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Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2. We found that otsB2 is essential for growth of M. tuberculosis in vitro as well as for the acute infection phase in mice following aerosol infection. By contrast, otsB2 is not essential for the chronic infection phase in mice, highlighting the substantial remodelling of trehalose metabolism during infection by M. tuberculosis. Blocking OtsB2 resulted in the accumulation of its substrate T6P, which appears to be toxic, leading to the self-poisoning of cells. Accordingly, blocking T6P production in a ΔotsA mutant abrogated otsB2 essentiality. T6P accumulation elicited a global upregulation of more than 800 genes, which might result from an increase in RNA stability implied by the enhanced neutralization of toxins exhibiting ribonuclease activity. Surprisingly, overlap with the stress response caused by the accumulation of another toxic sugar phosphate molecule, maltose-1-phosphate, was minimal. A genome-wide screen for synthetic lethal interactions with otsA identified numerous genes, revealing additional potential drug targets synergistic with OtsB2 suitable for combination therapies that would minimize the emergence of resistance to OtsB2 inhibitors.

Mycobacterium tuberculosis synthesizes intra- and extracellular α-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the α-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of α-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in α-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways. We now show that α-glucan in mycobacteria is exclusively assembled intracellularly utilizing the building block α-maltose-1-phosphate as the substrate for the maltosyltransferase GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some α-glucan is exported to form the α-glucan capsule. There is an unexpected convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate α-maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known, we have now established that GlgA forms this phosphosugar from ADP-glucose and glucose 1-phosphate 1000-fold more efficiently than its hitherto described glycogen synthase activity. The two routes are connected by the common precursor ADP-glucose, allowing compensatory flux from one route to the other. Having elucidated this unexpected configuration of the metabolic pathways underlying α-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant devoid of α-glucan could be constructed, showing a direct link between the GlgE pathway, α-glucan biosynthesis and virulence in a mouse infection model.

Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of MspA-like porins in slow-growing mycobacteria.

Abstract Urban evolutionary ecology is inherently interdisciplinary. Moreover, it is a field with global significance. However, bringing researchers and resources together across fields and countries is challenging. Therefore, an online collaborative research hub, where common methods and best practices are shared among scientists from diverse geographic, ethnic, and career backgrounds would make research focused on urban evolutionary ecology more inclusive. Here, we describe a freely available online research hub for toolkits that facilitate global research in urban evolutionary ecology. We provide rationales and descriptions of toolkits for: (1) decolonizing urban evolutionary ecology; (2) identifying and fostering international collaborative partnerships; (3) common methods and freely‐available datasets for trait mapping across cities; (4) common methods and freely‐available datasets for cross‐city evolutionary ecology experiments; and (5) best practices and freely available resources for public outreach and communication of research findings in urban evolutionary ecology. We outline how the toolkits can be accessed, archived, and modified over time in order to sustain long‐term global research that will advance our understanding of urban evolutionary ecology.

Abstract There is a growing recognition that responding to climate change necessitates urban adaptation. We sketch a transdisciplinary research effort, arguing that actionable research on urban adaptation needs to recognize the nature of cities as social networks embedded in physical space. Given the pace, scale and socioeconomic outcomes of urbanization in the Global South, the specificities and history of its cities must be central to the study of how well-known agglomeration effects can facilitate adaptation. The proposed effort calls for the co-creation of knowledge involving scientists and stakeholders, especially those historically excluded from the design and implementation of urban development policies.

