Nonadditivities of the Particle Sizes Hidden in Model Pair Potentials and Their Effects on Physical Adsorptions.

It is important to understand the mechanism of colloidal particle assembly near a substrate for development of drug delivery systems, micro-/nanorobots, batteries, heterogeneous catalysts, paints, and cosmetics. Understanding the mechanism is also important for crystallization of the colloidal particles and proteins. In this study, we calculated the physical adsorption of colloidal particles on a flat wall mainly using the integral equation theory, wherein small and large colloidal particles were employed. In the calculation system, like-charged electric double-layer potentials were used as pair potentials. In some cases, it was found that the small particles are more easily adsorbed. This result is unusual from the viewpoint of the Asakura-Oosawa theory, and we call it a "reversal phenomenon". Theoretical analysis revealed that the reversal phenomenon originates from the nonadditivities of the particle sizes. Using the knowledge obtained from this study, we invented a method to analyze the size nonadditivity hidden in model pair potentials. The method will be useful for confirmation of various simulation results regarding the adsorption and development of force fields for colloidal particles, proteins, and solutes.

Histopathology of fused triplet placenta in rat.

A fused triplet placenta was observed in a Wistar Hannover rat on gestation day 15. Each placenta (referred to as PL-A, PL-B, and PL-C) of this fused placenta was attached to one fetus each, but their fetal weights were lower than that of the fetus attached to the only normal placenta (referred to as PL-N) in this dam. Histopathologically, thinning of the trophoblastic septa and dilatation of the maternal sinusoid in the labyrinth zone were observed in PL-B and PL-C, but not in PL-A or PL-N. The points of placental fusion were at the junctional zone derived from each side of the placenta without connective tissues, and the septum was composed of trophoblastic giant cells. Although PL-A had a solitary metrial gland, PL-B and PL-C shared one metrial gland with one spiral artery terminus branching towards each labyrinth zone.

Effects of cyclophosphamide on rat placental development.

We examined the morphological effects of cyclophosphamide (CPA) on placental development in pregnant rats. CPA was administered as a single dose to pregnant rats intraperitoneally at 0 mg/kg (the control group), 25 mg/kg on gestation day (GD) 12 (the CPA GD 12-treated group), and 25 mg/kg on GD 14 (the CPA GD 14-treated group). The fetal and placental weight decreased in the CPA-treated groups, complete fetal resorption from GD 17 onwards in the CPA GD 12-treated group, and external malformations in the CPA GD 14-treated group. Histopathologically, CPA induced apoptosis and/or cell proliferation inhibition in each part of the placenta. In the labyrinth zone, syncytiotrophoblasts were selectively reduced, resulting in a small placenta. In the basal zone, the number of spongiotrophoblasts was reduced, resulting in hypoplasia of glycogen cell islands. In addition, a small number of interstitial trophoblasts invaded the metrial gland from the basal zone on GD 15. The severity of these lesions was higher in the CPA GD 12-treated group than in the CPA GD 14-treated group. In the metrial gland, although the number of uterine natural killer cells was reduced, metrial gland development was not affected.

Muscle synergies of multidirectional postural control in astronauts on Earth after a long-term stay in space.

Movements of the human biological system have adapted to the physical environment under the 1-g gravitational force on Earth. However, the effects of microgravity in space on the underlying functional neuromuscular control behaviors remain poorly understood. Here, we aimed to elucidate the effects of prolonged exposure to a microgravity environment on the functional coordination of multiple muscle activities. The activities of 16 lower limb muscles of 5 astronauts who stayed in space for at least 3 mo were recorded while they maintained multidirectional postural control during bipedal standing. The coordinated activation patterns of groups of muscles, i.e., muscle synergies, were estimated from the muscle activation datasets using a factorization algorithm. The experiments were repeated a total of five times for each astronaut, once before and four times after spaceflight. The compositions of muscle synergies were altered, with a constant number of synergies, after long-term exposure to microgravity, and the extent of the changes was correlated with the increased velocity of postural sway. Furthermore, the muscle synergies extracted 3 mo after the return were similar in their activation profile but not in their muscle composition compared with those extracted in the preflight condition. These results suggest that the modularity in the neuromuscular system became reorganized to adapt to the microgravity environment and then possibly reoptimized to the new sensorimotor environment after the astronauts were reexposed to a gravitational force. It is expected that muscle synergies can be used as physiological markers of the status of astronauts with gravity-dependent change.NEW & NOTEWORTHY The human neuromuscular system has adapted to the gravitational environment on Earth. Here, we demonstrated that prolonged exposure to a microgravity environment in space changes the functional coordination of multiple muscle activities regarding multidirectional standing postural control. Furthermore, the amount of change led to a greater regulatory balancing activity needed for postural control immediately after returning to Earth and differences in muscular coordination before space flight and 3 mo after the return to Earth.

