Modelling brain representations of abstract concepts

Abstract conceptual representations are critical for human cognition. Despite their importance, key properties of these representations remain poorly understood. Here, we used computational models of distributional semantics to predict multivariate fMRI activity patterns during the activation and contextualization of abstract concepts. We devised a task in which participants had to embed abstract nouns into a story that they developed around a given background context. We found that representations in inferior parietal cortex were predicted by concept similarities emerging in models of distributional semantics. By constructing different model families, we reveal the models’ learning trajectories and delineate how abstract and concrete training materials contribute to the formation of brain-like representations. These results inform theories about the format and emergence of abstract conceptual representations in the human brain.     

Prefrontal cortex activity related to abstract response strategies

Many monkeys adopt abstract response strategies as they learn to map visual symbols to responses by trial and error. According to the repeat-stay strategy, if a symbol repeats from a previous, successful trial, the monkeys should stay with their most recent response choice. According to the change-shift strategy, if the symbol changes, the monkeys should shift to a different choice. We recorded the activity of prefrontal cortex neurons while monkeys chose responses according to these two strategies. Many neurons had activity selective for the strategy used. In a subsequent block of trials, the monkeys learned fixed stimulus-response mappings with the same stimuli. Some neurons had activity selective for choosing responses based on fixed mappings, others for choosing based on abstract strategies. These findings indicate that the prefrontal cortex contributes to the implementation of the abstract response strategies that monkeys use during trial-and-error learning.     

Current concepts in cancer vaccine strategies

Cancer vaccines are entering a new phase of popularity, in part because of the recognition of when a therapeutic vaccine is most effective and the identification of appropriate target antigens. New technologies, most notably gene transfection into dendritic cell and DNA vaccination approaches, have spurred further clinical evaluations. While many researchers consider humoral responses as not being viable for large tumors, these responses may play a role in regulating micrometastases (i.e., adjuvant setting). The recent approval of antibodies as therapeutics for cancer treatment has lent to the viability of this therapy concept. The success of carbohydrate-conjugate vaccines in bacterial systems has also renewed interest in developing such vaccines for cancer immunotherapy. Carbohydrates can be further converted into peptide/protein mimetics with several of these mimetics in clinical trials. These mimetic forms can be manipulated into DNA vaccine types that may be combined into DNA cassettes that contain CTL-associated epitopes to further define a novel strategy for future vaccine development.     

Moral and religious influences on the amniocentesis decision

Abstract

As early as 1973 Fletcher documented moral problems families encountered as they struggled with the decision of whether or not to have amniocentesis. In this study we asked 202 women accepting and 50 women rejecting amniocentesis extensive questions about religious beliefs, behaviors, and beliefs about abortion. Members of small Protestant denominations were the most conservative. Catholics and other Protestants were intermediate with smaller differences between these middle groups. Those respondents claiming no religion or one of a non‐Christian denomination were the most liberal. Net predictors of acceptance of amniocentesis included respondents’ support for laws permitting abortion for medical reasons, negative responses about belief in the sanctity of life, having insurance, and the respondents’ political affiliation. Education and religious attendance were the most consistent net predictorsof moral attitudes. We concluded that the amniocentesis decision is influenced by many religious beliefs but is not completely determined by these.     

Design concepts and strategies for tissue engineering scaffolds

In the emerging field of tissue engineering and regenerative medicine, new viable and functional tissue is fabricated from living cells cultured on an artificial matrix in a simulated biological environment. It is evident that the specific requirements for the three main components, cells, scaffold materials, and the culture environment, are very different, depending on the type of cells and the organ-specific application. Identifying the variables within each of these components is a complex and challenging assignment, but there do exist general requirements for designing and fabricating tissue engineering scaffolds. Therefore, this review explores one of the three main components, namely, the key concepts, important parameters, and required characteristics related to the development and evaluation of tissue engineering scaffolds. An array of different design strategies will be discussed, which include mimicking the extra cellular matrix, responding to the need for mass transport, predicting the structural architecture, ensuring adequate initial mechanical integrity, modifying the surface chemistry and topography to provide cell signaling, and anticipating the material selection so as to predict the required rate of bioresorption. In addition, this review considers the major challenge of achieving adequate vascularization in tissue engineering constructs, without which no three-dimensional thick tissue such as the heart, liver, and kidney can remain viable.     

