Academic literature on the topic 'Evolutionary biology not elsewhere classified'

Viruses that are normally safely contained within their host spe­cies can emerge due to intense livestock farming, trade, travel, climate change and encroachment of human activities into new environments. The unexpected emergence of bluetongue virus (BTV), the prototype species of the genus Orbivirus, in economi­cally important livestock species (sheep and cattle) across the whole of Europe (since 1998), indicates that other orbiviruses represent a potential further threat to animal and human popula­tions in Europe and elsewhere. The genus Orbivirus is the largest within the family Reoviridae, containing 22 virus species, as well as 14 unclassified orbiviruses, some of which may repre­sent additional or novel species. The orbiviruses are transmitted primarily by arthropod vectors (e.g. Culicoides, mosquitoes or ticks). Viral genome sequence data provide a basis for virus taxonomy and diagnostic test development, and make it possible to address fundamental questions concerning virus biology, pathogenesis, virulence and evolution, that can be further explored in mutation and reverse genetics studies. Genome sequences also provide criteria for the classification of novel isolates within individual Orbivirus species, as well as the identification of different sero­types, topotypes, reassortants and even closely related but dis­tinct virus lineages. Full-length genome characterization of Tilligerry virus (TILV), a member of the Eubenangee virus species, and Mitchell River virus (MRV), a member of the Warrego virus species, have revealed highly conserved 5’ and 3’ terminal hexanucleotide sequences. Phylogenetic analyses of orbivirus T2 ‘sub-core-shell’ protein sequences reinforce the hypothesis that this protein is an important evolutionary marker for these viruses. The T2 protein shows high levels of amino acid (AA) sequence identity (> 91%) within a single Orbivirus species / serogroup, which can be used for species identification. The T2-protein gene has therefore been given priority in sequencing studies. The T2 protein of TILV is closely related to that of Eubenangee virus (~91% identity), con­firming that they are both members of the same Eubenangee virus species. Although TILV is reported to be related to BTV in serological assays, the TILV T2 protein shows only 68-70% AA identity to BTV. This supports its current classification within a different serogroup (Eubenangee). Warrego virus and MRV are currently classified as two distinct members (different serotypes) within the Warrego virus species. However, they show only about 79% AA identity in their T2 pro­tein (based on partial sequences). It is therefore considered likely that they could be reclassified as members of distinct Orbivirus species. The taxonomic classification of MRV will be reviewed after generating full length sequences for the entire genomes of both viruses. The taxonomic status of each of these viruses will also be tested further by co-infections and attempts to create reassortants between them (only viruses belonging to the same species can reassort their genome segments). TILV and MRV are the first viruses from their respective serogroups / virus species to be genetically fully characterized, and will provide a basis for the further characterization / identification of additional viruses within each group / species. These data will assist in the devel­opment of specific diagnostic assays and potentially in control of emerging diseases. The sequences generated will also help to evaluate current diagnostic [reverse transcriptase - polymerase chain reaction (RT-PCR)] tests for BTV, African horse sickness virus, epizootic haemorrhagic disease virus, etc., in silico, by identifying any possibility of cross reactivity.

The history of our planet is underpinned by roughly 4 billion years of microbial evolution. From its emergence in a (probably) hot and anoxic environment, microbial life has evolved to colonize every available niche on our planet, including the inside and outside of other organisms. Yet, the emergence and evolution of microbial metabolism remains a major unsolved problem. How have microbes adapted to colonize every available environmental niche, including other organisms? How did they evolve to colonize mammals and our human ancestors? Answers to these questions will allow us to understand the emergence and evolution of life on our planet, inform the search for life elsewhere and, in the making, reveal important insight that will help us fight infections.

Many Christian scholars have argued that standard versions of evolutionary theory and orthodox theological commitments can be reconciled. Some theistic evolutionists or “evolutionary creationists” have argued that evolutionary mechanisms such as random mutation and natural selection are nothing less than God’s way of creating. Though I dispute the logical coherence of these attempted reconciliations elsewhere, I argue here that there is little reason for Christians to attempt them, since an accumulating body of evidence from multiple subdisciplines of biology casts doubt on the creative power of the main evolutionary mechanisms. Thus, rather than addressing the question, “Can a meaningful doctrine of divine providence or creation be reconciled with mainstream evolutionary theory?” this essay will address the question of whether Christians should, or need to, attempt such a reconciliation at all.

‘Replaying the tape’ is an intriguing ‘would it happen again?’ exercise. With respect to broad evolutionary innovations, such as photosynthesis, the answers are central to our search for life elsewhere. Photosynthesis permits a large planetary biomass on Earth. Specifically, oxygenic photosynthesis has allowed an oxygenated atmosphere and the evolution of large metabolically demanding creatures, including ourselves. There are at least six prerequisites for the evolution of biological carbon fixation: a carbon-based life form; the presence of inorganic carbon; the availability of reductants; the presence of light; a light-harvesting mechanism to convert the light energy into chemical energy; and carboxylating enzymes. All were present on the early Earth. To provide the evolutionary pressure, organic carbon must be a scarce resource in contrast to inorganic carbon. The probability of evolving a carboxylase is approached by creating an inventory of carbon-fixation enzymes and comparing them, leading to the conclusion that carbon fixation in general is basic to life and has arisen multiple times. Certainly, the evolutionary pressure to evolve new pathways for carbon fixation would have been present early in evolution. From knowledge about planetary systems and extraterrestrial chemistry, if organic carbon-based life occurs elsewhere, photosynthesis—although perhaps not oxygenic photosynthesis—would also have evolved.

