Aluminium and breast cancer: sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology

This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action.

The aluminium content of breast tissue taken from women with breast cancer

The aetiology of breast cancer is multifactorial. While there are known genetic predispositions to the disease it is probable that environmental factors are also involved. Recent research has demonstrated a regionally specific distribution of aluminium in breast tissue mastectomies while other work has suggested mechanisms whereby breast tissue aluminium might contribute towards the aetiology of breast cancer. We have looked to develop microwave digestion combined with a new form of graphite furnace atomic absorption spectrometry as a precise, accurate and reproducible method for the measurement of aluminium in breast tissue biopsies. We have used this method to test the thesis that there is a regional distribution of aluminium across the breast in women with breast cancer. Microwave digestion of whole breast tissue samples resulted in clear homogenous digests perfectly suitable for the determination of aluminium by graphite furnace atomic absorption spectrometry. The instrument detection limit for the method was 0.48 μg/L. Method blanks were used to estimate background levels of contamination of 14.80 μg/L. The mean concentration of aluminium across all tissues was 0.39 μg Al/g tissue dry wt. There were no statistically significant regionally specific differences in the content of aluminium. We have developed a robust method for the precise and accurate measurement of aluminium in human breast tissue. There are very few such data currently available in the scientific literature and they will add substantially to our understanding of any putative role of aluminium in breast cancer. While we did not observe any statistically significant differences in aluminium content across the breast it has to be emphasised that herein we measured whole breast tissue and not defatted tissue where such a distribution was previously noted. We are very confident that the method developed herein could now be used to provide accurate and reproducible data on the aluminium content in defatted tissue and oil from such tissues and thereby contribute towards our knowledge on aluminium and any role in breast cancer.

Reduced-order modeling of light transport in tissue for real-time monitoring of brain hemodynamics using diffuse optical tomography

This paper proposes a new reconstruction method for diffuse optical tomography using reduced-order models of light transport in tissue. The models, which directly map optical tissue parameters to optical flux measurements at the detector locations, are derived based on data generated by numerical simulation of a reference model. The reconstruction algorithm based on the reduced-order models is a few orders of magnitude faster than the one based on a finite element approximation on a fine mesh incorporating a priori anatomical information acquired by magnetic resonance imaging. We demonstrate the accuracy and speed of the approach using a phantom experiment and through numerical simulation of brain activation in a rat's head. The applicability of the approach for real-time monitoring of brain hemodynamics is demonstrated through a hypercapnic experiment. We show that our results agree with the expected physiological changes and with results of a similar experimental study. However, by using our approach, a three-dimensional tomographic reconstruction can be performed in ∼3  s per time point instead of the 1 to 2 h it takes when using the conventional finite element modeling approach

High night temperature induces contrasting responses for spikelet fertility, spikelet tissue temperature, flowering characteristics and grain quality in rice

Climate change is increasing night temperature (NT) more than day temperature (DT) in rice-growing areas. Effects of combinations of NT (24-35°C) from microsporogenesis to anthesis at one or more DT (30 or 35°C) at anthesis on rice spikelet fertility, temperature within spikelets, flowering pattern, grain weight per panicle, amylose content and gel consistency were investigated in contrasting rice cultivars under controlled environments. Cultivars differed in spikelet fertility response to high NT, with higher fertility associated with cooler spikelets (P < 0.01). Flowering dynamics were altered by high NT and a novel high temperature tolerance complementary mechanism, shorter flower open duration in cv. N22, was identified. High NT reduced spikelet fertility, grain weight per panicle, amylose content and gel consistency, whereas high DT reduced only gel consistency. Night temperature >27°C was estimated to reduce grain weight. Generally, high NT was more damaging to grain weight and selected grain quality traits than high DT, with little or no interaction between them. The critical tolerance and escape traits identified, i.e. spikelet cooling, relatively high spikelet fertility, earlier start and peak time of anthesis and shorter spikelet anthesis duration can aid plant breeding programs targeting resilience in warmer climates.

Endophytic bacterial community composition in wheat (Triticum aestivum) is determined by plant tissue type, developmental stage and soil nutrient availability

Aims: To understand effects of tissue type, growth stage and soil fertilisers on bacterial endophyte communities of winter wheat (Triticum aestivum cv. Hereward). Methods: Endophytes were isolated from wheat grown under six fertiliser conditions in the long term Broadbalk Experiment at Rothamsted Research, UK. Samples were taken in May and July from root and leaf tissues. Results: Root and leaf communities differed in abundance and composition of endophytes. Endophytes were most abundant in roots and the Proteobacteria were most prevalent. In contrast, Firmicutes and Actinobacteria, the Gram positive phyla, were most prevalent in the leaves. Both fertiliser treatment and sample time influenced abundance and relative proportions of each phylum and genus in the endosphere. A higher density of endophytes was found in the Nil input treatment plants. Conclusions: Robust isolation techniques and stringent controls are critical for accurate recovery of endophytes. The plant tissue type, plant growth stage, and soil fertiliser treatment all contribute to the composition of the endophytic bacterial community in wheat. These results should help facilitate targeted development of endophytes for beneficial applications in agriculture.

