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The morphology and molecular phylogeny of a new ciliate, Conchophthirus sinanodontae n. sp., which was discovered in the freshwater mussel Sinanodonta woodiana (Lea, 1834) from the Chilsancheon River, Buyeo-gun, South Korea, were investigated. The new species was characterized and could be distinguished from congeners by a combination of characters including the ovate body outline, four to six oral polykinetids deeply embedded in the upper wall of the buccal cavity, six to ten vestibular kineties, 34-49 ventral and 36-53 dorsal somatic kineties. The genetic differences among C. sinanodontae n. sp. and other congeners with available 18S rDNA sequences further support its distinctness. Moreover, the phylogenetic analyses based on the 18S rDNA sequences show that the new species clusters with other congeners, corroborating the monophyly of the genus Conchophthirus. The Conchophthirus clade nests within the cluster of Dexiotricha spp., Loxocephalus luridus, and Haptophrya spp., 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 Elsevier GmbH. All rights reserved.)

Owing to their theranostic properties, cerium oxide (CeO 2 ) nanoparticles have attracted considerable attention for their key applications in nanomedicine. In this study, ultrasmall CeO 2 nanoparticles (particle diameter = 1-3 nm) as X-ray contrast agents with an antioxidant effect were investigated for the first time. The nanoparticles were coated with hydrophilic and biocompatible poly(acrylic acid) (PAA) and poly(acrylic acid- co -maleic acid) (PAAMA) to ensure satisfactory colloidal stability in aqueous media and low cellular toxicity. The synthesized nanoparticles were characterized using high-resolution transmission electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, cell viability assay, photoluminescence spectroscopy, and X-ray computed tomography (CT). Their potential as X-ray contrast agents was demonstrated by measuring phantom images and in vivo CT images in mice injected intravenously and intraperitoneally. The X-ray attenuation of these nanoparticles was greater than that of the commercial X-ray contrast agent Ultravist and those of larger CeO 2 nanoparticles reported previously. In addition, they exhibited an antioxidant effect for the removal of hydrogen peroxide. The results confirmed that the PAA- and PAAMA-coated ultrasmall CeO 2 nanoparticles demonstrate potential as highly sensitive radioprotective or theranostic X-ray contrast agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Magnetite nanoparticles (Fe 3 O 4 NPs) have been intensively investigated because of their potential biomedical applications due to their high saturation magnetization. In this study, core-shell Fe 3 O 4 @C NPs (core = Fe 3 O 4 NPs and shell = amorphous carbons, d avg = 35.1 nm) were synthesized in an aqueous solution. Carbon coating terminated with hydrophilic -OH and -COOH groups imparted excellent biocompatibility and hydrophilicity to the NPs, making them suitable for biomedical applications. The Fe 3 O 4 @C NPs exhibited ideal relaxometric properties for T 2 magnetic resonance imaging (MRI) contrast agents (i.e., high transverse and negligible longitudinal water proton spin relaxivities), making them exclusively induce only T 2 relaxation. Their T 2 MRI performance as contrast agents was confirmed in vivo by measuring T 2 MR images in mice before and after intravenous injection.

Melatonin, which is produced from tryptophan, exerts various biological functions, including the regulation of circadian rhythm, sedative agents, and antioxidant ability. Therefore, we conducted two experiments with early-weaned rats and pigs to investigate the antioxidant and sedative effects of melatonin. In the rat experiment, a total of 42 rats (21 days old) were used, and the antioxidant capacity was determined. Next, we used 120 early-weaned piglets (21 days old) to conduct a 5-week experiment to evaluate the reductive effect of melatonin on energy-wasting movement, including roaming and fight states. Dietary melatonin supplementation significantly improved growth in both rats and pigs compared to the control groups. Additionally, rats fed a melatonin-supplemented diet showed advanced antioxidant capacity with a decrease in hepatic malondialdehyde concentration compared to rats fed a basal diet. Moreover, dietary melatonin ingestion increased resting and feeding behaviors and reduced roaming and fight behaviors during Days 8-21 compared to the control diet group. Collectively, early weaned animals given dietary melatonin supplementation showed improved growth through upregulation of hepatic antioxidant capacity and minimization of energy-wasting behavior, including roaming and fight states, after pigs' social hierarchy establishment., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2023 Korean Society of Animal Science and Technology.)

Strongylidium koreanum n. sp., a new soil ciliate from Jeju Island, South Korea, is described based on live observations, protargol impregnation, and molecular analysis of the 18S rRNA gene sequence. It is characterized by the following morphological features: cell outline more or less fusiform, posterior end broader than anterior end; grayish under low magnification; cortical granules absent; 23-32 adoral membranelles; three enlarged frontal cirri; buccal cirrus and postoral ventral cirrus present; 27-42 left and 15-28 right ventral cirri; 23-36 left and 30-46 right marginal cirri; three dorsal kineties; three caudal cirri; and two macronuclear nodules with two or three micronuclei. Phylogenetic analyses show that Strongylidium is monophyletic.

