Isabella Sarto-jackson

Recent debates in cognitive science revolve around a core concept of cognition beyond an anthropocentric perspective. Researchers have aimed at recreating evolutionarily inspired solutions equivalent to naturebased faculties in organisms. By using model organisms, scientists have begun to formulate a consensus view on what might be called basal cognition based on nervous system of simple organisms like sea slugs, flies, and flat worms. Noteworthy, Koshland (1983) pioneered this idea and traced cognition down to the ‘base’ of the phylogenetic tree by emphasizing analogies of the bacterial chemosensory system and information processing to those in neurons of complex organisms. Taking up this idea, we have argued that evolutionary ‘recent’ specializations of the nervous system have adopted cellular processes that have derived from ancient and fundamental cell survival processes (Sarto-Jackson and Tomaska, 2016). We will provide arguments for using yeast as a model system of basal cogni...

Building from the ideas of existential theorists [1, 2], Terror Management Theory (TMT) addresses the existential anxiety associated with people’s thoughts about their inevitable death. The theory is founded on two tenets: (a) that a primary instinct for humans is to preserve themselves; and (b) that humans are able to comprehend that they will ultimately fail at their goal of self-preservation. The clash between one’s self-preservation instinct and the outlook of one’s inevitable demise is, therefore, a potential source of existential fright and terror. TMT has focused on exploring how people keep these existential fears at bay. TMT proposes that people usually attempt not to think about their mortality to avoid being overwhelmed by this conflict. However, once they are reminded of their mortality, they feel existentially vulnerable. In order to avoid becoming overwhelmed by their mortal predicament, they activate two consecutive defense processes: They first respond by (a) proxima...

The role of narratives in clinical practice has long been underappreciated. This disregard is largely due to an overemphasis on reductionist interpretations of disease causes based on the primacy of the medical model of disease. This way of thinking has led to decontextualizing symptoms of disorders from patients’ lives. More recently, however, healthcare professionals have turned towards a biopsychosocial model that reintroduces sociocultural and psychosocial aspects into clinical diagnosis and treatment. To this end, narrative approaches have been increasingly explored as alternative diagnostic and therapeutic tools. Central to the narrative approach is the avoidance of pathologizing language that usually focuses on deficiencies. Instead, patients’ narratives are co-constructed and co-created together with the clinician or therapist to transform them into empowering stories about healing. To make narratives accessible and transformable for the patient, psychoeducational methods ca...

From Department of Biochemistry and Molecular Biology, Center for Brain Research 1 , Medical University of Vienna, Vienna, Austria 1 . Ecolé Normale Supérieure, Institut de Biologie de l’Ecole Normale Supérieure (IBENS) Paris France; Inserm U1024, Paris France; CNRS UMR8197, 75005 Paris, France 2 . Running Title: GABAA and P2X2 receptor interaction Address correspondence to: Isabella Sarto-Jackson, PhD, Department of Biochemistry and Molecular Biology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, Vienna-1090, Austria, Ph: +43 1 40160 34065, Fax: +43 1 40160 934054, E-mail: isabella.sarto-jackson@meduniwien.ac.at

Comparative models of GABA(A) receptors composed of alpha1 beta3 gamma2 subunits were generated using the acetylcholine-binding protein (AChBP) as a template and were used for predicting putative engineered cross-link sites between the alpha1 and the gamma2 subunit. The respective amino acid residues were substituted by cysteines and disulfide bond formation between subunits was investigated on co-transfection into human embryonic kidney (HEK) cells. Although disulfide bond formation between subunits could not be observed, results indicated that mutations studied influenced assembly of GABA(A) receptors. Whereas residue alpha1A108 was important for the formation of assembly intermediates with beta3 and gamma2 subunits consistent with its proposed location at the alpha1(+) side of GABA(A) receptors, residues gamma2T125 and gamma2P127 were important for assembly with beta3 subunits. Mutation of each of these residues also caused an impaired expression of receptors at the cell surface....