Abstract Urban ecological studies have the potential to expand our understanding of socioecological systems beyond that of an individual city or region. Cross‐comparative empirical work and synthesis are imperative to develop a general urban ecological theory. This can be achieved only if studies are replicable and generalizable. Transparency in methods reporting facilitates generalizability and replicability by documenting the decisions scientists make during the various steps of research design; this is particularly true for sampling design and selection because of their impact on both internal and external validity and the potential to unintentionally introduce bias. Three interdependent aspects of sample design are study sample selection (e.g., specific organisms, soils, or water), sample specification (measurement of specific variable of interest), and site selection (locations sampled). Of these, documentation of site selection—the where component of sample design—is underrepresented in the urban ecology literature. Using a stratified random sample of 158 papers from 12 major urban ecology journals, we investigated how researchers selected study sites in urban ecosystems and evaluated whether their site selection methods were transparent. We extracted data from these papers using a 50‐question, theory‐based questionnaire and a multiple‐reviewer approach. Our sample represented almost 45 years of urban ecology research across 40 different countries. We found that more than 80% of the papers we read were not transparent in their site selection methodology. We do not believe site selection methods are replicable for 70% of the papers read. Key weaknesses include incomplete descriptions of populations and sampling frames, urban gradients, sample selection methods, and property access. Low transparency in reporting the where methodology limits urban ecologists' ability to assess the internal and external validity of studies' findings and to replicate published studies; it also limits the generalizability of existing studies. The challenges of low transparency are particularly relevant in urban ecology, a field where standard protocols for site selection and delineation are still being developed. These limitations interfere with the fields' ability to build theory and inform policy. We conclude by offering a set of recommendations to increase transparency, replicability, and generalizability.

Abstract Sustainable urban systems (SUS) science is a new science integrating work across established and emerging disciplines, using diverse methods, and addressing issues at local, regional, national, and global scales. Advancing SUS requires the next generation of scholars and practitioners to excel at synthesis across disciplines and possess the skills to innovate in the realms of research, policy, and stakeholder engagement. We outline key tenets of graduate education in SUS, informed by historical and global perspectives. The sketch is an invitation to discuss how graduates in SUS should be trained to engage with the challenges and opportunities presented by continuing urbanization.

This article analyses the ego-documentary narratives authored by writers of the younger generation of the literature of the first wave of the Russian emigration. Writers like I. Odoevtseva (On the Banks of the Neva and On the Banks of the Seine), G. Kuznetsova (Grasse Diary), and N. Berberova (Italics Are Mine: Autobiography) turned out to be united by a common personal and literary fate. They established dialogue with literary predecessors, which largely determines the aesthetic position of the authors and their place in the literature of abroad. The memoirs of I. V. Odoevtseva, as memoirs of a participant in the literary life of the Silver Age and the first wave of emigration, make it possible to recreate and preserve the era in the faces of its most prominent representatives, not so much as poets but as unique people. The organisation of the narrative in the form of dialogues meets the task of directly “resurrecting” its characters in the mind of the future reader. G. N. Kuznetsova’s diary/memoir has a two-pronged task: firstly, it helps form an aesthetic idea of émigré life and the circle close to Bunin. Also, in the memory of the descendants, it not only preserves a man but also a unique artist, who was ahead of his time and felt dramatically at odds with his literary era. Finally, it depicts the complex process of formation and self-identification of a creative personality in their dialogue with the literary “forefathers”. N. N. Berberova, who creates a myth about herself and her contemporaries according to the laws of pan-aesthetic art, includes herself in the йmigrй literary canon with a “pantheon” of literary “ancestors” (with Khodasevich and Bunin at the centre): if not a writer of the first row, then an outstanding one, a talented creative personality keeping up with the times.

As lombalgias acometem a maioria dos equinos atletas, sendo estas, importantes causas de claudicação e queda de performance nestes animais. Contudo, localizar a origem destas alterações e quantificar a intensidade da dor não é uma tarefa fácil, uma vez que somente o exame físico destes atletas muitas vezes não é o bastante para encontrar o foco da lesão. A eficácia e rapidez no diagnóstico das enfermidades da coluna reduz o impacto econômico que estas alterações podem trazer, uma vez que o tratamento requer grande investimento. Entre as principais lombalgias, podem-se destacar a desmite do ligamento supra-espinhoso e o contato ou sobreposição dos processos espinhosos, também conhecida como Kissing Spines. O diagnóstico definitivo dessas patologias só é alcançado por meio de exames complementares, como a radiografia e a ultrassonografia. O presente estudo tem por objetivo revisar a anatomia e biomecânica, bem como as principais alterações da coluna equina e seus meios diagnósticos complementares, a fim de esclarecer a importância destas ferramentas diagnósticas da medicina equina.