Spontaneous seminoma in medaka (Oryzias latipes).

Although spontaneous development of seminoma is rare in medaka, we encountered spontaneous testicular tumors located within the abdominal cavity in two adult medakas. The growth patterns of the tumors were a combination of solid and cord arrangements in one of the two cases (Case I) and lobular in the other case (Case II). The tumor cells resembled the cells at different stages of spermatogenesis, and a small number of oocyte-like cells were also scattered within the tumor. The tumor with solid and cord patterns showed loss of normal testicular architecture, and the tumor cells had partly invaded the dorsal muscular tissue and metastasized to the liver, kidney, and eye. The tumor with a lobular pattern did not exhibit local invasion or metastasis. The tumors were diagnosed as seminomas based on their histopathological characteristics, and the tumor in Case I was observed to be more malignant than that in Case II.

Failure to gulp surface air induces swim bladder adenomas in Japanese medaka (Oryzias latipes).

In order to elucidate the effects of swim bladder inflation failure on swim bladder carcinogenesis, we investigated the sequential histopathological changes of swim bladders at 13, 24, 35, and 53 days post-hatch (dph) in medakas with an uninflated swim bladder, which was experimentally induced by denying access to the air-water interface between 0 and 6 dph. The reactive oxygen species (ROS) levels were measured at 24 dph. An uninflated swim bladder was induced in 47.3% of the fish denied access to the air-water interface (the denied group). The total incidence of swim bladder adenoma was 54.1% in the denied group; however, these tumors were observed in all fish with an uninflated swim bladder. In fact, these tumors were observed from 13 dph and onwards. The TBARS levels of the juveniles showed a 2.6-fold increase in fish with an uninflated swim bladder in the denied group compared to that in the control group. It is speculated that swim bladder inflation failure has some effects on the gas gland to produce ROS, leading to DNA damage in the gas glandular epithelium, which develops into swim bladder adenomas. Consequently, it is concluded that denying access to the air-water interface between 0 and 6 dph in medaka is an easy method of inducing swim bladder tumors in a short-term period, and is a useful method for producing tumor-bearing fish.

Effects of testosterone on rat placental development.

We investigated the morphological effects of testosterone on placental development in a rat model of polycystic ovarian syndrome (PCOS). Testosterone propionate (TP), which was subcutaneously administered to pregnant rats with 5 mg/animal from gestation day (GD) 14 to GD 18, induced a maternal weight reduction without mortality or clinical signs from GD 19 onwards. A decrease in fetal and placental weight, an increase in intrauterine growth retardation (IUGR) rates, and histological changes in the placenta were observed on GD 21 but not on GD15 or 17. Histopathologically, on GD 21, the trophoblast septa thickened, and the maternal sinusoids were narrowed in the labyrinth zone, resulting in a small placenta. Additionally, the placental weight, thickness, and histological morphology in the labyrinth zone on GD 21 in the TP-treated group were nearly identical to those on GD 17 in the control and TP-treated groups. Therefore, it was assumed that the testosterone-induced small placenta was induced in association with the developmental inhibition of the fetal part of the placentas from GD 17 onwards.

Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity.

