Correction to 'On the beneficent thickness of water'.

[This corrects the article DOI: 10.1098/rsfs.2019.0061.].

On the beneficent thickness of water.

In the 1930s, Lars Onsager published his famous 'reciprocal relations' describing free energy conversion processes. Importantly, these relations were derived on the assumption that the fluxes of the processes involved in the conversion were proportional to the forces (free energy gradients) driving them. For chemical reactions, however, this condition holds only for systems operating close to equilibrium-indeed very close; nominally requiring driving forces to be smaller than k B T. Fairly soon thereafter, however, it was quite inexplicably observed that in at least some biological conversions both the reciprocal relations and linear flux-force dependency appeared to be obeyed no matter how far from equilibrium the system was being driven. No successful explanation of how this 'paradoxical' behaviour could occur has emerged and it has remained a mystery. We here argue, however, that this anomalous behaviour is simply a gift of water, of its viscosity in particular; a gift, moreover, without which life almost certainly could not have emerged. And a gift whose appreciation we primarily owe to recent work by Prof. R. Dean Astumian who, as providence has kindly seen to it, was led to the relevant insights by the later work of Onsager himself.

Improved method for calibration of exchange flows for a physical transport box model of Tampa Bay, FL USA.

We report the results for both sequential and simultaneous calibration of exchange flows between segments of a 10-box, 1-dimensional, well mixed, bifurcated tidal mixing model for Tampa Bay. Calibrations were conducted for three model options having different mathematical expressions for evaporative loss. In approaching this project we asked three questions: does simultaneous calibration or sequential calibration yield better box model performance; which evaporation option best predicts observed salinities; and how well does model performance compare to more complex hydrodynamic models. Sequential calibration followed the classical salt balance and steady state approach. The nonlinear parameter estimator (PEST) was used for simultaneous calibration. The sequential approach proved useful in evaluating the three evaporation options. However, simultaneous calibration proved superior in predicting observed salinities but was ineffective in discerning differences between evaporation options. The simultaneously calibrated model produced residence times that fell within the range of more complex hydrodynamic models of Tampa Bay.

Contaminant profiles for surface water, sediment, flora and fauna associated with the mangrove fringe along middle and lower eastern Tampa Bay.

Contaminant concentrations are reported for surface water, sediment, flora and fauna collected during 2010-2011 from the mangrove fringe along eastern Tampa Bay, Florida. Concentrations of trace metals, chlorinated pesticides, atrazine, total polycyclic aromatic hydrocarbons, and polychlorinated biphenyls were species-, chemical- and location-specific. Contaminants in sediments did not exceed proposed individual sediment quality guidelines. Most sediment quality assessment quotients were less than one indicating the likelihood of no inhibitory effect based on chemical measurements alone. Faunal species typically contained more contaminants than plant species; seagrass usually contained more chemicals than mangroves. Bioconcentration factors for marine angiosperms were usually less than 10 and ranged between 1 and 31. Mercury concentrations (ppm) in blue crabs and fish did not exceed the U.S. Environmental Protection Agency fish tissue criterion of 0.3 and the U.S. Food and Drug Administration action level of 1.0. In contrast, total mercury concentrations in faunal species often exceeded guideline values for wildlife consumers of aquatic biota.

Modeling free energy availability from Hadean hydrothermal systems to the first metabolism.