Abstract Cities are uniquely complex systems regulated by interactions and feedbacks between nature and human society. Characteristics of human society—including culture, economics, technology and politics—underlie social patterns and activity, creating a heterogeneous environment that can influence and be influenced by both ecological and evolutionary processes. Increasing research on urban ecology and evolutionary biology has coincided with growing interest in eco‐evolutionary dynamics, which encompasses the interactions and reciprocal feedbacks between evolution and ecology. Research on both urban evolutionary biology and eco‐evolutionary dynamics frequently focuses on contemporary evolution of species that have potentially substantial ecological—and even social—significance. Still, little work fully integrates urban evolutionary biology and eco‐evolutionary dynamics, and rarely do researchers in either of these fields fully consider the role of human social patterns and processes. Because cities are fundamentally regulated by human activities, are inherently interconnected and are frequently undergoing social and economic transformation, they represent an opportunity for ecologists and evolutionary biologists to study urban “socio‐eco‐evolutionary dynamics.” Through this new framework, we encourage researchers of urban ecology and evolution to fully integrate human social drivers and feedbacks to increase understanding and conservation of ecosystems, their functions and their contributions to people within and outside cities.

This article considers a relevant issue connected with the first wave of Russian emigrants returning to their homeland in the works of N. N. Berberova, a representative of the younger generation of writers. The theme of return and images of the Soviet people are studied with reference to The Billancourt Manuscript from the cycle The Billancourt Tales (1930) and the novel The Last and the First (1929). The analysis of the narrative structure of the story The Billancourt Manuscript, which has a two-level organisation (description of the funeral of a friend of the narrator’s and reading his handwritten novel about his return to his homeland, Soviet Russia, the chronotope of a trip to the “dead” city and the author/main character’s meetings with relatives — Soviet people), reveals Berberova’s dystopian position as regards the idea of return, as well as aesthetic reflection on the tasks of émigré literature and the work as a “human document”. Return as “catching” of emigrant souls organised by the Soviet government in the novel The Last and the First is analysed in connection with the story of resettlement of ordinary immigrants to the French province of Provence. Pochvennichestvo in its basis, coming from the Slavophiles and Dostoevsky, the idea of spiritual salvation on earth, perceived not religiously, had a social, cultural, and generational meaning for the novice writer and was opposed to the utopia of return. The images and behaviour of the Soviet “catchers of souls”, the Kellerman father and son, unnecessarily bodily, focused on material benefits, unscrupulous, soulless, insidious, represent variants of new Soviet politicians, free from kinship and friendship, patriotism and compassion for their compatriots.

Abstract Urban ecosystems are rapidly expanding throughout the world, but how urban growth affects the evolutionary ecology of species living in urban areas remains largely unknown. Urban ecology has advanced our understanding of how the development of cities and towns change environmental conditions and alter ecological processes and patterns. However, despite decades of research in urban ecology, the extent to which urbanization influences evolutionary and eco‐evolutionary change has received little attention. The nascent field of urban evolutionary ecology seeks to understand how urbanization affects the evolution of populations, and how those evolutionary changes in turn influence the ecological dynamics of populations, communities, and ecosystems. Following a brief history of this emerging field, this Perspective article provides a research agenda and roadmap for future research aimed at advancing our understanding of the interplay between ecology and evolution of urban‐dwelling organisms. We identify six key questions that, if addressed, would significantly increase our understanding of how urbanization influences evolutionary processes. These questions consider how urbanization affects nonadaptive evolution, natural selection, and convergent evolution, in addition to the role of urban environmental heterogeneity on species evolution, and the roles of phenotypic plasticity versus adaptation on species’ abundance in cities. Our final question examines the impact of urbanization on evolutionary diversification. For each of these six questions, we suggest avenues for future research that will help advance the field of urban evolutionary ecology. Lastly, we highlight the importance of integrating urban evolutionary ecology into urban planning, conservation practice, pest management, and public engagement.

