A Unifying Theory of Biological Function

A new theory that naturalizes biological function is explained and compared with earlier etiological and causal role theories. Etiological theories explain functions from how they are caused over their evolutionary history. Causal role theories analyze how functional mechanisms serve the current capacities of their containing system. The new proposal unifies the key notions of both kinds of theories, but goes beyond them by explaining how functions in an organism can exist as factors with autonomous causal efficacy. The goal-directedness and normativity of functions exist in this strict sense as well. The theory depends on an internal physiological or neural process that mimics an organism’s fitness, and modulates the organism’s variability accordingly. The structure of the internal process can be subdivided into subprocesses that monitor specific functions in an organism. The theory matches well with each intuition on a previously published list of intuited ideas about biological functions, including intuitions that have posed difficulties for other theories

Chronic Metformin Associated Cardioprotection Against Infarction: Not Just a Glucose Lowering Phenomenon

Purpose: Clinical and experimental investigations demonstrated that metformin, a widely used anti-diabetic drug, exhibits cardioprotective properties against myocardial infarction. Interestingly, metformin was previously shown to increase the expression of PGC-1α a key controller of energy metabolism in skeletal muscle, which is down-regulated in diabetic conditions. We hypothesized that chronic treatment with metformin could protect the aged, diabetic heart against ischemia-reperfusion injury (IRI) by up-regulating PGC-1α and improving the impaired functionality of diabetic mitochondria. / Methods: Following 4 weeks of metformin (300 mg/kg) administered in the drinking water, 12 month-old diabetic Goto Kakizaki and non-diabetic Wistar rat hearts were assigned for infarct measurement following 35 min ischemia and 60 min reperfusion or for electron microscopy (EM) and Western blotting (WB) investigations. / Results: Metformin elicited a cardioprotective effect in both non-diabetic and diabetic hearts. In contrast with the diabetic non-treated hearts, the diabetic hearts treated with metformin showed more organized and elongated mitochondria and demonstrated a significant increase in phosphorylated AMPK and in PGC-1α expression. / Conclusions: In summary these results show for the first time that chronic metformin treatment augments myocardial resistance to ischemia-reperfusion injury, by an alternative mechanism in addition to the lowering of blood glucose. This consisted of a positive effect on mitochondrial structure possibly via a pathway involving AMPK activation and PGC-1α. Thus, metformin prescribed chronically to patients may lead to a basal state of cardioprotection thereby potentially limiting the occurrence of myocardial damage by cardiovascular events

Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis

<p>Abstract</p> <p>Background</p> <p>Carcinoma of the thyroid gland is an uncommon cancer, but the most frequent malignancy of the endocrine system. Most thyroid cancers are derived from the follicular cell. Follicular carcinoma (FTC) is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Opioid Growth Factor (OGF; chemical term - [Met⁵]-enkephalin) and its receptor, OGFr, form an inhibitory axis regulating cell proliferation. Both the peptide and receptor have been detected in a wide variety of cancers, and OGF is currently used clinically as a biotherapy for some non-thyroid neoplasias. This study addressed the question of whether the OGF-OGFr axis is present and functional in human thyroid follicular cell - derived cancer.</p> <p>Methods</p> <p>Utilizing human ATC (KAT-18), PTC (KTC-1), and FTC (WRO 82-1) cell lines, immunohistochemistry was employed to ascertain the presence and location of OGF and OGFr. The growth characteristics in the presence of OGF or the opioid antagonist naltrexone (NTX), and the specificity of opioid peptides for proliferation of ATC, were established in KAT-18 cells. Dependence on peptide and receptor were investigated using neutralization studies with antibodies and siRNA experiments, respectively. The mechanism of peptide action on DNA synthesis and cell survival was ascertained. The ubiquity of the OGF-OGFr axis in thyroid follicular cell-derived cancer was assessed in KTC-1 (PTC) and WRO 82-1 (FTC) tumor cells.</p> <p>Results</p> <p>OGF and OGFr were present in KAT-18 cells. Concentrations of 10^-6M OGF inhibited cell replication up to 30%, whereas NTX increased cell growth up to 35% relative to cultures treated with sterile water. OGF treatment reduced cell number by as much as 38% in KAT-18 ATC in a dose-dependent and receptor-mediated manner. OGF antibodies neutralized the inhibitory effects of OGF, and siRNA knockdown of OGFr negated growth inhibition by OGF. Cell survival was not altered by OGF, but DNA synthesis as recorded by BrdU incorporation was depressed by 28% in OGF-treated cultures compared to those exposed to sterile water. The OGF-OGFr axis was detected and functional in PTC (KTC-1) and FTC (WRO 82-1) cell lines.</p> <p>Conclusion</p> <p>These data suggest that OGF and OGFr are present in follicular-derived thyroid cancers, and that OGF serves in a tonically active inhibitory manner to maintain homeostasis of cell proliferation. These results may provide a biotherapeutic strategy in the treatment of these cancers.</p