The anxiolytic, anticonvulsant, muscle-relaxant, and sedative-hypnotic effects of benzodiazepine site ligands are mainly elicited by allosteric modulation of GABA receptors via their extracellular αx+/γ2- ( x = 1, 2, 3, 5) interfaces. In addition, a low affinity binding site at the homologous α+/β- interfaces was reported for some benzodiazepine site ligands. Classical benzodiazepines and pyrazoloquinolinones have been used as molecular probes to develop structure-activity relationship models for benzodiazepine site activity. Considering all possible α+/β- and α+/γ- interfaces, such ligands potentially interact with as many as 36 interfaces, giving rise to undesired side effects. Understanding the binding modes at their binding sites will enable rational strategies to design ligands with desired selectivity profiles. Here, we compared benzodiazepine site ligand interactions in the high affinity α1+/γ2- site with the homologous α1+/β3- site using a successive mutational approach. We ...

GABA-A receptors are the major inhibitory transmitter receptors in the brain and the site of action of many clinically important drugs. CGS 9895 and many other pyrazoloquinolinones are high affinity null modulators at the benzodiazepine (Bz) binding site and at higher concentrations also modulate the receptors via the α+β- interface. To gain insights into the interactions of CGS 9895 with both binding sites, we used our homology models to select γ2- side amino acid residues important for Bz binding and to incorporate them into the β3- side by site directed mutagenesis. These mutated β3 subunits were co-expressed with α subunits. The recombinant receptors were investigated by the two electrode voltage clamp method in Xenopus laevis oocytes and by radioligand binding assays. With only four mutations we were able to introduce a high affinity binding site for CGS 9895 into αβ3 receptors. Furthermore, GABA currents of several recombinant αβ3(mut) receptors could be modulated by the tested pyrazoloquinolinones ...

The role of narratives in clinical practice has long been underappreciated. This disregard is largely due to an overemphasis on reductionist interpretations of disease causes based on the primacy of the medical model of disease. This way of thinking has led to decontextualizing symptoms of disorders from patients' lives. More recently, however, healthcare professionals have turned towards a biopsychosocial model that reintroduces sociocultural and psychosocial aspects into clinical diagnosis and treatment. To this end, narrative approaches have been increasingly explored as alternative diagnostic and therapeutic tools. Central to the narrative approach is the avoidance of pathologizing language that usually focuses on deficiencies. Instead, patients' narratives are co-constructed and co-created together with the clinician or therapist to transform them into empowering stories about healing. To make narratives accessible and transformable for the patient, psychoeducational methods can be used to translate scientific and medical knowledge about the disease into stories described in everyday language that resonate with the patient's own life stories. Consequently, psychoeducational narratives enhance the patient's competence in coping with a physical or mental illness and re-contextualizing symptoms, and prompt an increased compliance with therapies.

If we want to learn how to deal with the COVID-19 pandemic, we have to embrace the complexity of this global phenomenon and capture interdependencies across scales and contexts. Yet, we still lack systematic approaches that we can use to deal holistically with the pandemic and its effects. In this Discussion, we first introduce a framework that highlights the systemic nature of the COVID-19 pandemic from the perspective of the total environment as a self-regulating and evolving system comprising of three spheres, the Geosphere, the Biosphere, and the Anthroposphere. Then, we use this framework to explore and organize information from the rapidly growing

Die Gehirnentwicklung eines Säuglings ist bei der Geburt noch nicht
abgeschlossen. Sie erfolgt postnatal durch neuroplastische Prozesse, die das frühkindliche Gehirn besonders lernfähig machen und soziale Bindung forcieren. Neuroplastizität erhöht aber auch die Vulnerabilität des Gehirns in Stresssituationen, ausgelöst durch negative Umwelteinflüsse, Vernachlässigung und Misshandlung. Toxischer Stress kann in weiterer Folge zu kognitiven Schäden und langfristig verstärkten Angstreaktionen führen.