AbstractWe discuss whether it is possible to test the universality of biology, a quest that is of paramount relevance for one of its most recent branches, namely astrobiology. We review this topic in terms of the relative roles played on the Earth biota by contingency and evolutionary convergence. Following the seminal contribution of Darwin, it is reasonable to assume that all forms of life known to us so far are not only terrestrial, but are descendants of a common ancestor that evolved on this planet at the end of a process of chemical evolution. We also raise the related question of whether the molecular events that were precursors to the origin of life on Earth are bound to occur elsewhere in the Universe, wherever the environmental conditions are similar to the terrestrial ones. We refer to ‘cosmic convergence’ as the possible occurrence elsewhere in the Universe of Earth-like environmental conditions. We argue that cosmic convergence is already suggested by observational data. The set of hypotheses for addressing the question of the universality of biology can be tested by future experiments that are feasible with current technology. We focus on landing on Europa and the broader implications of selecting the specific example of the right landing location. We have previously discussed the corresponding miniaturized equipment that is already in existence. The significance of these crucial points needs to be put into a wider scientific perspective, which is one of the main objectives of this review.

Background/Aims: Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the “Li” aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Methods: Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Results: Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35), 1b (n=31), 3b (n=16), 2a (n=8), 3a (n=6), and 1a (n=4). By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Conclusions: Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention.

ABSTRACT The ABC superfamily of genes is one of the largest in the genomes of both bacteria and eukaryotes. The proteins encoded by these genes all carry a characteristic 200- to 250-amino-acid ATP-binding cassette that gives them their family name. In bacteria they are mostly involved in nutrient import, while in eukaryotes many are involved in export. Seven different families have been defined in eukaryotes based on sequence homology, domain topology, and function. While only 6 ABC genes in Dictyostelium discoideum have been studied in detail previously, sequences from the well-advanced Dictyostelium genome project have allowed us to recognize 68 members of this superfamily. They have been classified and compared to animal, plant, and fungal orthologs in order to gain some insight into the evolution of this superfamily. It appears that many of the genes inferred to have been present in the ancestor of the crown organisms duplicated extensively in some but not all phyla, while others were lost in one lineage or the other.

Abstract Changes in the geography of Atlantic Canada since the last glacial maximum (LGM) are grouped into three phases. The first phase (LGM – ca. 13 ka BP) commences with glaciers at the edge of the continental shelves, and ends with the glaciers having retreated to near modern coasts. In the second phase (ca. 13 ka BP‑10 ka BP), glaciers were mainly on land; on the continental shelves there were scattered small ice caps and an outer-shelf archipelago. Early in phase three, beginning ca. 10 ka BP, glaciers were largely absent, and the archipelago was gradually submerging; elsewhere, falling relative sea levels caused emergence. Multibeam sonar mapping has revealed the geomorphic evidence of submerged terrestrial environments of phases II and III, including fluvial, deltaic, and coastal systems. The best-preserved fluvial systems are in Northumberland Strait and the Bras d’Or Lakes. Elsewhere, multibeam bathymetric data allow discrimination between fluvial and non-fluvial channels. Deltas were mainly preserved in the special circumstances of Newfoundland fjords. Submerged coastal systems are common in the Bras d’Or Lakes, but rare elsewhere. Landscape preservation is ascribed to special circumstances. Paleogeographic reconstructions have applications in the field of evolutionary biology and archaeology.

Geb was the first artificial life system to be classified as exhibiting open-ended evolutionary dynamics according to Bedau and Packard's evolutionary activity measures and is the only one to have been classified as such according to the enhanced version of that classification scheme. Its evolution is driven by biotic selection, that is (approximately), by natural selection rather than artificial selection. Whether or not Geb can generate an indefinite increase in maximum individual complexity is evaluated here by scaling two parameters: world length (which bounds population size) and the maximum number of neurons per individual. Maximum individual complexity is found to be asymptotically bounded when scaling either parameter alone. However, maximum individual complexity is found to be indefinitely scalable, to the extent evaluated so far (with run times in years and billions of reproductions per run), when scaling both world length and the maximum number of neurons per individual together. Further, maximum individual complexity is shown to scale logarithmically with (the lower of) maximum population size and maximum number of neurons per individual. This raises interesting questions and lines of thought about the feasibility of achieving complex results within open-ended evolutionary systems and how to improve on this order of complexity growth.

Life is the harnessing of chemical energy in such a way that the energy-harnessing device makes a copy of itself. No energy, no evolution. The ‘modern synthesis’ of the past century explained evolution in terms of genes, but this is only part of the story. While the mechanisms of natural selection are correct, and increasingly well understood, they do little to explain the actual trajectories taken by life on Earth. From a cosmic perspective—what is the probability of life elsewhere in the Universe, and what are its probable traits?—a gene-based view of evolution says almost nothing. Irresistible geological and environmental changes affected eukaryotes and prokaryotes in very different ways, ones that do not relate to specific genes or niches. Questions such as the early emergence of life, the morphological and genomic constraints on prokaryotes, the singular origin of eukaryotes, and the unique and perplexing traits shared by all eukaryotes but not found in any prokaryote, are instead illuminated by bioenergetics. If nothing in biology makes sense except in the light of evolution, nothing in evolution makes sense except in the light of energetics. This Special Issue of Philosophical Transactions examines the interplay between energy transduction and genome function in the major transitions of evolution, with implications ranging from planetary habitability to human health. We hope that these papers will contribute to a new evolutionary synthesis of energetics and genetics.

