MRSD: a web server for metabolic route search and design

SUMMARY: We present a tool called MRSD (Metabolic Route Search and Design) to search and design routes based on the weighted compound transform diagraph. The search submodule returns routes between a source and product compound within seconds in the network of one or multiple organisms based on data from KEGG. The design submodule designs a route from an appointed compound in an interactive mode. The two complementary functions, Metabolic Route Search and Design, can be broadly used in biosynthesis, bio-pharmaceuticals and the other related fields. AVAILABILITY: bioinfo.ustc.edu.cn/softwares/MRSD/.     

A REASSESSMENT OF THE IMPACT OF THE EXXON VALDEZ OIL SPILL ON HARBOR SEALS (PHOCA VITULINA RICHARDSI) IN PRINCE WILLIAM SOUND, ALASKA

Analyses of population trends and movements of harbor seals in Prince William Sound (PWS) casts doubt on published findings that 302 seals were killed by the Exxon Valdez oil spill in 1989. Assumptions that seals have 100% fidelity to a haul-out, that they were not displaced by the spill and associated disturbances, and that population trends throughout PWS varied similarly, except for oil spill effects, are not supported. Survey efforts to account for missing seals in 1989 were incomplete, too late in the year, and geographically limited. Basic assumptions required for statistical comparisons of oiled and unoiled haul-outs were violated. Fourteen dead seals, mostly pups, were recovered in PWS. Cause of death in most instances could not be determined, nor could the proportion that would have died naturally. Evidence does not support high unsubstantiated mortality, but is more consistent with seals avoiding or moving away from some oiled haul-outs. Interpretation of survey results requires consideration of temporal and regional variation. "Route A" surveys of central and eastern PWS do not represent population trends in western PWS or at glacial haul-outs. To adequately monitor population trends of PWS as a whole, broader sampling must be conducted on a routine basis.     

Route Optimization for Mobile IP

Route Optimization has been designed within the IETF to ameliorate the problem of triangle routing, a routing artifact introduced by Mobile IP's requirement to route packets destined for a mobile node by way of its home network. In this article, we describe the current protocol specification for the Route Optimization protocol, concentrating on design decisions and justifications. Once the basic mechanisms are explained, we show how they are applied to enable foreign agents to offer smooth handoffs for mobile nodes, and describe the security operations that enable reliable operation of this handoff between foreign agents with which a mobile node has no pre-existing security relationship. This revised version was published online in August 2006 with corrections to the Cover Date.     

Re-evaluating the Silk Road's Qinghai Route using dendrochronology

The opening of the Silk Road vigorously promoted economic and cultural exchanges between Central Asia, Europe, northern India and China. The easternmost section of the ancient trade route was established during the Qin-Han period (221 BC to 220 AD). Previous research has shown that there were three routes: the first is known as the “Hexi Route”, the second is known as the “Juyan Route” or “Prairie Route”, and the third is known as the “Qinghai Route”. The Qinghai Route has long been viewed as merely an auxiliary line of the Hexi Route which was used when the main Hexi Route was blocked by warfare. Others believe that the Qinghai Route was used during the 5th to 6th century when it was controlled by Tuyuhun Kingdom. Yet, by the 7th to 8th century, after the Tibetan occupation of the region, it was no longer a main trade route. Dendrochronology, the study of tree-rings, is a precise dating method that can be accurate to the year. In this study, wood remains excavated from tombs along the ancient Qinghai Route were studied by the means of dendrochronology in order to determine the date and better understand when Qinghai Route was used. In the tombs a lot of commercial goods such as silk products, pottery, lacquer carpentry were found. The date of the tombs determined by dendrochronology when viewed together with other archaeological data, showed that from the early Tang Dynasty to the High Tang Dynasty (early 7th century to late 8th century), the Qinghai Route was one of the routes of communication between the West and China. This disproves the hypothesis that this route was only used during the 5th to 6th century.     

The Green Design Apprenticeship

In order to convey the results of our industrial ecology research to broader audiences, the Green Design Institute research group at Carnegie Mellon University offers the Green Design Apprenticeship for local high school students. The Green Design Apprenticeship introduces participants to industrial ecology concepts and how they intersect with engineering. The content of the program has evolved to include the topics of life cycle assessment, energy and water resources, transportation, and the built environment. The program has resulted in exposing a new generation of scholars to industrial ecology and has also benefited the research of graduate students involved with the program. The process of developing the instructional materials for younger, novice students based on complex industrial ecology research was a challenging task requiring thoughtful and iterative planning. Through the development and delivery of the program, we have experienced awareness of where our own research fits into the larger industrial ecology scope, have improved our communication of complex industrial ecology concepts into simple terms, and have gained valuable insight for engaging students in our teaching.     

