Genetic effects of demographic bottleneck and recovery in Kinkazan Island and mainland populations of Japanese macaques (Macaca fuscata).

Populations of Japanese macaques were significantly reduced in most areas from the 1900s to the 1960s and then recovered mainly in the northeastern part of Honshu. A drastic reduction in population size reduces genetic variability through a bottleneck effect. Demographic expansion after the reduction that accumulates new mutations can reduce the bottleneck effects or drive the recovery of genetic variability. We examined the genetic status of a small island population (Kinkazan Island) and a larger mainland population (southern Tohoku) of Japanese macaques that experienced recent demographic bottlenecks and recovery using eight microsatellite loci. The two populations were significantly genetically different from each other. The Kinkazan population exhibited lower genetic variability, remarkable evidence of bottleneck (i.e., significant heterozygosity excess and lower frequency of rare alleles), and a considerably smaller effective population size based on genetic data than based on the current census size. These results indicate that the genetic status has not completely recovered from the demographic bottleneck despite a full recovery in census size on Kinkazan Island. New mutations might rarely have accumulated because of the small carrying capacity of the island. Therefore, the genetic variability of the population would have been restrained by the severe bottleneck size, small carrying capacity, and long-term isolation. On the other hand, the bottleneck effect seems to be limited in the southern Tohoku population considering higher genetic variability, non-significant heterozygosity excess in many mutation conditions, and the highest frequency of rare alleles.

Investigation of interfacial strength in nacre-mimicking tungsten heavy alloys for nuclear fusion applications.

Tungsten heavy alloys have been proposed as plasma facing material components in nuclear fusion reactors and require experimental investigation in their confirmation. For this purpose, a 90W-7Ni-3Fe alloy has been selected and microstructurally manipulated to present a multiphase brick-and-mortar structure of W-phase 'bricks' surrounded by a ductile 'mortar'. This work draws inspiration from nature to artificially imitate the extraordinary combination of strength and stiffness exhibited by mollusks and produce a nacre-mimicking metal matrix composite capable of withstanding the extremely hostile environment of the reactor interior and maintaining structural integrity. The underlying mechanisms behind this integrity have been probed through high-resolution structural and chemical characterization techniques and have revealed chemically diffuse phase boundaries exhibiting unexpected lattice coherency. These features have been attributed to an increase in the energy required for interfacial decohesion in these systems and the simultaneous expression of high strength and toughness in tungsten heavy alloys.

Nanoscale defect evaluation framework combining real-time transmission electron microscopy and integrated machine learning-particle filter estimation.

Observation of dynamic processes by transmission electron microscopy (TEM) is an attractive technique to experimentally analyze materials' nanoscale phenomena and understand the microstructure-properties relationships in nanoscale. Even if spatial and temporal resolutions of real-time TEM increase significantly, it is still difficult to say that the researchers quantitatively evaluate the dynamic behavior of defects. Images in TEM video are a two-dimensional projection of three-dimensional space phenomena, thus missing information must be existed that makes image's uniquely accurate interpretation challenging. Therefore, even though they are still a clustering high-dimensional data and can be compressed to two-dimensional, conventional statistical methods for analyzing images may not be powerful enough to track nanoscale behavior by removing various artifacts associated with experiment; and automated and unbiased processing tools for such big-data are becoming mission-critical to discover knowledge about unforeseen behavior. We have developed a method to quantitative image analysis framework to resolve these problems, in which machine learning and particle filter estimation are uniquely combined. The quantitative and automated measurement of the dislocation velocity in an Fe-31Mn-3Al-3Si autunitic steel subjected to the tensile deformation was performed to validate the framework, and an intermittent motion of the dislocations was quantitatively analyzed. The framework is successfully classifying, identifying and tracking nanoscale objects; these are not able to be accurately implemented by the conventional mean-path based analysis.

Study of beamlets extracted from a multi-aperture and five-stage acceleration system.

A beam optics study using the ITER-relevant high intense negative ion beams, such as 1 MeV, 200 A/m2, has been performed experimentally and analytically using a multi-aperture and five-stage accelerator. Initially, multi-beamlets generated from this accelerator were deflected in various directions due to the magnetic field and space charge repulsion between beams and showed various divergences. These had limited the pulse length and the beam energy. Compensation methods of the beamlet deflections have worked effectively and contributed to achieving the ITER requirement, the divergence angle of <7 mrad, and the deflection angle of <1 mrad for 1 MeV beam. The beam pulse has been gradually extended from 1 to 100 s and is now going to a longer pulse based on these results. One of the remaining issues is to understand and suppress peripheral components of the beam, namely, the halo, and to reduce the local heat loads observed around the aperture edge. This halo component has been successfully distinguished from the beam core by using a newly developed beam emittance measurement system for high intense beams. By combining this measured beam emittance and the beam simulation, it was clarified for the first time that the halo components are generated in an area of 1 mm width from the aperture edge.

Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

Chimpanzee Personality and the Arginine Vasopressin Receptor 1A Genotype.

Polymorphisms of the arginine vasopressin receptor 1a (AVPR1a) gene have been linked to various measures related to human social behavior, including sibling conflict and agreeableness. In chimpanzees, AVPR1a polymorphisms have been associated with traits important for social interactions, including sociability, joint attention, dominance, conscientiousness, and hierarchical personality dimensions named low alpha/stability, disinhibition, and negative emotionality/low dominance. We examined associations between AVPR1a and six personality domains and hierarchical personality dimensions in 129 chimpanzees (Pan troglodytes) living in Japan or in a sanctuary in Guinea. We fit three linear and three animal models. The first model included genotype, the second included sex and genotype, and the third included genotype, sex, and sex × genotype. All personality phenotypes were heritable. Chimpanzees possessing the long form of the allele were higher in conscientiousness, but only in models that did not include the other predictors; however, additional analyses suggested that this may have been a consequence of study design. In animal models that included sex and sex × genotype, chimpanzees homozygous for the short form of the allele were higher in extraversion. Taken with the findings of previous studies of chimpanzees and humans, the findings related to conscientiousness suggest that AVPR1a may be related to lower levels of impulsive aggression. The direction of the association between AVPR1a genotype and extraversion ran counter to what one would expect if AVPR1a was related to social behaviors. These results help us further understand the genetic basis of personality in chimpanzees.

In-situ straining and time-resolved electron tomography data acquisition in a transmission electron microscope.

This paper reports the preliminary results of a new in-situ three-dimensional (3D) imaging system for observing plastic deformation behavior in a transmission electron microscope (TEM) as a directly relevant development of the recently reported straining-and-tomography holder [Sato K et al. (2015) Development of a novel straining holder for transmission electron microscopy compatible with single tilt-axis electron tomography. Microsc. 64: 369-375]. We designed an integrated system using the holder and newly developed straining and image-acquisition software and then developed an experimental procedure for in-situ straining and time-resolved electron tomography (ET) data acquisition. The software for image acquisition and 3D visualization was developed based on the commercially available ET software TEMographyTM. We achieved time-resolved 3D visualization of nanometer-scale plastic deformation behavior in a Pb-Sn alloy sample, thus demonstrating the capability of this system for potential applications in materials science.

Genome-wide DNA markers to support genetic management for domestication and commercial production in a large rodent, the Ghanaian grasscutter (Thryonomys swinderianus).

Domestication and commercial production of the grasscutter, Thryonomys swinderianus, a large rodent, represents an important opportunity to secure sustainable animal protein for local communities in West Africa. To support production, DNA markers are required for population diversity assessment, pedigree analysis and marker-assisted selection. This study reports the application of double-digest RAD sequencing to simultaneously discover and genotype SNP markers in 24 wild and recently domesticated grasscutters. An initial panel of 1209 SNP loci was characterised from a total of more than 21 000 candidate loci containing single SNPs. This genome-wide resource represents the first application of its type to commercial production of a large rodent for food and advances the use of agricultural genomics in Ghana.

Top-down cortical input during NREM sleep consolidates perceptual memory.

During tactile perception, long-range intracortical top-down axonal projections are essential for processing sensory information. Whether these projections regulate sleep-dependent long-term memory consolidation is unknown. We altered top-down inputs from higher-order cortex to sensory cortex during sleep and examined the consolidation of memories acquired earlier during awake texture perception. Mice learned novel textures and consolidated them during sleep. Within the first hour of non-rapid eye movement (NREM) sleep, optogenetic inhibition of top-down projecting axons from secondary motor cortex (M2) to primary somatosensory cortex (S1) impaired sleep-dependent reactivation of S1 neurons and memory consolidation. In NREM sleep and sleep-deprivation states, closed-loop asynchronous or synchronous M2-S1 coactivation, respectively, reduced or prolonged memory retention. Top-down cortical information flow in NREM sleep is thus required for perceptual memory consolidation.