Breast cancer (BC) is the most common and most lethal cancer among women worldwide. More than a million and a half are diagnosed every year with more than 600,000 deaths among women worldwide. It is estimated than 1 in every 7 women will develop breast cancer in their life time. It is a major public health concern with high economic cost as well. BC is a multidimensional construct. Several dimensions of this construct have never been examined before in the United Arab Emirates (UAE). This study investigated major facets of the Quality of life (QOL) among women with BC in the UAE, compared it with a sample of age matched healthy group of women without any neoplastic background, changes in serum biomarkers of women with BC and to detect the impact of the disease on these biomarkers at the beginning of the disease before treatment started and then again 12 months later following treatment for the cancer and the role of ghrelin hormone in BC and depression at a tissue level and at serum level. In order to examine QOL with its all dimensions among women with BC, an epidemiological case-control study was conducted recruiting a sample of 300 women, 155 women with BC and 145 age-matched healthy women without any neoplastic background as a control group. This was carried out by using a series of standardized psychometric tools in addition to conducting a psychiatric diagnostic interview. Moreover, blood biomarker results were reviewed retrospectively for cases and controls at the beginning and then 12 months following treatment for BC. In relation to the histopathological characteristics and treatment modalities for BC, all pathology, medical and oncology data for 155 women with BC was retrieved from the computer system and analyzed retrospectively. Finally, in relation to ghrelin hormone, all mammary morphological types, normal, benign and malignant were examined with immunohistochemistry for the expression of ghrelin and its functioning receptor (GHS-R1a). Serum of the same women, whose mammary tissue sections were examined by IHC, was tested for ghrelin serum level to find out its link to BC and depression. This was carried out by Enzyme-Linked Immunosorbent Assay (ELISA). The results have demonstrated that women with BC had poor QOL in comparison to the control group. They had poor view of their body image and sexuality and moreover physical disability rate was high. They also tended to suppress negative emotions to a great extent. Anxiety symptoms were also high. Major depressive disorders and post traumatic disorders were lower among women with BC compared to healthy controls. Several risk factors turned to be linked to BC. These included age, having night shift work, hypertension, diabetes mellitus, oral contraceptive pills, hormonal replacement therapy and not breast feeding. In terms of significant traumatic life events, the Arabic version of the CESC English scale showed to have high validity and reliability among women with BC in the UAE. The results also showed that the levels of several serum haematological and biochemical markers seemed to be abnormal among women with BC compared to healthy control. These included elevated levels of platelet, basophils, liver enzymes, lactate dehydrogenase and tumour serum markers. On the other hand, they were low levels of serum magnesium, C-reactive protein and creatinine. Analysis of histopathological characteristics indicated that the aggressive biological nature of the disease was at the late stage and presentation to medical services for treatment. Clinically, women with BC seemed to have all treatment modalities for BC with high rate of mastectomy and axillary clearance. Regarding ghrelin hormone and it relation to BC, the results showed that malignant mammary tissues had an exclusive and differential immune-reactivity to ghrelin hormone, whereas its receptor, the GHS-R1a, was immune-reactive all mammary tissue morphological types. In addition, more metastasis to the lymph nodes was significantly correlated with more immune-reactivity to ghrelin receptor. The results for gene expression for pro-ghrelin, ghrelin and its receptors were inconclusive It is concluded that breast cancer is the most common cancer among women in the UAE. It attacks women at an earlier age than their counterparts in the West. More attention should to be allocated to the QOL and the unmet psychosocial needs of women with BC. This in turn would improve compliance to treatment and prognosis as well. It is also recommended that awareness campaigns and early screening should be applied for early detection of the disease to prevent late presentation to the medical services and other complications.

As far back as the 1920s, Otto Warburg observed that cancerous cells display an altered state of metabolism surrounding lipid biosynthesis. However, only until recently has metabolic reprogramming been a recognised hallmark of the disease. The number of cancer cases diagnosed is set to triple by 2030, demonstrating the need for disease prevention, improved diagnostic testing and personalised treatment therapies. However, with some cancers occurring in the brain and spinal cord, the type of treatment available can become challenging due to their locality. Such cancer types include meningioma and glioma which are the most common brain tumours diagnosed. An initial study involving human meningioma tissue revealed unusually high levels of the phosphatidylserine enriched with docosahexaenoic acid (DHA). In this study, the metabolism surrounding lipid biosynthesis was examined to establish if such alterations in lipid profiles were related to an altered state of metabolism. From the results gained, it can be suggested that meningioma does have an altered state of metabolism, evolving around serine as opposed to DHA. From the grade I and grade II meningioma tissues immunochemically examined, positive expressions of pyruvate kinase isoform 2 (PKM2) and phosphoglycerate dehydrogenase (PHGDH) were shown. Therefore, the results demonstrated that within meningioma tissues, serine can allosterically regulate the flux through glycolysis. The association that serine presence alone can alter the metabolic flux was demonstrated in the model organism, Lipomyces starkeyi. Those L. starkeyi cells supplemented with serine, displayed a 50% reduction in the amount of radiolabelled acetate taken up during exponential and stationary growth phases. The radiolabelled study also highlighted that with serine presence, de novo lipid biosynthesis was altered. Once synthesised, these neutral lipids go on to be 4 stored in membrane bound organelles. Within the phenotype of cancerous cells, such storage of neutral lipids into lipid droplets prevent lipotoxicity. The light microscopy study of L. starkeyi cells supplemented with serine demonstrated that the formation of such lipid droplets was enhanced during lipid accumulation. These findings suggest that the production, storage and mobilisation of lipids within serine supplemented cells are adapted to cellular requirements, promoting a cancerous phenotype. In order to gain an insight into the potential impact that an altered metabolic state may give to meningioma, a liposomal study was developed. Supplementation of both phosphatidylserine-consisting liposomes, as well as tumour-derived liposomes, enhanced the cellular viability of the non-cancerous cell line, SVG, during exponential phase. The supplementation of meningioma-derived liposomes also increased the viability of the non-cancerous human fetal glial SVG cell line, similar to that observed with phosphatidylserine containing liposomal preparations. Therefore, the data suggest that in fact, the phospholipid (phosphatidylserine), rather than the fatty acid (DHA) plays a role in cellular viability. It is concluded that the results gained from this study can be used clinically in the diagnosis and management of meningioma as well as other diseased cells displaying ectopic lipid accumulation. The observation that meningioma has an altered biochemistry may provide guidance when histologically grading meningioma tumours. For those tumours expressing the enzymes involved in serine biosynthesis, such as PKM2 and PHGDH, a targeted treatment therapy surrounding enzyme inhibitors can be examined. By targeting serine biosynthesis, the resources needed to enable a cancerous phenotype are depleted. Future research can examine such targeted therapies utilizing either the developed model organism, L. starkeyi or the conventional SVG and U87 cell lines.