Off-axis Hydrothermal Systems (HSs) are seen as the possible setting for the emergence of life. As the availability of free energy is a general requirement to drive any form of metabolism, we ask here under which conditions free energy generation by geologic processes is greatest and relate these to the conditions found at off-axis HSs. To do so, we present a conceptual model in which we explicitly capture the energetics of fluid motion and its interaction with exothermic reactions to maintain a state of chemical disequilibrium. Central to the interaction is the temperature at which the exothermic reactions take place. This temperature not only sets the equilibrium constant of the chemical reactions and thereby the distance of the actual state to chemical equilibrium, but these reactions also shape the temperature gradient that drives convection and thereby the advection of reactants to the reaction sites and the removal of the products that relate to geochemical free energy generation. What this conceptual model shows is that the positive feedback between convection and the chemical kinetics that is found at HSs favors a greater rate of free energy generation than in the absence of convection. Because of the lower temperatures and because the temperature of reactions is determined more strongly by these dynamics rather than an external heat flux, the conditions found at off-axis HSs should result in the greatest rates of geochemical free energy generation. Hence, we hypothesize from these thermodynamic considerations that off-axis HSs seem most conducive for the emergence of protometabolic pathways as these provide the greatest, abiotic generation rates of chemical free energy.

Comment on "A bacterium that can grow by using arsenic instead of phosphorus".

Wolfe-Simon et al. (Research Articles, 3 June 2011, p. 1163; published online 2 December 2010) argued that the bacterial strain GFAJ-1 can vary the elemental composition of its biomolecules by substituting arsenic for phosphorus. Although their data show that GFAJ-1 is an extraordinary extremophile, consideration of arsenate redox chemistry undermines the suggestion that arsenate can replace the physiologic functions of phosphate.

New "party pill" components in New Zealand: the synthesis and analysis of some ß-ketone analogues of 3,4-methylenedioxymethamphetamine (MDMA) including ßk-DMBDB (ß-ketone-N,N-dimethyl-1-(1,3-benzodioxol-5-yl)-2-butanamine).

In 2008, the New Zealand Government passed an amendment to reschedule what were, at the time, the active ingredients of 'party pills' in New Zealand. Since then, submissions of tablets and powders to the Institute of Environmental Science and Research (ESR) Limited have included ingredients not previously seen among drug seizures in New Zealand. These new components, confirmed by the synthesis of standards, included some beta-ketone (ßk) analogues of 3,4-methylenedioxyamphetamine (MDA). Though not yet seen in tablet or powder seizures, the synthesis and the analytical data for ßk-DMBDB ((beta-ketone)-N,N-dimethyl-1-(1,3-benzodioxol-5-yl)-2-butanamine) are reported here for the first time.

Serpentinization as a source of energy at the origin of life.

For life to have emerged from CO2, rocks, and water on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, minor formate, and ammonia, as well as calcium and traces of acetate, molybdenum and tungsten, to off-ridge alkaline hydrothermal springs that interfaced with the metal-rich carbonic Hadean Ocean. Silica and bisulfide were also delivered to these springs where cherts and sulfides were intersected by the alkaline solutions. The proton and redox gradients so generated represent a rich source of naturally produced chemiosmotic energy, stemming from geochemistry that merely had to be tapped, rather than induced, by the earliest biochemical systems. Hydrothermal mounds accumulating at similar sites in today's oceans offer conceptual and experimental models for the chemistry germane to the emergence of life, although the ubiquity of microbial communities at such sites in addition to our oxygenated atmosphere preclude an exact analogy.

Predicted current densities in the brain during transcranial electrical stimulation.

OBJECTIVE: We sought an electrical modeling approach to evaluate the potential application of finite element method (FEM) modeling to predict current pathways and intensities in the brain after transcranial electrical stimulation. METHODS: A single coronal MRI section through the head, including motor cortex, was modeled using FEM. White matter compartments with both anatomically realistic anisotropies in resistivity and with a homogeneous resistivity were modeled. Current densities in the brain were predicted for electrode sites on the scalp and after theoretical application of a conductive head restraint device. RESULTS: Localized current densities were predicted for the model with white matter anisotropies. Differences in predicted peak current densities were related to location of stimulation sites relative to deep sulci in the brain and scalp shunting that was predicted to increase with inter-electrode proximity. A conductive head restraint device was predicted to shunt current away from the brain when a constant current source was used. CONCLUSIONS: The complex geometry of different tissue compartments in the head and their contrasting resistivities may jointly determine the strength and location of current densities in the brain after transcranial stimulation. This might be predictable with FEM incorporating white matter anisotropies. Conductive head restraint devices during surgery may be contraindicated with constant current stimulation. SIGNIFICANCE: Individually optimized tcMEP monitoring and localized transcranial activation in the brain might be possible through FEM modeling.

