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Background Atypical sensory behavior disrupts behavioral adaptation in children with autism spectrum disorder (ASD); however, neural correlates of sensory dysfunction using magnetoencephalography (MEG) remain unclear. Method We used MEG to measure the cortical activation elicited by visual (uni)/audiovisual (multisensory) movies in 46 children (7–14 years) were included in final analysis: 13 boys with atypical audiovisual behavior in ASD (AAV+), 10 without this condition, and 23 age-matched typically developing boys. Results The AAV+ group demonstrated an increase in the cortical activation in the bilateral insula in response to unisensory movies and in the left occipital, right superior temporal sulcus (rSTS), and temporal regions to multisensory movies. These increased responses were correlated with severity of the sensory impairment. Increased theta-low gamma oscillations were observed in the rSTS in AAV+. Conclusion The findings suggest that AAV is attributed to atypical neural networks centered on the rSTS.

Objective Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments. Methods We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information. Results We identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI. Conclusion Our patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.

Neuroinflammation contributes to the severity of various neurological disorders, including epilepsy. Tuberous sclerosis complex (TSC) is a condition that results in the overactivation of the mammalian target of rapamycin (mTOR) pathway, which has been linked to the activation of microglia responsible for neuroinflammation. To clarify the involvement of neuroinflammation in the neuropathophysiology of TSC, we performed a positron emission tomography (PET) study using the translocator protein (TSPO) radioligand, [This cross-sectional study included 18 patients with TSC (6 in the no-seizure group, 6 in the refractory seizure group, and 6 in the mTOR-inhibitor [mTOR-i] group). All participants underwent [Most cortical tubers with hyperintensity on FLAIR and hypo- or isointensity on T1WI showed microglial activation. The extent of microglial activation was significantly greater in the refractory seizure group than in the no-seizure or mTOR-i groups (p 0.001). The extent of microglial activation in subjects without mTOR-i treatment correlated positively with epilepsy severity (r = 0.822, P = 0.001) and negatively with cognitive function (r = -0.846, p = 0.001), but these correlations were not present in the mTOR-i group (r = 0.232, P = 0.658, r = 0.371, P = 0.469, respectively).Neuroinflammation is associated with the severity of epilepsy and cognitive dysfunction in brains with TSC. mTOR-i may suppress the extent of neuroinflammation in TSC. Investigating the spread of microglial activation using TSPO-PET in these patients may help to predict the progression of neuropathy by assessing the degree of neuroinflammation and therefore be useful for determining how aggressive the treatment should be and in assessing the effectiveness of such treatment in patients with TSC.

The bitterling Tanakia lanceolata is a primary freshwater fish with wide distribution range in Japan; therefore, analysis of this species will yield much information on the formation of Japanese freshwater fish fauna. However, populations of this species are threatened by several human activities. To reveal the genetic population structure of T. lanceolata and the process of its formation, as well as its genetic status, we conducted phylogenetic analyses and estimated divergence times based on partial sequences of the mitochondrial DNA cytochrome b gene, using specimens collected across the distribution range. The results of the analysis showed that Japanese T. lanceolata is monophyletic and consists of seven local population groups that diverged from the Late Pliocene to the Middle Pleistocene. The population structure in western Japan was similar to that of other freshwater fishes (e.g., separation by the Suzuka Mountains), although there were several differences in population boundaries and the presence/absence of a secondary contact zone. The Central Highlands in central Honshu are the primary, or at least the most effective, geological barrier responsible for population divergence in Japanese freshwater fish species. However, the small genetic differentiation of the T. lanceolata population between the western and eastern sides of the Central Highlands suggested recent dispersal and gene flow across the region after uplift of the highlands. The genetic population structure indicated extensive genetic disturbance in the Kanto Region. Our results provide information on the formation process of the Japanese freshwater fish fauna, which could aid conservation efforts toward T. lanceolata.

