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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
The naturalization of alien Reeves's muntjacs (Muntiacus reevesi) on Izu-Oshima Island, Tokyo, Japan, has proceeded intensively over the last five decades. To clarify whether the gastrointestinal helminths of these animals were brought from their original endemic area or were newly acquired in Japan, 32 Reeves's muntjacs trapped on the island were parasitologically examined. In addition to Gongylonema pulchrum in the oesophagus (34.4% prevalence), Chabaudstrongylus ninhae (Dróżdż, 1967) (Trichostrongylidae: Cooperiinae) and Oesophagostomum muntiacum Jian, 1989 (Chabertiidae: Oesophagostominae) were prevalent in the small (28.1%) and large (46.9%) intestines, respectively. For the first time, these trichostrongylid or chabertiid worms were genetically characterized based on partial nucleotide sequences of the nuclear ribosomal RNA gene (rDNA) and mitochondrial DNA cytochrome c oxidase subunit 1 gene (cox-1), and the phylogenetic relationships with other members of their family were explored. Since these two intestinal nematode species are inherent in muntjacs, this study demonstrates a new distribution of exotic helminth species in Japan in accordance with the naturalization of alien mammalian hosts. The molecular genetic data collected here could assist the taxonomic assessment of morphological variants in different Muntiacus spp. and/or of different geographical origins. Furthermore, our data may help to define the phylogenetic relationships among such isolates.
In order to improve a large posterior glottal gap and/or aspiration, injections of augmentation substances should not only be administered at the mid-membranous vocal fold in the thyroarytenoid muscle, but also at the cartilaginous portion of the vocal fold to make adduction arytenopexy possible.
Ten adult human larynges were investigated using the whole-organ serial section technique.
Vertical thickness of the posterior aspect of the thyroarytenoid muscle was relatively thin (3.4 ± 0.4 mm), especially in females (3.2 ± 0.3 mm). Consequently, care should be taken to ensure the correct depth of needle placement. If the needle is placed too deep, augmentation substances are injected into the lateral cricoarytenoid muscle, located beneath the thyroarytenoid muscle, or into the paraglottic space, located inferolateral to the thyroarytenoid muscle.
The injection location and the amount of injected material should be modified based on the pathological conditions of the voice disorder and aspiration.
The gullet worms, classical Gongylonema pulchrum and newly differentiated Gongylonema nepalensis, are prevalent in various mammals in Japan and Sardinia, Italy, respectively. The former species is cosmopolitan in distribution, dwelling in the mucosa of the upper digestive tract of a variety of domestic and wild mammals, and also humans. At present, the geographical distribution of G. nepalensis is known in Nepal and Sardinia, with the nematode having been recorded from the oesophagus of water buffaloes (Nepal), cattle, sheep, goats and wild mouflon (Sardinia). To clarify their natural transmission cycles among domestic and wild mammals, the present study analysed the ribosomal RNA gene (rDNA) and mitochondrial cytochrome c oxidase subunit 1 gene (cox1) of worms of various origins: G. pulchrum worms from sika deer, wild boars, Japanese macaques, and feral alien Reeves's muntjacs in Japan, and G. nepalensis worms from a red fox and a wild boar in Sardinia. Although the internal transcribed spacer (ITS) regions of rDNA and partial cox1 nucleotide sequences of G. pulchrum from native wild mammals in Japan were distinct from those of the worms in cattle, the worms from feral alien Reeves's muntjacs showed the cattle-type ITS genotype and cox1 cattle-I and II haplotypes. The rDNA and cox1 nucleotide sequences of G. nepalensis from a red fox in Sardinia were almost identical to those of the worms from domestic and wild ruminants on the island. The ecological interaction between domestic and wild mammals and their susceptibility to different Gongylonema spp. must be considered when trying to elucidate this spirurid's transmission dynamics in nature.
Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.
SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.
SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.
Section 4 of the FM14 focus on the outreach action and advocacy in the context of IAUs 2020-2030 Strategic Plan. This paper also contains supplementary materials that point to contributed talks and poster presentations that can be found online.