Evidence for the effect of serotonin receptor 1A gene (HTR1A) polymorphism on tractability in Thoroughbred horses.

Tractability, or how easily animals can be trained and controlled, is an important behavioural trait for the management and training of domestic animals, but its genetic basis remains unclear. Polymorphisms in the serotonin receptor 1A gene (HTR1A) have been associated with individual variability in anxiety-related traits in several species. In this study, we examined the association between HTR1A polymorphisms and tractability in Thoroughbred horses. We assessed the tractability of 167 one-year-old horses reared at a training centre for racehorses using a questionnaire consisting of 17 items. A principal components analysis of answers contracted the data to five principal component (PC) scores. We genotyped two non-synonymous single nucleotide polymorphisms (SNPs) in the horse HTR1A coding region. We found that one of the two SNPs, c.709G>A, which causes an amino acid change at the intracellular region of the receptor, was significantly associated with scores of four of five PCs in fillies (all Ps < 0.05) and one PC in colts (P < 0.01). Horses carrying an A allele at c.709G>A showed lower tractability. This result provides the first evidence that a polymorphism in a serotonin-related gene may affect tractability in horses with the effect partially different depending on sex.

Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration.

Copy number variations in the amylase gene (AMY2B) in Japanese native dog breeds.

A recent study suggested that increased copy numbers of the AMY2B gene might be a crucial genetic change that occurred during the domestication of dogs. To investigate AMY2B expansion in ancient breeds, which are highly divergent from modern breeds of presumed European origins, we analysed copy numbers in native Japanese dog breeds. Copy numbers in the Akita and Shiba, two ancient breeds in Japan, were higher than those in wolves. However, compared to a group of various modern breeds, Akitas had fewer copy numbers, whereas Shibas exhibited the same level of expansion as modern breeds. Interestingly, average AMY2B copy numbers in the Jomon-Shiba, a unique line of the Shiba that has been bred to maintain their appearance resembling ancestors of native Japanese dogs and that originated in the same region as the Akita, were lower than those in the Shiba. These differences may have arisen from the earlier introduction of rice farming to the region in which the Shiba originated compared to the region in which the Akita and the Jomon-Shiba originated. Thus, our data provide insights into the relationship between the introduction of agriculture and AMY2B expansion in dogs.

DEEP BIOSPHERE. Exploring deep microbial life in coal-bearing sediment down to ~2.5 km below the ocean floor.

Microbial life inhabits deeply buried marine sediments, but the extent of this vast ecosystem remains poorly constrained. Here we provide evidence for the existence of microbial communities in ~40° to 60°C sediment associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas compositions. Concentrations of indigenous microbial cells below 1.5 km ranged from <10 to ~10(4) cells cm(-3). Peak concentrations occurred in lignite layers, where communities differed markedly from shallower subseafloor communities and instead resembled organotrophic communities in forest soils. This suggests that terrigenous sediments retain indigenous community members tens of millions of years after burial in the seabed.

Development of a novel straining holder for transmission electron microscopy compatible with single tilt-axis electron tomography.

We have developed a newly designed straining specimen holder for in situ transmission electron microscopy (TEM) compatible with high-angle single tilt-axis electron tomography. The holder can deform a TEM specimen under tensile stress with the strain rate between 1.5 × 10(-6) and 5.2 × 10(-3) s(-1). We have also confirmed that the maximum tilt angle of the specimen holder reaches ±60° with a rectangular shape aluminum specimen. The new specimen holder, termed as 'straining and tomography holder', will have wide range potential applications in materials science.

Evaluation of the potassium adsorption capacity of a potassium adsorption filter during rapid blood transfusion.

The concentration of extracellular potassium in red blood cell concentrates (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium adsorption filter (PAF) can eliminate the potassium at normal blood transfusion. This study aimed to investigate the potassium adsorption capacity of a PAF during rapid blood transfusion. We tested several different potassium concentrations under a rapid transfusion condition using a pressure bag. The adsorption rates of the 70-mEq/l model were 76·8%. The PAF showed good potassium adsorption capacity, suggesting that this filter may provide a convenient method to prevent hyperkalemia during rapid blood transfusion.

A software tool for automatic analysis of selected area diffraction patterns within Digital Micrograph™.

