla Chlamydiae, Verrucomicrobia, Lentisphaerae and Planctomycetes suggesting a specific linkage among them. The absence of this protein in Poribacteria, which branches separately from other members of the PVC clade, indicates that it is not specifically related to the PVC clade of bacteria. The molecular markers described here in addition to clarifying the evolutionary relationships among the PVC clade of bacteria also provide novel tools for their identification and for genetic and biochemical studies on these organisms.

  12. Insight into ligand selectivity in HCV NS5B polymerase: molecular dynamics simulations, free energy decomposition and docking

    OpenAIRE

    Li, Tong; Froeyen, Matheus; Herdewijn, Piet

    2009-01-01

    Abstract Modeling studies were performed on HCV NS5B polymerase in an effort to design new inhibitors. The binding models of five different scaffold inhibitors were investigated and compared by using molecular dynamics simulations, free energy calculation and decomposition. Our results show Tyr448 plays the most critical role in the binding of most inhibitors. In addition, favorable contributions of residues Pro197, Arg200, Cys366, Met414 and Tyr448 in a deep hydrophobic pocket pro...

  13. New insights into heat induced structural changes of pectin methylesterase on fluorescence spectroscopy and molecular modeling basis

    Science.gov (United States)

    Nistor, Oana Viorela; Stănciuc, Nicoleta; Aprodu, Iuliana; Botez, Elisabeta

    2014-07-01

    Heat-induced structural changes of Aspergillus oryzae pectin methylesterase (PME) were studied by means of fluorescence spectroscopy and molecular modeling, whereas the functional enzyme stability was monitored by inactivation studies. The fluorescence spectroscopy experiments were performed at two pH value (4.5 and 7.0). At both pH values, the phase diagrams were linear, indicating the presence of two molecular species induced by thermal treatment. A red shift of 7 nm was observed at neutral pH by increasing temperature up to 60 °C, followed by a blue shift of 4 nm at 70 °C, suggesting significant conformational rearrangements. The quenching experiments using acrylamide and iodide demonstrate a more flexible conformation of enzyme with increasing temperature, especially at neutral pH. The experimental results were complemented with atomic level observations on PME model behavior after performing molecular dynamics simulations at different temperatures. The inactivation kinetics of PME in buffer solutions was fitted using a first-order kinetics model, resulting in activation energy of 241.4 ± 7.51 kJ mol-1.

  14. Molecular Dynamics Simulations of Voltage Gated Cation Channels: Insights on Voltage-Sensor Domain Function and Modulation

    Directory of Open Access Journals (Sweden)

    Lucie eDelemotte

    2012-05-01

    Full Text Available Since their discovery in the 1950s, the structure and function of voltage gated cation channels (VGCC has been largely understood thanks to results stemming from electrophysiology, pharmacology, spectroscopy and structural biology. Over the past decade, computational methods such as molecular dynamics (MD simulations have also contributed, providing molecular level information that can be tested against experimental results, thereby allowing the validation of the models and protocols. Importantly, MD can shed light on elements of VGCC function that cannot be easily accessed through classical experiments. Here, we review the results of recent MD simulations addressing key questions that pertain to the function and modulation of the VGCC’s voltage sensor domain (VSD highlighting: 1 the movement of the S4-helix basic residues during channel activation, articulating how the electrical driving force acts upon them; 2 the nature of the VSD intermediate states on transitioning between open and closed states of the VGCC; and 3 the molecular level effects on the VSD arising from mutations of specific S4 positively charged residues involved in certain genetic diseases.

  15. High molecular weight SOA formation during limonene ozonolysis: insights from ultrahigh-resolution FT-ICR mass spectrometry characterization

    Directory of Open Access Journals (Sweden)

    S. Kundu

    2012-06-01

    Full Text Available The detailed molecular composition of laboratory generated limonene ozonolysis secondary organic aerosol (SOA was studied using ultrahigh-resolution Fourier transform ion cyclotron resonance (FT-ICR mass spectrometry. Approximately 1200 molecular formulas were identified in the SOA over the mass range of 140 to 850 Da. Four characteristic groups of high relative abundance species were observed; they indicate an array of accretion products that retain a large fraction of the limonene skeleton. The identified molecular formulas of each of the groups are related to one another by CH2, O and CH2O homologous series. The CH2 and O homologous series of the low molecular weight (MW SOA (m/z < 300 are explained with a combination of functionalization and fragmentation of radical intermediates and reactive uptake of gas-phase carbonyls. They include isomerization and elimination reactions of Criegee radicals, reactions between alkyl peroxy radicals, and scission of alkoxy radicals resulting from the Criegee radicals. The presence of compounds with 10–15 carbon atoms in the first group (e.g. C11H18O6 provides evidence for SOA formation by the reactive uptake of gas-phase carbonyls during limonene ozonolysis. The high MW compounds (m/z > 300 were found to constitute a significant number fraction of the identified SOA components. The formation of high MW compounds was evaluated by molecular formula trends, fragmentation analysis of select high MW compounds and a comprehensive reaction matrix including the identified low MW SOA, hydroperoxides and Criegee radicals as building blocks. Although the formation of high MW SOA may occur via a variety of radical and non-radical reaction channels, the combined approach indicates a greater importance of the non-condensation reactions over aldol and ester condensation reaction channels. Among these hemi-acetal reactions appear to be most

  16. Molecular Radiocarbon Dating of Tropical Lake Sediments: Insights into the Chronology of Leaf Wax Stable Isotope Records

    Science.gov (United States)

    Douglas, P. M.; Pagani, M.; Eglinton, T. I.; Brenner, M.; Curtis, J. H.; Hodell, D. A.

    2010-12-01

    Leaf wax δD and δ13C measurements in marine and lacustrine sediment cores are promising proxies for past climatic and environmental change. However, a number of studies of marine sediments indicate centennial to millennial scale offsets between the radiocarbon ages of leaf waxes and the age of surrounding sediments due to long-term storage of these lipids in soils. These offsets present a complication for the interpretation of leaf wax stable isotope records that has not been thoroughly addressed. We present leaf wax δD, δ13C and Δ14C values for a sediment core from Lake Chichancanab in southeastern Mexico. This lake was previously studied using mineralogical (gypsum) and carbonate isotopic (δ18O) climate proxies, which indicated a sequence of severe droughts from 750 to 1000 AD, coincident with the collapse of the Classic Maya civilization. A suite of leaf wax δD values was plotted against the original sediment core chronology, which was developed using radiocarbon dates on terrestrial macrofossils. The leaf wax results also indicated major hydrological variability over the past 3000 years, but were not temporally coherent with the other climate proxy records. Leaf wax radiocarbon ages are 400 to 1200 years older than terrestrial macrofossil radiocarbon ages from the same depths, suggesting that leaf waxes are retained in the watershed for extended periods prior to deposition in the lake. We fit a 2nd-order polynomial equation to the depth profile of leaf wax radiocarbon ages (r2 =0.99) and refit the leaf wax δD profile to this “leaf wax age model”. This approach yielded much greater coherence with mineralogical and carbonate isotopic proxy records, including evidence for a period of severe drought (35‰ D-enrichment) from 750 to 1000 A.D. Our results indicate that long-term storage of leaf waxes in drainage basin soils can lead to temporal inaccuracies in leaf wax stable isotope records. These inaccuracies, however, can be corrected using a

  17. The role of Phe82 and Phe351 in auxin-induced substrate perception by TIR1 ubiquitin ligase: a novel insight from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Ge-Fei Hao

    Full Text Available It is well known that Auxin plays a key role in controlling many aspects of plant growth and development. Crystal structures of Transport inhibitor response 1 (TIR1, a true receptor of auxin, were very recently determined for TIR1 alone and in complexes with auxin and different synthetic analogues and an Auxin/Indole-3-Acetic Acid (Aux/IAA substrate peptide. However, the dynamic conformational changes of the key residues of TIR1 that take place during the auxin and substrate perception by TIR1 and the detailed mechanism of these changes are still unclear. In the present study, various computational techniques were integrated to uncover the detailed molecular mechanism of the auxin and Aux/IAA perception process; these simulations included molecular dynamics (MD simulations on complexes and the free enzyme, the molecular mechanics Poisson Boltzmann surface area (MM-PBSA calculations, normal mode analysis, and hydrogen bond energy (HBE calculations. The computational simulation results provided a reasonable explanation for the structure-activity relationships of auxin and its synthetic analogues in view of energy. In addition, a more detailed model for auxin and Aux/IAA perception was also proposed, indicating that Phe82 and Phe351 played a pivotal role in Aux/IAA perception. Upon auxin binding, Phe82 underwent conformational changes to accommodate the subsequent binding of Aux/IAA. As a result, auxin enhances the TIR1-Aux/IAA interactions by acting as a "molecular glue". Besides, Phe351 acts as a "fastener" to further improve the substrate binding. The structural and mechanistic insights obtained from the present study will provide valuable clues for the future design of promising auxin analogues.

  18. The molecular mechanism of bisphenol A (BPA as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD simulations.

    Directory of Open Access Journals (Sweden)

    Lanlan Li

    Full Text Available Bisphenol A (BPA can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA.

  19. Molecular insight in the purification of immunoglobulin by pseudobiospecific ligand l-histidine and histidyl moieties in histidine ligand affinity chromatography (HLAC) by molecular docking.

    Science.gov (United States)

    Savane, Tushar S; Kumar, Sanjit; Janakiraman, Vignesh Narasimhan; Kamalanathan, Agamudi S; Vijayalakshmi, Mookambeswaran A

    2016-05-15

    Pseudobiospecific ligand l-histidine is an inexpensive, highly stable, non-toxic ligand explored successfully over the last twenty years for the purification of immunoglobulins in immobilised histidine ligand affinity chromatography. It is of great interest to know the molecular recognition sites of IgG to immobilized l-histidine. Here, we have used an in silico approach to explore the molecular recognition of l-histidine by IgG. We have assessed the feasible binding modes of histidine and its moieties at different sites of IgG and considered only those binding conformations which are exhibited via the imidazole ring NH group or any other OH donating group apart from the ones which are terminally conjugated with the support matrix. We categorised binding site into two categories; category I: inner binding groove and category II: surface binding groove and observed that the hinge region of IgG has most favourable binding pocket for l-histidine and histidyl moieties. Ser and Tyr residues on the hinge region make several significant interactions with l-histidine and histidyl moieties. In case of Fc region of IgG, l-histidine and histidyl moieties closely resemble the binding modes of Protein A, biomimetic ligand 22/8 and B domain of SpA to IgG. In addition to these we have also observed a significant binding site for l-histidine and histidyl moieties at Fab region of IgG. PMID:26476866

  20. Insights into the phylogeny of sporadotrichid ciliates (Protozoa, Ciliophora: Hypotricha) based on genealogical analyses of multiple molecular markers

    Science.gov (United States)

    Hu, Xiaoyan; Hu, Xiaozhong; Al-Rasheid, Khaled A. S.; Al-Farraj, Saleh A.; Song, Weibo

    2011-01-01

    The sporadotrichid ciliates are an especially diverse group. A number of investigators have studied the morphological, morphogenetic, and molecular relationships among members of this group. Despite this, a consistent classification is still lacking and several important questions about the phylogenetic relationships within this group remain unsolved. To improve our understanding of these relationships, we constructed phylogenetic trees using the nucleotide sequences of the small-subunit rRNA (SSrRNA) gene and amino acid sequences of actin I and α-tubulin. Analyses of SSrRNA gene sequences indicated that: 1) the Sporadotrichida sensu Lynn (2008) and the Oxytrichidae are polyphyletic; 2) the Uroleptus species, which are classified to urostylids, formed a sister group with the oxytrichids; 3) Halteria grandinella, which is grouped morphologically with oligotrich species, clustered within the oxytrichids. These results are congruent with previous studies based on SSrRNA gene sequences. However, the amino acid sequences of actin I and α-tubulin yielded different topologies. The main results are: 1) in all phylogenetic trees, the genus Oxytricha was paraphyletic; 2) Uroleptus was sister to a subset of Urostyla and Holosticha, albeit with low supporting values; 3) Halteria grandinella was separated distantly from the Oxytrichidae in trees inferred from actin I amino acid sequences but clustered with oligotrichids in the α-tubulin analysis. The inconsistency among the trees inferred from these different molecular markers may be caused by rapidly accumulated genetic characterizations of ciliates. Further studies with additional molecular markers and sampling of more taxa are expected to better address the relationships among sporadotrichids.

  1. Charge and spin transport in single and packed ruthenium-terpyridine molecular devices: Insight from first-principles calculations.

    Science.gov (United States)

    Morari, C; Buimaga-Iarinca, L; Rungger, I; Sanvito, S; Melinte, S; Rignanese, G-M

    2016-01-01

    Using first-principles calculations, we study the electronic and transport properties of rutheniumterpyridine molecules sandwiched between two Au(111) electrodes. We analyse both single and packed molecular devices, more amenable to scaling and realistic integration approaches. The devices display all together robust negative differential resistance features at low bias voltages. Remarkably, the electrical control of the spin transport in the studied systems implies a subtle distribution of the magnetisation density within the biased devices and highlights the key role of the Au(111) electrical contacts. PMID:27550064

  2. Insights into the Mechanical Properties of the Kinesin Neck Linker Domain from Sequence Analysis and Molecular Dynamics Simulations

    OpenAIRE

    Hariharan, Venkatesh; Hancock, William O.

    2009-01-01

    The 14–18 amino acid kinesin neck linker domain links the core motor to the coiled-coil dimerization domain. One puzzle is that the neck linker appears too short for the 4 nm distance each linker must stretch to enable an 8 nm step – when modeled as an entropic spring, high inter-head forces are predicted when both heads are bound to the microtubule. We addressed this by analyzing the length of the neck linker across different kinesin families and using molecular dynamics simulations to model...

  3. Insights into the anthrax lethal factor–substrate interaction and selectivity using docking and molecular dynamics simulations

    OpenAIRE

    Dalkas, Georgios A; Papakyriakou, Athanasios; Vlamis-Gardikas, Alexios; Spyroulias, Georgios A

    2009-01-01

    The anthrax toxin of the bacterium Bacillus anthracis consists of three distinct proteins, one of which is the anthrax lethal factor (LF). LF is a gluzincin Zn-dependent, highly specific metalloprotease with a molecular mass of ∼90 kDa that cleaves most isoforms of the family of mitogen-activated protein kinase kinases (MEKs/MKKs) close to their amino termini, resulting in the inhibition of one or more signaling pathways. Previous studies on the crystal structures of uncomplexed LF and LF com...

  4. Charge and spin transport in single and packed ruthenium-terpyridine molecular devices: Insight from first-principles calculations

    Science.gov (United States)

    Morari, C.; Buimaga-Iarinca, L.; Rungger, I.; Sanvito, S.; Melinte, S.; Rignanese, G.-M.

    2016-01-01

    Using first-principles calculations, we study the electronic and transport properties of rutheniumterpyridine molecules sandwiched between two Au(111) electrodes. We analyse both single and packed molecular devices, more amenable to scaling and realistic integration approaches. The devices display all together robust negative differential resistance features at low bias voltages. Remarkably, the electrical control of the spin transport in the studied systems implies a subtle distribution of the magnetisation density within the biased devices and highlights the key role of the Au(111) electrical contacts. PMID:27550064

  5. Insights into the structure and inhibition of Giardia intestinalis arginine deiminase: homology modeling, docking, and molecular dynamics studies.

    Science.gov (United States)

    Trejo-Soto, Pedro Josué; Aguayo-Ortiz, Rodrigo; Yépez-Mulia, Lilián; Hernández-Campos, Alicia; Medina-Franco, José Luis; Castillo, Rafael

    2016-04-01

    Giardia intestinalis arginine deiminase (GiADI) is an important metabolic enzyme involved in the energy production and defense of this protozoan parasite. The lack of this enzyme in the human host makes GiADI an attractive target for drug design against G. intestinalis. One approach in the design of inhibitors of GiADI could be computer-assisted studies of its crystal structure, such as docking; however, the required crystallographic structure of the enzyme still remains unresolved. Because of its relevance, in this work, we present a three-dimensional structure of GiADI obtained from its amino acid sequence using the homology modeling approximation. Furthermore, we present an approximation of the most stable dimeric structure of GiADI identified through molecular dynamics simulation studies. An in silico analysis of druggability using the structure of GiADI was carried out in order to know if it is a good target for design and optimization of selective inhibitors. Potential GiADI inhibitors were identified by docking of a set of 3196 commercial and 19 in-house benzimidazole derivatives, and molecular dynamics simulation studies were used to evaluate the stability of the ligand-enzyme complexes. PMID:26017138

  6. Insight into interaction mechanism of the inhibitor pDI5W with MDM2 based on molecular dynamics

    International Nuclear Information System (INIS)

    The p53-MDM2 interaction has been an important target of drug design curing cancers. In this work, molecular dynamics (MD) simulation coupled with molecular mechanics/Poisson Boltzmann surface area method (MM-PBSA) was performed to calculate the binding free energy of peptide inhibitor pDI6W to MDM2. The results show that van der Waals energy is the dominant factor of the pDI6W— MDM2 interaction. Cross-correlation matrix calculated suggests that the main motion of the residues in MMDM2 induced by the inhibitor binding is anti-correlation motion. The calculations of residue-residue interactions between pDI6W and MDM2 not only prove that five residues Phe19', Trp22', Trp23', Leu26' and Thr27' from pDI6W can produce strong interaction with MDM2, but also show that CH-π, CH-CH and π-π interactions drive the binding of pDI6W in the hydrophobic cleft of MDM2. This study can provide theoretical helps for anti-cancer drug designs. (authors)

  7. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  8. Binding interaction of a gamma-aminobutyric acid derivative with serum albumin: an insight by fluorescence and molecular modeling analysis.

    Science.gov (United States)

    Pal, Uttam; Pramanik, Sumit Kumar; Bhattacharya, Baisali; Banerji, Biswadip; C Maiti, Nakul

    2016-01-01

    gamma-Aminobutyric acid (GABA) is a naturally occurring inhibitory neurotransmitter and some of its derivatives showed potential to act as neuroprotective agents. With the aim of developing potential leads for anti-Alzheimer's drugs, in this study we synthesized a novel GABA derivative, methyl 4-(4-((2-(tert-butoxy)-2-oxoethyl)(4-methoxyphenyl)amino)benzamido)butanoate by a unique method of Buchwald-Hartwig cross coupling synthesis; with some modification the yield was significant (97 %) and spectroscopic analysis confirmed that the compound was highly pure (98.8 % by HPLC). The druglikeness properties such as logP, logS, and polar surface area were 3.87, -4.86 and 94.17 Å(2) respectively and it satisfied the Lipinski's rule of five. We examined the binding behavior of the molecule to human serum albumin (HSA) and bovine serum albumin (BSA) which are known as universal drug carrier proteins. The molecule binds to the proteins with low micromolar efficiency and the calculated binding constants were 3.85 and 2.75 micromolar for BSA and HSA, respectively. Temperature dependent study using van't Hoff equation established that the binding was thermodynamically favorable and the changes in the Gibb's free energy, ΔG for the binding process was negative. However, the binding of the molecule to HSA was enthalpy driven and the change of enthalpy (ΔH) was -10.63 kJ/mol, whereas, the binding to BSA was entropy driven and the change in entropy ΔS was 222 J/mol. The molecular docking analysis showed that the binding sites of the molecule lie in the groove between domain I and domain III of BSA, whereas it is within the domain I in case of HSA, which also supported the different thermodynamic nature of binding with HSA and BSA. Molecular dynamics analysis suggested that the binding was stable with time and provided further details of the binding interaction. Molecular dynamics study also highlighted the effect of this ligand binding on the serum albumin structure. PMID

  9. Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials.

    Science.gov (United States)

    Tsyshevsky, Roman V; Sharia, Onise; Kuklja, Maija M

    2016-01-01

    This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our own first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects. PMID:26907231

  10. Molecular Theory of Detonation Initiation: Insight from First Principles Modeling of the Decomposition Mechanisms of Organic Nitro Energetic Materials

    Directory of Open Access Journals (Sweden)

    Roman V. Tsyshevsky

    2016-02-01

    Full Text Available This review presents a concept, which assumes that thermal decomposition processes play a major role in defining the sensitivity of organic energetic materials to detonation initiation. As a science and engineering community we are still far away from having a comprehensive molecular detonation initiation theory in a widely agreed upon form. However, recent advances in experimental and theoretical methods allow for a constructive and rigorous approach to design and test the theory or at least some of its fundamental building blocks. In this review, we analyzed a set of select experimental and theoretical articles, which were augmented by our own first principles modeling and simulations, to reveal new trends in energetic materials and to refine known existing correlations between their structures, properties, and functions. Our consideration is intentionally limited to the processes of thermally stimulated chemical reactions at the earliest stage of decomposition of molecules and materials containing defects.

  11. Structural heterogeneity and dynamics in liquid PbSiO3: insight from analysis and visualization of molecular dynamics data

    Science.gov (United States)

    Yen, N. V.; Hong, N. V.; Hung, P. K.; Huy, N. V.

    2015-06-01

    The structure and dynamics of liquid lead silicate (PbSiO3) are investigated by molecular dynamics simulation with the pair potentials. The models of PbSiO3 consisting of 5000 atoms (1000 Pb, 1000 Si, and 3000 O atoms) are constructed at 3200 K and in a 0-35 GPa pressure range. The local structure, polymorphism, and dynamics in liquid PbSiO3 are investigated through pair radial distribution function, coordination distribution, topology structure of basic structural units, and mean square displacement. Short-range order (SRO) and intermediate-range order (IRO) are clarified by visualization of simulated data. The local environment around Pb+2 and Si+4 ions, the network structure of SiOx (x = 4, 5, 6) and PbOn (n = 3 - 9) polyhedra, and the correlation between structure and dynamics, as well as their change under compression, are also discussed in detail.

  12. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  13. A revised classification of the family Dasyatidae (Chondrichthyes: Myliobatiformes) based on new morphological and molecular insights.

    Science.gov (United States)

    Last, Peter R; Naylor, Gavin J P; Manjaji-Matsumoto, B Mabel

    2016-01-01

    The higher-level taxonomy of the stingrays (Dasyatidae) has never been comprehensively reviewed. Recent phylogenetic studies, supported by morphological data, have provided evidence that the group is monophyletic and consists of four major subgroups, the subfamilies Dasyatinae, Neotrygoninae, Urogymninae and Hypolophinae. A morphologically based review of 89 currently recognised species, undertaken for a guide to the world's rays, indicated that most of the currently recognised dasyatid genera are not monophyletic groups. These findings were supported by molecular analyses using the NADH2 gene for about 77 of these species, and this topology is supported by preliminary analyses base on whole mitochondrial genome comparisons. These molecular analyses, based on data generated from the Chondrichthyan Tree of Life project, are the most taxon-rich data available for this family. Material from all of the presently recognised genera (Dasyatis, Pteroplatytrygon and Taeniurops [Dasyatinae]; Neotrygon and Taeniura [Neotrygoninae]; Himantura and Urogymnus [Urogymninae]; and Makararaja and Pastinachus [Hypolophinae]), are included and their validity largely supported. Urogymnus and the two most species rich genera, Dasyatis and Himantura, are not considered to be monophyletic and were redefined based on external morphology. Seven new genus-level taxa are erected (Megatrygon and Telatrygon [Dasyatinae]; Brevitrygon, Fluvitrygon, Fontitrygon, Maculabatis and Pateobatis [Urogymninae], and an additional three (Bathytoshia, Hemitrygon and Hypanus [Dasyatinae]) are resurrected from the synonymy of Dasyatis. The monotypic genus Megatrygon clustered with 'amphi-American Himantura' outside the Dasyatidae, and instead as the sister group of the Potamotrygonidae and Urotrygonidae. Megatrygon is provisionally retained in the Dasyatinae pending further investigation of its internal anatomy. The morphologically divergent groups, Bathytoshia and Pteroplatytrygon, possibly form a single

  14. Molecular and Electronic Structure of Cyclic Trinuclear Gold(I) Carbeniate Complexes: Insights for Structure/Luminescence/Conductivity Relationships

    Energy Technology Data Exchange (ETDEWEB)

    McDougaldJr, Roy N [University of North Texas; Chilukuri, Bhaskar [University of North Texas; Jia, Huiping [University of Texas at Dallas; Perez, Michael R [University of Texas at Dallas; Rabaa, Hassan [Ibn Tofail Univ, ESCTM, Morocco; Wang, Xiaoping [ORNL; Nesterov, Vladimir [University of North Texas; Cundari, Thomas R. [University of North Texas; Gnade, Bruce E [University of Texas at Dallas; Omary, Mohammad A [University of North Texas

    2014-01-01

    An experimental and computational study of correlations between solid-state structure and optical/electronic properties of cyclotrimeric gold(I) carbeniates, [Au-3(RN=COR')(3)] (R, R' = H, Me, Bu-n, or (c)Pe), is reported. Synthesis and structural and photophysical characterization of novel complexes [Au-3(MeN=(COBu)-Bu-n)(3)], [Au-3((BuN)-Bu-n=COMe)(3)], [Au-3((BuN)-Bu-n=(COBu)-Bu-n)(3)], and [Au-3((c)PeN=COMe)(3)] are presented. Changes in R and R' lead to distinctive variations in solid-state stacking, luminescence spectra, and conductive properties. Solid-state emission and excitation spectra for each complex display a remarkable dependence on the solid-state packing of the cyclotrimers. The electronic structure of [Au-3(RN=COR')(3)] was investigated via molecular and solid-state simulations. Calculations on [Au-3(HN=COH)(3)] models indicate that the infinitely extended chain of eclipsed structures with equidistant Au-Au intertrimer aurophilic bonding can have lower band gaps, smaller Stokes shifts, and reduced reorganization energies (lambda). The action of one cyclotrimer as a molecular nanowire is demonstrated via fabrication of an organic field effect transistor and shown to produce a p-type field effect. Hole transport for the same cyclotrimer-doped within a poly(9-vinylcarbazole) host-produced a colossal increase in current density from similar to 1 to similar to 1000 mA/cm(2). Computations and experiments thus delineate the complex relationships between solid-state morphologies, electronic structures, and optoelectronic properties of gold(I) carbeniates.

  15. Insights into the complex formed by matrix metalloproteinase-2 and alloxan inhibitors: molecular dynamics simulations and free energy calculations.

    Directory of Open Access Journals (Sweden)

    Ilenia Giangreco

    Full Text Available Matrix metalloproteinases (MMP are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S(1' specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S(1' subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC(50 = 7.06 is found for BAM, a compound exhibiting also selectivity (>20 towards MMP-2, as compared to MMP-9, the other member of the gelatinases.

  16. The transcriptome of Trichuris suis--first molecular insights into a parasite with curative properties for key immune diseases of humans.

    Directory of Open Access Journals (Sweden)

    Cinzia Cantacessi

    Full Text Available BACKGROUND: Iatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD and ulcerative colitis, in humans. Although it is understood that short-term T. suis infection in people with such diseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response. METHODOLOGY/PRINCIPAL FINDINGS: As a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ∼65,000,000 reads were generated and assembled into ∼20,000 contiguous sequences ( = contigs; ∼17,000 peptides were predicted and classified based on homology searches, protein motifs and gene ontology and biological pathway mapping. CONCLUSIONS: These analyses provided interesting insights into a number of molecular groups, particularly predicted excreted/secreted molecules (n = 1,288, likely to be involved in the parasite-host interactions, and also various molecules (n = 120 linked to chemokine, T-cell receptor and TGF-β signalling as well as leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity, which are likely to be immuno-regulatory or -modulatory in the infected host. This information provides a conceptual framework within which to test the immunobiological basis for the curative effect of T. suis infection in humans against some immune diseases. Importantly, the T. suis transcriptome characterised herein provides a curated resource for detailed studies of the immuno-molecular biology of this parasite, and will underpin future genomic and proteomic explorations.

  17. Cardiac Channel Molecular Autopsy: Insights From 173 Consecutive Cases of Autopsy-Negative Sudden Unexplained Death Referred for Postmortem Genetic Testing

    Science.gov (United States)

    Tester, David J.; Medeiros-Domingo, Argelia; Will, Melissa L.; Haglund, Carla M.; Ackerman, Michael J.

    2012-01-01

    Objective To perform long QT syndrome and catecholaminergic polymorphic ventricular tachycardia cardiac channel postmortem genetic testing (molecular autopsy) for a large cohort of cases of autopsy-negative sudden unexplained death (SUD). Methods From September 1, 1998, through October 31, 2010, 173 cases of SUD (106 males; mean ± SD age, 18.4±12.9 years; age range, 1-69 years; 89% white) were referred by medical examiners or coroners for a cardiac channel molecular autopsy. Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, a comprehensive mutational analysis of the long QT syndrome susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) and a targeted analysis of the catecholaminergic polymorphic ventricular tachycardia type 1–associated gene (RYR2) were conducted. Results Overall, 45 putative pathogenic mutations absent in 400 to 700 controls were identified in 45 autopsy-negative SUD cases (26.0%). Females had a higher yield (26/67 [38.8%]) than males (19/106 [17.9%]; P<.005). Among SUD cases with exercise-induced death, the yield trended higher among the 1- to 10-year-olds (8/12 [66.7%]) compared with the 11- to 20-year-olds (4/27 [14.8%]; P=.002). In contrast, for those who died during a period of sleep, the 11- to 20-year-olds had a higher yield (9/25 [36.0%]) than the 1- to 10-year-olds (1/24 [4.2%]; P=.01). Conclusion Cardiac channel molecular autopsy should be considered in the evaluation of autopsy-negative SUD. Several interesting genotype-phenotype observations may provide insight into the expected yields of postmortem genetic testing for SUD and assist in selecting cases with the greatest potential for mutation discovery and directing genetic testing efforts. PMID:22677073

  18. Molecular insights into the historic demography of bowhead whales: understanding the evolutionary basis of contemporary management practices

    Science.gov (United States)

    Phillips, C D; Hoffman, J I; George, J C; Suydam, R S; Huebinger, R M; Patton, J C; Bickham, J W

    2013-01-01

    Patterns of genetic variation observed within species reflect evolutionary histories that include signatures of past demography. Understanding the demographic component of species' history is fundamental to informed management because changes in effective population size affect response to environmental change and evolvability, the strength of genetic drift, and maintenance of genetic variability. Species experiencing anthropogenic population reductions provide valuable case studies for understanding the genetic response to demographic change because historic changes in the census size are often well documented. A classic example is the bowhead whale, Balaena mysticetus, which experienced dramatic population depletion due to commercial whaling in the late 19th and early 20th centuries. Consequently, we analyzed a large multi-marker dataset of bowhead whales using a variety of analytical methods, including extended Bayesian skyline analysis and approximate Bayesian computation, to characterize genetic signatures of both ancient and contemporary demographic histories. No genetic signature of recent population depletion was recovered through any analysis incorporating realistic mutation assumptions, probably due to the combined influences of long generation time, short bottleneck duration, and the magnitude of population depletion. In contrast, a robust signal of population expansion was detected around 70,000 years ago, followed by a population decline around 15,000 years ago. The timing of these events coincides to a historic glacial period and the onset of warming at the end of the last glacial maximum, respectively. By implication, climate driven long-term variation in Arctic Ocean productivity, rather than recent anthropogenic disturbance, appears to have been the primary driver of historic bowhead whale demography. PMID:23403722

  19. Permafrost Meta-Omics and Climate Change

    Science.gov (United States)

    Mackelprang, Rachel; Saleska, Scott R.; Jacobsen, Carsten Suhr; Jansson, Janet K.; Taş, Neslihan

    2016-06-01

    Permanently frozen soil, or permafrost, covers a large portion of the Earth's terrestrial surface and represents a unique environment for cold-adapted microorganisms. As permafrost thaws, previously protected organic matter becomes available for microbial degradation. Microbes that decompose soil carbon produce carbon dioxide and other greenhouse gases, contributing substantially to climate change. Next-generation sequencing and other -omics technologies offer opportunities to discover the mechanisms by which microbial communities regulate the loss of carbon and the emission of greenhouse gases from thawing permafrost regions. Analysis of nucleic acids and proteins taken directly from permafrost-associated soils has provided new insights into microbial communities and their functions in Arctic environments that are increasingly impacted by climate change. In this article we review current information from various molecular -omics studies on permafrost microbial ecology and explore the relevance of these insights to our current understanding of the dynamics of permafrost loss due to climate change.

  20. Predicting ecological regime shift under climate change:New modelling techniques and potential of molecular-based approaches

    Institute of Scientific and Technical Information of China (English)

    Richard STAFFORD; V.Anne SMITH; Dirk HUSMEIER; Thomas GRIMA; Barbara-ann GUINN

    2013-01-01

    Ecological regime shift is the rapid transition from one stable community structure to another,often ecologically inferior,stable community.Such regime shifts are especially common in shallow marine communities,such as the transition of kelp forests to algal turfs that harbour far lower biodiversity.Stable regimes in communities are a result of balanced interactions between species,and predicting new regimes therefore requires an evaluation of new species interactions,as well as the resilience of the ‘stable' position.While computational optimisation techniques can predict new potential regimes,predicting the most likely community state of the various options produced is currently educated guess work.In this study we integrate a stable regime optimisation approach with a Bayesian network used to infer prior knowledge of the likely stress of climate change (or,in practice,any other disturbance) on each component species of a representative rocky shore community model.Combining the results,by calculating the product of the match between resilient computational predictions and the posterior probabilities of the Bayesian network,gives a refined set of model predictors,and demonstrates the use of the process in determining community changes,as might occur through processes such as climate change.To inform Bayesian priors,we conduct a review of molecular approaches applied to the analysis of the transcriptome of rocky shore organisms,and show how such an approach could be linked to measureable stress variables in the field.Hence species-specific microarrays could be designed as biomarkers of in situ stress,and used to inform predictive modelling approaches such as those described here.