A low technology fermentation system for biodegradation of cellulose based waste material is described. Using a substrate of thermally bonded paper plastic laminate in a defined mineral salts medium the cellulolytic nicrofungus Trichoderma viride XXI 2% 458 was shown to effect the separation of the laminate into its components by enzymic degradation of the paper. This aerobically induced separation occurred within 14 days compared to upto 90 days by purely physical means. Growth of the fungus within the fermentation system was found to provide conditions that control the growth of contaminating microorganisms. Carbonolytic enzyme activity of Trichoderma viride was investigated by measurenent of substrate weight loss and by reduction in the viscosity of soluble substrate analogues when acted upon by filtrate front-the fermentation systais. An investigation of the effect of changes in carbon to nitrogen ratios during fermentation indicated that maximum carbonolytic enzyme activity occurred at a carbon to nitrogen ratio of 0.6:1 within this system. An examination of three other cellulolytic fungi in order to assess their potential as biodegradative organisms within the fermentation system showed that under microthermophilic conditions only Acrenonium stricturn approached the biodegradative activity of Trichoderma viride at mesophilic temperatures. The products of fermentation by Trichoderma viride were examined; protein levels in the residual cellulolytic substrate following biodegradation of paper plastic laminate were determined and found to reach levels of up to 9% following 35 days fermentation. The amino acid composition of protein produced by Trichoderma viride when grown on a range of substrates was determined and found to contain a wide range of essential and non essential amino acids. An investigation of mycotoxins both in the culture medium and residual paper component was undertaken. Comparisons with eleven common mycotoxin standards revealed no positive identifications under the conditions investigated.

T-cells are present in the immune system to fight against invaders. Once their job is done, suppressing their activity is an important step in maintaining a proper immune response. Myeloid derived suppressor cells (MDSCs) are immune cells that suppress T-cell activity. Currently, MDSCs are defined as a heterogeneous population of immature cells that are derived in the bone marrow and travel to the site of inflammation or cancer. Two major subtypes of MDSCs have been identified in mice and humans, monocyte-like MDSCs (M-MDSC) and granulocyte MDSCs (G-MDSC). G-MDSCs typically make up the majority of the total population of MDSCs but are less T-cell suppressive than M-MDSCs. One of the major problems in the study of MDSCs is that the current marker system for subtypes does not differentiate between precursor MDSCs (lacking suppressive ability) and functional MDSCs (those with suppressive ability). Therefore, using cancer models in mice, we investigated the development and potential to classify precursor MDSCs from functional MDSCs. While MDSCs have been highlighted as a target cell to inhibit in cancer, in other conditions, such as pregnancy, MDSCs have been shown to be beneficial in maintaining a normal pregnancy. Therefore, targeting the increase of MDSCs in abnormal pregnancy conditions like pre-eclampsia may act as a prevention or therapeutic strategy. Finally, it is known that many dietary components can act as modulators of immune cells. Specifically, the polyphenol like phytochemical, curcumin has been shown to act as an anti-inflammatory agent with the potential to modulate multiple immune cells. Therefore, we propose two different studies to investigate the potential of curcumin as either an inhibitor and/or promotor of MDSCs in a disease-specific context. Together the role of phytochemicals as immunomodulators of MDSCs is still very young, in part due to the complexity of phytochemicals themselves, but the studies cited here provide evidence that the field is ripe for additional questions to be asked.

Utilizing environmental DNA (eDNA) for the detection of species in the field is a potentially cost-effective and time-saving technology that may be useful in understanding the distribution and abundance of threatened or endangered species such as the Eastern Massasauga (Sistrurus catenatus). I describe the development of an eDNA assay for the species and evaluate its ability to detect eDNA in laboratory and field conditions. In the field samples, I also investigated the potential for abiotic conditions to influence eDNA detection. Species-specific primers and probe were designed to amplify a 152 bp segment of the massasauga COI gene. Target eDNA could be detected in samples containing as little as 100 copies of target DNA/μL. Water samples collected from laboratory housed snakes indicated that eDNA can be detected in water 56 days after massasauga removal. Field samples were taken from crayfish burrows, known overwintering habitat for the species, from four sites that vary in snake use as ascertained by traditional visual surveys. Of the 60 burrows sampled, seven had a positive detection for massasauga eDNA with no difference in detection rate between DNA extracted from burrow water and burrow sediment. Occupancy models fitted to burrow water indicated that larger amounts of total DNA in a sample may increase the probability of detection of a massasauga eDNA. Large confidence intervals in site occupancy (ѱ) and burrow detection (Θ) values suggest that a larger sample size is needed for more reliable occupancy models. Abiotic conditions within crayfish burrows varied among sites but correlation with eDNA detection was not supported. Estimates of qPCR detection within a burrow with eDNA (ρ) suggest that up to 10 qPCR replicates per burrow sample may be necessary. Further studies need to examine eDNA degradation in the field, improve upon the limit of detection, and sample a larger number of sites for eDNA sampling to be a stand-alone survey method for Eastern Massasaugas.

Regulation of metabolism in mammalian cells is achieved through a complex interplay between cellular signaling, metabolic reactions, and transcriptional changes. The modeling of metabolic fluxes in a cell requires the knowledge of all these mechanisms, some of which may be unknown. A cybernetic approach provides a framework to model these complex interactions through the implicit accounting of such regulatory mechanisms, assuming a biological “goal”. The goal-oriented control policies of cybernetic models have been used to predict metabolic phenomena ranging from complex substrate uptake patterns and dynamic metabolic flux distributions to the behavior of gene knockout strains. The premise underlying the cybernetic framework is that the regulatory processes affecting metabolism can be mathematically formulated as a cybernetic objective through variables that constrain the network to achieve a specified biological “goal”.