The morphology and molecular phylogeny of a new soil ciliate, Keronopsis koreana n. sp., which was discovered in soil from Jindo-gun, South Korea, were investigated. The new species is characterized by the following morphological features: cell more or less ellipsoid or ovoid, both ends broadly rounded; cortical granules irregularly distributed, colorless, 1 µm across; 35-54 adoral membranelles; 12-23 cirri in frontal corona; two frontal and two frontoventral cirral rows; two or three buccal cirri; 23-38 left and 22-37 right marginal cirri; three bipolar dorsal kineties; and two macronuclear nodules and three to five micronuclei. Phylogenetic analyses show that Keronopsis koreana n. sp. is placed within a clade containing K. helluo (type species of Keronopsis) and species belonging to Paraholosticha, Uroleptoides, Parabistichella, Orthoamphisiella, Lamtostyla, and Bistichella in non-dorsomarginalian hypotrichs. Also, the sequences belonging to the Keronopsidae did not cluster together. In addition, a new combination is provided: Parabistichella tasmaniensis (Blatterer and Foissner, 1988) n. comb. (original combination: Keronopsis tasmaniensis)., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

The Carney complex (CNC) is an autosomal dominant disorder characterized by endocrine and nonendocrine tumors. Loss-of-function variants of protein kinase A regulatory subunit 1 alpha (PRKAR1A) are common causes of CNC. Here, we present the case of a patient with CNC with a novel PRKAR1A missense variant. A 21-year-old woman was diagnosed with CNC secondary to acromegaly and adrenal Cushing syndrome. Genetic analysis revealed a novel missense heterozygous variant of PRKAR1A (c.176A>T). Her relatives, suspected of having CNC, also carried the same variant. RNA analysis revealed that this variant led to nonsense-mediated mRNA decay. In vitro functional analysis of the variant confirmed its role in increasing protein kinase A activity and cyclic adenosine monophosphate levels. This study broadens our understanding of the genetic spectrum of CNC. We suggest that PRKAR1A genetic testing and counseling be recommended for patients with CNC and their families.

Hydrophilic and biocompatible PAA-coated ultrasmall Gd 2 O 3 nanoparticles (d avg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd 2 O 3 and cRGD/FA-PAA-Gd 2 O 3 nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T 1 magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd 2 O 3 nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd 2 O 3 nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd 2 O 3 nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd 2 O 3 nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd 2 O 3 nanoparticles, which prolonged their circulation in the blood.

Numerous organisms use the Earth's magnetic field as a sensory cue for migration, body alignment, or food search. Despite some contradictory reports, yet it is generally accepted that humans do not sense the geomagnetic field. Here, we demonstrate that a magnetic field resonance mechanism mediates light-dependent magnetic orientation in men, using a rotary chair experiment combined with a two-alternative forced choice paradigm. Two groups of subjects were classified with different magnetic orientation tendencies depending on the food context. Magnetic orientation of the subjects was sensitive to the wavelength of incident light and was critically dependent on blue light reaching the eyes. Importantly, it appears that a magnetic field resonance-dependent mechanism mediates these responses, as evidenced by disruption or augmentation of the ability to orient by radiofrequency magnetic fields at the Larmor frequency and the dependence of these effects on the angle between the radiofrequency and geomagnetic fields. Furthermore, inversion of the vertical component of the geomagnetic field revealed a non-canonical inclination compass effect on the magnetic orientation. These results establish the existence of a human magnetic sense and suggest an underlying quantum mechanical magnetoreception mechanism., (© 2022. The Author(s).)

Water proton spin relaxivities, colloidal stability, and biocompatibility of nanoparticle magnetic resonance imaging (MRI) contrast agents depend on surface-coating ligands. In this study, hydrophilic and biocompatible polyethylenimines (PEIs) of different sizes (M n = 1200 and 60,000 amu) were used as surface-coating ligands for ultrasmall holmium oxide (Ho 2 O 3 ) nanoparticles. The synthesized PEI1200- and PEI60000-coated ultrasmall Ho 2 O 3 nanoparticles, with an average particle diameter of 2.05 and 1.90 nm, respectively, demonstrated low cellular cytotoxicities, good colloidal stability, and appreciable transverse water proton spin relaxivities (r 2 ) of 13.1 and 9.9 s -1 mM -1 , respectively, in a 3.0 T MR field with negligible longitudinal water proton spin relaxivities (r 1 ) (i.e., 0.1 s -1 mM -1 ) for both samples. Consequently, for both samples, the dose-dependent contrast changes in the longitudinal (R 1 ) and transverse (R 2 ) relaxation rate map images were negligible and appreciable, respectively, indicating their potential as efficient transverse T 2 MRI contrast agents in vitro.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (d avg = 1.76 nm). Higher positive (brighter or T 1 ) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T 1 MRI contrast agents in tumor imaging via GlcN effects.

In this study, hydrophilic and biocompatible chitosan oligosaccharide lactate (COL)-coated ultra-small gadolinium oxide nanoparticles (NPs) were synthesized through a one-pot polyol method and characterized by various experimental techniques. The In Vitro cellular cytotoxicity assay indicated that the COL-coated gadolinium oxide NPs were non-toxic up to 500 μ M Gd. In addition, their water proton spin relaxivities (i.e., r 1 and r ₂) were estimated to be 13.0 and 27.0 s -1 mM -1 , respectively, which are higher than those of commercial magnetic resonance imaging (MRI) contrast agents. The application potential of the solution sample as a T 1 MRI contrast agent was demonstrated In Vitro by measuring map images in which dose-dependent contrast enhancements were observed.

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln 2 O 3 ) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T 2 ) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r 2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r 1 values were negligible at all MR fields, indicating their exclusive induction of T 2 relaxations with negligible induction of T 1 relaxations. Their effectiveness as T 2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T 2 MR images at a 9.4 T MR field after intravenous administration into mice tails.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (M w = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd 2 O 3 ) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd 2 O 3 nanoparticles (d avg = 1.8 nm and a avg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r 1 ) of 40.6 s -1 mM -1 (r 2 /r 1 = 1.56, where r 2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd 2 O 3 nanoparticles as a T 1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T 1 MR images at the 3.0 T MR field.

Nanoparticles are considered potential candidates for a new class of magnetic resonance imaging (MRI) contrast agents. Negative MRI contrast agents require high magnetic moments. However, if nanoparticles can exclusively induce transverse water proton spin relaxation with negligible induction of longitudinal water proton spin relaxation, they may provide negative contrast MR images despite having low magnetic moments, thus acting as an efficient T 2 MRI contrast agent. In this study, carbon-coated paramagnetic dysprosium oxide (DYO@C) nanoparticles (core = DYO = Dy x O y ; shell = carbon) were synthesized to explore their potential as an efficient T 2 MRI contrast agent at 3.0 T MR field. Since the core DYO nanoparticles have an appreciable (but not high) magnetic moment that arises from fast 4f-electrons of Dy(III) ( 6 H 15/2 ), the DYO@C nanoparticles exhibited an appreciable transverse water proton spin relaxivity (r 2 ) with a negligible longitudinal water proton spin relaxivity (r 1 ). Consequently, they acted as a very efficient T 2 MRI contrast agent, as proven from negative contrast enhancements seen in the in vivo T 2 MR images.

Ultrasmall Bi₂O₃ nanoparticles ( d avg = 1.5 nm) coated with biocompatible and hydrophilic D-glucuronic acid were prepared for the first time through a simple one-step polyol process and their potential as CT contrast agents were investigated by measuring their X-ray attenuation properties. Their observed X-ray attenuation power was stronger than that of a commercial iodine CT contrast agent at the same atomic concentration, as consistent with the magnitudes of atomic X-ray attenuation coefficients (i.e., Bi > I), and much stronger at the same number density. The results indicate that the nanoparticle sample is a potential CT contrast agent.

The study of ultra-small paramagnetic gadolinium oxide (Gd 2 O 3 ) nanoparticles (NPs) as in vivo positive (T 1 ) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd 2 O 3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd 2 O 3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r 1 ) value of 36.2 s -1 mM -1 (r 2 /r 1 = 2.0; r 2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r 1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T 1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T 1 MRI contrast agent.

Certain long-distance migratory animals, such as salmon and sea turtles, are thought to imprint on the magnetic field of their natal area and to use this information to help them return as adults. Despite a growing body of indirect support for such imprinting, direct experimental evidence thereof remains elusive. Here, using the fruit fly as a magnetoreceptive model organism, we demonstrate that exposure to a specific geographic magnetic field during a critical period of early development affected responses to a matching magnetic field gradient later in life. Specifically, hungry flies that had imprinted on a specific magnetic field from 1 of 3 widely separated geographic locations responded to the imprinted field, but not other magnetic fields, by moving downward, a geotactic behavior associated with foraging. This same behavior occurred spontaneously in the progeny of the next generation: female progeny moved downward in response to the field on which their parents had imprinted, whereas male progeny did so only in the presence of these females. These results represent experimental evidence that organisms can learn and remember a magnetic field to which they were exposed during a critical period of development. Although the function of the behavior is not known, one possibility is that imprinting on the magnetic field of a natal area assists flies and their offspring in recognizing locations likely to be favorable for foraging and reproduction., Competing Interests: The authors declare no competing interest.

