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Referring to Niklas Luhmann’s theory, this brief commentary on the text by Eyal et al. (2024) argues that trust — compared to distrust — increases the possibilities available to the decision-maker. Those who trust can keep more possibilities open and nevertheless decide, because they do not need to know all the details. This “controlled indifference” would be especially valuable in our society, where the multiplication of risks requires us to constantly make decisions under conditions of uncertainty — that is, incomplete information. When the awareness of risks increases, however, trust tends to decrease regardless of the competence of decision-makers or the transparency of decisions, because the increase in information highlights the complexity of the factors involved, and the decision to trust appears itself increasingly risky.

ObjectivesPrecision Medicine (PM) uses advanced Machine Learning (ML) techniques and big data to develop personalized treatments, but healthcare still relies on traditional statistical procedures not targeted on individuals. This study investigates the impact of ML on epidemiology.MethodsA quantitative analysis of the articles in PubMed for the years 2000–2019 was conducted to investigate the use of statistical methods and ML in epidemiology. Using structural topic modelling, two groups of topics were identified and analysed over time: topics closer to the clinical side of epidemiology and topics closer to the population side.ResultsThe curve of the prevalence of topics associated with population epidemiology basically corresponds to the curve of the relative statistical methods, while the more dynamic curve of clinical epidemiology broadly reproduces the trend of algorithmic methods.ConclusionThe findings suggest that a renewed separation between clinical epidemiology and population epidemiology is emerging, with clinical epidemiology taking more advantage of recent developments in algorithmic techniques and moving closer to bioinformatics, whereas population epidemiology seems to be slower in this innovation.

The last decade has seen a significant growth in the adoption of low-cost air quality monitoring systems (LCAQMSs), mostly driven by the need to overcome the spatial density limitations of traditional regulatory grade networks. However, urban air quality monitoring scenarios have proved extremely challenging for their operative deployment. In fact, these scenarios need pervasive, accurate, personalized monitoring solutions along with powerful data management technologies and targeted communications tools; otherwise, these scenarios can lead to a lack of stakeholder trust, awareness, and, consequently, environmental inequalities. The AirHeritage project, funded by the EU’s Urban Innovative Action (UIA) program, addressed these issues by integrating intelligent LCAQMSs with conventional monitoring systems and engaging the local community in multi-year measurement strategies. Its implementation allowed us to explore the benefits and limitations of citizen science approaches, the logistic and functional impacts of IoT infrastructures and calibration methodologies, and the integration of AI and geostatistical sensor fusion algorithms for mobile and opportunistic air quality measurements and reporting. Similar research or operative projects have been implemented in the recent past, often focusing on a limited set of the involved challenges. Unfortunately, detailed reports as well as recorded and/or cured data are often not publicly available, thus limiting the development of the field. This work openly reports on the lessons learned and experiences from the AirHeritage project, including device accuracy variance, field recording assessments, and high-resolution mapping outcomes, aiming to guide future implementations in similar contexts and support repeatability as well as further research by delivering an open datalake. By sharing these insights along with the gathered datalake, we aim to inform stakeholders, including researchers, citizens, public authorities, and agencies, about effective strategies for deploying and utilizing LCAQMSs to enhance air quality monitoring and public awareness on this challenging urban environment issue.

Dealing with opaque algorithms, the frequent overlap between transparency and explainability produces seemingly unsolvable dilemmas, as the much-discussed trade-off between model performance and model transparency. Referring to Niklas Luhmann's notion of communication, the paper argues that explainability does not necessarily require transparency and proposes an alternative approach. Explanations as communicative processes do not imply any disclosure of thoughts or neural processes, but only reformulations that provide the partners with additional elements and enable them to understand (from their perspective) what has been done and why. Recent computational approaches aiming at post-hoc explainability reproduce what happens in communication, producing explanations of the working of algorithms that can be different from the processes of the algorithms.

This short introduction presents the symposium ‘Explaining Machines’. It locates the debate about Explainable AI in the history of the reflection about AI and outlines the issues discussed in the contributions.

Solar irradiance data provided by the Copernicus program are crucial for several scientific, environmental, and energy management applications, but their validation by means of ground-based measurements may be necessary, especially if daily and hourly data resolutions are required. The validation process not only ensures that reliable information is available for solar energy resource planning, power plant performance assessment, and grid integration, but also contributes to the improvement of the Copernicus system itself. Ground-based stations offer site-specific data, allowing for comprehensive assessments of the system’s performance. This work presents a comparative statistical analysis of solar irradiance data provided by the Copernicus system and ground-based measurements on a seasonal basis at three specific Italian reference sites, showing a maximum average relative error of less than 7% for hourly horizontal global irradiance in the irradiance range defined by the IEC 61724-2.