Two new species of pike gudgeon, Pseudogobio agathonectris from western Honshu, Japan, and P. polysticta from eastern Honshu, Japan, are described, and P. esocinus (Temminck and Schlegel 1846) is redescribed. The two new species were previously considered to be P. esocinus, which had been only a nominal species of the genus from Japan. The two species are distinguishable from P. esocinus by following a combination of characters: tip of pectoral spiny soft ray not reaching that of 6th soft fin ray, and tip of outer edge of pectoral fin strongly curved posteriorly; long barbel (15.3–36.9% of HL in P. agathonectris, 16.9–34.8% in P. polysticta, respectively), with the tip commonly extending beyond vertical through anterior edge of eye; 10–14 (modally 13) and 12–14 (13) pectoral soft fin rays; long mouth (33.2–45.3% of HL and 29.6–42.0%); short length between anus and anal fin origin (16.5–21.4% of SL and 15.9–22.4%), with 11–14 (12) and 11–16 (12) scales; and small body size (at most 150 mm SL). Pseudogobio agathonectris is distinguishable from P. polysticta by the canonical discriminant functions based on five meristic and 25 morphometric characters, and distinct dark blotches and obscure black spots on dorsal and lateral body (vs. obscure blotches and many distinct spots).

ObjectiveTuberous sclerosis complex (TSC) is a genetic disease that arises from TSC1 or TSC2 abnormalities and induces the overactivation of the mammalian/mechanistic target of rapamycin pathways. The neurological symptoms of TSC include epilepsy and tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Although TAND affects TSC patients' quality of life, the specific region in the brain associated with TAND remains unknown. We examined the association between white matter microstructural abnormalities and TAND, using diffusion tensor imaging (DTI).MethodsA total of 19 subjects with TSC and 24 age-matched control subjects were enrolled. Tract-based spatial statistics (TBSS) were performed to assess group differences in fractional anisotropy (FA) between the TSC and control groups. Atlas-based association analysis was performed to reveal TAND-related white matter in subjects with TSC. Multiple linear regression was performed to evaluate the association between TAND and the DTI parameters; FA and mean diffusivity in seven target regions and projection fibers.ResultsThe TBSS showed significantly reduced FA in the right hemisphere and particularly in the inferior frontal occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), and genu of corpus callosum (CC) in the TSC group relative to the control group. In the association analysis, intellectual disability was widely associated with all target regions. In contrast, behavioral problems and autistic features were associated with the limbic system white matter and anterior limb of the internal capsule (ALIC) and CC.ConclusionThe disruption of white matter integrity may induce underconnectivity between cortical and subcortical regions. These findings suggest that TANDs are not the result of an abnormality in a specific brain region, but rather caused by connectivity dysfunction as a network disorder. This study indicates that abnormal white matter connectivity including the limbic system is relevant to TAND. The analysis of brain and behavior relationship is a feasible approach to reveal TAND related white matter and neural networks. TAND should be carefully assessed and treated at an early stage.

Testosterone deficiency is commonly observed in male patients with chronic obstructive pulmonary disease (COPD), which is characterized by chronic inflammation of the airways and pulmonary emphysema. Although clinical trials have indicated that testosterone replacement therapy can improve respiratory function in patients with COPD, the role of testosterone in the pathogenesis of COPD remains unclear. The aim of this study was to explore the effect of testosterone deficiency on the development of pulmonary emphysema in orchiectomized (ORX) mice exposed to porcine pancreatic elastase (PPE). ORX mice developed more severe emphysematous changes 21 d after PPE inhalation than non-ORX mice. Testosterone propionate supplementation significantly reduced PPE-induced emphysematous changes in ORX mice. PPE exposure also increased the number of neutrophils and T cells in bronchoalveolar lavage fluid (BALF) of mice that had undergone ORX and sham surgery. T cell counts were significantly higher in the BALF of ORX mice than of sham mice. Testosterone supplementation reduced the infiltration of T cells into BALF and alleviated emphysematous changes in the lungs of ORX mice. Our findings suggest that testosterone, a male-specific hormone, may suppress the development of pulmonary emphysema through the regulation of T cell-mediated immunity.