At the time of birth, infant brain development is by no means complete. Neuroplastic processes that occur postnatally provide the child’s brain with a profound adaptedness to learn and form social bonds. Neuroplasticity,
however, also increases the brain’s vulnerability to stress situations triggered by negative environmental impact, neglect and abuse. Subsequently, toxic stress can lead to cognitive impairment and long-term, heightened anxiety.

Evolutionary epistemology (EE) has experienced a continuous rise over the last decades. Important new theoretical considerations and novel empirical findings have been integrated into the existing framework (Gontier and Bradie 2018). In this paper, I would like to suggest three lines of research that I believe will significantly contribute to further advance EE: (1) ontogenetic considerations, (2) key ideas from cognitive biology, and (3) the framework of the Extended Evolutionary Synthesis. (1) EE, in particular the program of the evolution of epistemological mechanisms (EEM), seeks to provide a phylogenetic account of the generation of cognitive processes underlying knowledge creation (Bradie and Harms 2017). Traditionally, EE and EEM have been oriented towards an account of evolutionary theory that mainly drew from the tenets of the Modern Synthesis. The Modern Synthesis largely dismisses ontogenetic processes and considers them irrelevant for evolutionary explanations. If anything, the role of development in evolution is believed to be that of a constraint. There is, however, ample evidence for a tight intertwinement of developmental and evolutionary processes. Organisms employ their cognitive apparatus to interact with the environment in order to achieve a fully functioning perceptual and cognitive nervous system. Also, ontogeny provides generative potentials to enable variations that natural selection can act upon. EEM's agenda may, therefore, strongly benefit from bringing together ontogenetic and phylogenetic approaches. To grapple with this challenge, an alternative vision of the evolutionary theory termed Extended Evolutionary Synthesis (Pigliucci and Müller 2010) could be used. This extended evolutionary theory explores relationships between the processes of individual development and phenotypic change during evolution (i.e., EvoDevo) and can provide a more suitable framework for EEM to draw from. (2) In recent years, cog-nitive biology has gained momentum as an independent research field. Cognitive biology builds on the concepts of EEM and understands knowledge as a biogenic phenomenon. Its main objective is also the formulation of substantiated interrelations between cognition and * Isabella Sarto-Jackson 1 3 evolution but it focuses on cognitive functionality at all levels of biological organization. It thus employs a "vertical" approach that encompasses nested hierarchies which span from single molecules, cells, and tissues to the organismal level, communities, and societies. In contrast to cognitive biology, EEM is here understood to adopt a "horizontal" approach that focuses on phylogenetic explanations of cognition and knowledge acquisition (Kovac 2006). Linking EEM with the key ideas of cognitive biology could make EEM's research program stronger as it can more easily accommodate phylogenetic and ontogenetic questions within a hierarchical, multilevel perspective. This is of particular importance for a more comprehensive account of cognition since living systems are subject to context-dependent causal influences from different organizational levels. (3) In addition to EEM, there is a second program of EE. This program has been labeled evolutionary epistemology of theories (EET) and understands the increase in human knowledge, such as scientific theories, as natural-istic accounts of evolution. Both, EEM and EET initially drew from the core concepts of the Modern Synthesis. Several scholars have severely criticized the analogies made between EET and the Neo-Darwinian key processes of evolution. In particular processes of random mutation, the rate of variation, natural selection as the unique driving force, and the adap-tationist agenda are believed to reveal disanalogies. In contrast to the Modern Synthesis, the Extended Evolutionary Synthesis not only recognizes developmental processes but also ecological interactions and systems dynamics as well as social and cultural evolutionary reciprocity as important evolutionary processes. Concepts of the Extended Evolutionary Synthesis are therefore expected to be more fruitful for re-conceptualizing parallels between scientific theorizing and biological evolution.