  1. Predicting ecological regime shift under climate change: New modelling techniques and potential of molecular-based approaches

    Directory of Open Access Journals (Sweden)

    Richard STAFFORD, V. Anne SMITH, Dirk HUSMEIER, Thomas GRIMA, Barbara-ann GUINN

    2013-06-01

    Full Text Available Ecological regime shift is the rapid transition from one stable community structure to another, often ecologically inferior, stable community. Such regime shifts are especially common in shallow marine communities, such as the transition of kelp forests to algal turfs that harbour far lower biodiversity. Stable regimes in communities are a result of balanced interactions between species, and predicting new regimes therefore requires an evaluation of new species interactions, as well as the resilience of the ‘stable’ position. While computational optimisation techniques can predict new potential regimes, predicting the most likely community state of the various options produced is currently educated guess work. In this study we integrate a stable regime optimisation approach with a Bayesian network used to infer prior knowledge of the likely stress of climate change (or, in practice, any other disturbance on each component species of a representative rocky shore community model. Combining the results, by calculating the product of the match between resilient computational predictions and the posterior probabilities of the Bayesian network, gives a refined set of model predictors, and demonstrates the use of the process in determining community changes, as might occur through processes such as climate change. To inform Bayesian priors, we conduct a review of molecular approaches applied to the analysis of the transcriptome of rocky shore organisms, and show how such an approach could be linked to measureable stress variables in the field. Hence species-specific microarrays could be designed as biomarkers of in situ stress, and used to inform predictive modelling approaches such as those described here [Current Zoology 59 (3: 403–417, 2013].

  2. High molecular weight SOA formation during limonene ozonolysis: insights from ultrahigh-resolution FT-ICR mass spectrometry characterization

    Directory of Open Access Journals (Sweden)

    S. Kundu

    2012-01-01

    Full Text Available The detailed molecular composition of secondary organic aerosols (SOA from limonene ozonolysis was studied using ultrahigh-resolution Fourier transform ion cyclotron resonance (FT-ICR mass spectrometry. High molecular weight (MW compounds (m/z > 300 were found to constitute a significant number fraction of the identified SOA components. Double bond equivalents (DBE = the number of rings plus the number of double bonds increased with MW. The O:C ratios and relative abundances of compounds decreased with increasing MW. The mass spectra of limonene contain 4 distinct clusters of negative ions: Group I (140 < m/z < 300, Group II (300 < m/z < 500, Group III (500 < m/z < 700 and Group IV (700 < m/z < 850. A number of CH2 and O homologous series of low MW SOA (Group 1 with carbon number 7–15 and oxygen number 3–9 were observed. Their occurrence can be explained with isomerization and elimination reactions of Criegee radicals, reactions between alkyl peroxy radicals, and scission of alkoxy radicals resulting from the Criegee radicals. Additionally, fragmentation analysis and observations of formaldehyde homologous series provide evidence for aerosol growth by the reactive uptake of generated gas-phase carbonyls in limonene ozonolysis. The decreasing O:C ratios between group of compounds indicated the importance of condensation (aldol and esterification reaction pathways for high MW compound formation. However, the prominent DBE changes of 2 between the groups of compounds and selected fragmentation (MS/MS analysis of Group II and Group III ions indicated a predominance of non-condensation (hydroperoxide, Criegee and hemi-acetal reaction pathways. A reaction matrix created with the combination of low MW SOA, hydroperoxides, and Criegee radicals indicated higher frequencies for the hemi-acetal and condensation reaction pathways. Overall, the combined approach confirms the importance of non

  3. Analysis of Molecular Geochemistry of Soil Organic Matter from 17-year Reciprocal Transplant Experiment in Arid Ecosystem: Simulated Climate Pertubation

    Science.gov (United States)

    Hess, N. J.; Tfaily, M.; Bailey, V. L.; McCue, L. A.

    2014-12-01

    Successful development of chemical profiles that link soil carbon vulnerability and resilience to climate change would greatly facilitate assessment of soil ecosystems response to global climate change. Additionally these signatures could be used to support the design of sustainable agricultural and food/energy crop security practices. We test this possibility using soils obtained from a 17-year reciprocal soil transplant experiment between two elevations in the arid environment of eastern Washington [1]. 30-cm diameter soil cores were reciprocally transplanted between the upper and lower sites. Cores were also transplanted in place to control for disturbance. Extracted subcores were incubated in environmental chambers and measured microbial respiration revealed statically a significant decrease in respiratory response as a function of temperature in cores transferred from low elevation to high elevation. We use ultra high resolution mass spectrometry to identify thousands of organic molecules and changes in geochemistry that would indicate the vulnerability of the soil ecosystem to climate perturbation. In our experiments we used methanol extraction followed by direct injection to 12 T ESI FT-ICR MS to identify about 4000 of individual compounds in about 200 mg soils at sub ppm mass accuracy. Chemical formulae were assigned to approximately 65% of the measured peaks using a modified Kujawinski pipeline and second order Kendrick transformations [2] resulted in approximately 75% assigned peaks. Our preliminary analysis finds that while the bulk C content of soils from the cooler, wetter conditions at the upper elevation is approximately twice that of the warmer, drier conditions at lower elevation, the molecular soil geochemistry is remarkably similar. Detailed analysis reveals subtle differences in the lipid, carbohydrate, and condensed hydrocarbon compositional makeup of the soil. Additionally, of the more than 17,000 individual compounds identified approximately

  4. On the structure of crystalline and molten cryolite: Insights from the ab initio molecular dynamics in NpT ensemble

    Science.gov (United States)

    Bučko, Tomáš; Šimko, František

    2016-02-01

    Ab initio molecular dynamics simulations in isobaric-isothermal ensemble have been performed to study the low- and the high-temperature crystalline and liquid phases of cryolite. The temperature induced transitions from the low-temperature solid (α) to the high-temperature solid phase (β) and from the phase β to the liquid phase have been simulated using a series of MD runs performed at gradually increasing temperature. The structure of crystalline and liquid phases is analysed in detail and our computational approach is shown to reliably reproduce the available experimental data for a wide range of temperatures. Relatively frequent reorientations of the AlF6 octahedra observed in our simulation of the phase β explain the thermal disorder in positions of the F- ions observed in X-ray diffraction experiments. The isolated AlF63-, AlF52-, AlF4-, as well as the bridged Al 2 Fm 6 - m ionic entities have been identified as the main constituents of cryolite melt. In accord with the previous high-temperature NMR and Raman spectroscopic experiments, the compound AlF5 2 - has been shown to be the most abundant Al-containing species formed in the melt. The characteristic vibrational frequencies for the AlFn 3 - n species in realistic environment have been determined and the computed values have been found to be in a good agreement with experiment.

  5. pH effects on the structural dynamics of cutinase from Trichoderma reesei: insights from molecular dynamics simulations.

    Science.gov (United States)

    Duan, Mei Lin; Liu, Lin; Du, Juan; Yao, Xiao Jun

    2015-11-01

    Cutinases are utilized in a variety of industries for the hydrolysis of a broad range of substrates, such as cutin, polyesters, soluble esters, insoluble short- and long-chain triglycerides. The novel cutinase from Trichoderma reesei (Tr) attracted much attention due to its two rare characteristics distinct from the classical cutinases: it possesses a lid covering its active site and its optimal activity at acidic pH. However, the structural basis for pH preference and the function of lid is still not well understood. In this work, total of six initial systems were set up either under acidic or basic pH conditions (closed-apo, open-apo and open-holo). Then, molecular dynamics (MD) simulations were performed to make a better understanding of structural dynamics of Tr cutinase under different pH conditions for the first time. The results mainly suggest that it is easier to open for the lid under an acidic pH condition. In addition, the binding of long-chain triglyceride is more stable at lower pH than higher pH. These findings elucidate that how pH influences Tr cutinase at the atomistic level. The structural and dynamic details would be useful for rational enzyme design for acidic cutinase. PMID:26387959

  6. Insights into the Thiamine Diphosphate Enzyme Activation Mechanism: Computational Model for Transketolase Using a Quantum Mechanical/Molecular Mechanical Method.

    Science.gov (United States)

    Nauton, Lionel; Hélaine, Virgil; Théry, Vincent; Hecquet, Laurence

    2016-04-12

    We propose the first computational model for transketolase (TK), a thiamine diphosphate (ThDP)-dependent enzyme, using a quantum mechanical/molecular mechanical method on the basis of crystallographic TK structures from yeast and Escherichia coli, together with experimental kinetic data reported in the literature with wild-type and mutant TK. This model allowed us to define a new route for ThDP activation in the enzyme environment. We evidenced a strong interaction between ThDP and Glu418B of the TK active site, itself stabilized by Glu162A. The crucial point highlighted here is that deprotonation of ThDP C2 is not performed by ThDP N4' as reported in the literature, but by His481B, involving a HOH688A molecule bridge. Thus, ThDP N4' is converted from an amino form to an iminium form, ensuring the stabilization of the C2 carbanion or carbene. Finally, ThDP activation proceeds via an intermolecular process and not by an intramolecular one as reported in the literature. More generally, this proposed ThDP activation mechanism can be applied to some other ThDP-dependent enzymes and used to define the entire TK mechanism with donor and acceptor substrates more accurately. PMID:26998737

  7. Molecular-Level Insights into the Reactivity of Siloxane-Based Electrolytes at a Lithium-Metal Anode

    Energy Technology Data Exchange (ETDEWEB)

    Assary, Rajeev S.; Lu, Jun; Luo, Xiangyi; Zhang, Xiaoyi; Ren, Yang; Wu, Huiming; Albishri, Hassan M.; El-Hady, D. A.; Al-Bogami, A. S.; Curtiss, Larry A.; Amine, Khalil

    2014-07-21

    A molecular-level understanding of the reactions that occur at the lithium-metal anode/electrolyte interphase is essential to improve the performance of Li–O2 batteries. Experimental and computational techniques are applied to explore the reactivity of tri(ethylene glycol)-substituted trimethylsilane (1NM3), a siloxane-based ether electrolyte, at the lithium-metal anode. In situ/ex situ X-ray diffraction and Fourier-transform infrared spectroscopy studies provide evidence of the formation of lithium hydroxide and lithium carbonates at the anode upon gradual degradation of the metallic lithium anode and the solvent molecules in the presence of oxygen. Density functional calculations performed to obtain a mechanistic understanding of the reductive decomposition of 1NM3 indicate that the decomposition does not require any apparent barrier to produce lithium hydroxide and lithium carbonates when the reduced 1NM3 solvent molecules interact with the oxygen crossing over from the cathode. This study indicates that degradation may be more significant in the case of the 1NM3 solvent, compared to linear ethers such as tetraglyme or dioxalone, because of its relatively high electron affinity. Also, both protection of the lithium metal and prevention of oxygen crossover to the anode are essential for minimizing electrolyte and anode decomposition.

  8. Structural and dynamical properties of the porins OmpF and OmpC: insights from molecular simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Amit; Hajjar, Eric; Ruggerone, Paolo; Ceccarelli, Matteo, E-mail: matteo.ceccarelli@dsf.unica.i [Istituto Officina dei Materiali/CNR UOS SLACS, c/o Department of Physics, University of Cagliari, SP Monserrato-Sestu Km 0.700, Monserrato I-09042 (Italy)

    2010-11-17

    In this paper we investigate the structural and dynamical properties of the two major porins (OmpF and OmpC) in Escherichia coli, using molecular dynamics (MD) simulations. In particular we characterized the atomic fluctuations, correlated motions, temperature dependence, solvent-accessible cross-sectional area and water dynamics in the key regions of the two channels. Our in-depth analysis allows us to highlight the importance of both the key conserved and substituted residues between OmpF and OmpC. The latter is characterized by a narrower and longer constriction region with respect to OmpF. OmpC also showed a higher stability upon increasing temperature. We then present the results of transport properties by using accelerated MD simulations to probe the diffusion of norfloxacin (a fluoroquinolone antibiotic) through the two porins OmpF/OmpC. Our study constitutes a step forward towards understanding the structure-function relationship of the two porins' channels. This will benefit the research of antibacterials with improved permeation properties and nanopores that aim to use these porins as sensing systems.

  9. Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking, molecular dynamics and MM/PBSA studies.

    Science.gov (United States)

    Yang, Zhiwei; Wu, Fei; Yuan, Xiaohui; Zhang, Lei; Zhang, Shengli

    2016-04-01

    Recently, ganoderic acids (GAs) give rise to the attractive candidates of novel neuraminidase (NA) inhibitors. However, there is still no evident conclusion about their binding patterns. To this end, docking, molecular dynamics and MM/PBSA methods were combined to study the binding profiles of GAs with the N1 protein and familiar H274Y and N294S mutations (A/Vietnam/1203/04 stain). It was found that the binding affinities of ganoderic acid DM and Z (ΔGbind, -16.83 and -10.99 kcal mol(-1)) are comparable to that of current commercial drug oseltamivir (-23.62 kcal mol(-1)). Electrostatic interaction is the main driving force, and should be one important factor to evaluate the binding quality and rational design of NA inhibitors. The 150-loop residues Asp151 and Arg152 played an important role in the binding processes. Further analysis revealed that ganoderic acid DM is a potential source of anti-influenza ingredient, with novel binding pattern and advantage over oseltamivir. It had steric hindrance on the 150 cavity of N1 protein, and exerted activities across the H274Y and N294S mutations. This work also pointed out how to effectively design dual-site NA inhibitors and reinforce their affinities. These findings should prove valuable for the in-depth understanding of interactions between NA and GAs, and warrant the experimental aspects to design novel anti-influenza drugs. PMID:26905206

  10. Molecular Evidence for Convergence and Parallelism in Evolution of Complex Brains of Cephalopod Molluscs: Insights from Visual Systems.

    Science.gov (United States)

    Yoshida, M A; Ogura, A; Ikeo, K; Shigeno, S; Moritaki, T; Winters, G C; Kohn, A B; Moroz, L L

    2015-12-01

    Coleoid cephalopods show remarkable evolutionary convergence with vertebrates in their neural organization, including (1) eyes and visual system with optic lobes, (2) specialized parts of the brain controlling learning and memory, such as vertical lobes, and (3) unique vasculature supporting such complexity of the central nervous system. We performed deep sequencing of eye transcriptomes of pygmy squids (Idiosepius paradoxus) and chambered nautiluses (Nautilus pompilius) to decipher the molecular basis of convergent evolution in cephalopods. RNA-seq was complemented by in situ hybridization to localize the expression of selected genes. We found three types of genomic innovations in the evolution of complex brains: (1) recruitment of novel genes into morphogenetic pathways, (2) recombination of various coding and regulatory regions of different genes, often called "evolutionary tinkering" or "co-option", and (3) duplication and divergence of genes. Massive recruitment of novel genes occurred in the evolution of the "camera" eye from nautilus' "pinhole" eye. We also showed that the type-2 co-option of transcription factors played important roles in the evolution of the lens and visual neurons. In summary, the cephalopod convergent morphological evolution of the camera eyes was driven by a mosaic of all types of gene recruitments. In addition, our analysis revealed unexpected variations of squids' opsins, retinochromes, and arrestins, providing more detailed information, valuable for further research on intra-ocular and extra-ocular photoreception of the cephalopods. PMID:26002349

  11. Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction

    Science.gov (United States)

    Nichol, Sarah; Tracey, Alan; Holroyd, Nancy; Cotton, James A.; Stanley, Eleanor J.; Zarowiecki, Magdalena; Liu, Jimmy Z.; Huckvale, Thomas; Cooper, Philip J.; Grencis, Richard K.; Berriman, Matthew

    2014-01-01

    Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. Here we present the genome sequences of the human-infective Trichuris trichiura and the murine laboratory model T. muris. Based on whole transcriptome analyses we identify many genes that are expressed in a gender- or life stage-specific manner and characterise the transcriptional landscape of a morphological region with unique biological adaptations, namely bacillary band and stichosome, found only in whipworms and related parasites. Using RNAseq data from whipworm-infected mice we describe the regulated Th1-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identifies numerous potential new drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection. PMID:24929830

  12. Structural and dynamical properties of the porins OmpF and OmpC: insights from molecular simulations

    International Nuclear Information System (INIS)

    In this paper we investigate the structural and dynamical properties of the two major porins (OmpF and OmpC) in Escherichia coli, using molecular dynamics (MD) simulations. In particular we characterized the atomic fluctuations, correlated motions, temperature dependence, solvent-accessible cross-sectional area and water dynamics in the key regions of the two channels. Our in-depth analysis allows us to highlight the importance of both the key conserved and substituted residues between OmpF and OmpC. The latter is characterized by a narrower and longer constriction region with respect to OmpF. OmpC also showed a higher stability upon increasing temperature. We then present the results of transport properties by using accelerated MD simulations to probe the diffusion of norfloxacin (a fluoroquinolone antibiotic) through the two porins OmpF/OmpC. Our study constitutes a step forward towards understanding the structure-function relationship of the two porins' channels. This will benefit the research of antibacterials with improved permeation properties and nanopores that aim to use these porins as sensing systems.

  13. Molecular Origin of Gerstmann-Str ussler-Scheinker Syndrome: Insight from Computer Simulation of an Amyloidogenic Prion Peptide

    Energy Technology Data Exchange (ETDEWEB)

    Diadone, Isabella [University of L' Aquila, L' Aquila, Italy; DiNola, Alfredo [University of Rome; Smith, Jeremy C [ORNL

    2011-01-01

    Prion proteins become pathogenic through misfolding. Here, we characterize the folding of a peptide consisting of residues 109 122 of the Syrian hamster prion protein (the H1 peptide) and of a more amyloidogenic A117V point mutant that leads in humans to an inheritable form of the Gerstmann-Straeussler-Scheinker syndrome. Atomistic molecular dynamics simulations are performed for 2.5 s. Both peptides lose their -helical starting conformations and assume a -hairpin that is structurally similar in both systems. In each simulation several unfolding/refolding events occur, leading to convergence of the thermodynamics of the conformational states to within 1 kJ/mol. The similar stability of the -hairpin relative to the unfolded state is observed in the two peptides. However, substantial differences are found between the two unfolded states. A local minimum is found within the free energy unfolded basin of the A117V mutant populated by misfolded collapsed conformations of comparable stability to the -hairpin state, consistent with increased amyloidogenicity. This population, in which V117 stabilizes a hydrophobic core, is absent in the wild-type peptide. These results are supported by simulations of oligomers showing a slightly higher stability of the associated structures and a lower barrier to association for the mutated peptide. Hence, a single point mutation carrying only two additional methyl groups is here shown to be responsible for rather dramatic differences of structuring within the unfolded (misfolded) state.

  14. Many-particle fragmentation processes in atomic and molecular physics. New insight into the world of correlation

    International Nuclear Information System (INIS)

    Full text: Correlated many-particle dynamics in Coulombic systems, which is one of the unsolved fundamental problems in AMO-physics, can now be experimentally approached with so far unprecedented completeness and precision. The recent development of the COLTRIMS technique (COLd Target Recoil Ion Momentum Spectroscopy) provides a coincident multifragment imaging technique for eV and sub-eV fragment detection. In its completeness it is as powerful as the bubble chamber in high energy physics. In recent benchmark experiments quasi snapshots (duration as short an atto-sec) of the correlated dynamics between electrons and nuclei has been made for atomic and molecular objects. This new imaging technique has opened a powerful observation window into the hidden world of many-particle dynamics. The principle of the new reaction microscope (synonym: COLTRIMS) will be presented. If imaging detectors based on fast delay-line position read-out are used multi-hit detection is possible. Even two particles hitting the detector at the 'same' instant (Δt < 1 ns) can simultaneously be detected. The number of detected multi-hits is practically only limited by the electronics needed to store in event mode all information. Several examples for COLTRIMS data will be shown: double excitation and ionization of He as well as complete differential data in momentum space for many particle fragmentation of molecules by ions and photons. The obtained information on e-e correlation is discussed

  15. Molecular Technologies in Serbian Lowland Forestry under Climate Changes - Possibilities and Perspectives

    Directory of Open Access Journals (Sweden)

    Branislav Trudić

    2014-12-01

    Full Text Available Background and Purpose: Vojvodina province, the northern part of the Republic of Serbia, is predominantly lowland agricultural region with over 75% of arable land which in previous years, has been highly impacted by drought. The annual precipitation is lower than 700 mm and it is the limit for the growth and development of natural forest vegetation. Unfortunately, the atmospheric precipitation is still a major source of water for plant biodiversity. Taking these facts into account, it is highly recommended to primarily use the xerothermic tree species, which have a well-developed root system for “classical” afforestation. Some species from Salicaceae and Fagaceae like poplars, willows, oaks and beeches are surely the best option for afforestation in temperate zones strongly influenced by drought. Conclusions: In order to develop stress-based genomic information in Populus and the rest of woody plant species from Vojvodina, an integrated genetic research needs to be done. The aim of this particular paper is to analyse and summarize data regarding stress-based biotechnology perspectives in Vojvodina and to give recommendations for future forest tree breeding. Drought as a strong negative ecological factor must be carefully considered. In order to achieve sustainability, new forest management plans must consider wide approaches, from molecular to ecosystem level.

  16. Structure and function of cytochrome P450S in insect adaptation to natural and synthetic toxins: insights gained from molecular modeling.

    Science.gov (United States)

    Schuler, Mary A; Berenbaum, May R

    2013-09-01

    Over evolutionary time, insect herbivores have adapted to the presence of natural toxins and more recently to synthetic insecticides in or on the plants they consume. Biochemical analyses and molecular modeling of the cytochrome P450 monooxygenases (P450s) that metabolize these compounds have provided insight into the many variations affecting their catalytic activity. Phylogenetically distinct P450s may metabolize similar substrates, and phylogenetically similar P450s may metabolize different substrates; as well, some P450s process broad arrays of both phytochemicals and synthetic insecticides, while closely related P450s are restricted to a narrow range of phytochemicals. Mapped on the predicted three-dimensional structures of insect P450s developed from available mammalian P450 crystal structures, differences in multiple regions of the insect proteins reveal the evolutionary processes occurring as P450 genes have duplicated and diverged. Analyses of site-directed mutants in select lepidopteran and dipteran P450s demonstrate that slight changes in the catalytic site, the putative product release channel, and the proximal surface (interacting with electron transfer partners such as cytochrome P450 reductase and cytochrome b5) yield pronounced activity differences. Additionally, changes in the catalytic site and in the linker region preceding the proline-hinge influence P450 folding. With predicted structures available for many mammalian P450s involved in metabolism of xenobiotics, it is possible to record allelic variation relative to catalytically important regions in the overall P450 structure and to predict functionally critical differences. Together with information on the relative levels of allelic variant transcripts, comprehensive characterization of the mechanisms that modulate metabolism of natural and synthetic xenobiotics in insects can yield insights into plant-insect coevolution and into novel approaches for chemical pest management. PMID:24036972

  17. Characterization of small HSPs from Anemonia viridis reveals insights into molecular evolution of alpha crystallin genes among cnidarians.

    Directory of Open Access Journals (Sweden)

    Aldo Nicosia

    Full Text Available Gene family encoding small Heat-Shock Proteins (sHSPs containing α-crystallin domain are found both in prokaryotic and eukaryotic organisms; however, there is limited knowledge of their evolution. In this study, two small HSP genes termed AvHSP28.6 and AvHSP27, both organized in one intron and two exons, were characterised in the Mediterranean snakelocks anemone Anemonia viridis. The release of the genome sequence of Hydra magnipapillata and Nematostella vectensis enabled a comprehensive study of the molecular evolution of α-crystallin gene family among cnidarians. Most of the H. magnipapillata sHSP genes share the same gene organization described for AvHSP28.6 and AvHSP27, differing from the sHSP genes of N. vectensis which mainly show an intronless architecture. The different genomic organization of sHSPs, the phylogenetic analyses based on protein sequences, and the relationships among Cnidarians, suggest that the A.viridis sHSPs represent the common ancestor from which H. magnipapillata genes directly evolved through segmental genome duplication. Additionally retroposition events may be considered responsible for the divergence of sHSP genes of N. vectensis from A. viridis. Analyses of transcriptional expression profile showed that AvHSP28.6 was constitutively expressed among different tissues from both ectodermal and endodermal layers of the adult sea anemones, under normal physiological conditions and also under different stress condition. Specifically, we profiled the transcriptional activation of AvHSP28.6 after challenges with different abiotic/biotic stresses showing induction by extreme temperatures, heavy metals exposure and immune stimulation. Conversely, no AvHSP27 transcript was detected in such dissected tissues, in adult whole body cDNA library or under stress conditions. Hence, the involvement of AvHSP28.6 gene in the sea anemone defensome is strongly suggested.

  18. Exceptional response to cetuximab monotherapy in a patient with metastatic oropharyngeal squamous cell carcinoma: a molecular insight

    Directory of Open Access Journals (Sweden)

    Peddi P

    2016-02-01

    Full Text Available Prakash Peddi,1 Bhavna Paryani,2 Amol Takalkar,2 Paige Bundrick,3 John Ponugupati,4 Binu Nair,5 Hazem El-Osta1 1Department of Medicine, Division of Hematology-Oncology, 2Department of Radiology, 3Department of Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, 4Oncology Department, Herbert J Thomas Memorial Hospital, South Charleston, WV, 5Baylor Scott & White Medical Center - Waxahachie, Waxahachie, TX, USA Background: Metastatic head and neck squamous cell carcinoma (HNSCC carries a very poor prognosis. A better understanding of the molecular driver of the disease and the identification of biomarkers of response remain paramount for an effective personalized therapy. Case report: We report an original case of a 56-year-old patient diagnosed with metastatic HNSCC to both kidneys, who experienced a long-lasting complete response to a single-agent cetuximab, a monoclonal antibody-targeting EGFR. Comprehensive multiplatform biomarker analysis of the tumor revealed the presence of phosphatidyl-inositol 3 kinase mutation, EGFR overexpression, and the absence of PD-1/PD-L1 expression. Since PI3K, a downstream effector of EGFR, is activated, the tumor regression may have occurred mainly through a cetuximab-induced immune-mediated response, rather than EGFR signal blockade. It is plausible that this effect was enhanced by the lack of PD-1 and PD-L1 expression. Conclusion: Our case proposes that the absence of PD-1 and PD-L1 expression in conjunction with EGFR overexpression may correlate with better response to cetuximab in HNSCC. This hypothesis needs to be examined through a large clinical trial. Keywords: biomarker, cetuximab, EGFR blockade, exceptional response, head and neck squamous cell carcinoma

  19. Low-temperature molecular motions in lipid bilayers in the presence of sugars: insights into cryoprotective mechanisms.

    Science.gov (United States)

    Konov, Konstantin B; Isaev, Nikolay P; Dzuba, Sergei A

    2014-10-30

    Sugars and sugar alcohols can stabilize biological systems under extreme conditions of desiccation and freezing. Phospholipid bilayers solvated by aqueous solutions of sucrose, trehalose, and sorbitol at concentrations of 0.2 and 1 M and containing incorporated spin-labeled stearic acids were studied by electron spin echo (ESE) spectroscopy, a pulsed version of electron paramagnetic resonance (EPR). The phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and the stearic acids were labeled with nitroxide 4,4-dimethyl-oxazolidine-1-oxyl (DOXYL) attached rigidly at either the 5th or 16th carbon positions. The ratio of the echo time traces for the two field positions in the EPR spectrum possessing the largest and smallest anisotropies gave the anisotropic contribution to the echo decay, which obeys exponential time dependence with good accuracy. At low temperatures, the anisotropic contribution is induced by stochastic (or diffusive) orientational vibrations of the molecule as a whole (i.e., stochastic molecular librations), with the exponential decay rate Wanis proportional to τc, where is the mean angular amplitude of the motion and τc is the correlation time. In all cases, it was found that Wanis begins to increase sharply above 170-200 K, which was ascribed to the dynamical transition known for biological systems at these temperatures. For hydration by the sucrose and trehalose solutions, Wanis was found to increase noticeably also above ∼120 K, which was explained by bilayer expansion due to direct bonding of sugar molecules to the bilayer surface. The Wanis temperature dependencies were found to be close to those obtained for the simple systems of the nitroxide spin probe TEMPONE in aqueous sorbitol and sugar 1 M solutions. This correlation suggests a possible mechanism of cryoprotective action of sorbitol and sugars due to the similarity of low-temperature motions in the membrane and in the cryoprotectant-containing surrounding liquid

  20. Dispersion and shear-induced orientation of anisotropic nanoparticle filled polymer nanocomposites: insights from molecular dynamics simulation.

    Science.gov (United States)

    Zheng, Zijian; Wang, Zixuan; Wang, Lu; Liu, Jun; Wu, Youping; Zhang, Liqun

    2016-07-01

    Although a large number of studies have been performed to study the dispersion behavior of spherical nanoparticles (NPs) in the polymer matrix, little effort has been directed to anisotropic NPs via simulation, which is convenient for controlling the physical parameters compared to experiment. In this work we adopt molecular dynamics simulation to study polymer nanocomposites filled with anisotropic NPs such as graphene and carbon nanotubes (CNTs). We investigate the effects of the grafting position, grafting density, the length and flexibility of the grafted chains on the dispersion of graphene and CNTs. In particular, we find that when the grafting position is located on the surface center of the graphene or the middle of the CNT, the dispersion state is the best, leading to the greatest stress-strain behavior. Meanwhile, the mechanical property can be further strengthened by introducing chemical couplings in the interfacial region, by chemically tethering the grafted chains to the matrix chains. To monitor the processing effect, we exert a dynamic periodic shear deformation in the x direction with its gradient in the y direction. Polymer chains are found to align in the x direction, graphene sheets align in the xoz plane and CNTs orientate in the z direction. We study the effects of the shear amplitude, the shear frequency, polymer-NP interaction strength and volume fraction of NPs on the stress-strain behavior. We also observe that the relaxation process following the shear deformation deteriorates the mechanical performance, resulting from the disorientation of polymer chains and NPs. In general, this work could provide valuable guidance in manipulating the distribution and alignment of graphene and CNTs in the polymer matrix. PMID:27196704

  1. Employing conformational analysis in the molecular modeling of agrochemicals: insights on QSAR parameters of 2,4-D

    Directory of Open Access Journals (Sweden)

    Matheus Puggina de Freitas

    2013-12-01

    Full Text Available A common practice to compute ligand conformations of compounds with various degrees of freedom to be used in molecular modeling (QSAR and docking studies is to perform a conformational distribution based on repeated random sampling, such as Monte-Carlo methods. Further calculations are often required. This short review describes some methods used for conformational analysis and the implications of using selected conformations in QSAR. A case study is developed for 2,4-dichlorophenoxyacetic acid (2,4-D, a widely used herbicide which binds to TIR1 ubiquitin ligase enzyme. The use of such an approach and semi-empirical calculations did not achieve all possible minima for 2,4-D. In addition, the conformations and respective energies obtained by the semi-empirical AM1 method do not match the calculated trends obtained by a high level DFT method. Similar findings were obtained for the carboxylate anion, which is the bioactive form. Finally, the crystal bioactive structure of 2,4-D was not found as a minimum when using Monte-Carlo/AM1 and is similarly populated with another conformer in implicit water solution according to optimization at the B3LYP/aug-cc-pVDZ level. Therefore, quantitative structure-activity relationship (QSAR methods based on three dimensional chemical structures are not fundamental to provide predictive models for 2,4-D congeners as TIR1 ubiquitin ligase ligands, since they do not necessarily reflect the bioactive conformation of this molecule. This probably extends to other systems.

  2. Dispersion and shear-induced orientation of anisotropic nanoparticle filled polymer nanocomposites: insights from molecular dynamics simulation

    Science.gov (United States)

    Zheng, Zijian; Wang, Zixuan; Wang, Lu; Liu, Jun; Wu, Youping; Zhang, Liqun

    2016-07-01

    Although a large number of studies have been performed to study the dispersion behavior of spherical nanoparticles (NPs) in the polymer matrix, little effort has been directed to anisotropic NPs via simulation, which is convenient for controlling the physical parameters compared to experiment. In this work we adopt molecular dynamics simulation to study polymer nanocomposites filled with anisotropic NPs such as graphene and carbon nanotubes (CNTs). We investigate the effects of the grafting position, grafting density, the length and flexibility of the grafted chains on the dispersion of graphene and CNTs. In particular, we find that when the grafting position is located on the surface center of the graphene or the middle of the CNT, the dispersion state is the best, leading to the greatest stress–strain behavior. Meanwhile, the mechanical property can be further strengthened by introducing chemical couplings in the interfacial region, by chemically tethering the grafted chains to the matrix chains. To monitor the processing effect, we exert a dynamic periodic shear deformation in the x direction with its gradient in the y direction. Polymer chains are found to align in the x direction, graphene sheets align in the xoz plane and CNTs orientate in the z direction. We study the effects of the shear amplitude, the shear frequency, polymer–NP interaction strength and volume fraction of NPs on the stress–strain behavior. We also observe that the relaxation process following the shear deformation deteriorates the mechanical performance, resulting from the disorientation of polymer chains and NPs. In general, this work could provide valuable guidance in manipulating the distribution and alignment of graphene and CNTs in the polymer matrix.

