Probing the link between oestrogen receptors and oesophageal cancer

Background

Elevated pre-operative neutrophil: lymphocyte ratio (NLR) has been identified as a predictor of survival in patients with hepatocellular and colorectal cancer. The aim of this study was to examine the prognostic value of an elevated preoperative NLR following resection for oesophageal cancer.

Methods

Patients who underwent resection for oesophageal carcinoma from June 1997 to September 2007 were identified from a local cancer database. Data on demographics, conventional prognostic markers, laboratory analyses including blood count results, and histopathology were collected and analysed.

Results

A total of 294 patients were identified with a median age at diagnosis of 65.2 (IQR 59-72) years. The median pre-operative time of blood sample collection was three days (IQR 1-8). The median neutrophil count was 64.2 × 10^-9/litre, median lymphocyte count 23.9 × 10^-9/litre, whilst the NLR was 2.69 (IQR 1.95-4.02). NLR did not prove to be a significant predictor of number of involved lymph nodes (Cox regression, p = 0.754), disease recurrence (p = 0.288) or death (Cox regression, p = 0.374). Furthermore, survival time was not significantly different between patients with high (≥ 3.5) or low (< 3.5) NLR (p = 0.49).

Conclusion

Preoperative NLR does not appear to offer useful predictive ability for outcome, disease-free and overall survival following oesophageal cancer resection.     

Probing the link between citrate and malonyl-CoA in perfused rat hearts

Little is known about the sources of cytosolic acetyl-CoA used for the synthesis of malonyl-CoA, a key regulator of fatty acid oxidation in the heart. We tested the hypothesis that citrate provides acetyl-CoA for malonyl-CoA synthesis after its mitochondrial efflux and cleavage by cytosolic ATP-citrate lyase. We expanded on a previous study where we characterized citrate release from perfused rat hearts (Vincent G, Comte B, Poirier M, and Des Rosiers C. Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis. Am J Physiol Endocrinol Metab 278: E846-E856, 2000). In the present study, we show that citrate release rates, ranging from 6 to 22 nmol/min, can support a net increase in malonyl-CoA concentrations induced by changes in substrate supply, at most 0.7 nmol/min. In experiments with [U-(13)C](lactate + pyruvate) and [1-(13)C]oleate, we show that the acetyl moiety of malonyl-CoA is derived from both pyruvate and long-chain fatty acids. This (13)C-labeling of malonyl-CoA occurred without any changes in its concentration. Hydroxycitrate, an inhibitor of ATP-citrate lyase, prevents increases in malonyl-CoA concentrations and decreases its labeling from [U-(13)C](lactate + pyruvate). Our data support at least a partial role of citrate in the transfer from the mitochondria to cytosol of acetyl units for malonyl-CoA synthesis. In addition, they provide a dynamic picture of malonyl-CoA metabolism: even when the malonyl-CoA concentration remains constant, there appears to be a constant need to supply acetyl-CoA from various carbon sources, both carbohydrates and lipids, for malonyl-CoA synthesis.     

Possible origin of life between mica sheets

The mica hypothesis is a new hypothesis about how life might have originated. The mica hypothesis provides simple solutions to many basic questions about the origins of life. In the mica hypothesis, the spaces between mica sheets functioned as the earliest cells. These ‘cells’ between mica sheets are filled with potassium ions, and they provide an environment in which: polymer entropy is low; cyclic wetting and drying can occur; molecules can evolve in isolated spaces and also migrate and ligate to form larger molecules. The mica hypothesis also proposes that mechanical energy (work) is a major energy source that could have been used on many length scales to form covalent bonds, to alter polymer conformations, and to bleb daughter cells off protocells. The mica hypothesis is consistent with many other origins hypotheses, including the RNA, lipid, and metabolic ‘worlds’. Therefore the mica hypothesis has the potential to unify origins hypotheses, such that different molecular components and systems could simultaneously evolve in the spaces between mica sheets.     

Analysis of the link between a definition of sustainability and the life cycle methodologies

Purpose

It has been claimed that in order to assess the sustainability of products, a combination of the results from a life cycle assessment (LCA), social life cycle assessment (SLCA) and life cycle costing (LCC) is needed. Despite the frequent reference to this claim in the literature, very little explicit analysis of the claim has been made. The purpose of this article is to analyse this claim.