Gadolinium neutron capture therapy (GdNCT) is considered as a new promising cancer therapeutic technique. Nevertheless, limited GdNCT applications have been reported so far. In this study, surface-modified ultrasmall gadolinium oxide nanoparticles (UGNPs) with cancer-targeting ability ( d avg = 1.8 nm) were for the first time applied to the in vivo GdNCT of cancer using nude model mice with cancer, primarily because each nanoparticle can deliver hundreds of Gd to the cancer site. For applications, the UGNPs were grafted with polyacrylic acid (PAA) for biocompatibility and colloidal stability, which was then conjugated with cancer-targeting arginylglycylaspartic acid (RGD) (shortly, RGD-PAA-UGNPs). The solution sample was intravenously administered into the tails of nude model mice with cancer. At the time of the maximum accumulation of the RGD-PAA-UGNPs at the cancer site, which was monitored using magnetic resonance imaging, the thermal neutron beam was locally irradiated onto the cancer site and the cancer growth was monitored for 25 days. The cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs, indicating that the surface-modified UGNPs with cancer-targeting ability are potential materials applicable to the in vivo GdNCT of cancer., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The Earth's geomagnetic field (GMF) is known to influence magnetoreceptive creatures, from bacteria to mammals as a sensory cue or a physiological modulator, despite it is largely thought that humans cannot sense the GMF. Here, we show that humans sense the GMF to orient their direction toward food in a self-rotatory chair experiment. Starved men, but not women, significantly oriented toward the ambient/modulated magnetic north or east, directions which had been previously food-associated, without any other helpful cues, including sight and sound. The orientation was reproduced under blue light but was abolished under a blindfold or a longer wavelength light (> 500 nm), indicating that blue light is necessary for magnetic orientation. Importantly, inversion of the vertical component of the GMF resulted in orientation toward the magnetic south and blood glucose levels resulting from food appeared to act as a motivator for sensing a magnetic field direction. The results demonstrate that male humans sense GMF in a blue light-dependent manner and suggest that the geomagnetic orientations are mediated by an inclination compass., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We aimed to review and provide a quality improvement for the document utilized by the relevant Korean government body to verify and evaluate foreign university/college graduates’ eligibility for nursing and qualification to take the Korean nursing licensing examination., Methods: This was a descriptive study. We analyzed the current Korean qualification system for foreign graduates to Korean nursing licensing examination and the same system utilized in some other countries. Then, we created a draft of the reviewed qualification standards document based on the 2 prior analyses and their comparisons, and applied a questionnaire in an open hearing with 5 experts to enhance the draft’s quality. Finally, we presented and discussed the final draft., Results: The reviewed criteria of the qualification standards included confirming whether the foreign graduate’s university has an accreditation provided by its relevant government body, the exclusion of foreign graduates’ provision of several documents previously required, a minimum number of credits (1,000 hours) for their original course, a 3-year minimum enrollment period for their original course, and a mandatory reassessment of the foreign graduates’ university recognition in a 5-year cycle., Discussion: We believe that by creating a review draft that addresses the flaws of the current document utilized to determine the qualification for foreign graduates to take the Korean nursing licensing examination, we have simplified it for a better understanding of the application process. We hope that this draft will contribute to a more objective and equitable qualification process for foreign university nurse graduates in Korea.

D-glucuronic acid-coated ultrasmall chromium oxide (Cr2O3) nanoparticles were synthesized by a one-pot polyol method and their relaxometric and optical properties were investigated. The as-synthesized D-glucuronic acid-coated nanoparticles were amorphous owing to ultrasmall particle diameters (davg = 2.0 nm), whereas orthorhombic Cr2O3 nanoparticles with two size groups (davg = 3.6 and 5.7 nm) were observed after thermogravimetric analysis (900 °C) as a result of particle growth. The nanoparticles exhibited size-dependent UV-visible absorption maxima at 238, 274, and 372 nm with increasing particle diameter, corresponding to band gaps of 5.13, 4.45, and 3.28 eV, respectively. D-glucuronic acid-coated ultrasmall Cr2O3 nanoparticles revealed low water proton relaxivities of r1 = 0.05 s-1mM-1 and r2 = 0.20 s-1mM-1, consistent with the antiferromagnetic property of Cr2O3. They showed good biocompatibility up to 500 μM of Cr.

High-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. We report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project when prioritizing disease-causing variants. KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.

Monodisperse and ultrasmall gadolinium oxide (Gd 2 O 3 ) nanoparticle colloids ( d avg = 1.5 nm) (nanoparticle colloid = nanoparticle coated with hydrophilic ligand) were synthesized and their performance as a multifunctional tumor theragnostic agent was investigated. The aqueous ultrasmall nanoparticle colloidal suspension was stable and non-toxic owing to hydrophilic polyacrylic acid (PAA) coating that was partly conjugated with rhodamine B (Rho) for an additional functionalization (mole ratio of PAA : Rho = 5 : 1). First, the ultrasmall nanoparticle colloids performed well as a powerful T 1 magnetic resonance imaging (MRI) contrast agent: they exhibited a very high longitudinal water proton relaxivity ( r 1 ) of 22.6 s -1 mM -1 ( r 2 / r 1 = 1.3, r 2 = transverse water proton relaxivity), which was ∼6 times higher than those of commercial Gd-chelates, and high positive contrast enhancements in T 1 MR images in a nude mouse after intravenous administration. Second, the ultrasmall nanoparticle colloids were applied to gadolinium neutron capture therapy (GdNCT) in vitro and exhibited a significant U87MG tumor cell death (28.1% net value) after thermal neutron beam irradiation, which was 1.75 times higher than that obtained using commercial Gadovist. Third, the ultrasmall nanoparticle colloids exhibited stronger fluorescent intensities in tumor cells than in normal cells owing to conjugated Rho, proving their pH-sensitive fluorescent tumor cell detection ability. All these results together demonstrate that ultrasmall Gd 2 O 3 nanoparticle colloids are the potential multifunctional tumor theragnostic agent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The field cricket ( Gryllus bimaculatus ) is commonly consumed as food in different parts of the world. This study was performed to characterize the chitosan extracted from crickets and to assess its potential use to the growing functional market. The degree of deacetylation (DA), Fourier-transform infrared spectra, X-ray diffraction patterns, molecular mass, scanning electron microscopy spectra, and color were measured. Cricket chitosan nanoparticles were prepared, and the optimal conditions were identified. The molecular mass of the cricket chitosan was lower than that of commercial chitosan; however, the DA, FTIR, and XRD spectra were similar. The particle size (208.27 ± 3.47 nm), zeta potential (35.72 ± 1.29 mV), and polydispersity index (PDI: 0.27 ± 0.03) of the cricket chitosan NPs were superior to the commercial. Addition of NaCl reduced the cricket chitosan NPs size up to 15.5%. This finding is a novel trial to prove the availability of the insect chitosan with a low molecular mass as an active carrier source.