Cybernetic theory builds on the perspective that regulation is organized towards achieving goals relevant to an organism’s survival or displaying a specific phenotype in response to a stimulus. While cybernetic models have been established by prior work carried out in bacterial systems, we show its applicability to more complex biological systems with a predefined goal. We have modeled eicosanoid, a well-characterized set of inflammatory lipids derived from arachidonic acid, metabolism in mouse bone marrow derived macrophage (BMDM) cells stimulated by Kdo2-Lipid A (KLA, a chemical analogue of Lipopolysaccharide found on the surface of bacterial cells) and adenosine triphosphate (ATP, a danger signal released in response to surrounding cell death) using cybernetic control variables. Here, the cybernetic goal is inflammation; the hallmark of inflammation is the expression of cytokines which act as autocrine signals to stimulate a pro-inflammatory response. Tumor necrosis factor (TNF)-α is an exemplary pro-inflammatory marker and can be designated as a cybernetic objective for modeling eicosanoid—prostaglandin (PG) and leukotriene (LK)—metabolism. Transcriptomic and lipidomic data for eicosanoid biosynthesis and conversion were obtained from the LIPID Maps database. We show that the cybernetic model captures the complex regulation of PG metabolism and provides a reliable description of PG formation using the treatment ATP stimulation. We then validated our model by predicting an independent data set, the PG response of KLA primed ATP stimulated BMDM cells.

The process of inflammation is mediated by the production of multiple cytokines, chemokines, and lipid mediators each of which contribute to specific individual objectives. For such complex processes in mammalian systems, a cybernetic objective based on a single protein/component may not be sufficient to capture all the biological processes thereby necessitating the use of multiple objectives. The choice of the objective function has been made by intuitive considerations in this thesis. If objectives are conjectured, an argument can be made for numerous alternatives. Since regulatory effects are estimated from unregulated kinetics, one encounters the risk of multiplicity in this regard giving rise to multiple models. The best model is of course that which is able to predict a comprehensive set of perturbations. Here, we have extended our above model to also capture the dynamics of LKs. We have used migration as a biological goal for LK using the chemoattractant CCL2 as a key representative molecule describing cell activation leading to an inflammatory response where a goal composed of multiple cybernetic objectives is warranted. Alternative model objectives included relating both branches of the eicosanoid metabolic network to the inflammatory cytokine TNF-α, as well as the simple maximization of all metabolic products such that each equally contributes to the inflammatory system outcome. We were again able to show that all three cybernetic objectives describing the LK and PG branches for eicosanoid metabolism capture the complex regulation and provide a reliable description of eicosanoid formation. We performed simulated drug and gene perturbation analyses on the system to identify differences between the models and propose additional experiments to select the best cybernetic model.

The advantage to using cybernetic modeling is in its ability to capture system behavior without the same level of detail required for these interactions as standard kinetic modeling. Given the complexity of mammalian systems, the cybernetic goal for mammalian cells may not be based solely on survival or growth but on specific context dependent cellular responses. In this thesis, we have laid the groundwork for the application of cybernetic modeling in complex mammalian systems through a specific example case of eicosanoid metabolism in BMDM cells, illustrated the case for multiple objectives, and highlighted the extensibility of the cybernetic framework to other complex biological systems.

Worldwide, as many as 1 billion people suffer from neurological disorders. Fundamentally, neurological disorders are caused by dysregulation of biochemical signaling within neurons, leading to deficits in learning and memory formation. To identify better preventative and therapeutic strategies for patients of neurological disorders, we require a better understanding of how biochemical signaling is regulated within neurons.

Biochemical signaling at the connections between neurons, called synapses, regulates dynamic shifts in a synapse’s size and connective strength. Called synaptic plasticity, these shifts are initiated by calcium ion (Ca²⁺) flux into message-receiving structures called dendritic spines. Within dendritic spines, Ca²⁺ binds sensor proteins such as calmodulin (CaM). Importantly, Ca²⁺/CaM may bind and activate a wide variety of proteins, which subsequently facilitate signaling pathways regulating the dendritic spine’s size and connective strength.

In this thesis, I use computational models to characterize molecular mechanisms regulating Ca²⁺-dependent protein signaling within the dendritic spine. Specifically, I explore how Ca²⁺/CaM differentially activates binding partners and how these binding partners transduce signals downstream. For this, I present deterministic models of Ca²⁺, CaM, and CaM-dependent proteins, and in analyzing model output I demonstrate in-part that competition for CaM-binding alone may be sufficient to set the Ca²⁺ frequency-dependence of protein activation. Subsequently, I adapt my deterministic models into particle-based, spatial-stochastic frameworks to quantify how spatial effects influence model output, showing evidence that spatial gradients of Ca²⁺/CaM may set spatial gradients of activated proteins downstream. Additionally, I incorporate into my models the most detailed model to-date of Ca²⁺/CaM-dependent protein kinase II (CaMKII), a multi-subunit protein essential to synaptic plasticity. With this detailed model of CaMKII, my analysis suggests that the many subunits of CaMKII provide avidity effects that significantly increase the protein’s effective affinity for binding partners, particularly Ca²⁺/CaM. Altogether, this thesis provides a detailed analysis of Ca²⁺-dependent signaling within dendritic spines, characterizing molecular mechanisms that may be useful for the development of novel therapeutics for patients of neurological disorders.