Proving the concept of a data broker as an emergent alternative to supra-enterprise EPR systems.

Electronic Patient Records systems configured into large enterprise models have become the assumed best route forward. In England, as in several other countries, this has expanded to a major meta-enterprise procurement programme. However, concerns are raised that such systems lack user ownership, and experience from other sectors shows difficulties with large enterprise systems. At a time of great change and once again shifting organizations, is this move simply building large and ponderous edifices with unstable materials? Latest software engineering research is now demonstrating the potential of an alternative model, enabling trusted information brokers to search out in real time at point of use data held in registered local and departmental systems. If successful, this could enable a new and less cumbersome paradigm. The data could move where needed whatever the service configuration. A concept demonstrator has been built set in the context of health and social care in England. It is important for all technological support to the health sector to be reviewed as new technologies emerge so as to identify and exploit new opportunities, and the results of this 3 year project show that the health record information broker route merits further investigative research.

Improved prediction of fatal myocardial infarction using the ankle brachial index in addition to conventional risk factors: the Edinburgh Artery Study.

BACKGROUND: Prediction of major cardiovascular and cerebrovascular events using conventional risk factor models is limited. Noninvasive measures of subclinical atherosclerosis such as the ankle brachial index (ABI) could improve risk prediction and provide more focused primary prevention strategies. We wished to determine the added value of a low ABI in the prediction of long-term risk of cardiovascular and cerebrovascular events and death. METHODS AND RESULTS: In 1988, 1592 men and women 55 to 74 years of age were randomly selected from the age-sex registers of 11 general practices in Edinburgh, Scotland, and followed up over a period of 12 years for incident events. After adjustment for age and sex, an ABI < or =0.9 was predictive of an increased risk of fatal myocardial infarction (MI), cardiovascular death, all-cause death, combined fatal and nonfatal MI, and total cardiovascular events. After further adjustment for prevalent cardiovascular disease, diabetes, and conventional risk factors, a low ABI was independently predictive of the risk of fatal MI. Addition of the ABI significantly (P< or =0.01) increased the predictive value of the model for fatal MI compared with a model containing risk factors alone. Comparison of areas under receiver operator characteristic curves confirmed that a model including the ABI discriminated marginally better than one without. CONCLUSIONS: Addition of the ABI significantly improved prediction of fatal MI over and above that of conventional risk factors. We recommend that the ABI be incorporated into routine cardiovascular screening and that the potential of its inclusion into cardiovascular scoring systems (with a view to improving their accuracy) now be examined.

Effects of hypoxia on isolated vessels and perfused gills of rainbow trout.

