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Alzheimer disease is a dementing disorder characterized pathologically by Aβ deposition, neurofibrillary tangles, and neuronal loss. Although aged animals of many species spontaneously develop Aβ deposits, only 2 species (chimpanzee and wolverine) have been reported to develop Aβ deposits and neurofibrillary tangles in the same individual. Here, the authors demonstrate the spontaneous occurrence of Aβ deposits and neurofibrillary tangles in captive cheetahs (Acinonyx jubatus). Among 22 cheetahs examined in this study, Aβ deposits were observed in 13. Immunostaining (AT8) revealed abnormal intracellular tau immunoreactivity in 10 of the cheetahs with Aβ deposits, and they were mainly distributed in the parahippocampal cortex and CA1 in a fashion similar to that in human patients with Alzheimer disease. Ultrastructurally, bundles of straight filaments filled the neuronal somata and axons, consistent with tangles. Interestingly, 2 of the cheetahs with the most severe abnormal tau immunoreactivity showed clinical cognitive dysfunction. The authors conclude that cheetahs spontaneously develop age-related neurodegenerative disease with pathologic changes similar to Alzheimer disease. [ABSTRACT FROM PUBLISHER]

Purpose: To determine the involvement of c-Jun NH[sub 2]-terminal kinase-1 (JNK1) and possibly of HSP27 in heat-induced apoptosis of human monoblastic leukaemia U937 cells. Materials and methods: Dominant negative JNK1 (APF), in which the phosphorylation sites Thr-Pro-Tyr were changed to Ala-ProPhe, was overexpressed in U937 cells. Cell viability and DNA fragmentation were analysed by the erythrosin-B dye exclusion test and by agarose gel electrophoresis, respectively. Expression of activated caspase-9, phosphorylated JNK1, JNK2, p38 and HSP27 was examined by Western blotting. JNK1 kinase assay was also performed using c-Jun as a substrate. Results: Loss of viability, activated cleavage form of caspase-9 and DNA fragmentation were rapid in U937 cells after 44°C hyperthermia, while overexpression of dominant negative JNK1 interfered with phosphorylation or activation of JNK1 without avecting that of JNK2 or p38/SAPK, and apparently delayed or reduced cleavage and activation of caspase-9, DNA fragmentation and cell death. Heat-induced phosphorylation of HSP27, observed in parental U937 cells, was suppressed and only slightly detectable in jnk1 mutant cells. Conclusions: Prolonged phosphorylation or activation of JNK1 was considered important for heat-induced apoptosis and JNK1 may control the process possibly through phosphorylation of HSP27 and caspase-9 activation in U937 cells. [ABSTRACT FROM AUTHOR]

In the present study, covalently bound lipids were found in clavus material and their lipid classes were determined by high-performance thin-layer chromatography (HPTLC). Clavus material, pulverized completely in a Mikro-Dismembrator II, was exhaustively extracted three times with chloroform/methanol (2∶1, 1∶1 and 1∶2 v/v) at 80‡C for l h each time and this sequence of extractions was repeated to obtain the unbound lipid-free residue which was saponified and then extracted with chloroform. The extract proved to comprise several bands of lipids covalently bound through an ester-like linkage. These were identified as free fatty acids, cholesterol, ceramides and glucocerebrosides by HPTLC. However, Ω-hydroxy fatty acids were not detected in the lipids. To analyse the fatty acids amide-linked to the bound ceramides, the latter were isolated by preparative HPTLC and subjected to mild acid hydrolysis. Since the bound ceramides constituted neither Ω-hydroxy fatty acids nor α-hydroxy fatty acids, they were not identified as hydroxyl-acylsphingosines. [ABSTRACT FROM AUTHOR]

Objective: This study examined the experiences of multidisciplinary medical professionals in providing daily clinical care for patients with amyotrophic lateral sclerosis (ALS), with a focus placed on their persistence in sustaining clinical care for this patient group., Methods: A questionnaire survey was administered to multidisciplinary medical professionals involved in ALS care at three hospitals in western Kanagawa Prefecture, Japan. The questionnaire results were used to examine the relationships between years of medical experience, years of ALS care experience, self-evaluation, and motivation to continue providing clinical care to patients with ALS., Results: Of the 269 questionnaires distributed and 164 collected by the multidisciplinary medical professionals, 143 (53%) were deemed valid. Analysis revealed an association between "years of medical experience" with both "self-assessment of clinical care for ALS patients practice experience" and "commitment to continue clinical care for ALS patients," as well as between "years of ALS medical experience" and "self-assessment of clinical care for ALS patients.", Conclusion: Medical professionals with more than ten years of medical experience expressed their commitment to continue providing medical care in a comprehensive self-assessment of both the positive and negative aspects of their practice. Negative evaluations can be used to identify and improve ALS medical practices.

