Relational Basis of the Organism's Self-organization A Philosophical Discussion

In this thesis, I discuss the organism’s self-organization from the perspective of relational ontology. I critically examine scientific and philosophical sources that appeal to the concept of self-organization. By doing this, I aim to carry out a thorough investigation into the underlying reasons of emergent order within the ontogeny of the organism. Moreover, I focus on the relation between universal dynamics of organization and the organization of living systems. I provide a historical review of the development of modern ideas related to self-organization. These ideas have been developed in relation to various research areas including thermodynamics, molecular biology, developmental biology, systems theory, and so on. In order to develop a systematic understanding of the concept, I propose a conceptual distinction between transitional self-organization and regulative self-organization. The former refers to the spontaneous emergence of order, whereas the latter refers to the self-maintaining characteristic of the living systems. I show the relation between these two types of organization within biological processes. I offer a critical analysis of various theories within the organizational approach. Several ideas and notions in these theories originate from the early studies in cybernetics. More recently, autopoiesis and the theory of biological autonomy asserted certain claims that were critical toward the ideas related to self-organization. I advocate a general theory of self-organization against these criticisms. I also examine the hierarchical nature of the organism’s organization, as this is essential to understand regulative self-organization. I consider the reciprocal relation between bottom-up and top-down dynamics of organization as the basis of the organism’s individuation. To prove this idea, I appeal to biological research on molecular self-assembly, pattern formation (including reaction-diffusion systems), and the self-organized characteristic of the immune system. Finally, I promote the idea of diachronic emergence by drawing support from biological self-organization. I discuss the ideas related to constraints, potentiality, and dynamic form in an attempt to reveal the emergent nature of the organism. To demonstrate the dynamicity of form, I examine research into biological oscillators. I draw the following conclusions: synchronic condition of the organism is irreducibly processual and relational, and this is the basis of the organism’s potentiality for various organizational states

Coupling Infusion and Gyration for the Nanoscale Assembly of Functional Polymer Nanofibers Integrated with Genetically Engineered Proteins

Nanofibers featuring functional nanoassemblies show great promise as enabling constituents for a diverse range of applications in areas such as tissue engineering, sensing, optoelectronics, and nanophotonics due to their controlled organization and architecture. An infusion gyration method is reported that enables the production of nanofibers with inherent biological functions by simply adjusting the flow rate of a polymer solution. Sufficient polymer chain entanglement is obtained at Berry number > 1.6 to make bead-free fibers integrated with gold nanoparticles and proteins, in the diameter range of 117-216 nm. Integration of gold nanoparticles into the nanofiber assembly is followed using a gold-binding peptide tag genetically conjugated to red fluorescence protein (DsRed). Fluorescence microscopy analysis corroborated with Fourier transform infrared spectroscopy (FTIR) data confirms the integration of the engineered red fluorescence protein with the nanofibers. The gold nanoparticle decorated nanofibers having red fluorescence protein as an integral part keep their biological functionality including copper-induced fluorescence quenching of the DsRed protein due to its selective Cu(+2) binding. Thus, coupling the infusion gyration method in this way offers a simple nanoscale assembly approach to integrate a diverse repertoire of protein functionalities into nanofibers to generate biohybrid materials for imaging, sensing, and biomaterial applications