Summary: Record climate extremes are reducing urban liveability, compounding inequality, and threatening infrastructure. Adaptation measures that integrate technological, nature-based, and social solutions can provide multiple co-benefits to address complex socioecological issues in cities while increasing resilience to potential impacts. However, there remain many challenges to developing and implementing integrated solutions. In this Viewpoint, we consider the value of integrating across the three solution sets, the challenges and potential enablers for integrating solution sets, and present examples of challenges and adopted solutions in three cities with different urban contexts and climates (Freiburg, Germany; Durban, South Africa; and Singapore). We conclude with a discussion of research directions and provide a road map to identify the actions that enable successful implementation of integrated climate solutions. We highlight the need for more systematic research that targets enabling environments for integration; achieving integrated solutions in different contexts to avoid maladaptation; simultaneously improving liveability, sustainability, and equality; and replicating via transfer and scale-up of local solutions. Cities in systematically disadvantaged countries (sometimes referred to as the Global South) are central to future urban development and must be prioritised. Helping decision makers and communities understand the potential opportunities associated with integrated solutions for climate change will encourage urgent and deliberate strides towards adapting cities to the dynamic climate reality.

Many of the world’s major cities have implemented tree planting programs based on assumed environmental and social benefits of urban forests. Recent studies have increasingly tested these assumptions and provide empirical evidence for the contributions of tree planting programs, as well as their feasibility and limits, for solving or mitigating urban environmental and social issues. We propose that current evidence supports local cooling, stormwater absorption, and health benefits of urban trees for local residents. However, the potential for urban trees to appreciably mitigate greenhouse gas emissions and air pollution over a wide array of sites and environmental conditions is limited. Consequently, urban trees appear to be more promising for climate and pollution adaptation strategies than mitigation strategies. In large part, this is due to space constraints limiting the extent of urban tree canopies relative to the current magnitude of emissions. The most promising environmental and health impacts of urban trees are those that can be realized with well-stewarded tree planting and localized design interventions at site to municipal scales. Tree planting at these scales has documented benefits on local climate and health, which can be maximized through targeted site design followed by monitoring, adaptive management, and studies of long-term eco-evolutionary dynamics.

The analysis of immunosuppressive drugs allows the physician to monitor, and eventually correct, immunosuppressive therapy. The panel of molecules under evaluation includes cyclosporine A (CsA), tacrolimus, sirolimus, and everolimus. Initially, assays were performed by immunometric methods, but in the past few years this methodology has been largely superseded by a more accurate and specific technique, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), which is now considered the “gold standard” for immunosuppressant analysis. Both LC-MS/MS and often also immunoassays require a preanalytical manual sample preparation, which involves time-consuming sequential operations whose traceability is often hampered and adds up to the probability of gross errors. The aim of this work was to compare an “open” LC-MS/MS with a fully automated system, consisting of LC instrumentation combined with a triple quadrupole MS, named Thermo ScientificTM CascadionTM SM Clinical Analyzer (Cascadion). Such automated systems suit the requirements of the reference method and are designed to completely eliminate all of the manual procedures. More than 2000 immunosuppressant samples were analyzed both with the open LC-MS/MS and with Cascadion. Statistics allowed the evaluation of linearity, intra- and inter-assay CV%, bias %, limit of detection and of quantitation, and Passing–Bablok and Bland–Altman plots. Results indicated a good correlation between the two methods. In both cases, methods confirmed their suitability for diagnostic settings. Cascadion could provide support when the presence of specialized personnel is lacking, and/or when great productivity and continuous workflow are required.