Previous studies of motility at low temperatures in Chlamydomonas reinhardtii have been conducted at temperatures of up to 15 °C. In this study, we report that C. reinhardtii exhibits unique motility at a lower temperature range (-8.7 to 1.7 °C). Cell motility was recorded using four low-cost, easy-to-operate observation systems. Fast Fourier transform (FFT) analysis at room temperature (20-27 °C) showed that the main peak frequency of oscillations ranged from 44 to 61 Hz, which is consistent with the 60 Hz beat frequency of flagella. At lower temperatures, swimming velocity decreased with decreasing temperature. The results of the FFT analysis showed that the major peak shifted to the 5-18 Hz range, suggesting that the flagellar beat frequency was decreasing. The FFT spectra had distinct major peaks in both temperature ranges, indicating that the oscillations were regular. This was not affected by the wavelength of the observation light source (white, red, green or blue LED) or the environmental spatial scale of the cells. In contrast, cells in a highly viscous (3.5 mPa·s) culture at room temperature showed numerous peaks in the 0-200 Hz frequency band, indicating that the oscillations were irregular. These findings contribute to a better understanding of motility under lower-temperature conditions in C. reinhardtii .

Background: Adjuvant durvalumab after chemoradiation has become the standard of care for patients with stage III NSCLC, according to the PACIFIC trial. Whether biomarkers before durvalumab for patients with stage III NSCLC showed predictive and prognostic effects remains unknown., Methods: This is a retrospective study in the Fujieda Municipal General Hospital between October 2018 and March 2022. We assessed the predictive value of the Prognostic Nutritional Index (PNI) in stage III non-small cell lung cancer (NSCLC) patients treated with durvalumab after chemoradiation., Results: After applying the inclusion and exclusion criteria, the study included 56 patients for further analysis. The median follow-up period was 17.6 months (range, 3.0-45.4 months). According to receiver operating characteristic curve results, the PNI cutoff value to predict overall survival (OS) was 37.9, with sensitivity and specificity at 67.9% and 67.9%. Accordingly, the patients were divided into low- and high-PNI groups. Patients with the low-PNI group had a significantly shorter progression-free survival compared to the high-PNI group (median, 9.1 vs. 21.3 months, p  = 0.032). OS was also shorter in the low-PNI group (median, 19.0 months vs. not reached, p  < 0.001). In the multivariate Cox hazards regression analyses, the high-PNI was an independent prognostic factor for OS (hazard ratio, 0.187; 95% confidence interval, 0.046-0.760; p  = 0.019)., It seems that PNI could be used as a predictor for OS in patients with stage III NSCLC treated with durvalumab after chemoradiation.KEY MESSAGESInadequate immunocompetence and nutritional status after chemoradiation therapy may result in poor antitumor efficacy of ICIs.Pretreatment immune and nutritional assessment using PNI could be considered an independent predictor for the survival of stage III NSCLC patients treated with durvalumab after chemoradiation therapy.

Thyroid hormones play a critical role in the initiation of the sensitive period of filial imprinting. The amount of thyroid hormones in the brains of chicks increases intrinsically during the late embryonic stages and peaks immediately before hatching. After hatching, a rapid imprinting-dependent inflow of circulating thyroid hormones into the brain occurs via vascular endothelial cells during imprinting training. In our previous study, inhibition of hormonal inflow impeded imprinting, indicating that the learning-dependent inflow of thyroid hormones after hatching is critical for the acquisition of imprinting. However, it remained unclear whether the intrinsic thyroid hormone level just before hatching affects imprinting. Here, we examined the effect of temporal thyroid hormone decrease on embryonic day 20 on approach behavior during imprinting training and preference for the imprinting object. To this end, methimazole (MMI; a thyroid hormone biosynthesis inhibitor) was administered to the embryos once a day on days 18-20. Serum thyroxine (T 4 ) was measured to evaluate the effect of MMI. In the MMI-administered embryos, the T 4 concentration was transiently reduced on embryonic day 20 but recovered to the control level on post-hatch day 0. At the beginning of imprinting training on post-hatch day 1, control chicks approached the imprinting object only when the object was moving. In the late phase of training, control chicks subsequently approached towards the static imprinting object. On the other hand, in the MMI-administered chicks, the approach behavior decreased during the repeated trials in the training, and the behavioral responses to the imprinting object were significantly lower than those of control chicks. This indicates that their persistent responses to the imprinting object were impeded by a temporal thyroid hormone decrease just before hatching. Consequently, the preference scores of MMI-administered chicks were significantly lower than those of control chicks. Furthermore, the preference score on the test was significantly correlated with the behavioral responses to the static imprinting object in the training. These results indicate that the intrinsic thyroid hormone level immediately before hatching is crucial for the learning process of imprinting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Serizawa, Aoki, Mori, Fujita, Yamaguchi, Matsushima and Homma.)

