Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Etiology in a taxonomy of illnesses

According to what Robert Koch termed the etiological standpoint, illnesses are best understood and controlled by focusing on their causes, including in their definitions and, thus, in the construction of their taxonomies. In some ways flawed, this standpoint has been misunderstood and misapplied. A taxonomy based solely on etiology was an unrealistic dream in the context of 'the bacteriological revolution', and it also is unrealistic in the present context of 'the genetic revolution.' We argue that the illnesses in a taxonomy of them are in some cases best defined directly in terms of their respective somatic anomalies, in some others indirectly by the unique and universal etiology of that anomaly (left unspecified) in a 'deeper' somatic anomaly, and in yet others as a combination of these; and when the somatic anomaly for direct definition remains unknown, it is to be defined indirectly by the clinical syndrome that is its patient-relevant manifestation, possibly in conjunction with a somatic cause. We note, also, that these taxonomic issues have no material bearing on epidemiologists' etiologic research for the knowledge base of community-level preventive medicine.

Strengthening of laterality of verbal and visuospatial functions during childhood and adolescence

Cognitive functions in the child's brain develop in the context of complex adaptive processes, determined by genetic and environmental factors. Little is known about the cerebral representation of cognitive functions during development. In particular, knowledge about the development of right hemispheric (RH) functions is scarce. Considering the dynamics of brain development, localization and lateralization of cognitive functions must be expected to change with age. Twenty healthy subjects (8.6-20.5 years) were examined with fMRI and neuropsychological tests. All participants completed two fMRI tasks known to activate left hemispheric (LH) regions (language tasks) and two tasks known to involve predominantly RH areas (visual search tasks). A laterality index (LI) was computed to determine the asymmetry of activation. Group analysis revealed unilateral activation of the LH language circuitry during language tasks while visual search tasks induced a more widespread RH activation pattern in frontal, superior temporal, and occipital areas. Laterality of language increased between the ages of 8-20 in frontal (r = 0.392, P = 0.049) and temporal (r = 0.387, P = 0.051) areas. The asymmetry of visual search functions increased in frontal (r = -0.525, P = 0.009) and parietal (r = -0.439, P = 0.027) regions. A positive correlation was found between Verbal-IQ and the LI during a language task (r = 0.585, P = 0.028), while visuospatial skills correlated with LIs of visual search (r = -0.621, P = 0.018). To summarize, cognitive development is accompanied by changes in the functional representation of neuronal circuitries, with a strengthening of lateralization not only for LH but also for RH functions. Our data show that age and performance, independently, account for the increases of laterality with age.

Teaching and assessment of implant dentistry in undergraduate and postgraduate education: a European consensus

This paper constitutes a summary of the consensus documents agreed at the First European Workshop on Implant Dentistry University Education held in Prague on 19-22 June 2008. Implant dentistry is becoming increasingly important treatment alternative for the restoration of missing teeth, as patients expectations and demands increase. Furthermore, implant related complications such as peri-implantitis are presenting more frequently in the dental surgery. This consensus paper recommends that implant dentistry should be an integral part of the undergraduate curriculum. Whilst few schools will achieve student competence in the surgical placement of implants this should not preclude the inclusion of the fundamental principles of implant dentistry in the undergraduate curriculum such as the evidence base for their use, indications and contraindications and treatment of the complications that may arise. The consensus paper sets out the rationale for the introduction of implant dentistry in the dental curriculum and the knowledge base for an undergraduate programme in the subject. It lists the competencies that might be sought without expectations of surgical placement of implants at this stage and the assessment methods that might be employed. The paper also addresses the competencies and educational pathways for postgraduate education in implant dentistry.

Critical appraisal of meta-analyses: an introductory guide for the practicing surgeon

ABSTRACT: Meta-analyses are an essential tool of clinical research. Meta-analyses of individual randomized controlled trials frequently constitute the highest possible level of scientific evidence for a given research question and allow surgeons to rapidly gain a comprehensive understanding of an important clinical issue. Moreover, meta-analyses often serve as cornerstones for evidence-based surgery, treatment guidelines, and knowledge transfer. Given the importance of meta-analyses to the medical (and surgical) knowledge base, it is of cardinal importance that surgeons have a basic grasp of the principles that guide a high-quality meta-analysis, and be able to weigh objectively the advantages and potential pitfalls of this clinical research tool. Unfortunately, surgeons are often ill-prepared to successfully conduct, critically appraise, and correctly interpret meta-analyses. The objective of this educational review is to provide surgeons with a brief introductory overview of the knowledge and skills required for understanding and critically appraising surgical meta-analyses as well as assessing their implications for their own surgical practice.

