Articles posted online ahead of print

Articles posted online ahead of print (POAP) are manuscripts that have been peer reviewed and accepted for publication by the Editorial Board. They have, furthermore, been copy-edited and formatted in the journal style. They have not, however, been proof-read by the author(s). Articles POAP are considered published and the date of the web posting will be included on the final printed version. POAP is an optional service offered to authors for the benefit of subscribers. It is, therefore, possible that not all articles that will be published in the journal will be POAP. After corrected proofs are received and final pagination assigned the article will be designated POAP-final and it will remain on the POAP page until the corresponding issue contents have been updated on the journal website. Articles POAP can be cited in the usual way, starting with author(s), title, journal name, volume number, year and pages, but if final pagination has not yet been assigned, one should write "in press" and the doi may be given.


An estimate of the chronic exposure to neurotoxins of a neurologically injured pilot

J.J. Ramsden
Clore Laboratory, The University of Buckingham, MK18 1EG, England

DOI: 10.4024/09RA16A.jbpc.16.02
Publication date (web): 30 June 2016
Copyright © 2016 Collegium Basilea and AMSI

ABSTRACT. A recent case study reported on a civil aviation pilot who suddenly died after having been grounded for over a year suffering from serious neurological complaints. Post-mortem investigations revealed extensive neurological damage of the type associated with exposure to organophosphates. The pilot had never suffered an acute exposure incident, hence the need to estimate chronic occupational and nonoccupational exposures. The only significant source of organophosphates in the pilot’s life was contamination of aircraft cabin air by the antiwear additives (tricresyl phosphates, TCP) present in jet engine lubricating oil. Exposure to these compounds has been estimated. It is very small compared to the terrestrial workplace exposure limit (for tri-ortho-cresyl phosphate). This finding raises a number of questions requiring further investigation, including: is TCP toxicity enhanced by simultaneous exposure to other neurotoxins found in aircraft cabin air, such as toluene? Is it enhanced by the mildly hypoxic conditions of the aircraft cabin? Could genetic variation render certain individuals much more sensitive to low chronic exposure? Besides, very little is presently known about the effects of ultralong, ultralow exposures typical of the pilot’s workplace environment. This also requires further investigation.

Special copy editor's note(s) for this paper:
None.


Revisting red blood cell heterogeneity, membrane molecules and surface charge changes in normal, anaemic and thalassaemic red blood cells for blood microsample test development

J.N. Mehrishi and Angela Risso
The Cambridge Blood, Umbilical Cord Blood Stem Cells for Cell–Gene Thalassaemia, Sickle Cell Therapy and Cultivated RBC Research Initiative, 13 Macfarlane Close, Impington, Cambridge, CB24 9LZ, UK
Department of Agriculture and Environmental Sciences, University of Udine, via delle Scienze 91, 33100 Udine, Italy

DOI: 10.4024/05ME16A.jbpc.16.01
Publication date (web): 31 March 2016
Copyright © 2016 Collegium Basilea and AMSI

ABSTRACT. Mammalian cells are covered by a complex of glycoproteins, glycolipids, glycosphingolipids and proteoglycans, forming a dense 70–100 nm thin layer termed the glycocalyx. This is rich in sialoglycoproteins; the cell membrane sialic acid residues (SAs) are important components that play a rôle in determining cell structure, survival, chemical–electrical properties and functions such as recognition and homing. SAs contribute a substantial (~60%) electrical charge, which is one of the major physicochemical factors governing a wide variety of interactions. When these SA sites are compromised or poorly expressed, such as in aging red blood cells (RBCs) or in blood disorders, for instance thalassaemia, erythrophagocytosis is hastened and anaemia can ensue. Centrifugation of RBCs on a Percoll density-gradient provides a reasonably acceptable separation of fractions of RBCs. Analyses of biochemical and physical parameters of these RBC subsets have shown that each fraction is enriched successively in the lightest young (Y-RBC), middle aged (M-RBC), and the densest old red cells (O-RBC). Recently, Percoll density-gradient-fractionated RBCs from blood samples of beta-thalassaemia intermedia patients were shown to have a very large number of high density RBCs. Furthermore, in beta-thalassaemia intermedia not only do RBCs show physicochemical alterations of the membrane, but also changes in the levels of expression of the membrane proteins CD47 and CD55. In view of these observations, we propose that we have the basis for developing quantitative, rapid tests on microsamples of blood for monitoring the physiology and surface markers of RBCs to be applied to the clinical monitoring of blood disorders. At present, microsample blood tests using 0.1–1.0 mL (20–200 drops) for monitoring in clinics seems feasible at very low cost for a battery of several ligands, using fluorescence microscopy, imaging and flow cytometry.

Special copy editor's note(s) for this paper:
None.


Flight crew exposure to bleed air and health effects: what is the problem?