  3. New insights into the molecular epidemiology of Trichinella infection in domestic pigs, wild boars, and bears in Romania.

    Science.gov (United States)

    Nicorescu, Isabela Madalina Dragoi; Ionita, Mariana; Ciupescu, Laurentiu; Buzatu, Cristian Vasile; Tanasuica, Rodica; Mitrea, Ioan Liviu

    2015-09-15

    Trichinellosis is a food-borne zoonosis caused by the parasitic nematode Trichinella, characterized by an extremely wide host range and geographical distribution. In Romania, it is recognized as one of the most serious zoonotic diseases. A cross-sectional study, covering all regions of Romania, was conducted in 2014 to investigate and update the prevalence of Trichinella infection among domestic pigs, wild boars, and bears. Additional, molecular identification of Trichinella species circulating among these animals was performed in order to establish the biogeography of Trichinella species within the seven geographical regions of Romania. For this, a total of 113,383 pigs raised in non-controlled housing conditions (backyards), 5596 hunted wild boars and 147 hunted bears were subjected to Trichinella analysis. The highest prevalence of Trichinella infections was found in bears (12.93%), followed by wild boars (1.66%) and domestic pigs (0.20%). Of 294 Trichinella isolates that tested positive by multiplex PCR, 219 (74.49%) were identified as Trichinella spiralis, 66 (22.45%) as Trichinella britovi, and 9 isolates (3.06%) as mixed infections of T. spiralis and T. britovi. T. spiralis was more prevalent in domestic pigs (165/228; 72.37%) than in game (63/228; 27.63%), while T. britovi showed a higher prevalence in game (50/75; 66.66%) than in domestic pigs (25/75; 33.33%). Moreover, the present study revealed a significant host- and area- related distribution of Trichinella species within the seven regions of Romania. Therefore, these findings are of epidemiological relevance, updating data on the prevalence and distribution of Trichinella species circulating among domestic and wild animals in South-Eastern Europe. PMID:26238657

  4. Insights into the Molecular Activation Mechanism of the RhoA-specific Guanine Nucleotide Exchange Factor, PDZRhoGEF

    Energy Technology Data Exchange (ETDEWEB)

    Bielnicki, Jakub A.; Shkumatov, Alexander V.; Derewenda, Urszula; Somlyo, Avril V.; Svergun, Dmitri I.; Derewenda, Zygmunt S. (EMBL); (UV)

    2012-10-09

    PDZRhoGEF (PRG) belongs to a small family of RhoA-specific nucleotide exchange factors that mediates signaling through select G-protein-coupled receptors via G{alpha}{sub 12/13} and activates RhoA by catalyzing the exchange of GDP to GTP. PRG is a multidomain protein composed of PDZ, regulators of G-protein signaling-like (RGSL), Dbl-homology (DH), and pleckstrin-homology (PH) domains. It is autoinhibited in cytosol and is believed to undergo a conformational rearrangement and translocation to the membrane for full activation, although the molecular details of the regulation mechanism are not clear. It has been shown recently that the main autoregulatory elements of PDZRhoGEF, the autoinhibitory 'activation box' and the 'GEF switch,' which is required for full activation, are located directly upstream of the catalytic DH domain and its RhoA binding surface, emphasizing the functional role of the RGSL-DH linker. Here, using a combination of biophysical and biochemical methods, we show that the mechanism of PRG regulation is yet more complex and may involve an additional autoinhibitory element in the form of a molten globule region within the linker between RGSL and DH domains. We propose a novel, two-tier model of autoinhibition where the activation box and the molten globule region act synergistically to impair the ability of RhoA to bind to the catalytic DH-PH tandem. The molten globule region and the activation box become less ordered in the PRG-RhoA complex and dissociate from the RhoA-binding site, which may constitute a critical step leading to PRG activation.

  5. Spinning gland transcriptomics from two main clades of spiders (order: Araneae--insights on their molecular, anatomical and behavioral evolution.

    Directory of Open Access Journals (Sweden)

    Francisco Prosdocimi

    Full Text Available Characterized by distinctive evolutionary adaptations, spiders provide a comprehensive system for evolutionary and developmental studies of anatomical organs, including silk and venom production. Here we performed cDNA sequencing using massively parallel sequencers (454 GS-FLX Titanium to generate ∼80,000 reads from the spinning gland of Actinopus spp. (infraorder: Mygalomorphae and Gasteracantha cancriformis (infraorder: Araneomorphae, Orbiculariae clade. Actinopus spp. retains primitive characteristics on web usage and presents a single undifferentiated spinning gland while the orbiculariae spiders have seven differentiated spinning glands and complex patterns of web usage. MIRA, Celera Assembler and CAP3 software were used to cluster NGS reads for each spider. CAP3 unigenes passed through a pipeline for automatic annotation, classification by biological function, and comparative transcriptomics. Genes related to spider silks were manually curated and analyzed. Although a single spidroin gene family was found in Actinopus spp., a vast repertoire of specialized spider silk proteins was encountered in orbiculariae. Astacin-like metalloproteases (meprin subfamily were shown to be some of the most sampled unigenes and duplicated gene families in G. cancriformis since its evolutionary split from mygalomorphs. Our results confirm that the evolution of the molecular repertoire of silk proteins was accompanied by the (i anatomical differentiation of spinning glands and (ii behavioral complexification in the web usage. Finally, a phylogenetic tree was constructed to cluster most of the known spidroins in gene clades. This is the first large-scale, multi-organism transcriptome for spider spinning glands and a first step into a broad understanding of spider web systems biology and evolution.

  6. Insights into affinity and specificity in the complexes of α-lytic protease and its inhibitor proteins: binding free energy from molecular dynamics simulation†

    Science.gov (United States)

    Cieplak, Piotr

    2014-01-01

    We report the binding free energy calculation and its decomposition for the complexes of α-lytic protease and its protein inhibitors using molecular dynamics simulation. Standard mechanism serine protease inhibitors eglin C and OMTKY3 are known to have strong binding affinity for many serine proteases. Their binding loops have significant similarities, including a common P1 Leu as the main anchor in the binding interface. However, recent experiments demonstrate that the two inhibitors have vastly different affinity towards α-lytic protease (ALP), a bacterial serine protease. OMTKY3 inhibits the enzyme much more weakly (by ~106 times) than eglin C. Moreover, a variant of OMTKY3 with five mutations, OMTKY3M, has been shown to inhibit 104 times more strongly than the wild-type inhibitor. The underlying mechanisms for the unusually large difference in binding affinities and the effect of mutation are not well understood. Here we use molecular dynamics simulation with molecular mechanics–Poisson Boltzmann/surface area method (MM-PB/SA) to investigate quantitatively the binding specificity. The calculated absolute binding free energies correctly differentiate the thermodynamic stabilities of these protein complexes, but the magnitudes of the binding affinities are systematically overestimated. Analysis of the binding free energy components provides insights into the molecular mechanism of binding specificity. The large ΔΔGbind between eglin C and wild type OMTKY3 towards ALP is mainly attributable to the stronger nonpolar interactions in the ALP-eglin C complex, arising from a higher degree of structural complementarity. Here the electrostatic interaction contributes to a lesser extent. The enhanced inhibition in the penta-mutant OMTKY3M over its wild type is entirely due to an overall improvement in the solvent-mediated electrostatic interactions in the ALP-OMTKY3M complex. The results suggest that for these protein-complexes and similar enzyme-inhibitor systems

  7. Insights into affinity and specificity in the complexes of alpha-lytic protease and its inhibitor proteins: binding free energy from molecular dynamics simulation.

    Science.gov (United States)

    Deng, Nan-Jie; Cieplak, Piotr

    2009-07-01

    We report the binding free energy calculation and its decomposition for the complexes of alpha-lytic protease and its protein inhibitors using molecular dynamics simulation. Standard mechanism serine protease inhibitors eglin C and OMTKY3 are known to have strong binding affinity for many serine proteases. Their binding loops have significant similarities, including a common P1 Leu as the main anchor in the binding interface. However, recent experiments demonstrate that the two inhibitors have vastly different affinity towards alpha-lytic protease (ALP), a bacterial serine protease. OMTKY3 inhibits the enzyme much more weakly (by approximately 10(6) times) than eglin C. Moreover, a variant of OMTKY3 with five mutations, OMTKY3M, has been shown to inhibit 10(4) times more strongly than the wild-type inhibitor. The underlying mechanisms for the unusually large difference in binding affinities and the effect of mutation are not well understood. Here we use molecular dynamics simulation with molecular mechanics-Poisson Boltzmann/surface area method (MM-PB/SA) to investigate quantitatively the binding specificity. The calculated absolute binding free energies correctly differentiate the thermodynamic stabilities of these protein complexes, but the magnitudes of the binding affinities are systematically overestimated. Analysis of the binding free energy components provides insights into the molecular mechanism of binding specificity. The large DeltaDeltaG(bind) between eglin C and wild type OMTKY3 towards ALP is mainly attributable to the stronger nonpolar interactions in the ALP-eglin C complex, arising from a higher degree of structural complementarity. Here the electrostatic interaction contributes to a lesser extent. The enhanced inhibition in the penta-mutant OMTKY3M over its wild type is entirely due to an overall improvement in the solvent-mediated electrostatic interactions in the ALP-OMTKY3M complex. The results suggest that for these protein-complexes and

  8. From DNA repair to proteome protection: new molecular insights for preventing non-melanoma skin cancers and skin aging.

    Science.gov (United States)

    Emanuele, Enzo; Spencer, James M; Braun, Martin

    2014-03-01

    Non-melanoma skin cancers (NMSC) are the most common human neoplasms and continue to represent an important public health issue with greater than one million cases diagnosed each year. The primary factor contributing to the molecular pathogenesis of NMSC is unprotected skin exposure to ultraviolet (UV) radiation, ie, UVA (wavelength: 315-400 nm) and UVB rays (wavelength: 280-315 nm) with additional albeit less damaging factors of infrared radiation (wavelength: ~750 nm-1 mm) and environmental pollutants. Skin carcinogenesis by DNA damage is the current predominant paradigm of UV toxicity, which may be caused by direct damaging effects of energy deposited by photons or indirect oxidative action of short-lived reactive oxygen species (ROS) formed from water that reacts with biomacromolecules. UV rays are capable to induce direct both DNA damages, mainly consisting in the formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPDs), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8OHdG). Growing evidence also suggests that the efficiency of DNA repair after exposure to UV radiation is crucially dependent on the levels of oxidative protein damage, including but not limited to DNA repair proteins. Besides DNA lesions, UV-induced oxidative stress can indeed result in carbonylation of proteins, a major form of irreversible protein damage that inactivates their biological function. Interestingly, microorganisms characterized by extreme resistance to UV rays have an intrinsic capacity to protect their proteome, rather than genome, from radiation-induced damage, suggesting that protein carbonylation (PC) may serve as a reliable and innovative biomarker of UV photodamage. This review discusses the main DNA and protein markers of UV-induced damage (eg, CPDs, 8OHdG, and PC) and their relationship and importance to the current understanding of skin carcinogenesis. The identification of key DNA

  9. Comparative transcripts profiling reveals new insight into molecular processes regulating lycopene accumulation in a sweet orange (Citrus sinensis red-flesh mutant

    Directory of Open Access Journals (Sweden)

    Zhang Jianchen

    2009-11-01

    Full Text Available Abstract Background Interest in lycopene metabolism and regulation is growing rapidly because accumulative studies have suggested an important role for lycopene in human health promotion. However, little is known about the molecular processes regulating lycopene accumulation in fruits other than tomato so far. Results On a spontaneous sweet orange bud mutant with abnormal lycopene accumulation in fruits and its wild type, comparative transcripts profiling was performed using Massively Parallel Signature Sequencing (MPSS. A total of 6,877,027 and 6,275,309 reliable signatures were obtained for the wild type (WT and the mutant (MT, respectively. Interpretation of the MPSS signatures revealed that the total number of transcribed gene in MT is 18,106, larger than that in WT 17,670, suggesting that newly initiated transcription occurs in the MT. Further comparison of the transcripts abundance between MT and WT revealed that 3,738 genes show more than two fold expression difference, and 582 genes are up- or down-regulated at 0.05% significance level by more than three fold difference. Functional assignments of the differentially expressed genes indicated that 26 reliable metabolic pathways are altered in the mutant; the most noticeable ones are carotenoid biosynthesis, photosynthesis, and citrate cycle. These data suggest that enhanced photosynthesis and partial impairment of lycopene downstream flux are critical for the formation of lycopene accumulation trait in the mutant. Conclusion This study provided a global picture of the gene expression changes in a sweet orange red-flesh mutant as compared to the wild type. Interpretation of the differentially expressed genes revealed new insight into the molecular processes regulating lycopene accumulation in the sweet orange red-flesh mutant.

  10. Dietary salt loading and ion-poor water exposure provide insight into the molecular physiology of the rainbow trout gill epithelium tight junction complex.

    Science.gov (United States)

    Kolosov, Dennis; Kelly, Scott P

    2016-08-01

    This study utilized dietary salt loading and ion-poor water (IPW) exposure of rainbow trout (Oncorhynchus mykiss) to further understand the role of fish gill epithelium tight junction (TJ) physiology in salt and water balance. Gill morphology, biochemistry and molecular physiology were examined, with an emphasis on genes encoding TJ proteins. Fish were either fed a control or salt-enriched diet (~10 % NaCl) for 4 weeks prior to IPW exposure for 24 h. Serum [Na(+)], [Cl(-)] and muscle moisture content were unaltered by salt feeding, but changed in response to IPW irrespective of diet. Dietary salt loading altered the morphology (reduced Na(+)-K(+)-ATPase-immunoreactive cell numbers and surface exposure of mitochondrion-rich cells), biochemistry (decreased vacuolar-type H(+)-ATPase activity) and molecular physiology (decreased nkaα1a and cftrII mRNA abundance) of the gill in a manner indicative of reduced active ion uptake activity. But in control fish and not salt-fed fish, gill mRNA abundance of nkaα1c increased and nbc decreased after IPW exposure. Genes encoding TJ proteins were typically either responsive to salt feeding or IPW, but select genes responded to combined experimental treatment (e.g. IPW responsive but only if fish were salt-fed). Therefore, using salt feeding and IPW exposure, new insights into what factors influence gill TJ proteins and the role that specific TJ proteins might play in regulating the barrier properties of the gill epithelium have been acquired. In particular, evidence suggests that TJ proteins in the gill epithelium, or the regulatory networks that control them, respond independently to external or internal stimuli. PMID:27083431

  11. Structures of Human Cyctochrome P450 2E1: Insights Into the Binding of Inhibitors And Both Small Molecular Weight And Fatty Acid Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Porubsky, P.R.; Meneely, K.M.; Scott, E.E.

    2009-05-21

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 {angstrom} for an indazole complex and 2.6 {angstrom} for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr{sup 303} within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe{sup 478} aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved {sup 216}QXXNN{sup 220} residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed {omega}-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

  12. Insight into the molecular composition of laboratory organic residues produced from interstellar/pre-cometary ice analogues using very high resolution mass spectrometry

    Science.gov (United States)

    Danger, G.; Fresneau, A.; Abou Mrad, N.; de Marcellus, P.; Orthous-Daunay, F.-R.; Duvernay, F.; Vuitton, V.; Le Sergeant d'Hendecourt, L.; Thissen, R.; Chiavassa, T.

    2016-09-01

    Experimental simulations in the laboratory may provide important information about the chemical evolution occurring in various astrophysical objects such as extraterrestrial ices. Interstellar or (pre)cometary ice analogues made of H2O, CH3OH, and NH3 at 77 K, when subjected to an energetic process (VUV photons, electrons or ions) and then warmed-up to room temperature, lead, in the laboratory, to the formation of an organic residue. In this paper we expand our previous analysis of the residues in order to obtain a better insight into their molecular content. Data analyses show that three different chemical groups are present in the residue in the negative electrospray ionization (ESI) mode: CHN, CHO and CHNOsbnd whereas only two groups are detected in the positive ESI mode: CHN and CHNO. In both cases, the CHNO group is the most abundant. The application of specific data treatment shows that residue mainly contains aliphatic linear molecules or cyclic structures connected to unsaturated chemical functions such as esters, carboxylic acids, amides or aldehydes. In lower abundances, some molecules do present aromatic structures. The comparison of our residue with organic compounds detected in the Murchison meteorite gives an interesting match, which suggests that laboratory simulation of interstellar ice chemistry is relevant to understand astrophysical organic matter evolution.

  13. Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibiotics mainly produced by Trichoderma spp.

    Science.gov (United States)

    Shi, Wei-Ling; Chen, Xiu-Lan; Wang, Li-Xia; Gong, Zhi-Ting; Li, Shuyu; Li, Chun-Long; Xie, Bin-Bin; Zhang, Wei; Shi, Mei; Li, Chuanyou; Zhang, Yu-Zhong; Song, Xiao-Yan

    2016-04-01

    Trichodermaspp. are well known biocontrol agents that produce a variety of antibiotics. Peptaibols are a class of linear peptide antibiotics mainly produced byTrichoderma Alamethicin, the most studied peptaibol, is reported as toxic to plants at certain concentrations, while the mechanisms involved are unclear. We illustrated the toxic mechanisms of peptaibols by studying the growth-inhibitory effect of Trichokonin VI (TK VI), a peptaibol fromTrichoderma longibrachiatumSMF2, onArabidopsisprimary roots. TK VI inhibited root growth by suppressing cell division and cell elongation, and disrupting root stem cell niche maintenance. TK VI increased auxin content and disrupted auxin response gradients in root tips. Further, we screened theArabidopsisTK VI-resistant mutanttkr1tkr1harbors a point mutation inGORK, which encodes gated outwardly rectifying K(+)channel proteins. This mutation alleviated TK VI-induced suppression of K(+)efflux in roots, thereby stabilizing the auxin gradient. Thetkr1mutant also resisted the phytotoxicity of alamethicin. Our results indicate that GORK channels play a key role in peptaibol-plant interaction and that there is an inter-relationship between GORK channels and maintenance of auxin homeostasis. The cellular and molecular insight into the peptaibol-induced inhibition of plant root growth advances our understanding ofTrichoderma-plant interactions. PMID:26850879

  14. Molecular and structural analysis of Legionella DotI gives insights into an inner membrane complex essential for type IV secretion

    Science.gov (United States)

    Kuroda, Takuya; Kubori, Tomoko; Thanh Bui, Xuan; Hyakutake, Akihiro; Uchida, Yumiko; Imada, Katsumi; Nagai, Hiroki

    2015-01-01

    The human pathogen Legionella pneumophila delivers a large array of the effector proteins into host cells using the Dot/Icm type IVB secretion system. Among the proteins composing the Dot/Icm system, an inner membrane protein DotI is known to be crucial for the secretion function but its structure and role in type IV secretion had not been elucidated. We report here the crystal structures of the periplasmic domains of DotI and its ortholog in the conjugation system of plasmid R64, TraM. These structures reveal a striking similarity to VirB8, a component of type IVA secretion systems, suggesting that DotI/TraM is the type IVB counterpart of VirB8. We further show that DotI and its partial paralog DotJ form a stable heterocomplex. R64 TraM, encoded by the conjugative plasmid lacking DotJ ortholog, forms a homo-hexamer. The DotI-DotJ complex is distinct from the core complex, which spans both inner and outer membranes to form a substrate conduit, and seems not to stably associate with the core complex. These results give insight into VirB8-family inner membrane proteins essential for type IV secretion and aid towards understanding the molecular basis of secretion systems essential for bacterial pathogenesis. PMID:26039110

  15. Non-destructive foraminiferal paleoclimatic proxies: A brief insight

    Digital Repository Service at National Institute of Oceanography (India)

    Saraswat, R.

    Non-Destructive Foraminiferal Paleoclimatic Proxies: A Brief Insight The knowledge of past climate can help us to understand imminent climatic changes. Oceans are the vast archives of past climate. Various indirect techniques termed as proxies...

  16. Climate change and Ecotone boundaries: Insights from a cellular automata ecohydrology model in a Mediterranean catchment with topography controlled vegetation patterns

    Science.gov (United States)

    Caracciolo, Domenico; Noto, Leonardo Valerio; Istanbulluoglu, Erkan; Fatichi, Simone; Zhou, Xiaochi

    2014-11-01

    Regions of vegetation transitions (ecotones) are known to be highly sensitive to climate fluctuations. In this study, the Cellular-Automata Tree Grass Shrub Simulator (CATGraSS) has been modified, calibrated and used with downscaled future climate scenarios to examine the role of climate change on vegetation patterns in a steep mountainous catchment (1.3 km2) located in Sicily, Italy. In the catchment, north-facing slopes are mostly covered by trees and grass, and south-facing slopes by Indian Fig opuntia and grass, with grasses dominating as elevation grows. CATGraSS simulates solar radiation, evapotranspiration, and soil moisture in space and time. Each model cell can hold a single plant type or can be bare soil. Plant competition is modeled explicitly through mortality and the establishment of individual plants in open spaces. In this study, CATGraSS is modified to account for heterogeneity in soil thickness and tested in the study catchment using the historical climate of the region. Predicted vegetation patterns are compared with those obtained from satellite images. Results of model under current climate underscore the importance of solar irradiance and soil thickness, especially in the uplands where soil is shallow, in determining vegetation composition over complex terrain. A stochastic weather generator is used to generate future climate change scenarios for the catchment by downscaling GCM realizations in space and time. Future increase in atmospheric CO2 concentration was considered through modifying the vegetation water use efficiency and stomatal resistance for our study site. Model results suggest that vegetation pattern is highly sensitive to temperature and rainfall variations provided by climate scenarios (30% reduction of the annual precipitation and a 2.8 °C increase of the mean annual temperature). Future climate change is predicted to bring a considerable reorganization of the plant composition following topographic patterns, leading to a

  17. Insight Into Climate Variations Of The Early Middle Eocene: High-Resolution Benthic Stable Isotope Data From Site 1408, Newfoundland Ridge

    OpenAIRE

    Wu, Fei

    2015-01-01

    The middle Eocene is a transitional period from the greenhouse early Eocene to the ice-house Eocene-Oligocene Transition. Due to lack of high-resolution records, the details of this long-term cooling trend are not clear. Low-resolution atmospheric CO2 records suggest declining, but highly variable levels during the middle Eocene which might have driven transient climate variations. However, high-resolution stable isotope records are lacking to document the true climate patterns over this peri...

  18. Molecular insights into Parkinson's disease

    OpenAIRE

    Thomas, Bobby; Beal, M. Flint

    2011-01-01

    Parkinson’s disease is a neurodegenerative movement disorder characterized by loss of midbrain dopaminergic neurons leading to motor abnormalities and autonomic dysfunctions. Despite intensive research, the etiology of Parkinson’s disease remains poorly understood leaving us with no effective therapeutic options. However, the recent identification of genes linked to heritable forms of Parkinson’s disease has revolutionized research in the field and has begun to provide new clues to disease pa...

  19. Compensatory role of double mutation N348I/M184V on nevirapine binding landscape: insight from molecular dynamics simulation.

    Science.gov (United States)

    Karubiu, Wilson; Bhakat, Soumendranath; Soliman, Mahmoud E S

    2014-10-01

    Non-nucleoside reverse transcriptase inhibitors (NNRTI) have emerged as gold standards in current anti-AIDS drug discovery and development by allosterically inhibiting HIV reverse transcriptase (HIV-RT). Connection sub-domain mutation, N348I and the M184V active site mutation decreases HIV-1 RT susceptibility to NNRTI, nevirapine (NVP), whereas concurrence of both mutations improves enzyme susceptibility to NVP. Molecular dynamics simulation and enhanced post-dynamics analyses were applied to gain molecular insight into occurrence of N348I, M184V and N348I/M184V double mutations and their effect on NVP binding landscape. Results showed that the presence of the double mutation (N348I/M184V) ameliorates the drastic effects of connection sub-domain mutation, N348I alone on NVP binding, which correlates with experimental findings. We showed that the binding of NVP to the NNRTI binding pocket (NNIBP) is drastically distorted in the presence of connection sub-domain mutation, N348I and may further explain the impaired motions of mutant RTs compared to the wild type. The residue based fluctuation further suggested that the occurrence of N348I decreased the overall flexibility of NVP-HIV-RT complex whereas concurrence of N348I/M184V double mutation restored the conformational flexibility as compared to single mutant. This phenomenon was further validated by the trends of binding free energy as well as the per-residue footprints which showed an increased ∆Gbind in case of N348I/M184V double mutant as compared to N348I variant. Further, for the first time residue interaction network highlighted the structural changes due to occurrence of M184V and N348I mutations which gives a conclusive evidence of these mutations. This work provides the most comprehensive analysis of NVP resistance and the impact of double (N348I/M184V) mutation to date from a dynamics perspective and provides information that should prove useful for understanding the drug resistance mechanism against

  20. Structural changes of humic acids from sinking organic matter and surface sediments investigated by advanced solid-state NMR: Insights into sources, preservation and molecularly uncharacterized components

    Science.gov (United States)

    Mao, Jingdong; Tremblay, Luc; Gagné, Jean-Pierre

    2011-12-01

    Knowledge of the structural changes that particulate organic matter (POM) undergoes in natural systems is essential for determining its reactivity and fate. In the present study, we used advanced solid-state NMR techniques to investigate the chemical structures of sinking particulate matter collected at different depths as well as humic acids (HAs) extracted from these samples and underlying sediments from the Saguenay Fjord and the St. Lawrence Lower Estuary (Canada). Compared to bulk POM, HAs contain more non-polar alkyls, aromatics, and aromatic C-O, but less carbohydrates (or carbohydrate-like structures). In the two locations studied, the C and N contents of the samples (POM and HAs) decreased with depth and after deposition onto sediments, leaving N-poor but O-enriched HAs and suggesting the involvement of partial oxidation reactions during POM microbial degradation. Advanced NMR techniques revealed that, compared to the water-column HAs, sedimentary HAs contained more protonated aromatics, non-protonated aromatics, aromatic C-O, carbohydrates (excluding anomerics), anomerics, OC q, O-C q-O, OCH, and OCH 3 groups, but less non-polar alkyls, NCH, and mobile CH 2 groups. These results are consistent with the relatively high reactivity of lipids and proteins or peptides. In contrast, carbohydrate-like structures were selectively preserved and appeared to be involved in substitution and copolymerization reactions. Some of these trends support the selective degradation (or selective preservation) theory. The results provide insights into mechanisms that likely contribute to the preservation of POM and the formation of molecules that escape characterization by traditional methods. Despite the depletion of non-polar alkyls with depth in HAs, a significant portion of their general structure survived and can be assigned to a model phospholipid. In addition, little changes in the connectivities of different functional groups were observed. Substituted and copolymerized

  1. COOH-Terminal Clustering of Autoantibody and T-Cell Determinants on the Structure of GAD65 Provide Insights Into the Molecular Basis of Autoreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Fenalti, Gustavo; Hampe, Christiane S.; Arafat, Yasir; Law, Ruby H.P.; Banga, J. Paul; Mackay, Ian R.; Whisstock, James C.; Buckle, Ashley M.; Rowley, Merrill J. (UWASH); (King’s College); (Monash)

    2008-11-19

    To gain structural insights into the autoantigenic properties of GAD65 in type 1 diabetes, we analyzed experimental epitope mapping data in the context of the recently determined crystal structures of GAD65 and GAD67, to allow 'molecular positioning' of epitope sites for B- and T-cell reactivity. Data were assembled from analysis of reported effects of mutagenesis of GAD65 on its reactivity with a panel of 11 human monoclonal antibodies (mAbs), supplemented by use of recombinant Fab to cross-inhibit reactivity with GAD65 by radioimmunoprecipitation of the same mAbs. COOH-terminal region on GAD65 was the major autoantigenic site. B-cell epitopes were distributed within two separate clusters around different faces of the COOH-terminal domain. Inclusion of epitope sites in the pyridoxal phosphate- and NH{sub 2}-terminal domains was attributed to the juxtaposition of all three domains in the crystal structure. Epitope preferences of different mAbs to GAD65 aligned with different clinical expressions of type 1 diabetes. Epitopes for four of five known reactive T-cell sequences restricted by HLA DRB1*0401 were aligned to solvent-exposed regions of the GAD65 structure and colocalized within the two B-cell epitope clusters. The continuous COOH-terminal epitope region of GAD65 was structurally highly flexible and therefore differed markedly from the equivalent region of GAD67. Structural features could explain the differing antigenicity, and perhaps immunogenicity, of GAD65 versus GAD67. The proximity of B- and T-cell epitopes within the GAD65 structure suggests that antigen-antibody complexes may influence antigen processing by accessory cells and thereby T-cell reactivity.

  2. Structural models of zebrafish (Danio rerio NOD1 and NOD2 NACHT domains suggest differential ATP binding orientations: insights from computational modeling, docking and molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Jitendra Maharana

    Full Text Available Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 and NOD2 are cytosolic pattern recognition receptors playing pivotal roles in innate immune signaling. NOD1 and NOD2 recognize bacterial peptidoglycan derivatives iE-DAP and MDP, respectively and undergoes conformational alternation and ATP-dependent self-oligomerization of NACHT domain followed by downstream signaling. Lack of structural adequacy of NACHT domain confines our understanding about the NOD-mediated signaling mechanism. Here, we predicted the structure of NACHT domain of both NOD1 and NOD2 from model organism zebrafish (Danio rerio using computational methods. Our study highlighted the differential ATP binding modes in NOD1 and NOD2. In NOD1, γ-phosphate of ATP faced toward the central nucleotide binding cavity like NLRC4, whereas in NOD2 the cavity was occupied by adenine moiety. The conserved 'Lysine' at Walker A formed hydrogen bonds (H-bonds and Aspartic acid (Walker B formed electrostatic interaction with ATP. At Sensor 1, Arg328 of NOD1 exhibited an H-bond with ATP, whereas corresponding Arg404 of NOD2 did not. 'Proline' of GxP motif (Pro386 of NOD1 and Pro464 of NOD2 interacted with adenine moiety and His511 at Sensor 2 of NOD1 interacted with γ-phosphate group of ATP. In contrast, His579 of NOD2 interacted with the adenine moiety having a relatively inverted orientation. Our findings are well supplemented with the molecular interaction of ATP with NLRC4, and consistent with mutagenesis data reported for human, which indicates evolutionary shared NOD signaling mechanism. Together, this study provides novel insights into ATP binding mechanism, and highlights the differential ATP binding modes in zebrafish NOD1 and NOD2.

  3. Early to middle Miocene climate evolution: New insights from IODP Sites U1335, U1337 and U1338 (eastern equatorial Pacific Ocean)

    Science.gov (United States)

    Kochhann, Karlos G. D.; Holbourn, Ann; Kuhnt, Wolfgang; Lyle, Mitch; Raffi, Isabella; Channell, James E.; Andersen, Nils

    2015-04-01

    The lower to middle Miocene (~20 to 13 Ma) carbonate-rich sedimentary successions recovered at Integrated Ocean Drilling Program (IODP) Sites U1335, U1337 and U1338 allow unsurpassed resolution over the Climatic Optimum (16.9-14.7 Ma) and the transition into a colder climate mode after 13.9 Ma with re-establishment of permanent Antarctic ice sheets. High-resolution (1-10 kyr) stable carbon (δ13C) and oxygen (δ18O) isotopes of well-preserved epibenthic foraminifera (Cibicidoides mundulus and Planulina wuellerstorfi) from these three sites show that the Climatic Optimum was characterized by high-amplitude climate variations and intense perturbations of the carbon cycle. Episodes of peak warmth coincided with transient shoaling of the carbonate compensation depth and enhanced carbonate dissolution in the deep ocean. The U1335 and U1337 records additionally reveal that the rapid global warming and/or polar ice melting event, marking the onset of the Climatic Optimum at ~16.9 Ma, was coupled to a massive increase in carbonate dissolution, indicated by sharp drops in carbonate percentages and accumulation rates and by the fragmentation or complete dissolution of planktonic foraminifers. After ~14.7 Ma, stepwise global cooling, culminating with extensive ice growth over Antarctica at ~13.8 Ma, coincide with enhanced opal and benthic foraminiferal accumulation rates, suggesting that increased siliceous productivity and organic carbon burial may have contributed to CO2 drawdown. Integration of age models derived from orbitally-tuned, high-resolution isotopes, biostratigraphic data and magnetic reversals allows further constraints on the temporal sequence of events and helps unravel the drivers of early to middle Miocene climate variations.