A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition

Hepatocellular carcinoma (HCC) ranks as the fifth most common and the second deadliest cancer worldwide. HCC is extremely resistant to the conventional chemotherapeutics. Hence, it is vital to develop new treatment options. Chalcones were previously shown to have anticancer activities in other cancer types. In this study, 11 chalcones along with quercetin, papaverin, catechin, Sorafenib and 5FU were analyzed for their bioactivities on 6 HCC cell lines and on dental pulp stem cells (DPSC) which differentiates into hepatocytes, and is used as a model for untransformed control cells. 3 of the chalcones (1, 9 and 11) were selected for further investigation due to their high cytotoxicity against liver cancer cells and compared to the other clinically established compounds. Chalcones did not show significant bioactivity ([Formula: see text]) on dental pulp stem cells. Cell cycle analysis revealed that these 3 chalcone-molecules induced SubG1/G1 arrest. Akt protein phosphorylation was inhibited by these molecules in PTEN deficient, drug resistant, mesenchymal like Mahlavu cells leading to the activation of p21 and the inhibition of NF[Formula: see text]B-p65 transcription factor. Hence the chalcones induced apoptotic cell death pathway through NF[Formula: see text]B-p65 inhibition. On the other hand, these molecules triggered p21 dependent activation of Rb protein and thereby inhibition of cell cycle and cell growth in liver cancer cells. Involvement of PI3K/Akt pathway hyperactivation was previously described in survival of liver cancer cells as carcinogenic event. Therefore, our results indicated that these chalcones can be considered as candidates for liver cancer therapeutics particularly when PI3K/Akt pathway involved in tumor development

Microvascular dysfunction as a link between obesity, insulin resistance and hypertension

Impaired microvascular dilatation from any cause and impaired insulin-mediated capillary recruitment in particular result in suboptimal delivery of glucose and insulin to skeletal muscle, and subsequently impairment of glucose disposal (insulin resistance). In addition, microvascular dysfunction, through functional and/or structural arteriolar and capillary drop-out, and arteriolar constriction, increases peripheral resistance and thus blood pressure. Microvascular dysfunction may thus constitute a pathway that links insulin resistance and hypertension. Overweight and obesity may be an important cause of microvascular dysfunction. Mechanisms linking overweight and obesity to microvascular dysfunction include changes in the secretion of adipokines leading to increased levels of free fatty acids and inflammatory mediators, and decreased levels of adiponectin all of which may impair endothelial insulin signaling. Microvascular dysfunction may thus constitute a new treatment target in the prevention of type 2 diabetes mellitus and hypertension

Effect of fulvic acids on lead-induced oxidative stress to metal sensitive Vicia faba L. plant

Lead (Pb) is a ubiquitous environmental pollutant capable to induce various morphological, physiological, and biochemical functions in plants. Only few publications focus on the influence of Pb speciation both on its phytoavailability and phytotoxicity. Therefore, Pb toxicity (in terms of lipid peroxidation, hydrogen peroxide induction, and photosynthetic pigments contents) was studied in Vicia faba plants in relation with Pb uptake and speciation. V. faba seedlings were exposed to Pb supplied as Pb(NO3)2 or complexed by two fulvic acids (FAs), i.e. Suwannee River fulvic acid (SRFA) and Elliott Soil fulvic acid (ESFA), for 1, 12, and 24 h under controlled hydroponic conditions. For both FAs, Pb uptake and translocation by Vicia faba increased at low level (5 mg l−1), whereas decreased at high level of application (25 mg l−1). Despite the increased Pb uptake with FAs at low concentrations, there was no influence on the Pb toxicity to the plants. However, at high concentrations, FAs reduced Pb toxicity by reducing its uptake. These results highlighted the role of the dilution factor for FAs reactivity in relation with structure; SRFA was more effective than ESFA in reducing Pb uptake and alleviating Pb toxicity to V. faba due to comparatively strong binding affinity for the heavy metal

The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: a preliminary molecular framework for gossypol enantiomers

To compare the effect of racemic gossypol with its (–)/(–) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. Methods: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5- sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 ProfilerTM PCR Array (SuperArray, Frederick, MD). Results: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 μM of racemic gossypol alone and 3 μM of AT-101 alone resulted in significant down-regulation (≥ 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. Conclusion: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment

Post-Partum Pituitary Insufficiency and Livedo Reticularis Presenting a Diagnostic Challenge in a Resource Limited Setting in Tanzania: A Case Report, Clinical Discussion and Brief Review of Existing Literature.

Pituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available. A 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature. Post partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome

Transposase-DNA complex structures reveal mechanisms for conjugative transposition of antibiotic resistance

Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes