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Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out. [ABSTRACT FROM AUTHOR]

The International Commission on Radiological Protection (ICRP), recently expressed concern that "a shortage of investment in training, education, research, and infrastructure seen in many sectors and countries may compromise society's ability to properly manage radiation risks" and in 2022 announced the "Vancouver call for action to strengthen expertise in radiological protection worldwide". As representatives of organisations in formal relations with ICRP, we decided to promote this position paper to declare and emphasise that strengthening the expertise in radiological protection is a collective priority for all of us., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Abstract: This report summarizes effects of anthropogenic electric, magnetic, and electromagnetic fields in the frequency range from 0 to 100 MHz on flora and fauna, as presented at an international workshop held on 5-7 November in 2019 in Munich, Germany. Such fields may originate from overhead powerlines, earth or sea cables, and from wireless charging systems. Animals and plants react differentially to anthropogenic fields; the mechanisms underlying these responses are still researched actively. Radical pairs and magnetite are discussed mechanisms of magnetoreception in insects, birds, and mammals. Moreover, several insects as well as marine species possess specialized electroreceptors, and behavioral reactions to anthropogenic fields have been reported. Plants react to experimental modifications of their magnetic environment by growth changes. Strong adverse effects of anthropogenic fields have not been described, but knowledge gaps were identified; further studies, aiming at the identification of the interaction mechanisms and the ecological consequences, are recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Abstract: This report summarizes the effects of anthropogenic radiofrequency electromagnetic fields with frequencies above 100 MHz on flora and fauna presented at an international workshop held on 5-7 November 2019 in Munich, Germany. Anthropogenic radiofrequency electromagnetic fields at these frequencies are commonplace; e.g., originating from transmitters used for terrestrial radio and TV broadcasting, mobile communication, wireless internet networks, and radar technologies. The effects of these radiofrequency fields on flora, fauna, and ecosystems are not well studied. For high frequencies exceeding 100 MHz, the only scientifically established action mechanism in organisms is the conversion of electromagnetic into thermal energy. In accordance with that, no proven scientific evidence of adverse effects in animals or plants under realistic environmental conditions has yet been identified from exposure to low-level anthropogenic radiofrequency fields in this frequency range. Because appropriate field studies are scarce, further studies on plants and animals are recommended., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Childhood leukemia (CL) is undoubtedly caused by a multifactorial process with genetic as well as environmental factors playing a role. But in spite of several efforts in a variety of scientific fields, the causes of the disease and the interplay of possible risk factors are still poorly understood. To push forward the research on the causes of CL, the German Federal Office for Radiation Protection has been organizing recurring international workshops since 2008 every two to three years. In November 2019 the 6th International Workshop on the Causes of CL was held in Freising and brought together experts from diverse disciplines. The workshop was divided into two main parts focusing on genetic and environmental risk factors, respectively. Two additional special sessions addressed the influence of natural background radiation on the risk of CL and the progress in the development of mouse models used for experimental studies on acute lymphoblastic leukemia, the most common form of leukemia worldwide. The workshop presentations highlighted the role of infections as environmental risk factor for CL, specifically for acute lymphoblastic leukemia. Major support comes from two mouse models, the Pax 5 +/- and Sca1- ETV6-RUNX1 mouse model, one of the major achievements made in the last years. Mice of both predisposed models only develop leukemia when exposed to common infections. These results emphasize the impact of gene-environment-interactions on the development of CL and warrant further investigation of such interactions - especially because genetic predisposition is detected with increasing frequency in CL. This article summarizes the workshop presentations and discusses the results in the context of the international literature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schmidt, Hornhardt, Erdmann, Sánchez-García, Fischer, Schüz and Ziegelberger.)

The International Commission on Non-Ionizing Radiation Protection issued guidelines in 1998 for limiting public and occupational exposure to radiofrequency electromagnetic fields (100 kHz to 300 GHz). As part of the process of updating this advice, a 2-d workshop titled "A closer look at the thresholds of thermal damage" was held from 26-28 May 2015 in Istanbul to re-examine the thermal basis of the guidelines and to provide further information on heat-related effects and thresholds of thermal damage. Overall, the workshop provided much useful information relevant to revision of the guidelines. Participants indicated that the effects of heating from radiofrequency fields are consistent with those from other sources, and that the information derived from those studies can be applied to radiofrequency-induced heating. Another conclusion was that absolute temperature of tissues was more important for thermal damage than temperature change. The discussion suggested that the 6-min averaging time used in international guidelines was valid for whole-body exposures but with a large uncertainty: 30 min may be a more appropriate averaging time for localized exposures, and less than 1 min for implanted medical devices. The duration of whole-body radiofrequency exposure is a critical parameter that often determines the effect threshold, but this will be affected by other, ongoing thermoregulation, which is dependant on many factors. The thresholds for localized radiofrequency exposure were difficult to determine because of the potential range of exposure conditions and the possibility of radiofrequency-induced local hotspots. Suggestions for future dose metrics and further research were discussed and are included in this report.