Il volume raccoglie i contributi presentati nel convegno tenutosi a Genova nell’aprile 2016 sulla Gender Archaeology, che rappresenta uno dei più recenti approcci antropologici impiegati nello studio della coroplastica.

Resumo: este artigo apresenta o nível de atendimento à NBR-10.157/87, na implantação do Aterro Sanitário da cidade de Anápolis-GO. Utilizou-se ferramentas de geotecnologia para modelamento, agrupamento e disposição de dados objetivando a tomada de decisão quanto à aplicação à norma pertinente. Com base nos resultados obtidos pôde-se concluir que a maioria dos itens dispostos na norma foram atendidos, com exceção a três itens: 1) Proximidade a núcleos residenciais urbanos; 2) Distância para lençol freático; 3) Extensão da bacia de drenagem. Estes itens não puderam ser avaliados pela ausência de dados. Palavras-chave: Resíduos Sólidos Urbanos. Geotecnologias. Aterro Sanitário.

The exhibition catalogue Figurines. A Microcosmos of Clay is reviewed by Marina Albertocchi.

Marina Albertocchi recensisce il libro Figurines de terre cuite en Méditerranée grecque et romaine, 2. Iconographie et contextes. Edited by A. Muller and E. Lafli. Pp. 700, Presses Universitaires du Septentrion, Villeneuve d’Ascq 2015. ISBN 978-2-7574-1133-9.

Aim of the paper is twofold: first of all to draw a picture on the status quaestionis regarding the study of the plain ware at Gortyn, particularly for Roman and Late Roman periods, and secondly to outline some new research perspectives on this subject. The data collected thanks to the publications of the material brought to light in the recent excavations carried out in Gortyn allowed us to gain a clear image of the pottery production during these phases, for so long neglegted in the archaeological literature. But it’s surely with the study of the huge amount of pottery discovered in the archaeological investigations now carried out in different areas of the Roman settlement that we can improve (together with archaeometrical analyses, up to now not existing) the knowledge of the Gortynian plain ware in the different phases of its long history.

Urbanization and the resulting changes in land cover have myriad impacts on ecological systems. Monitoring these changes across large spatial extents and long time spans requires synoptic remotely sensed data with an appropriate temporal sequence. We developed a multi-temporal land cover dataset for a six-county area surrounding the Seattle, Washington State, USA, metropolitan region. Land cover maps for 1986, 1991, 1995, 1999, and 2002 were developed from Landsat TM images through a combination of spectral unmixing, image segmentation, multi-season imagery, and supervised classification approaches to differentiate an initial nine land cover classes. We then used ancillary GIS layers and temporal information to define trajectories of land cover change through multiple updating and backdating rules and refined our land cover classification for each date into 14 classes. We compared the accuracy of the initial approach with the landscape trajectory modifications and determined that the use of landscape trajectory rules increased our ability to differentiate several classes including bare soil (separated into cleared for development, agriculture, and clearcut forest) and three intensities of urban. Using the temporal dataset, we found that between 1986 and 2002, urban land cover increased from 8 to 18% of our study area, while lowland deciduous and mixed forests decreased from 21 to 14%, and grass and agriculture decreased from 11 to 8%. The intensity of urban land cover increased with 252 km2 in Heavy Urban in 1986 increasing to 629 km2 by 2002. The ecological systems that are present in this region were likely significantly altered by these changes in land cover. Our results suggest that multi-temporal (i.e., multiple years and multiple seasons within years) Landsat data are an economical means to quantify land cover and land cover change across large and highly heterogeneous urbanizing landscapes. Our data, and similar temporal land cover change products, have been used in ecological modeling of past, present, and likely future changes in ecological systems (e.g., avian biodiversity, water quality). Such data are important inputs for ecological modelers, policy makers, and urban planners to manage and plan for future landscape change.