KEY POINTS: During long-duration spaceflights, some astronauts develop structural ocular changes including optic disc oedema that resemble signs of intracranial hypertension. In the present study, intracranial pressure was estimated non-invasively (nICP) using a model-based analysis of cerebral blood velocity and arterial blood pressure waveforms in 11 astronauts before and after long-duration spaceflights. Our results show that group-averaged estimates of nICP decreased significantly in nine astronauts without optic disc oedema, suggesting that the cephalad fluid shift during long-duration spaceflight rarely increased postflight intracranial pressure. The results of the two astronauts with optic disc oedema suggest that both increases and decreases in nICP are observed post-flight in astronauts with ocular alterations, arguing against a primary causal relationship between elevated ICP and spaceflight associated optical changes. Cerebral blood velocity increased independently of nICP and spaceflight-associated ocular alterations. This increase may be caused by the reduced haemoglobin concentration after long-duration spaceflight. ABSTRACT: Persistently elevated intracranial pressure (ICP) above upright values is a suspected cause of optic disc oedema in astronauts. However, no systematic studies have evaluated changes in ICP from preflight. Therefore, ICP was estimated non-invasively before and after spaceflight to test whether ICP would increase after long-duration spaceflight. Cerebral blood velocity in the middle cerebral artery (MCAv) was obtained by transcranial Doppler sonography and arterial pressure in the radial artery was obtained by tonometry, in the supine and sitting positions before and after 4-12 months of spaceflight in 11 astronauts (10 males and 1 female, 46 ± 7 years old at launch). Non-invasive ICP (nICP) was computed using a validated model-based estimation method. Mean MCAv increased significantly after spaceflight (ANOVA, P = 0.007). Haemoglobin decreased significantly after spaceflight (14.6 ± 0.8 to 13.3 ± 0.7 g/dL, P < 0.001). A repeated measures correlation analysis indicated a negative correlation between haemoglobin and mean MCAv (r = -0.589, regression coefficient = -4.68). The nICP did not change significantly after spaceflight in the 11 astronauts. However, nICP decreased significantly by 15% in nine astronauts without optic disc oedema (P < 0.005). Only one astronaut increased nICP to relatively high levels after spaceflight. Contrary to our hypothesis, nICP did not increase after long-duration spaceflight in the vast majority (>90%) of astronauts, suggesting that the cephalad fluid shift during spaceflight does not systematically or consistently elevate postflight ICP in astronauts. Independently of nICP and ocular alterations, the present results of mean MCAv suggest that long-duration spaceflight may increase cerebral blood flow, possibly due to reduced haemoglobin concentration.

The skin mycobiome of an astronaut during a 1-year stay on the International Space Station.

Analysis of the skin mycobiome of an astronaut during a 1-year stay on the International Space Station (ISS) revealed an increased relative abundance of Malassezia restricta and level of Malassezia colonization, and the presence of Cyberlindnera jadinii and Candida boidinii, uncommon skin mycobiome taxa. Similar observations were made in astronauts during a 6-month stay on the ISS (Med Mycol. 2016; 54: 232-239). Future plans for extended space travel should consider the effect of high levels of Malassezia colonization over long periods on astronauts' skin, and the abnormal proliferation of uncommon microorganisms that may occur in closed environments such as the ISS.

Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva.

As part of a series of studies regarding the microbiota in manned space environments, we isolated the fungal strains from nasal and pharyngeal smears and saliva of 21 astronauts preflight, in-flight, and postflight. On the ground, 120 strains from 43 genera of environmental fungi were isolated from the astronauts. The dominant fungal genera were Cladosporium, Penicillium, and Aspergillus. Only 18 strains from four genera were isolated from the astronauts inside the International Space Station. These fungi are currently thought to be harmless, but regular screening and cleaning are necessary to prevent fungus-related health disorders.

A case report of RccHanTM: WIST rat with multiple neoplastic and non-neoplastic proliferative lesions.

It is extremely rare to have multiple spontaneous proliferative lesions in young adult rats. Here, we report the occurrence of different proliferative lesions in multiple tissues of a 7-week-old female rat in a 1-week repeated toxicity study. Grossly, multiple white patches and nodules in the bilateral kidneys, femoral and subcutaneous masses, and a nodule in the liver were observed. Renal lesions were diagnosed as renal mesenchymal tumors. One of the femoral subcutaneous masses was diagnosed as an adenolipoma consisting of mammary epithelial cells and mature adipocytes. The other femoral and abdominal subcutaneous masses were diagnosed as lipomas consisting of mature adipocytes. The liver nodule was diagnosed as non-regenerative hepatocellular hyperplasia, which was characterized by the proliferation of slightly hypertrophic hepatocytes. In the cauda equina, the growth of enlarged Schwann cells around the axon was observed, and this lesion was diagnosed as a neuroma.

Comparison of acute inhalation toxicity of sulfuric acid by the inhalation and intratracheal instillation methods.