Helga Nowotny, Professor emerita of Science and Technology Studies at ETH Zurich, is a leading scholar in the social studies of science and technology. In her extensive publications she dealt, among other topics, with social and individual structuring of time, technological innovation, uncertainty, social effects of AI, and the interaction between biological life and social life. Always intensely engaged in research policy, Nowotny is one of the founding members of the European Research Council and was its President from 2010 to 2013. In this conversation with Elena Esposito, she talks about her scientific biography, the role of technologies in the experience of time, and the relationship between STS and sociology of science. Drawing on her experience in the organization and funding of science at EU level, she also reflects on the relationship between research and science policy and on the ongoing transformations in the way of doing research and in gender issues.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder evolving over the lifetime of individuals. The oral and gut microbial ecosystems are closely connected to each other and the brain and are potentially involved in neurodevelopmental diseases. This narrative review aims to identify all the available evidence emerging from observational studies focused on the role of the oral microbiome in ASD. A literature search was conducted using PubMed and the Cochrane Library for relevant studies published over the last ten years. Overall, in autistic children, the oral microbiota is marked by the abundance of several microbial species belonging to the Proteobacteria phylum and by the depletion of species belonging to the Bacteroidetes phylum. In mouse models, the oral microbiota is marked by the abundance of the Bacteroidetes phylum. Oral dysbiosis in ASD induces changes in the human metabolome, with the overexpression of metabolites closely related to the pathogenesis of ASD, such as acetate, propionate, and indoles, together with the underexpression of butyrate, confirming the central role of tryptophan metabolism. The analysis of the literature evidences the close relationship between oral dysbiosis and autistic core symptoms; the rebuilding of the oral and gut ecosystems by probiotics may significantly contribute to mitigating the severity of ASD symptoms.

Algorithmic predictions are used in insurance to assess the risk exposure of potential customers. This article examines the impact of digital tools on the field of motor insurance, where telematics devices produce data about policyholders’ driving styles. The individual’s resulting behavioural score is combined with their actuarial score to determine the price of the policy or additional incentives. Current experimentation is moving in the direction of proactivity: instead of waiting for a claim to arise, insurance companies engage in coaching and other interventions to mitigate risk. The article explores the potential consequences of these practices on the social function of insurance, which makes risks bearable by socialising them over a pool of insured individuals. The introduction of behavioural variables and the corresponding idea of fairness could instead isolate individuals in their exposure to risk and affect their attitude towards future initiatives.

Lidando com técnicas opacas de aprendizagem de máquinas, a questão crucial tornou-se a interpretabilidade do trabalho dos algoritmos e dos seus resultados. O artigo argumenta que a mudança para a interpretação requer um movimento da inteligência artificial para uma forma inovadora de comunicação artificial. Em muitos casos o objetivo da explicação não é revelar os procedimentos das máquinas, mas sim comunicar com elas e obter informação relevante e controlada. Como as explicações humanas não exigem transparência das ligações neurais ou processos de pensamento, as explicações algorítmicas não têm de revelar as operações da máquina, mas têm de produzir reformulações que façam sentido para os seus interlocutores. Este movimento tem consequências importantes para a comunicação jurídica, onde a ambiguidade desempenha um papel fundamental. O problema da interpretação nos argumentos jurídicos, argumenta o artigo, não é que os algoritmos não explicam o suficiente, mas que devem explicar muito e com muita precisão, restringindo a liberdade de interpretação e a contestabilidade das decisões jurídicas. A consequência pode ser uma possível limitação da autonomia da comunicação jurídica que está na base do Estado de direito moderno.

In this essay the editors-in-chief reflect on recent development of the journal and introduce the Symposium on Revising. We at Sociologica do not aim to be a major journal of sociology, but we do aspire to be a leading journal. Here we briefly gesture to four areas in which we aspire to leadership. These include: identifying vital topics for sociological debate; offering an alternative editorial model where the review process is not regarded as gate keeping; promoting greater diversity of formats for presenting sociological ideas beyond the one-size-fits-all model of Introduction – Theory – Data & Methods – Findings – Discussion – Conclusion; and presenting critical reflections on the practice of sociology.