Local hypoxia dilates systemic and constricts pulmonary blood vessels in mammals without neural or humoral involvement. The direct effects of hypoxia on isolated vessels from bony fish have not been examined. In the present study, isolated vessels (efferent branchial artery, EBA; coeliacomesenteric artery, CMA; ventral aorta, VA; and anterior cardinal vein, ACV) from rainbow or steelhead trout (Oncorhynchus mykiss) were subjected to either passive load (resting tension) or contracted with a ligand or 50 mM KCl and then subjected to 60 min of hypoxia by N(2) administration and an additional 30 min of normoxia. All vessels were usually refractory to hypoxia under conditions of resting tension. EBAs, CMAs and VAs pre-contracted with a receptor-mediated ligand were all significantly relaxed by hypoxia and only VAs recovered significantly upon subsequent restoration of normoxia. In contrast, tension in all arteries pre-contracted with 50 mM KCl was elevated further in response to hypoxia. Conversely, ligand-contracted ACVs responded to hypoxia with a further increase in tension, whereas KCl-contracted ACVs relaxed. During apparently random 2-3-week periods EBA and CMA from steelhead and EBA from rainbow trout were hyper-reactive to hypoxia. Steelhead vessels responded to hypoxia with a rapid contraction that increased in magnitude over 3 days. These contractions were independent of pre-stimulation and they were dose-dependent upon PO(2). In isolated gills, hypoxic perfusate produced an immediate but transient elevation of resistance (R(GILL)) in all four gill arches. R(GILL) increased by as much as 30% of initial values and this response was unaltered upon a second hypoxic exposure. These studies demonstrate that isolated vascular segments of rainbow trout are indeed responsive to hypoxia and that these differential responses are vessel and tone dependent and the overall response may be altered by as yet unknown seasonal or environmental factors. Hypoxia-induced arterial relaxation is blocked by elevated external [K(+)], implicating alteration of transmembrane K(+) conductance and/or membrane potential in this depressor response. K(+)-channel closure or voltage-gated Ca(2+) influx cannot account for arterial vasoconstriction due to hypoxia during KCl contractions. Vascular responses to hypoxia could have a profound impact on local flow in vivo and could mediate ventilation-perfusion matching in the branchial circulation of fish.

Intracellular and extracellular calcium utilization during hypoxic vasoconstriction of cyclostome aortas.

Hypoxic vasoconstriction (HV) is an intrinsic response of mammalian pulmonary and cyclostome aortic vascular smooth muscle. The present study examined the utilization of calcium during HV in dorsal aortas (DA) from sea lamprey and New Zealand hagfish. HV was temporally correlated with increased free cytosolic calcium (Ca2+c) in lamprey DA. Extracellular calcium (Ca2+o) did not contribute significantly to HV in lamprey DA, but it accounted for 38.1 +/- 5.3% of HV in hagfish DA. Treatment of lamprey DA with ionomycin, ryanodine, or caffeine added to thapsigargin-reduced HV, whereas HV was augmented by BAY K 8644. Methoxyverapamil (D600) in zero Ca2+o did not affect HV in lamprey DA, nor did it prevent further constriction when Ca2+o was restored during hypoxia in hagfish DA. Removal of extracellular sodium (Na+o) caused a constriction in both species. Lamprey DA relaxed to prehypoxic tension following return to normoxia in zero Na+o, whereas relaxation was inhibited in hagfish DA. Relaxation following HV was inhibited in lamprey DA when Na+o and Ca2+o were removed. These results show that HV is correlated with [Ca2+]c in lamprey DA and that Na+/Ca2+ exchange is used during HV in hagfish but not lamprey DA. Multiple receptor types appear to mediate stored intracellular calcium release in lamprey DA, and L-type calcium channels do not contribute significantly to constriction in either cyclostome.

Blood and extracellular fluid volume in whole body and tissues of the Pacific hagfish, Eptatretus stouti.