For use as positive ( T 1 ) magnetic resonance imaging contrast agents (MRI-CAs), gadolinium oxide (Gd 2 O 3 ) nanoparticle colloids ( i.e. nanoparticles coated with hydrophilic ligands) should be stable, non-toxic, and ultrasmall in particle diameter for renal excretion. In addition, they should have a high longitudinal water proton relaxivity ( r 1 ) and r 2 / r 1 ratio that is close to one ( r 2 = transverse water proton relaxivity) for high-performance. In this study, we report ultrasmall Gd 2 O 3 nanoparticle colloids [coating material = polyacrylic acid, M w = ∼5100 Da] satisfying these conditions. The particle diameter was monodisperse with an average value of 2.0 ± 0.1 nm. The colloidal suspension exhibited a high r 1 value of 31.0 ± 0.1 s -1 mM -1 and r 2 / r 1 ratio of 1.2, where r 1 was ∼8 times higher than that of commercial Gd-chelates: the cooperative induction model was proposed to explain this. The effectiveness of the colloidal suspension as a high-performance T 1 MRI-CA was confirmed by taking in vivo T 1 MR images in a mouse after intravenous administration. Highly positive contrast enhancements were observed in various organs of the mouse such as the liver, kidneys, and bladder. The colloidal suspension was then excreted through the bladder., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This corrects the article DOI: 10.1038/ncomms13637.

Throughout the long history of various therapeutic trials of transcranial magnetic stimulation (TMS), some TMS protocols have been reported to be clearly effective in the treatment of neurodegenerative diseases. Despite promising results from repetitive TMS (rTMS) using low frequency electromagnetic fields (EMFs) for neurodegenerative diseases, the low reproducibility has hampered the clinical applications of rTMS. Here, based on the notion of radical pair mechanism explaining magnetoreception in living organisms, we propose a new perspective that rTMS with controlled geomagnetic field (rTMS-GMF) can be an efficient and reproducible therapeutic approach for neurodegenerative diseases. In addition, combined consideration of imprinted GMF and/or EMFs in patients' earlier life may augment the potential efficacy of the rTMS-GMF. The investigation of this approach is intriguing and may have a high impact on the technical suitability and clinical application of the rTMS-GMF in the near future.

Filamentous fungi are able to differentiate morphologically and adapt the metabolism to internal and external cues. One major regulator is the so-called velvet protein, VeA, best studied in Aspergillus nidulans. The protein interacts with several other proteins to regulate light sensing, the balance between asexual and sexual development, penicillin biosynthesis or mycotoxin production. Here, we characterized a novel VeA-interacting protein, VipA. The 334 amino acid long protein comprises a FAR1-like DNA-binding domain, known from plant transcription factors like FHY3 (Far-red elongated hypocotyl 3). VipA interacted not only with VeA, but also with the WC orthologue LreA in the nuclei and with the phytochrome FphA in the cytoplasm. Conidia and cleistothecia formation was similarly affected in a vipA-deletion strain as in an fphA mutant. However, the effect was less pronounced, suggesting a modulating and not an essential role in light sensing. In addition, VipA modulated heme biosynthesis in response to light through association with the hemB promoter, the gene encoding 5-aminolevulinic acid dehydratase. After illumination of A. nidulans mycelia with white light the intracellular heme concentration increased by 30% in comparison to a vipA-deletion mutant. Hence, VipA couples heme biosynthesis to the illumination conditions., (© 2017 John Wiley & Sons Ltd.)

Background: The purpose of this study was to calculate the measurement uncertainty of the process of bone mineral density (BMD) analysis using dual energy X-ray absorptiometry with traceability., Methods: Between March 2015 and October 2016, among healthy participants in their 20s and 30s, the study included those who had not taken calcium, vitamin D supplements and steroids and were without a history of osteoporosis, osteopenia and diseases related to osteoporosis. Relational expression of the model was established based on Guide to the Expression of Uncertainty in Measurements and Eurachem and the uncertainty from each factor was evaluated., Results: The combined standard uncertainty was 0.015, while the expanded uncertainty was 0.0298. The factor-specific standard uncertainties that occurred in the process of measuring BMD were 0.72% for the calibration curve, 0.9% for the internal quality control (IQC) using Aluminum Spine Phantom, 0.58% for European Spine Phantom (ESP), and 0.9% for the inspector precision (IP)., Conclusions: The combined standard uncertainty of the spine BMD corrected with ESP was 0.015 when measured at one time and targeting one participant. The uncertainties of the accuracy of the IQC and the IP were higher than that of the other factors. Therefore, there will be a need for establishment of protocols to lower these uncertainties., Competing Interests: No potential conflict of interest relevant to this article was reported.