Objective We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs). Methods In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20–30 mg/kg/day) for 1 year, in addition to previous treatment. Results All nine enrolled patients (mean age: 66.3 ± 44.3 months) exhibited marked decreases in levels of CD16, a glycosylphosphatidylinositol-anchored protein, on blood granulocytes. The underlying genetic causes of IGDs were PIGO, PIGL, and unknown gene mutations in two, two, and five patients, respectively. Six patients experienced seizures, while all patients presented with developmental delay (mean developmental age: 11.1 ± 8.1 months). Seizure frequencies were markedly (>50%) and drastically (>90%) reduced in three and one patients who experienced seizures, respectively. None of the patients presented with seizure exacerbation. Eight of nine patients exhibited modest improvements in development (P = 0.14). No adverse events were observed except for mild transient diarrhea in one patient. Conclusion One year of daily high-dose pyridoxine treatment was effective in the treatment of seizures in more than half of our patients with IGDs and modestly improved development in the majority of them. Moreover, such treatment was reasonably safe. These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm our findings. (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number: UMIN000024185.)

The Chinese false gudgeon, Abbottina rivularis, is a common cyprinid fish that is widely distributed throughout continental East Asia, but exhibits a restricted, discontinuous distribution in western Japan, including Honshu and Kyushu islands. In this study, analyses of mitochondrial (cytochrome b) and nuclear (glyt, myh6, and RAG1) genes were conducted to investigate patterns and magnitudes of intraspecific differentiation among A. rivularis populations in Japan and adjacent continental areas. Phylogenetic analysis of the mitochondrial gene sequences resolved four major lineages—the Japan lineage (JL), a northern continental lineage (NCL), and two southern continental lineages (SCL1 and SCL2)—with uncorrected pairwise sequence distances of 9.4–15.2% (estimated divergence times, 7.9–17.1 Myr). Two lineages (JL and SCL1) occurred in both the Honshu and Kyushu districts of Japan. Compared with populations in continental areas, most Japanese populations exhibited less genetic diversity. The JL was divided into two well-differentiated sub-lineages distributed on Honshu and Kyushu islands, respectively. Kyushu Island, as well as areas on Honshu where the species is known to have been introduced, also harbored the SCL1 lineage, which constituted most of the populations on Kyushu. The applied nuclear DNA data strongly suggest that hybridization between the Japan and continental lineages has occurred on Kyushu Island. The artificial introduction hypothesis, instead of a two-origin scenario, best explains the origin of the SCL1 in Japan.

Objective Autism spectrum disorder (ASD) is a developmental disorder characterized by communication deficits and social difficulties, and individuals with ASD frequently exhibit varied levels of language abilities. However, the neurophysiological mechanisms underlying their language deficits remain unclear. To gain insight into the neurophysiological mechanisms of receptive language deficits, we assessed cortical activation patterns in adolescents with ASD during silent word-reading. Methods We used magnetoencephalography to measure cortical activation during a silent word-reading task in 14 adolescent boys with high-functioning ASD and 17 adolescent boys with typical development (TD). Results Compared with participants with TD, those with ASD exhibited significantly decreased cortical activation in the left middle temporal gyrus, left temporoparietal junction, bilateral superior temporal gyrus, left posterior insula, and right occipitotemporal gyrus, and increased activation in the right anterior insula. Participants with ASD also exhibited a lack of left-lateralization in the central sulcus and abnormal right-lateralization in the anterior insula area. Furthermore, in participants with ASD, we found that abnormal activation of the right central sulcus correlated significantly with lower visual word comprehension scores, and that decreased activation of the right anterior insula correlated significantly with the severity of social interaction difficulties. Conclusion Our findings suggest that atypical cortical activation and lateralization in the temporal-frontal area, which is associated with higher-order language processing functions, such as semantic analysis, may play a crucial role in visual word comprehension and social interaction difficulties in adolescents with ASD.