Serotonin (5-hydroxytryptamine, 5-HT) is a phylogenetically conserved modulator of numerous aspects of neural functions. Serotonergic neurons in the dorsal and median raphe nucleus provide ascending innervation to the entire forebrain and midbrain. Another important neural modulatory system exists in the midbrain, the dopaminergic system, which is associated to reward processing and motivation control. Dopaminergic neurons are distributed and clustered in the brain, classically designated as groups A8-A16. Among them, groups A8-A10 associated with reward processing and motivation control are located in the midbrain and projected to the forebrain. Recently, midbrain dopaminergic neurons were shown to be innervated by serotonergic neurons and modulated by 5-HT, with the crosstalk between serotonergic and dopaminergic systems attracting increased attention. In birds, previous studies revealed that midbrain dopaminergic neurons are located in the A8-A10 homologous clusters. However, the detailed distribution of dopaminergic neurons and the crosstalk between serotonergic and dopaminergic systems in the bird are poorly understood. To improve the understanding of the regulation of the dopaminergic by the serotonergic system, we performed in situ hybridization in the chick brainstem. We prepared RNA probes for chick orthologues of dopaminergic neuron-related genes; tyrosine hydroxylase ( TH ) and dopa decarboxylase ( DDC ), noradrenaline related genes; noradrenaline transporter ( NAT ) and dopamine beta-hydroxylase ( DBH ), and serotonin receptor genes; 5-HTR1A , 5-HTR1B , 5-HTR1D , 5-HTR1E , 5-HTR1F , 5-HTR2A , 5-HTR2B , 5-HTR2C , 5-HTR3A , 5-HTR4 , 5-HTR5A , and 5-HTR7. We confirmed that the expression of tyrosine hydroxylase (TH) and NAT was well matched in all chick dopaminergic nuclei examined. This supported that the compensation of the function of dopamine transporter (DAT) by NAT is a general property of avian dopaminergic neurons. Furthermore, we showed that 5-HTR1A and 5-HTR1B were expressed in midbrain dopaminergic nuclei, suggesting the serotonergic regulation of the dopaminergic system via these receptors in chicks. Our findings will help us understand the interactions between the dopaminergic and serotonergic systems in birds at the molecular level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujita, Aoki, Mori, Serizawa, Kihara-Negishi, Homma and Yamaguchi.)

Species delimitation within the genus Goodyera is challenging among closely related species, because of phenotypic plasticity, ecological variation, and hybridization that confound identification methods based solely on morphology. In this study, we investigated the identity of Goodyeracrassifolia H.-J.Suh, S.-W.Seo, S.-H.Oh & T.Yukawa, morphologically similar to Goodyeraschlechtendaliana Rchb.f. This recently described taxon has long been known in Japan as "Oh-miyama-uzura" or "Gakunan" and considered a natural hybrid of G.schlechtendaliana and G.similis Blume (= G.velutina Maxim. ex Regel). Because the natural hybrid between G.schlechtendaliana and G.similis was described as G.×tamnaensis N.S.Lee, K.S.Lee, S.H.Yeau & C.S.Lee before the description of G.crassifolia , the latter might be a synonym of G.×tamnaensis . Consequently, we investigated species boundaries and evolutionary history of G.crassifolia and its closely related taxa based on multifaceted evidence. Consequently, morphological examination enabled us to distinguish G.crassifolia from other closely related species owing to the following characteristics: coriaceous leaf texture, laxly flowered inflorescence, long pedicellate ovary, large and weakly opened flowers, and column with lateral appendages. Ecological investigation indicates that G.crassifolia (2 n = 60) is agamospermous, requiring neither pollinators nor autonomous self-pollination for fruit set, whereas G.schlechtendaliana (2 n = 30) is neither autogamous nor agamospermous but is obligately pollinator-dependent. MIG-seq-based phylogenetic analysis provided no evidence of recent hybridization between G.crassifolia and its close congeners. Thus, molecular phylogeny reconstructed from MIG-seq data together with morphological, cytological, and ecological analyses support the separation of G.crassifolia as an independent species., (Kenji Suetsugu, Shun K. Hirota, Narumi Nakato, Yoshihisa Suyama, Shunsuke Serizawa.)