Mixed Zn(II)/Gd(III) oxide nanoparticles (~8 mole%Zn) with d(avg) of 2.1 nm were synthesized. The D-glucuronic acid coated Zn(II)/Gd(III) oxide nanoparticles showed a longitudinal water proton relaxivity (r₁) of 12.3 s⁻¹mM⁻¹ with r₂/r₁ = 1.1, corresponding to an ideal condition for T₁ MRI contrast agent. We attribute this to reduced magnetization of the mixed nanoparticles owing to non-magnetic Zn in the nanoparticles. Their effectiveness as a T₁ MRI contrast agent was confirmed by acquiring In Vivo T₁ MR images of a mouse after intravenous injection.

Background: Voluntary apnea during breath-hold diving (BHD) induces cardiovascular changes including bradycardia, reduced cardiac output, and arterial hypertension. Although the impacts of repetitive BHD on cardiovascular health have been studied previously, the long-term risk for kidney dysfunction has never been investigated., Methods: A cross-sectional propensity score-matched study was performed to evaluate the influence of repetitive long-lasting BHD on kidney function. Using matching propensity scores (PS), 715 breath-hold female divers (Haenyeo) and non-divers were selected for analysis from 1,938 female divers and 3,415 non-divers, respectively. The prevalence of chronic kidney disease (CKD) defined as an estimated glomerular filtration rate (eGFR) calculated to be less than 60 ml/min/1.73 m 2 was investigated in both diver and non-diver groups., Results: The prevalence of CKD was significantly higher in breath-hold divers compared with non-divers after PS matching (12.6% vs. 8.0%, P = 0.004). In multivariate analysis, BHD activity was significantly associated with the risk of CKD in an unmatched cohort (OR, 1.976; 95% CI, 1.465-2.664). In the PS-matched cohort, BHD remained the independent risk factor for CKD even after adjusting for multiple covariates (OR 1.967; 95% CI, 1.341-2.886)., Conclusion: Shallow but repetitive intermittent apnea by BHD, sustained for a long period of time, may potentially cause a deterioration in kidney function, as a long-term consequence.

Human genomes are routinely compared against a universal reference. However, this strategy could miss population-specific and personal genomic variations, which may be detected more efficiently using an ethnically relevant or personal reference. Here we report a hybrid assembly of a Korean reference genome (KOREF) for constructing personal and ethnic references by combining sequencing and mapping methods. We also build its consensus variome reference, providing information on millions of variants from 40 additional ethnically homogeneous genomes from the Korean Personal Genome Project. We find that the ethnically relevant consensus reference can be beneficial for efficient variant detection. Systematic comparison of human assemblies shows the importance of assembly quality, suggesting the necessity of new technologies to comprehensively map ethnic and personal genomic structure variations. In the era of large-scale population genome projects, the leveraging of ethnicity-specific genome assemblies as well as the human reference genome will accelerate mapping all human genome diversity.

Background: Appropriate vertical movement is critical for the survival of flying animals. Although negative geotaxis (moving away from Earth) driven by gravity has been extensively studied, much less is understood concerning a static regulatory mechanism for inducing positive geotaxis (moving toward Earth)., Results: Using Drosophila melanogaster as a model organism, we showed that geomagnetic field (GMF) induces positive geotaxis and antagonizes negative gravitaxis. Remarkably, GMF acts as a sensory cue for an appetite-driven associative learning behavior through the GMF-induced positive geotaxis. This GMF-induced positive geotaxis requires the three geotaxis genes, such as cry, pyx and pdf, and the corresponding neurons residing in Johnston's organ of the fly's antennae., Conclusions: These findings provide a novel concept with the neurogenetic basis on the regulation of vertical movement by GMF in the flying animals.

Water-soluble and biocompatible D-glucuronic acid coated Na 2 WO 4 and BaCO 3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na 2 WO 4 and BaCO 3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na 2 WO 4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+) ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