New self-assembling multifunctional templates for the biofabrication and controlled self-release of cultured tissue

The need to source live human tissues for research and clinical applications has been a major driving force for the development of new biomaterials. Ideally, these should elicit the formation of scaffold-free tissues with native-like structure and composition. In this study, we describe a biologically interactive coating that combines the fabrication and subsequent self-release of live purposeful tissues using template–cell–environment feedback. This smart coating was formed from a self-assembling peptide amphiphile comprising a proteasecleavable sequence contiguous with a cell attachment and signaling motif. This multifunctional material was subsequently used not only to instruct human corneal or skin fibroblasts to adhere and deposit discreet multiple layers of native extracellular matrix but also to govern their own self-directed release from the template solely through the action of endogenous metalloproteases. Tissues recovered through this physiologically relevant process were carrier-free and structurally and phenotypically equivalent to their natural counterparts. This technology contributes to a new paradigm in regenerative medicine, whereby materials are able to actively direct and respond to cell behavior. The novel application of such materials as a coating capable of directing the formation and detachment of complex tissues solely under physiological conditions can have broad use for fundamental research and in future cell and tissue therapies.

Freezing skeletal muscle tissue does not affect its decomposition in soil: Evidence from temporal changes in tissue mass, microbial activity and soil chemistry based on excised samples

The study of decaying organisms and death assemblages is referred to as forensic taphonomy, or more simply the study of graves. This field is dominated by the fields of entomology, anthropology and archaeology. Forensic taphonomy also includes the study of the ecology and chemistry of the burial environment. Studies in forensic taphonomy often require the use of analogues for human cadavers or their component parts. These might include animal cadavers or skeletal muscle tissue. However, sufficient supplies of cadavers or analogues may require periodic freezing of test material prior to experimental inhumation in the soil. This study was carried out to ascertain the effect of freezing on skeletal muscle tissue prior to inhumation and decomposition in a soil environment under controlled laboratory conditions. Changes in soil chemistry were also measured. In order to test the impact of freezing, skeletal muscle tissue (Sus scrofa) was frozen (−20 °C) or refrigerated (4 °C). Portions of skeletal muscle tissue (∼1.5 g) were interred in microcosms (72 mm diameter × 120 mm height) containing sieved (2 mm) soil (sand) adjusted to 50% water holding capacity. The experiment had three treatments: control with no skeletal muscle tissue, microcosms containing frozen skeletal muscle tissue and those containing refrigerated tissue. The microcosms were destructively harvested at sequential periods of 2, 4, 6, 8, 12, 16, 23, 30 and 37 days after interment of skeletal muscle tissue. These harvests were replicated 6 times for each treatment. Microbial activity (carbon dioxide respiration) was monitored throughout the experiment. At harvest the skeletal muscle tissue was removed and the detritosphere soil was sampled for chemical analysis. Freezing was found to have no significant impact on decomposition or soil chemistry compared to unfrozen samples in the current study using skeletal muscle tissue. However, the interment of skeletal muscle tissue had a significant impact on the microbial activity (carbon dioxide respiration) and chemistry of the surrounding soil including: pH, electroconductivity, ammonium, nitrate, phosphate and potassium. This is the first laboratory controlled study to measure changes in inorganic chemistry in soil associated with the decomposition of skeletal muscle tissue in combination with microbial activity.

Fetal programming of adipose tissue function: an evolutionary perspective

Obesity is an escalating threat of pandemic proportions and has risen to such unrivaled prominence in such a short period of time that it has come to define a whole generation in many countries around the globe. The burden of obesity, however, is not equally shared among the population, with certain ethnicities being more prone to obesity than others, while some appear to be resistant to obesity altogether. The reasons behind this ethnic basis for obesity resistance and susceptibility, however, have remained largely elusive. In recent years, much evidence has shown that the level of brown adipose tissue thermogenesis, which augments energy expenditure and is negatively associated with obesity in both rodents and humans, varies greatly between ethnicities. Interestingly, the incidence of low birth weight, which is associated with an increased propensity for obesity and cardiovascular disease in later life, has also been shown to vary by ethnic background. This review serves to reconcile ethnic variations in BAT development and function with ethnic differences in birth weight outcomes to argue that the variation in obesity susceptibility between ethnic groups may have its origins in the in utero programming of BAT development and function as a result of evolutionary adaptation to cold environments.

Orexin restores aging-related brown adipose tissue dysfunction in male mice

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

Soils of contrasting pH affect the decomposition of buried mammalian (Ovis aries) skeletal muscle tissue

Little is known about the effect of edaphic conditions on the decomposition of buried mammalian tissues. To address this, we set up a replicated incubation study with three fresh soils of contrasting pH: a Podsol (acidic), a Cambisol (neutral), and a Rendzina (alkaline), in which skeletal muscle tissue (SMT) of known mass was allowed to decompose. Our results clearly demonstrated that soil type had a considerable effect on the decomposition of SMT buried in soil. Differences in the rate of decomposition were up to three times greater in the Podsol compared with the Rendzina. The rate of microbial respiration was correlated to the rate of soft tissue loss, which suggests that the decomposition of SMT is dependent on the microbial community present in the soil. Decompositional by-products caused the pH of the immediate soil environment to change, becoming more alkaline at first, before acidifying. Our results demonstrate the need for greater consideration of soil type in future taphonomic studies.

