Distinct Linkage Research Articles

Tailoring the Polarity of Charge Carriers in Graphene–Porphine–Graphene Molecular Junctions through Linkage Motifs

The ability to control the nature of charge carriers in single-molecule junctions is of paramount importance to the design of molecular scale CMOS logic circuits. One major limitation is that the present methods for tuning the polarity of the charge carriers in molecular junctions always rely on chemical modifications of certain moieties of the central molecule. Here we investigate this issue by computing the electronic transport properties of graphene–porphine–graphene (GPG) molecular junctions with the nonequilibrium Green’s function formalism combined with density functional theory. Our calculations show that the dominant charge carriers in these GPG junctions can be tuned from holes to electrons by simply varying the number of C–C covalent bonds formed at the porphine-graphene interfaces. When porphine is doubly fused to graphene, it exhibits p-type transport behavior; in contrast, the triply fused one displays n-type behavior. The cause of this is that distinct linkage motifs lead to a rearrangement of the molecular levels participating in charge transport. It is the first time that such effect is shown without using a chemical modification of the porphine. In addition, hydrogen tautomerization reaction in porphine induces a dramatic conductance switch for the doubly fused GPG junctions, suggesting promising applications of this system as two-level molecular switch or memory unit with binary digits.

Regulation of the Tumor-Suppressor BECLIN 1 by Distinct Ubiquitination Cascades.

Autophagy contributes to cellular homeostasis through the degradation of various intracellular targets such as proteins, organelles and microbes. This relates autophagy to various diseases such as infections, neurodegenerative diseases and cancer. A central component of the autophagy machinery is the class III phosphatidylinositol 3-kinase (PI3K-III) complex, which generates the signaling lipid phosphatidylinositol 3-phosphate (PtdIns3P). The catalytic subunit of this complex is the lipid-kinase VPS34, which associates with the membrane-targeting factor VPS15 as well as the multivalent adaptor protein BECLIN 1. A growing list of regulatory proteins binds to BECLIN 1 and modulates the activity of the PI3K-III complex. Here we discuss the regulation of BECLIN 1 by several different types of ubiquitination, resulting in distinct polyubiquitin chain linkages catalyzed by a set of E3 ligases. This contribution is part of the Special Issue “Ubiquitin System”.

An occupational ergonomics in the Indonesian state mandatory sustainable forest management instrument: A review

Designed as a biodiversity-maintenance concept, Sustainable Forest Management (SFM) considers not only forest for its ecological function, but also forestry workers whom play a significant role in executing the SFM program in the implementation stage. By using occupational ergonomics approach, this paper aims to examine how the Indonesian mandatory SFM certification, the so-called Pengelolaan Hutan Produksi Lestari (PHPL) positioned forestry workers in its SFM scheme. This issue is important since forestry work is a well-known profession with high occupational safety and health (OSH) risk. Content analysis on occupational ergonomics-related national policies and the mandatory PHPL Criteria and Indicators (C&I), and interviews with forest managers, PHPL auditor, and forestry workers indicate the poor performance of the instrument to assess the occupational-ergonomics-related factors at a practical level. This study reveals that PHPL is more of administrative liability obligation fulfillments rather than performance-based fulfillments (meanwhile, OSH status should be seen as an outcome of a good safety culture rather than an artifact/document). This study verifies content-overlap among the verifiers, content mismatch between the verifiers and the actual characteristic of forest operation, and the absence of distinct assessment standard. This study also discovers the existence of “ergonomics holes” in the PHPL C&I: (1) promoting a safe working environment for forestry workers, (2) distinct organization structural linkage on safety responsibility assignments, (3) emergency procedure, (4) distinct qualification for heavy machine operator and chemical technician, (5) sub-contract workers, and (6) the importance of management commitment and workers' participation. Revision on PHPL should seriously consider integrating OSH and well-being aspect as mentioned in Indonesia's national policies concerning manpower and occupational safety.

Towards an Understanding of HRDLean Strategy Linkages: A Multicase Study of Four U.S. Based Firms

The link between HRD and Lean strategy is not well explored in the existing literature and lacks empirical depth regarding how the two conceptual domains are connected. Specifically, we focus on the role of HRD in organizations undergoing Lean strategy implementation. We adopt a qualitative multicase study approach and identify ways in which organizations develop HRD and Lean strategy linkages (HRDLean). Building on previous research, we investigate four firms, all involved in the implementation of Lean strategy, and present a three‐phase emergent model that reflects our study findings regarding the distinct HRDLean linkages developed in these organizations. The model representing the case study data identifies sense making, alignment, and value‐enabling mechanisms as three distinctive outcomes that enhance the value of HRD in Lean strategy implementation. The strength of the HRDLean linkages demonstrate the value of integrating HRD with Operations for sustaining unit‐level performance and positively influence the perceptions of HRD contributions to organizational strategy in general. The implications for enhancing the role of HRD in organizations implementing strategy are explored.

