Crystal structure of a novel type of odorant binding protein from Anopheles gambiae, belonging to the C+ class

International audienceAnopheles gambiae (Agam) relies on its olfactory system to target human prey, leading eventually to injection of Plasmodium falciparum, the malaria vector. Odorant-binding proteins (OBPs) are the first line of proteins involved in odorant recognition. They interact with olfactory receptors and thus constitute an interesting target for insect control. We undertook a large-scale study of proteins belonging to the olfactory system of Agam with the aim of preventing insect bites by designing strong olfactory repellents. We determined the 3D structures of several Agam OBPs alone or in complex with model compounds. Here, we report the first 3D structure of a member of the OBP C+ class, AgamOBP47, which has a longer sequence than classical OBPs and contains 6 disulphide bridges. AgamOBP47 possesses a core of six a-helices and three disulphide bridges, similar to the classical OBP fold. Two extra loops and the N- and C-terminal extra segments contain two additional a-helices and are maintained together by three disulphide bridges. They are embrace the classical OBP core domain. The binding site of OBP47 is located between the core and the additional domains. Two crevices are observed on opposite sides of OBP47, which are joined together by a shallow channel of sufficient size to accommodate a model of the best tested ligand. The binding sites of C+ class OBPs exhibit therefore different characteristics of their binding site, as compared to classical OBPs, which should leave to markedly diverse functional implications

A De Novo Designed Metalloenzyme for the Hydration of CO 2

Protein design will ultimately allow for the creation of artificial enzymes with novel functions and unprecedented stability. To test our current mastery of nature’s approach to catalysis, a Zn II metalloenzyme was prepared using de novo design. α 3 DH 3 folds into a stable single‐stranded three‐helix bundle and binds Zn II with high affinity using His 3 O coordination. The resulting metalloenzyme catalyzes the hydration of CO 2 better than any small molecule model of carbonic anhydrase and with an efficiency within 1400‐fold of the fastest carbonic anhydrase isoform, CAII, and 11‐fold of CAIII. Chasing down the cheetah : A synthetic metalloenzyme was created that is capable of catalyzing the hydration of carbon dioxide with an efficiency within 1400‐fold of carbonic anhydrase II, one of the most efficient enzymes known. This designed zinc enzyme performs better than small‐molecule models of carbonic anhydrase. Picture: Zn purple, N dark blue, O red, C cyan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108029/1/anie_201404925_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108029/2/7900_ftp.pd

The challenge of systemic food change: Insights from cities

An emerging literature recognizes cities as the optimal scale for food policy innovation, pointing to their pervasive emphasis on the adoption of a systemic approach to address the complex socio-ecological issues that have disrupted the internal metabolism of the food system. To date, however, no empirical effort has been made to identify the meanings and goals attributed to such an approach by municipal actors who are concretely involved with its implementation. To begin to fill this gap, this paper analyzes data (collected through a semi-structured questionnaire and a focus group) from 33 cities across the globe as part of a project that aimed to understand how a systemic approach to food is interpreted and applied in different urban contexts and, more broadly, whether there is a gap between food systems theory and practice. The analysis highlights a widespread emphasis on food policy integration and on the creation of an inclusive governance context but it also uncovers low levels of engagement by city governments with key food system actors operating at higher governance scales. As the paper concludes, there are substantial knowledge gaps that raise the need for a new research and policy agenda focused on the dialectical relationships between ordinary food practices and infrastructural transformations to enhance understanding of the role of food in place-making processes and to meet the challenge of systemic food change

Commons-Based Governance under Uncertainty: The Role of Behaviours and Information