Objective: The purpose of this study was to compare clinical findings and outcomes of Enterprise and Solitaire stent-assisted coiling (SAC)., Materials and Methods: Between January 2012 and March 2014, 86 patients (mean age, 60.3 years) harboring 89 aneurysms were treated with Enterprise (n = 57) or Solitaire (n = 32) SAC. The patients' demographics, angiographic results, and clinical outcomes were reviewed retrospectively., Results: There were no cases of stent navigation, deployment failure, arterial dissection, or intraoperative aneurysmal rupture. Angiographic follow-up imaging was available for 86 (96.6%) aneurysms (Enterprise group, n = 55; Solitaire group, n = 31). Immediate postoperative and follow-up angiographic results showed no flow or only minimal flow into the neck in 83% (Enterprise group, 77.2%; Solitaire group, 93.8%) and 95.3% (Enterprise group, 92.7%; Solitaire group, 100%) of SAC-treated aneurysms, respectively. Both stent groups showed good immediate postoperative and follow-up clinical outcomes. Excepting 2 cases, all patients achieved modified Rankin Scale scores of 0. Coil loop or tail protrusion into the parent artery was observed in 17 (29.8%) and 7 (21.9%) cases in the Enterprise and Solitaire groups, respectively. No statistically significant difference in terms of angiographic results or clinical outcomes was observed between the groups., Conclusion: Excellent and comparable clinical and angiographic outcomes for wide-neck intracranial aneurysms were achieved using both stents. Because of its higher radial strength and better vessel wall apposition, we cautiously propose that the Solitaire stent may be more effective for SAC of aneurysms harboring a large or severe tortuous parent artery.

The TMR ratio of Co2Fe6B2/MgO-based p-MTJ spin valves stacked with a [Co/Pd]n-SyAF layer decreased rapidly when the ex situ magnetic annealing temperature (Tex) was increased from 275 to 325 °C, and this decrease was associated with degradation of the Co2Fe6B2 pinned layer rather than the Co2Fe6B2 free layer. At a Tex above 325 °C the amorphous Co2Fe6B2 pinned layer was transformed into a face-centered-cubic (fcc) crystalline layer textured from [Co/Pd]n-SyAF, abruptly reducing the Δ1 coherence tunneling of perpendicular-spin-torque electrons between the (100) MgO tunneling barrier and the fcc Co2Fe6B2 pinned layer.

The tunnel magnetoresistance (TMR) ratio of a cobalt-iron-boron (CoFeB)-based perpendicular-magnetic-tunnel-junction (p-MTJ) spin valve is extremely sensitive to both nanoscale Co2Fe6B2 free- and pinned-layer thicknesses. The TMR ratio peaks at a Co2Fe6B2 free-layer thickness of 1.05 nm, while it peaks at a Co2Fe6B2 pinned-layer thickness of 1.59 nm, achieving 104%. The amount of tantalum diffused into the MgO tunneling barrier (originated from a tantalum seed) decreases with increasing Co2Fe6B2 free-layer thickness, while the amount of palladium diffused from a [Co/Pd]n SyAF layer decreases with increasing Co2Fe6B2 pinned-layer thickness, determining the crystallinity of the MgO tunneling barrier and the TMR ratio. In addition, the TMR ratio tended to decrease when the Co2Fe6B2 free layer and the Co2Fe6B2 pinned layer switched characteristics from interface-perpendicular anisotropic to in-plane anisotropic.

Background: Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells., Methods: To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7(F/F):RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction., Results: Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1)., Conclusion: Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s(-1) mM(-1) and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

The null pigmentation mutant (npgA1) in Aspergillus nidulans results in a phenotype with colorless organs, decreased branching growth, delayed of asexual spore development, and aberrant cell wall structure. The npgA gene was isolated from A. nidulans to investigate these pleiomorphic phenomena of npgA1 mutant. Sequencing analysis of the complementing gene indicated that it contained a 4'-phosphopantetheinyl transferase (PPTase) superfamily domain. Enzymatic assay of the PPTase, encoded by the npgA gene, was implemented in vivo and in vitro. Loss-of-function of LYS5, which encoded a PPTase in Saccharomyces cerevisiae, was functionally complemented by NpgA, and Escherichia coli-derived NpgA revealed phosphopantetheinylation activity with the elaboration of 3'5'-ADP. Deletion of the npgA gene caused perfectly a lethal phenotype and the absence of asexual/sexual sporulation and secondary metabolites such as pigments in A. nidulans. However, a cross feeding effect with A. nidulans wild type allowed recovery from deletion defects, and phased-culture filtrate from the wild type were used to verify that the npgA gene was essential for formation of metabolites needed for development as well as growth. In addition, forced expression of npgA promoted the formation of conidia and cleistothecia as well as growth. These results indicate that the npgA gene is involved in the phosphopantetheinylation required for primary biological processes such as growth, asexual/sexual development, and the synthesis of secondary metabolites in A. nidulans.

Incretin-based therapy such as GLP-1 receptor agonists and DPP-4 inhibitors for type 2 diabetes mellitus is characterized by glucose-dependent insulin secretion and glucose-inhibited glucagon secretion. Recently, autophagy deficiency in islet β cells has been shown to contribute to the pathogenesis of type 2 diabetes mellitus however, with the role of incretin has not been established. To evaluate the role of autophagy in incretin effects, 8-week-old male β cell-specific Atg7 knockout (Atg7(Δβ cell)) mice and wild-type mice were administered vildagliptin for 12 weeks. Vildagliptin treatment improved glucose intolerance and hypoinsulinemia; however, it failed to suppress serum glucagon levels after glucose loading in the Atg7(Δβ cell) mice. Ex vivo glucose-induced glucagon suppression was also blunted in the islets from vildagliptin-treated Atg7(Δβ cell) mice. The α cell mass was not affected by β cell autophagy deficiency or vildagliptin. However, glucagon mRNA expression was significantly increased by vildagliptin in the autophagy-deficient islets, and was significantly reduced by vildagliptin in wild-type islets. Pancreatic glucagon contents were not in agreement with the changes in mRNA expression, suggesting a dysregulation in glucagon translation and secretion. In vitro studies revealed that glucose-stimulated cAMP production was impaired in the autophagy-deficient islets exposed to exendin-4. Taken together, the results suggest that the constitutive autophagy in β cells could regulate incretin-induced glucagon expression and release in α cells, and that cAMP may play a role in this process.