How can sociologists observe a war "in the making"? In issuing an "instant call for papers," the editors of Sociologica suggest three lines of research: the semantics and the symbolic representation of war (of any war, but especially of this war); how political, military, economic, and social options and alternatives enter and exit the realm of the possible in connection with shifts in war semantics; how our understanding of "the day after," that is of the future after the war is over, binds and even determines decisions in the present.

Digital prediction tools increasingly complement or replace other practices of coping with an uncertain future. The current COVID-19 pandemic, it seems, is further accelerating the spread of prediction. The prediction of the pandemic yields a pandemic of prediction. In this paper, we explore this dynamic, focusing on contagion models and their transmission back and forth between two domains of society: public health and public safety. We connect this movement with a fundamental duality in the prevention of contagion risk concerning the two sides of being-at-risk and being-a-risk. Both in the spread of a disease and in the spread of criminal behavior, a person at risk can be a risk to others and vice versa. Based on key examples, from this perspective we observe and interpret a circular movement in three phases. In the past, contagion models have moved from public health to public safety, as in the case of the Strategic Subject List used in the policing activity of the Chicago Police Department. In the present COVID-19 pandemic, the analytic tools of policing wander to the domain of public health – exemplary of this movement is the cooperation between the data infrastructure firm Palantir and the UK government’s public health system NHS. The expectation that in the future the predictive capacities of digital contact tracing apps might spill over from public health to policing is currently shaping the development and use of tools such as the Corona-Warn-App in Germany. In all these cases, the challenge of pandemic governance lies in managing the connections and the exchanges between the two areas of public health and public safety while at the same time keeping the autonomy of each.

Fashion seems to be opening to a trend towards ethnic and multicultural content, and even to a modest fashion based on the desire to avoid attracting attention. The paper discusses the possibility that fashion has a social impact, contrasting it with Simmel’s “abstractness:” the claim that fashion has no reason and cannot have a reason – and if it does, this is not the reason why we follow it. Fashion goes by and this is its real content, beyond the forms it takes over time. The open question is whether a modest fashion can still be modest, or whether it has to give up its nature in order to be fashionable – and whether this is a price that is worth paying.

The condition of social isolation due to the Covid-19 pandemic makes most of us aware of the value of sociality – which we now lack. But society is not only sociality, and in the current emergency we perceive it as global interconnectedness that makes the crisis spread from one geographical area to another and between different fields of society. The common response to a global emergency is a call for coordination – the idea that we should “tighten up.” In sociology, this reference to unity and coordination is discussed as integration. The paper argues, referring to systems theory, that the problem of our functionally differentiated society is not lack of integration, but rather an excess of integration. When there are difficulties in one area of society, all others are forced to make serious adjustments. In dealing with threats that come from the environment, the opportunities for rationality in society lie in the maintenance and exploitation of differences, not in their elimination. This hypotheses is discussed dealing with integration on three levels: 1) the consequences of the emergency on the relationships between different fields (or functional subsystems) of society: systemic integration; 2) the effects of the pandemic on the conditions of inclusion and exclusion of individuals in society: social integration; 3) the spread of the emergency in all regions of the world and the consequences for globalization: geographical integration.

There is an increasing scientific interest in studying vehicular traffic pollution in road tunnels. This is due both to the interest in evaluating the effect that the different polluting gases can have on the driving style of motorists and also to the hypothesis that tunnels could be considered as closed systems in which the vehicular traffic–pollution correlation is easier to study because it is more easily separated from other effects. In this work, a system of low-cost IoT sensor nodes for the detection of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), particulate matters (PM1, PM2.5, PM10), relative humidity (RH) and temperature (T) has been installed in an Italian tunnel, where vehicular traffic has been measured and classified for type of vehicles. The results of the measurement campaign, which lasted 3 months, from April to June 2022, allowed us to state that road tunnels actually behave like closed and isolated systems in which pollution may be directly correlated to the traffic volume and type. Furthermore, data show that quite high values of the major pollutants are observable in the tunnel in comparison to the external environment. As such, IoT sensor nodes may contribute to a distributed measuring approach on the road tunnel system mechanics assessment including, as an example, the operational impacts of forced ventilation.