Objective The purpose of the present study was to clarify the relationship between white matter tracts and cognitive symptoms in children with high-functioning autism spectrum disorder (ASD). Methods We examined the cognitive functions of 17 children with high-functioning ASD and 18 typically developing (TD) controls and performed diffusion tensor imaging (DTI) tractography. We compared the results between the groups and investigated the correlations between the cognitive scores and DTI parameters within each group. Results The Comprehension scores in the ASD group exhibited a positive correlation with mean diffusivity (MD) in the forceps minor (F minor). In the TD group, the Comprehension scores were positively correlated with fractional anisotropy (FA) in the right inferior fronto-occipital fasciculus (IFO) and left anterior thalamic radiation (ATR), and negatively correlated with MD in the left ATR, radial diffusivity (RD) in the right IFO, and RD in the left ATR. Additionally, a positive correlation was observed between the Matching Numbers scores and MD in the left uncinate fasciculus and F minor, and RD in the F minor. Furthermore, the Sentence Questions scores exhibited a positive correlation with RD in the right inferior longitudinal fasciculus. Relative to TD controls, the specific tract showing a strong correlation with the cognitive scores was reduced in the ASD group. Conclusion Our findings indicate that white matter tracts connecting specific brain areas may exhibit a weaker relationship with cognitive functions in children with ASD, resulting in less efficient cognitive pathways than those observed in TD children.

This study investigates the use of expansion steel pipe piles for the reinforcement of relatively loose (sandy) soil under small building foundations. The expansion steel pipe piles used in this study are frequently used as rock bolts in tunnel excavation in Europe. The diameter of these pipes expands from 36 to 54 mm through the application of high‐pressure water. In this study, field load tests confirm the reinforcement effect of expansion steel pipe piles. The results can be summarized as follows: (a) The region of the surrounding soil compressed by the expansion of the piles is approximately 8 times (450 mm) the pipe diameter, as measured from the pile center. (b) The maximum friction resistance of the expansion steel pipe piles is approximately 3 times greater than that of conventional steel pipes with the same diameter. (c) The finite cavity expansion theory was used to estimate the maximum friction resistance, and the analytical results correlate strongly with the field test results.

Background Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. Methods Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. Results Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. Conclusions The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema.

Inherited GPI (glycosylphosphatidylinositol) deficiencies (IGDs), a recently defined group of diseases, show a broad spectrum of symptoms. Hyperphosphatasia mental retardation syndrome, also known as Mabry syndrome, is a type of IGDs. There are at least 26 genes involved in the biosynthesis and transport of GPI-anchored proteins; however, IGDs constitute a rare group of diseases, and correlations between the spectrum of symptoms and affected genes or the type of mutations have not been shown. Here, we report four newly identified and five previously described Japanese families with PIGO (phosphatidylinositol glycan anchor biosynthesis class O) deficiency. We show how the clinical severity of IGDs correlates with flow cytometric analysis of blood, functional analysis using a PIGO-deficient cell line, and the degree of hyperphosphatasia. The flow cytometric analysis and hyperphosphatasia are useful for IGD diagnosis, but the expression level of GPI-anchored proteins and the degree of hyperphosphatasia do not correlate, although functional studies do, with clinical severity. Compared with PIGA (phosphatidylinositol glycan anchor biosynthesis class A) deficiency, PIGO deficiency shows characteristic features, such as Hirschsprung disease, brachytelephalangy, and hyperphosphatasia. This report shows the precise spectrum of symptoms according to the severity of mutations and compares symptoms between different types of IGD.