Distribution and incorporation mode of the herbicide MCPA in soil derived organo-clay complexes

ABSTRACTThe incorporation of xenobiotics into soil, especially via covalent bonds or sequestration has a major influence on the environmental behavior including toxicity, mobility, and bioavailability. The incorporation mode of 4-chloro-2-methylphenoxyacetic acid (MCPA) into organo-clay complexes has been investigated under a low (8.5 mg MCPA/kg soil) and high (1000 mg MCPA/kg soil) applied concentration, during an incubation period of up to 120 days. Emphasis was laid on the elucidation of distinct covalent linkages between non-extractable MCPA residues and humic sub-fractions (humic acids, fulvic acids, and humin). The cleavage of compounds by a sequential chemical degradation procedure (OH−, BBr3, RuO4, TMAH thermochemolysis) revealed for both concentration levels ester/amide bonds as the predominate incorporation modes followed by ether linkages. A possible influence of the soil microbial activity on the mode of incorporation could be observed in case of the high level samples. Structure elucidation identified MCPA as the only nonextractable substance, whereas the metabolite 4-chloro-2-methylphenol was additionally found as bioavailable and bioaccessible compound.

Complex pectin metabolism by gut bacteria reveals novel catalytic functions.

Carbohydrate polymers drive microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron utilizes the most structurally complex glycan known; the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but one of its 21 distinct glycosidic linkages. We show that rhamnogalacturonan-II side-chain and backbone deconstruction are coordinated, to overcome steric constraints, and that degradation reveals previously undiscovered enzyme families and novel catalytic activities. The degradome informs revision of the current structural model of RG-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycans in the human diet.

Hemodialysis Disparities in African Americans: The Deeply Integrated Concept of Race in the Social Fabric of Our Society.

End-stage renal disease (ESRD) is one of the starkest examples of racial/ethnic disparities in health. Racial/ethnic minorities are 1.5 to nearly 4 times more likely than their non-Hispanic White counterparts to require renal replacement therapy (RRT), with African Americans suffering from the highest rates of ESRD. Despite improvements over the last 25 years, substantial racial differences are persistent in dialysis quality measures such as RRT modality options, dialysis adequacy, anemia, mineral and bone disease, vascular access, and pre-ESRD care. This report will outline the current status of racial disparities in key ESRD quality measures and explore the impact of race. While the term race represents a social construct, its association with health is more complex. Multiple individual and community level social determinants of health are defined by the social positioning of race in the U.S., while biologic differences may reflect distinct epigenetic changes and linkages to ancestral geographic origins. Together, these factors conspire to influence dialysis outcomes among African Americans with ESRD.

Synergistic effects and the co-existence of networks in clusters

Network systems like clusters are characterized by the coexistence of relational architectures with ties and nodes of different nature. While recent research has analysed how a set of structural features shape the dynamics and effects of one cluster network, the outstanding question is to what extent such features and outcomes are influenced by the concomitance of distinct content-related linkages. This paper integrates both network and evolutionary economic geography perspectives to develop and test a model that links innovation performance with the benefits that stem from technical and business relations. Data collected in a biotech cluster in the Valencia region (Spain) demonstrate the changing effect of brokerage and overlapping ties on innovation as a function of knowledge shared. Findings extend the theoretical understanding of how knowledge diffuses in clusters and provide valuable insights for both practitioners and policy makers.

Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne.

The post-translational modification of proteins with polyubiquitin regulates virtually all aspects of cell biology. Eight distinct chain linkage types co-exist in polyubiquitin and are independently regulated in cells. This 'ubiquitin code' determines the fate of the modified protein. Deubiquitinating enzymes of the ovarian tumour (OTU) family regulate cellular signalling by targeting distinct linkage types within polyubiquitin, and understanding their mechanisms of linkage specificity gives fundamental insights into the ubiquitin system. Here we reveal how the deubiquitinase Cezanne (also known as OTUD7B) specifically targets Lys11-linked polyubiquitin. Crystal structures of Cezanne alone and in complex with monoubiquitin and Lys11-linked diubiquitin, in combination with hydrogen-deuterium exchange mass spectrometry, enable us to reconstruct the enzymatic cycle in great detail. An intricate mechanism of ubiquitin-assisted conformational changes activates the enzyme, and while all chain types interact with the enzymatic S1 site, only Lys11-linked chains can bind productively across the active site and stimulate catalytic turnover. Our work highlights the plasticity of deubiquitinases and indicates that new conformational states can occur when a true substrate, such as diubiquitin, is bound at the active site.