Abstract Scrapie in goats has been known since 1942, the archetype of prion diseases in which only prion protein (PrP) in misfolded state (PrPSc) acts as infectious agent with fatal consequence. Emergence of bovine spongiform encephalopathy (BSE) with its zoonotic behaviour and detection in goats enhanced fears that its source was located in small ruminants. However, in goats knowledge on prion strain typing is limited. A European-wide study is presented concerning the biochemical phenotypes of the protease resistant fraction of PrPSc (PrPres) in over thirty brain isolates from transmissible spongiform encephalopathy (TSE) affected goats collected in seven countries. Three different scrapie forms were found: classical scrapie (CS), Nor98/atypical scrapie and one case of CH1641 scrapie. In addition, CS was found in two variants—CS-1 and CS-2 (mainly Italy)—which differed in proteolytic resistance of the PrPres N-terminus. Suitable PrPres markers for discriminating CH1641 from BSE (C-type) appeared to be glycoprofile pattern, presence of two triplets instead of one, and structural (in)stability of its core amino acid region. None of the samples exhibited BSE like features. BSE and these four scrapie types, of which CS-2 is new, can be recognized in goats with combinations of a set of nine biochemical parameters.

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother–infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period.

The use of algorithmic prediction in insurance is regarded as the beginning of a new era, because it promises to personalise insurance policies and premiums on the basis of individual behaviour and level of risk. The core idea is that the price of the policy would no longer refer to the calculated uncertainty of a pool of policyholders, with the consequence that everyone would have to pay only for her real exposure to risk. For insurance, however, uncertainty is not only a problem – shared uncertainty is a resource. The availability of individual risk information could undermine the principle of risk-pooling and risk-spreading on which insurance is based. The article examines this disruptive change first by exploring the possible consequences of the use of predictive algorithms to set insurance premiums. Will it endanger the principle of mutualisation of risks, producing new forms of discrimination and exclusion from coverage? In a second step, we analyse how the relationship between the insurer and the policyholder changes when the customer knows that the company has voluminous, and continuously updated, data about her real behaviour.

Traditional societies were defined by a prevalence of the past in the definition of the present. United States (US) society seems to show the opposite trend: the present is defined as the preparation of the future. Financial temporality can be seen as an example of the present use of the future, transforming future possibilities into available wealth. As the financial crisis has shown, however, the temporality of the future is more complex and circular. This article deals with quantitative easing (QE) as a financial instrument with an essentially temporal nature (in the sense that it uses time and acts on the future and on expectations). The success of QE in the US economy reveals essential aspects of US temporality, but also raises questions as to how it may differ from European temporality. The analysis of QE measures and their impact also offers ways to assess whether and by which means politics can intervene into finance, as well as what consequences and uncertainties are created in the process.

This editorial note turns the attention of sociology to the immediate and pressing present of the COVID-19 pandemic with the aim of understanding the potentially long-term consequences of this extraordinary moment. We suggest to focus on important topics such as the meaning of social change related to COVID-19, the newly emerging social practices due to lockdown measures, the emotional and cognitive impact of the absence of important social rituals, and the political and social effects of enhanced surveillance in our societies. We offer Sociologica as an open forum to host contributions on these topics or on other research questions connected with the COVID-19 crisis.

An editorial introduction to a tribute to Alessandro Pizzorno.

In the previous issue of Sociologica, 13(1), 2019, we published a provocative essay by Philippe Schmitter, "Vices and Virtues of ‘Populisms’." As part of our commitment to sociological debate, we invited comments by five leading scholars in the field.

A pervasive assessment of air quality in an urban or mobile scenario is paramount for personal or city-wide exposure reduction action design and implementation. The capability to deploy a high-resolution hybrid network of regulatory grade and low-cost fixed and mobile devices is a primary enabler for the development of such knowledge, both as a primary source of information and for validating high-resolution air quality predictive models. The capability of real-time and cumulative personal exposure monitoring is also considered a primary driver for exposome monitoring and future predictive medicine approaches. Leveraging on chemical sensing, machine learning, and Internet of Things (IoT) expertise, we developed an integrated architecture capable of meeting the demanding requirements of this challenging problem. A detailed account of the design, development, and validation procedures is reported here, along with the results of a two-year field validation effort.

The authors wish to make the following corrections to this paper [...]