Una efficace governance dell'acqua di irrigazione è fondamentale per affrontare il futuro e la sostenibilità dei sistemi alimentari. I limiti alla gestione delle risorse idriche per la produzione primaria sono sempre più evidenti e complessità, incertezza e comportamenti umani ricevono sempre più considerazione. Per far fronte a questi fenomeni la comunità e le azioni collettive stanno emergendo come i domini più appropriati di analisi. Infatti la buona gestione di una risorsa condivisa dipende in gran parte da un'azione coordinata a livello individuale per ridurre la vulnerabilità del sistema a livello macro. Ma la cooperazione può essere in gioco quando si verificano cambiamenti imprevedibili e rapidi, minando in tal modo la capacità di resilienza e adattamento di una comunità. Nonostante la ricerca nel settore manca ancora la comprensione su fattori che favoriscono o limitano la cooperazione in condizioni di variabilità di una risorsa come l’acqua. Per contribuire a tale dibattito la presente ricerca si interessa a come i comportamenti cooperativi sono affetti dall’ incertezza e della conseguente interazione con i sistemi socio-ecologici. A tal fine proponiamo un modello che integra incertezza delle risorse disponibili, processi cognitivi e comportamenti sociali nel processo decisionale. Identifichiamo l'esperienza, l'accesso alle informazioni, la reciprocità e la rete come fattori di supporto a comportamenti cooperativi per utilizzatori delle risorse idriche in condizioni di incertezza di disponibilità.Effective irrigation water governance is crucial to address the future and sustainability of food systems. Limits to the governance of water resources for primary production are becoming more evident and complexity, uncertainty and human dimensions are receiving more consideration. To address these phenomena community level and collective actions issues are emerging as the most appropriate domains of analysis. In fact successful management of a shared resource largely depends on coordinated action at individual level that will reduce sector vulnerability at macro level. But cooperation can be at stake when unpredictable and rapid changes occur, thus undermining the capacity of community resiliency and adaptation. Despite the literature there is still lack of understanding concerning successful and constrains factors enabling cooperation under water changing conditions. To contribute the debate on how cooperative behaviours are affected by uncertainty and dig deeper in socio-ecological systems interactions, we propose an agent-based model integrating water resource uncertainty, cognitive processes and social behaviours into decision-making. We identify experience, access to information, reciprocity and network as factors supporting cooperative behaviours of resource users under water changing conditions

Generalization Bounds for Causal Regression: Insights, Guarantees and Sensitivity Analysis

Many algorithms have been recently proposed for causal machine learning. Yet, there is little to no theory on their quality, especially considering finite samples. In this work, we propose a theory based on generalization bounds that provides such guarantees. By introducing a novel change-of-measure inequality, we are able to tightly bound the model loss in terms of the deviation of the treatment propensities over the population, which we show can be empirically limited. Our theory is fully rigorous and holds even in the face of hidden confounding and violations of positivity. We demonstrate our bounds on semi-synthetic and real data, showcasing their remarkable tightness and practical utility

Sculpting Metal‐binding Environments in De Novo Designed Three‐helix Bundles

De novo protein design is a biologically relevant approach used to study the active centers of native metalloproteins. In this review, we will first discuss the design process in achieving α3D, a de novo designed three‐helix bundle peptide with a well‐defined fold. We will then cover our recent work in functionalizing the α3D framework by incorporating a tris(cysteine) and tris(histidine) motif. Our first design contains the thiol‐rich sites found in metalloregulatory proteins that control the levels of toxic metal ions (Hg, Cd, and Pb). The latter design recapitulates the catalytic site and activity of a natural metalloenzyme carbonic anhydrase. The review will conclude with future design goals aimed at introducing an asymmetric metal‐binding site in the α3D framework.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110624/1/85_ftp.pd

Family Size Evolution in Drosophila Chemosensory Gene Families: A Comparative Analysis with a Critical Appraisal of Methods

Gene turnover rates and the evolution of gene family sizes are important aspects of genome evolution. Here, we use curated sequence data of the major chemosensory gene families from Drosophila-the gustatory receptor, odorant receptor, ionotropic receptor, and odorant-binding protein families-to conduct a comparative analysis among families, exploring different methods to estimate gene birth and death rates, including an ad hoc simulation study. Remarkably, we found that the state-of-the-art methods may produce very different rate estimates, which may lead to disparate conclusions regarding the evolution of chemosensory gene family sizes in Drosophila. Among biological factors, we found that a peculiarity of D. sechellia's gene turnover rates was a major source of bias in global estimates, whereas gene conversion had negligible effects for the families analyzed herein. Turnover rates vary considerably among families, subfamilies, and ortholog groups although all analyzed families were quite dynamic in terms of gene turnover. Computer simulations showed that the methods that use ortholog group information appear to be the most accurate for the Drosophila chemosensory families. Most importantly, these results reveal the potential of rate heterogeneity among lineages to severely bias some turnover rate estimation methods and the need of further evaluating the performance of these methods in a more diverse sampling of gene families and phylogenetic contexts. Using branch-specific codon substitution models, we find further evidence of positive selection in recently duplicated genes, which attests to a nonneutral aspect of the gene birth-and-death process

Silver Complexation by Metallacryptates

We report the first complete characterization of metallycryptates encapsulating Ag(i) cations: carboxylato ligands derived from l-proline and l-alanine chelate and bridge six Cu(ii) centres arranged in a slightly distorted octahedral fashion