Exposure to extremely low-frequency magnetic fields (ELF-MF) was evaluated in an International Agency for Research on Cancer (IARC) Monographs as "possibly carcinogenic to humans" in 2001, based on increased childhood leukemia risk observed in epidemiological studies. We conducted a hazard assessment using available scientific evidence published before March 2015, with inclusion of new research findings from the Advanced Research on Interaction Mechanisms of electroMagnetic exposures with Organisms for Risk Assessment (ARIMMORA) project. The IARC Monograph evaluation scheme was applied to hazard identification. In ARIMMORA for the first time, a transgenic mouse model was used to mimic the most common childhood leukemia: new pathogenic mechanisms were indicated, but more data are needed to draw definitive conclusions. Although experiments in different animal strains showed exposure-related decreases of CD8+ T-cells, a role in carcinogenesis must be further established. No direct damage of DNA by exposure was observed. Overall in the literature, there is limited evidence of carcinogenicity in humans and inadequate evidence of carcinogenicity in experimental animals, with only weak supporting evidence from mechanistic studies. New exposure data from ARIMMORA confirmed that if the association is nevertheless causal, up to 2% of childhood leukemias in Europe, as previously estimated, may be attributable to ELF-MF. In summary, ARIMMORA concludes that the relationship between ELF-MF and childhood leukemia remains consistent with possible carcinogenicity in humans. While this scientific uncertainty is dissatisfactory for science and public health, new mechanistic insight from ARIMMORA experiments points to future research that could provide a step-change in future assessments. Bioelectromagnetics. 37:183-189, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

The International Agency for Research on Cancer (IARC) has classified high as well as low-frequency fields as "possibly carcinogenic to humans" (Group 2B). For high frequency fields the recent assessment is based mainly on weak positive associations described in some epidemiological studies between glioma and acoustic neuroma and the use of mobile and other wireless phones. Also for lowfrequency fields the evidence is based on epidemiological findings revealing a statistic association between childhood leukemia (CL) and low-level magnetic fields. The basic findings are already 10 years old. They have since been supported by further epidemiological studies. However, the knowledge on the main/crucial question of causality has not improved. This fact and in addition the small, but statistically significant increased incidence of CL in the surrounding of German nuclear power plants have motivated the German Office for Radiation Protection (BfS) to work toward a better understanding of the main causes of CL. A long-term strategic research agenda has been developed which builds on an interdisciplinary, international network and aims at clarifying the aetiology of childhood acute lymphoblastic leukemia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Binding properties of six heterologously expressed pheromone-binding proteins (PBPs) identified in the silkmoths Antheraea polyphemus and Antheraea pernyi were studied using tritium-labelled pheromone components, ( E, Z)-6,11-hexadecadienyl acetate ((3)H-Ac1) and ( E, Z)-6,11-hexadecadienal ((3)H-Ald), common to both species. In addition, a known ligand of PBP and inhibitor of pheromone receptor cells, the tritium-labelled esterase inhibitor decyl-thio-1,1,1-trifluoropropanone ((3)H-DTFP), was tested. The binding of ligands was measured after native gel electrophoresis and cutting gel slices. In both species, PBP1 and PBP3 showed binding of (3)H-Ac1. In competition experiments with (3)H-Ac1 and the third unlabelled pheromone component, ( E, Z)-4,9-tetradecadienyl acetate (Ac2), the PBP1 showed preferential binding of Ac1, whereas PBP3 preferentially bound Ac2. The PBP2 of both species bound (3)H-Ald only. All of the six PBPs strongly bound (3)H-DTFP. Among unlabelled pheromone derivatives, alcohols were revealed to be the best competitors for (3)H-Ac1 and (3)H-Ald bound to PBPs. No pH influence was found for (3)H-Ac1 binding to, or its release from, the PBP3 of A. polyphemus and A. pernyi between pH 4.0 and pH 7.5. The data indicate binding preference of each of the three PBP-subtypes (1-3) for a specific pheromone component and support the idea that PBPs contribute to odour discrimination, although to a smaller extent than receptor activation.