Methods

An interpretation of the goals of sustainability, as outlined in the report Our Common Future (WCED 1987), which is the basis for most literature on sustainability assessment in the LCA community, is presented and detailed to a level enabling an analysis of the relation to the impact categories at midpoint level considered in life cycle (LC) methodologies.

Results

The interpretation of the definition of sustainability as outlined in Our Common Future (WCED 1987) suggests that the assessment of a product's sustainability is about addressing the extent to which product life cycles affect poverty levels among the current generation, as well as changes in the level of natural, human and produced and social capital available for the future population. It is shown that the extent to which product life cycles affect poverty to some extent is covered by impact categories included in existing SLCA approaches. It is also found that the extent to which product life cycles affect natural capital is well covered by LCA, and human capital is covered by both LCA and SLCA but in different ways. Produced capital is not to any large extent considered in any of the LC methodologies. Furthermore, because of the present level of knowledge about what creates and destroys social capital, it is difficult to assess how it relates to the LC methodologies. It is also found that the LCC is only relevant in the context of a life cycle sustainability assessment (LCSA) if focusing on the monetary gains or losses for the poor. Yet, this is an aspect which is already considered in several SLCA approaches.

Conclusions

The current consensus that LCSA can be performed through combining the results from an SLCA, LCA and LCC is only partially supported in this article: The LCSA should include both an LCA and an SLCA, which should be expanded to better cover how product life cycles affect poverty and produced capital. The LCC may be included if it has as a focus to asses income gains for the poor.     

Macromolecules and the origin of life

From our knonwledge of present day organisms, it is hard to imagine a living assembly, even at its most primitive stage, without macromolecules.In order to look for the macromolecules which possibly participated in the assembly of the primitive organisms, the reaction and formation of polymers in HCN under irradiation of ultraviolet ray of 184.9 nm. was studied.As a example of a simple way of producing an assembly of macromolecules, the mechanism of coacervation was studied by using gelatin as the material.     

Chance and the origin of life

Random chemical reactions in the Earth's primitive hydrosphere could have generated no more than 200 bits of information, whereas the first Darwinian organism must have encoded about a million bits, and therefore could not have arisen by chance. This information gap is bridged by separating reproduction from organism, and postulating a reproductive chemical community that would generate information by proto-Darwinian evolution. The information content of the initial comunity could have been as low as 160 bits, and its evolution might have led to the first Darwinian cell.     

Clay and the origin of life

Research concerning the possible role of clay in chemical evolution is reviewed. The probable importance of clays in the origin of life is assessed.     

Chance and the origin of life

Random chemical reactions in the Earth's primitive hydrosphere could have generated no more than 200 bits of information, whereas the first Darwinian organism must have encoded about a million bits, and therefore could not have arisen by chance. This information gap is bridged by separating reproduction from organism, and postulating a reproductive chemical community that would generate information by proto-Darwinian evolution. The information content of the initial community could have been as low as 160 bits, and its evolution might have led to the first Darwinian cell.     

Symbiosis and the origin of life

The paper uses chemical kinetic arguments and illustrations by computer modelling to discuss the origin and evolution of life. Complex self-reproducing chemical systems cannot arise spontaneously, whereas simple auto-catalytic systems can, especially in an irradiated aqueous medium. Self-reproducing chemical particles of any complexity, in an appropriate environment, have a self-regulating property which permits long-term survival. However, loss of materials from the environment can lead to continuing decay which is circumvented by physical union between different kinds of self-reproducing particles. The increasing complexity produced by such unions (symbioses) is irreversible so that the chemical system evolves. It is suggested that evolution by successive symbioses brough about the change from simple, spontaneously arising, auto-catalytic particles to complex prokaryotic cells.     

On the origin of life

On the basis of the recently proposed new fundamental equation of mathematical biophysics, a suggestion is made for a theory of the formation of a primitive cell from nonliving material. The discussion includes a suggestion for a quantitative formulation of the degree of biological organization. It is shown that according to the fundamental equation of mathematical biophysics, organization of the nonliving material may spontaneously increase under certain conditions, leading to a formation of a primitive organism. This process however, is a very slow one, requiring time intervals of several years or even decades. This may account for the failure in observing or artificially producing spontaneous generation.