Recently, intratracheal instillation has been focused on as a simple, low-cost alternative to the inhalation method. In this study, intratracheal instillation of sulfuric acid, a typical acidic compound, was performed to compare the acute toxicity of acidic compounds that could cause damage to the respiratory system between intratracheal instillation and inhalation. Sulfuric acid was administered to male rats at doses of 0.7, 2, 7, 20, and 60 mg/kg by dividing the total dose into four doses. General condition and body weight were examined up to 14 days after administration, and macropathological and histopathological examinations were performed. The half-lethal dose was then estimated. All animals administered 20 and 60 mg/kg sulfuric acid and one animal administered 2 mg/kg sulfuric acid died within 4 h after administration. No abnormalities were observed in other animals. At 20 and 60 mg/kg, multiple red foci or diffuse red areas were macroscopically observed in the lungs. In these lesions, histopathologically, clefts between the mucosal epithelium and basement membrane and necrosis of the alveolar epithelium were observed. Deaths in these groups may have resulted from lung injury. No notable changes were observed in other animals. Therefore, the half-lethal dose of sulfuric acid by intratracheal instillation was estimated as 7-20 mg/kg. The acute toxicity by intratracheal instillation was evaluated with two-fold sensitivity since the exposure at the half-lethal sulfuric acid concentration in inhalation studies was calculated as 43.2 mg/kg.

Swim bladder tumor in the young adult scoliotic medaka (Oryzias latipes).

A swim bladder tumor was detected in one scoliotic medaka aged 22 weeks. The tumor was located in the dorsal abdominal cavity, with maximum dimension of 1,850 × 1,500 µm. No swim bladder lumen was identified, and the region where the swim bladder lumen would have been located, was replaced with adipose tissues. The tumor was a non-invasive, expansile, and encapsulated solid mass with a few cysts, and comprised a homogenous population of well-differentiated, densely packed, gas glandular epithelium-like cells. The tumor mass was connected to a rete mirabile that showed a hyperplastic capillary plexus; however, the tumor cells did not invade the rete mirabile, thereby revealing that the tumor was an adenoma originating from the gas glandular epithelium of the swim bladder. Since proliferative lesions in the swim bladder have been reported in some teleosts with skeletal deformations, including medaka, the occurrence of a spontaneous swim bladder tumor in teleosts is considered to be closely associated with various types of skeletal deformation, and spinal curvature in particular.

Swim bladder tumors in the wavy medaka (Oryzias latipes).

Swim bladder tumors were detected in three out of 28 wavy medakas aged about 2 years old, all of which displayed abnormal swimming patterns caused by their spinal curvature. The tumors were located in the dorsal abdominal cavity. The swim bladder lumen was not detected in the region where it was originally assumed to be located, and that region was replaced with adipose tissue. The tumors were non-invasive, expansile, and encapsulated solid masses composed of a homogenous population of well-differentiated, densely packed, gas glandular epithelium-like cells. The tumor masses were connected to the rete mirabile, but the tumor cells did not infiltrate into them. Histopathologically, these tumors were diagnosed as adenomas originating from the gas glandular epithelium of the swim bladder. Spontaneous swim bladder tumors are rare in medaka, with an incidence of 0.02%; however, in the present study of wavy medaka, the incidence was much higher (10.7%). The long-term physical effects on the gas gland caused by swim bladder deformation considered to be a secondary effect of the spinal curvature may be an important factor in the proliferation of the gas glandular epithelium in the wavy medaka, resulting in the higher incidence of swim bladder tumors.

Sequential histological changes in the liver of medaka exposed to methylazoxymethaol acetate.

We performed a medaka bioassay for the carcinogenicity of methylazoxymethaol acetate (MAM-Ac) to examine the sequential histological changes in the liver from 3 days after exposure until tumor development. The medaka were exposed to MAM-Ac at a concentration of 2 ppm for 24 hours, and were necropsied at 3, 7, 10, 14, 21, 28, 35, 42, 49, 60, and 91 days after exposure. MAM-Ac induced four cases of hepatocellular adenoma and one case of hepatocellular carcinoma in 8 fish after 60 or 91 days of exposure. Histological changes in the liver until tumor development were divided into three phases. In the cytotoxic phase (1-10 days), MAM-Ac-exposed hepatocytes showed vacuolar degeneration and underwent necrosis and apoptosis, resulting in multiple foci of hepatocyte loss. In the repopulation phase (14-35 days), the areas of hepatocyte loss were filled with hepatic cysts and the remaining hepatocytes were surrounded by hepatic stellate-like cells (or spindle cells) and gradually disappeared. In the proliferation phase (42-91 days), the original hepatic parenchyma was regenerated and progressively replaced by regenerative hyperplastic nodules and/or liver neoplasms. The medaka retained a strong hepatocyte regenerative ability in response to liver injury. It is considered that this ability promotes the proliferation of initiated hepatocytes in multistep carcinogenesis and influences the development of liver tumor over a short period in medaka.