Non-traumatic bone fractures in cancer patients are usually pathological fractures due to bone metastases. In head and neck cancer patients, clavicle stress fractures may occur as a result of atrophy of the trapezius muscle after neck dissection in which the accessory nerve becomes structurally or functionally damaged.
A 71-year-old man underwent modified radical neck dissection with accessory nerve preservation and post-operative radiotherapy for submandibular lymph node metastases of tongue cancer. Four weeks after the radiotherapy, a clavicle fracture, with osteomyelitis and abscess formation in the pectoralis major muscle, occurred. Unlike in simple stress fracture, long-term antibiotic administration and drainage surgery were required to suppress the inflammation.
As seen in the present patient, clavicle stress fractures may occur even after neck dissection in which the accessory nerve is preserved, and may be complicated by osteomyelitis and abscess formation owing to risk factors such as radiotherapy, tracheostomy and contiguous infection.
Cats are known to be the main reservoir for Bartonella henselae and Bartonella clarridgeiae, which are the agents of ‘cat-scratch disease’ in humans. In the present study, we investigated the prevalence of the two Bartonella species on 1754 cat bloods collected from all prefectures in Japan during 2007–2008 by a nested-polymerase chain reaction (PCR) targeting the 16S–23S rRNA internal transcribed spacer region. Overall, Bartonella DNA was detected in 4·6% (80/1754) of the cats examined. The nested-PCR showed that 48·8% (39/80) of the positive cats were infected with B. henselae mono-infection, 33·8% (27/80) with B. clarridgeiae mono-infection and 17·5% (14/80) were infected with both species. The prevalence (5·9%; 65/1103) of Bartonella infection in the western part of Japan was significantly higher than that (2·3%; 15/651) of eastern Japan (P < 0·001). Statistical analysis of the cats examined suggested a significant association between Bartonella infection and FeLV infection (OR = 1·9; 95% CI = 1·1–3·4), but not with FIV infection (OR = 1·6; 95% CI = 1·0–2·6).
Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8–10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for ‘fetal programming,’ which appears to have evolved phylogenetically early.
There is growing evidence that the cells in the maculae flavae are tissue stem cells of the human vocal fold mucosa, and that the maculae flavae are a candidate for a stem cell niche. The role of microenvironment in the maculae flavae of the human vocal fold mucosa was investigated.
Anterior maculae flavae from six surgical specimens were cultured in a mesenchymal stem cell growth medium or a Dulbecco's modified Eagle's medium.
Using mesenchymal stem cell growth medium, the subcultured cells formed a colony-forming unit, and cell division reflected asymmetric self-renewal. This indicates that these cells are mesenchymal stem cells or stromal stem cells in the bone marrow. Using Dulbecco's modified Eagle's medium, the subcultured cells showed symmetric cell division without a colony-forming unit.
A proper microenvironment in the maculae flavae of the human vocal fold mucosa is necessary to be effective as a stem cell niche that maintains the stemness of the contained tissue stem cells.
There is growing evidence to suggest that cells in the maculae flavae are tissue stem cells of the human vocal fold and maculae flavae are a stem cell niche.
Three newborn vocal folds were investigated. Immunoreactivity to antibodies directed to cytokeratin, desmin, glial fibrillary acidic protein, vimentin, cluster of differentiation 34, cluster of differentiation 45, collagen type I, telomerase reverse transcriptase, SOX17 and stage-specific embryonic antigen 3 was investigated.
The cells in the newborn maculae flavae expressed haematopoietic markers (cluster of differentiation 34, cluster of differentiation 45) and collagen type I, which are the major makers of bone marrow derived circulating fibrocytes. The cells expressed epithelium, muscle, neural and mesenchymal cell associated proteins, and endodermal marker, indicating that they are undifferentiated and express proteins of all three germ layers. The cells also expressed stage-specific embryonic antigen 3 and telomerase reverse transcriptase.