Using structured decision‐making to set restoration objectives when multiple values and preferences exist

Achieving global targets for restoring native vegetation cover requires restoration projects to identify and work toward common management objectives. This is made challenging by the different values held by concerned stakeholders, which are not often accounted for. Additionally, restoration is time‐dependent and yet there is often little explicit acknowledgment of the time frames required to achieve outcomes. Here, we argue that explicitly incorporating value and time considerations into stated objectives would help to achieve restoration goals. We reviewed the peer‐reviewed literature on restoration of terrestrial vegetation and found that while there is guidance on how to identify and account for stakeholder values and time considerations, there is little evidence these are being incorporated into decision‐making processes. In this article, we explore how a combination of stakeholder surveys and workshops can be used within a structured decision‐making framework to facilitate the integration of diverse stakeholder values and time frame considerations to set restoration objectives. We demonstrate this approach with a case of restoration decision‐making at a regional scale (southeast Queensland, Australia) with a view to this experience supporting similar restoration projects elsewhere.     

Great apes' risk-taking strategies in a decision making task

We investigate decision-making behaviour in all four non-human great ape species. Apes chose between a safe and a risky option across trials of varying expected values. All species chose the safe option more often with decreasing probability of success. While all species were risk-seeking, orangutans and chimpanzees chose the risky option more often than gorillas and bonobos. Hence all four species' preferences were ordered in a manner consistent with normative dictates of expected value, but varied predictably in their willingness to take risks.     

Determination of non-market values to inform conservation strategies for the threatened Alistana–Sanabresa cattle breed

Livestock breed-related public good functions are often used to justify support for endangered breed conservation despite the fact that little is known about such non-market values. We show how stated preference techniques can be used to assess the non-market values that people place on livestock breeds. Through the application of a case study choice experiment survey in Zamora province, Spain, the total economic value (TEV) of the threatened Alistana–Sanabresa (AS) cattle breed was investigated. An analysis of the relative importance of the non-market components of its TEV and an assessment of the socio-economic variables that influence people’s valuation of such components is used to inform conservation strategy design. Overall, the findings reveal that the AS breed had significant non-market values associated with it and that the value that respondents placed on each specific public good function also varied significantly. Functions related with indirect use cultural and existence values were much more highly valued than landscape maintenance values. These high cultural and existence values (totalling over 80% of TEV) suggest that an AS in situ conservation strategy will be required to secure such values. As part of such a strategy, incentive mechanisms will be needed to permit farmers to capture some of these public good values and thus be able to afford to maintain breed population numbers at socially desirable levels. One such mechanism could be related to the development of breed-related agritourism initiatives, with a view to enhancing private good values and providing an important addition to continued direct support. Where linked with cultural dimensions, niche product market development, including through improving AS breed-related product quality and brand recognition may also have a role to play as part of such an overall conservation and use strategy. We conclude that livestock breed conservation strategies with the highest potential to maximise societal welfare would be those that secure the breed-related functions that people value most, with appropriate in situ conservation interventions and strategies being identified accordingly.     