Convergence in relationships between leaf traits, spectra and age across diverse canopy environments and two contrasting tropical forests.

Leaf age structures the phenology and development of plants, as well as the evolution of leaf traits over life histories. However, a general method for efficiently estimating leaf age across forests and canopy environments is lacking. Here, we explored the potential for a statistical model, previously developed for Peruvian sunlit leaves, to consistently predict leaf ages from leaf reflectance spectra across two contrasting forests in Peru and Brazil and across diverse canopy environments. The model performed well for independent Brazilian sunlit and shade canopy leaves (R2 =0.75-0.78), suggesting that canopy leaves (and their associated spectra) follow constrained developmental trajectories even in contrasting forests. The model did not perform as well for mid-canopy and understory leaves (R2 =0.27-0.29), because leaves in different environments have distinct traits and trait developmental trajectories. When we accounted for distinct environment-trait linkages - either by explicitly including traits and environments in the model, or, even better, by re-parameterizing the spectra-only model to implicitly capture distinct trait-trajectories in different environments - we achieved a more general model that well-predicted leaf age across forests and environments (R2 =0.79). Fundamental rules, linked to leaf environments, constrain the development of leaf traitsand allow for general prediction of leaf age from spectra across species, sites and canopy environments.

Synthesis of Isomeric Phosphoubiquitin Chains Reveals that Phosphorylation Controls Deubiquitinase Activity and Specificity

SummaryUbiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages.

Characterizing two types of transient intraseasonal oscillations in the Eastern Tibetan Plateau summer rainfall

During summer, the intraseasonal disturbances over the Eastern Tibetan Plateau (ETP) can initiate development of severe weather system downstream. Previous studies yielded inconsistent results on the intraseasonal variability (ISV) of summer rainfall in terms of periodicity, genesis process and propagation pathway over the EPT based on small samples. In this study, we detected two dominant peaks of transient ISV, centered on quasi-biweekly (12–24) days (QBW) and quasi-9 (8–11) days using daily rainfall data over the ETP during the period of 1992–2012. Composite analysis revealed that the two ISVs were predominantly associated with the non-stationary wave trains, which traveled along different pathways. For the QBW, its mid-latitude wave train featured a upper-level southeastward migration, originating in Northern Europe and traveling via the East European Plain, the Ural Mountains, Lake Balkhash–Lake Baikal, the Mongolian Plateau, and then continued southward to the ETP and South Asia; and its tropical wave train was characterized with a northwestward/northward migration in low-level, starting from the Philippine Sea (PS)–South China Sea (SCS) region, moving over northern Bay of Bengal–SCS region, and arriving over the southern fridge of TP and southern China. In contrast, for quasi-9-day, the most significant mid-latitudes variability featured an eastward propagating upper-level wave train, originating from Western Europe, passing across the Mediterranean, the Black and Caspian seas, arriving over the TP, and moving towards East Asia; and the most evident tropical variability exhibited a clear northwestward/westward migration of a low-level wave train, originating from PS, passing over Taiwan, and subsequently moving towards southeastern China. Their different spatiotemporal features of associated wave trains caused their distinct linkages with eastern China rainfall anomalies. A “meridional pattern” with a giant Ural Mountain Ridge was the most remarkable precursory signals in upstream region before the QBW wet phase occurrence, which was different from the quasi-9-day. The major processes generating the local wet spells for the two modes were commonly linked to the preceding boundary warming, the upper-level negative vorticity and low-level prevalent winds, which triggered the ascending anomaly and lower tropospheric pre-moistening. We also discussed the co-variation of the wave trains between mid-latitudes and low-latitudes. The distinct evolution related with the two ISVs over the ETP described here may provide a useful guidance for 2–3 weeks (extended range) forecasts over the ETP and its downstream regions.