Morphology and physiology of rat placenta for toxicological evaluation.

The placenta plays a pivotal role in fetal growth, and placental dysfunction and injury are associated with embryo/fetal toxicity. Histological examination of the rat placenta for safety evaluation provides valuable clues to the mechanisms of this toxicity. However, the placenta has specific and complex biological features unlike those of other organs, and placental structure dramatically changes depending on the time during the gestation period. Thus, time-dependent histopathological examination of the rat placenta should be performed based on the understanding of normal developmental changes in morphology and function. The placentas of rats and humans are both anatomically classified as discoid and hemochorial types. However, there are differences between rats and humans in terms of placental histological structure, the fetal-maternal interface, and the function of the yolk sac. Therefore, extrapolation of placental toxicity from rats to humans should be done cautiously in the evaluation of risk factors. This review describes the development, morphology, physiology, and toxicological features of the rat placenta and the differences between the rat and human placenta to enable accurate evaluation of reproductive and developmental toxicity in studies.

The effects of ß-naphthoflavone on rat placental development.

The morphological effects of ß-naphthoflavone (ß-NF) on placental development in pregnant rats were examined. ß-NF, administered to pregnant rats intraperitoneally at 15 mg/kg bw from gestation day (GD) 9 to GD 14, had no effect on maternal body weight gain, mortality, or clinical sign. In the ß-NF-exposed rats, intrauterine growth retardation (IUGR) rates increased on GDs 17 and 21, although there was no effect on fetal mortality rate, fetal or placental weight, or external fetal abnormality. Histopathologically, ß-NF induced apoptosis and inhibition of cell proliferation of the trophoblastic septa in the labyrinth zone, resulting in its poor development. In the basal zone, ß-NF induced spongiotrophoblast apoptosis and delayed glycogen islet regression, resulting in their cystic degeneration. ß-NF-induced CYP1A1 expression was detected in the endothelial cells of the fetal capillaries in the labyrinth zone and in the endothelial cells of the spiral arteries in the metrial gland, but not in any trophoblasts. This indicates that CYP1A1 is inducible in the endothelial cells of the fetal capillaries in the labyrinth zone, and that these cells have an important role in metabolizing CYP1A1 inducers crossing the placental barrier.

Dynamic cerebral autoregulation after confinement in an isolated environment for 14 days.

BACKGROUND: To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation. METHODS: We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity. RESULTS: Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement. CONCLUSION: The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation. TRIAL REGISTRATION: UMIN000020703 , Registered 2016/01/22.

Autopsy Cases of Motorcyclists Dying of Trauma or Disease.

We aimed to provide a better estimation of health-related motorcycle fatalities by comparing the backgrounds, mechanisms of injuries, and injury severity of victims who died of collision versus those who died of disease. We retrospectively analyzed autopsy records of 29 motorcyclists (mean age, 61.0 ± 21.0 years), none of whom had been driving under the influence of alcohol. Altogether, 22 (75.9%) had died of trauma, and 7 had died of disease. The disease-death victims were significantly older and had a significantly higher prevalence of a medical history compared with those with trauma-related death (100% vs 45.5%, P = 0.01), especially of lifestyle diseases (100% vs 13.6%, P < 0.001) and heart or cerebrovascular disease (57.1% vs 13.6%, P = 0.02). All of the victims who were affected by disease and 50% of trauma-death victims had fallen on the road without a vehicle collision (P = 0.02). Mean Injury Severity Score of the trauma-death group was significantly higher than that of the disease-death group (48.1 vs 9.1, P < 0.001). A forensic autopsy should be performed for all motorcyclist fatalities to diagnose a disease-related death during motorcycle riding. To reduce the incidence of these accidents, motorcyclists should maintain a good physical status.

Databases for technical aspects of immunohistochemistry.

With the aims of sharing information about the technical aspects of immunohistochemistry (IHC) and making it possible to make a suitable choice of antibody for histopathological examination, this technical report describes the results of a questionnaire administered during the period of 2014 to 2015 to members of the Conference on Experimental Animal Histopathology. It also describes the immunological properties of primary antibodies (clone, supplier, catalog number, species reactivity, etc.) and the IHC staining conditions (fixing solution, fixing time, embedding, antigen retrieval method, antibody dilution, incubation time, incubation temperature, positive control tissue, secondary antibody information, etc.) for a total number of 733 primary antibodies (425 kinds of primary antibody).