The human brain is equipped with physiological, neural, and cognitive capacities that enable it to respond flexibly to ever-changing natural and social conditions. This capacity of the brain to reorganize itself, called neuroplasticity, is particularly marked in childhood. The high malleability of the brain at this stage provides the basis for wide-ranging learning, but leaves it vulnerable to negative environmental and social factors. Neuroplastic events that occur in response to abusive or neglecting environments can strongly interfere with the adaptive shaping of neural pathways between the prefrontal cortex and the limbic system, compromising judgment and self-control. Traumatic experiences during development can also have other effects on brain plasticity that are mediated by epigenetic mechanisms, and these effects can impair the developing oxytocin system, adversely affecting attachment and bonding. Mature individuals seek out niches that match the internal mental structures shaped during their early years, and will even alter the environment to make it match the internal structures. In the case of those who suffered childhood abuse, this can lead to maltreatment of the next generation. Addressing the societal challenge of child abuse and maltreatment requires broad interdisciplinary endeavors, uniting neuroscientists and social education workers to break the vicious circle.

There is a conceptual crisis in the biomedical sciences  that  is  particularly  salient  in  psychopathology research. Underlying the crisis is a controversy that pertains to the current medical model of disease that largely draws from causal-mechanistic explanations. The bedrock of this model is the analysis of biological part-dysfunctions that aims at unequivocally defining a pathological condition and demarcating it from its neighboring entities. This endeavor has led to a quest for physiological, biochemical, and genetic signatures. Yet, so far there is little evidence for reliable biomarkers for any mental disorder. The contemporary biomedical paradigm largely ignores historical, dynamic, and system-level aspects—a view that has contributed much to the conceptual disjunction of the patient as a person from his/her disease. Notwithstanding the impressive progress in the biomedical sciences, increasingly more critics question whether the constituting framework is sufficient to convey a comprehensive understanding of illnesses, especially mental illnesses. Thus, the medical model urgently requires an update. But rather than revamping it by methodological advancements, it will be necessary to critically review its philosophical roots. The most problematic issues that require reworking are: the preponderance of the biostatistical theory; the undue decoupling of physiological from evolutionary explanations of function; the clinging to the Modern Synthesis (if etiological aspects are ever considered); and the neglect of dynamic and system-level properties. The proposed overhaul requires the heeding of historical explanations that draw from the Extended Evolutionary Synthesis as well as systems biology approaches for tackling multilevel and dynamic phenomena of complex systems.

Our primary goal in this article is to discuss the cross-talk between
biological and cultural factors that become manifested in the individual brain development, neural wiring, neurochemical homeostasis, and behavior. We will show that behavioral propensities are the product of both cultural and biological factors and an understanding of these interactive processes can provide deep insights into why people behave the way they do. This interdisciplinary perspective is offered in an effort to generate dialog and empirical work among scholars interested in merging aspects of anthropology and neuroscience, and anticipates that
biological and cultural anthropology converge. We discuss new theoretical developments, hypothesis-testing strategies, and cross-disciplinary methods of observation and data collection. We believe that the exigency of integrating anthropology and the neurosciences is indisputable and anthropology’s role in an emerging interdisciplinary science of human behavior will be critical because its focus is, and
has always been, on human biological and cultural systems.

TRAVEL GRANTS for the 4th EASPLS (European Advanced Seminars in the Philosophy of the Life Sciences) available at:
http://www.ishpssb.org/news/24-meetings/off-year-workshops/154-2016-ishpssb-off-year-workshops

DEADLINE: Call for Abstracts for the 4th EASPLS is 31 MARCH 2016
5 – 9 September 2016
KLI Klosterneuburg (Austria)