Two proteins of the IP3 transduction pathway were identified by Western blots in homogenates of isolated pheromone-sensitive sensilla of the silkmoth Antheraea polyphemus. A 110 kDa protein was recognized by an antiserum raised against the Drosophila phospholipase C beta (PLC beta p121) and a 80kDa protein was labelled by an antiserum against a synthetic peptide of a conserved region of protein kinase C (PKC). Incubation of homogenized sensory hairs with the main sex pheromone component, (E,Z) 6-11 hexadecadienyl acetate, resulted in a 6-fold increase in the activity of PKC compared to controls without pheromone. In contrast, incubation with pheromone did not affect the activity of protein kinase A (PKA). Activation of PKC by the membrane permeable dioctanoylglycerol led to excitation of the pheromone-sensitive receptor neurons. These data support the current concept that pheromone perception of moths is mediated by the IP3 transduction pathway.

Females of the sibling silkmoth species Antheraea polyphemus and A. pernyi use the same three sex pheromone components in different ratios to attract conspecific males. Accordingly, the sensory hairs on the antennae of males contain three receptor cells sensitive to each of the pheromone components. In agreement with the number of pheromones used, three different pheromone-binding proteins (PBPs) could be identified in pheromone-sensitive hairs of both species by combining biochemical and molecular cloning techniques. MALDI-TOF MS of sensillum lymph droplets from pheromone-sensitive sensilla trichodea of male A. polyphemus revealed the presence of three major peaks with m/z of 15702, 15752 and 15780 and two minor peaks of m/z 15963 and 15983. In Western blots with four antisera raised against different silkmoth odorant-binding proteins, immunoreactivity was found only with an anti-(Apol PBP) serum. Free-flow IEF, ion-exchange chromatography and Western blot analyses revealed at least three anti-(Apol PBP) immunoreactive proteins with pI values between 4.4 and 4.7. N-Terminal sequencing of these three proteins revealed two proteins (Apol PBP1a and Apol PBP1b) identical in the first 49 amino acids to the already known PBP (Apol PBP1) [Raming, K. , Krieger, J. & Breer, H. (1989) FEBS Lett. 256, 2215-2218] and a new PBP having only 57% identity with this amino-acid region. Screening of antennal cDNA libraries with an oligonucleotide probe corresponding to the N-terminal end of the new A. polyphemus PBP, led to the discovery of full length clones encoding this protein in A. polyphemus (Apol PBP3) and in A. pernyi (Aper PBP3). By screening the antennal cDNA library of A. polyphemus with a digoxigenin-labelled A. pernyi PBP2 cDNA [Krieger, J., Raming, K. & Breer, H. (1991) Biochim. Biophys. Acta 1088, 277-284] a homologous PBP (Apol PBP2) was cloned. Binding studies with the two main pheromone components of A. polyphemus and A. pernyi, the (E,Z)-6, 11-hexadecadienyl acetate (AC1) and the (E,Z)-6,11-hexadecadienal (ALD), revealed that in A. polyphemus both Apol PBP1a and the new Apol PBP3 bound the 3H-labelled acetate, whereas no binding of the 3H-labelled aldehyde was found. In A. pernyi two PBPs from sensory hair homogenates showed binding affinity for the AC1 (Aper PBP1) and the ALD (Aper PBP2), respectively.

An earlier study (Pophof 1998) showed that the esterase inhibitor decyl-thio-trifluoropropanone inhibited the responses of two receptor neurons of the moth Antheraea tuned to straight-chain pheromone components, an acetate and an aldehyde, respectively. Here we report that decyl-thio-trifluoropropanone also inhibited the responses of two pheromone receptor neurons of Bombyx mori to bombykol and bombykal. In contrast, decyl-thio-trifluoropropanone activated receptor neurons of the moth Imbrasia cyrtherea tuned to the pheromone component (Z)-5-decenyl 3-methyl-butanoate. However, decyl-thio-trifluoropropanone did not affect the responses of two receptor neurons of B. mori females specialized to the plant volatiles benzoic acid and linalool, respectively. These results indicate that decyl-thio-trifluoropropanone, besides inhibiting the sensillar esterase, interferes with proteins involved specifically in the excitation of pheromone receptor neurons. In binding studies with radiolabelled decyl-thio-trifuoroproparopnone, the inhibitor was bound by the pheromone-binding protein of A. polyphemus. However, the amount of decyl-thio-trifluoropropanone causing response inhibition was 300 times lower than the amount of pheromone-binding protein present in the sensilla. Since the amount of decyl-thio-trifluoropropanone adsorbed corresponded to about the maximum number of receptor molecules calculated per sensillum, we expect that decyl-thio-trifluoropropanone, probably in complex with pheromone-binding protein, competitively inhibits the pheromone receptor molecules.