  4. Glacial climate transitions in the Southern Hemisphere - New insights from cosmogenic 10Be in rocks and 14C in tree-rings

    International Nuclear Information System (INIS)

    Full text: The study of global climate change recorded and archived in corals, tree-rings, glacial deposits, ocean sediments and ice cores reveals a complex scale of variations ranging from major glacial cycles (100,000 years), millennial (1,000 years) timescales and even decadal changes (i.e. ENSO). 'Global patterns' of climate cycles are inferred principally from Northern Hemisphere records and modelling approaches. For the major glacial-interglacial cycles this seems to be reliable - however data is now emerging that on the millennial scale of climate change particularly over the Last Glacial-Interglacial Transition (20,000 to 10,000 years ago) and through the Holocene, things are not so simple, let alone 'global'. Critical questions are now being asked as to the synchronicity, intensity and mode of abrupt climate patterns across Earth's hemispheres. However, with a paucity of Southern Hemisphere studies, answers are not readily available. Long-lived cosmogenic radioisotopes, such as 10Be, 14C, 26Al and 36Cl, are produced by cosmic ray bombardment of Earth's atmosphere and lithosphere. The measurement by Accelerator Mass Spectrometry of concentration profiles of these radioactive 'clocks' and 'tracers' in climate archives is emerging as key parameters to provide the essential chronological frameworks and rates of climate processes to address these vexing questions. This talk will present 2 examples of cosmogenic isotopes in the study of Southern Hemisphere climate change records. The first relates to application of in-situ produced 10Be and 26Al in glacially transported surface rocks to determine the chronology of glacial cycles in Tasmania and New Zealand during the last deglaciation. The Younger Dryas (YD) is a major short term and intense climatic reversal towards colder temperatures occurring between 11,500-12,800 cal year BP superimposed on the last deglaciation. Its presence has now been identified in most, if not all, of the northern hemisphere archives

  5. Using long-term ecosystem service and biodiversity data to study the impacts and adaptation options in response to climate change: insights from the global ILTER sites network

    Czech Academy of Sciences Publication Activity Database

    Vihervaara, P.; D'Amato, D.; Forsius, M.; Angelstam, P.; Baessler, C.; Balvanera, P.; Boldgiv, B.; Bourgeron, P.; Dick, J.; Kanka, R.; Klotz, S.; Maass, M.; Melecis, V.; Petřík, Petr; Shibata, H.; Tang, J.; Thompson, J.; Zacharias, S.

    2013-01-01

    Roč. 5, č. 1 (2013), s. 53-66. ISSN 1877-3435 R&D Projects: GA MŠk 7AMB12SK156 Institutional support: RVO:67985939 Keywords : climate change * long-term ecological monitoring * prmanen research plot Subject RIV: EF - Botanics Impact factor: 2.758, year: 2013

  6. Terrestrial carbon cycle responses to drought and climate stress: New insights using atmospheric observations of CO2 and delta13C

    Science.gov (United States)

    Alden, Caroline B.

    Atmospheric concentrations of carbon dioxide (CO2) continue to rise well into the second decade of the new millennium, in spite of broad-scale human understanding of the impacts of fossil fuel emissions on the earth's climate. Natural sinks for CO2 that are relevant on human time scales---the world's oceans and land biosphere---appear to have kept pace with emissions. The continuously increasing strength of the land biosphere sink for CO2 is surpassing expectations given our understanding of the CO2 fertilization and warming effects on the balance between photosynthesis and respiration, especially in the face of ongoing forest degradation. The climate and carbon cycle links between the atmosphere and land biosphere are not well understood, especially at regional (100 km to 10,000 km) scales. The climate modulating effects of changing plant stomatal conductance in response to temperature and water availability is a key area of uncertainty. Further, the differential response to climate change of C3 and C4 plant functional types is not well known at regional scales. This work outlines the development of a novel application of atmospheric observations of delta13C of CO2 to investigate the links between climate and water and carbon cycling and the integrated responses of C3 and C4 ecosystems to climate variables. A two-step Bayesian batch inversion for 3-hourly, 1x1º CO2 fluxes (step one), and for 3-hourly 1x1º delta13C of recently assimilated carbon (step two) is created here for the first time, and is used to investigate links between regional climate indicators and changes in delta13C of the biosphere. Results show that predictable responses of regional-scale, integrated plant discrimination to temperature, precipitation and relative humidity anomalies can be recovered from atmospheric signals. Model development, synthetic data simulations to test sensitivity, and results for the year 2010 are presented here. This dissertation also includes two other applications

  7. Oxygen isotope ratios (18O/16O) of hemicellulose-derived sugar biomarkers in plants, soils and sediments as paleoclimate proxy II: Insight from a climate transect study

    Science.gov (United States)

    Tuthorn, Mario; Zech, Michael; Ruppenthal, Marc; Oelmann, Yvonne; Kahmen, Ansgar; Valle, Héctor Francisco del; Wilcke, Wolfgang; Glaser, Bruno

    2014-02-01

    The oxygen isotopic composition of precipitation (δ18Oprec) is well known to be a valuable (paleo-)climate proxy. Paleosols and sediments and hemicelluloses therein have the potential to serve as archives recording the isotopic composition of paleoprecipitation. In a companion paper (Zech et al., 2014) we investigated δ18Ohemicellulose values of plants grown under different climatic conditions in a climate chamber experiment. Here we present results of compound-specific δ18O analyses of arabinose, fucose and xylose extracted from modern topsoils (n = 56) along a large humid-arid climate transect in Argentina in order to answer the question whether hemicellulose biomarkers in soils reflect δ18Oprec. The results from the field replications indicate that the homogeneity of topsoils with regard to δ18Ohemicellulose is very high for most of the 20 sampling sites. Standard deviations for the field replications are 1.5‰, 2.2‰ and 1.7‰, for arabinose, fucose and xylose, respectively. Furthermore, all three hemicellulose biomarkers reveal systematic and similar trends along the climate gradient. However, the δ18Ohemicellulose values (mean of the three sugars) do not correlate positively with δ18Oprec (r = -0.54, p fucose and xylose do not simply reflect δ18Oprec but rather δ18Oleaf water. The correlation between measured δ18Ohemicellulose and modeled δ18Oleaf water is highly significant (r = 0.81, p < 0.001, n = 20). This finding can be attributed to the evaporative 18O enrichment of leaf water during transpiration. Model sensitivity tests using a Péclet-modified Craig-Gordon (PMCG) model corroborate that relative air humidity is a very rigorous climate parameter influencing δ18Oleaf water, whereas temperature is of minor importance. While oxygen exchange and degradation effects on δ18O values of hemicelluloses sugar biomarkers seem to be negligible (Zech et al., 2012), further effects that need to be considered when interpreting δ18Ohemicellulose

  8. Climate change and human disturbance can lead to local extinction of Alpine rock ptarmigan: new insight from the western Italian Alps.

    Directory of Open Access Journals (Sweden)

    Simona Imperio

    Full Text Available Alpine grouses are particularly vulnerable to climate change due to their adaptation to extreme conditions and to their relict distributions in the Alps where global warming has been particularly marked in the last half century. Grouses are also currently threatened by habitat modification and human disturbance, and an assessment of the impact of multiple stressors is needed to predict the fate of Alpine populations of these birds in the next decades. We estimated the effect of climate change and human disturbance on a rock ptarmigan population living in the western Italian Alps by combining an empirical population modelling approach and stochastic simulations of the population dynamics under the a1B climate scenario and two different disturbance scenarios, represented by the development of a ski resort, through 2050.The early appearance of snow-free ground in the previous spring had a favorable effect on the rock ptarmigan population, probably through a higher reproductive success. On the contrary, delayed snowfall in autumn had a negative effect possibly due to a mismatch in time to molt to white winter plumage which increases predation risk. The regional climate model PROTHEUS does not foresee any significant change in snowmelt date in the study area, while the start date of continuous snow cover is expected to be significantly delayed. The net effect in the stochastic projections is a more or less pronounced (depending on the model used decline in the studied population. The addition of extra-mortality due to collision with ski-lift wires led the population to fatal consequences in most projections. Should these results be confirmed by larger studies the conservation of Alpine populations would deserve more attention. To counterbalance the effects of climate change, the reduction of all causes of death should be pursued, through a strict preservation of the habitats in the present area of occurrence.

  9. Climate change and human disturbance can lead to local extinction of Alpine rock ptarmigan: new insight from the western Italian Alps.

    Science.gov (United States)

    Imperio, Simona; Bionda, Radames; Viterbi, Ramona; Provenzale, Antonello

    2013-01-01

    Alpine grouses are particularly vulnerable to climate change due to their adaptation to extreme conditions and to their relict distributions in the Alps where global warming has been particularly marked in the last half century. Grouses are also currently threatened by habitat modification and human disturbance, and an assessment of the impact of multiple stressors is needed to predict the fate of Alpine populations of these birds in the next decades. We estimated the effect of climate change and human disturbance on a rock ptarmigan population living in the western Italian Alps by combining an empirical population modelling approach and stochastic simulations of the population dynamics under the a1B climate scenario and two different disturbance scenarios, represented by the development of a ski resort, through 2050.The early appearance of snow-free ground in the previous spring had a favorable effect on the rock ptarmigan population, probably through a higher reproductive success. On the contrary, delayed snowfall in autumn had a negative effect possibly due to a mismatch in time to molt to white winter plumage which increases predation risk. The regional climate model PROTHEUS does not foresee any significant change in snowmelt date in the study area, while the start date of continuous snow cover is expected to be significantly delayed. The net effect in the stochastic projections is a more or less pronounced (depending on the model used) decline in the studied population. The addition of extra-mortality due to collision with ski-lift wires led the population to fatal consequences in most projections. Should these results be confirmed by larger studies the conservation of Alpine populations would deserve more attention. To counterbalance the effects of climate change, the reduction of all causes of death should be pursued, through a strict preservation of the habitats in the present area of occurrence. PMID:24260581

  10. Molecular characterization of UGT94F2 and UGT86C4, two glycosyltransferases from Picrorhiza kurrooa: comparative structural insight and evaluation of substrate recognition.

    Directory of Open Access Journals (Sweden)

    Wajid Waheed Bhat

    Full Text Available Uridine diphosphate glycosyltransferases (UGTs are pivotal in the process of glycosylation for decorating natural products with sugars. It is one of the versatile mechanisms in determining chemical complexity and diversity for the production of suite of pharmacologically active plant natural products. Picrorhiza kurrooa is a highly reputed medicinal herb known for its hepato-protective properties which are attributed to a novel group of iridoid glycosides known as picrosides. Although the plant is well studied in terms of its pharmacological properties, very little is known about the biosynthesis of these important secondary metabolites. In this study, we identified two family-1 glucosyltransferases from P. kurrooa. The full length cDNAs of UGT94F4 and UGT86C4 contained open reading frames of 1455 and 1422 nucleotides, encoding polypeptides of 484 and 473 amino acids respectively. UGT94F2 and UGT86C4 showed differential expression pattern in leaves, rhizomes and inflorescence. To elucidate whether the differential expression pattern of the two Picrorhiza UGTs correlate with transcriptional regulation via their promoters and to identify elements that could be recognized by known iridoid-specific transcription factors, upstream regions of each gene were isolated and scanned for putative cis-regulatory elements. Interestingly, the presence of cis-regulatory elements within the promoter regions of each gene correlated positively with their expression profiles in response to different phytohormones. HPLC analysis of picrosides extracted from different tissues and elicitor-treated samples showed a significant increase in picroside levels, corroborating well with the expression profile of UGT94F2 possibly indicating its implication in picroside biosynthesis. Using homology modeling and molecular docking studies, we provide an insight into the donor and acceptor specificities of both UGTs identified in this study. UGT94F2 was predicted to be an iridoid

  11. Molecular insights into how a deficiency of amylose affects carbon allocation – carbohydrate and oil analyses and gene expression profiling in the seeds of a rice waxy mutant

    Directory of Open Access Journals (Sweden)

    Zhang Ming-Zhou

    2012-12-01

    Full Text Available Abstract Background Understanding carbon partitioning in cereal seeds is of critical importance to develop cereal crops with enhanced starch yields for food security and for producing specified end-products high in amylose, β-glucan, or fructan, such as functional foods or oils for biofuel applications. Waxy mutants of cereals have a high content of amylopectin and have been well characterized. However, the allocation of carbon to other components, such as β-glucan and oils, and the regulation of the altered carbon distribution to amylopectin in a waxy mutant are poorly understood. In this study, we used a rice mutant, GM077, with a low content of amylose to gain molecular insight into how a deficiency of amylose affects carbon allocation to other end products and to amylopectin. We used carbohydrate analysis, subtractive cDNA libraries, and qPCR to identify candidate genes potentially responsible for the changes in carbon allocation in GM077 seeds. Results Carbohydrate analysis indicated that the content of amylose in GM077 seeds was significantly reduced, while that of amylopectin significantly rose as compared to the wild type BP034. The content of glucose, sucrose, total starch, cell-wall polysaccharides and oil were only slightly affected in the mutant as compared to the wild type. Suppression subtractive hybridization (SSH experiments generated 116 unigenes in the mutant on the wild-type background. Among the 116 unigenes, three, AGP, ISA1 and SUSIBA2-like, were found to be directly involved in amylopectin synthesis, indicating their possible roles in redirecting carbon flux from amylose to amylopectin. A bioinformatics analysis of the putative SUSIBA2-like binding elements in the promoter regions of the upregulated genes indicated that the SUSIBA2-like transcription factor may be instrumental in promoting the carbon reallocation from amylose to amylopectin. Conclusion Analyses of carbohydrate and oil fractions and gene expression

  12. Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80

    Directory of Open Access Journals (Sweden)

    Meysam Mobasheri

    2015-12-01

    Full Text Available Amphotericin B (AmB and Nystatin (Nys are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG molecular dynamics (MD simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80 to gain insight into the behavior of these polyene antibiotics (PAs in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i the dominant kinetics of drugs encapsulation over self-association; (ii significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii monomeric solubilization of the drugs; (iv contribution of drug-micelle interactions to the solubilization; (v suppressed diffusivity of the encapsulated drugs; (vi high loading capacity of the micelle; and (vii the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i limited diffusion of water; and (ii perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug

  13. Vegetation and climate history in arid western China during MIS2: New insights from pollen and grain-size data of the Balikun Lake, eastern Tien Shan

    Science.gov (United States)

    Zhao, Yongtao; An, Cheng-Bang; Mao, Limi; Zhao, Jiaju; Tang, Lingyu; Zhou, Aifeng; Li, Hu; Dong, Weimiao; Duan, Futao; Chen, Fahu

    2015-10-01

    Marine Isotope Stage (MIS) 2 is mostly a cold period encompassing the Last Glacial Maximum (LGM), but the regional expression of MIS2 in arid areas of China is not well known. In this paper, we use high-resolution lacustrine pollen and grain-size records from Balikun Lake to infer vegetation, lake evolution, and climate in arid western China during MIS2. Our results suggest that: 1) the regional vegetation around Balikun was mainly dominated by desert and/or desert-steppe, and Balikun Lake was relatively shallow and experienced high aeolian input during MIS2; 2) distinctive runoff from mountain glacial meltwater in the eastern parts of the Balikun basin caused a high relative abundance of Artemisia pollen during the LGM (26.5-19.2 cal kyr BP), while simultaneously the desert areas expanded as indicated by the high abundance of desert shrubs (e.g., Elaeagnaceae, Rhamnaceae, Hippophae). This cold and dry LGM climate triggered a substantial lowering of lake level; 3) an extremely cold and dry climate prevailing from 17.0 to 15.2 cal kyr BP, correlated with Heinrich event 1 (H1), would explain the low vegetation cover found then; and 4) the warm and humid Bølling/Allerød interstadial (BA: ca. 15-ca. 13 cal kyr BP) is clearly recorded in the Balikun region by the development of wetland herb communities (e.g., Poaceae, Cyperaceae, Typha), and the lake level rose due to increased runoff. Our results challenge the traditional view of cold and wet climatic conditions and high lake levels in arid western China during the LGM, and we propose that changes in local temperature modulated by July insolation was an indispensable factor in triggering vegetation evolution in the Balikun region during MIS2.

  14. Criminality and climate change

    Science.gov (United States)

    White, Rob

    2016-08-01

    The impacts of climate change imply a reconceptualization of environment-related criminality. Criminology can offer insight into the definitions and dynamics of this behaviour, and outline potential areas of redress.

  15. Will anticipated future climatic conditions affect belowground C utilization? - Insights into the role of microbial functional groups in a temperate heath/grassland.

    Science.gov (United States)

    Reinsch, Sabine; Michelsen, Anders; Sárossy, Zsuzsa; Egsgaard, Helge; Kappel Schmidt, Inger; Jakobsen, Iver; Ambus, Per

    2013-04-01

    The global terrestrial soil organic matter stock is the biggest terrestrial carbon pool (1500 Pg C) of which about 4 % is turned over annually. Thus, terrestrial ecosystems have the potential to accelerate or diminish atmospheric climate change effects via belowground carbon processes. We investigated the effect of elevated CO2 (510 ppm), prolonged spring/summer droughts and increased temperature (1 ˚C) on belowground carbon allocation and on the recovery of carbon by the soil microbial community. An in-situ 13C-carbon pulse-labeling experiment was carried out in a temperate heath/grassland (Denmark) in May 2011. Recently assimilated 13C-carbon was traced into roots, soil and microbial biomass 1, 2 and 8 days after pulse-labeling. The importance of the microbial community in C utilization was investigated using 13C enrichment patterns in microbial functional groups on the basis of phospholipid fatty acids (PLFAs) in roots. Gram-negative and gram-positive bacteria were distinguished from the decomposer groups of actinomycetes (belonging to the group of gram-positive bacteria) and saprophytic fungi. Mycorrhizal fungi specific PLFAs were not detected probably due to limited sample size in combination with restricted sensitivity of the used GC-c-IRMS setup. Climate treatments did not affect 13C allocation into roots, soil and microbial biomass carbon and also the total microbial biomass size stayed unchanged as frequently observed. However, climate treatments changed the composition of the microbial community: elevated CO2 significantly reduced the abundance of gram-negative bacteria (17:0cy) but did not affect the abundance of decomposers. Drought favored the bacterial community whereas increased temperatures showed reduced abundance of gram-negative bacteria (19:0cy) and changed the actinomycetes community (10Me16:0, 10Me18:0). However, not only the microbial community composition was affected by the applied climatic conditions, but also the activity of microbial

  16. Toward evaluating the effect of climate change on investments in the water resources sector: insights from the forecast and analysis of hydrological indicators in developing countries

    Science.gov (United States)

    Strzepek, Kenneth; Jacobsen, Michael; Boehlert, Brent; Neumann, James

    2013-12-01

    The World Bank has recently developed a method to evaluate the effects of climate change on six hydrological indicators across 8951 basins of the world. The indicators are designed for decision-makers and stakeholders to consider climate risk when planning water resources and related infrastructure investments. Analysis of these hydrological indicators shows that, on average, mean annual runoff will decline in southern Europe; most of Africa; and in southern North America and most of Central and South America. Mean reference crop water deficit, on the other hand, combines temperature and precipitation and is anticipated to increase in nearly all locations globally due to rising global temperatures, with the most dramatic increases projected to occur in southern Europe, southeastern Asia, and parts of South America. These results suggest overall guidance on which regions to focus water infrastructure solutions that could address future runoff flow uncertainty. Most important, we find that uncertainty in projections of mean annual runoff and high runoff events is higher in poorer countries, and increases over time. Uncertainty increases over time for all income categories, but basins in the lower and lower-middle income categories are forecast to experience dramatically higher increases in uncertainty relative to those in the upper-middle and upper income categories. The enhanced understanding of the uncertainty of climate projections for the water sector that this work provides strongly support the adoption of rigorous approaches to infrastructure design under uncertainty, as well as design that incorporates a high degree of flexibility, in response to both risk of damage and opportunity to exploit water supply ‘windfalls’ that might result, but would require smart infrastructure investments to manage to the greatest benefit.

  17. Toward evaluating the effect of climate change on investments in the water resources sector: insights from the forecast and analysis of hydrological indicators in developing countries

    International Nuclear Information System (INIS)

    The World Bank has recently developed a method to evaluate the effects of climate change on six hydrological indicators across 8951 basins of the world. The indicators are designed for decision-makers and stakeholders to consider climate risk when planning water resources and related infrastructure investments. Analysis of these hydrological indicators shows that, on average, mean annual runoff will decline in southern Europe; most of Africa; and in southern North America and most of Central and South America. Mean reference crop water deficit, on the other hand, combines temperature and precipitation and is anticipated to increase in nearly all locations globally due to rising global temperatures, with the most dramatic increases projected to occur in southern Europe, southeastern Asia, and parts of South America. These results suggest overall guidance on which regions to focus water infrastructure solutions that could address future runoff flow uncertainty. Most important, we find that uncertainty in projections of mean annual runoff and high runoff events is higher in poorer countries, and increases over time. Uncertainty increases over time for all income categories, but basins in the lower and lower-middle income categories are forecast to experience dramatically higher increases in uncertainty relative to those in the upper-middle and upper income categories. The enhanced understanding of the uncertainty of climate projections for the water sector that this work provides strongly support the adoption of rigorous approaches to infrastructure design under uncertainty, as well as design that incorporates a high degree of flexibility, in response to both risk of damage and opportunity to exploit water supply ‘windfalls’ that might result, but would require smart infrastructure investments to manage to the greatest benefit. (letter)

  18. Influence of high-order mechanics on simulation of glacier response to climate change: insights from Haig Glacier, Canadian Rocky Mountains

    Directory of Open Access Journals (Sweden)

    S. Adhikari

    2013-04-01

    Full Text Available Evolution of glaciers in response to climate change has mostly been simulated using simplified dynamical models. Because these models do not account for the influence of high-order physics, corresponding results may exhibit some biases. For Haig Glacier in the Canadian Rocky Mountains, we test this hypothesis by comparing simulation results obtained from 3-D numerical models that deal with different assumptions concerning ice-flow physics, ranging from simple shear-deformation to comprehensive Stokes flow. In glacier retreat scenarios, we find a minimal role of high-order mechanics in glacier evolution, as geometric effects at our site (the presence of an overdeepened bed result in limited horizontal movement of ice (flow speed on the order of a few meters per year. Consequently, high-order and reduced models all predict that Haig Glacier ceases to exist by ca. 2080 under ongoing climate warming. The influence of high-order mechanics is evident, however, in glacier advance scenarios, where ice speeds are greater and ice dynamical effects become more important. To generalize these findings for other glacier applications, we advise that high-order mechanics are important and therefore should be considered while modelling the evolution of active glaciers. Reduced model predictions may, however, be adequate for other glaciologic and topographic settings, particularly where flow speeds are low.

  19. Late Quaternary changes in bat palaeobiodiversity and palaeobiogeography under climatic and anthropogenic pressure: new insights from Marie-Galante, Lesser Antilles

    Science.gov (United States)

    Stoetzel, Emmanuelle; Royer, Aurélien; Cochard, David; Lenoble, Arnaud

    2016-07-01

    Data on Lesser Antillean Late Quaternary fossil bat assemblages remains limited, leading to their general exclusion from studies focusing on Caribbean bat palaeobiodiversity and palaeobiogeography. Additionally, the role of climatic versus human pressure driving changes in faunal communities remains poorly understood. Here we describe a fossil bat assemblage from Blanchard Cave on Marie-Galante in the Lesser Antilles, which produced numerous bat remains from a well-dated, stratified context. Our study reveals the occurrence of at least 12 bat species during the Late Pleistocene and Early Holocene on Marie-Galante, whereas only eight species are currently known on the island. Among these 12 species, six are extirpated and one is extinct. Faunal changes within the Blanchard sequence indicate variations in Pleistocene bat species representation in the Lesser Antilles to have been influenced by climatic conditions, with "northern species" (Greater Antilles) favored during glacial conditions and "southern species" (southern Lesser Antilles) during interglacial events. However, few species disappeared at the end of the Late Pleistocene, with most of the extinction/extirpation events occurring during the Holocene. This pattern suggests human activities in the Lesser Antilles to have played a major role in bat turnover during the late Holocene.

  20. Charred wood remains in the natufian sequence of el-Wad terrace (Israel): New insights into the climatic, environmental and cultural changes at the end of the Pleistocene

    Science.gov (United States)

    Caracuta, Valentina; Weinstein-Evron, Mina; Yeshurun, Reuven; Kaufman, Daniel; Tsatskin, Alexander; Boaretto, Elisabetta

    2016-01-01

    The major social and economic changes associated with the rise of a sedentary lifestyle and the gradual transition to food production in the southern Levant are often considered to have been triggered by climate changes at the end of the Pleistocene (∼20,000-11,000 years BP). This explanation, however, is biased by the scarcity of high-resolution climate records directly associated with human activity and the lack of refined palaeoecological studies from multi-stratified sites in the area. Here, we present the results of an anthracological analysis, carried out on charcoals collected along a continuous column of archaeological sediments in the Natufian site of el-Wad Terrace (Mount Carmel, Israel). We also present the carbon isotopes analysis of 14C-dated archaeological remains of Amygdalus sp. The analyses of charcoal shows the predominance of an oak forest including Quercus calliprinos and ithaburensis around the site during the Early Natufian building phase (∼14,600-13,700 cal BP), and the values of Δ13C point to a high rainfall rate. This period is followed by a marked decrease in the local rainfall between ∼13,700 and 12,000 cal BP). The reduction, culturally associated with the latest Early Natufian and the Late Natufian, is independently recorded by the speleothems of the region: Soreq Cave and Jerusalem Cave. This period incorporates an increase in drought tolerant species such as Amygdalus sp. Thermo-Mediterranean species, such as Olea europaea and Ceratonia siliqua, as well as Pistacia palaestina, which dominate the modern landscape, become established in the Holocene. We conclude that the Natufian settlement at el-Wad Terrace flourished in the context of oak forests, and subsequently occupation intensity decreased in concurrence to the drying trend. This shift does not correspond to the cultural typology (i.e. Early Natufian vs. Late Natufian). Human response to climate change at the terminal Pleistocene Levant was multifaceted and localized. Its

  1. Litter decomposition over broad spatial and long time scales investigated by advanced solid-state NMR: insight into effects of climate, litter quality, and time

    Science.gov (United States)

    Mao, J.; Chen, N.; Harmon, M. E.; Li, Y.; Cao, X.; Chappell, M.

    2012-12-01

    Advanced 13C solid-state NMR techniques were employed to study the chemical structural changes of litter decomposition across broad spatial and long time scales. The fresh and decomposed litter samples of four species (Acer saccharum (ACSA), Drypetes glauca (DRGL), Pinus resinosa (PIRE), and Thuja plicata (THPL)) incubated for up to 10 years at four sites under different climatic conditions (from Arctic to tropical forest) were examined. Decomposition generally led to an enrichment of cutin and surface wax materials, and a depletion of carbohydrates causing overall composition to become more similar compared with original litters. However, the changes of main constituents in the four litters were inconsistent with the four litters following different pathways of decomposition at the same site. As decomposition proceeded, waxy materials decreased at the early stage and then gradually increased in PIRE; DRGL showed a significant depletion of lignin and tannin while the changes of lignin and tannin were relative small and inconsistent for ACSA and THPL. In addition, the NCH groups, which could be associated with either fungal cell wall chitin or bacterial wall petidoglycan, were enriched in all litters except THPL. Contrary to the classic lignin-enrichment hypothesis, DRGL with low-quality C substrate had the highest degree of composition changes. Furthermore, some samples had more "advanced" compositional changes in the intermediate stage of decomposition than in the highly-decomposed stage. This pattern might be attributed to the formation of new cross-linking structures, that rendered substrates more complex and difficult for enzymes to attack. Finally, litter quality overrode climate and time factors as a control of long-term changes of chemical composition.

  2. What can scientific practice look like in a classroom? Insights from scientists' critique of high school students' climate change argumentation practice

    Science.gov (United States)

    Walsh, E.; McGowan, V. C.

    2015-12-01

    The Next Generation Science Standards promote a vision in which learners engage in authentic knowledge in practice to tackle personally consequential science problems in the classroom. However, there is not yet a clear understanding amongst researchers and educators of what authentic practice looks like in a classroom and how this can be accomplished. This study explores these questions by examining interactions between scientists and students on a social media platform during two pilot enactments of a project-based curriculum focusing on the ecological impacts of climate change. During this unit, scientists provided feedback to students on infographics, visual representations of scientific information meant to communicate to an audience about climate change. We conceptualize the feedback and student work as boundary objects co-created by students and scientists moving between the school and scientific contexts, and analyze the structure and content of the scientists' feedback. We find that when giving feedback on a particular practice (e.g. argumentation), scientists would provide avenues, critiques and questions that incorporated many other practices (e.g. data analysis, visual communication); thus, scientists encouraged students to participate systemically in practices instead of isolating one particular practice. In addition, scientists drew attention to particular habits of mind that are valued in the scientific community and noted when students' work aligned with scientific values. In this way, scientists positioned students as capable of participating "scientifically." While traditionally, incorporating scientific inquiry in a classroom has emphasized student experimentation and data generation, in this work, we found that engaging with scientists around established scientific texts and data sets provided students with a platform for developing expertise in other important scientific practices during argment construction.

  3. Oxygen isotope ratios (18O/16O) of hemicellulose-derived sugar biomarkers in plants, soils and sediments as paleoclimate proxy I: Insight from a climate chamber experiment

    Science.gov (United States)

    Zech, Michael; Mayr, Christoph; Tuthorn, Mario; Leiber-Sauheitl, Katharina; Glaser, Bruno

    2014-02-01

    The oxygen isotopic composition of cellulose is a valuable proxy in paleoclimate research. However, its application to sedimentary archives is challenging due to extraction and purification of cellulose. Here we present compound-specific δ18O results of hemicellulose-derived sugar biomarkers determined using gas chromatography-pyrolysis-isotope ratio mass spectrometry, which is a method that overcomes the above-mentioned analytical challenges. The biomarkers were extracted from stem material of different plants (Eucalyptus globulus, Vicia faba and Brassica oleracea) grown in climate chamber experiments under different climatic conditions. The δ18O values of arabinose and xylose range from 31.4‰ to 45.9‰ and from 28.7‰ to 40.8‰, respectively, and correlate highly significantly with each other (R = 0.91, p hemicellulose-derived sugar biomarkers, like cellulose, reflect the oxygen isotopic composition of plant source water altered by climatically controlled evapotranspirative 18O enrichment of leaf water. While relative air humidity controls most rigorously the evapotranspirative 18O enrichment, the direct temperature effect is less important. However, temperature can indirectly exert influence via plant physiological reactions, namely by influencing the transpiration rate which affects δ18Oleaf water due to the Péclet effect. In a companion paper (Tuthorn et al., this issue) we demonstrate the applicability of the hemicellulose-derived sugar biomarker δ18O method to soils and provide evidence from a climate transect study confirming that relative air humidity exerts the dominant control on evapotranspirative 18O enrichment of leaf water. Finally, we present a conceptual model for the interpretation of δ18Ohemicellulose records and propose that a combined δ18Ohemicellulose and δ2Hn-alkane biomarker approach is promising for disentangling δ18Oprecipitation variability from evapotranspirative 18O enrichment variability in future paleoclimate studies

  4. The "dirty weather" diaries of Reverend Richard Davis: insights about early colonial-era meteorology and climate variability for northern New Zealand, 1839-1851

    Science.gov (United States)

    Lorrey, Andrew M.; Chappell, Petra R.

    2016-03-01

    Reverend Richard Davis (1790-1863) was a colonial-era missionary stationed in the Far North of New Zealand who was a key figure in the early efforts of the Church Mission Society. He kept meticulous meteorological records for the early settlements of Waimate North and Kaikohe, and his observations are preserved in a two-volume set in the Sir George Grey Special Collections in the Auckland Central Library. The Davis diary volumes are significant because they constitute some of the earliest land-based meteorological measurements that were continually chronicled for New Zealand. The diary measurements cover nine years within the 1839-1851 time span that are broken into two parts: 1839-1844 and 1848-1851. Davis' meteorological recordings include daily 9 a.m. and noon temperatures and midday pressure measurements. Qualitative comments in the diary note prevailing wind flow, wind strength, cloud cover, climate variability impacts, bio-indicators suggestive of drought, and notes on extreme weather events. "Dirty weather" comments scattered throughout the diary describe disturbed conditions with strong winds and driving rainfall. The Davis diary entries coincide with the end of the Little Ice Age (LIA) and they indicate southerly and westerly circulation influences and cooler winter temperatures were more frequent than today. A comparison of climate field reconstructions derived from the Davis diary data and tree-ring-based winter temperature reconstructions are supported by tropical coral palaeotemperature evidence. Davis' pressure measurements were corroborated using ship log data from vessels associated with iconic Antarctic exploration voyages that were anchored in the Bay of Islands, and suggest the pressure series he recorded are robust and can be used as "station data". The Reverend Davis meteorological data are expected to make a significant contribution to the Atmospheric Circulation Reconstructions across the Earth (ACRE) project, which feeds the major data

  5. The "Dirty Weather" diaries of Reverend Richard Davis: insights about early Colonial-era meteorology and climate variability for Northern New Zealand, 1839-1851

    Science.gov (United States)

    Lorrey, A. M.; Chappell, P. R.