Does repeated burial of skeletal muscle tissue (Ovis aries) in soil affect subsequent decomposition?

The repeated introduction of an organic resource to soil can result in its enhanced degradation. This phenomenon is of primary importance in agroecosystems, where the dynamics of repeated nutrient, pesticide, and herbicide amendment must be understood to achieve optimal yield. Although not yet investigated, the repeated introduction of cadaveric material is an important area of research in forensic science and cemetery planning. It is not currently understood what effects the repeated burial of cadaveric material has on cadaver decomposition or soil processes such as carbon mineralization. To address this gap in knowledge, we conducted a laboratory experiment using ovine (Ovis aries) skeletal muscle tissue (striated muscle used for locomotion) and three contrasting soils (brown earth, rendzina, podsol) from Great Britain. This experiment comprised two stages. In Stage I skeletal muscle tissue (150 g as 1.5 g cubes) was buried in sieved (4.6 mm) soil (10 kg dry weight) calibrated to 60% water holding capacity and allowed to decompose in the dark for 70 days at 22 °C. Control samples comprised soil without skeletal muscle tissue. In Stage II, soils were weighed (100 g dry weight at 60% WHC) into 1285 ml incubation microcosms. Half of the soils were designated for a second tissue amendment, which comprised the burial (2.5 cm) of 1.5 g cube of skeletal muscle tissue. The remaining half of the samples did not receive tissue. Thus, four treatments were used in each soil, reflecting all possible combinations of tissue burial (+) and control (−). Subsequent measures of tissue mass loss, carbon dioxide-carbon evolution, soil microbial biomass carbon, metabolic quotient and soil pH show that repeated burial of skeletal muscle tissue was associated with a significantly greater rate of decomposition in all soils. However, soil microbial biomass following repeated burial was either not significantly different (brown earth, podsol) or significantly less (rendzina) than new gravesoil. Based on these results, we conclude that enhanced decomposition of skeletal muscle tissue was most likely due to the proliferation of zymogenous soil microbes able to better use cadaveric material re-introduced to the soil.

Microbial decomposition of skeletal muscle tissue (Ovis aries) in a sandy loam soil at different temperatures

A laboratory experiment was conducted to determine the effect of temperature (2, 12, 22 °C) on the rate of aerobic decomposition of skeletal muscle tissue (Ovis aries) in a sandy loam soil incubated for a period of 42 days. Measurements of decomposition processes included skeletal muscle tissue mass loss, carbon dioxide (CO2) evolution, microbial biomass, soil pH, skeletal muscle tissue carbon (C) and nitrogen (N) content and the calculation of metabolic quotient (qCO2). Incubation temperature and skeletal muscle tissue quality had a significant effect on all of the measured process rates with 2 °C usually much lower than 12 and 22 °C. Cumulative CO2 evolution at 2, 12 and 22 °C equaled 252, 619 and 905 mg CO2, respectively. A significant correlation (P<0.001) was detected between cumulative CO2 evolution and tissue mass loss at all temperatures. Q10s for mass loss and CO2 evolution, which ranged from 1.19 to 3.95, were higher for the lower temperature range (Q10(2– 12 °C)>Q10(12–22 °C)) in the Ovis samples and lower for the low temperature range (Q10(2–12 °C)tissue mass loss and cumulative CO2 evolution suggest that tissue decomposition was most efficient at 2 °C. These phenomena may be due to lower microbial catabolic requirements at lower temperature.

A laboratory incubation method for determining the rate of microbiological degradation of skeletal muscle tissue in soil

A controlled laboratory experiment is described, in principle and practice, which can be used for the of determination the rate of tissue decomposition in soil. By way of example, an experiment was conducted to determine the effect of temperature (12°C, 22°C) on the aerobic decomposition of skeletal muscle tissue (Organic Texel × Suffolk lamb (Ovis aries)) in a sandy loam soil. Measurements of decomposition processes included muscle tissue mass loss, microbial CO2 respiration, and muscle tissue carbon (C) and nitrogen (N). Muscle tissue mass loss at 22°C always was greater than at 12°C (p < 0.001). Microbial respiration was greater in samples incubated at 22°C for the initial 21 days of burial (p < 0.01). All buried muscle tissue samples demonstrated changes in C and N content at the end of the experiment. A significant correlation (p < 0.001) was demonstrated between the loss of muscle tissue-derived C (C1) and microbially-respired C (Cm) demonstrating CO2 respiration may be used to predict mass loss and hence biodegradation. In this experiment Q10 (12°C - 22°C) = 2.0. This method is recommended as a useful tool in determining the effect of environmental variables on the rate of decomposition of various tissues and associated materials.