The concerns related to particulate matter’s health effects alongside the increasing demands from citizens for more participatory, timely, and diffused air quality monitoring actions have resulted in increasing scientific and industrial interest in low-cost particulate matter sensors (LCPMS). In the present paper, we discuss 50 LCPMS models, a number that is particularly meaningful when compared to the much smaller number of models described in other recent reviews on the same topic. After illustrating the basic definitions related to particulate matter (PM) and its measurements according to international regulations, the device’s operating principle is presented, focusing on a discussion of the several characterization methodologies proposed by various research groups, both in the lab and in the field, along with their possible limitations. We present an extensive review of the LCPMS currently available on the market, their electronic characteristics, and their applications in published literature and from specific tests. Most of the reviewed LCPMS can accurately monitor PM changes in the environment and exhibit good performances with accuracy that, in some conditions, can reach R2 values up to 0.99. However, such results strongly depend on whether the device is calibrated or not (using a reference method) in the operative environment; if not, R2 values lower than 0.5 are observed.

The debate on the right to be forgotten on Google involves the relationship between human information processing and digital processing by algorithms. The specificity of digital memory is not so much its often discussed inability to forget. What distinguishes digital memory is, instead, its ability to process information without understanding. Algorithms only work with data (i.e. with differences) without remembering or forgetting. Merely calculating, algorithms manage to produce significant results not because they operate in an intelligent way, but because they “parasitically” exploit the intelligence, the memory, and the attribution of meaning by human actors. The specificity of algorithmic processing makes it possible to bypass the paradox of remembering to forget, which up to now blocked any human-based forgetting technique. If you decide to forget some memory, the most immediate effect is drawing attention to it, thereby activating remembering. Working differently from human intelligence, however, algorithms can implement, for the first time, the classical insight that it might be possible to reinforce forgetting not by erasing memories but by multiplying them. After discussing several projects on the web which implicitly adopt this approach, the article concludes by raising some deeper problems posed when algorithms use data and metadata to produce information that cannot be attributed to any human being.

¿Pueden los observadores observar la economía desde el exterior? Desarrollos recientes en la s ociología económica tienden a desdibujar la clásica distinción y combinación entre economía y sociedad, y a avanzar hacia un modelo en el que el observador se encuentra necesariamente dentro de la sociedad que él describe. El comportamiento de los agentes financieros se puede analizar mediante la combina - ción de dos conceptos: el concurso de belleza y el riesgo moral – una combinación que permite una tra - ducción de su comportamiento en los términos y tradición de la teoría de la observación. El concurso de b elleza de Keynes puede ser interpretado como un reconocimiento sistemático de la observación de segundo orden: los operadores financieros observan principalmente a otros observadores y lo que estos observan. Esta observación produce circularidades peculiar es – incluyendo el insoluble problema del riesgo moral, el cual reproduce el famoso modelo de Merton de las profecías autocumplidas y autofrus - tradas en el campo de las finanzas. Sin embargo, si las finanzas consisten en observaciones de segundo orden, ento nces sus movimientos no pueden ser explicados más con referencia al mundo, sino con refe - rencia a la observación y sus estructuras: la referencia a la realidad de las finanzas es proporcionada cre - cientemente por calificaciones crediticias que solo pueden ofrecer información respecto de lo que los demás observan. La expansión de las calificaciones crediticias en las últimas décadas y las dudas sobre su fiabilidad están relacionadas con el movimiento generalizado de la sociedad moderna hacia la obser - vación de segundo orden, lo cual produce problemas y enigmas específicos, así como estructuras y restricciones.

El presente artículo aborda los problemas relativos a la comprensión del dinero en la sociedad moderna. En la actualidad no existe una teoría sociológica adecuada para comprender las funciones y especificidades del dinero. Frente a esto el presente artículo se propone comprender al dinero en el contexto de una dimensión temporal, específicamente como un "medio de aplazamiento". Se abordan a continuación algunas consecuencias de la monetarización de la economía de la sociedad y se analizan algunas características de la economía de los "derivados". El artículo concluye con consideraciones relativas al nuevo carácter de la economía monetaria.

Sheep CH1641-like transmissible spongiform encephalopathy isolates have shown molecular similarities to bovine spongiform encephalopathy (BSE) isolates. We report that the prion protein PrPSc from sheep BSE is extremely resistant to denaturation. This feature, combined with the N-terminal PrPSc cleavage, allowed differentiation of classical scrapie, including CH1641-like, from natural goat BSE and experimental sheep BSE.