    2015-08-01

    Reverend Richard Davis (1790-1863) was a Colonial-era missionary stationed in the Far North of New Zealand who was a key figure in the early efforts of the Church Mission Society. He kept meticulous meteorological records for the early settlements of Waimate North and Kaikohe, and his observations are preserved in a two-volume set in the rare manuscripts archive at the Auckland City Library. The Davis diary volumes are significant because they constitute some of the earliest land-based meteorological measurements that were continually chronicled for New Zealand. The diary measurements cover nine years within the 1839-1851 timespan that are broken into two parts: 1839-1844 and 1848-1851. Davis' meteorological recordings include daily 9 AM and noon temperatures and mid-day pressure measurements. Qualitative comments in the diary note prevailing wind flow, wind strength, cloud cover, climate variability impacts, bio-indicators suggestive of drought, and notes on extreme weather events. "Dirty weather" comments scattered throughout the diary describe disturbed conditions with strong winds and driving rainfall. The Davis diary entries coincide with the end of the Little Ice Age (LIA) and they indicate southerly and westerly circulation influences and cooler winter temperatures were more frequent than today. A comparison of climate field reconstructions derived from the Davis diary data and tree ring-based winter temperature reconstructions are supported by tropical coral palaeotemperature evidence. Davis' pressure measurements were corroborated using ship log data from vessels associated with iconic Antarctic exploration voyages that were anchored in the Bay of Islands, and suggest the pressure series he recorded are robust and can be used as `station data'. The Reverend Davis meteorological data are expected to make a significant contribution to the Atmospheric Circulation Reconstructions across the Earth (ACRE) project, which feeds the major data requirements for the

  6. Probabilistic Projections of Future Sea-Level Change and Their Implications for Flood Risk Management: Insights from the American Climate Prospectus

    Science.gov (United States)

    Kopp, R. E., III; Delgado, M.; Horton, R. M.; Houser, T.; Little, C. M.; Muir-Wood, R.; Oppenheimer, M.; Rasmussen, D. M., Jr.; Strauss, B.; Tebaldi, C.

    2014-12-01

    Global mean sea level (GMSL) rise projections are insufficient for adaptation planning; local decisions require local projections that characterize risk over a range of timeframes and tolerances. We present a global set of local sea level (LSL) projections to inform decisions on timescales ranging from the coming decades through the 22nd century. We present complete probability distributions, informed by a combination of expert community assessment, expert elicitation, and process modeling [1]. We illustrate the application of this framework by estimating the joint distribution of future sea-level change and coastal flooding, and associated economic costs [1,2]. In much of the world in the current century, differences in median LSL projections are due primarily to varying levels of non-climatic uplift or subsidence. In the 22nd century and in the high-end tails, larger ice sheet contributions, particularly from the Antarctic ice sheet (AIS), contribute significantly to site-to-site differences. Uncertainty in GMSL and most LSL projections is dominated by the uncertain AIS component. Sea-level rise dramatically reshapes flood risk. For example, at the New York City (Battery) tide gauge, our projections indicate a likely (67% probability) 21st century LSL rise under RCP 8.5 of 65--129 cm (1-in-20 chance of exceeding 154 cm). Convolving the distribution of projected sea-level rise with the extreme value distribution of flood return periods indicates that this rise will cause the current 1.80 m `1-in-100 year' flood event to occur an expected nine times over the 21st century -- equivalent to the expected number of `1-in-11 year' floods in the absence of sea-level change. Projected sea-level rise for 2100 under RCP 8.5 would likely place 80-160 billion of current property in New York below the high tide line, with a 1-in-20 chance of losses >190 billion. Even without accounting for potential changes in storms themselves, it would likely increase average annual storm

  7. Evaluation of the biointeraction of colorant flavazin with human serum albumin: insights from multiple spectroscopic studies, in silico docking and molecular dynamics simulation.

    Science.gov (United States)

    Peng, Wei; Ding, Fei; Jiang, Yu-Ting; Sun, Ying; Peng, Yu-Kui

    2014-06-01

    Azo compounds are the largest chemical class of agents frequently used as colorants in a variety of consumer goods and farm produce; therefore, they may become a hazard to public health, because numerous azo compounds and their metabolites are proven to be carcinogens and mutagens. Herein several qualitative and quantitative analytical techniques, including steady state and time-resolved fluorescence, circular dichroism (CD), computer-aided molecular docking as well as molecular dynamics simulation, were employed to ascertain the molecular recognition between the principal vehicle of ligands in human plasma, albumin and a model azo compound, flavazin. The results show that the albumin spatial structure was changed in the presence of flavazin with a decrease of α-helix suggesting partial protein destabilization/self-regulation, as derived from steady state fluorescence, far-UV CD and detailed analyses of three-dimensional fluorescence spectra. Time-resolved fluorescence further evinced that the recognition mechanism is related to albumin-flavazin adduct formation with an association intensity of 10(4) M(-1), and the driving forces were found to be chiefly π-π interactions, hydrophobic interactions and hydrogen bonds. The specific binding domain of flavazin in protein was defined from molecular docking; subdomain IIA (Sudlow's site I) was found to retain high affinity for the ligand flavazin. This finding corroborates the results of competitive ligand displacement experiments, a hydrophobic 8-anilino-1-naphthalenesulfonic acid probe study and protein denaturation results, placing flavazin at the warfarin-azapropazone site. Based on molecular dynamics simulation, it can be said with certainty that the results of molecular docking are credible, and the key amino acid residues participating in the molecular recognition of flavazin by protein are clearly Trp-214, Arg-222 and Lys-436. The outcomes presented here will help to further comprehend the molecular recognition

  8. Insights into electron tunneling across hydrogen-bonded base-pairs in complete molecular circuits for single-stranded DNA sequencing

    OpenAIRE

    Lee, Myeong H.; Sankey, Otto F.

    2009-01-01

    We report a first-principles study of electron ballistic transport through a molecular junction containing deoxycytidine-monophosphate (dCMP) connected to metal electrodes. A guanidinium ion and guanine nucleobase are tethered to gold electrodes on opposite sides to form hydrogen bonds with the dCMP molecule providing an electric circuit. The circuit mimics a component of a potential device for sequencing unmodified single-stranded DNA. The molecular conductance is obtained from DFT Green’s f...

  9. Bialaba Migrants from the Northern of Benin to Nigeria, in Search of Productive Land—Insights for Living with Climate Change

    Directory of Open Access Journals (Sweden)

    Vanessa Dreier

    2015-03-01

    Full Text Available The concept of Environmental Migration has been broadly discussed by the international scientific community. Especially developing countries will have to develop strategies to cope with a rising number of people migrating at national and international levels due to climatic changes and environmental degradation. This paper will critically analyze the term Environmental Migration and sets it in relation to a case study conducted in northwest Benin in August/October of 2013 with Bialaba, analyzing their temporary migration pattern to Nigeria. The aim is to reveal current discussions on the term “Environmental Migration”/“Environmental Migrant” and to discuss its conceptual limits. The qualitative study in this working paper was conducted in the form of 36 interviews with farmers in the Dassari watershed North of Benin and surrounding villages as well as with stakeholders of the local government and NGOs active in the research area. Research results are presented in the following paper to clarify migration motives for the Bialaba of northwest Benin towards Nigeria aiming to stimulate discussions on the topic and to promote new research pathways.

  10. How is global climate policy interpreted on the ground? Insights from the analysis of local discourses about forest management and REDD+ in Indonesia

    Directory of Open Access Journals (Sweden)

    Sarah Milne

    2016-06-01

    Full Text Available The implementation of "reducing emissions from deforestation and forest degradation" (REDD+ will inevitably be affected by local social and political dynamics, with the potential for success depending significantly on cooperation from a range of stakeholders at the subnational level. Building on recent critical research on REDD+, we look at how global policy is interpreted locally by actors who are likely to be involved in REDD+ implementation. We do this by examining local stakeholder perceptions of REDD+ and forest management in two contrasting provinces of Indonesia, Riau and Papua, where deforestation rates are high and low, respectively. Using data collected from stakeholder workshops, we conduct a discourse analysis that reveals how subnational actors perceive and position themselves around REDD+ and forest governance. The results reveal six discourses common to both case-study provinces, which variously conflict and converge as they are employed by different actors. Seen together, these discourses provide critical insights into the subnational policy environment, which is largely a product of Indonesia's underlying land and forest politics, and they indicate in turn how REDD+ in practice is likely to be interpreted and reconstituted at the local level. A key finding is that local discourses can be grouped around two divergent positions on REDD+: one that supports forest exploitation and sees limited prospects in forest carbon, and one that embraces sustainable forest management and expresses conditional support for REDD+ subject to benefit-sharing and property arrangements. REDD+ practitioners will therefore need to craft policies and project processes that account for these discursive dynamics.

  11. From climate target to emission reduction. New insights in the options to reduce climate change effects; Van klimaatdoel naar emissiereductie. Nieuwe inzichten in de mogelijkheden voor beperking van klimaatverandering

    Energy Technology Data Exchange (ETDEWEB)

    Van Vuuren, D.; Berk, B.; Farla, J. [Milieu- en Natuurplanbureau MNP, Bilthoven (Netherlands); De Vos, R. [Ecofys, Utrecht (Netherlands)

    2006-11-15

    The target in the European Union to limit the rise of temperature to a maximum of 2 degrees Celsius can only be realized by stabilizing the concentration of greenhouse gases on a low level. Related emission reduction can be technically realized at a cost of 1-2% of the Gross National Product and far-going climate policy, including a large package of measures and more countries that participate. [Dutch] De EU doelstelling (beperking van de wereldwijde temperatuurstijging tot hooguit 2 graden) kan alleen met hoge zekerheid worden bereikt bij stabilisatie van broeikasgasconcentraties op lage niveau's. De hiervoor benodigde emissie-reducties zijn technisch mogelijk tegen directe kosten van zo'n 1-2% van het BNP. De inzet van verregaand klimaatbeleid, inclusief een breed pakket van maatregelen en een verbreding van deelnemende landen is dan wel noodzakelijk.

  12. Climate-relevant physical properties of molecular constituents relevant for isoprene-derived secondary organic aerosol material

    Directory of Open Access Journals (Sweden)

    M. A. Upshur

    2014-06-01

    Full Text Available Secondary organic aerosol (SOA particles, formed from gas-phase biogenic volatile organic compounds (BVOCs, contribute large uncertainties to the radiative forcing that is associated with aerosols in the climate system. Reactive uptake of surface-active organic oxidation products of BVOCs at the gas–aerosol interface can potentially decrease the overall aerosol surface tension and therefore influence their propensity to act as cloud condensation nuclei (CCN. Here, we synthesize and measure some climate-relevant physical properties of SOA particle constituents consisting of the isoprene oxidation products α-, δ-, and cis- and {trans-β-IEPOX (isoprene epoxide, as well as syn- and anti-2-methyltetraol. Following viscosity measurements, we use octanol-water partition coefficients to quantify the relative hydrophobicity of the oxidation products while dynamic surface tension measurements indicate that aqueous solutions of α- and trans-β-IEPOX exhibit significant surface tension depression. We hypothesize that the surface activity of these compounds may enhance aerosol CCN activity, and that trans-β-IEPOX may be highly relevant for surface chemistry of aerosol particles relative to other IEPOX isomers.

  13. Holocene climate change, permafrost, and cryogenic carbonate formation: insights from a recently deglaciated, high-elevation cave in the Austrian Alps

    Directory of Open Access Journals (Sweden)

    C. Spötl

    2014-04-01

    Full Text Available Cryogenically formed carbonate particles represent a rather new class of speleothems whose origin is directly linked to the presence of perennial ice in the subsurface. Recent studies concluded that dating these deposits provides important time constraints on the presence and the thickness of permafrost e.g. during the last glacial period. More precisely, these carbonates require the coexistence of water and ice and hence record episodes of permafrost thawing. To shed more light on the origin of the coarsely crystalline variety of these cryogenic cave carbonates – CCCcoarse for short – we examined a high-elevation cave site in the western part of the Austrian Alps which is located in an area dominated by permafrost features and transformed from an ice cave into an essentially ice-free cave during the past decade. Two side chambers of the main gallery revealed cryogenic calcite deposits whose isotopic composition indicates that they formed in individual pools of water carved in ice which underwent very slow freezing under closed-system conditions, i.e. enclosed in ice. 230Th dating shows that most of these carbonates formed ca. 2600 yr BP. Based on comparisons with other palaeoclimate archives in the Alps this thawing episode did not occur during a climate optimum, nor did CCCcoarse form in this cave during e.g. the Roman or the Medieval Warm Periods. Our results suggest that the occurrence of CCCcoarse, at least in mountain regions characterized by discontinuous permafrost, may be more stochastic than previously thought. Given the inherent heterogeneity of karst aquifers and the important role of localized water infiltration in modifying the thermal structure of the subsurface we caution against attributing CCCcoarse occurrences solely to peak warming conditions, while confirming the unique significance of these deposits in providing robust age constraints on permafrost thawing episodes.

  14. Insights into electron tunneling across hydrogen-bonded base-pairs in complete molecular circuits for single-stranded DNA sequencing

    Science.gov (United States)

    Lee, Myeong H.; Sankey, Otto F.

    2009-01-01

    We report a first-principles study of electron ballistic transport through a molecular junction containing deoxycytidine-monophosphate (dCMP) connected to metal electrodes. A guanidinium ion and guanine nucleobase are tethered to gold electrodes on opposite sides to form hydrogen bonds with the dCMP molecule providing an electric circuit. The circuit mimics a component of a potential device for sequencing unmodified single-stranded DNA. The molecular conductance is obtained from DFT Green's function scattering methods and is compared to estimates from the electron tunneling decay constant obtained from the complex band structure. The result is that a complete molecular dCMP circuit of 'linker((CH2)2)-guanidinium-phosphate-deoxyribose-cytosine-guanine' has a very low conductance (of the order of fS) while the hydrogen-bonded guanine-cytosine base-pair has a moderate conductance (of the order of tens to hundreds of nS). Thus, while the transverse electron transfer through base-pairing is moderately conductive, electron transfer through a complete molecular dCMP circuit is not. The gold Fermi level is found to be aligned very close to the HOMO for both the guanine-cytosine base-pair and the complete molecular dCMP circuit. Results for two different plausible geometries of the hydrogen-bonded dCMP molecule reveal that the conductance varies from fS for an extended structure to pS for a slightly compressed structure.

  15. Consumer Insights

    Institute of Scientific and Technical Information of China (English)

    JANKOT

    2004-01-01

    Fang Jun, the head of consumer and market insights of Unilever Shanghai, has summarized his early life as a market in two sentences: rush about to study market changes;act all day to observe consumer behavior. And now?"Tell stories, conduct interviews and piece together different data; calculate numbers,build models and write reports."

  16. Science insights.

    Science.gov (United States)

    Tanabe, Kazuyuki

    2015-06-01

    "Below is an essay by Prof. Tanabe originally written in Japanese. It gives an insight to Prof. Tanabe's inquiring mind and his approach to science. He also seek, as always, to inspire and nudge the young to scientific discovery". PMID:25463310

  17. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Georg Lenz

    2015-05-01

    Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  18. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Energy Technology Data Exchange (ETDEWEB)

    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  19. Oil-source correlation of the pre-Tertiary in the Huanghua Depression: Insights from stable carbon isotopes and molecular markers

    Institute of Scientific and Technical Information of China (English)

    YANG Yongcai; ZHANG Zhihuan; LI Wei; QIN Liming; FANG Chaohe; LIN Yuxiang; LIU Hua

    2008-01-01

    Stable carbon isotopes were used together with molecular markers to constrain genetic relationships between sandstone extracts and potential source rocks in the pre-Tertiary in the Huanghua Depression, North China.Comparison of the extracts from Permo-Carboniferous terrigenous mudstones and Ordovician marine carbonates indicated that their prominent differences are in stable carbon isotopes, molecular markers and thermal maturity.Although the extracts of the Mesozoic and Lower Permian Xiashihezi Formation sandstones have some similar isotopic characteristics, molecular markers data provide a good correlation between the Upper Jurassic-Lower Cretaceous oils and the Upper Carboniferous Taiyuan Formation mudstones, and between the Lower Permian Xiashihezi Formation oils and the Lower Permian mudstones. The results showed that the Upper Jurassic-Lower Cretaceous sandstone oils were derived chiefly from the Upper Carboniferous Taiyuan Formation terrigenous mudstones and that the Lower Permian Xiashihezi Formation oils were sourced from the Lower Permian Shanxi Formation and Xiashihezi Formation terdgenous mudstones.

  20. Spatial Self-Organization of Vegetation Subject to Climatic Stress—Insights from a System Dynamics—Individual-Based Hybrid Model

    Science.gov (United States)

    Vincenot, Christian E.; Carteni, Fabrizio; Mazzoleni, Stefano; Rietkerk, Max; Giannino, Francesco

    2016-01-01

    In simulation models of populations or communities, individual plants have often been obfuscated in favor of aggregated vegetation. This simplification comes with a loss of biological detail and a smoothing out of the demographic noise engendered by stochastic individual-scale processes and heterogeneities, which is significant among others when studying the viability of small populations facing challenging fluctuating environmental conditions. This consideration has motivated the development of precise plant-centered models. The accuracy gained in the representation of plant biology has then, however, often been balanced by the disappearance in models of important plant-soil interactions (esp. water dynamics) due to the inability of most individual-based frameworks to simulate complex continuous processes. In this study, we used a hybrid modeling approach, namely integrated System Dynamics (SD)—Individual-based (IB), to illustrate the importance of individual plant dynamics to explain spatial self-organization of vegetation in arid environments. We analyzed the behavior of this model under different parameter sets either related to individual plant properties (such as seed dispersal distance and reproductive age) or the environment (such as intensity and yearly distribution of precipitation events). While the results of this work confirmed the prevailing theory on vegetation patterning, they also revealed the importance therein of plant-level processes that cannot be rendered by reaction-diffusion models. Initial spatial distribution of plants, reproductive age, and average seed dispersal distance, by impacting patch size and vegetation aggregation, affected pattern formation and population survival under climatic variations. Besides, changes in precipitation regime altered the demographic structure and spatial organization of vegetation patches by affecting plants differentially depending on their age and biomass. Water availability influenced non

  1. Spatial Self-Organization of Vegetation Subject to Climatic Stress-Insights from a System Dynamics-Individual-Based Hybrid Model.

    Science.gov (United States)

    Vincenot, Christian E; Carteni, Fabrizio; Mazzoleni, Stefano; Rietkerk, Max; Giannino, Francesco

    2016-01-01

    In simulation models of populations or communities, individual plants have often been obfuscated in favor of aggregated vegetation. This simplification comes with a loss of biological detail and a smoothing out of the demographic noise engendered by stochastic individual-scale processes and heterogeneities, which is significant among others when studying the viability of small populations facing challenging fluctuating environmental conditions. This consideration has motivated the development of precise plant-centered models. The accuracy gained in the representation of plant biology has then, however, often been balanced by the disappearance in models of important plant-soil interactions (esp. water dynamics) due to the inability of most individual-based frameworks to simulate complex continuous processes. In this study, we used a hybrid modeling approach, namely integrated System Dynamics (SD)-Individual-based (IB), to illustrate the importance of individual plant dynamics to explain spatial self-organization of vegetation in arid environments. We analyzed the behavior of this model under different parameter sets either related to individual plant properties (such as seed dispersal distance and reproductive age) or the environment (such as intensity and yearly distribution of precipitation events). While the results of this work confirmed the prevailing theory on vegetation patterning, they also revealed the importance therein of plant-level processes that cannot be rendered by reaction-diffusion models. Initial spatial distribution of plants, reproductive age, and average seed dispersal distance, by impacting patch size and vegetation aggregation, affected pattern formation and population survival under climatic variations. Besides, changes in precipitation regime altered the demographic structure and spatial organization of vegetation patches by affecting plants differentially depending on their age and biomass. Water availability influenced non-linearly total

  2. New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes.

    Science.gov (United States)

    Lee, Timmy; Misra, Sanjay

    2016-08-01

    Vascular access dysfunction remains a major cause of morbidity and mortality in hemodialysis patients. At present there are few effective therapies for this clinical problem. The poor understanding of the pathobiology that leads to arteriovenous fistula (AVF) and graft (AVG) dysfunction remains a critical barrier to development of novel and effective therapies. However, in recent years we have made substantial progress in our understanding of the mechanisms of vascular access dysfunction. This article presents recent advances and new insights into the pathobiology of AVF and AVG dysfunction and highlights potential therapeutic targets to improve vascular access outcomes. PMID:27401527

  3. Bacterial-induced expression of RAB18 protein in Orzya sativa salinity stress and insights into molecular interaction with GTP ligand.

    Science.gov (United States)

    Jha, Yachana; Sablok, Gaurav; Subbarao, Naidu; Sudhakar, Raja; Fazil, M H U Turabe; Subramanian, R B; Squartini, Andrea; Kumar, Sunil

    2014-09-01

    In the present research, we have studied the inoculation effects of two root-associated plant growth-promoting rhizobacteria (PGPR) in rice and provide the pieces of evidence that the inoculation of the PGPR could potentially result in inducing the expression of the salt stress-related RAB18 plant gene under varying degrees of salinity stress. The sequenced putative gene of RAB18 of Oryza sativa in this study is 740 bp long, has a content of 44.4%, and a molecular weight of 492 102.00 Da. BLAST homology patterns revealed sequence similarity with the previously sequenced RAB in model plant species. We demonstrate the mode of action of this stress-related protein by performing comparative modeling of Q10RT8 (Os03g0146000 protein, homolog of the sequenced RAB18; O. sativa subsp. japonica) using energy minimization, molecular dynamic simulations, and molecular docking of a guanosine triphosphate (GTP) ligand with the protein. The docking results indicated that Ser21, Ala22, Lys25, Asp68, Ala70, Glu73, and Arg74 are important determinant residues for functional interaction with the GTP ligand. The present research contributes to the understanding of the PGPR inoculation in salinity stress. Additionally, it provides the layout of the understanding of the molecular interactions between RAB and GTP ligand. PMID:25042706

  4. Mechanistic Insights into Radical-Mediated Oxidation of Tryptophan from ab Initio Quantum Chemistry Calculations and QM/MM Molecular Dynamics Simulations.

    Science.gov (United States)

    Wood, Geoffrey P F; Sreedhara, Alavattam; Moore, Jamie M; Wang, John; Trout, Bernhardt L

    2016-05-12

    An assessment of the mechanisms of (•)OH and (•)OOH radical-mediated oxidation of tryptophan was performed using density functional theory calculations and ab initio plane-wave Quantum Mechanics/Molecular Mechanics (QM/MM) molecular dynamics simulations. For the (•)OH reactions, addition to the pyrrole ring at position 2 is the most favored site with a barrierless reaction in the gas phase. The subsequent degradation of this adduct through a H atom transfer to water was intermittently observed in aqueous-phase molecular dynamics simulations. For the (•)OOH reactions, addition to the pyrrole ring at position 2 is the most favored pathway, in contrast to the situation in the model system ethylene, where concerted addition to the double bond is preferred. From the (•)OOH position 2 adduct QM/MM simulations show that formation of oxy-3-indolanaline occurs readily in an aqueous environment. The observed transformation starts from an initial rupture of the O-O bond followed by a H atom transfer with the accompanying loss of an (•)OH radical to solution. Finally, classical molecular dynamics simulations were performed to equate observed differential oxidation rates of various tryptophan residues in monoclonal antibody fragments. It was found that simple parameters derived from simulation correlate well with the experimental data. PMID:27082439

  5. What's Right with My Mouse Model? New Insights into the Molecular and Cellular Basis of Cognition from Mouse Models of Rubinstein-Taybi Syndrome

    Science.gov (United States)

    Josselyn, Sheena A.

    2005-01-01

    The first gene-targeting studies that examined learning and memory in mice were performed in 1992 (Grant et al. 1992; Silva et al. 1992). The ultimate goal of this new field was to understand the molecular and cellular process underlying normal cognition and how they may be altered in disease states. In the years since these pioneering studies,…

  6. Insights into the inhibition and mechanism of compounds against LPS-induced PGE2 production: a pathway network-based approach and molecular dynamics simulations.

    Science.gov (United States)

    Zhang, Xinzhuang; Gu, Jiangyong; Cao, Liang; Ma, Yimin; Su, Zhenzhen; Luo, Fang; Wang, Zhenzhong; Li, Na; Yuan, Gu; Chen, Lirong; Xu, Xiaojie; Xiao, Wei

    2014-12-01

    In comparison to the current target-based screening approach, it is increasingly evident that active lead compounds based on disease-related phenotypes are more likely to be translated to clinical trials during drug development. That is, because human diseases are in essence the outcome of the abnormal function of multiple genes, especially in complex diseases. Therefore, as a conventional technology in the early phase of active lead compound discovery, computational methods that can connect molecular interactions and disease-related phenotypes to evaluate the efficacy of compounds are in urgently required. In this work, a computational approach that integrates molecular docking and pathway network analysis (network efficiency and network flux) was developed to evaluate the efficacy of a compound against LPS-induced Prostaglandin E2(PGE2) production. The predicted results were then validated in vitro, and a correlation with the experimental results was analyzed using linear regression. In addition, molecular dynamics (MD) simulations were performed to explore the molecular mechanism of the most potent compounds. There were 12 hits out of 28 predicted ingredients separated from Reduning injection (RDN). The predicted results have a good agreement with the experimental inhibitory potency (IC50) (correlation coefficient = 0.80). The most potent compounds could target several proteins to regulate the pathway network. This might partly interpret the molecular mechanism of RDN on fever. Meanwhile, the good correlation of the computational model with the wet experimental results might bridge the gap between molecule-target interactions and phenotypic response, especially for multi-target compounds. Therefore, it would be helpful for active lead compound discovery, the understanding of the multiple targets and synergic essence of traditional Chinese medicine (TCM). PMID:25228393

  7. Comparative proteome analysis of psychrophilic versus mesophilic bacterial species: Insights into the molecular basis of cold adaptation of proteins

    OpenAIRE

    Reddy Boojala; Metpally Raghu

    2009-01-01

    Abstract Background Cold adapted or psychrophilic organisms grow at low temperatures, where most of other organisms cannot grow. This adaptation requires a vast array of sequence, structural and physiological adjustments. To understand the molecular basis of cold adaptation of proteins, we analyzed proteomes of psychrophilic and mesophilic bacterial species and compared the differences in amino acid composition and substitution patterns to investigate their likely association with growth temp...

  8. Insights into affinity and specificity in the complexes of α-lytic protease and its inhibitor proteins: binding free energy from molecular dynamics simulation†

    OpenAIRE

    Deng, Nan-Jie; Cieplak, Piotr

    2009-01-01

    We report the binding free energy calculation and its decomposition for the complexes of α-lytic protease and its protein inhibitors using molecular dynamics simulation. Standard mechanism serine protease inhibitors eglin C and OMTKY3 are known to have strong binding affinity for many serine proteases. Their binding loops have significant similarities, including a common P1 Leu as the main anchor in the binding interface. However, recent experiments demonstrate that the two inhibitors have va...

  9. Quantum chemical insights into the dependence of porphyrin basicity on the meso-aryl substituents: thermodynamics, buckling, reaction sites and molecular flexibility.

    Science.gov (United States)

    Presselt, Martin; Dehaen, Wim; Maes, Wouter; Klamt, Andreas; Martínez, Todd; Beenken, Wichard J D; Kruk, Mikalai

    2015-06-01

    The chemical and sensing properties of porphyrins are frequently tuned via the introduction of peripheral substituents. In the context of the exceptionally fast second protonation step in the case of 5,10,15,20-tetraphenylporphyrin (TPP), as compared to porphin and 5,10,15,20-tetramesitylporphyrin (TMesP), we investigated the macrocycle-substituent interactions of these three porphyrin derivatives in detail. Using quantum chemical thermodynamics calculations, the analysis of geometric structures, torsional profiles, electrostatic potential distributions, and particularly the analysis of molecular flexibilities via ab initio molecular dynamics simulations, we obtained a comprehensive picture of the reactivities of the studied porphyrins and how these are influenced by the meso-substituents. As compared to porphin and TMesP the second protonation of TPP is energetically more favorable and is particularly energetically comparable to its first protonation, instead of being significantly less favorable like in the case of porphyrin and TMesP. Additionally, the second TPP protonation is facilitated by an interplay between out-of-plane (oop) distortion of the protonation site and a pronounced electrostatic binding spot at the protonation site. Furthermore, the second protonation is particularly facilitated in the case of TPP by the large oop-flexibility of the diprotonated species as unraveled by ab initio molecular dynamics simulations. PMID:25959745

  10. Insight into the effect of inhibitor resistant S130G mutant on physico-chemical properties of SHV type beta-lactamase: a molecular dynamics study.

    Directory of Open Access Journals (Sweden)

    Mohd Hassan Baig

    Full Text Available Bacterial resistance is a serious threat to human health. The production of β-lactamase, which inactivates β-lactams is most common cause of resistance to the β-lactam antibiotics. The Class A enzymes are most frequently encountered among the four β-lactamases in the clinic isolates. Mutations in class A β-lactamases play a crucial role in substrate and inhibitor specificity. SHV and TEM type are known to be most common class A β-lactamases. In the present study, we have analyzed the effect of inhibitor resistant S130G point mutation of SHV type Class-A β-lactamase using molecular dynamics and other in silico approaches. Our study involved the use of different in silico methods to investigate the affect of S130G point mutation on the major physico-chemical properties of SHV type class A β-lactamase. We have used molecular dynamics approach to compare the dynamic behaviour of native and S130G mutant form of SHV β-lactamase by analyzing different properties like root mean square deviation (RMSD, H-bond, Radius of gyration (Rg and RMS fluctuation of mutation. The results clearly suggest notable loss in the stability of S130G mutant that may further lead to decrease in substrate specificity of SHV. Molecular docking further indicates that S130G mutation decreases the binding affinity of all the three inhibitors in clinical practice.

  11. Bioassay-guided isolation, identification and molecular ligand-target insight of lipoxygenase inhibitors from leaves of Anisomeles malabarica R.Br.

    Directory of Open Access Journals (Sweden)

    A Sudha

    2014-01-01

    Full Text Available Background: Anisomeles malabarica R. Br. (Lamiaceae is extensively used in traditional medicine in major parts of India for several medicinal purposes, including their use in rheumatism. Materials and Methods: The air-dried leaves of A. malabarica were extracted with ethanol, defatted with n-hexane and then successively partitioned into chloroform and n-butanol fractions. Bioassay-guided fractionation and purification of chloroform fraction from A. malabarica lead to the isolation of lipoxygenase (LOX inhibitors. The structures of isolated compounds were elucidated by ultraviolet, infrared, 1 H nuclear magnetic resonance (NMR, 13 C NMR and mass spectrometry spectroscopic techniques and assessed further by in vitro soybean lipoxygenase (sLOX assay. In addition, the enzyme type inhibition was evaluated through molecular docking technique as a part of computational study. Results: The bioactive compounds 3, 4 dihydroxy benzoic acid (1 and 4′, 5, 7-trihydroxyflavone (2 were isolated from chloroform fraction of A. malabarica, whose bioactivity was observed to be dose-dependent compared to n-butanol fraction. Among the compounds, 3, 4 dihydroxy benzoic acid showed significant sLOX inhibitory activity with 74.04% ±2.6% followed by 4′, 5, 7-trihydroxyflavone (34.68% ±1.9%. The computational analysis of compounds showed their molecular interaction with important amino acid residues and nonheme iron atom in the catalytic site of LOX by enlightening their potential binding mode at molecular level. Conclusions: The LOX inhibitory constituents were identified from A. malabarica by means of bioassay-guided fractionation process. The results derived from in vitro and computational experiments confirm the potential of the isolated compounds and provide additional evidence for its traditional use in inflammatory disorders.

  12. Structural and dynamical insights on HLA-DR2 complexes that confer susceptibility to multiple sclerosis in Sardinia: a molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Sardinia is a major Island in the Mediterranean with a high incidence of multiple sclerosis, a chronic autoimmune inflammatory disease of the central nervous system. Disease susceptibility in Sardinian population has been associated with five alleles of major histocompatibility complex (MHC class II DRB1 gene. We performed 120 ns of molecular dynamics simulation on one predisposing and one protective alleles, unbound and in complex with the two relevant peptides: Myelin Basic Protein and Epstein Barr Virus derived peptide. In particular we focused on the MHC peptide binding groove dynamics. The predisposing allele was found to form a stable complex with both the peptides, while the protective allele displayed stability only when bound with myelin peptide. The local flexibility of the MHC was probed dividing the binding groove into four compartments covering the well known peptide anchoring pockets. The predisposing allele in the first half cleft exhibits a narrower and more rigid groove conformation in the presence of myelin peptide. The protective allele shows a similar behavior, while in the second half cleft it displays a narrower and more flexible groove conformation in the presence of viral peptide. We further characterized these dynamical differences by evaluating H-bonds, hydrophobic and stacking interaction networks, finding striking similarities with super-type patterns emerging in other autoimmune diseases. The protective allele shows a defined preferential binding to myelin peptide, as confirmed by binding free energy calculations. All together, we believe the presented molecular analysis could help to design experimental assays, supports the molecular mimicry hypothesis and suggests that propensity to multiple sclerosis in Sardinia could be partly linked to distinct peptide-MHC interaction and binding characteristics of the antigen presentation mechanism.