Transmission of mitochondrial DNA disorders: possibilities for the elimination of mutated mitochondria

The recent article by D.T. Brown et al. (2006) discusses the transmission of mitochondrial DNA disorders. In the second part, the authors describe certain techniques that can be potentially used to eliminate the transmission of mutated mtDNA from mother to offspring. It is our opinion that this brief account needs broader explanation. Moreover, some approaches mentioned are not always correctly interpreted.     

Migratory connectivity of American woodcock derived using satellite telemetry

American woodcock (Scolopax minor; woodcock) migratory connectivity (i.e., association between breeding and wintering areas) is largely unknown, even though current woodcock management is predicated on such associations. Woodcock are currently managed in the Eastern and Central management regions in the United States with the boundary between management regions analogous to the boundary between the Atlantic and Mississippi flyways, based largely on analysis of band returns from hunters. Factors during migration influence survival and fitness, and existing data derived from banding and very high frequency telemetry provide only coarse-scale information to assess factors influencing woodcock migratory movement patterns and behavior. To assess whether current management-region boundaries correspond with woodcock migratory connectivity in the Central Management Region and to describe migration patterns with higher resolution than has been previously possible, we deployed satellite transmitters on 73 woodcock (25 adult and 28 juvenile females, and 8 adult and 12 juvenile males) and recorded 87 autumn or spring migration paths from 2014 to 2016. Marked woodcock used 2 primary migrations routes: a Western Route and a Central Route. The Western Route ran north-south, connecting the breeding and wintering grounds within the Central Management Region. The hourglass-shaped Central Route connected an area on the wintering grounds reaching from Texas to Florida, to sites throughout northeastern North America in both the Eastern Management Region and Central Management Region and woodcock following this route migrated through the area between the Appalachian Mountains and the Mississippi Alluvial Valley in western Tennessee during autumn and spring. Two of 17 woodcock captured associated with breeding areas in Michigan, Wisconsin, or Minnesota migrated to wintering sites in the Eastern Management Region and 12 marked woodcock captured on wintering areas in Texas and Louisiana migrated to breeding sites in the Eastern Management Region. Woodcock that used the Western Route exhibited high concentrations of stopovers during spring in the Arkansas Ozark Mountains and northern Missouri, and along the Mississippi River on the border between Wisconsin and Minnesota, and autumn concentrations of stopovers in southwestern Iowa, central Missouri, the Arkansas portion of the Ozark Mountains, and around the junction of Texas, Louisiana, Oklahoma, and Arkansas. Woodcock that used the Central Route exhibited high concentrations of stopovers during spring in northern Mississippi through western Tennessee, western Kentucky, and the Missouri Bootheel, and autumn concentrations of stopovers in northern Illinois, southwestern Ohio, and the portions of Kentucky and Tennessee west of the Appalachian Mountains. We suggest that current management of woodcock based on 2 management regions may not be consistent with the apparent lack of strong migratory connectivity we observed. Our results also suggest where management of migration habitat might be most beneficial to woodcock. © 2019 The Wildlife Society.     

Mutualism is not restricted to tree-killing bark beetles and fungi: the ecological stoichiometry of secondary bark beetles,fungi, and a scavenger

1. All bark beetles are in symbiosis with fungi. Although obligate mutualisms with fungi are common with tree-killing bark beetles (primaries), fungi associated with non-tree-killing bark beetles (secondaries) are usually dismissed as commensals. 2. Using an ecological stoichiometric approach, we show secondaries are also involved in nutrition-based mutualisms, some of which appear obligate, and that differences in symbiont provisioning efficiency have a potent effect on beetle carbon (C): nitrogen (N): phosphorus (P) ratios. 3. Some secondary beetles have high P contents and require efficient P provisioning via fungi, while others have low P contents that may allow them to exploit less efficient fungi or a broader range of species with variable efficiencies. A co-occurring scavenger that feeds on nutrient-poor bark beetle frass (excrement/boring residues) exhibited the lowest phosphorus content yet recorded for an invertebrate. 4. Our results generally support the growth-rate hypothesis that posits differences in C:P and N:P ratios in consumers are due to differential allocation of P to P-rich RNA to support growth. However, while the beetle species that accumulated the most biomass was considerably enriched in P and that with the least biomass was P-poor, one beetle species that was P-rich was also small possibly due to limitation by an element other than P. 5. Our results indicate that fungi are important to a broader range of bark beetles than previously recognised. Additional research is needed to describe how these various symbioses influence forest ecosystems via differential effects of fungi on host beetle fitness.     

Main migration routes of adventitious plants in Czechoslovakia

At the present time, three main migration routes of adventitious plants can be distinguished and defined in Czechoslovakia: (1) the Eastern Route, (2) the Elbe (Labe) Route, and (3) the Pannonian Route. Plant species approximately referring to individual routes are listed, too.     