Mitochondria as the decision makers for cancer cell fate: from signaling pathways to therapeutic strategies

As pivotal players in cellular metabolism, mitochondria have a double-faceted role in the final decision of cell fate. This is true for all cell types, but it is even more important and intriguing in the cancer setting.Mitochondria regulate cell fate in many diverse ways: through metabolism, by producing ATP and other metabolites deemed vital or detrimental for cancer cells; through the regulation of Ca²⁺ homeostasis, especially by the joint participation of the endoplasmic reticulum in a membranous tethering system for Ca²⁺ signaling called mitochondria-ER associated membranes (MAMs); and by regulating signaling pathways involved in the survival of cancer cells such as mitophagy. Recent studies have shown that mitochondria can also play a role in the regulation of inflammatory pathways in cancer cells, for example, through the release of mitochondrial DNA (mtDNA) involved in the activation of the cGAS-cGAMP-STING pathway.In this review, we aim to explore the role of mitochondria as decision makers in fostering cancer cell death or survival depending on the tumor cell stage and describe novel anticancer therapeutic strategies targeting mitochondria.     

Excitotoxic mechanisms in stroke: an update of concepts and treatment strategies

Cerebral damage as a consequence of glutamate-mediated excitotoxicity represents a major consequence of stroke. However, the development of effective clinical treatments for this potentially devastating condition has been largely unsuccessful to date, despite promising basic research. This review will focus on the latest advances in our understanding of the excitotoxic process including the release of glutamate as a neurotransmitter and the potential contribution of complexins, the important role of astrocytes, including its involvement in glutamate uptake, alterations in glutamate transporter levels, reversed glutamate uptake, and the vesicular release of glutamate. Recent progress in our understanding of the involvement of excitotoxicity in white matter injury following ischemic insults is also discussed, as is oxidative stress and ischemic tolerance, along with an update on the use of treatment strategies with potential therapeutic benefit including stimulation of neurogenesis. Such key issues are at the heart of future interventions directed at limiting the extent of the excitotoxic process, and remain a viable consideration for effective stroke management.     

Fed-batch cultivation of animal cells using different medium design concepts and feeding strategies

In animal cell cultivation, cell density and product concentration are often low due to the accumulation of toxic end-products such as ammonia and lactate and/or the depletion of essential nutrients. A hybridoma cell line (CRL-1606) was cultivated in T-flasks using a newly devised medium feeding strategy. The goals were to decrease ammonia and lactate formation by the design of an initial medium which would provide a starting environment to achieve optimal cell growth. This was followed by using a stoichiometric equation governing animal cell growth and then designing a supplemental medium for feeding strategy used to control the nutritional environment. The relationship between the stoichiometric demands for glutamine and nonessential amino acids was also studied. Through stoichiometric feeding, nutrient concentrations were controlled reasonably well. Consequently, the specific production rate of lactate was decreased by fourfold compared with conventional fed-batch culture and by 26-fold compared with conventional batch culture. The specific production rate of ammonia was decreased by tenfold compared with conventional fed-batch culture and by 50-fold compared with conventional batch culture. Most importantly, total cell density and monoclonal antibody concentration were increased by five- and tenfold respectively, compared with conventional batch culture. (c) 1994 John Wiley & Sons, Inc.     

Cometabolism of trichloroethylene: concepts, limitations and available strategies for sustained biodegradation

Due to its toxicity and persistence in the environment, trichloroethylene (TCE) has become a major soil and groundwater contaminant in many countries. A group of aliphatic- and aromatic-degrading bacteria expressing nonspecific oxygenases have been reported to transform TCE through aerobic cometabolism in the presence of primary substrate such as methane, ammonia, propane, phenol, toluene or cumene. This paper reviews the fundamentals and results of TCE cometabolism from laboratory and field studies. The limitations associated with TCE cometabolism including the causes and effects of substrate and/or inducer utilization rate and depletion, enzyme inhibition and inactivation, and cytotoxicity during TCE oxidation among various TCE-degrading bacteria and enzymes are discussed. In addition, the potential strategies e.g. addition of primary substrate/inducer or external energy substrate, use of a two-stage reactor and application of cell immobilization for sustained TCE degradation are highlighted. The review summarizes important information on TCE cometabolism, which is necessary for developing efficient TCE bioremediation approaches.