The role of action representations in thematic object relations

A number of studies have explored the role of associative/event-based (thematic) and categorical (taxonomic) relations in the organization of object representations. Recent evidence suggests that thematic information may be particularly important in determining relationships between manipulable artifacts. However, although sensorimotor information is on many accounts an important component of manipulable artifact representations, little is known about the role that action may play during the processing of semantic relationships (particularly thematic relationships) between multiple objects. In this study, we assessed healthy and left hemisphere stroke participants to explore three questions relevant to object relationship processing. First, we assessed whether participants tended to favor thematic relations including action (Th+A, e.g., wine bottle—corkscrew), thematic relationships without action (Th-A, e.g., wine bottle—cheese), or taxonomic relationships (Tax, e.g., wine bottle—water bottle) when choosing between them in an association judgment task with manipulable artifacts. Second, we assessed whether the underlying constructs of event relatedness, action relatedness, and categorical relatedness determined the choices that participants made. Third, we assessed the hypothesis that degraded action knowledge and/or damage to temporo-parietal cortex, a region of the brain associated with the representation of action knowledge, would reduce the influence of action on the choice task. Experiment 1 showed that explicit ratings of event, action, and categorical relatedness were differentially predictive of healthy participants' choices, with action relatedness determining choices between Th+A and Th-A associations above and beyond event and categorical ratings. Experiment 2 focused more specifically on these Th+A vs. Th-A choices and demonstrated that participants with left temporo-parietal lesions, a brain region known to be involved in sensorimotor processing, were less likely than controls and tended to be less likely than patients with lesions sparing that region to use action relatedness in determining their choices. These data indicate that action knowledge plays a critical role in processing of thematic relations for manipulable artifacts

Marine epibenthic functional diversity on Flemish Cap (north- west Atlantic)—Identifying trait responses to the environment and mapping ecosystem functions

Aim To characterize the functional diversity and selected ecological functions of marine epibenthic invertebrate communities at the ecosystem scale and to evaluate the relative contributions of environmental filtering, including bottom-contact fishing, and competitive interactions to benthic community assembly. Location Flemish Cap, an ecosystem production unit and fishing bank in the high seas of the north-west Atlantic Ocean. Methods Through the use of Hierarchical Modelling of Species Communities (HMSC), we have explored seven community response traits to the environment applied to 105 epibenthic species and evaluated the influence of such traits on the community assembly processes. Assumed bioturbation, nutrient cycling and habitat provision functions, linked to individual or a combination of biological traits, were mapped using random forest modelling. Results Functional richness within benthic communities reached an asymptote for trawl sets with roughly more than 30 species. Assemblages on top of the Flemish Cap (Peer reviewe

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Author Correction: Ecology, evolution and spillover of coronaviruses from bats.

In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002–2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat–coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic

CD133 expression in chemo-resistant Ewing sarcoma cells

<p>Abstract</p> <p>Background</p> <p>Some human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT) are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance.</p> <p>Methods</p> <p>Expression of the CD133-encoding <it>PROM1 </it>gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and <it>in vivo </it>tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays.</p> <p>Results</p> <p><it>PROM1 </it>expression was either absent or extremely low in most tumors. However, <it>PROM1 </it>was highly over-expressed in 4 of 48 cases. Two of the 4 patients with <it>PROM1 </it>over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of <it>PROM1 </it>in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny.</p> <p>Conclusions</p> <p>Up to 10% of ESFT express high levels of <it>PROM1</it>. In some tumors and cell lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in <it>PROM1</it>/CD133 expression in ESFT tumors and cell lines and confirm that high levels of <it>PROM1 </it>expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of <it>PROM1/</it>CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT.</p

Molecular and cellular characterization of ABCG2 in the prostate

BACKGROUND: Identification and characterization of the prostate stem cell is important for understanding normal prostate development and carcinogenesis. The flow cytometry-based side population (SP) technique has been developed to isolate putative adult stem cells in several human tissue types including the prostate. This phenotype is mainly mediated by the ATP-binding cassette membrane transporter ABCG2. METHODS: Immunolocalization of ABCG2 was performed on normal prostate tissue obtained from radical prostatectomies. Normal human prostate SP cells and ABCG2(+ )cells were isolated and gene expression was determined with DNA array analysis and RT-PCR. Endothelial cells were removed by pre-sorting with CD31. RESULTS: ABCG2 positive cells were localized to the prostate basal epithelium and endothelium. ABCG2(+ )cells in the basal epithelium constituted less than 1% of the total basal cell population. SP cells constituted 0.5–3% of the total epithelial fraction. The SP transcriptome was essentially the same as ABCG2(+ )and both populations expressed genes indicative of a stem cell phenotype, however, the cells also expressed many genes in common with endothelial cells. CONCLUSION: These results provide gene expression profiles for the prostate SP and ABCG2(+ )cells that will be critical for studying normal development and carcinogenesis, in particular as related to the cancer stem cell concept

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity in vivo. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies

Detection and Characterization of CD133+ Cancer Stem Cells in Human Solid Tumours

Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency.Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer

Resilience trinity: safeguarding ecosystem functioning and services across three different time horizons and decision contexts

Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi-faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time-horizons: i) reactive, when there is an imminent threat to ES resilience and a high pressure to act, ii) adjustive, when the threat is known in general but there is still time to adapt management, and iii) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology, and engineering are often implicitly focussing on provident, adjustive, or reactive resilience, respectively, but these different notions and of resilience and their corresponding social, ecological, and economic trade-offs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer-term management actions are not missed while urgent threats to ES are given priority