The cells in the newborn maculae flavae are undifferentiated cells arising from the differentiation of bone marrow cells. The results of this study are consistent with the hypothesis that the cells in maculae flavae are tissue stem cells.
A fully coherent free electron laser (FEL) seeded with a higher-order harmonic (HH) pulse from high-order harmonic generation (HHG) is successfully operated for a sufficiently prolonged time in pilot user experiments by using a timing drift feedback. For HHG-seeded FELs, the seeding laser pulses have to be synchronized with electron bunches. Despite seeded FELs being non-chaotic light sources in principle, external laser-seeded FELs are often unstable in practice because of a timing jitter and a drift between the seeding laser pulses and the accelerated electron bunches. Accordingly, we constructed a relative arrival-timing monitor based on non-invasive electro-optic sampling (EOS). The EOS monitor made uninterrupted shot-to-shot monitoring possible even during the seeded FEL operation. The EOS system was then used for arrival-timing feedback with an adjustability of 100 fs for continual operation of the HHG-seeded FEL. Using the EOS-based beam drift controlling system, the HHG-seeded FEL was operated over half a day with an effective hit rate of 20%–30%. The output pulse energy was
at the 61.2 nm wavelength. Towards seeded FELs in the water window region, we investigated our upgrade plan to seed high-power FELs with HH photon energy of 30–100 eV and lase at shorter wavelengths of up to 2 nm through high-gain harmonic generation (HGHG) at the energy-upgraded SPring-8 Compact SASE Source (SCSS) accelerator. We studied a benefit as well as the feasibility of the next HHG-seeded FEL machine with single-stage HGHG with tunability of a lasing wavelength.
This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion.
A case–control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated.
Results for HMGB1 were dichotomised into positive staining scores (score, 5–7) and negative scores (0–4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6–26.5) after adjusting for other factors.
In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.
Magnetic/fluorescent (magnetofluorescent) materials have become one of the most important tools in the imaging modality in vivo using magnetic resonance imaging (MRI) and fluorescence imaging. We succeeded in fabricating magnetofluorescent nanoparticles (MFNPs) consisting of silicon/magnetite composite nanoparticles. Our unique synthetic approach can control simultaneously the magnetic and fluorescence behaviors by varying the particle size, demonstrating the superparamagnetic behavior and green fluorescence for the MFNPs having mean diameter of 3.0 nm, and the ferromagnetic behavior without fluorescence for the MFNPs having mean diameter more than 5.0 nm. More intriguingly, the MFNPs with superparamagnetism can detect green fluorescence even after the magnetic guidance of MFNPs by the commercial neodymium magnet. Additionally, the MFNPs having two magnetic behaviors also possess good biocompatibility.
The aim of the present study was to examine the effects of brilliant cresyl blue (BCB) staining on mitochondrial functions in porcine oocytes. Cumulus–oocyte complexes (COCs) collected from slaughterhouse-derived porcine ovaries were cultured with (13 μM) or without (0 μM, control) BCB for 60 min. Mitochondrial functions in oocytes were examined immediately after staining or after in vitro maturation. The BCB-stained oocytes produced reactive oxygen species (ROS) at higher levels than control oocytes immediately after staining (2.2-fold, P < 0.001) and after maturation (1.7-fold, P < 0.001). The adenosine triphosphate (ATP) content and mitochondrial membrane potential (MMP) in oocytes were similar for the two groups immediately after staining. However, ATP and relative MMP levels were significantly (P < 0.05) lower in BCB-treated oocytes than in the control (2.18 versus 2.83 pM and 0.82 versus 1.0, respectively). There was no difference in mitochondrial DNA copy number between the two groups after maturation. The ATP content in early developmental stage embryos (3 days after parthenogenetic activation) was lower in the BCB-stained group than that in the control group but the difference was not significant. In conclusion, BCB staining of oocytes at the immature stage compromises mitochondrial functions throughout oocyte maturation, but function is restored during early embryo development.