C. van Netten
School of Population and Public Health, Faculty of Medicine, University of British Columbia, 2206 East Mall, Vancouver, B.C., Canada, V6T 1Z3

DOI: 10.4024/14NE15A.jbpc.15.04
Publication date (web): 26 December 2015
Copyright © 2015 Collegium Basilea and AMSI

ABSTRACT. Flight crew members have suffered, and currently are suffering, from health effects alleged to be caused by exposure to contaminated air from the ventilation system within the aircraft due to sporadic leakage of oil seals inside the engines (i.e., bleed air events). In order to obtain some sort of recognition from their employers that the health complaints are work-related, the affected individuals have to provide objective evidence that this is indeed the case. This article identifies some of the agents that can be expected to be present in the air when jet turbine oils, and some hydraulic fluids, are exposed to temperatures that are associated with normal engine operation. These agents include, among others, formaldehyde, carbon monoxide and tricresyl phosphate isomers. Since air quality monitoring for these agents is not done in aircraft, a small air sampler was developed that can be deployed by flight crew members when they encounter a bleed air event, providing objective evidence to the employer of air exposure. Since turbine oils contain a characteristic set of tricresyl phosphate isomers, their presence in the air indicates oil seal leakage and exposure to all the other agents associated with bleed air events.

Special copy editor's note(s) for this paper:
None.


Glyphosate nontoxicity: the genesis of a scientific fact

M. Cuhra
GenØk—Centre for Biosafety, The Science Park, P.O. Box 6418, 9294 Tromsø, Norway
and
Faculty of Health Sciences UiT, Arctic University of Norway, Tromsø, Norway

DOI: 10.4024/08CU15A.jbpc.15.03
Publication date (web): 30 September 2015
Copyright © 2015 Collegium Basilea and AMSI

ABSTRACT. Repetition of a 1978 experiment on the toxicity of glyphosate chemicals in water-flea Daphnia magna showed surprising results. In the 31 years which had passed between the two series of experiments, the toxicity of glyphosate had apparently become 300 times stronger! Further investigation into this enigmatic paradox discloses unfortunate aspects of laboratory researcher cultures as well as fundamental challenges in current regulatory approval of chemicals and the epistemology of risk-assessment.

Special copy editor's note(s) for this paper:
None.


Glyphosate, pathways to modern diseases IV: Cancer and related pathologies

A. Samsel and S. Seneff
Research Scientist, Deerfield, NH 03037, USA
Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA

DOI: 10.4024/11SA15R.jbpc.15.03
Publication date (web): 30 September 2015
Copyright © 2015 Collegium Basilea and AMSI

ABSTRACT. Glyphosate is the active ingredient in the pervasive herbicide, Roundup, and its usage, particularly in the United States, has increased dramatically in the last two decades, in step with the widespread adoption of Roundup®-Ready core crops. The World Health Organization recently labelled glyphosate as “probably carcinogenic.” In this paper, we review the research literature, with the goal of evaluating the carcinogenic potential of glyphosate. Glyphosate has a large number of tumorigenic effects on biological systems, including direct damage to DNA in sensitive cells, disruption of glycine homeostasis, succinate dehydrogenase inhibition, chelation of manganese, modification to more carcinogenic molecules such as N-nitrosoglyphosate and glyoxylate, disruption of fructose metabolism, etc. Epidemiological evidence supports strong temporal correlations between glyphosate usage on crops and a multitude of cancers that are reaching epidemic proportions, including breast cancer, pancreatic cancer, kidney cancer, thyroid cancer, liver cancer, bladder cancer and myeloid leukaemia. Here, we support these correlations through an examination of Monsanto’s early studies on glyphosate, and explain how the biological effects of glyphosate could induce each of these cancers. We believe that the available evidence warrants a reconsideration of the risk/benefit trade-off with respect to glyphosate usage to control weeds, and we advocate much stricter regulation of glyphosate.

Special copy editor's note(s) for this paper:
None.


Why glyphosate is not the issue with Roundup

G.E. Séralini
Institute of Biology and EA2608, Network on Risks, Quality and Sustainable Environment MRSH, University of Caen Normandy, Esplanade de la Paix, 14032 Caen Cedex, France

DOI: 10.4024/12SE15R.jbpc.15.03
Publication date (web): 30 September 2015
Copyright © 2015 Collegium Basilea and AMSI