The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating ligand-size was investigated. Both r1 and r2 values decreased with increasing ligand-size. We attributed this to the ligand-size effect. In addition the effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR field.

Ultrasmall lanthanide oxide nanoparticles are promising materials as new magnetic resonance imaging (MRI) contrast agents because of their appreciable longitudinal (r 1 ) or transverse (r 2 ) water proton relaxivities at ultrasmall particle diameters. Two systems of d-glucuronic acid coated ultrasmall Ln/Mn (Ln = Gd and Dy) oxide nanoparticles with an average particle diameter of 2.0 nm were explored. The d-glucuronic acid coated ultrasmall Gd/Mn oxide nanoparticles showed strong positive contrast enhancements in 1.5 tesla T 1 MR images while the d-glucuronic acid coated ultrasmall Dy/Mn oxide nanoparticles showed appreciable negative contrast enhancements in 1.5 tesla T 2 MR images, proving their potential as T 1 and T 2 MRI contrast agents, respectively.

Epigenetic and transcriptional control of gene expression must be coordinated in response to external signals to promote alternative multicellular developmental programs. The membrane-associated trimeric complex VapA-VipC-VapB controls a signal transduction pathway for fungal differentiation. The VipC-VapB methyltransferases are tethered to the membrane by the FYVE-like zinc finger protein VapA, allowing the nuclear VelB-VeA-LaeA complex to activate transcription for sexual development. Once the release from VapA is triggered, VipC-VapB is transported into the nucleus. VipC-VapB physically interacts with VeA and reduces its nuclear import and protein stability, thereby reducing the nuclear VelB-VeA-LaeA complex. Nuclear VapB methyltransferase diminishes the establishment of facultative heterochromatin by decreasing histone 3 lysine 9 trimethylation (H3K9me3). This favors activation of the regulatory genes brlA and abaA, which promote the asexual program. The VapA-VipC-VapB methyltransferase pathway combines control of nuclear import and stability of transcription factors with histone modification to foster appropriate differentiation responses., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The mpkB gene of Aspergillus nidulans encodes a MAP kinase homologous to Fus3p of Saccharomyces cerevisiae which is involved in conjugation process. MpkB is required for completing the sexual development at the anastomosis and post-karyogamy stages. The mpkB deletion strain could produce conidia under the repression condition of conidiation such as sealing and even in the submerged culture concomitant with persistent brlA expression, implying that MpkB might have a role in timely regulation of brlA expression. The submerged culture of the deletion strain showed typical autolytic phenotypes including decrease in dry cell mass (DCM), disorganization of mycelial balls, and fragmentation of hyphae. The chiB, engA and pepJ genes which are encoding cell wall hydrolytic enzymes were transcribed highly in the submerged culture. Also, we observed that the enzyme activity of chitinase and glucanase in the submerged culture of mpkB deletion strain was much higher than that of wild type. The deletion of mpkB also caused a precocious germination of conidia and reduction of spore viability. The expression of the vosA gene, a member of velvet gene family, was not observed in the mpkB deletion strain. These results suggest that MpkB should have multiple roles in germination and viability of conidia, conidiation and autolysis through regulating the expression of vosA and brlA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Professional and public concern about the potential adverse effects of man-made electromagnetic fields (EMF) on the human body has dramatically expanded in recent years. Despite numerous attempts to investigate this issue, the long-standing challenge of reproducibility surrounding alternating EMF effects on human health remains unresolved. Our chief aim was to investigate a plausible mechanism for this phenomenon., Materials and Methods: Growth of cultured human cancer cells, DU145 and Jurkat, exposed to power frequency magnetic field (MF) (60 Hz, 1 mT) for 3 days, was determined using a 2-(4-Iodophenyl)- 3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay and a trypan blue exclusion assay. This experiment was repeated at incubators long-term monitoring period up to 5.3 years. A periodogram analysis was performed to investigate periodic patterns in the MF and sham effects on cell growth., Results: Unlike conventional assumptions, the MF effect on growth in both cell types was promotive or suppressive in a period-dependent manner. The converse cell growth induced by the MF was consistent in incubators, with little variation., Conclusions: Spatiotemporal evidence suggests that the period-dependent converse cell growth by the MF may contribute to the poor reproducibility and explain the adverse effects observed in previous experimental and epidemiological investigations. Additionally, the novel approach of this study may be applied to design features required to experimentally determine the effects of EMF on living organisms in a convincing manner.