A software package "SADP Tools" is developed as a complementary diffraction pattern analysis tool. The core program, called AutoSADP, is designed to facilitate automated measurements of d-spacing and interplaner angles from TEM selected area diffraction patterns (SADPs) of single crystals. The software uses iterative cross correlations to locate the forward scattered beam position and to find the coordinates of the diffraction spots. The newly developed algorithm is suitable for fully automated analysis and it works well with asymmetric diffraction patterns, off-zone axis patterns, patterns with streaks, and noisy patterns such as Fast Fourier transforms of high-resolution images. The AutoSADP tool runs as a macro for the Digital Micrograph program and can determine d-spacing values and interplanar angles based on the pixel ratio with an accuracy of better than about 2%.

Molecular characterisation of the quinolone resistance-determining region (QRDR) of the parC gene locus in viridans-group streptococci.

Forty-eight isolates of viridans-group streptococci (VGS) from adults and children in the community are examined for their resistance to ciprofloxacin phenotypically by determination of the minimum inhibitory concentration (MIC). In addition, the parC gene locus is amplified and sequenced in all isolates and mutations noted. Overall, 44 VGS organisms were found to be susceptible to ciprofloxacin by the broth microdilution method, and the remaining four strains had intermediate susceptibility. Reduced MICs were observed with intermediate strains when reserpine was added to the broth, inhibiting any efflux activity. Overall, the effect of adding reserpine to the broth medium was to add one doubling dilution to the MIC in the case of Streptococcus mitis, S. oralis and S. salivarius, as well as to increase the MIC by two doubling dilutions in two of the three S. parasanguinis isolates. Amino acid sequence analysis of the quinolone resistance-determining region (QRDR) of the parC gene locus showed good correlation to the phenotypic resistance to ciprofloxacin, where no confirmed mutation conferring quinolone resistance was found. Eleven amino acid positions showed discordance with S. pneumoniae R6 and eight (S52, F55, S58, N91, E135, K137, F141 and S167) were common in the VGS species examined. In addition, minor substitutions were found at three positions (D51, T54 and V86). In conclusion, this study demonstrates the low occurrence of ciprofloxacin resistance in a population of VGS isolated from the community. In addition, several silent mutations were noted in VGS organisms without any increase in MIC against ciprofloxacin.

[Pleomorphic carcinoma of the lung; report of a case].

A 83-year-old male was referred to our hospital for further examination of abnormal shadow on chest radiography. Chest computed tomography (CT) showed a tumor mass in his right lung. Bronchoscopy brushing cytology revealed non-small cell lung carcinoma and right middle lobectomy was performed. Histological findings showed large cell carcinoma comprised of spindle cell component, finally diagnosing as pleomorphic carcinoma of the lung. Although he was diagnosed as pT2N0M0 (stage IA) after the operation, massive liver metastasis was found 7 months later. We report this case with references to the literatures on pleomorphic carcinoma of the lung.

Molecular analysis and characterisation of the full-length flagellin C gene (flaC) from Campylobacter lari.

A degenerate polymerase chain reaction (PCR) primer pair (f-ClflaC/r-ClflaC) was constructed in silico to amplify flaC and its adjacent genetic loci from Campylobacter lari isolates. Approximately 1.45 kbp amplicons, including the sequences encoding the flaC structural gene of 750 bp, putative promoter, rho-independent intrinsic terminator regions and partial sequences of two putative open reading frames (ORFs), immediately upstream and downstream of the gene, were identified in 16 C. lari isolates (four urease-negative [UN] C. lari; 12 urease-positive thermophilic campylobacters [UPTC)]). All 16 flaC structural genes commenced with an ATG start codon and terminated with a TAA stop codon and probable ribosome-binding sites were identified in all 16 isolates. These probably indicate a monocistronic operon structure for the flaC gene in C. lari isolates. In addition, the putative flaC gene ORFs were deduced to be similar in 747 bp among all 26 thermophilic Campylobacter isolates examined, resulting in a similar calculated molecular weight of approximately 26.6-26.9 kDa. The flaC from C. lari was different from the flaA-like sequence and the shorter flaA of UPTC isolates found previously. Reverse transcription PCR and Northern blot hybridisation analyses identified flaC transcription in C. lari cells. The transcription initiation site for the flaC gene was also determined by primer extension analysis. A dendrogram constructed, based on the nucleotide sequence information of flaC from 17 C. lari isolates, demonstrated that the C. lari isolates were genetically variable and formed two minor clusters for UN C. lari and UPTC.