ABSTRACT. Roundup and other glyphosate-based herbicides are the most widely used pesticides in the world; their residues are among the main pollutants in surface waters. Their use has increased through the spraying of 80% of edible agricultural GMOs, which also contain high levels of their residues. They are composed of glyphosate (35–40% in general) and adjuvants that are around 1,000 times more toxic than glyphosate alone, and are also endocrine disruptors below toxic thresholds. All endocrine disruptors (ED) are also nervous system disruptors (ND), because they act as “spam” for cell–cell communication, in the sense that they are spurious messages (or molecules) sent to a group of organisms or cells, impeding and slowing down, and in some cases accelerating, the physiological communication system. Therefore, they should be called ENDs (endocrine and nervous system disruptors). From 0.1 ppb in chronic tests in vivo, Roundup is highly tumorigenic, provoking hormone-dependent tumours, other hormonal imbalances, and important liver and kidney toxicities. Pesticide adjuvants play the same role in other pesticide formulations. The declared active principles often appear to be by far the least toxic compounds after water in formulations. Unfortunately for public health, they are the only substances tested by companies for regulatory purposes over the long term in vivo. Thus, the acceptable daily intakes deduced from these tests are 1000–10 000 times too high. In regulatory tests the deleterious effects in rats are compared with historical data on rat pathologies. Analysis of laboratory rodent feeds sourced from five continents reveals that they are so contaminated by pollutants that comparison to these hence inappropriate controls generally masks the chronic pathologies provoked by the pesticides and other chemicals tested. The disputes with industry representatives and lobby groups that arose in the course of this research are also summarized in this short review. Finally, potential methods of improving transparency and advancing scientific knowledge are recommended.

Special copy editor's note(s) for this paper:
None.


Study of CeO2 nanoparticle interactions with biological cells and lipid bilayers

A.L. Popov, I.I. Selezneva, N.S. Kurnakov, V.K. Ivanov and P.A. Grigoriev§,∗
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia
Kurnakov Institute of General and Inorganic Chemistry Russian Academy of Sciences, Moscow, Russia
§ Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia

DOI: 10.4024/01PO14A.jbpc.14.01
Publication date (web): 10 November 2014
Copyright © 2014 Collegium Basilea and AMSI

ABSTRACT. We studied the action of different doses of CeO2 nanoparticles on HEp-2 cells, NCTC L929 fibroblasts and model lipid bilayer membranes. The MTT-test of the mitochondrial dehydrogenase activity of the NCTC L929 fibroblasts and HEp-2 epithelial cells showed that there is no difference in the viability of the cells in media with 10–5–10–11 M of CeO2, stabilized by sodium citrate, and the viability of the cells in medium without CeO2. It was shown that neither the lipid membrane conductance nor the surface charge of the lipid bilayer interface were changed in the 10–5–10–11 M range of nanoparticle concentrations. The results indicate low cell toxicity of the CeO2 nanoparticles.

Special copy editor's note(s) for this paper:
None.


Autoantibody markers of neural degeneration are associated with post-mortem histopathological alterations of a neurologically injured pilot

Mohamed B. Abou-Donia,†,∗ F.R.W. van de Goot and M.F.A. Mulder§
Duke University Medical Center, Durham, North Carolina 27710, USA
Symbiant BV, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands
§ Aviation Medical Consult, Karbouwstraat 14, 1402 VC Bussum, The Netherlands

DOI: 10.4024/05AB14A.jbpc.14.03
Publication date (web): 27 July 2014
Copyright © 2014 Collegium Basilea and AMSI

ABSTRACT. There are numerous concerns regarding the neurotoxicity of contaminated air inside pressurized aircraft. Neurological symptoms have been seen in many aircrew personnel who have reportedly been exposed to the potentially toxic breathable air in airliners. Symptoms, allegedly contracted by aircrew and passengers, are thought to be caused by a single large exposure or repetitive cumulative low-level exposures to toxic chemicals in the airliner internal air. Genetic variation plays a rôle. We report here the case of a 43-year old airline pilot who presented with neurological deficits and other symptoms. The pilot died without regaining good health. In vivo blood had been collected ante mortem. Analysis of the serum confirmed grossly elevated levels of serum autoantibody biomarkers for neuronal cell degeneration compared with a control group. At autopsy, various tissues underwent histopathological assessment. Brain and spinal tissues exhibited axonal degeneration and demyelination. Peripheral nerves showed T-lymphocyte infiltration and demyelination. T-lymphocytes had infiltrated the heart muscle tissue. The post-mortem tests and pathological examination of the nervous system confirm the autoantibody biomarker results. Differential diagnosis showed that the work environment, clinical condition, histopathology and serum biomarkers for nervous system injury are consistent with organophosphate-induced neurotoxicity. The results also showed that exposure to organophosphates rendered the nervous system and heart tissue sensitive and predisposed to further injury.

Special copy editor's note(s) for this paper:
None.


Properties of ion channels formed by peroxiredoxin-6 in the lipid bilayers: cluster channel inactivation

P.A. Grigoriev, M.G. Sharapov and V.I. Novoselov

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia

DOI: 10.4024/09GR14A.jbpc.14.03
Publication date (web): 9 December 2014
Copyright © 2014 Collegium Basilea and AMSI

ABSTRACT. We show that the antioxidant protein peroxirdoxin-6 forms cation-selective ion cluster-type channels in phosphatidylcholine bilayer membranes. The cluster channel consists of several (from three to ten) conducting subunits—monochannels—each with a conductance of about 350 pS in 200 mM KCl. Mean dwell time in the open state of the cluster is voltage-dependent. It exponentially diminishes with increasing membrane voltage. A possible molecular mechanism of the channel’s inactivation is discussed.

Special copy editor's note(s) for this paper:
None.