This work report the preliminary results of crowdfunding/crowdsensing campaign run in Italy aimed to functional test of a smart air quality monitoring infrastructure. Design and implementation of the cooperative monitoring infrastructure are described along with details of crowdfunding campaign. Participating users received, for a whole month, a field validated electrochemical sensors based air quality monitoring node and a companion APP capable of reporting sophisticated concentration estimations. Calibration functions are actually based on machine learning components correcting for environmental and non target gas interferences. Data gathered in the cloud allowed for evaluation of acceptability and reliability of the node as well as for mapping concentrations measurements inside city landscape through an ad-hoc GUI.

The text tries to propose a concept of the present compatible with the assumptions of systems theory and to show its possible relevance. It should be a »modalized« present, interpreting past and future as non-actual »modes« of the present actual at the time and comparing them with other forms of non-actuality – starting from the study of temporal semantics in historical perspective. The sense of temporal categories arises then from the contraposition of different horizons of past and future – those of different presents, but also those that have not become actual, not even as possibilities. These very abstract reflections are then applied to the concrete topics of risk and of fashion, in order to show the necessity of a concept of present including also non-quantitative aspects.

In this work, we describe a cooperative air quality sensor architecture based on crowdfunded, mobile, electrochemical sensor based, monitoring systems. The platform aims to produce enhanced information on personal pollutant exposure and enable cooperative reconstruction of high resolution pictures of air pollution in the urban landscape. The calibrated devices are connected to smartphones that provide georeferenced visualization of personal exposure and session based log capabilities. A cloud based interface provides a sensor fusion based mapping capability exploiting google maps APIs. An in-lab calibration by linear regression with temperature correction has been computed and preliminary results have been reported. A small set of calibrated devices will be shipped to crowdfunders for extended field tests in different italian cities.

Prion diseases are classically characterized by the accumulation of pathological prion protein (PrP(Sc)) with the protease resistant C-terminal fragment (PrP(res)) of 27-30 kDa. However, in both humans and animals, prion diseases with atypical biochemical features, characterized by PK-resistant PrP internal fragments (PrP(res)) cleaved at both the N and C termini, have been described. In this study we performed a detailed comparison of the biochemical features of PrP(Sc) from atypical prion diseases including human Gerstmann-Sträussler-Scheinker disease (GSS) and variably protease-sensitive prionopathy (VPSPr) and in small ruminant Nor98 or atypical scrapie. The kinetics of PrP(res) production and its cleavage sites after PK digestion were analyzed, along with the PrP(Sc) conformational stability, using a new method able to characterize both protease-resistant and protease-sensitive PrP(Sc) components. All these PrP(Sc) types shared common and distinctive biochemical features compared to PrP(Sc) from classical prion diseases such as sporadic Creutzfeldt-Jakob disease and scrapie. Notwithstanding, distinct biochemical signatures based on PrP(res) cleavage sites and PrP(Sc) conformational stability were identified in GSS A117V, GSS F198S, GSS P102L and VPSPr, which allowed their specific identification. Importantly, the biochemical properties of PrP(Sc) from Nor98 and GSS P102L largely overlapped, but were distinct from the other human prions investigated. Finally, our study paves the way towards more refined comparative approaches to the characterization of prions at the animal-human interface.

Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc), a disease-associated isoform of the host-encoded cellular protein (PrP(C)). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc). However, PrP(Sc) is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc) aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C) and PrP(Sc) by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrP(Sc) solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2) values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2) values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc), we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc) aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc) conformational stabilities of protease-resistant and protease-sensitive PrP(Sc) and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep.

The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. At first, we found a differential susceptibility of bank and field voles compared to C57Bl/6 and wood mice. Voles showed high susceptibility to sheep scrapie but were resistant to bovine spongiform encephalopathy, whereas C57Bl/6 and wood mice displayed opposite features. Infection with mouse-adapted scrapie 139A was faster in voles than in C57Bl/6 and wood mice. Moreover, a glycoprofile change was observed in voles, which was reverted upon back passage to mice. All strains replicated much faster in voles than in mice after adapting to the new species. PrP sequence comparison indicated a correlation between the transmission patterns and amino acids at positions 154 and 169 (Y and S in mice, N and N in voles). This correlation was confirmed when inoculating three additional rodent species: gerbils, spiny mice and oldfield mice with sheep scrapie and 139A. These rodents were chosen because oldfield mice do have the 154N and 169N substitutions, whereas gerbil and spiny mice do not have them. Our results suggest that PrP residues 154 and 169 drive the susceptibility, molecular phenotype and replication rate of prion strains in rodents. This might have implications for the assessment of host range and molecular traceability of prion strains, as well as for the development of improved animal models for prion diseases.