Background: Small bowel adenocarcinoma (SBA) accounts for et al. reported 1 case of brain metastasis out of 217 SBA cases, but details of the clinical course of the case were unclear. Our case might be the first report covering the full clinical course, pathological findings, and genetic data. Here, we report a very rare case of brain metastasis from poorly differentiated SBA. Case Description: A 54-year-old man who suffered from abdominal pain and melena visited a nearby hospital. This patient had no risk factors for SBA. He underwent partial resection of the jejunum with regional lymphadenectomy and combined resection of the transverse colon. Pathological diagnosis was poorly differentiated adenocarcinoma, pT4N2M0 Stage IIIB (UICC-TNM: 8th edition). One month after curative surgery, liver metastasis was detected by a computed tomography (CT) scan, and then, palliative chemotherapy was started. During the third-line chemotherapy, a brain tumor on the left cerebellum was detected by the CT scan. Tumor resection was performed, and the histopathological features coincided with the primary jejunum tumor. Based on surgical, radiological, pathological, and genetic findings, this brain tumor was comprehensively diagnosed as a metastasis from poorly differentiated SBA. Conclusion: Here, we experienced a very rare case of brain metastasis from poorly differentiated SBA.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that causes degeneration of anterior horn cells in the human spinal cord and subsequent loss of motor neurons. The severe form of SMA is among the genetic diseases with the highest infant mortality. Although SMA has been considered incurable, newly developed drugs—nusinersen and onasemnogene abeparvovec—improve the life prognoses and motor functions of affected infants. To maximize the efficacy of these drugs, treatments should be started at the pre-symptomatic stage of SMA. Thus, newborn screening for SMA is now strongly recommended. Herein, we provide some data based on our experience of SMA diagnosis by genetic testing in Japan. A total of 515 patients suspected of having SMA or another lower motor neuron disease were tested. Among these patients, 228 were diagnosed as having SMA with survival motor neuron 1 (SMN1) deletion. We analyzed the distribution of clinical subtypes and ages at genetic testing in the SMN1-deleted patients, and estimated the SMA incidence based on data from Osaka and Hyogo prefectures, Japan. Our data showed that confirmed diagnosis by genetic testing was notably delayed, and the estimated incidence was 1 in 30,000–40,000 live births, which seemed notably lower than in other countries. These findings suggest that many diagnosis-delayed or undiagnosed cases may be present in Japan. To prevent this, newborn screening programs for SMA (SMA-NBS) need to be implemented in all Japanese prefectures. In this article, we also introduce our pilot study for SMA-NBS in Osaka Prefecture.

In this study, we analyzed long-term trends in calcium (Ca) concentrations for 70 Norwegian lakes spanning a broad geographical range and for a wide range of ambient drivers. A striking decline in Ca concentrations was observed during the past 30 yr. The trend was most pronounced in southern, previously acidified localities, while there were weaker and less consistent patterns for central and northern regions. For previously acidified areas, this observed decline in Ca is likely related to base cation depletion or reduced Ca mobilization as a consequence of reduced H2SO4-deposition. However, lower chloride concentrations, increased runoff and forest density (represented by Normalized Difference Vegetation Index, NDVI) also exerted strong negative impacts on Ca-concentrations. For lakes with a significant negative trend (n = 34), the average decline was −11.05% per decade, corresponding to −0.023 mg Ca L−1 yr−1. This trend may pull levels of Ca in these already Ca-deficient poor lakes toward, or below, critically low levels for a range of organisms. A somewhat paradoxical effect of the successful battle against anthropogenic acidification is thus that it may impose an increased Ca-deficiency of freshwater ecosystems.

To elucidate the origins of the endemic fish of Lake Biwa, an ancient lake in Japan, and the role of the lake in the diversification of freshwater fish in western Japan, we established a molecular phylogenetic framework with an absolute time scale and inferred the historical demography of a large set of fish species in and around the lake. We used mtDNA sequences obtained from a total of 190 specimens, including 11 endemic species of Lake Biwa and their related species, for phylogenetic analyses with divergence time estimations and from a total of 2319 specimens of 42 species (including 14 endemics) occurring in the lake for population genetic analyses. Phylogenetic analysis suggested that some of the endemic species diverged from their closest relatives earlier (1.3–13.0 Ma) than the period in which the present environmental characteristics of the lake started to develop (ca. 0.4 Ma), whereas others diverged more recently (after 0.4 Ma). In contrast, historical demographic parameters suggested that almost all species, including endemic and nonendemic ones, expanded their populations after the development of the present lake environment. In phylogeographic analyses, common or very close haplotypes of some species were obtained from Lake Biwa and other regions of western Japan. The phylogenetic and historical demographic evidence suggests that there was a time lag between phylogenetic divergence and population establishment and that phenotypic adaptation of some endemic species to the limnetic environment occurred much later than the divergences of those endemic lineages. Population structure and phylogeographic patterns suggest that Lake Biwa has functioned not only as the center of adaptive evolution but also as a reservoir for fish diversity in western Japan.