Environmental DNA (eDNA) is being used increasingly for biomonitoring of communities (e.g., microbes, macroinvertebrates, fish species) across terrestrial and aquatic ecosystems. Developing methods that combine eDNA approaches with metagenomic barcoded amplicon sequencing (eDNA-metabarcoding) are now providing a powerful noninvasive and cost-effective means for comprehensively surveying biodiversity in a wide range of habitats. Invasive species have a substantial impact on the ecology and economics of the Great Lakes region, and eDNAmetabarcoding methods have recently been applied in monitoring non-native, as well as native, fish populations in the freshwater systems there. In this research, we validated an eDNAmetabarcoding approach that uses established platforms, the MiFish/MitoFish pipeline, for fish community monitoring on Lake Michigan. For validation, we compared survey results from our eDNA-metabarcoding approach to those obtained using traditional surveys (e.g., electrofishing and seining). We also sampled a closed 180,000-gallon freshwater fish tank system to see how well our methods characterized a known native fish population that resided in the tank. Finally, we applied the approach to monitoring invasive and native fish populations in southern Lake Michigan at a site that is currently undergoing restoration to improve the aquatic habitats.. We were able to reliably capture the fish community structure of the native fish tank as well as those of open waters on the lake using our methods. Diversity patterns detected at the restoration site using our eDNA-metabarcoding approach accurately reflected those of the historical record, which have taken many years to establish by conventional means. Overall, this study suggests eDNAmetabarcoding is an efficient, credible, and powerful approach to biomonitoring.

Breast cancer is the predominant cancer diagnosed among women, and the second most deadly cancer. The vast majority of cancer-related deaths is caused by the metastatic spread of cancer from the primary tumor to a distant site in the body. Therefore, new strategies which minimize breast cancer metastasis are imperative to improve patient survival. Cancer cells which acquire anchorage independence, or the ability to survive without extracellular matrix attachment, and metabolic flexibility have increased potential to metastasize. In the present studies, the ability to survive detachment and subsequent metabolic changes were determined in human Harvey-ras transformed MCF10A-ras breast cancer cells. Detachment resulted in reduced viability in a time-dependent manner with the lowest cell viability observed at forty hours. In addition, decreased cell viability was observed in both glutamine and glucose depleted detached conditions, suggesting a dependence on both nutrients for detached survival. Compared to attached cells, detached cells had reduced total pool sizes of pyruvate, lactate, α-ketoglutarate, fumarate, malate, alanine, serine, and glutamate, suggesting the metabolic stress which occurs under detached conditions. However, intracellular citrate and aspartate pools were unchanged, demonstrating a preference to maintain these pools in detached conditions. Compared to attached cells, detached cells had suppressed glutamine metabolism, as determined by decreased glutamine flux into the TCA cycle and reduced mRNA abundance of glutamine metabolizing enzymes. Further, detached glucose anaplerosis through pyruvate dehydrogenase activity was decreased, while pyruvate carboxylase (PC) expression and activity were increased. A switch in metabolism was observed away from glutamine anaplerosis to a preferential utilization of PC activity to replenish the TCA cycle, determined by reduced PC mRNA abundance in detached cells treated with a cell-permeable analog of α-ketoglutarate, the downstream metabolite of glutamine which enters the TCA cycle. These results suggest that detached cells elevate PC to increase flux of carbons into the TCA cycle when glutamine metabolism is reduced.

Vitamin D is recognized for its role in preventing breast cancer progression, and recent studies suggest that regulation of energy metabolism may contribute to its anticancer effects. Vitamin D primarily acts on target tissue through its most active metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)₂D). The present work investigated 1,25(OH)₂D’s effects on viability of detached cells through regulation of energy metabolism. Treatment of MCF10A-ras cells with 1,25(OH)₂D resulted in decreased viability of detached cells. While 1,25(OH)₂D treatment did not affect many of the glucose metabolism outcomes measured, including intracellular pyruvate and lactate pool sizes, glucose flux to pyruvate and lactate, and mRNA abundance of enzymes involved in glucose metabolism, 1,25(OH)₂D treatment reduced detached PC expression and glucose flux through PC. A reduction in glutamine metabolism was observed with 1,25(OH)₂D treatment, although no 1,25(OH)₂D target genes were identified. Further, PC depletion by shRNA decreased cell viability in detached conditions with no additional effect with 1,25(OH)₂D treatment. Moreover, PC overexpression resulted in increased detached cell viability and inhibited 1,25(OH)₂D’s negative effects on viability. These results suggest that 1,25(OH)₂D reduces detached cell viability through regulation of PC. Collectively this work identifies a key metabolic adaptation where detached cells increase PC expression and activity to compensate for reduced glutamine metabolism and that 1,25(OH)₂D may be utilized to reverse this effect and decrease detached cell viability. These results contribute to an increased understanding of metastatic processes and the regulation of these processes by vitamin D, which may be effective in preventing metastasis and improve breast cancer patient survival.