  13. Influence of Chirality of Crizotinib on Its MTH1 Protein Inhibitory Activity: Insight from Molecular Dynamics Simulations and Binding Free Energy Calculations.

    Directory of Open Access Journals (Sweden)

    Yuzhen Niu

    Full Text Available As a promising target for the treatment of lung cancer, the MutT Homolog 1 (MTH1 protein can be inhibited by crizotinib. A recent work shows that the inhibitory potency of (S-crizotinib against MTH1 is about 20 times over that of (R-crizotinib. But the detailed molecular mechanism remains unclear. In this study, molecular dynamics (MD simulations and free energy calculations were used to elucidate the mechanism about the effect of chirality of crizotinib on the inhibitory activity against MTH1. The binding free energy of (S-crizotinib predicted by the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA and Adaptive biasing force (ABF methodologies is much lower than that of (R-crizotinib, which is consistent with the experimental data. The analysis of the individual energy terms suggests that the van der Waals interactions are important for distinguishing the binding of (S-crizotinib and (R-crizotinib. The binding free energy decomposition analysis illustrated that residues Tyr7, Phe27, Phe72 and Trp117 were important for the selective binding of (S-crizotinib to MTH1. The adaptive biasing force (ABF method was further employed to elucidate the unbinding process of (S-crizotinib and (R-crizotinib from the binding pocket of MTH1. ABF simulation results suggest that the reaction coordinates of the (S-crizotinib from the binding pocket is different from (R-crizotinib. The results from our study can reveal the details about the effect of chirality on the inhibition activity of crizotinib to MTH1 and provide valuable information for the design of more potent inhibitors.

  14. Rare loss-of-function mutation in complement component C3 provides insight into molecular and pathophysiological determinants of complement activity

    OpenAIRE

    Sfyroera, Georgia; Ricklin, Daniel; Reis, Edimara S.; Chen, Hui; Wu, Emilia L.; Kaznessis, Yiannis N.; Ekdahl, Kristina N.; Nilsson, Bo; Lambris, John D.

    2015-01-01

    The plasma protein C3 is a central element in the activation and effector functions of the complement system. A hereditary dysfunction of C3 that prevents complement activation via the alternative pathway (AP) was described previously in a Swedish family, but its genetic cause and molecular consequences have remained elusive. Here we provide these missing links by pinpointing the dysfunction to a point mutation in the β-chain of C3 (c.1180T>C; p.Met373Thr). In the patient’s plasma, AP activit...

  15. Coordination Numbers of K+ and Na+ Ions Inside the Selectivity Filter of the KcsA Potassium Channel: Insights from First Principles Molecular Dynamics

    OpenAIRE

    Bucher, Denis; Guidoni, Leonardo; Carloni, Paolo; Rothlisberger, Ursula

    2010-01-01

    Quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello simulations were performed to estimate the coordination numbers of K+ and Na+ ions in the selectivity filter of the KcsA channel, and in water. At the DFT/BLYP level, K+ ions were found to display an average coordination number of 6.6 in the filter, and 6.2 in water. Na+ ions displayed an average coordination number of 5.2 in the filter, and 5.0 in water. A comparison was made with the average coordination numbers obtained from usin...

  16. Structural Determinants of Improved Fluorescence in a Family of Bacteriophytochrome-Based Infrared Fluorescent Proteins: Insights from Continuum Electrostatic Calculations and Molecular Dynamics Simulations.

    Science.gov (United States)

    Feliks, Mikolaj; Lafaye, Céline; Shu, Xiaokun; Royant, Antoine; Field, Martin

    2016-08-01

    Using X-ray crystallography, continuum electrostatic calculations, and molecular dynamics simulations, we have studied the structure, protonation behavior, and dynamics of the biliverdin chromophore and its molecular environment in a series of genetically engineered infrared fluorescent proteins (IFPs) based on the chromophore-binding domain of the Deinococcus radiodurans bacteriophytochrome. Our study suggests that the experimentally observed enhancement of fluorescent properties results from the improved rigidity and planarity of the biliverdin chromophore, in particular of the first two pyrrole rings neighboring the covalent linkage to the protein. We propose that the increases in the levels of both motion and bending of the chromophore out of planarity favor the decrease in fluorescence. The chromophore-binding pocket in some of the studied proteins, in particular the weakly fluorescent parent protein, is shown to be readily accessible to water molecules from the solvent. These waters entering the chromophore region form hydrogen bond networks that affect the otherwise planar conformation of the first three rings of the chromophore. On the basis of our simulations, the enhancement of fluorescence in IFPs can be achieved either by reducing the mobility of water molecules in the vicinity of the chromophore or by limiting the interactions of the nearby protein residues with the chromophore. Finally, simulations performed at both low and neutral pH values highlight differences in the dynamics of the chromophore and shed light on the mechanism of fluorescence loss at low pH. PMID:27471775

  17. Inhibitory effect of synthetic aromatic heterocycle thiosemicarbazone derivatives on mushroom tyrosinase: Insights from fluorescence, (1)H NMR titration and molecular docking studies.

    Science.gov (United States)

    Xie, Juan; Dong, Huanhuan; Yu, Yanying; Cao, Shuwen

    2016-01-01

    Three structurally similar aromatic heterocyclic compounds 2-thiophenecarboxaldehyde (a), 2-furaldehyde (b), 2-pyrrolecarboxaldehyde (c) were chosen and a series of their thiosemicarbazone derivatives(1a-3a, 1b-3b and 1c-3c) were synthesized to evaluate their biological activities as mushroom tyrosinase inhibitors. The inhibitory effects of these compounds on tyrosinase were investigated by using spectrofluorimetry, (1)H NMR titration and molecular docking techniques. From the results of fluorescence spectrum and (1)H NMR titration, it was found that forming complexes between the sulfur atom from thiourea and copper ion of enzyme center may play a key role for inhibition activity. Moreover, investigation of (1)H NMR spectra further revealed that formation of hydrogen bond between inhibitor and enzyme may be helpful to above complexes formation. The results were well coincident with the suggestion of molecular docking and obviously showed that 2-thiophone N(4)-thiosemicarbazone (1a), 2-furfuran N(4)-thiosemicarbazone (1b) and 2-pyrrole N(4)-thiosemicarbazone (1c) are potential inhibitors which deserves further investigation. PMID:26213029

  18. Insights into the molecular basis of action of the AT1 antagonist losartan using a combined NMR spectroscopy and computational approach.

    Science.gov (United States)

    Zervou, Maria; Cournia, Zoe; Potamitis, Constantinos; Patargias, George; Durdagi, Serdar; Grdadolnik, Simona Golic; Mavromoustakos, Thomas

    2014-03-01

    The drug:membrane interactions for the antihypertensive AT1 antagonist losartan, the prototype of the sartans class, are studied herein using an integrated approach. The pharmacophore arrangement of the drug was revealed by rotating frame nuclear Overhauser effect spectroscopy (2D ROESY) NMR spectroscopy in three different environments, namely water, dimethyl sulfoxide (DMSO), and sodium dodecyl sulfate (SDS) micellar solutions mimicking conditions of biological transport fluids and membrane lipid bilayers. Drug association with micelles was monitored by diffusion ordered spectroscopy (2D DOSY) and drug:micelle intermolecular interactions were characterized by ROESY spectroscopy. The localisation of the drug in the micellar environment was investigated by introducing 5-doxyl and 16-doxyl stearic acids. The use of spin labels confirmed that losartan resides close to the micelle:water interface with the hydroxymethyl group and the tetrazole heterocyclic aromatic ring facing the polar surface with the potential to interact with SDS charged polar head groups in order to increase amphiphilic interactions. The spontaneous insertion, the diffusion pathway and the conformational features of losartan were monitored by Molecular Dynamics (MD) simulations in a modeled SDS micellar aggregate environment and a long exploratory MD run (580ns) in a phospholipid dipalmitoylphosphatidylcholine (DPPC) bilayer with the AT1 receptor embedded. MD simulations were in excellent agreement with experimental results and further revealed the molecular basis of losartan:membrane interactions in atomic-level detail. This applied integrated approach aims to explore the role of membranes in losartan's pathway towards the AT1 receptor. PMID:24374319

  19. Molecular Insight into Substrate Recognition and Catalysis of Baeyer-Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in the Biosynthesis of Anticancer Agent Mithramycin

    Energy Technology Data Exchange (ETDEWEB)

    Bosserman, Mary A.; Downey, Theresa; Noinaj, Nicholas; Buchanan, Susan K.; Rohr, Jürgen [NIH; (Kentucky)

    2014-02-14

    Baeyer–Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C–C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed us to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.

  20. Molecular insight into the differential anti-androgenic activity of resveratrol and its natural analogs: in silico approach to understand biological actions.

    Science.gov (United States)

    Chakraborty, Sandipan; Kumar, Avinash; Butt, Nasir A; Zhang, Liangfen; Williams, Raquema; Rimando, Agnes M; Biswas, Pradip K; Levenson, Anait S

    2016-04-26

    The androgen receptor (AR) is a therapeutic target for the treatment of prostate cancer. Androgen receptor reactivation during the androgen-independent stage of prostate cancer is mediated by numerous mechanisms including expression of AR mutants and splice variants that become non-responsive to conventional anti-androgenic agents. Resveratrol and its natural analogs exhibit varying degrees of anti-androgenic effects on tumor growth suppression in prostate cancer. However, the structural basis for the observed differential activity remains unknown. Here, anti-androgenic activities of resveratrol and its natural analogs, namely, pterostilbene, piceatannol and trimethoxy-resveratrol were studied in LNCaP cells expressing T877A mutant AR and atomistic simulations were employed to establish the structure activity relationship. Interestingly, essential hydrogen bonding contacts and the binding energies of resveratrol analogs with AR ligand binding domain (LBD), emerge as key differentiating factors for varying anti-androgenic action. Among all the analogs, pterostilbene exhibited strongest anti-androgenic activity and its binding energy and hydrogen bonding interactions pattern closely resembled pure anti-androgen, flutamide. Principal component analysis of our simulation studies revealed that androgenic compounds bind more strongly to AR LBD compared to anti-androgenic compounds and provide conformational stabilization of the receptor in essential subspace. The present study provides critical insight into the structure-activity relationship of the anti-androgenic action of resveratrol analogs, which can be translated further to design novel highly potent anti-androgenic stilbenes. PMID:27063447

  1. First assessment on the molecular phylogeny of Anatololacerta (Squamata, Lacertidae) distributed in Southern Anatolia: insights from mtDNA and nDNA markers.

    Science.gov (United States)

    Candan, Kamil; Kankılıç, Tolga; Güçlü, Özgür; Kumlutaş, Yusuf; Durmuş, Salih Hakan; Lymberakis, Petros; Poulakakis, Nikos; Ilgaz, Çetin

    2016-05-01

    The genus Anatololacerta (Lacertidae) occurs mainly in Anatolia (western and southern Turkey) and on the Aegean islands Samos, Ikaria, and Rhodos. Although its taxonomy has long been debated and is currently nascent, three morphological species have been attributed to this genus: Anatololacerta anatolica, Anatololacerta oertzeni, and Anatololacerta danfordi. Here, we investigated the evolutionary history of A. oertzeni and Anatololacerta danfordi based on both mitochondrial and nuclear markers (16S rRNA and cmos). In total, 34 Anatololacerta specimens were analyzed using maximum likelihood (ML) and Bayesian inference (BI) methods. Our results supported the presence of four well-supported lineages: two belongs to A. oertzeni and two to A. danfordi. The temporal diversification of these lineages probably started with the divergence of the first A. oertzeni lineage from western Antalya at 7.9 Mya. The other two major splits may have occurred in early Pliocene (4.4 Mya: the divergence of the second A. oertzeni from A. danfordi) and in late Pliocene (2.7 Mya: the divergence of the two lineages of A. danfordi). The phylogeographical scenario suggests that the major diversification events (from late Miocene to late Pliocene) could be related with climatic oscillations (such as the late Miocene aridification and the Messinian Salinity Crisis) and tectonic movements (such as the uplift of the central Taurus mountain). PMID:25489775

  2. Molecular phylogeography and ecological niche modelling of a widespread herbaceous climber, Tetrastigma hemsleyanum (Vitaceae): insights into Plio-Pleistocene range dynamics of evergreen forest in subtropical China.

    Science.gov (United States)

    Wang, Yi-Han; Jiang, Wei-Mei; Comes, Hans Peter; Hu, Feng Sheng; Qiu, Ying-Xiong; Fu, Cheng-Xin

    2015-04-01

    Warm-temperate evergreen (WTE) forest represents the typical vegetation type of subtropical China, but how its component species responded to past environmental change remains largely unknown. Here, we reconstruct the evolutionary history of Tetrastigma hemsleyanum, an herbaceous climber restricted to the WTE forest. Twenty populations were genotyped using chloroplast DNA sequences and nuclear microsatellite loci to assess population structure and diversity, supplemented by phylogenetic dating, ancestral area reconstructions and ecological niche modeling (ENM) of the species distributions during the Last Glacial Maximum (LGM) and at present. Lineages in Southwest vs Central-South-East China diverged through climate/tectonic-induced vicariance of an ancestral southern range during the early Pliocene. Long-term stability in the Southwest contrasts with latitudinal range shifts in the Central-South-East region during the early-to-mid-Pleistocene. Genetic and ENM data strongly suggest refugial persistence in situ at the LGM. Pre-Quaternary environmental changes appear to have had a persistent influence on the population genetic structure of this subtropical WTE forest species. Our findings suggest relative demographic stability of this biome in China over the last glacial-interglacial cycle, in contrast with palaeobiome reconstructions showing that this forest biome retreated to areas of today's tropical South China during the LGM. PMID:25639152

  3. Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells.

    Science.gov (United States)

    Sasidharan, Abhilash; Swaroop, Siddharth; Chandran, Parwathy; Nair, Shantikumar; Koyakutty, Manzoor

    2016-07-01

    Despite graphene being proposed for a multitude of biomedical applications, there is a dearth in the fundamental cellular and molecular level understanding of how few-layer graphene (FLG) interacts with human primary cells. Herein, using human primary umbilical vein endothelial cells as model of vascular transport, we investigated the basic mechanism underlying the biological behavior of graphene. Mechanistic toxicity studies using a battery of cell based assays revealed an organized oxidative stress paradigm involving cytosolic reactive oxygen stress, mitochondrial superoxide generation, lipid peroxidation, glutathione oxidation, mitochondrial membrane depolarization, enhanced calcium efflux, all leading to cell death by apoptosis/necrosis. We further investigated the effect of graphene interactions using cDNA microarray analysis and identified potential adverse effects by down regulating key genes involved in DNA damage response and repair mechanisms. Single cell gel electrophoresis assay/Comet assay confirmed the DNA damaging potential of graphene towards human primary cells. PMID:26970024

  4. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders; Pedersen, Anette A.; Østergaard, Henrik; Overgaard, Michael T.; Olsen, Ole H.; Gandhi, Prafull S

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic...... properties. Extensive studies have revealed two putative pathways for this allosteric communication. Here we provide further details of this allosteric communication by investigating FVIIa loop swap variants containing the 170 loop of trypsin that display TF-independent enhanced activity. Using x......-ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation is...

  5. New Insights into the Molecular Dynamics of P3HT:PCBM Bulk Heterojunction: A Time-of-Flight Quasi-Elastic Neutron Scattering Study.

    Science.gov (United States)

    Guilbert, Anne A Y; Zbiri, Mohamed; Jenart, Maud V C; Nielsen, Christian B; Nelson, Jenny

    2016-06-16

    The molecular dynamics of organic semiconductor blend layers are likely to affect the optoelectronic properties and the performance of devices such as solar cells. We study the dynamics (5-50 ps) of the poly(3-hexylthiophene) (P3HT): phenyl-C61-butyric acid methyl ester (PCBM) blend by time-of-flight quasi-elastic neutron scattering, at temperatures in the range 250-360 K, thus spanning the glass transition temperature region of the polymer and the operation temperature of an OPV device. The behavior of the QENS signal provides evidence for the vitrification of P3HT upon blending, especially above the glass transition temperature, and the plasticization of PCBM by P3HT, both dynamics occurring on the picosecond time scale. PMID:27192930

  6. Conformational alterations induced by novel green 16-E2-16 gemini surfactant in xanthine oxidase: Biophysical insights from tensiometry, spectroscopy, microscopy and molecular modeling.

    Science.gov (United States)

    Akram, Mohd; Bhat, Imtiyaz Ahmad; Bhat, Waseem Feeroze; Kabir-ud-Din

    2015-11-01

    Herein we report the interaction of a biodegradable gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) dichloride (16-E2-16) with bovine milk xanthine oxidase (XO), employing tensiometry, fluorescence spectroscopy, UV spectroscopy, far-UV circular dichroism spectroscopy (CD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and computational molecular modeling. Surface tension results depict substantial changes in the micellar as well as interfacial parameters (CMC, ΠCMC, γCMC, Γmax, Amin, ΔGmic° and ΔGads°) of 16-E2-16 gemini surfactant upon XO combination, deciphering the interaction of XO with the gemini surfactant. Fluorescence measurements reveal that 16-E2-16 gemini surfactant causes quenching in the xanthine oxidase (XO) fluorescence spectra via static procedure and the values of various evaluated binding parameters (KSV, Kb, kq, ΔGb° and n) describe that 16-E2-16 effectively binds to XO. Three dimensional fluorescence, 8-anilino-1-naphthalene sulfonic acid (ANS) binding, F1F3 ratio, UV, CD, FTIR, SEM and TEM results delineate changes in the secondary structure of xanthine oxidase. Molecular docking results provide complement to the steady-state fluorescence findings and support the view that quenching occurs due to non-polar environment experienced by aromatic residues of the enzyme. The results of this study can help scientists to tune the conformation of an enzyme (XO) with biocompatible amphiphilic microstructures, which will help to unfold further understanding in the treatment modes of various diseases like gout, hyperuricemia, liver and brain necrosis. PMID:26057098

  7. Molecular insights into the mechanisms of liver-associated diseases in early-lactating dairy cows: hypothetical role of endoplasmic reticulum stress.

    Science.gov (United States)

    Ringseis, R; Gessner, D K; Eder, K

    2015-08-01

    The transition period represents the most critical period in the productive life of high-yielding dairy cows due to both metabolic and inflammatory stimuli, which challenge the liver and predispose dairy cows to develop liver-associated diseases such as fatty liver and ketosis. Despite the fact that all high-yielding dairy cows are affected by marked metabolic stress due to a severe negative energy balance (NEB) during early lactation, not all cows develop liver-associated diseases. Although the reason for this is largely unknown, this indicates that the capacity of the liver to cope with metabolic and inflammatory challenges varies between individual high-yielding dairy cows. Convincing evidence exists that endoplasmic reticulum (ER) stress plays a key role in the development of fatty liver, and it has been recently shown that ER stress occurs in the liver of high-yielding dairy cows. This indicates that ER stress may be involved in the development of liver-associated diseases in dairy cows. The present review shows that the liver of dairy cows during early lactation is exposed to several metabolic and inflammatory challenges, such as non-esterified fatty acids, tumour necrosis factor α, interleukin-1β, reactive oxygen species and lipopolysaccharides, which are known inducers of ER stress. Thus, ER stress may represent a molecular basis for fatty liver development and account for the frequent occurrence of fatty liver and ketosis in high-yielding dairy cows. Interindividual differences between dairy cows in the activation of hepatic stress response pathways, such as nuclear factor E2-related factor 2, which is activated during ER stress and reduces the sensitivity of tissues to oxidative and inflammatory damage, might provide an explanation at the molecular level for differences in the capacity to cope with pathological inflammatory challenges during early lactation and the susceptibility to develop liver-associated diseases between early-lactating dairy cows

  8. Molecular characterization and expression profile of three Fem-1 genes in Eriocheir sinensis provide a new insight into crab sex-determining mechanism.

    Science.gov (United States)

    Song, Chengwen; Cui, Zhaoxia; Hui, Min; Liu, Yuan; Li, Yingdong

    2015-11-01

    The FEM-1 protein of Caenorhabditis elegans plays a crucial role in the nematode sex-determination pathway. Here, we reported the characterization of three members of Fem-1 gene family in Eriocheir sinensis (designated EsFem-1a, EsFem-1b, and EsFem-1c), which were homologs of the nematode FEM-1 protein. The amino acid sequences of EsFem-1a, EsFem-1b, and EsFem-1c contained eight, nine, and eight ankyrin repeats, respectively. None of the ankyrin repeats had its own specific signature, and the evolution of ankyrin repeat was not completely independent. The predicted three-dimensional structure of EsFem-1 proteins exhibited highly similar superhelical conformation, especially the N-terminal six contiguous ankyrin repeats, which provided a binding surface for the protein-protein interaction. Phylogenetic tree based on the amino acid sequences revealed that EsFem-1a, EsFem-1b, and EsFem-1c were divided into three obvious separated clades. EsFem-1 genes were highly expressed in fertilized egg, 2-4 cell and blastula stage comparing with larval stage (P<0.01), which suggested they might be maternal genes. They also showed a certain degree of sexually dimorphic expression in some tissues. Notably, the highest expression of EsFem-1a was in the hepatopancreas, with EsFem-1b in testes and EsFem-1c in muscle (P<0.05), which indicated their potential role in a broad array of tissues. In addition, the genes initially involved in sex differentiation were not limited to those specifically expressed in the developing gonad. Taken together, these results suggested that EsFem-1 might function in crab early sex determination and late gonad development. The identification of Fem-1 gene family in E. sinensis provides a new insight into crab sex-determination mechanism. PMID:26188322

  9. Mapping of the Co-Transcriptomes of UPEC-Infected Macrophages Reveals New Insights into the Molecular Basis of Host-Pathogen Interactions in Human and Mouse

    KAUST Repository

    Mavromatis, Charalampos Harris

    2014-01-01

    provides both a unique co-culture approach to study infection in vitro and a technological framework for simultaneously capturing global changes in hostpathogen interactions at the transcriptional level in co-cultures. In conclusion, this work has generated new insights into the mechanisms that UPEC strains exploit to persist within the mouse intramacrophage environment, as well as differences in the transcriptional repertoire of HMDM and BMM challenged with the same UPEC strain.

  10. Characterization of two coleopteran α-amylases and molecular insights into their differential inhibition by synthetic α-amylase inhibitor, acarbose.

    Science.gov (United States)

    Channale, Sonal M; Bhide, Amey J; Yadav, Yashpal; Kashyap, Garima; Pawar, Pankaj K; Maheshwari, V L; Ramasamy, Sureshkumar; Giri, Ashok P

    2016-07-01

    Post-harvest insect infestation of stored grains makes them unfit for human consumption and leads to severe economic loss. Here, we report functional and structural characterization of two coleopteran α-amylases viz. Callosobruchus chinensis α-amylase (CcAmy) and Tribolium castaneum α-amylase (TcAmy) along with their interactions with proteinaceous and non-proteinaceous α-amylase inhibitors. Secondary structural alignment of CcAmy and TcAmy with other coleopteran α-amylases revealed conserved motifs, active sites, di-sulfide bonds and two point mutations at spatially conserved substrate or inhibitor-binding sites. Homology modeling and molecular docking showed structural differences between these two enzymes. Both the enzymes had similar optimum pH values but differed in their optimum temperature. Overall, pattern of enzyme stabilities were similar under various temperature and pH conditions. Further, CcAmy and TcAmy differed in their substrate affinity and catalytic efficiency towards starch and amylopectin. HPLC analysis detected common amylolytic products like maltose and malto-triose while glucose and malto-tetrose were unique in CcAmy and TcAmy catalyzed reactions respectively. At very low concentrations, wheat α-amylase inhibitor was found to be superior over the acarbose as far as complete inhibition of amylolytic activities of CcAmy and TcAmy was concerned. Mechanism underlying differential amylolytic reaction inhibition by acarbose was discussed. PMID:27132147

  11. The rotational excitation of HCN and HNC by He: New insights on the HCN/HNC abundance ratio in molecular clouds

    CERN Document Server

    Sarrasin, E; Wernli, M; Faure, A; Cernicharo, J; Lique, F

    2010-01-01

    Modeling of molecular emission from interstellar clouds requires the calculation of rates for excitation by collisions with the most abundant species. The present paper focuses on the calculation of rate coefficients for rotational excitation of the HCN and HNC molecules in their ground vibrational state in collision with He. The calculations are based on new two-dimensional potential energy surfaces obtained from highly correlated \\textit{ab initio} calculations. Calculations of pure rotational (de)excitation cross sections of HCN and HNC by He were performed using the essentially exact close-coupling method. Cross sections for transitions among the 8 first rotational levels of HCN and HNC were calculated for kinetic energies up to 1000 cm$^{-1}$. These cross sections were used to determine collisional rate constants for temperatures ranging from 5 K to 100 K. A propensity for even $\\Delta j$ transitions is observed in the case of HCN--He collisions whereas a propensity for odd $\\Delta j$ transitions is obse...

  12. The role of fusion in ant chromosome evolution: insights from cytogenetic analysis using a molecular phylogenetic approach in the genus mycetophylax.

    Science.gov (United States)

    Cardoso, Danon Clemes; das Graças Pompolo, Silvia; Cristiano, Maykon Passos; Tavares, Mara Garcia

    2014-01-01

    Among insect taxa, ants exhibit one of the most variable chromosome numbers ranging from n = 1 to n = 60. This high karyotype diversity is suggested to be correlated to ants diversification. The karyotype evolution of ants is usually understood in terms of Robertsonian rearrangements towards an increase in chromosome numbers. The ant genus Mycetophylax is a small monogynous basal Attini ant (Formicidae: Myrmicinae), endemic to sand dunes along the Brazilian coastlines. A recent taxonomic revision validates three species, Mycetophylax morschi, M. conformis and M. simplex. In this paper, we cytogenetically characterized all species that belongs to the genus and analyzed the karyotypic evolution of Mycetophylax in the context of a molecular phylogeny and ancestral character state reconstruction. M. morschi showed a polymorphic number of chromosomes, with colonies showing 2n = 26 and 2n = 30 chromosomes. M. conformis presented a diploid chromosome number of 30 chromosomes, while M. simplex showed 36 chromosomes. The probabilistic models suggest that the ancestral haploid chromosome number of Mycetophylax was 17 (Likelihood framework) or 18 (Bayesian framework). The analysis also suggested that fusions were responsible for the evolutionary reduction in chromosome numbers of M. conformis and M. morschi karyotypes whereas fission may determines the M. simplex karyotype. These results obtained show the importance of fusions in chromosome changes towards a chromosome number reduction in Formicidae and how a phylogenetic background can be used to reconstruct hypotheses about chromosomes evolution. PMID:24489918

  13. The history of the introduction of the giant river prawn, Macrobrachium cf. rosenbergii (Decapoda, Palaemonidae, in Brazil: new insights from molecular data

    Directory of Open Access Journals (Sweden)

    Gabriel Iketani

    2011-01-01

    Full Text Available The giant river prawn, Macrobrachium cf. rosenbergii, is one of the most cultivated freshwater prawns in the world and has been introduced into more than 40 countries. In some countries, this prawn is considered an invasive species that requires close monitoring. Recent changes in the taxonomy of this species (separation of M. rosenbergii and M. dacqueti require a re-evaluation of introduced taxa. In this work, molecular analyses were used to determine which of these two species was introduced into Brazil and to establish the geographic origin of the introduced populations that have invaded Amazonian coastal waters. The species introduced into Brazil was M. dacqueti through two introduction events involving prawns originating from Vietnam and either Bangladesh or Thailand. These origins differ from historical reports of the introductions and underline the need to confirm the origin of other exotic populations around the world. The invading populations in Amazonia require monitoring not only because the biodiversity of this region may be affected by the introduction, but also because admixture of different native haplotypes can increase the genetic variability and the likelihood of persistence of the invading species in new habitats.

  14. Taxonomic position of several enigmatic Polyommatus (Agrodiaetus species (Lepidoptera, Lycaenidae from Central and Eastern Iran: insights from molecular and chromosomal data

    Directory of Open Access Journals (Sweden)

    Vladimir Lukhtanov

    2014-12-01

    Full Text Available The species-rich subgenus Polyommatus (Agrodiaetus has become one of the best studied groups of Palearctic blue butterflies (Lepidoptera, Lycaenidae. However, the identity and phylogenetic position of some rare taxa from Iran have remained unclear. An enigmatic, recently described Central Iranian species P. (A. shirkuhensis ten Hagen et Eckweiler, 2001 has been considered as a taxon closely related either to P. (A. eckweileri ten Hagen, 1998 or to P. (A. baltazardi (de Lesse, 1962. P. (A. baltazardi, in its turn, was treated as a taxon close to Iranian-Pakistani P. (A. bogra Evans, 1932. Here we used a combination of molecular and chromosomal markers to show that none of these hypotheses was true. Instead, P. (A. shirkuhensis was recovered as a member of a species group close to P. (A. cyaneus (Staudinger, 1899. From genetically closest species, P. (A. kermansis (de Lesse, 1962, P. (A. cyaneus and P. (A. sennanensis (de Lesse, 1959, it differs by the wing coloration. From morphologically similar P. (A. mofidii (de Lesse, 1963 and P. (A. sorkhensis Eckweiler, 2003, it differs by its chromosome number, n=21. P. (A. bogra and P. (A. baltazardi were found to be members of two different species groups and, thus, are not closely related.

  15. Dual Inhibitory Pathways of Metallofullerenol Gd@C82(OH)22 on Matrix Metalloproteinase-2: Molecular insight into drug-like nanomedicine

    Science.gov (United States)

    Kang, Seung-Gu; Araya-Secchi, Raul; Wang, Deqiang; Wang, Bo; Huynh, Tien; Zhou, Ruhong

    2014-04-01

    Cancer metastasis is an important criterion to evaluate tumor malignancy. Matrix metalloproteinases (MMPs) play a crucial role in cancer proliferation and migration by virtue of their proteolytic functions in angiogenesis and extracelluar matrix (ECM) degradation, making them potential targets of anti-metastaic therapeutics. Recently we showed with both in vivo and in vitro experiments that metallofullerenol Gd@C82(OH)22 can effectively inhibit MMP-2 and MMP-9 with high antitumoral efficacy. Furthermore, our in silico study revealed that Gd@C82(OH)22 could indirectly inhibit the proteolysis of MMP-9 via allosteric modulation exclusively at the ligand specificity S1' loop. Here, we expand our study toward another gelatinase, MMP-2, using molecular dynamics simulations. Despite the high structural similarity with 64.3% sequence identity, their responses to Gd@C82(OH)22 were quite different. Toward MMP-2, Gd@C82(OH)22 could block either the Zn2+-catalylitic site directly or the S1' loop indirectly. Surface electrostatics uniquely determines the initial adsorption of Gd@C82(OH)22 on MMP-2, and then its further location of the most favorable binding site(s). These findings not only illustrated how the inhibitory mechanism of Gd@C82(OH)22 is distinguished between the two gelatinase MMPs with atomic details, but also shed light on the de novo design of anti-metastatic nanotherapeutics with enhanced target specificity.

  16. A novel C-type lysozyme from Mytilus galloprovincialis: insight into innate immunity and molecular evolution of invertebrate C-type lysozymes.

    Directory of Open Access Journals (Sweden)

    Qing Wang

    Full Text Available A c-type lysozyme (named as MgCLYZ gene was cloned from the mussel Mytilus galloprovincialis. Blast analysis indicated that MgCLYZ was a salivary c-type lysozyme which was mainly found in insects. The nucleotide sequence of MgCLYZ was predicted to encode a polypeptide of 154 amino acid residues with the signal peptide comprising the first 24 residues. The deduced mature peptide of MgCLYZ was of a calculated molecular weight of 14.4 kD and a theoretical isoelectric point (pI of 8.08. Evolution analysis suggested that bivalve branch of the invertebrate c-type lysozymes phylogeny tree underwent positive selection during evolution. By quantitative real-time RT-PCR (qRT-PCR analysis, MgCLYZ transcript was widely detected in all examined tissues and responded sensitively to bacterial challenge in hemocytes and hepatopancreas. The optimal temperature and pH of recombinant MgCLYZ (rMgCLYZ were 20°C and 4, respectively. The rMgCLYZ displayed lytic activities against Gram-positive bacteria including Micrococcus luteus and Staphyloccocus aureus, and Gram-negative bacteria including Vibrio anguillarum, Enterobacter cloacae, Pseudomonas putida, Proteus mirabilis and Bacillus aquimaris. These results suggest that MgCLYZ perhaps play an important role in innate immunity of M. galloprovincialis, and invertebrate c-type lysozymes might be under positive selection in a species-specific manner during evolution for undergoing adaptation to different environment and diverse pathogens.

  17. Crystal Structure and Substrate Specificity of Human Thioesterase 2: INSIGHTS INTO THE MOLECULAR BASIS FOR THE MODULATION OF FATTY ACID SYNTHASE.