Whole-body and 20 individual-tissue (51)Cr-RBC (red cell space; RCS) and (99)Tc-diethylenetriaminepentaacetic acid (extracellular space; ECS) spaces were measured in seven unanesthetized Pacific hagfish (Eptatretus stouti). Volume indicators were administered via a dorsal aortic cannula implanted the previous day. Blood samples were collected at 6, 12, 18, and 24 h after injection. Tissues were removed at 24 h and radioactivity was measured; tissue water content (percent of wet weight) was determined by desiccation at 95 degrees C for 48 h. Mixing rates of both indicators were identical and were essentially complete by 12 h, indicating that blood convection is the rate-limiting process. At 24 h, the whole-body RCS was 19.3+/-2.1 mL kg(-1) body weight, and the ECS was 338.5+/-15.2 mL kg(-1) body weight. Blood volume estimated from the 24-h RCS and the mean central hematocrit (14%) was 137.9 mL kg(-1) body weight. Liver RCS (118.6+/-30.5 microL g(-1) tissue weight) was twice that of any other tissue and was also the most variable, ranging from 59 to 263 microL g(-1), whereas liver ECS (406.0+/-34.3 microL g(-1)) was in the range of other tissues, and water content (66.9%+/-3.5%) was low. Gill RCS (55.9+/-5.7 microL g(-1)), ECS (415.3+/-37.7 microL g(-1)), and percent water (83.1%+/-0.8%) were higher than most other tissues. RCS, ECS, and percent water were consistently lowest in ovum (1.1+/-0.02 microL g(-1), 111.1+/-4.3 microL g(-1), 51.3%+/-3.5%, respectively). Tongue, notocord, and myotome had generally lower RCS (2.1+/-0.4, 2.2+/-0.5, 7.1+/-0.1 microL g(-1), respectively) and ECS (121.2+/-7.0, 246.3+/-17.4, 185.3+/-16.7 microL g(-1), respectively), although their water content was in the midrange (74.7+/-0.5, 81.2+/-1.6, 74.4%+/-0.6%, respectively). Skin had a low RCS (6.8+/-1.1) and midrange ECS (387.5+/-28.0) but very low water content (61.2%+/-2.1%). These findings confirm that hagfish blood volume is at least twice as large as other fish, whereas our estimate of extracellular fluid volume is larger than previously reported and more in line with the predicted interstitial volume. RCS, ECS, and water content vary, often independently, between tissues, which may perhaps be indicative of specific tissue needs or functions. A distinct spleen is lacking in hagfish, and the liver appears to serve this function by sequestering red cells. To our knowledge, this is the first report of tissue ECS in Myxiniformes.

Increased facial temperature as an early warning in Sudden Infant Death Syndrome.

The promotion of supine sleeping position in young infants has resulted in significant declines in the incidence of Sudden Infant Death Syndrome although little is understood in terms of mechanisms. We hypothesize that supine sleeping position promotes appropriate thermal regulation via the face and head which is the major source of infant heat loss. By facilitating temperature regulation, the supine position ensures that the centre for thermoregulation in the hypothalamus does not become dysfunctional due to local temperature fluctuations. Because these hypothalamic, thermoregulatory neurones are synaptically linked to those regulating respiration in the medulla, adequate temperature control by the infant maintains normal respiration. In contrast, an increase in face and head temperature over and above core temperature would suggest thermoregulatory stress and an increased likelihood of respiratory apnoea.

Angiotensin signaling and receptor types in teleost fish.

Despite advances characterizing mammalian angiotensin receptors, the phylogeny of fish angiotensin receptors remains unclear. Three aspects of receptor function: (1) the nature of the ligand; (2) the second messenger system activated by it; and (3) the pharmacological profile of specific antagonists, are examined to provide insight into the fish receptor. (1) The octapeptide sequences of fish and mammalian angiotensin II (ANG II) are nearly homologous, differing only at the first and fifth residues. Both peptides are almost equally efficacious and equipotent in heterologous systems and both contain key agonist switches Tyr(4) and Phe(8) necessary to activate mammalian AT(1)-type receptors. (2) ANG II increases inositol trisphosphate production, and elevates intracellular calcium in fish tissues consistent with activation of the AT(1) receptor. (3) However, the specific mammalian sartan-type AT(1) antagonists, e.g. losartan, produce inconsistent results in fish often acting as partial agonists, or inhibiting only at elevated concentrations. Because sartans and ANG II act at distinct sites on the AT(1) receptor, we propose that the teleost receptor is an AT(1)-type receptor that is fairly well conserved with respect to both the ANG binding site and coupling to the second messenger system, whereas the sartan binding site has been poorly conserved. The evidence for non-AT(1) type ANG II receptors in teleosts is limited. Mammalian AT(2) receptor antagonists are generally ineffective but may block at elevated, non-specific doses. Truncated ANG II fragments, ANG III and ANG IV, are often less potent than ANG II, however, their receptors have not been examined. Preliminary studies in trout indicate that angiotensin 1-7 may have a mild vasodilatory effect; additional work is needed to determine if non-AT(1)-type receptors are involved.