Membrane computing investigates models of computation inspired by certain features of biological cells, especially features arising because of the presence of membranes. Because of their inherent large-scale parallelism, membrane computing models (called P systems) can be fully exploited only through the use of a parallel computing platform. However, it is an open question whether it is feasible to develop an efficient and useful parallel computing platform for membrane computing applications. Such a computing platform would significantly outperform equivalent sequential computing platforms while still achieving acceptable scalability, flexibility and extensibility. To move closer to an answer to this question, I have investigated a novel approach to the development of a parallel computing platform for membrane computing applications that has the potential to deliver a good balance between performance, flexibility, scalability and extensibility. This approach involves the use of reconfigurable hardware and an intelligent software component that is able to configure the hardware to suit the specific properties of the P system to be executed. As part of my investigations, I have created a prototype computing platform called Reconfig-P based on the proposed development approach. Reconfig-P is the only existing computing platform for membrane computing applications able to support both system-level and region-level parallelism. Using an intelligent hardware source code generator called P Builder, Reconfig-P is able to realise an input P system as a hardware circuit in various ways, depending on which aspects of P systems the user wishes to emphasise at the implementation level. For example, Reconfig-P can realise a P system in a rule-oriented manner or in a region-oriented manner. P Builder provides a unified implementation framework within which the various implementation strategies can be supported. The basic principles of this framework conform to a novel design pattern called Content-Form-Strategy. The framework seamlessly integrates the currently supported implementation approaches, and facilitates the inclusion of additional implementation strategies and additional P system features. Theoretical and empirical results regarding the execution time performance and hardware resource consumption of Reconfig-P suggest that the proposed development approach is a viable means of attaining a good balance between performance, scalability, flexibility and extensibility. Most of the existing computing platforms for membrane computing applications fail to support nondeterministic object distribution, a key aspect of P systems that presents several interesting implementation challenges. I have devised an efficient algorithm for nondeterministic object distribution that is suitable for implementation in hardware. Experimental results suggest that this algorithm could be incorporated into Reconfig-P without too significantly reducing its performance or efficiency.
Thesis (PhDInformationTechnology)--University of South Australia, 2010

Cancer is the second leading cause of death in the world. Almost everyone’s life is in some way or other affected by cancer. Yet, when faced with a cancer diagnosis, many of us will confront questions we had never before considered: Is cancer one disease, or many? If many, how many exactly? How is cancer classified? What does it mean, exactly, to say that cancer is “genetic,” or “familial”? What exactly are the causes of cancer, and how do scientists come to know about them? When do we have good reason to believe that this or that is a risk factor for cancer? These questions are (in part) empirical ones; however, they are also (in part) philosophical. That is, they are questions about what and how we come to know. They are about how we define and classify disease, what counts as a “natural” classification, what it means to have good evidence, and how we pick out causes as more or less significant. This book takes a close look at these philosophical questions, by examining the conceptual and methodological challenges that arise in cancer research, in disciplines as diverse as cell and molecular biology, epidemiology, clinical medicine, and evolutionary biology.

<em>Abstract</em>.—There has been considerable interest in the systematics and classification of Cutthroat Trout since the 1800s. Cutthroat Trout native to western North America (currently classified as <em>Oncorhynchus clarkii</em>) have historically been grouped or separated using many different classification schemes. Since the 1960s, Robert Behnke has been a leader in these efforts. Introductions of nonnative trout (other forms of Cutthroat Trout, and Rainbow Trout <em>O. mykiss</em>) have obscured some historical patterns of distribution and differentiation. Morphological and meristic analyses have often grouped the various forms of Cutthroat Trout together based on the shared presence of the “cutthroat mark,” high scale counts along the lateral line, and the presence of basibranchial teeth. Spotting patterns and counts of gill rakers and pyloric caeca have in some cases been helpful in differentiation of groups (e.g., Coastal Cutthroat Trout <em>O. c. clarkii</em>, Lahontan Cutthroat Trout <em>O. c. henshawi</em>, and Westslope Cutthroat Trout <em>O. c. lewisi</em>) currently classified as subspecies. The historical genetic methods of allozyme genotyping through protein electrophoresis and chromosome analyses were often helpful in differentiating the various subspecies of Cutthroat Trout. Allozyme genotyping allowed four major groups to be readily recognized (Coastal Cutthroat Trout, Westslope Cutthroat Trout, the Lahontan Cutthroat Trout subspecies complex, and Yellowstone Cutthroat Trout <em>O. c. bouvieri </em>subspecies complex) while chromosome analyses showed similarity between the Lahontan and Yellowstone Cutthroat trout subspecies complex trout (possibly reflecting shared ancestral type) and differentiated the Coastal and Westslope Cutthroat trouts from each other and those two groups. DNA results may yield higher resolution of evolutionary relationships of Cutthroat Trout and allow incorporation of ancient museum samples. Accurate resolution of taxonomic differences among various Cutthroat Trout lineages, and hybridization assessments, requires several approaches and will aid in conservation of these charismatic and increasingly rare native fishes.

The unusual behavior of cleaner fish has attracted both popular and scientific curiosity since its discovery early in the 20th century. These fish apparently make their living by removing external parasites from “host” fishes of other species (some also remove bacteria or diseased and injured tissue). When they approach cleaners, hosts assume an unusual motionless posture that allows cleaners to feed from their scales, from their gill cavities, or even inside their mouths. For their trouble, cleaner fish get a meal, and hosts get a good cleaning. The interaction between cleaner fish and their hosts is generally classified as a mutualism, or mutually beneficial interaction between species. Stories about this and other mutualisms have become staples of nature documentaries and the popular literature and have helped lure many students into a lifetime of studying biology. From the perspective of evolutionary ecology, however, the cleaner-host relationship is anything but straightforward (Poulin and Grutter 1996). First, it is not at all clear that this interaction confers reciprocal fitness benefits. Despite several decades of effort, only one study has shown that cleaners significantly reduce hosts’ parasite loads (Grutter 1999), and none has yet demonstrated that reducing parasite loads increases host success. Since cleaners often gouge the host’s flesh, particularly when parasites are few, the interaction is often more costly than beneficial. Second, if cleaning does not confer an advantage, it is not evident why hosts should tolerate and even actively solicit cleaners’ attention. In fact, sometimes hosts lure cleaners only to eat them, but the conditions under which it might be beneficial for a host to doublecross its cleaners like this remain unexplored. Third, we don’t really understand how cleaning behaviors arose in the first place, considering that the first individuals that approached hosts to feed on parasites were very likely eaten. Despite this constraint, cleaning has apparently evolved multiple times; it is found in at least five families, in both marine and freshwater species, and in both the temperate zone and the tropics.