Misaligned spin and orbital axes cause the anomalous precession of DI Herculis

The orbits of binary stars precess as a result of general relativistic effects, forces arising from the asphericity of the stars, and forces from additional stars or planets in the system. For most binaries, the theoretical and observed precession rates are in agreement. One system, however -- DI Herculis -- has resisted explanation for 30 years. The observed precession rate is a factor of four slower than the theoretical rate, a disagreement that once was interpreted as evidence for a failure of general relativity. Among the contemporary explanations are the existence of a circumbinary planet and a large tilt of the stellar spin axes with respect to the orbit. Here we report that both stars of DI Herculis rotate with their spin axes nearly perpendicular to the orbital axis (contrary to the usual assumption for close binary stars). The rotationally induced stellar oblateness causes precession in the direction opposite to that of relativistic precession, thereby reconciling the theoretical and observed rates.Comment: Nature, in press [11 pg

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Enrichment of antioxidant capacity and vitamin E in pita made from barley

This study aimed to enhance total antioxidant and vitamin E content of pita bread, by replacing 50% of the standard baker's flour with flours milled from covered (WI2585 and Harrington) or hulless (Finniss) barley genotypes, previously shown to have high antioxidant and vitamin E levels at harvest. Pita breads were made from either 100% baker's flour (control) or 50% malt flour, whole-grain flour, or flour from barley grains pearled at 10%, 15%, and 20% grain weight. Antioxidant capacity and vitamin E content of flours and pitas were determined by their ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals and high performance liquid chromatography, respectively. The physical and sensory properties of the pitas were also assessed. All pitas made from either whole grain or pearled barley flour had a higher antioxidant capacity and most also had higher vitamin E content than standard pita. The antioxidant and vitamin E levels were reduced in pearled compared to whole grains, however the extent of that reduction varied among genotypes. The greatest antioxidant and vitamin E levels were found in pita made from malt flour or Finniss whole grain flour. Furthermore, sensory analysis suggested these pitas were acceptable to consumers and retained similar physical and sensory properties to those in the control pita.Thi Thu Dung Do, Beverly Muhlhausler, Amanda Box and Amanda J. Abl

Factors associated with disease progression in early-diagnosed pulmonary arterial hypertension associated with systemic sclerosis: longitudinal data from the DETECT cohort

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort. METHODS: Patients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression. RESULTS: Of 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship). CONCLUSION: More than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc

Young neutron stars with soft gamma ray emission and anomalous X-ray pulsar

The observational properties of Soft Gamma Repeaters and Ano\-malous X-ray Pulsars (SGR/AXP) indicate to necessity of the energy source different from a rotational energy of a neutron star. The model, where the source of the energy is connected with a magnetic field dissipation in a highly magnetized neutron star (magnetar) is analyzed. Some observational inconsistencies are indicated for this interpretation. The alternative energy source, connected with the nuclear energy of superheavy nuclei stored in the nonequilibrium layer of low mass neutron star is discussed.Comment: 29 pages, 13 figures, Springer International Publishing Switzerland 2016 A.W. Alsabti, P. Murdin (eds.), Handbook of Supernova

Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success