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

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Estudo do alcance do retalho do músculo grande dorsal para o revestimento cutâneo da coluna An anatomic study of latissimus dorsi and its suitability for spinal soft tissue coverage

INTRODUÇÃO: A crescente indicação cirúrgica na terapêutica das patologias da coluna vertebral, ocasionada pela melhoria tecnológica aplicada ao tratamento cirúrgico, que proporciona cada vez mais uma cirurgia mais segura, mais rápida, menos invasiva e com melhores resultados funcionais, tem nos levado a um aumento nas complicações pós-operatórias da coluna vertebral. As complicações podem ser mecânicas, biológicas, estruturais ou relacionadas ao material de síntese. As infecções em cirurgia de coluna vertebral, embora raras, ocorrem em 3-6%, constituem um dilema para o cirurgião de coluna, além de graves desdobramentos clínicos para o paciente. A importância do uso do retalho do grande dorsal esta implicada na tentativa de cobertura de partes moles e melhora no padrão vascular regional. OBJETIVO: Avaliar a confiabilidade do retalho do músculo grande dorsal para cobertura de defeitos cutâneos na coluna. MATERIAL E MÉTODO: Foram dissecados 17 músculos grande dorsal de cadáver e medido o quanto eles passavam da linha média na altura de C7, T7 e transição toracolombar. RESULTADOS E CONCLUSÃO: O estudo anatômico realizado comprovou a eficácia desse método.<br>INTRODUCTION: There has been a dramatic increase in spine surgery. New surgical instrumentation and less invasive techniques make surgical procedure faster, safer, achieving better functional results. With this increasing number of operations, the number of back surgery failures has also increased. Complications may be mechanical, biological, or related to problems on instrumentation frames. The rate of spinal infections lies between 3-6 % and it´s still a challenge. After debridement and removal of all infected nonviable soft tissue, it is sometimes difficult to obtain wound closure. Pedicled latissimus dorsi muscle flap coverage provides wound healing by promoting vascularized tissue to reduce dead spaces, enhancing local oxygen delivery, and facilitating antibiotic concentration. OBJECTIVE: Evaluate the suitability of the latissimus dorsi flap for covering spinal skin defects. MATERIAL AND METHODS: 17 cadaveric latissimus dorsi flaps were made, measuring how much they surpassed the middle line at C7, T7 and thocaolumbar transition. RESULTS AND CONCLUSION: This study warrants the suitability of this flap to cover spinal skin defects

Functional Interaction between Acyl-CoA Synthetase 4, Lipooxygenases and Cyclooxygenase-2 in the Aggressive Phenotype of Breast Cancer Cells

The acyl-CoA synthetase 4 (ACSL4) is increased in breast cancer, colon and hepatocellular carcinoma. ACSL4 mainly esterifies arachidonic acid (AA) into arachidonoyl-CoA, reducing free AA intracellular levels, which is in contradiction with the need for AA metabolites in tumorigenesis. Therefore, the causal role of ACSL4 is still not established. This study was undertaken to determine the role of ACSL4 in AA metabolic pathway in breast cancer cells. The first novel finding is that ACSL4 regulates the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin in MDA-MB-231 cells. We also found that ACSL4 is significantly up-regulated in the highly aggressive MDA-MB-231 breast cancer cells. In terms of its overexpression and inhibition, ACSL4 plays a causal role in the control of the aggressive phenotype. These results were confirmed by the increase in the aggressive behaviour of MCF-7 cells stably transfected with a Tet-off ACSL4 vector. Concomitantly, another significant finding was that intramitochondrial AA levels are significantly higher in the aggressive cells. Thus, the esterification of AA by ACSL4 compartmentalizes the release of AA in mitochondria, a mechanism that serves to drive the specific lipooxygenase metabolization of the fatty acid. To our knowledge, this is the first report that ACSL4 expression controls both lipooxygenase and cyclooxygenase metabolism of AA. Thus, this functional interaction represents an integrated system that regulates the proliferating and metastatic potential of cancer cells. Therefore, the development of combinatory therapies that profit from the ACSL4, lipooxygenase and COX-2 synergistic action may allow for lower medication doses and avoidance of side effects