Insight into the process of product expulsion in cellobiohydrolase Cel6A from Trichoderma reesei by computational modeling

Glycoside hydrolase cellulase family 6 from Trichoderma reesei (TrCel6A) is an important cellobiohydrolase to hydrolyze cellooligosaccharide into cellobiose. The knowledge of enzymatic mechanisms is critical for improving the conversion efficiency of cellulose into ethanol or other chemicals. However, the process of product expulsion, a key component of enzymatic depolymerization, from TrCel6A has not yet been described in detail. Here, conventional molecular dynamics and steered molecular dynamics (SMD) were applied to study product expulsion from TrCel6A. Tyr103 may be a crucial residue in product expulsion given that it exhibits two different posthydrolytic conformations. In one conformation, Tyr103 rotates to open the ?3 subsite. However, Tyr103 does not rotate in the other conformation. Three different routes for product expulsion were proposed on the basis of the two different conformations. The total energy barriers of the three routes were calculated through SMD simulations. The total energy barrier of product expulsion through Route 1, in which Tyr103 does not rotate, was 22.2 kcal·mol^?1. The total energy barriers of product expulsion through Routes 2 and 3, in which Tyr103 rotates to open the ?3 subsite, were 10.3 and 14.4 kcal·mol^?1, respectively. Therefore, Routes 2 and 3 have lower energy barriers than Route 1, and Route 2 is the thermodynamically optimal route for product expulsion. Consequently, the rotation of Tyr103 may be crucial for product release from TrCel6A. Results of this work have potential applications in cellulase engineering.     

Synthesis of 6I-amino-6I-deoxy-2I-VII,3I-VII-tetradeca-O-methyl-cyclomaltoheptaose

The preparation of 6(I)-amino-6(I)-deoxy-2(I-VII),3(I-VII)-tetradeca-O-methyl-cyclomaltoheptaose is reported. Two different routes (A and B), both starting from beta-cyclodextrin (betaCD), have been examined. Route A involved: (i) synthesis of heptakis(6-O-tert-butyldimethylsilyl)-betaCD from betaCD; (ii) permethylation of the secondary hydroxyl groups with methyl iodide and sodium hydride; (iii) desilylation of the primary hydroxyls with ammonium fluoride; (iv) monotosylation at O-6 position of per-(2,3-O-methyl)-betaCD; (5) nucleophilic replacement of the tosyl group with azide anion; (v) reduction of the azido group by catalytic transfer hydrogenation using hydrazine hydrate in the presence of Pd/C in methanol/water. Route B started from the known 6(I)-monoazido-6(I)-monodeoxy-beta-CD (two steps from beta-CD) and entailed: (i) protection of the remaining primary hydroxyls using tert-butyldimethylsilylchloride (TBDMSCl); (ii) exhaustive methylation of the secondary hydroxyls with methyl iodide and sodium hydride; (iii) removal of the TBDMS protecting groups with ammonium fluoride; (iv) reduction of the azido group as above. Route A was found to be less convenient than Route B due to the inherent difficulty of controlling the monotosylation of per-(2,3-O-methyl)-betaCD.     

On mitigating emissions leakage under biofuel policies

A reason for much pessimism about the environmental benefits of today's biofuels, essentially corn and sugarcane ethanol, is the so‐called indirect land‐use change (ILUC) emissions associated with expanding biofuel production. While there exist several simulation‐based estimates of indirect emissions, the empirical basis underlying key input parameters to such simulations is not beyond doubt, while empirical verification of indirect emissions is hard. Regardless, regulators have adopted global warming intensity ratings for biofuels based on those simulations and in some case are holding regulated firms accountable for (some forms of) leakage. Suffice to say that both the estimates of and the approach to regulating leakage are controversial. The objective of this study is therefore to review a wider economic in order to identify a broader set of policy options for mitigating emissions leakage. We find that controlling leakage by affixing responsibility to regulated firms lacks support in the broader literature, which emphasizes alternative approaches.     

Best of both worlds: Combining ecological and social research to inform conservation decisions in a Neotropical biodiversity hotspot

Conservation decision is a challenging and risky task when it aims at prioritizing species or protected areas (PAs) to prevent extinction while ensuring fair treatment of all stakeholders. Better conservation decisions are those made upon a broader evidence base that includes both ecological and social considerations. However, in some of the most biodiverse ecosystems on Earth — tropical forests, for instance — multicriteria decision-making has been constrained by the following (i) ecological and social datasets available have been obtained in an independent, non-integrated manner, with social data typically more scarce than ecological ones, and (ii) capacity in social and/or interdisciplinary data analysis among decision-maker is limited. We describe a conservation prioritization exercise that combined findings from independent ecological and social research conducted in the Brazilian Atlantic Forest, and propose methods to integrate, analyze and visualize data. We found that the outcomes based on combined ecological and social research findings were, in some cases, different from those based on any of these lines of evidence alone. Indeed, the input from relatively basic social research significantly changed the outcomes of decision-making based on the results of ecological research. Results corroborate the importance and cost-effectiveness of broadening the interdisciplinary evidence base for conservation decision-making, even when social data is scarce and analytical capacity is limited.     

