Despite its ubiquity and significance, behavioral habituation is poorly understood in terms of the underlying neural circuit mechanisms. Here, we present evidence that habituation arises from potentiation of inhibitory transmission within a circuit motif commonly repeated in the nervous system. In Drosophila, prior odorant exposure results in a selective reduction of response to this odorant. Both short-term (STH) and long-term (LTH) forms of olfactory habituation require function of the rutabaga-encoded adenylate cyclase in multiglomerular local interneurons (LNs) that mediate GABAergic inhibition in the antennal lobe; LTH additionally requires function of the cAMP response element-binding protein (CREB2) transcription factor in LNs. The odorant selectivity of STH and LTH is mirrored by requirement for NMDA receptors and GABA A receptors in odorant-selective, glomerulus-specific projection neurons (PNs). The need for the vesicular glutamate transporter in LNs indicates that a subset of these GABAergic neurons also releases glutamate. LTH is associated with a reduction of odorant-evoked calcium fluxes in PNs as well as growth of the respective odorant-responsive glomeruli. These cellular changes use similar mechanisms to those required for behavioral habituation. Taken together with the observation that enhancement of GABAergic transmission is sufficient to attenuate olfactory behavior, these data indicate that habituation arises from glomerulus-selective potentiation of inhibitory synapses in the antennal lobe. We suggest that similar circuit mechanisms may operate in other species and sensory systems.abituation is a specific form of implicit learning in which repeated exposure to an unreinforced stimulus results in a decreased behavioral response (1-3). By filtering out such constant sensory input, habituation enhances an animal's ability to focus its cognitive resources on novel or salient features of the environment. Thus, habituation serves as a building block for normal cognition (2, 4). Although it has been studied in many different contexts, causal connections between mechanisms, neuronal changes, and behavioral habituation have not been clearly identified (2). Given our current understanding, it remains unclear whether similar or distinct mechanisms underlie different forms of habituation; also unclear is how these mechanisms compare with those mechanisms used in consolidation or extinction of associative memory (1, 5).The olfactory system provides an experimentally accessible circuit in which to analyze mechanisms that underlie different timescales of behavioral habituation (4, 6, 7). Particularly useful is the adult Drosophila olfactory system, which has organization similar to that of mammals (8, 9). Here, olfactory sensory neurons (OSNs) expressing a single type of functional odorant receptor molecules (ORs) send axons to the antennal lobe and synapse onto (i) glomerulus-specific projection neurons (PNs) that project to the mushroom body and lateral horn, (ii) multiglomerular local interneurons (LNs...

Aging in custody and the rising population of elderly prisoners are creating compelling challenges for criminal justice, prison and public healthcare systems. Geriatric syndrome and higher prevalence of co-morbidities amongst older inmates result in heightened vulnerability in prison environments. Empirical research addressing older adults' access to medical care in detention is scarce; therefore, this study assessed access to medical care in prison from the perspective of older prisoners in Switzerland. We interviewed a sample of 35 older inmates (average age 61 years) on their experience of healthcare accessibility in prison; data were qualitatively analysed and major themes regarding evaluation of their access to medical services were extracted. Our findings identified three barriers to accessing health services in prison including psychological obstacles, negative consequences of healthcare utilization, and environmental hurdles. We advocate facilitating older inmates' access to medical care in order to relieve the psychological burden of seeking health services in detention and adequately informing them of their right to demand these services, thereby lessening the negative consequences of their requests. We suggest further training of prison and medical staff for better management of age-related issues in prison can ease the environmental obstacles.

Emergence of novel genome engineering technologies such as clustered regularly interspaced short palindromic repeat (CRISPR) has refocused attention on unresolved ethical complications of synthetic biology. Biosecurity concerns, deontological issues and human right aspects of genome editing have been the subject of in-depth debate; however, a lack of transparent regulatory guidelines, outdated governance codes, inefficient time-consuming clinical trial pathways and frequent misunderstanding of the scientific potential of cutting-edge technologies have created substantial obstacles to translational research in this area. While a precautionary principle should be applied at all stages of genome engineering research, the stigma of germline editing, synthesis of new life forms and unrealistic presentation of current technologies should not arrest the transition of new therapeutic, diagnostic or preventive tools from research to clinic. We provide a brief review on the present regulation of CRISPR and discuss the translational aspect of genome engineering research and patient autonomy with respect to the "right to try" potential novel non-germline gene therapies.

Molecular Systems Engineering (MSE) is a paradigm shift in both engineering and life sciences. While the field is still in its infancy the perspectives of MSE in revolutionising technology is promising. MSE will offer a wide range of applications in clinical, biotechnological and engineering fields while simultaneously posing serious questions on the ethical and societal aspects of such technology. The moral and societal aspects of MSE need systematic investigation from scientific and social perspectives. In a democratic setting, the societal outcomes of MSE's cutting-edge technology need to be consulted and influenced by society itself. For this purpose MSE needs inclusive public engagement strategies that bring together the public, ethicists, scientists and policy makers for optimum flow of information that maximizes the impact of public engagement. In this report we present an MSE consortium and its ethics framework for establishing a proactive approach in the study of the ethics of MSE technology. Keywords: Art of molecule · Ethics · Molecular systems engineering · Proactive ethics · Public engagement · Society Molecular Systems EngineeringThe origin of life, i.e. how early life form(s) appeared on earth, is still a mystery not only for science but also for philosophy. In 2014, scientists simulated an extra-terrestrial high-power strike that triggered the synthesis of nucleobases -the ingredients of life -from formamide. [1] Formation of nucleobases from formamide about 4 billion years ago is one of the possible scenarios that could explain the sudden emergence of RNA (ribonucleic acid) as the earliest precursor of life. Deciphering the processes of abiogenesis potentially enables scientists to write their own recipe of genetic code and re-create exotic life forms as not seen before. The emergence of interdisciplinary fields such as synthetic biology, together with systems approaches in discovery science (e.g. systems chemistry and systems biology) are revolutionizing our traditional attitude in the life sciences and open, as yet unprecedented, possibilities to develop novel applications in medical science, pharmaceutical and agricultural industries.Synthetic biology takes advantage of multiple problem-solving strategies: it permits us to determine a minimal gene setting that constitutes a living cellular form (top-down approach), and to construct synthetic biological systems, protocells and living cells (bottom-up approach) with the ultimate goal: to redesign life. [2] Systems biology integrates this information into computational models and mathematical formulae that can describe the structure of the system. [3] The bottom-up approach of synthetic biology in the construction of living cells/organisms requires an in-depth understanding of chemical structure of molecules and their behaviour within dynamic chemo-biological networks. Systems chemistry assists synthetic biology by addressing the molecular prerequisites of self-replication and self-reproduction; systems chemistry contributes to synthet...