    Science.gov (United States)

    Ritchie, Melissa K; Johnson, Lynnette C; Clodfelter, Jill E; Pemble, Charles W; Fulp, Brian E; Furdui, Cristina M; Kridel, Steven J; Lowther, W Todd

    2016-02-12

    The type I fatty acid synthase (FASN) is responsible for the de novo synthesis of palmitate. Chain length selection and release is performed by the C-terminal thioesterase domain (TE1). FASN expression is up-regulated in cancer, and its activity levels are controlled by gene dosage and transcriptional and post-translational mechanisms. In addition, the chain length of fatty acids produced by FASN is controlled by a type II thioesterase called TE2 (E.C. 3.1.2.14). TE2 has been implicated in breast cancer and generates a broad lipid distribution within milk. The molecular basis for the ability of the TE2 to compete with TE1 for the acyl chain attached to the acyl carrier protein (ACP) domain of FASN is unknown. Herein, we show that human TE1 efficiently hydrolyzes acyl-CoA substrate mimetics. In contrast, TE2 prefers an engineered human acyl-ACP substrate and readily releases short chain fatty acids from full-length FASN during turnover. The 2.8 Å crystal structure of TE2 reveals a novel capping domain insert within the α/β hydrolase core. This domain is reminiscent of capping domains of type II thioesterases involved in polyketide synthesis. The structure also reveals that the capping domain had collapsed onto the active site containing the Ser-101-His-237-Asp-212 catalytic triad. This observation suggests that the capping domain opens to enable the ACP domain to dock and to place the acyl chain and 4'-phosphopantetheinyl-linker arm correctly for catalysis. Thus, the ability of TE2 to prematurely release fatty acids from FASN parallels the role of editing thioesterases involved in polyketide and non-ribosomal peptide synthase synthases. PMID:26663084

  18. A new insight into the isotropic-nematic phase transition in lyotropic solutions of semiflexible polymers: density-functional theory tested by molecular dynamics.

    Science.gov (United States)

    Egorov, Sergei A; Milchev, Andrey; Virnau, Peter; Binder, Kurt

    2016-06-14

    Semiflexible polymers in solution are studied for a wide range of both contour length L and persistence length lp as a function of monomer concentration under good solvent conditions. Both density-functional theory (DFT) and molecular dynamics (MD) simulation methods are used, and a very good agreement between both techniques is observed for rather stiff polymers. Evidence for a new mechanism of order parameter fluctuations in the nematic phase is presented, namely collective deformations of bundles of wormlike chains twisted around each other, and the typical wavelengths and amplitudes of these modes are estimated. These long wavelength fluctuations cause a reduction of the order parameter in comparison with the DFT prediction. It is also found that DFT becomes unreliable for rather flexible polymers in predicting that the transition from the isotropic (I)-phase to the nematic (N)-phase still exists at very high monomer concentrations (which in reality does not occur). However, under conditions when DFT is accurate, it provides reliable predictions also for the width of the I-N two-phase coexistence region, which are difficult to obtain from MD in spite of the use of very large systems (up to 500 000 monomers) by means of graphics processing units (GPU). For short and not very stiff chains, a pre-transitional chain stretching is found in the isotropic phase near the I-N-transition, not predicted by theories. A comparison with theoretical predictions by Khokhlov-Semenov, Odijk, and Chen reveals that the scaled transition densities are not simply functions of L/lp only, as these theories predict, but depend on d/lp (where d is the chain diameter) as well. Chain properties in the nematically ordered phase are compared to those of chains confined in tubes, and the deflection length concept is tested. Eventually, some consequences for the interpretation of experiments are spelled out. PMID:27249320

  19. Viable But Not Culturable (VBNC) state of Brettanomyces bruxellensis in wine: New insights on molecular basis of VBNC behaviour using a transcriptomic approach.

    Science.gov (United States)

    Capozzi, Vittorio; Di Toro, Maria Rosaria; Grieco, Francesco; Michelotti, Vania; Salma, Mohammad; Lamontanara, Antonella; Russo, Pasquale; Orrù, Luigi; Alexandre, Hervé; Spano, Giuseppe

    2016-10-01

    The spoilage potential of Brettanomyces bruxellensis in wine is strongly connected with the aptitude of this yeast to enter in a Viable But Non Culturable (VBNC) state when exposed to the harsh wine conditions. In this work, we characterized the VBNC behaviour of seven strains of B. bruxellensis representing a regional intraspecific biodiversity, reporting conclusive evidence for the assessment of VBNC as a strain-dependent character. The VBNC behaviour was monitored by fluorescein diacetate staining/flow cytometry for eleven days after addition of 0.4, 0.6, 0.8, 1 and 1.2 mg/L of molecular SO2 (entrance in the VBNC state) and after SO2 removal (exit from the VBNC state). Furthermore, one representative strain was selected and RNA-seq analysis performed after exposure to 1.2 mg/L SO2 and during the recovery phase. 30 and 1634 genes were identified as differentially expressed following VBNC entrance and 'resuscitation', respectively. The results reported strongly suggested that the entrance in the SO2-induced VBNC state in B. bruxellensis is associated with both, sulfite toxicity and oxidative stress response, confirming the crucial role of genes/proteins involved in redox cell homeostasis. Among the genes induced during recovery, the expression of genes involved in carbohydrate metabolism and encoding heat shock proteins, as well as enriched categories including amino acid transport and transporter activity was observed. The evidences of a general repression of genes involved in DNA replication suggest the occurrence of a true resuscitation of cell rather than a simple regrowth. PMID:27375260

  20. Insights into the Lactonase Mechanism of Serum Paraoxonase 1 (PON1): Experimental and Quantum Mechanics/Molecular Mechanics (QM/MM) Studies.

    Science.gov (United States)

    Le, Quang Anh Tuan; Kim, Seonghoon; Chang, Rakwoo; Kim, Yong Hwan

    2015-07-30

    Serum paraoxonase 1 (PON1) is a versatile enzyme for the hydrolysis of various substrates (e.g., lactones, phosphotriesters) and for the formation of a promising chemical platform γ-valerolactone. Elucidation of the PON1-catalyzed lactonase reaction mechanism is very important for understanding the enzyme function and for engineering this enzyme for specific applications. Kinetic study and hybrid quantum mechanics/molecular mechanics (QM/MM) method were used to investigate the PON1-catalyzed lactonase reaction of γ-butyrolactone (GBL) and (R)-γ-valerolactone (GVL). The activation energies obtained from the QM/MM calculations were in good agreement with the experiments. Interestingly, the QM/MM energy barriers at MP2/3-21G(d,p) level for the lactonase of GVL and GBL were respectively 14.3-16.2 and 11.5-13.1 kcal/mol, consistent with the experimental values (15.57 and 14.73 kcal/mol derived from respective kcat values of 36.62 and 147.21 s(-1)). The QM/MM energy barriers at MP2/6-31G(d) and MP2/6-31G(d,p) levels were also in relatively good agreements with the experiments. Importantly, the difference in the QM/MM energy barriers at MP2 level with all investigated basis sets for the lactonase of GVL and GBL were in excellent agreement with the experiments (0.9-3.1 and 0.8 kcal/mol, respectively). A detailed mechanism for the PON1-catalyzed lactonase reaction was also proposed in this study. PMID:26146888

  1. The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency.

    Science.gov (United States)

    Montioli, Riccardo; Paiardini, Alessandro; Kurian, Manju A; Dindo, Mirco; Rossignoli, Giada; Heales, Simon J R; Pope, Simon; Voltattorni, Carla Borri; Bertoldi, Mariarita

    2016-06-01

    We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339). Arg347 appears to interact with Phe103, as well as with both Leu333 and Asp345. We have then prepared and characterized the artificial F103L, R347K and D345A mutants. F103L, D345A and R347K exhibit about 13-, 97-, and 345-fold kcat decrease compared to the wild-type AADC, respectively. However, unlike F103L, the R347G, R347K and R347Q mutants as well as the D345A variant appear to be more defective in catalysis than in protein folding. Moreover, the latter mutants, unlike the wild-type protein and the F103L variant, share a peculiar binding mode of dopa methyl ester consisting of formation of a quinonoid intermediate. This finding strongly suggests that their catalytic defects are mainly due to a misplacement of the substrate at the active site. Taken together, our results highlight the importance of the Arg347-Leu333-Asp345 hydrogen-bonds network in the catalysis of AADC and reveal the molecular basis for the pathogenicity of the variants R347. Following the above results, a therapeutic treatment for patients bearing the mutation R347G is proposed. PMID:26994895

  2. Network models provide insights into how oriens–lacunosum-moleculare and bistratified cell interactions influence the power of local hippocampal CA1 theta oscillations

    Directory of Open Access Journals (Sweden)

    Katie A Ferguson

    2015-08-01

    Full Text Available Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those between oriens--lacunosum-moleculare (OLM interneurons and bistratified cells (BiCs, make their contribution to network rhythms difficult to determine experimentally. We created network models that are tied to experimental work at both cellular and network levels to explore how these interneuron interactions affect the power of local oscillations. Our cellular models were constrained with properties from patch clamp recordings in the CA1 region of an intact hippocampus preparation in vitro. Our network models are composed of three different types of interneurons: parvalbumin-positive (PV+ basket and axo-axonic cells (BC/AACs, PV+ BiCs, and somatostatin-positive OLM cells. Also included is a spatially extended pyramidal cell model to allow for a simplified local field potential representation, as well as experimentally-constrained, theta frequency synaptic inputs to the interneurons. The network size, connectivity, and synaptic properties were constrained with experimental data. To determine how the interactions between OLM cells and BiCs could affect local theta power, we explored a number of OLM-BiC connections and connection strengths.We found that our models operate in regimes in which OLM cells minimally or strongly affected the power of network theta oscillations due to balances that, respectively, allow compensatory effects or not. Inactivation of OLM cells could result in no change or even an increase in theta power. We predict that the dis-inhibitory effect of OLM cells to BiCs to pyramidal cell interactions plays a critical role in the power of network theta oscillations. Our network models reveal a dynamic interplay between different classes of interneurons in influencing local theta

  3. Synthesis, structure elucidation, and redox properties of 99Tc complexes of lacunary Wells-Dawson polyoxometalates: insights into molecular 99Tc-metal oxide interactions.

    Science.gov (United States)

    McGregor, Donna; Burton-Pye, Benjamin P; Howell, Robertha C; Mbomekalle, Israel M; Lukens, Wayne W; Bian, Fang; Mausolf, Edward; Poineau, Frederic; Czerwinski, Kenneth R; Francesconi, Lynn C

    2011-03-01

    The isotope (99)Tc (β(max), 293.7; half-life, 2.1 × 10(5) years) is an abundant product of uranium-235 fission in nuclear reactors and is present throughout the radioactive waste stored in underground tanks at the Hanford and Savannah River sites. Understanding and controlling the extensive redox chemistry of (99)Tc is important in identifying tunable strategies to separate (99)Tc from spent fuel and from waste tanks and, once separated, to identify and develop an appropriately stable waste form for (99)Tc. Polyoxometalates (POMs), nanometer-sized models for metal oxide solid-state materials, are used in this study to provide a molecular level understanding of the speciation and redox chemistry of incorporated (99)Tc. In this study, (99)Tc complexes of the (α(2)-P(2)W(17)O(61))(10-) and (α(1)-P(2)W(17)O(61))(10-) isomers were prepared. Ethylene glycol was used as a "transfer ligand" to minimize the formation of TcO(2)·xH(2)O. The solution structures, formulations, and purity of Tc(V)O(α(1)/α(2)-P(2)W(17)O(61))(7-) were determined by multinuclear NMR. X-ray absorption spectroscopy of the complexes is in agreement with the formulation and structures determined from (31)P and (183)W NMR. Preliminary electrochemistry results are consistent with the EXAFS results, showing a facile reduction of the Tc(V)O(α(1)-P(2)W(17)O(61))(7-) species compared to the Tc(V)O(α(2)-P(2)W(17)O(61))(7-) analog. The α(1) defect is unique in that a basic oxygen atom is positioned toward the α(1) site, and the Tc(V)O center appears to form a dative metal-metal bond with a framework W site. These attributes may lead to the assistance of protonation events that facilitate reduction. Electrochemistry comparison shows that the Re(V) analogs are about 200 mV more difficult to reduce in accordance with periodic trends. PMID:21268605

  4. Speciation and thermodynamic properties of zinc in sulfur-rich hydrothermal fluids: Insights from ab initio molecular dynamics simulations and X-ray absorption spectroscopy

    Science.gov (United States)

    Mei, Yuan; Etschmann, Barbara; Liu, Weihua; Sherman, David M.; Testemale, Denis; Brugger, Joël

    2016-04-01

    Chlorine and sulfur are the main elements involved in the complexing of metals in ore-forming fluids. The nature and thermodynamic properties of the Zn(II)-Cl complexes have been investigated by previous experimental and theoretical studies and are now well established up to high temperatures (600 °C). In contrast, the role of bisulfide complexes for zinc speciation in sulfur-bearing fluids remains poorly known, and a better understanding of Zn(II)-HS complexation is required for modeling zinc transport in magmatic and metamorphic fluids and for optimizing the hydrometallurgical processing of sulfide ores. We have conducted ab initio molecular dynamics (MD) simulations to calculate the speciation of Zn(II)-HS complexes from ambient to hydrothermal-magmatic conditions (25-600 °C, up to 2000 bar). These theoretical calculations were complemented by X-ray absorption spectroscopy (XAS) measurements of Zn(II) in HS--rich solutions at 200-500 °C and 600-1000 bar. The speciation and geometrical properties predicted by the ab initio MD simulations and the in situ XAS data are in excellent agreement. Upon heating from room temperature to 250 °C, Zn(II) speciation in HS--rich solutions shows a transition from the sixfold octahedral hexaaquo complex [Zn(H2O)6]2+ to fourfold tetrahedral [Zn(HS)n(H2O)4-n]2-n complexes (n = 1-4). Ab initio MD simulations also show that at temperatures > 250 °C, the threefold trigonal-planar [Zn(HS)3]- complex becomes increasingly stable, and predominates in S-rich solutions; in contrast, chloro-complexes display a tetrahedral geometry at 25-500 °C, while trigonal planar ZnCl3- predominates at temperatures > 500 °C. The stability constants of Zn(II)-HS complexes were calculated by thermodynamic integration of constrained ab initio MD simulations at 200, 350 and 600 °C. The stability constants generated from this study predict that zinc can be transported by HS- at high temperature in reduced, neutral to alkaline solutions, while Zn

  5. Inherent dynamics of head domain correlates with ATP-recognition of P2X4 receptors: insights gained from molecular simulations.

    Directory of Open Access Journals (Sweden)

    Li-Dong Huang

    Full Text Available P2X receptors are ATP-gated ion channels involved in many physiological functions, and determination of ATP-recognition (AR of P2X receptors will promote the development of new therapeutic agents for pain, inflammation, bladder dysfunction and osteoporosis. Recent crystal structures of the zebrafish P2X4 (zfP2X4 receptor reveal a large ATP-binding pocket (ABP located at the subunit interface of zfP2X4 receptors, which is occupied by a conspicuous cluster of basic residues to recognize triphosphate moiety of ATP. Using the engineered affinity labeling and molecular modeling, at least three sites (S1, S2 and S3 within ABP have been identified that are able to recognize the adenine ring of ATP, implying the existence of at least three distinct AR modes in ABP. The open crystal structure of zfP2X4 confirms one of three AR modes (named AR1, in which the adenine ring of ATP is buried into site S1 while the triphosphate moiety interacts with clustered basic residues. Why architecture of ABP favors AR1 not the other two AR modes still remains unexplored. Here, we examine the potential role of inherent dynamics of head domain, a domain involved in ABP formation, in AR determinant of P2X4 receptors. In silico docking and binding free energy calculation revealed comparable characters of three distinct AR modes. Inherent dynamics of head domain, especially the downward motion favors the preference of ABP for AR1 rather than AR2 and AR3. Along with the downward motion of head domain, the closing movement of loop139-146 and loop169-183, and structural rearrangements of K70, K72, R298 and R143 enabled ABP to discriminate AR1 from other AR modes. Our observations suggest the essential role of head domain dynamics in determining AR of P2X4 receptors, allowing evaluation of new strategies aimed at developing specific blockers/allosteric modulators by preventing the dynamics of head domain associated with both AR and channel activation of P2X4 receptors.

  6. Corporate Climate Change

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The American Chamber of Commerce, the People's Republic of China (AmCham-China) and the American Chamber of Commerce in Shanghai recently released "American Corporate Experience in a Changing China: Insights From AmCham Business Climate Surveys, 1999-2005." Excerpts of the report follow:

  7. Climate for change

    International Nuclear Information System (INIS)

    Climate for Change: Non-State Actors and the Global Politics of the Greenhouse provides a challenging explanation of the forces that have shaped the international global warming debate. Unlike existing books on the politics of climate change, this book concentrates on how non-stage actors, such as scientific, environmental and industry groups, as opposed to governmental organisations, affect political outcomes in global fora on climate change. It also provides insights in to the role of the media in influencing the agenda. The book draws on a range of analytical approaches to assess and explain the influence of these non-governmental organisations in the course of global climate change politics. The book will be of interest to all researchers and policy-makers associated with climate change, and will be used on university courses in international relations, politics and environmental studies. (Author)

  8. Earth science: An extended yardstick for climate variability

    Science.gov (United States)

    Meckler, Nele

    2016-06-01

    Decoded and precisely dated information encrypted in stalagmites from a cave in China reveal past climatic changes and provide insight into the complex interactions in today's climate system. See Letter p.640

  9. Molecular Insights in MLL Rearranged Acute Leukemia

    NARCIS (Netherlands)

    R.W. Stam (Ronald)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence (~80%) of rearrangements of the MLL gene, resistance to several important chemotherapeutic drugs, and a poor treatment outcome. With overall survival rates for infant ALL not exceeding 50%

  10. Molecular Insights into Phospholipid -- NSAID Interactions

    Science.gov (United States)

    Babu Boggara, Mohan; Krishnamoorti, Ramanan

    2007-03-01

    Non steroidal anti inflammatory drugs (NSAIDs) e.g. Aspirin and Ibuprofen, with chronic usage cause gastro intestinal (GI) toxicity. It has been shown experimentally that NSAIDs pre-associated with phospholipids reduce the GI toxicity and also increase the therapeutic activity of these drugs compared to the unmodified ones. Using all atomistic simulations and two different methodologies, we studied the partitioning behavior of two model NSAIDs (Aspirin and Ibuprofen) as a function of pH and drug loading. The results from two methodologies are consistent in describing the equilibrium drug distribution in the bilayers. Additionally, the heterogeneity in density and polarity of the bilayer in the normal direction along with the fact that NSAIDs are amphiphilic (all of them have a carboxylic acid group and a non-polar part consisting of aromatic moieties), indicate that the diffusion mechanism in the bilayer is far different compared to the same in a bulk medium. This study summarizes the various effects of NSAIDs and their behavior inside the lipid bilayer both as a function of pH and drug concentration.

  11. Conflict in a changing climate

    Science.gov (United States)

    Carleton, T.; Hsiang, S. M.; Burke, M.

    2016-05-01

    A growing body of research illuminates the role that changes in climate have had on violent conflict and social instability in the recent past. Across a diversity of contexts, high temperatures and irregular rainfall have been causally linked to a range of conflict outcomes. These findings can be paired with climate model output to generate projections of the impact future climate change may have on conflicts such as crime and civil war. However, there are large degrees of uncertainty in such projections, arising from (i) the statistical uncertainty involved in regression analysis, (ii) divergent climate model predictions, and (iii) the unknown ability of human societies to adapt to future climate change. In this article, we review the empirical evidence of the climate-conflict relationship, provide insight into the likely extent and feasibility of adaptation to climate change as it pertains to human conflict, and discuss new methods that can be used to provide projections that capture these three sources of uncertainty.

  12. Climate sensitivity, sea level and atmospheric carbon dioxide

    OpenAIRE

    Hansen, James; Sato, Makiko; Russell, Gary; Kharecha, Pushker

    2013-01-01

    Cenozoic temperature, sea level and CO2 co-variations provide insights into climate sensitivity to external forcings and sea level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise paleoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity 3 +/- 1{\\deg}C for 4 W/m2 CO2 forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, bu...

  13. The fluid dynamics of climate

    CERN Document Server

    Palazzi, Elisa; Fraedrich, Klaus

    2016-01-01

    This volume provides an overview of the fluid aspects of the climate system, focusing on basic aspects as well as recent research developments. It will bring together contributions from diverse fields of the physical, mathematical and engineering sciences. The volume will be useful to doctorate students, postdocs and researchers working on different aspects of atmospheric, oceanic and environmental fluid dynamics. It will also be of interest to researchers interested in quantitatively understanding how fluid dynamics can be applied to the climate system, and to climate scientists willing to gain a deeper insight into the fluid mechanics underlying climate processes.

  14. A Proposal for Mapping Historic Irrigation Channels to Reveal Insights into Agro-Climatic Systems: A Case Study in Upper Austria. GI_Forum 2013 – Creating the GISociety|

    OpenAIRE

    Neuwirth, Christian; Eisank, Clemens; D'Oleire-Oltmanns, Sebastian

    2016-01-01

    Recently, the remains of two historic irrigation channels were re-discovered in the Upper Austrian municipality of Regau. Since the current average precipitation in the region is sufficient to sustain a productive agricultural land use, the irrigation channels raise several questions related to climate variability. To verify different hypotheses such as the construction as a response to a changing climate or the assumed purpose of grassland irrigation, potential coherences are discussed. In a...

  15. Functional cereals for production in new and variable climates.

    Science.gov (United States)

    Henry, Robert J; Rangan, Parimalan; Furtado, Agnelo

    2016-04-01

    Adaptation of cereal crops to variable or changing climates requires that essential quality attributes are maintained to deliver food that will be acceptable to human consumers. Advances in cereal genomics are delivering insights into the molecular basis of nutritional and functional quality traits in cereals and defining new genetic resources. Understanding the influence of the environment on expression of these traits will support the retention of these essential functional properties during climate adaptation. New cereals for use as whole grain or ground to flour for other food products may be based upon the traditional species such as rice and wheat currently used in these food applications but may also include new options exploiting genomics tools to allow accelerated domestication of new species. PMID:26828379

  16. Climate protection in practice: how municipalities master their ambitious climate protection goals

    International Nuclear Information System (INIS)

    This paper offers insights into the multifarious challenges facing municipalities in the field of municipal climate protection. It outlines typical local situations and explains the most important features of municipal climate protection: its specific goals and concepts and climate protection management and networking. It pinpoints success criteria and challenges and closes with some critical reflection.

  17. Climate change: Recent findings

    International Nuclear Information System (INIS)

    In the late eighties several reports have been published on climate change and sea level rise. In the meantime insights may have changed due to the availability of better and more observations and/or more advanced climate models. The aim of this report is to present the most recent findings with respect to climate change, in particular of sea level rise, storm surges and river peak flows. These climate factors are important for the safety of low-lying areas with respect to coastal erosion and flooding. In the first chapters a short review is presented of a few of the eighties reports. Furthermore, the predictions by state of the art climate models at that time are given. The reports from the eighties should be considered as 'old' information, whereas the IPCC supplement and work, for example, by Wigley should be considered as new information. To assess the latest findings two experts in this field were interviewed: dr J. Oerlemans and dr C.J.E. Schuurmans, a climate expert from the Royal Netherlands Meteorological Institute (KNMI). Their views are presented together with results published in recent papers on the subject. On the basis of this assessment, the report presents current knowledge regarding predictions of climate change (including sea-level rise) over the next century, together with an assessment of the uncertainties associated with these predictions. 14 figs., 11 tabs., 24 refs

  18. Climate Change

    Science.gov (United States)

    ... in a place over a period of time. Climate change is major change in temperature, rainfall, snow, or ... by natural factors or by human activities. Today climate changes are occurring at an increasingly rapid rate. Climate ...

  19. Populus Responses to Edaphic and Climatic Cues: Emerging Evidence from Systems Biology Research

    Energy Technology Data Exchange (ETDEWEB)

    Wullschleger, Stan D [ORNL; Weston, David [ORNL; Davis, John M [University of Florida

    2009-01-01

    The emergence of Populus as a model system for tree biology continues to be driven by a community of scientists dedicated to developing the resources needed to undertake genetic and functional genomic studies in this genus. As a result, understanding the molecular processes that underpin the growth and development of cottonwood, aspen, and hybrid poplar has steadily increased over the last several decades. Recently, our ability to examine the basic mechanisms whereby trees respond to a changing climate and resource limitations has benefited greatly from the sequencing of the P. trichocarpa genome. This landmark event has laid a solid foundation upon which biologists can now quantify, in breathtaking and unprecedented detail, the diversity of genes, proteins, and metabolites that govern the growth and development of some of the longest living and tallest growing organisms on Earth. Although the challenges likely to be encountered by scientists who work with trees are many, recent literature provides a few examples where a systems approach, one that focuses on integrating transcriptomic, proteomic, and metabolomic analyses, is beginning to provide insights into the molecular-scale response of poplars to their climatic and edaphic environment. In this review, our objectives are to look at evidence from studies that examine the molecular response of poplar to edaphic and climatic cues and highlight instances where two or more omic-scale measurements confirm and hopefully expand our inferences about mechanisms contributing to observed patterns of response. Based on conclusions drawn from these studies, we propose that three requirements will be essential as systems biology in poplar moves to reveal unique insights. These include use of genetically-defined individuals (e.g., pedigrees or transgenics) in studies; incorporation of modeling as a complement to transcriptomic, proteomic and metabolomic data; and inclusion of whole-tree and stand-level phenotypes to place

  20. Grabbing the 'clean slate' : The politics of the intersection of land grabbing, disasters and climate change : Insights from a local Philippine community in the aftermath of super typhoon Haiyan

    NARCIS (Netherlands)

    M. Uson (Maria Angelina Mariano)

    2015-01-01

    textabstractLand grabs in the wake of a disaster are nothing new. However this phenomenon gains certain particularities and interest when it happens within the current context of climate change policy initiatives and the global land rush. This nexus produces a new set of political processes containi

  1. INSIGHT, PSYCHOPATHOLOGY & SCHIZOPHRENIA

    OpenAIRE

    Armstrongh, K.P. Lincoln; Chandrasekaran, R.; Perme, Bojir

    2002-01-01

    25 inpatients with schizophrenia were examined to explore the relationship between insight and psychopathology and illness severity over a four-week period. The average degree of insight improved irrespective of the type of recovery. There was no consistent relationship between the changes in insight and changes in psychopathology. The severity of mental illness and awareness of mental disorder showed a semi-independent pattern of association. It is concluded that insight operates to some ext...

  2. Classroom climate in Serbia: The perspective of primary school teachers

    OpenAIRE

    Ševkušić Slavica; Anđelković Sonja; Milin Vladeta

    2014-01-01

    The goal of this research is to gain insight into the classroom climate in schools in Serbia from the perspective of teachers. To realize this goal, we set up two research questions: (1) How do teachers assess the importance of certain aspects of the classroom climate and their own engagement in creating favourable climate, and (2) which factors determine the quality of classroom climate. We considered four dimensions of classroom climate: equality in commu...

  3. Toward a safer moral climate.

    Science.gov (United States)

    Rodney, Patricia; Doane, Gweneth Hartrick; Storch, Janet; Varcoe, Colleen

    2006-10-01

    The authors define moral climate in the context of health care as the implicit and explicit values that drive health-care delivery and shape the workplaces in which care is delivered. Over the past six years, their research has focused on describing the moral climates of nurses' workplaces and improving them. In this article, the authors argue that nurses in direct care delivery roles have the insights, expertise and interpersonal skills required to create a much safer moral climate for practice. To make this happen, nurses require opportunities for self-reflection and for true collaboration with their colleagues in management and administration and other health-care disciplines. PMID:17094365

  4. Teaching Climate Social Science and Its Practices: A Two-Pronged Approach to Climate Literacy

    Science.gov (United States)

    Shwom, R.; Isenhour, C.; McCright, A.; Robinson, J.; Jordan, R.

    2014-12-01

    The Essential Principles of Climate Science Literacy states that a climate-literate individual can: "understand the essential principles of Earth's climate system, assess scientifically credible information about climate change, communicate about climate and climate change in a meaningful way, and make informed and responsible decisions with regard to actions that may affect climate." We argue that further integration of the social science dimensions of climate change will advance the climate literacy goals of communication and responsible actions. The underlying rationale for this argues: 1) teaching the habits of mind and scientific practices that have synergies across the social and natural sciences can strengthen students ability to understand and assess science in general and that 2) understanding the empirical research on the social, political, and economic processes (including climate science itself) that are part of the climate system is an important step for enabling effective action and communication. For example, while climate literacy has often identified the public's faulty mental models of climate processes as a partial explanation of complacency, emerging research suggests that the public's mental models of the social world are equally or more important in leading to informed and responsible climate decisions. Building student's ability to think across the social and natural sciences by understanding "how we know what we know" through the sciences and a scientific understanding of the social world allows us to achieve climate literacy goals more systematically and completely. To enable this integration we first identify the robust social science insights for the climate science literacy principles that involve social systems. We then briefly identify significant social science contributions to climate science literacy that do not clearly fit within the seven climate literacy principles but arguably could advance climate literacy goals. We conclude

  5. New insights into domestication of carrot from root transcriptome analyses

    NARCIS (Netherlands)

    Rong, J.; Lammers, Y.; Strasburg, J.L.; Schidlo, N.S.; Ariyurek, Y.; Jong, de T.J.; Klinkhamer, P.G.L.; Smulders, M.J.M.; Vrieling, K.

    2014-01-01

    Background - Understanding the molecular basis of domestication can provide insights into the processes of rapid evolution and crop improvement. Here we demonstrated the processes of carrot domestication and identified genes under selection based on transcriptome analyses. Results - The root transcr

  6. Oedipus and insight.

    Science.gov (United States)

    Michels, R

    1986-10-01

    Insight is a core concept in psychoanalytic theory. The Oedipus myth has been a central metaphor in the evolution of psychoanalytic theory, particularly the psychoanalytic theory of development. Similarly, Sophocles' drama, its relation to the myth, and its repeated reinterpretation throughout the ages provide a valuable metaphor for our understanding of the role of insight in psychoanalysis and in development. We may have underestimated the importance of insight in normal development while oversimplifying its significance as an agent of therapeutic change. PMID:3797556

  7. Dreaming and insight

    OpenAIRE

    Edwards, Christopher L; Perrine Marie RUBY; Malinowski, Josie E.; Bennett, Paul D.; Blagrove, Mark T.

    2013-01-01

    This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to ...

  8. Revisiting the evolutionary events in Allium subgenus Cyathophora (Amaryllidaceae): Insights into the effect of the Hengduan Mountains Region (HMR) uplift and Quaternary climatic fluctuations to the environmental changes in the Qinghai-Tibet Plateau.

    Science.gov (United States)

    Li, Min-Jie; Tan, Jin-Bo; Xie, Deng-Feng; Huang, De-Qing; Gao, Yun-Dong; He, Xing-Jin

    2016-01-01

    The respective roles that the Hengduan Mountains Region (HMR) uplift around 4-3 Ma and Quaternary climatic oscillations played in causing the environmental changes in the Qinghai-Tibet Plateau (QTP) remain unknown. Here, we reconstruct the evolutionary history of two varieties of Allium cyathophorum and A. spicatum of subgenus Cyathophora, restricted to the HMR and the western QTP, respectively. Forty-five populations were surveyed for chloroplast and nuclear sequence variation to evaluate phylogenetic relationships, dates of divergence and ancestral area/inflorescence reconstructions. In addition, analyses were conducted on discernable micromorphologies, cytotypes and seed size variation. Our results indicated that two varieties of A. cyathophorum are separate species, i.e. A. farreri and A. cyathophorum, and the initial split of Cyathophora was triggered by the HMR uplift around 4-3 Ma. Subsequently, A. spicatum originated through the strengthened aridification in the western QTP induced vicariance of the ancestral populations in the HMR during the early Pleistocene. A self-sustaining allotetraploid species from A. farreri and A. cyathophorum was established during an interglacial period of penultimate glaciation of the QTP. Seed size variation also supports these by the colonization-competition tradeoff among small and large seeds. Our findings appear to suggest that the HMR uplift could have strengthened the development of the Asian monsoon regimes in this region and aridification in the western QTP, while the Quaternary climatic oscillations spurred the allopatric species' range shifts and created new open microhabitat for the alloploid species. PMID:26458759

  9. Climate Informatics

    Science.gov (United States)

    Monteleoni, Claire; Schmidt, Gavin A.; Alexander, Francis J.; Niculescu-Mizil, Alexandru; Steinhaeuser, Karsten; Tippett, Michael; Banerjee, Arindam; Blumenthal, M. Benno; Ganguly, Auroop R.; Smerdon, Jason E.; Tedesco, Marco

    2013-01-01

    The impacts of present and potential future climate change will be one of the most important scientific and societal challenges in the 21st century. Given observed changes in temperature, sea ice, and sea level, improving our understanding of the climate system is an international priority. This system is characterized by complex phenomena that are imperfectly observed and even more imperfectly simulated. But with an ever-growing supply of climate data from satellites and environmental sensors, the magnitude of data and climate model output is beginning to overwhelm the relatively simple tools currently used to analyze them. A computational approach will therefore be indispensable for these analysis challenges. This chapter introduces the fledgling research discipline climate informatics: collaborations between climate scientists and machine learning researchers in order to bridge this gap between data and understanding. We hope that the study of climate informatics will accelerate discovery in answering pressing questions in climate science.