Foraging is the set of processes by which organisms acquire energy and nutrients, whether the food is directly consumed (feeding), stored for later consumption (hoarding), or given to other individuals (provisioning). Foraging behavior plays an important role in evolutionary biology, not only because it is a major determinant of the survival, growth, and reproductive success of foragers but also because of its impact on predator avoidance, pollination, and dispersal adaptations of potential food organisms. From a contemporary perspective, it is surprising how generally the fundamental role of behavior was neglected in early-20th-century studies of evolution and ecology. Following the development of quantitative techniques and field-oriented approaches by European ethologists, however, interest in foraging, along with other aspects of behavior grew rapidly. Most of this research has sought to describe, explain, and predict foraging behavior quantitatively. The development of an a priori predictive approach using optimality theory, in particular, has revealed a richness and complexity in the patterns of foraging that could not have been imagined only a few decades ago. My goal in this chapter is to provide a brief overview of the main issues in foraging behavior and the logical basis of current approaches. I wish to highlight the successes and potential value of these approaches, while recognizing the gaps and challenges for future research. Contemporary studies of foraging by evolutionary ecologists are based on the synthesis of two research traditions, both emerging during the 1960s. The ethological approach to behavior is illustrated by the research of K. von Frisch and his associates on honeybee foraging and N. Tinbergen and his group on searching behavior of birds. The ethologists’ recognition of behavior as an evolved phenotype, their emphasis on its ecological context, and their careful quantitative and experimental fieldwork set the stage for behavioral ecology (Curio 1976). They classified the behavioral components of foraging, an important contribution to much of the ecological work that followed, and identified a number of widespread characteristics such as localized search following the discovery of a prey (“area-restricted search”) and enhanced detection following experience of a particular prey type (“search image”). The theoretical approach to population ecology was foreshadowed by the Russian V. S. Ivlev.

‘Species and classification’ first considers the species problem and the biological species concept. It then discusses phylogenetic systematics, which involves the organization of species into higher taxa. Classification in science raises a deep philosophical issue as all objects can in principle be classified in more than one way. Is there a ‘correct’ way to assign organisms to species, and species to higher taxa? Classification of organisms was traditionally done using the Linnaean system, which served biologists well for years, and elements of it are still used today. However, the rise of evolutionary biology has led to fundamental changes in both the theory and practice of biological classification.

The study of malformations is an important tool to understand mechanisms and causes of development and regeneration. Moreover, malformations indicate the morphological potential of living beings. Hence, a deeper understanding of how, to what degree, and why organismal structures can deviate from their normal expression is interesting in an evolutionary and ecological context. Like other arthropods, and animals in general, crustaceans show a certain variety of naturally occurring malformations of different body parts. This review is restricted to those that affect the axes of appendages and the trunk. Hence, the various patterns of axis distortion are described and classified. At the general level, malformations concerning limbs are discriminated from those that alter other body outgrowths and those that affect the pattern of the trunk. Among malformation of limbs and other body appendages, misplaced structures, fissions, and fusions are classified. Conjoined twins and distorted body segments are the main features of trunk malformations. The putative causes of malformations are discussed with respect to comparative and experimental approaches. Furthermore, gene expression studies, theories, and models, such as Hans Meinhardt’s Boundary Model, are applied to explain malformations at the level of pattern formation. Apparently, many malformations are not genetic mutations and thus not inheritable, but are instead the result of distortions during early development and regeneration artifacts based on injuries, high temperature, and toxic substances. Compared with other arthropod groups, there are very few experimental studies addressing malformations in crustaceans. Hence, the causes for specific patterns of deformities remain largely obscure.

Dispersal is a term used for the dissemination of detached reproductive structures from parent plants to a new site. Disseminules include spores, seeds, fruits, whole inflorescences, whole plants, fragments of the parent plant, bulbs and bulbils. Fruit attributes related to a particular dispersal agent or dispersal syndromes are complex and have resulted from millions of years of evolution. In practice, dispersal is mainly local, although some species of sea coasts are well adapted for long-distance dispersal. Knowledge of the modes of plant dispersal is vital to the study of coastal dune ecology because of the clear correlation between diversity and dispersal mechanisms. From the evolutionary point of view, dispersal improves fitness of species: the progeny is able to colonize a new site and extend the range of the species. The fitness here will be defined as getting to a coastal site by using any vector for dispersal, colonization of the new site (germination, establishment and reproduction) and dispersal of the propagules of the immigrant from the new site. Dispersal confers many benefits to the populations of plant species. It reduces competition for limited space and resources in the parental location and the more widely dispersed the propagules, the greater are the chances for the offspring to colonize elsewhere. Dispersal increases the chances of survival and evolution of more fit strains of a species by occupying more diverse habitats than the parents, and speciation may eventually occur in response to new selective pressures. For species adapted to live along sea coasts, dispersal by sea is primarily directed for dissemination to another site by the sea coast. During dispersal several physiological changes may occur in the disseminules that facilitate colonization of the species at the new habitat. For example, Barbour (1972) reported that immersion of upper fruits of Cakile maritima in seawater stimulated their subsequent germination under controlled conditions. Seed coat dormancy may also be broken by abrasion of seeds in sand while being rolled along the sand surface. Considering the large number of species along coasts and on islands, only a very few species may be successfully disseminated in seawater.

Matrix population models (MPMs) are currently used in a range of fields, from basic research in ecology and evolutionary biology, to applied questions in conservation biology, management, and epidemiology. In MPMs individuals are classified into discrete stages, and the model projects the population over discrete time-steps. A rich analytical theory is available for these models, for both the linear deterministic case and for more complex dynamics including stochasticity and density dependence. This chapter provides a non comprehensive introduction to MPMs and some basic results on asymptotic dynamics, life history parameters, and sensitivities and elasticities of the long-term growth rate to projection matrix elements and to underlying parameters. We assume that readers are familiar with basic matrix calculations. Using examples with different kinds of demographic structure, we demonstrate how the general stage-structured model can be applied to each case.