!-Aminobutyric acid, type A (GABAA) receptors are ligand-gated chloride channels and are the major inhibitory transmitter receptors in the central nervous system. The majority of these receptors is composed of two a, two b, and one g subunits. To identify sequences important for subunit assembly, we generated C-terminally truncated and chimeric g3 constructs. From their ability to associate with full-length a1 and b3 subunits, we concluded that amino acid sequence g3(70–84) either directly interacts with a1 or b3 subunits or stabilizes a
contact site elsewhere in the protein. The observation that this sequence contains amino acid residues homologous to g2 residues contributing to the benzodiazepine binding site at the a1/g2 interface suggested that in a1b3g3 receptors the sequence !3(70–84) is located at the a1/g3 interface. In the absence of a1 subunits this sequence might allow assembly of b3 with g3 subunits. Other experiments indicated that sequences g3(86–95) and g3(94–107), which are homologous to previously identified sequences important for assembly of g2 subunits, are also important for assembly of g3 subunits. This indicates that during assembly of the GABAA receptor, more than one N-terminal sequence is important for binding to the same neighboring subunit. Whether the three sequences investigated are involved in direct interaction or stabilize other regions involved in intersubunit contacts has to be further studied.

GABAA receptors are the major inhibitory transmitter receptors in the central nervous system. The majority of these receptors is composed of two α, two β and one γ subunit that assemble around an aqueous pore and form an intrinsic chloride ion channel. Using full-length or truncated chimeric subunits it was demonstrated that homologous sequences from different subunit classes, α1(54–68), β3(52–66), and γ2(67–81), are important for assembly of GABAA receptors composed of α1, β3, and γ2 subunits. In addition, evidence was provided that these sequences all are located in topologically homologous regions of the different subunits. Finally, it was demonstrated that the sequences investigated cause a selective assembly with certain subunits only and thus influence subunit arrangement within GABAA receptors.

More than 30 years ago Dan Koshland published an inspirational essay presenting the bacterium as a model neuron (Koshland, Trends Neurosci 6:133–137, 1983). In the article he argued that there are several similarities between neurons and bacterial cells in “how signals are processed within a cell or how this processing machinery can be modified to produce plasticity”. He then explored the bacterial chemosensory system to emphasize its attributes that are analogous to information processing in neurons. In this review, we wish to expand Koshland’s original idea by adding the yeast cell to the list of useful models of a neuron. The fact that yeasts and neurons are specialized versions of the eukaryotic cell sharing all principal components sets the stage for a grand evolutionary tinkering where these components are employed in qualitatively different tasks, but following analogous molecular logic. By way of example, we argue that evolutionarily
conserved key components involved in polarization processes
(from budding or mating in Saccharomyces cervisiae to neurite outgrowth or spinogenesis in neurons) are shared between yeast and neurons. This orthologous conservation of modules makes S. cervisiae an excellent model organism to investigate neurobiological questions. We substantiate this claim by providing examples of yeast models used for studying neurological diseases.

Austrian Neuroscience Association (ANA)´s biennial meeting will take place in Salzburg from September 28th to September 30th, 2021. The meeting will include highly topical keynote lectures, exciting minisymposia, oral and poster presentations by ECRs, exhibitions and technical workshops as well as a public evening lecture.

“Hands-on” Workshop on Historical, Philosophical, and Interdisciplinary Writing & Publishing

Chair:
Isabella Sarto-Jackson (Biological Theory)

Discussants / Speakers:
Gregory Radick (Studies in History and Philosophy of Biological and Biomedical Sciences)
Michael Dietrich (Journal of the History of Biology)
Staffan Mueller-Wille (History and Philosophy of the Life Sciences)

Organizer:
ISHPSSB Education Committee

Aim:
The aim of this workshop is to familiarize PhD students and young scholars with the requirements for publishing in an academic journal. Participants should receive information about the reviewing and publishing process.
Firstly, young scholars should get acquainted with the idea that publishing their work is an eminent part of communicating their ideas. Secondly, information conveyed in this workshop should encourage young historians and philosophers to deal early in their career with the subject of how to get their work published and installing an appropriate workflow for publishing their work. Thirdly, tips and recommendations from the editors should help to reduce putative threshold fear of submitting one´s work.

Workshop participants are invited to send paper excerpts (abstract & maximum of 3 pages of their paper) via email to publicationworkshop@kli.ac.at for the plenary discussion. Papers sent should be either in a final stage (ready for submission to a journal) or have already been submitted and rejected (all documents can be sent anonymously).