Comunicação interna, diferenciação, integração e fragmentação na cultura organizacional em uma instituição particular de ensino superior

The university Brazilian scene has undergone significant changes in recent times, especially in the private higher education. Note that in addition to the expansion of private institutions, the system is organized in a very professional manner, focused on the market and looking for short-term results. In this sense, it is assumed that the communication processes are important for the management of educational processes, especially internal communication processes. However, when talking about internal organizational communication, the analysis can be applied to a level considered even more comprehensive, the organizational culture. Studies of organizational culture are conducted, according to Martin (2001), considering three perspectives: integration, differentiation and fragmentation. These perspectives are differentiated mainly by the degree of consensus among the members of the organization about the cultural events. This implies that even before an internal communication to adopt "uniform" procedures, the degree of consensus of individuals and groups about cultural events (largely due to the communication processes) shows variations among themselves. This study aimed to analyze the three perspectives of differentiation, integration and fragmentation are present in the manifestations of organizational culture of an institution of higher education, particularly from its internal communication. The research method adopted was the only case study with qualitative and exploratory approach. Data were collected from document analysis, semi-structured interviews and participant observation. The results achieved responded to the research problem and show that this study points out the manifestation of the triad of prospects for Martin (2001) occurring simultaneously, thus making the complex culture of IES. In this sense, the new studies addressing the organizational culture is suggested, using other theoretical models, as well as the replication of this study in other higher education institutions or a comparative study between two or more institutions.O cenário brasileiro universitário passou por transformações significativas nos últimos tempos, principalmente no ensino superior privado. Nota-se que além da expansão das instituições privadas, o sistema está organizado de forma bastante profissional, focado no mercado e buscando resultados de curto prazo. Neste sentido, supõe-se que os processos comunicacionais adquirem importância para a gestão dos processos educacionais, principalmente os processos comunicacionais internos. Entretanto, ao se falar em comunicação organizacional interna, a análise pode ser transposta para um nível considerado ainda mais abrangente, o da cultura organizacional. Os estudos sobre cultura organizacional são conduzidos, segundo Martin (2001), considerando-se três perspectivas: a integração, a diferenciação e a fragmentação. Essas perspectivas são diferenciadas, principalmente, pelo grau de consenso existente entre os membros da organização acerca das manifestações culturais. Isto implica dizer que, mesmo diante de uma comunicação interna que adote procedimentos “uniformes”, o grau de consenso dos indivíduos e grupos acerca das manifestações culturais (em grande parte decorrente dos processos comunicacionais) apresenta variações entre si. Este estudo teve como objetivo analisar como as três perspectivas de diferenciação, integração e fragmentação se fazem presentes nas manifestações da cultura organizacional de uma Instituição de Ensino Superior, particularmente a partir de sua comunicação interna.O método de pesquisa adotado foi o estudo de caso único com abordagem qualitativa e exploratória. Os dados foram coletados a partir de análise documental, entrevistas semiestruturadas e observação participante. Os resultados alcançados responderam ao problema de pesquisa e demonstram que, esse estudo aponta a manifestação da tríade das perspectivas de Martin (2001) ocorrendo simultaneamente, tornando assim a cultura da IES complexa. Neste sentido, sugere-se a realização de novos estudos abordando a cultura organizacional, utilizando outros modelos teóricos, bem como, a replicação desse estudo em outras Instituições de Ensino Superior ou ainda um estudo comparativo entre duas ou mais instituições

THE MILAN URBAN FOOD POLICY PACT: THE POTENTIAL OF FOOD AND THE KEY ROLE OF CITIES IN LOCALIZING SDGS

Food security for all is a non-negotiable goal to ensure human survival in a healthy planet. Advancing in this field requires a transition towards more integrated policies encompassing the complexity of the food paradigm and its multifuncitonality in a global context. Cities are now recognized as key food- actors and have reacted with place-based solution to the failures of national and global food related policies. Recent developments, like the Milan Urban Food Policy Pact (MUFPP), consolidate the role of cities as key players of the global food system and create a space for collaboration in which cities act with local solution to address global issues through a translocal approach that is redefining the concept of decentralised cooperation. Furthermore the MUFPP offers a vision of food security as key policy component able to underpin fair, inclusive and sustainable human development. Cities for long time have been responsible for the ecological decline of urban living conditions and yet they are hub of socio-ecological innovations from social kitchens to advanced business food models and integrated urban planning. This paper addresses some key questions related to the additional value that the MUFPP provides to cities and to the global agenda and what lever it can move to stimulate a change