Field biology of placozoans (Trichoplax): distribution, diversity, biotic interactions

The goal of this review is to highlight what little is known,and point to the bulk of what is yet to be learned, about thenatural history of placozoans in the field—in order tostimulate a broader search for placozoans and a fuller explorationof their distribution, diversity, and all other aspects of theirenigmatic lives. The documented geographic distribution of placozoanslies mostly in the nearshore, warm, marine waters of the tropicsand subtropics. Although placozoans have long been viewed asbenthic organisms, they can be more readily collected from thewater column, well above the sea bottom. The full life-historyof placozoans is unknown, including the nature of this abundantpelagic phase and all details of sexual reproduction and development.We note observations on the biota associated with placozoansin field collections, in particular the other regular membersof the microcommunity in which placozoans occur on our collectingplates and on some factors influencing this assemblage. Amongthe animals found are some potential predators against whichplacozoans appear to be defended, although the mechanisms arestill to be examined. Also yet to be uncovered is the full breadthof diversity in this phylum, certainly underrepresented by itssingle named species. We report here greatly expanded distributionsfor known haplotypes and fresh specimens that include a newhaplotype, and we review the evidence that many more almostcertainly await discovery. We also describe some methods forcollecting and handling these small, fragile animals.     

Patterns of seagrass macrobenthic biodiversity in the warm-temperate Knysna estuarine bay,Western Cape: a review

Aquatic Ecology - Knysna estuarine bay in South Africa's Garden Route National Park is that country's most significant estuarine system for biodiversity and conservation value. One...     

Effectiveness factor calculations for immobilized enzyme catalysts

The steady state, nonlinear diffusion equations which describe reactions in constrained enzyme solutions are of great interest in many biological and engineering applications. As in other types of nonlinear differential equations, exact analytical solutions do not exist except in some simplified cases. In this paper, a general procedure is presented for solving numerically for the substrate concentration profile and effectiveness factor utilizing the transformation method suggested by Na and Na. Design correlations for enzyme solutions constrained within spherical membranes are included. The use of a unique definition of the Thiele Modulus in these charts permits the clear illustration of the effects of substrate concentration and external mass transfer resistances on the overall effectiveness factor for the catalyst particle.     

Designing for emotion (among other things)

Using computational approaches to emotion in design appears problematic for a range of technical, cultural and aesthetic reasons. After introducing some of the reasons as to why I am sceptical of such approaches, I describe a prototype we built that tried to address some of these problems, using sensor-based inferencing to comment upon domestic ‘well-being’ in ways that encouraged users to take authority over the emotional judgements offered by the system. Unfortunately, over two iterations we concluded that the prototype we built was a failure. I discuss the possible reasons for this and conclude that many of the problems we found are relevant more generally for designs based on computational approaches to emotion. As an alternative, I advocate a broader view of interaction design in which open-ended designs serve as resources for individual appropriation, and suggest that emotional experiences become one of several outcomes of engaging with them.     

Selection,Morphological Integration,and Strepsirrhine Locomotor Adaptations

Clades with taxa that have multiple locomotor adaptations represent a direct way to test the relationship between adaptation and integration. If integration is influenced by functional requirements, integration should be most apparent where selection is strongest and less evident where selection has been relaxed. If integration is primarily regulated by genetic constraints, integration should be present irrespective of selection pressures. Here we use patterns of integration in the strepsirrhine fore- and hind limbs as a test case. Strepsirrhine locomotion is relatively well-studied, and there are multiple clades that share different locomotor modes. We found that quadrupeds have greater limb integration than vertical leapers. These results suggest that variation can be expressed if selection for integration is relaxed. However, an unexpected pattern was revealed, in which there appears to be some broader regulatory mechanism controlling overall limb integration. Our tests identified a strong correlation between integration of the forelimb and integration of the hind limb. This broader mechanism may be evidence of the primitive genetic control of limb integration.     

Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs)

Acid pump antagonists (APAs) such as the imidazo[1,2-a]pyridine AZD-0865 2 have proven efficacious at low oral doses in acid related gastric disorders. Herein we describe some of the broader SAR in this class of molecule and detail the discovery of an imidazo[1,2-a]pyridine 15 which has excellent efficacy in animal models of gastric acid secretion following oral administration, as well as a good overall developability profile. The discovery strategy focuses on use of heteroaryl and heterocyclic substituents at the C-6 position and optimization of developability characteristics through modulation of global physico-chemical properties.