Muscarinic acetylcholine receptors (mAChRs) play an important role in many brain functions. Our previous study revealed that the injection of mAChRs antagonist scopolamine into the intermediate medial mesopallium (IMM) region, which is critical for filial imprinting, impairs memory formation. In avian brains, four mAChR subtypes have been identified (M 2 , M 3 , M 4 and M 5 ). M 3 and M 5 receptors increase the excitability of neurons, whereas M 2 and M 4 receptors reduce the excitability. Because the scopolamine blocks all subtypes, the previous study did not identify which subtype contributes to the memory formation. By injecting several types of mAChR antagonists into the IMM, in this study we determined which mAChR subtype plays a critical role in imprinting. First, the effects of antagonists on the excitatory receptor subtypes M 3 and M 5 were examined. Injection of the M 3 antagonist (DAU5884) at 20 mM or the M 5 antagonist (ML381) at 2 mM impaired imprinting. Considering the pKi value of DAU5884, the impairment seems to be caused by DAU5884 binding to M 3 and/or M 4 receptors. Second, the effect of antagonists on the inhibitory receptor subtype M 2 was examined. The results showed that the M 2 antagonist (AQ-RA741) impaired imprinting at a concentration of 20 mM. Considering the pKi value of AQ-RA741, the impairment seems to be caused by AQ-RA741 binding to M 2 and/or M 4. The findings of this study suggests that the excitatory receptor subtypes M 3 and M 5 and the inhibitory receptor subtype M 2 and/or M 4 cooperate to achieve the appropriate balance of acetylcholine signaling to execute imprinting., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In filial imprinting, newly hatched chicks repeatedly approach a conspicuous object nearby and memorize it, even though it is an artificial object instead of their mother hen. Imprinting on an artificial object in a laboratory setting has a clear sensitive period from post hatch days 1-3 in the case of domestic chicks. However, the establishment of imprintability are difficult to investigate because of the limitations of the behavioral apparatus. In this study, we developed a novel behavioral apparatus, based on a running disc, to investigate the learning processes of imprinting in newly hatched domestic chicks. In the apparatus, the chick repeatedly approaches the imprinting object on the disc. The apparatus sends a transistor-transistor-logic signal every 1/10 turn of the disc to a personal computer through a data acquisition system following the chick's approach to the imprinting object on the monitor. The imprinting training and tests were designed to define the three learning processes in imprinting. The first process is the one in which chicks spontaneously approach the moving object. The second is an acquired process in which chicks approach an object even when it is static. In the third process, chicks discriminate between the differently colored imprinting object and the control object in the preference test. Using the apparatus, the difference in the chicks' behavior during or after the sensitive period was examined. During the sensitive period, the chicks at post hatch hour 12 and 18 developed the first imprinting training process. The chicks at post hatch hour 24 maintained learning until the second process. The chicks at post hatch hour 30 reached the discrimination process in the test. After the sensitive period, the chicks reared in darkness until post hatch day 4 exhibited poor first learning process in the training. Thus, this apparatus will be useful for the detection of behavioral changes during neuronal development and learning processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Aoki, Mori, Fujita, Serizawa, Yamaguchi, Matsushima and Homma.)

Microalgae in the Middle East can theoretically address food security without competing for arable land, but concerns exist around scalability and durability of production systems under the extreme heat. Large-scale Chlorella sorokiniana production was developed in outdoor raceway ponds in Oman and monitored for 2 years to gather data for commercial production. Biological and technical challenges included construction, indoor/outdoor preculturing, upscaling, relating productivity to water temperature and meteorological conditions, harvesting, drying, and quality control. Small cultivation systems required cooling for initial scale-up, but, despite maximum temperatures of 49.7 °C, water temperatures were at acceptable levels by evaporative cooling in larger raceway ponds. Contamination with Vampirovibrio chlorellavorus was identified by 16S rDNA amplicon sequencing and addressed by culture replacement. Productivities ranged from 8 to 30 g-dry weight m -2 d -1 , with estimated annual productivity of 16 g-dry weight m -2 d -1 as functions of solar intensity and water temperature, confirming that the region is suitable for commercial microalgae production., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A 46-year-old woman was diagnosed with acute promyelocytic leukemia (APL). The patient was given remission induction therapy with all-trans retinoic acid, and complete remission was achieved. Despite consolidation therapies with arsenic trioxide, daunorubicin and cytosine arabinoside (AraC), and gemtuzumab ozogamicin as well as maintenance therapy with tamibarotene, the patient experienced a relapse 6 months after the start of maintenance therapy. She was then given re-induction therapy with idarubicin+AraC and high-dose AraC, but remission was not achieved. Since the coordination of the unrelated donor had been completed at this time, she then underwent bone marrow transplantation with pre-conditioning of 4 Gy total body irradiation, fludarabine, and busulfan. However, on the 12th day after the transplantation, APL cells appeared in the peripheral blood and the disease progressed rapidly leading to the patient's death on the 15th day after the transplantation. APL usually has a good prognosis, and relapsed cases are often cured by autologous stem cell transplantation. However, this case was highly refractory to treatment and the patient deteriorated rapidly after the transplantation, suggesting a different pathogenesis from the usual from of APL.