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene which encodes dystrophin protein. Dystrophin defect affects cardiac muscle as well as skeletal muscle. Cardiac dysfunction is observed in all patients with DMD over 18 years of age, but there is no curative treatment for DMD cardiomyopathy. To establish novel experimental platforms which reproduce the cardiac phenotype of DMD patients, here we established iPS cell lines from T lymphocytes donated from two DMD patients, with a protocol using Sendai virus vectors. We successfully conducted the differentiation of the DMD patient-specific iPS cells into beating cardiomyocytes. DMD patient-specific iPS cells and iPS cell-derived cardiomyocytes would be a useful in vitro experimental system with which to investigate DMD cardiomyopathy.

Boreal lakes are impacted by climate change, reduced acid deposition, and changing loads of dissolved organic carbon (DOC) from catchments. We explored, using the process-based lake model MyLake, how changes in these pressures modulate ice phenology and the dissolved oxygen concentrations (DO) of a small boreal humic lake. The model was parametrized against year-round time series of water temperature and DO from a lake buoy. Observed trends in air temperature (+0.045°C yr−1) and DOC concentration (0.11 mg C L−1 yr−1, +1% annually) over the past 40 years were used as model forcings. A backcast of ice freezing and breakup dates revealed that ice breakup occurred on average 8 days earlier in 2014 than in 1974. The earlier ice breakup enhanced water column ventilation resulting in higher DO in the spring. Warmer water in late summer led to longer anoxic periods, as microbial DOC turnover increased. A long-term increase in DOC concentrations caused a decline in lake DO, leading to 15% more hypoxic days (

To reveal the primary historical events that affected the geographic differentiation in freshwater organisms in the Japanese archipelago, we investigated the phylogeny and phylogeographic structure of the widely distributed freshwater fish Pseudogobio esocinus. We conducted comprehensive phylogeographic analyses based on partial sequences of the mitochondrial DNA cytochrome b (cyt b) gene in 1,212 P. esocinus specimens from 201 locations in 136 river systems along with sequence data from related species. We also examined the entire cyt b sequence and three nuclear gene sequences for a subset of individuals to estimate the phylogenetic relationships and divergence times. Historical processes shaping the present phylogeographic patterns were inferred by the Bayesian skyline plot, mismatch distribution and nested clade phylogeographic analyses. The mitochondrial and nuclear DNA phylogenies showed that the Japanese P. esocinus was not monophyletic and consisted of three largely differentiated groups. Divided by the Central Highlands, two groups were distributed in southwestern Japan, with a third group in northeastern Japan. The estimated divergence time indicated that the framework of the present ranges of the three groups was formed during or before the Early Pliocene. In southwestern Japan, the two groups often occurred sympatrically and included several regional subgroups bounded by major mountain systems uplifted in the early Pleistocene, while in the northeastern Japanese group, recent (since about 0.3 million years ago) range expansion from the northwestern area was inferred. The results suggest the importance of the uplifting of the Central Highlands and interconnection with the continental area in the distribution and divergence of P. esocinus, which may have also influenced regional heterogeneity in the Japanese freshwater fauna. The contrasting phylogeographic patterns between northeastern and southwestern Japan probably reflect their topographic and geohistorical differences, and imply differences in the formation process of freshwater fauna between the two regions.