Before airborne odorant molecules can stimulate the olfactory receptor cells of animals that live on land, they have to pass through an aqueous solution that contains high concentrations of soluble odorant-binding proteins (OBPs). In insect sensilla the role of these OBPs for signal transduction is becoming multifaceted. Sensillum lymph perfusion experiments in the moth Antheraea polyphemus implied a solubilizer and carrier function of the pheromone-binding protein (PBP) and led to the conclusion that it is the pheromone-PBP complex which activates the postulated receptors. Recent results have shown the presence of two redox states of the PBP and a shift in pheromone binding from the reduced to the oxidized form, depending on the presence of sensory hair material. Thus, PBP oxidation might occur simultaneously with receptor cell activation and might lead to deactivation of the pheromone-PBP complex terminating the pheromone stimulation.

In pheromone-sensitive hairs of the male silkmoth Antheraea polyphemus, two electrophoretically distinct pheromone-binding proteins (PBPs) are present. They indicate no amino acid sequence diversity according to peptide mapping, but differ in their redox state, as shown by free-sulfhydryl-group-specific cleavage at cysteine residues with 2-nitro-5-thiocyanobenzoic acid. In kinetic studies, the pheromone was initially bound mainly by the reduced PBP but later by the oxidized PBP, where all six cysteine residues form disulfide bonds. This redox shift was observed only in the homogenate of isolated olfactory hairs, where proteins of the sensillum lymph and receptive dendrites are present. In control experiments with purified binding proteins, the proportion of pheromone bound to the oxidized PBP did not increase with increasing incubation time, suggesting that disulfide formation does not occur spontaneously but is mediated by the sensory hairs, possibly by interaction with the receptor cell membrane. These data suggest that arriving hydrophobic pheromone molecules are first bound by the reduced PBP and transported through the aqueous sensillum lymph towards the receptor molecules of the dendritic membrane. The oxidized complex might not be able to activate further receptors and, thus, effectively deactivate the pheromone molecules within the sensillum lymph.

We studied in individual males of Antheraea polyphemus the activity of the sensillar esterase, a pheromone-degrading enzyme present in the sensillum lymph surrounding the olfactory receptor cells. In parallel, receptor potentials from single pheromone-sensitive sensilla trichodea were recorded. Our screening revealed a large variability of the enzyme activity in individuals with similar electrophysiological responses. In some moths the sensillar esterase was not detectable, i.e. present with 100-fold less activity. However, such variable esterase activity showed no correlation to the time course of the receptor potential. Thus, enzymatic pheromone degradation does not seem to be involved in the rapid pheromone inactivation at the end of the stimulus, but rather serves as the final pheromone sequestration step.

Female sex pheromones applied to freshly isolated, living antennae of male Antheraea polyphemus and Bombyx mori led to an increase of cGMP. A 1:1 mixture of 2 pheromone components of Antheraea polyphemus blown for 10 sec in physiological concentrations over their antennal branches raised cGMP levels about 1.34-fold (+/- 0.08 SEM, n = 23) from a basal level of 3.0 +/- 0.6 (SEM, n = 20) pmol/mg protein. Similarly, bombykol elicited a 1.29-fold (+/- 0.13 SEM, n = 23) cGMP increase in antennae of male Bombyx mori from a basal level of 2.7 +/- 0.5 (SEM, n = 24) pmol/mg protein. No cross-sensitivity was found with respect to pheromones from either species. In antennae of female silkmoths, the cGMP response was missing upon stimulation with their own respective pheromones according to the known lack of pheromone receptor cells in the female. cAMP levels in the male antennae of 14.2 +/- 2.9 (SEM, n = 4) pmol/mg protein in A. polyphemus and 15.0 +/- 3.0 (SEM, n = 5) pmol/mg protein in B. mori were not affected by pheromone stimulation. Within 1-60 sec, the extent of cGMP increase in B. mori was independent of the duration of pheromone exposure. The levels of cGMP in pheromone-stimulated antennae of both species remained elevated for at least 10 min, i.e., much longer than the duration of the receptor potential measured in single-cell recordings. Guanylate cyclase activity was identified in homogenates of male and female antennae from both species. The Km of the guanylate cyclase from male B. mori for the preferential substrate MnGTP was 175 microM.(ABSTRACT TRUNCATED AT 250 WORDS)