Depositional systems in multiphase rifts: seismic case study from the Lofoten margin, Norway

AbstractThe evolution of depositional systems in multiphase rifts is influenced by the selective reactivation of faults between subsequent rift phases. The Middle Jurassic to Palaeocene tectonic history of the Lofoten margin, a segment of the North Atlantic rift system, is characterised by three distinct rift phases separated by long (>20 Myr) inter‐rift periods. The initial rift phase comprised a distinct fault initiation and linkage stage, whereas the later rift phases were characterised by selective reactivation of previously linked through‐going faults which resulted in immediate rift climax. Using 2‐D and 3‐D seismic reflection data in conjunction with shallow core data we present a 100 Myr record of shallow to deep marine depositional environments that includes deltaic clinoform packages, slope aprons and turbidite fans. The rapid re‐establishment of major faults during the later rift phases impacts on drainage systems and sediment supply. Firstly, the immediate localisation of strain and accumulation of displacement on few faults results in pronounced footwall uplift and possible fault block rotation along those faults, which makes it more likely for any antecedent fault‐transverse depositional systems to become reversed. Secondly, any antecedent axially‐sourced depositional systems that are inherited from the foregoing rift phase(s) are likely to be sustained after reactivation because such axial systems have already been directed around fault tips. Hence, the immediate localisation of strain through selective reactivation in the later rift phases restricts fault‐transverse sediment supply more than axial sediment supply, which is likely to be a key aspect of the tectono‐sedimentary evolution of multiphase rifts.

Distinct linkage between winter Tibetan Plateau snow depth and early summer Philippine Sea anomalous anticyclone

AbstractThis article demonstrates that the above‐normal Tibetan Plateau snow depth (TPSD) in winter appears to be followed by an intensified Philippine Sea anticyclone in June (PSAC‐J), and vice versa. This linkage is clearly independent of the relationship between the El Niño‐Southern Oscillation (ENSO) and the PSAC‐J. Moreover, winter TPSD anomalies are typically associated with a PSAC‐J pattern that shifts northwards compared with that associated with ENSO. A better understanding of the combined effects of the winter TPSD and ENSO on the PSAC‐J could improve our ability to predict both the East Asia summer monsoon and variations in the Meiyu–Changma–Baiu rainbelt.

Party–voter linkages derived from the calculus of voting model: Electoral mobilization in Ecuador

This article derives a theory of party–voter linkages. It uses the decision theoretic calculus of voting model to theorize about political party strategies to mobilize voters under democratic competition. I show that parties will devise categorically distinct linkage strategies to operate upon different terms in the calculus of voting model. In particular, the theory implies four strategies: programmatic, clientelist, symbolic, and vote-buying. I illustrate their empirical relevance with case narratives of four parties in Ecuador.

Synthesis, crystal structure, and optical property of a one-dimensional selenidostannate: [AEPPH2]2[Sn5Se12] (AEPP = N-aminoethylpiperazine)

A one-dimensional (1-D) selenidostannate, [AEPPH2]2[Sn5Se12] (AEPP=N-aminoethylpiperazine) (1), has been prepared under solvothermal condition and characterized. Single crystal X-ray analysis reveals that compound 1 crystallizes in the triclinic space group P-1, a=10.6351(7) Å, b=10.6850(7) Å, c=10.7771(7) Å, α=61.3440(10)°, β=62.4420(10)°, γ=67.4680(10). With distinct linkage modes between SnSe4 tetrahedrons and SnSe6 octahedrons, a secondary building unit (SBU) [Sn5Se14] is formed. Compound 1 contains infinite bead-like chains built up by the [Sn5Se14] SBUs, and the protonated [AEPPH2]2+ cations are located between the chain spaces. A pseudo 3-D network is formed through C–H···Se and N–H···Se hydrogen bonds between adjacent chains. Its optical property and theoretical band structure and density of state (DOS) calculations have also been studied.

Transcription factors, chromatin proteins and the diversification of Hemiptera

Availability of complete genomes provides a means to explore the evolution of enormous developmental, morphological, and behavioral diversity among insects. Hemipterans in particular show great diversity of both morphology and life history within a single order. To better understand the role of transcription regulators in the diversification of hemipterans, using sequence profile searches and hidden Markov models we computationally analyzed transcription factors (TFs) and chromatin proteins (CPs) in the recently available Rhodnius prolixus genome along with 13 other insect and 4 non-insect arthropod genomes. We generated a comprehensive collection of TFs and CPs across arthropods including 303 distinct types of domains in TFs and 139 in CPs. This, along with the availability of two hemipteran genomes, R. prolixus and Acyrthosiphon pisum, helped us identify possible determinants for their dramatic morphological and behavioral divergence. We identified five domain families (i.e. Pipsqueak, SAZ/MADF, THAP, FLYWCH and BED finger) as having undergone differential patterns of lineage-specific expansion in hemipterans or within hemipterans relative to other insects. These expansions appear to be at least in part driven by transposons, with the DNA-binding domains of transposases having provided the raw material for emergence of new TFs. Our analysis suggests that while R. prolixus probably retains a state closer to the ancestral hemipteran, A. pisum represents a highly derived state, with the emergence of asexual reproduction potentially favoring genome duplication and transposon expansion. Both hemipterans are predicted to possess active DNA methylation systems. However, in the course of their divergence, aphids seem to have expanded the ancestral hemipteran DNA methylation along with a distinctive linkage to the histone methylation system, as suggested by expansion of SET domain methylases, including those fused to methylated CpG recognition domains. Thus, differential use of DNA methylation and histone methylation might have played a role in emergence of polyphenism and cyclic parthenogenesis from the ancestral hemipteran.