ПРОСТОРНО-УРБАНИ РАЗВОЈ ТЕМЕРИНА

Temerin is settlements in the municipality of the same name, and њhose is center. This settlement by its characteristics is a very specific for area of Bačke and Vojvodina. One of its main characteristic is a specific spatial and urban development. Although the site of the present Temerin revealed several archaeological sites that attest to the presence of humans in prehistoric times, today’s settlement, under this name, is mentioned first time in the early 14th century. Over the centuries the Temerin developed and expanded in phases, forming elements of the composition of settlements with a number of specific features. Especially in this regard emphasize shape, structure and physiognomy of the settlement. The main characteristic of the physiognomy of the settlement is a large elongated north to south axis of Temerin, which is the main street, and also the longest street in the whole of Serbia (13 km). Along the major axis, and in some places there are strains in relation to linear the square in the form of parts as a result of subsequent colonization and phase expansion of Temerin. This paper aims to study the expansion and urban development Temerin throughout history.

Fortaleciéndo la soberanía alimentaria mediante la revalorización de saberes ecológicos locales: experiencia en los Andes bolivianos

Ethnobiology research contributes significantly to initiatives that aim to enhance food sovereignty among indigenous and/or traditional people. In Bolivia, one of the Latin-American countries that shows the highest poverty and undernourishment levels, the purpose of this research-action project was to enhance food sovereignty through the revitalization of the local ecological knowledge and to promote local technological innovation processes in the Andean community of Tallija-Confital. During a first step the endogenous knowledge and strategies related to food security and sovereignty were investigated, based on the principles and tools of the Revitalizing Participatory Research (RPR). In a second step local technical innovation processes were supported through a “knowledge dialogue” between exogenous and endogenous knowledge systems, focusing on the processing of the cañahua (Chenopodium pallidicaule Aellen) gluten. The research results demonstrate that Andean people have developed complex endogenous knowledge and strategies to adapt to socio-environmental changes that show a great potential to contribute to the enhancement of food sovereignty. Nevertheless, in the current globalized context that translates into new challenges for local communities, beyond the revitalization of local ecological knowledge, a dialogue between different knowledge systems can lead to important local technological innovation for the improvement of their well-being. Key words: food sovereignty, knowledge dialogue, endogenous development, technological innovation

Slow Cities: Sustainable Places in a Fast World

This article examines the Slow Food and Slow City movement as an alternative approach to urban development that focuses on local resources, economic and cultural strengths, and the unique historical context of a town. Following recent discussions about the politics of alternative economic development, the study examines the Slow City movement as a strategy to address the interdependencies between goals for economic, environmental, and equitable urban development. In particular, we draw on the examples of two Slow Cities in Germany—Waldkirch and Hersbruck, and show how these towns are retooling their urban policies. The study is placed in the context of alternative urban development agendas as opposed to corporate-centered development. We conclude the article by offering some remarks about the institutional and political attributes of successful Slow Cities and the transferability of the concept.

Modelling the system behaviour of wet snow avalanches using an expert system approach for risk management on high alpine traffic roads

The presented approach describes a model for a rule-based expert system calculating the temporal variability of the release of wet snow avalanches, using the assumption of avalanche triggering without the loading of new snow. The knowledge base of the model is created by using investigations on the system behaviour of wet snow avalanches in the Italian Ortles Alps, and is represented by a fuzzy logic rule-base. Input parameters of the expert system are numerical and linguistic variables, measurable meteorological and topographical factors and observable characteristics of the snow cover. Output of the inference method is the quantified release disposition for wet snow avalanches. Combining topographical parameters and the spatial interpolation of the calculated release disposition a hazard index map is dynamically generated. Furthermore, the spatial and temporal variability of damage potential on roads exposed to wet snow avalanches can be quantified, expressed by the number of persons at risk. The application of the rule base to the available data in the study area generated plausible results. The study demonstrates the potential for the application of expert systems and fuzzy logic in the field of natural hazard monitoring and risk management.

MRD's approach: Ideally suited to support Future Earth research agenda in mountains

Both Future Earth and Mountain Research and Development (MRD) aim to support production and dissemination of knowledge for sustainable development. As shown in Future Earth’s Strategic Research Agenda 2014, the global research community has begun to acknowledge its societal role and the need for a new type of research in which scientists link disciplines and coproduce transformation knowledge with stakeholders. Future Earth has defined three research themes that conceptualize the issues to be dealt with at the same time as the way in which this should be done. In many ways, MRD’s policy has made the journal a forerunner of Future Earth’s stipulated “step-change in research”. Indeed, MRD’s section policies aim to support similar contents and ways of producing these forms of knowledge. MRD publishes “systems knowledge” in its MountainResearch section, “target knowledge” in its MountainAgenda section, and “transformation knowledge” in its MountainDevelopment section. Each of these sections has dedicated review criteria to assess and enhance the quality of the knowledge presented in the papers. In this poster, we provide examples from each of the three sections of what the knowledge types look like, how they are assessed, and how they contribute to the three Future Earth themes.

Im physikalischen Verdichtungslabor: Wie Sprache das Denken und Handeln im Siedlungsbau beeinflusst

This article provides evidence from the Swiss context that the prevailing discourse of urban densification within the field of urban development is largely metaphorical in nature. It is dominated in particular by metaphors from the field of physics. As a result, aesthetic, social and ecological aspects are systematically downplayed or transformed into physical perspectives. Diffuse fears of densification and the ecological deficits associated with densification policies are thus made transparent. The article presents alternatives to physical framing and shows how reflecting on language can enrich sustainable urban development.