Date:
MONDAY July 17, 2017, at the ISHPSSB 2017 meeting in Sao Paolo
15:30-17:00 – Parallel sessions 3, ORGANIZED SESSIONS DIVERSE FORMAT

Format:
90 minutes workshop open to all participants of the ISHPSSB 2017 meeting, especially targeted at PhD students and early Post-docs.

Panel: about 45 min
Plenary (“hands-on” part for the audience): about 45 min following the panel

Topic:
a. Panel:
- Introduction to the journal by the EiC
- The reviewing process
o How are reviewers chosen
o Open versus single versus double blind reviews
o Acceptance/rejection rates
o Reasons for rejection
o From submission to publication: duration, pitfalls, etc.

- Tips for authors:
o How to select the appropriate journal for your paper
o Differences between writing for philosophical or biological readers
o How to deal with rejections

b. Plenary (“hands-on” part):
- Workshop participants will be invited to send paper excerpts via email to the ISHPSSB education committee (publicationworkshop@kli.ac.at); papers that can be sent should be either in a final stage (ready for submission to a journal) or have already been submitted and rejected
- the authors of the paper excerpts may remain anonymous
- all invited editors of the workshop will have access to the submitted paper excerpts
- paper excerpts will be discussed in the plenary; editors will give recommendations to the authors

Venue: Konrad Lorenz institute for Evolution and Cognition Research (KLI), Klosterneuburg (Austria), September 10-14, 2018
Directors: Sabina Leonelli (Exeter) & Thomas Reydon (Hannover)

The European Advanced School in the Philosophy of the Life Sciences (EASPLS) consortium will hold its fifth biennial summer school on September 10-14, 2018 at the Konrad Lorenz institute for Evolution and Cognition Research (KLI) in Klosterneuburg near Vienna, Austria. The overarching topic of EASPLS 2018 is interdisciplinarity in the life sciences and their philosophy. Young scholars (PhD students and early post-doctoral researchers) in the history, philosophy and social studies of the life sciences (including medicine) are invited to apply. The registration fee is € 570,- (including accommodation in single rooms, breakfasts and lunches, but not including travel expenses and dinners). Please find more details at: http://bit.ly/2mHYPdj.

The human brain has a truly remarkable capacity. It reorganizes itself, flexibly adjusting to fl uctuating environmental conditions – a process called neuroplasticity. Neuroplasticity provides the basis for wide-ranging learning and memory processes that are particularly profuse during childhood and adolescence. At the same time, the exceptional malleability of the developing brain leaves it highly vulnerable to negative impact from the surroundings. Abusive or neglecting social environments, as well as socioeconomic deprivation and poverty, cause toxic stress and complex traumas that can severely compromise cognitive development, emotional processing, self-perception, and executive brain functions. The neurophysiological changes entailed impair emotional regulation, lead to heightened anxiety, and afflict attachment and the formation of social bonds. Neuroplastic changes following severely adverse experiences are not something that a person grows out of and gets over. These experiences alter the neurobiological and
biochemical makeup and cause people to live in an emotionally relabeled world in which the evaluation of any social cue, their behavior, cognition, and state of mind are biased towards the negative. Even more worrying, detrimental neurophysiological consequences are not limited to the traumatized individual but are often transmitted to subsequent generations through a process of social niche construction, thereby creating a vicious cycle. Thus, the making and breaking forces of the brain are epitomized by parents, alloparents, peers, and our socioeconomic niche.
This book expounds on the formative role that the social environment plays in healthy brain development, especially during infancy, childhood, and adolescence. Based on scientific findings, the book advocates for bold measures and responsible stewardship to combat child abuse, maltreatment, and child poverty. By bringing together insights from neuroscience, evolutionary biology, and social education work, it lays out a fact-based, transdisciplinary endeavor that aims at rising to the societal challenge of providing a rewarding perspective to youth at risk. It will be a valuable resource for academics from social education, pedagogy, cognitive science, neuroscience, as well as professionals in the fields of social work, pedagogy, education, child welfare.