Hypoxic vasoconstriction of cyclostome systemic vessels: the antecedent of hypoxic pulmonary vasoconstriction?

Hypoxic vasoconstriction (HV) is an intrinsic response of mammalian pulmonary vascular smooth muscle (VSM). In the present study, HV was examined by myography of vessel rings from three primitive vertebrates: New Zealand hagfish (NZH), Pacific hagfish (PH), and sea lamprey (SL). Hypoxia dilated pre-gill arteries (ventral aorta, afferent branchial) from all species, whereas it contracted systemic arteries [dorsal aorta (DA), efferent branchial, celiacomesenteric]. DA HV was reproducible over several days, and it could be sustained in NZH for 8 h without adverse effects. Tension was proportional to PO(2), and half-maximal HV was obtained at PO(2) (mmHg) of 4.7 +/- 0. 2 (NZH), 0.8 +/- 0.1 (PH), and 10.7 +/- 1.9 (SL). HV did not require preconditioning (preexisting contractile stimulus) and was unaffected by elevated extracellular potassium (200 mM NZH; 80 mM SL); removal of the endothelium (NZH); or inhibitors of cyclooxygenase, lipoxygenase, cytochrome P-450 or antagonists of alpha-adrenergic, muscarinic, nicotinic, purinergic, or serotoninergic receptors. These results show that HV is an intrinsic feature of systemic VSM in cyclostomes and suggest that HV has been in the repertoire of VSM responses, since the origin of vertebrates. The exceptionally hardy HV in cyclostome DA may provide a useful model with which to examine both the phylogeny and mechanisms of this response.

Structure-apoptotic potency evaluations of novel sterols using human leukemic cells.

Three oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM-C7-14 human leukemic cells. In addition to testing 15-ketocholestenol (K15), 15-ketocholestenol hydroxyethyl ether (CK15), and 7-ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25-hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC > K15 > CK15 > CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c-myc mRNA was suppressed by all three oxysterols, with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.

Purification, structural characterization, and myotropic activity of endothelin from trout, Oncorhynchus mykiss.

Endothelin (ET) from a nontetrapod species has never been characterized, either structurally or biologically. A single molecular form of trout ET with 21-amino-acid residues was isolated in pure form from an extract of the kidney of the steelhead trout, Oncorhynchus mykiss and its primary structure established as Cys-Ser-Cys-Ala-Thr-Phe-Leu-Asp-Lys-Glu10-Cys-Val-Tyr-Phe-Cys-His- L eu-Asp-Ile-Ile20-Trp. This amino acid sequence shows only three substitutions (Ala4-->Ser, Thr5-->Ser, and Phe6-->Trp) compared with human ET-2, demonstrating that the structure of the peptide has been well conserved during evolution and that the pathway of posttranslational processing of preproendothelin in the trout is probably similar to that in mammals. Synthetic trout ET produced concentration-dependent constrictions of isolated rings of vascular tissue from trout efferent branchial artery (EBA; pD2 = 7. 90 +/- 0.06, n = 5), caeliacomesenteric artery (pD2 = 8.03 +/- 0. 04, n = 4), anterior cardinal vein (ACV; pD2 = 8.57 +/- 0.25, n = 4), and rat abdominal aorta (AO; pD2 = 8.86 +/- 0.08, n = 7). Trout and rat vessels were more sensitive to mammalian ET-1 than to trout ET (pD(2) for human ET-1 in: EBA = 9.12 +/- 0.14; ACV = 9.90 +/- 0.15; AO = 8.86 +/- 0.08), but there was no significant difference in the maximum tension produced by either peptide in these vessels.