Connectivity within estuaries: An otolith chemistry and muscle stable isotope approach

Understanding whether fish move among estuarine areas and habitats or show high site fidelity has major implications for habitat conservation and the safeguard of estuarine ecological integrity. Muscle stable isotopes (δ13C, δ15N) and otolith elemental composition (Li:Ca, Mg:Ca, Mn:Ca, Cu:Ca, Sr:Ca, Ba:Ca and Pb:Ca) were used to evaluate connectivity between two separate estuarine nursery areas in summer and autumn for juvenile age-0 Dicentrarchus labrax and Pomatoschistus microps. Distinct isotopic ratios and otolith elemental signatures were found between areas for D. labrax and P. microps, and in both sampling times. High classification accuracies to collection sites were achieved via otolith elemental signatures (80–94%), and a combined analysis using both muscle stable isotopes and otolith chemistry resulted in increased accuracy with no classification errors. Overall, low site connectivity was found for both species. The use of two distinct natural tags provided corroborative and complementary information on fish movement and intra-estuarine habitat use at different temporal scales, whilst elucidating distinct ecological and environmental linkages. Ultimately, the combined use of distinct natural tags showed great promise to unravel intra-estuarine connectivity patterns.

Structural Basis for the Catalytic Mechanism of DncV, Bacterial Homolog of Cyclic GMP-AMP Synthase

Cyclic dinucleotides (CDNs) play key roles as second messengers and signaling molecules in bacteria andmetazoans. The newly identified dinucleotide cyclase in Vibrio cholerae (DncV) produces three different CDNs containing two 3'-5' phosphodiester bonds, and its predominant product is cyclic GMP-AMP, whereas mammalian cyclic GMP-AMP synthase (cGAS) produces only cyclic GMP-AMP containing mixed 2'-5' phosphodiester bonds. We report the crystal structures of V.cholerae and Escherichia coli DncV in complex with various nucleotides in the pre-reaction states. The high-resolution structures revealed that DncV preferably recognizes ATP and GTP as acceptor and donor nucleotides, respectively, in the first nucleotidyl transfer reaction. Considering the recently reported intermediate structures, our pre-reaction state structures providethe precise mechanism of 3'-5' linked cyclic AMP-GMP production in bacteria. A comparison with cGAS in the pre-reaction states suggests that the orientation of the acceptor nucleotide primarily determines the distinct linkage specificities between DncV and cGAS.

Ubiquitin C-terminal hydrolases cleave isopeptide- and peptide-linked ubiquitin from structured proteins but do not edit ubiquitin homopolymers.

Modification of proteins with ubiquitin (Ub) occurs through a variety of topologically distinct Ub linkages, including Ube2W-mediated monoubiquitylation of N-terminal alpha amines to generate peptide-linked linear mono-Ub fusions. Protein ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs), many of which show striking preference for particular Ub linkage types. Here, we have screened for DUBs that preferentially cleave N-terminal Ub from protein substrates but do not act on Ub homopolymers. We show that members of the Ub C-terminal hydrolase (UCH) family of DUBs demonstrate this preference for N-terminal deubiquitylating activity as they are capable of cleaving N-terminal Ub from SUMO2 and Ube2W, while displaying no activity against any of the eight Ub linkage types. Surprisingly, this ability to cleave Ub from SUMO2 was 100 times more efficient for UCH-L3 when we deleted the unstructured N-terminus of SUMO2, demonstrating that UCH enzymes can cleave Ub from structured proteins. However, UCH-L3 could also cleave chemically synthesized isopeptide-linked Ub from lysine 11 (K11) of SUMO2 with similar efficiency, demonstrating that UCH DUB activity is not limited to peptide-linked Ub. These findings advance our understanding of the specificity of the UCH family of DUBs, which are strongly implicated in cancer and neurodegeneration but whose substrate preference has remained unclear. In addition, our findings suggest that the reversal of Ube2W-mediated N-terminal ubiquitylation may be one physiological role of UCH DUBs in vivo.