The Japanese Lepisorus thunbergianus complex contains diploid and tetraploid races of L. thunbergianus and a hexaploid species, L. mikawanus. Here, we performed molecular phylogenetic analysis on this complex to delimit species and to elucidate the evolutionary origins of tetraploid and hexaploid species. Chloroplast DNA (cpDNA) phylogeny supported the monophyly of the complex. Based on a single-copy nuclear gene (PgiC) tree, the tetraploid L. thunbergianus samples could be classified into two variants: an allotetraploid of hybrid origin between diploid L. thunbergianus and Japanese L. angustus and another allotetraploid of hybrid origin between diploid L. thunbergianus and an unknown diploid race of L. tosaensis. These variants can be recognized morphologically and distinguished from their parent species. Hence, here we described these allopolyploids as new species, L. nigripes and L. kuratae, respectively. The hexaploid species L. mikawanus has three types of PgiC alleles, each of which was derived from diploid L. thunbergianus, L. tosaensis, and Japanese L. angustus, while cpDNA shows that it is included in Japanese L. thunbergianus clade. Based on the cpDNA phylogeny and PgiC nucleotide sequences, we therefore concluded that L. mikawanus is an allohexaploid that originated through hybridization between tetraploid species, L. nigripes and an unknown ancestral diploid race of L. tosaensis.

In pesticide risk management in Japan, predicted environmental concentrations are estimated by a tiered approach, and the Ministry of the Environment also performs field surveys to confirm the maximum concentrations of pesticides with risk concerns. To contribute to more efficient and effective field surveys, we developed the Pesticide Chemicals High Resolution Estimation Method (PeCHREM) for estimating spatially and temporally variable emissions of various paddy herbicides from paddy fields to the environment. We used PeCHREM and the G-CIEMS multimedia environmental fate model to predict day-to-day environmental concentration changes of 25 herbicides throughout Japan. To validate the PeCHREM/G-CIEMS model, we also conducted a field survey, in which river waters were sampled at least once every two weeks at seven sites in six prefectures from April to July 2009. In 20 of 139 sampling site-herbicide combinations in which herbicides were detected in at least three samples, all observed concentrations differed from the corresponding prediction by less than one order of magnitude. We also compared peak concentrations and the dates on which the concentrations reached peak values (peak dates) between predictions and observations. The peak concentration differences between predictions and observations were less than one order of magnitude in 66% of the 166 sampling site-herbicide combinations in which herbicide was detected in river water. The observed and predicted peak dates differed by less than two weeks in 79% of these 166 combinations. These results confirm that the PeCHREM/G-CIEMS model can improve the efficiency and effectiveness of surveys by predicting the peak concentrations and peak dates of various herbicides.

We determined the respiratory uptake and depuration kinetics of perfluorooctanesulfonate (PFOS) in Perinereis wilsoni, a polychaete sandworm used as a model species to investigate the fate of chemical pollutants in coastal environments. The sandworms were kept in gravel-packed containers, and the water levels were varied cyclically to mimic the tides. We used seawater kept at 17.1°C. A 7-day exposure period was followed by a 9-day depuration period. The dissolved PFOS concentration averaged 28 ng/L during the exposure period. Sandworm samples were collected regularly for analysis of PFOS concentrations, and a first-order-kinetics model was applied to the concentrations. The respiratory absorption efficiency of PFOS was estimated to be 11% that of oxygen, which is higher than the corresponding estimates reported for several fish species. The estimated depuration half-life of 15 days was comparable to previously reported estimates for fish and oligochaete species. The bioconcentration factor was 470.