  10. Climate Change

    Science.gov (United States)

    ... can be caused by natural factors or by human activities. Today climate changes are occurring at an increasingly rapid rate. Climate change can affect our health. It can lead to More heat-related illness ...

  11. The Social Impact of Climate

    Science.gov (United States)

    Hsiang, S. M.

    2013-12-01

    Managing climate change requires that we understand the social value of climate-related decisions. Rational decision-making demands that we weigh the potential benefits of climate-related investments against their costs. To date, it has been challenging to quantify the relative social benefit of living under different climatic conditions, so policy debates tend to focus on investment costs without considering their benefits. Here I will discuss challenges and advances in the measurement of climate's impact on society. By linking data and methods across physical and social sciences, we are beginning to understand when, where, and how climatic conditions have a causal impact on human wellbeing. I will present examples from this burgeoning interdisciplinary field that quantify the effect of temperature on macroeconomic performance, the effects of climate on human conflict, and the long-term health and economic impact of tropical cyclones. Each of these examples provide new insight into previously unknown benefits of various climate management strategies. I conclude by describing new efforts to systematically gather and compare findings from across the research community to support informed and rational climate management decisions.

  12. Local Climate Action Plans in climate change mitigation - examining the case of Denmark

    DEFF Research Database (Denmark)

    Damsø, Tue Noa Jacques; Kjær, Tyge; Christensen, Thomas Budde

    2016-01-01

    The article examines the climate action plans (CAPs) of local governments (LGs) in Denmark. Applying a quantitative content analysis approach, all available Danish LG action plans within the climate and energy field has been collected and coded, giving insight into the extent of LG CAPs. We asses...

  13. Adaptation to climate change in urban areas: climate-greening London, Rotterdam, and Toronto

    NARCIS (Netherlands)

    Mees, H.L.P.; Driessen, P.P.J.

    2011-01-01

    This article aims to gain insight into the governance capacity of cities to adapt to climate change through urban green planning, which we will refer to as climate-greening. The use of green space is considered a no-regrets adaptation strategy, since it not only absorbs rainfall and moderates temper

  14. Triple oxygen and sulfur isotope analyses of sulfate extracted from voluminous volcanic ashes in the Oligocene John Day Formation: insight into dry climate conditions and ozone contribution to supereruptions

    Science.gov (United States)

    Workman, J.; Bindeman, I. N.; Martin, E.; Retallack, G.; Palandri, J. L.; Weldon, N.

    2014-12-01

    Large volume pyroclastic silicic eruptions emit hundreds of megatons of SO2 into the troposphere and stratosphere that is oxidized into sulfuric acid (H2SO4) by a variety of reactions with mass independent oxygen signatures (MIF), Δ17O>0. Sulfuric acid is then preserved as gypsum in parental volcanic deposits. Diagenic effects are mass dependent and can dilute, but otherwise do not affect MIF ratios. Pleistocene Yellowstone and Bishop tuffs and modern volcanic eruptions preserved under arid climate conditions in North American playa lakes, preserve small amounts of volcanic sulfate as gypsum. This gypsum's Δ17O>0, in combination with isotopic variations of δ18O, δ33S and δ34S is distinct from sedimentary sulfate and reveals its original MIF sulfate isotopic signal and the effect of super eruptions on the atmosphere, and ozone consumption in particular. We use linear algebraic equations to resolve volcanic versus sedimentary (MIF=0) sources. We have found that many large volume ignimbrites have very high initial Δ17O in volcanic sulfate that can only be acquired from reaction with stratospheric ozone. We here investigate nine thick (>2 m) ash beds ranging in age from ~33-23 Ma in the John Day Formation of central Oregon, including massive 28.6 Ma Picture Gorge tuff of newly identified Crooked River supercaldera. The 28.6 Ma Picture Gorge tuff (PGT) has the highest measured Δ17O of 3.5‰, and other tuffs (Tin Roof, Biotite, Deep Creek) have +1.3 to 3.4‰ Δ17O excesses. Sulfate from modern smaller tropospheric eruptions studied for comparison have a resolvable 0.4‰ range consistent with liquid-phase based H2O2 oxidation. The PGT is coeval with the ignimbrite flare-up in western N. America, the 28-29 Ma eruption of the 5000 km3 Fish Canyon tuff and the 28 Ma Never Summer Field eruption in Nebraska-Colorado that have the highest measured Δ17O of 6‰ (Bao et al. 2003). We speculate on the climatic/atmospheric effects of these multiple ~28 Ma supereruptions

  15. Achievements and opportunities from ESF Research Networking Programme: Natural molecular structures as drivers and tracers of terrestrial C fluxes, and COST Action 639: Greenhouse gas budget of soils under changing climate and land use

    Science.gov (United States)

    Boeckx, P.; Rasse, D.; Jandl, R.

    2009-04-01

    One of the activities of the European Science Foundation (ESF, www.esf.org) is developing European scale Research Networking Programmes (RNPs). RNPs lay the foundation for nationally funded research groups to address major scientific and research infrastructure issues, in order to advance the frontiers of existing science. MOLTER (www.esf.org/molter or www.molter.no) is such an RNP. MOLTER stands for "Natural molecular structures as drivers and tracers of terrestrial C fluxes" aims at stimulating the use of isotopic and organic chemistry to study carbon stabilization and biogeochemistry in terrestrial ecosystems and soils in particular. The understanding of the formation, stabilization and decomposition of complex organic compounds in the environment is currently being revolutionized by advanced techniques in identification, quantification, and origin tracing of functional groups and individual molecules. MOLTER focuses on five major research themes: - Molecular composition and turnover time of soil organic matter; - Plant molecular structures as drivers of C stabilisation in soils; - Fire transformations of plant and soil molecular structures - Molecular markers in soils; - Dissolved organic molecules in soils: origin, functionality and transport. These research themes are covered via the following activities: - Organisation of international conferences; - Organisation of specific topical workshops; - Organisation of summer schools for PhD students; - Short- and long-term exchange grants for scientists. MOLTER is supported by research funding or performing agencies from Austria, Belgium, France, Germany, the Netherlands, Norway, Romania, Spain, Sweden, Switzerland and the United Kingdom. The ESF is also the implementing agency of COST (European Cooperation in Science and Technology, www.cost.esf.org), one of the longest-running European instruments supporting cooperation among scientists and researchers across Europe. COST Action 639 "Greenhouse gas budget of

  16. Climate change or variable weather: Rethinking Danish homeowners' perceptions of floods and climate

    DEFF Research Database (Denmark)

    Baron, Nina; Petersen, Lars Kjerulf

    2015-01-01

    understand homeowners’ perception of climate change and local flood risk. Ingold argues that those perceptions are shaped by people’s experiences with and connections to their local landscape. People experience the local variability of the weather, and not global climate change as presented in statistical...... approaches gives new insights as to why people living in flood-prone areas are not very concerned about climate change....

  17. Climate Change

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn; Hansen, Ernst Jan de Place

    2011-01-01

    This paper presents the effects of climate change relevant for Denmark, including the change in mean year values as well as the extent of maximum and minimum extremes. Described by the Intergovernmental Panel on Climate Change, the assumptions that the scenarios are based on were outlined and...... evaluated in a Danish context. The uncertainty of the scenarios leaves major challenges that, if not addressed and taken into account in building design, will grow far more serious as climate change progresses. Cases implemented in the Danish building stock illustrate adaptation to climate change and...... illustrate how building design can include mitigating measures to counteract climate change. Cases studied were individual buildings as well as the urban environment. Furthermore the paper describes some of the issues that must be addressed, as the building sector is investing in measures to adapt to climate...

  18. Climate change

    International Nuclear Information System (INIS)

    Based on contributions on 120 French and foreign scientists representing different disciplines (mathematics, physics, mechanics, chemistry, biology, medicine, and so on), this report proposes an overview of the scientific knowledge and debate about climate change. It discusses the various indicators of climate evolution (temperatures, ice surfaces, sea level, biological indicators) and the various factors which may contribute to climate evolution (greenhouse gases, solar radiation). It also comments climate evolutions in the past as they can be investigated through some geological, thermal or geochemical indicators. Then, the authors describe and discuss the various climate mechanisms: solar activity, oceans, ice caps, greenhouse gases. In a third part, the authors discuss the different types of climate models which differ by the way they describe processes, and the current validation process for these models

  19. Climate Change

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn; Hansen, Ernst Jan de Place

    2011-01-01

    This paper presents the effects of climate change relevant for Denmark, including the change in mean year values as well as the extent of maximum and minimum extremes. Described by the Intergovernmental Panel on Climate Change, the assumptions that the scenarios are based on were outlined...... and evaluated in a Danish context. The uncertainty of the scenarios leaves major challenges that, if not addressed and taken into account in building design, will grow far more serious as climate change progresses. Cases implemented in the Danish building stock illustrate adaptation to climate change...... and illustrate how building design can include mitigating measures to counteract climate change. Cases studied were individual buildings as well as the urban environment. Furthermore the paper describes some of the issues that must be addressed, as the building sector is investing in measures to adapt to climate...

  20. Insight cognitif et schizophrenie

    OpenAIRE

    W. El-Hage; Lafay, N.; Wassouf, I.; Jaafari, N.

    2011-01-01

    Resume La schizophrenie est souvent associee a une meconnaissance du trouble severe et persistante. Ce deficit d?insight est correle a l?hypofrontalite mais independant du pronostic de la maladie ou du quotient intellectuel. L?insight cognitif est defini comme la difference entre la capacite de reflexion sur soi et la certitude dans cette reflexion. Cette capacite est trouvee diminuee dans la schizophrenie mais augmentee en cas de depression. Ainsi, la schizophrenie avec comorbidit...

  1. Climate variability and climate change

    International Nuclear Information System (INIS)

    Changes of variability with climate change are likely to have a substantial impact on vegetation and society, rivaling the importance of changes in the mean values themselves. A variety of paleoclimate and future climate simulations performed with the GISS global climate model is used to assess how the variabilities of temperature and precipitation are altered as climate warms or cools. In general, as climate warms, temperature variability decreases due to reductions in the latitudinal temperature gradient and precipitation variability increases together with the intensity of the hydrologic cycle. If future climate projections are accurate, the reduction in temperature variability will be minimized by the rapid change in mean temperatures, but the hydrologic variability will be amplified by increased evapotranspiration. Greater hydrologic variability would appear to pose a potentially severe problem for the next century. 19 refs.; 3 figs.; 2 tabs

  2. Climate variability and climate change

    International Nuclear Information System (INIS)

    Changes of variability with climate change are likely to have a substantial impact on vegetation and society, rivaling the importance of changes in the mean values themselves. A variety of paleoclimate and future climate simulations performed with the GISS global climate model is used to assess how the variabilities of temperature and precipitation are altered as climate warms or cools. In general, as climate warms, temperature variability decreases due to reductions in the latitudinal temperature gradient and precipitation variability increases together with the intensity of the hydrologic cycle. If future climate projections are accurate, the reduction in temperature variability will be minimized by the rapid change in mean temperatures, but the hydrologic variability will be amplified by increased evapotranspiration. Greater hydrologic variability would appear to pose a potentially severe problem for the next century

  3. Pattern recognition: recent insights from Dectin-1

    OpenAIRE

    Reid, Delyth M.; Gow, Neil AR; Brown, Gordon D.

    2009-01-01

    The β-glucan receptor Dectin-1 is an archetypical non-toll-like pattern recognition receptor expressed predominantly by myeloid cells, which can induce its own intracellular signalling and can mediate a variety of cellular responses, such as cytokine production. Recent identification of the components of these signalling pathways, such as Syk kinase, CARD9 and Raf-1, has provided novel insights into the molecular mechanisms underlying Dectin-1 function. Furthermore, a broader appreciation of ...

  4. Climate change versus land management in the Po Plain (Northern Italy) during the Bronze Age: New insights from the VP/VG sequence of the Terramara Santa Rosa di Poviglio

    Science.gov (United States)

    Cremaschi, Mauro; Mercuri, Anna Maria; Torri, Paola; Florenzano, Assunta; Pizzi, Chiara; Marchesini, Marco; Zerboni, Andrea

    2016-03-01

    The sedimentary infilling of the moat surrounding the Villaggio Piccolo of the Terramara Santa Rosa di Poviglio was analysed in order to obtain palaeoenvironmental inferences from sediments and pollen assemblage. The high-resolution stratigraphic sequence preserves evidence of the environmental changes that occurred in the Po Plain, in Northern Italy, during the Late Holocene. Our interdisciplinary approach permitted to study climatic and anthropic contributions to the environmental changes in this region. The relationships between these changes and land-use changes were investigated focussing on adaptive strategies of the Terramare people during the Middle and Recent Bronze ages (1550-1170 yr BC). The Terramare are archaeological remains of banked and moated villages, located in the central alluvial plain of the Po river. The Terramara of Santa Rosa consists of two adjoining settlements (Villaggio Grande and Villaggio Piccolo); the moat that separates the two parts of the site is c. 23 m large and reaches a maximum depth of 4 m from the extant ground level. The stratigraphic sequence VP/VG exposed by archaeological excavation inside the moat was sampled for pedosedimentary, thin section, and pollen analyses. Chronology is based on archaeological evidence, stratigraphic correlations and radiocarbon dating. Pedosedimentary features and biological records (pollen of aquatics and algal remains) demonstrate that shallow water, probably subjected to seasonal water-level oscillations, has always been present in the moat. In the lower units of the sequence, the laminations indicate standing water, while occurrence of reworked pollen testified the supply of sediments to the plain from catchment zones located in the Apennine. Open vegetation was widespread; economy was based on wood management, fruit collection on the wild or from cultivated woody plants, crop fields with a fairly diversified set of cereals especially increasing in variety during dryness or phases of water

  5. Population dynamics of Agriophyllum squarrosum, a pioneer annual plant endemic to mobile sand dunes, in response to global climate change.

    Science.gov (United States)

    Qian, Chaoju; Yin, Hengxia; Shi, Yong; Zhao, Jiecai; Yin, Chengliang; Luo, Wanyin; Dong, Zhibao; Chen, Guoxiong; Yan, Xia; Wang, Xiao-Ru; Ma, Xiao-Fei

    2016-01-01

    Climate change plays an important role in the transition of ecosystems. Stratigraphic investigations have suggested that the Asian interior experienced frequent transitions between grassland and desert ecosystems as a consequence of global climate change. Using maternally and bi-parentally inherited markers, we investigated the population dynamics of Agriophyllum squarrosum (Chenopodiaceae), an annual pioneer plant endemic to mobile sand dunes. Phylogeographic analysis revealed that A. squarrosum could originate from Gurbantunggut desert since ~1.6 Ma, and subsequently underwent three waves of colonisation into other deserts and sandy lands corresponding to several glaciations. The rapid population expansion and distribution range shifts of A. squarrosum from monsoonal climate zones suggested that the development of the monsoonal climate significantly enhanced the population growth and gene flow of A. squarrosum. These data also suggested that desertification of the fragile grassland ecosystems in the Qinghai-Tibetan Plateau was more ancient than previously suggested and will be aggravated under global warming in the future. This study provides new molecular phylogeographic insights into how pioneer annual plant species in desert ecosystems respond to global climate change, and facilitates evaluation of the ecological potential and genetic resources of future crops for non-arable dry lands to mitigate climate change. PMID:27210568

  6. Climate Physics

    Science.gov (United States)

    Space, William

    2007-01-01

    Numerous connections exist between climate science and topics normally covered in physics and physical science courses. For instance, lessons on heat and light can be used to introduce basic climate science, and the study of electric circuits provides a context for studying the relationship between electricity consumption and carbon pollution. To…

  7. Climate change

    NARCIS (Netherlands)

    Marchal, V.; Dellink, R.; Vuuren, D.P. van; Clapp, C.; Chateau, J.; Magné, B.; Lanzi, E.; Vliet, J. van

    2012-01-01

    This chapter analyses the policy implications of the climate change challenge. Are current emission reduction pledges made in Copenhagen/Cancun enough to stabilise the climate and limit global average temperature increase to 2 oC? If not, what will the consequences be? What alternative growth pathwa

  8. Climate change and climate policy

    International Nuclear Information System (INIS)

    The climate issue is a great political and scientific challenge for several reasons: (1) There are many uncertain aspects of the climate problem, such as future emission of climate gases, the response of the climate system upon these gases, and the effects of climate changes. (2) It is probable, however, that anthropogenic emission of climate gases, deforestation etc. will cause noticeable climate changes in the future. This might be observed as increased frequency of extreme weather situations. This appears to be a greater threat than a gradual increase of temperature and precipitation. (3) Since the climate system is large and react only relatively slowly on changes in for instance the emission of climate gases, the climate problem can only be solved by means of long-term measures. (4) The climate changes may be irreversible. A rational short-term strategy is to ensure maximum flexibility, which can be done by ''slowing down'' (curtailing emissions) and by avoiding irreversible actions as much as possible. The long-term challenge is to develop an economically responsible alternative to the present fossil-based energy system that permits carbon-efficient technologies to compete on price with coal and unconventional oil and gas. Norway is in a special position by being a large exporter of fossil fuel and at the same time wanting to appear responsible in environmental matters. This combination may incur considerable expenses upon Norway and it is therefore important that environmental commitments like the Kyoto agreement can be honoured to the lowest possible cost. The costs can be minimized by: (1) minimizing the measure costs in Norway, (2) working to make the international quota price as low as possible, and (3) reducing the loss of petroleum income as much as possible. This report describes the earth's climate history, the forces behind climatic changes and what the prospects for the future look like. It also reviews what is being done to curtail the emission of

  9. From climate assessment to climate services

    OpenAIRE

    Visbeck, Martin

    2008-01-01

    The Intergovernmental Panel for Climate Change has convinced the public that climate change is real. To tackle it, the panel needs complementary climate services that provide continuous climate information for all regions and the globe.

  10. Dreaming and insight

    Directory of Open Access Journals (Sweden)

    Christopher L Edwards

    2013-12-01

    Full Text Available This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years. Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996 therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams. The need to distinguish ‘aha’ experiences as a result of discovering a waking life source for part of a dream, from ‘aha’ experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared.

  11. Dreaming and insight.

    Science.gov (United States)

    Edwards, Christopher L; Ruby, Perrine M; Malinowski, Josie E; Bennett, Paul D; Blagrove, Mark T

    2013-01-01

    This paper addresses claims that dreams can be a source of personal insight. Whereas there has been anecdotal backing for such claims, there is now tangential support from findings of the facilitative effect of sleep on cognitive insight, and of REM sleep in particular on emotional memory consolidation. Furthermore, the presence in dreams of metaphorical representations of waking life indicates the possibility of novel insight as an emergent feature of such metaphorical mappings. In order to assess whether personal insight can occur as a result of the consideration of dream content, 11 dream group discussion sessions were conducted which followed the Ullman Dream Appreciation technique, one session for each of 11 participants (10 females, 1 male; mean age = 19.2 years). Self-ratings of deepened self-perception and personal gains from participation in the group sessions showed that the Ullman technique is an effective procedure for establishing connections between dream content and recent waking life experiences, although wake life sources were found for only 14% of dream report text. The mean Exploration-Insight score on the Gains from Dream Interpretation questionnaire was very high and comparable to outcomes from the well-established Hill (1996) therapist-led dream interpretation method. This score was associated between-subjects with pre-group positive Attitude Toward Dreams (ATD). The need to distinguish "aha" experiences as a result of discovering a waking life source for part of a dream, from "aha" experiences of personal insight as a result of considering dream content, is discussed. Difficulties are described in designing a control condition to which the dream report condition can be compared. PMID:24550849

  12. OpenGL Insights

    CERN Document Server

    Cozzi, Patrick

    2012-01-01

    Get Real-World Insight from Experienced Professionals in the OpenGL Community With OpenGL, OpenGL ES, and WebGL, real-time rendering is becoming available everywhere, from AAA games to mobile phones to web pages. Assembling contributions from experienced developers, vendors, researchers, and educators, OpenGL Insights presents real-world techniques for intermediate and advanced OpenGL, OpenGL ES, and WebGL developers. Go Beyond the Basics The book thoroughly covers a range of topics, including OpenGL 4.2 and recent extensions. It explains how to optimize for mobile devices, explores the design

  13. Climatic change

    International Nuclear Information System (INIS)

    This book proposes both a scientific and societal approach of a phenomenon which is today the object of lot of debates. Climates perception is illustrated with examples taken in various modern civilizations and in the history of mankind. The Sahara example illustrates the notion of climate evolution. The last chapters are devoted to forecasting and scenarios for the future, taking into account the share of uncertainty. The controversies generated by these forecasts and the Kyoto protocol stakes demonstrate the tight links between the scientific, economical and political aspects in climatic change debates. (J.S.)

  14. Climate Change Adaptation: Lessons from Urban Economics

    OpenAIRE

    Kahn, Matthew E.

    2014-01-01

    In an urbanizing world economy featuring thousands of cities, households and firms have strong incentives to make locational investments and self protection choices to reduce their exposure to new climate change induced risks. This pursuit of self interest reduces the costs imposed by climate change. This paper develops a dynamic compensating differentials model to explore how the “menu” offered by a system of cities insures us against emerging risks. Insights from urban economics offer a ser...

  15. Making Sustainable Energy Choices: Insights on the Energy/Water/Land Nexus

    Energy Technology Data Exchange (ETDEWEB)

    2014-10-01

    This periodic publication summarizes insights from the body of NREL analysis work. In this issue of Analysis Insights, we examine the implications of our energy choices on water, land use, climate, developmental goals, and other factors. Collectively, NREL's work helps policymakers and investors understand and evaluate energy choices within the complex web of connections, or nexus, between energy, water, and land.

  16. Computational study on the unbinding pathways of B-RAF inhibitors and its implication for the difference of residence time: insight from random acceleration and steered molecular dynamics simulations.

    Science.gov (United States)

    Niu, Yuzhen; Li, Shuyan; Pan, Dabo; Liu, Huanxiang; Yao, Xiaojun

    2016-02-21

    B-RAF kinase is a clinically validated target implicated in melanoma and advanced renal cell carcinoma (RCC). PLX4720 and TAK-632 are promising inhibitors against B-RAF with different dissociation rate constants (koff), but the specific mechanism that determines the difference of their dissociation rates remains unclear. In order to understand the kinetically different behaviors of these two inhibitors, their unbinding pathways were explored by random acceleration and steered molecular dynamics simulations. The random acceleration molecular dynamics (RAMD) simulations show that PLX4720 dissociates along the ATP-channel, while TAK-632 dissociates along either the ATP-channel or the allosteric-channel. The steered molecular dynamics (SMD) simulations reveal that TAK-632 is more favorable to escape from the binding pocket through the ATP-channel rather than the allosteric-channel. The PMF calculations suggest that TAK-632 presents longer residence time, which is in qualitative agreement with the experimental koff(koff = 3.3 × 10(-2) s(-1) and ΔGoff = -82.17 ± 0.29 kcal mol(-1) for PLX4720; koff = 1.9 × 10(-5) s(-1) and ΔGoff = -39.73 ± 0.79 kcal mol(-1) for PLX4720). Furthermore, the binding free decomposition by MM/GBSA illustrates that the residues K36, E54, V57, L58, L120, I125, H127, G146 and D147 located around the allosteric binding pocket play important roles in determining the longer residence time of TAK-632 by forming stronger hydrogen bond and hydrophobic interactions. Our simulations provide valuable information to design selective B-RAF inhibitors with long residence time in the future. PMID:26862741

  17. Habitable Climates

    CERN Document Server

    Spiegel, David S; Scharf, Caleb A

    2007-01-01

    The Earth is only partially habitable according to the standard liquid-water definition. We reconsider planetary habitability in the framework of energy-balance models, the simplest seasonal models in physical climatology, to assess the spatial and temporal habitability of Earth-like planets. In order to quantify the degree of climatic habitability of our models, we define several metrics of fractional habitability. Previous evaluations of habitable zones may have omitted important climatic conditions by focusing on close Solar System analogies. For example, we find that model pseudo-Earths with different rotation rates or different land-ocean fractions generally have fractional habitabilities that differ significantly from that of the Earth itself. Furthermore, the stability of a planet's climate against albedo-feedback snowball events strongly impacts its habitability. Therefore, issues of climate dynamics may be central in assessing the habitability of discovered terrestrial exoplanets, especially if astro...

  18. Climate catastrophes

    Science.gov (United States)

    Budyko, Mikhail

    1999-05-01

    Climate catastrophes, which many times occurred in the geological past, caused the extinction of large or small populations of animals and plants. Changes in the terrestrial and marine biota caused by the catastrophic climate changes undoubtedly resulted in considerable fluctuations in global carbon cycle and atmospheric gas composition. Primarily, carbon dioxide and other greenhouse gas contents were affected. The study of these catastrophes allows a conclusion that climate system is very sensitive to relatively small changes in climate-forcing factors (transparency of the atmosphere, changes in large glaciations, etc.). It is important to take this conclusion into account while estimating the possible consequences of now occurring anthropogenic warming caused by the increase in greenhouse gas concentration in the atmosphere.

  19. Climatic change

    International Nuclear Information System (INIS)

    In spite of man's remarkable advances in technology, ultimately he is still dependent on the Earth's climatic system for food and fresh water. The recent occurrences in certain regions of the world of climatic extremes such as excessive rain or droughts and unseasonably high or low temperatures have led to speculation that a major climatic change is occurring on a global scale. Some point to the recent drop in temperatures in the northern hemisphere as an indication that the Earth is entering a new ice age. Others see a global warming trend that may be due to a build-up of carbon dioxide in the atmosphere. An authoritative report on the subject has been prepared by a World Meteorological Organization Panel of Experts on Climatic Change. Excerpts from the report are given. (author)

  20. Climate Reconstructions

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Paleoclimatology Program archives reconstructions of past climatic conditions derived from paleoclimate proxies, in addition to the Program's large...

  1. Climate engineering

    OpenAIRE

    Platt, Ulrich

    2014-01-01

    Es klingt wie eine Mischung aus Größenwahn und Science Fiction: Wissenschaftler wollen das Klima mit Hightechverfahren beeinflussen. "Climate engineering" heißt der Fachbegriff. Natürlich geht es dabei nicht um den verregneten Sommer, sondern um den globalen Klimawandel. Campus-Reporter Nils Birschmann hat sich bei den Umweltforschern der Uni Heidelberg umgehört, ob was dran ist am "climate engineering". Der Beitrag erschien in der Sendereihe "Campus-Report" - einer Beitragsreihe, in ...

  2. High Molecular Weight Complex Analysis of Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1): Structural Insights into LMP-1’s Homo-Oligomerization and Lipid Raft Association

    Science.gov (United States)

    Wrobel, Christopher M.; Geiger, Timothy R.; Nix, Rebecca N.; Robitaille, Aaron M.; Balser, Sandra; Cervantes, Alfredo; Gonzalez, Miguel; Martin, Jennifer M.

    2013-01-01

    LMP-1 is a constitutively active Tumor Necrosis Factor Receptor analog encoded by Epstein-Barr virus. LMP-1 activation correlates with oligomerization and raft localization, but direct evidence of LMP-1 oligomers is limited. We report that LMP-1 forms multiple high molecular weight native LMP-1 complexes when analyzed by BN-PAGE, the largest of which are enriched in detergent resistant membranes. The largest of these high molecular weight complexes are not formed by purified LMP-1 or by loss of function LMP-1 mutants. Consistent with these results we find a dimeric form of LMP-1 that can be stabilized by disulfide crosslinking. We identify cysteine 238 in the C-terminus of LMP-1 as the crosslinked cysteine. Disulfide crosslinking occurs post-lysis but the dimer can be crosslinked in intact cells with membrane permeable crosslinkers. LMP-1/C238A retains wild type LMP-1 NF-κB activity. LMP-1’s TRAF binding, raft association and oligomerization are associated with the dimeric form of LMP-1. Our results suggest the possibility that the observed dimeric species results from inter-oligomeric crosslinking of LMP-1 molecules in adjacent core LMP-1 oligomers. PMID:24075898

  3. Climate certificates

    International Nuclear Information System (INIS)

    Reduced emissions of climate gases at the lowest cost require international cooperation in order to ensure that the most cost-efficient measures are taken. A market for emission rights is one way of achieving this. However, creating the right conditions for such a market to operate requires an unambiguous definition of the product to be traded. In this PM, the Swedish Power Association sketches out how such a product could be defined, and how a market for the resulting unambiguously defined product could be operated internationally, in parallel with other markets for energy products. Trade in climate certificates could become a joint EU approach to achieving common results within the field of climate policy. The main features of the proposal are as follows: Electricity producers would be allowed to issue climate certificates for electricity produced without climate-affecting emissions, e.g. in wind power plants. 1 kWh of electricity produced without emissions would entitle the utility to issue a climate certificate for 1 kWh. Electricity from power stations having low emissions, e.g. modern natural gas-fired plants, would entitle the utility to issue certificates in proportion to how much lower their emissions were in comparison with those from conventional coal-fired power stations. The number of certificates would be reduced by an individual coefficient, related directly to the quantity of climate-affecting emissions from the plant concerned. They would be traded and noted on markets in the various member countries. The certificates would not be nationally restricted, but could be traded across borders. Exchanges would be authorised by national authorities, in accordance with overall EU directives. These authorised exchanges would act as certification bodies, checking that certificates had been properly issued in accordance with a corresponding volume of electricity production. Electricity and certificates could be purchased from different suppliers. The

  4. Using Data from Climate Science to Teach Introductory Statistics

    Science.gov (United States)

    Witt, Gary

    2013-01-01

    This paper shows how the application of simple statistical methods can reveal to students important insights from climate data. While the popular press is filled with contradictory opinions about climate science, teachers can encourage students to use introductory-level statistics to analyze data for themselves on this important issue in public…

  5. World energy insight 2011

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-11-15

    The World Energy Insight 2011 is the official publication of the World Energy Council. It includes interviews, articles and case studies from a distinguished panel of World Energy Council Officers, CEOs, government ministers, academics and opinion formers from all areas of the energy sector and provides perspectives from around the globe. Government, industry and NGO's offer both policy and technology perspectives. The insights within this publication add to the work that WEC is doing to provide the forum for energy leaders, along with the on-going WEC studies and programmes on Energy Policies, 2050 Energy Scenarios, Energy Resources & Technologies, Energy for Urban Innovation, Rules Of Energy Trade and Global Energy Access.

  6. Trouble, Strategic Insights

    OpenAIRE

    Moran, Daniel

    2002-01-01

    Strategic Insights are authored monthly by analysts with the Center for Contemporary Conflict (CCC). The CCC is the research arm of the National Security Affairs Department at the Naval Postgraduate School in Monterey, California. The views expressed here are those of the author and do not necessarily represent the views of the Naval Postgraduate School, the Department of Defense, or the U.S. Government.

  7. Update on INSIGHTS Development

    Energy Technology Data Exchange (ETDEWEB)

    Not Listed; Eric Burgett

    2011-09-01

    INSIGHTS is a transformational separate effects testing capability to perform in situ irradiation studies and characterization of the microscale behavior of nuclear fuel materials under a wide variety of in-pile conditions. Separate effects testing including growth, irradiation, and monitoring of these materials, and encompasses the full science based approach for fuels development from the nanoscale to the mesoscale behavior of the sample material and other defects driven by the modeling and simulation efforts of INL.

  8. Climate change. Managing the risks

    International Nuclear Information System (INIS)

    In order to address the key question if a targeted approach to climate change response is feasible, different aspects of this question are analyzed. First, the scientific and political aspects of different options to determine specific long-term objectives for climate change are evaluated on the basis of the current scientific insights and the experiences over the last 5 years to develop climate objectives. Preliminary directions for such objectives are given. Next, important analytical tools are discussed that can be applied to analyze the different options and their implications in detail. In order to evaluate the implications of mitigation options, strategies that are consistent with the preliminary climate goals are analyzed in the third part. In chapter 2, the concept of long-term environmental goals, derived from critical levels of climate change, is discussed. Also a historical perspective is provided. A new, systematic regionalized and risk-based approach to elaborate the ultimate objective of the Framework Convention on Climate Change is proposed. In chapter 3 scenarios and integrated models are discussed. Central is the description of scenarios that were developed with RlVM's Integrated Model to Assess the Greenhouse Effect (IMAGE) and the US-EPA's Atmospheric Stabilization Framework (ASF). In chapter 4 potential long-term international emissions control strategies for the different sources and sinks of the most important greenhouse gases are analyzed. Carbon dioxide from energy, carbon dioxide from deforestation, and non-CO2 greenhouse gases are dealt with subsequently. The dissertation ends with general conclusions and recommendations for the further design of a targeted approach to climate change response, the development of analytical tools to support policy development in the area of climate change, and strategies that are consistent with preliminary long-term environmental goals. 66 figs., 8 tabs., 417 refs., 1 appendix

  9. The politics of insight.

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-06-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

  10. The politics of insight

    Science.gov (United States)

    Salvi, Carola; Cristofori, Irene; Grafman, Jordan; Beeman, Mark

    2016-01-01

    Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs. PMID:26810954

  11. Striatal neurodevelopment is dysregulated in purine metabolism deficiency and impacts DARPP-32, BDNF/TrkB expression and signaling: new insights on the molecular and cellular basis of Lesch-Nyhan Syndrome.