Natural stochasticity can pose challenges in managing the quality of the environment, or hinder understanding of the system structure. It is problematic because unfavourable stochastic events cancel management efforts and because a favourable stochastic event may overestimate perceived success. This paper presents a variance-based modelling method that can be used to quantify the extent to which natural stochasticity can affect the target environment. We use a case study of a eutrophication assessment of a Norwegian lake, Årungen, using a lake model, MyLake, in order to present the method, and to investigate how this method could assist in answering scientific and management questions. Here we contrasted two effects of nutrient loading in runoff (partially controllable by policies) and meteorology (purely natural stochastic events), illustrated in the case study, in order to achieve the season-by-season quantification of mutually confounding factors of stochastic events. The results indicate that, for example, variation in runoff volume was most prevalent during autumn and winter, while variation in phosphorus inflow was most extensive from late winter to early spring. Thermal-related properties in the lake were well predicted by the model, and showed that the time of thermocline formation varied among years by more than 1 month, from mid-April to mid-May, whereas loading was the most important factor for phytoplankton biomass and water transparency. Mild winters and greater inputs of suspended matter and phosphorus were followed by increased phytoplankton biomass and light attenuation. These findings also suggest that future changes in the global climate may have important implications for local water management decision-making. The present method of disentangling mutually confounding factors is not limited to lake water quality studies and may also provide utility in other types of aquatic system modelling.

Objective: To determine the prognostic factors for encephalopathy with bright tree appearance (BTA) in the acute phase through retrospective case evaluation. Methods: We recruited 10 children with encephalopathy who presented with BTA and classified them into 2 groups. Six patients with evident regression and severe psychomotor developmental delay after encephalopathy were included in the severe group, while the remaining 4 patients with mild mental retardation were included in the mild group. We retrospectively analyzed their clinical symptoms, laboratory data, and magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings. Results: Patients in the severe group developed subsequent complications such as epilepsy and severe motor impairment. Univariate analysis revealed that higher maximum lactate dehydrogenase (LDH) levels (p = 0.055) were a weak predictor of poor outcome. Maximum creatinine levels were significantly higher (p < 0.05) and minimal platelet counts were significantly lower (p < 0.05) in the severe group than in the mild group. Acute renal failure was not observed in any patient throughout the study. MRS of the BTA lesion during the BTA period showed elevated lactate levels in 5 children in the severe group and 1 child in the mild group. MRI performed during the chronic phase revealed severe brain atrophy in all patients in the severe group. Conclusions: Higher creatinine and LDH levels and lower platelet counts in the acute phase correlated with poor prognosis. Increased lactate levels in the BTA lesion during the BTA period on MRS may predict severe physical and mental disability.

Objective Individuals with autism spectrum disorder (ASD) often show characteristic differences in auditory processing. To clarify the mechanisms underlying communication impairment in ASD, we examined auditory language processing with both anatomical and functional methods. Methods We assessed the language abilities of adolescents with ASD and typically developing (TD) adolescents, and analyzed the surface-based morphometric structure between the groups using magnetic resonance imaging. Furthermore, we measured cortical responses to an auditory word comprehension task with magnetoencephalography and performed network-based statistics using the phase locking values. Results We observed no structural differences between the groups. However, the volume of the left ventral central sulcus (vCS) showed a significant correlation with linguistic scores in ASD. Moreover, adolescents with ASD showed weaker cortical activation in the left vCS and superior temporal sulcus. Furthermore, these regions showed differential correlations with linguistic scores between the groups. Moreover, the ASD group had an atypical gamma band (25–40 Hz) network centered on the left vCS. Conclusions Adolescents with ASD showed atypical responses on the auditory word comprehension task and functional brain differences. Significance Our results suggest that phonological processing and gamma band cortical activity play a critical role in auditory language processing-related pathophysiology in adolescents with ASD.

The genetic population structure of the small cyprinid Hemigrammocypris rasborella, distributed widely in lowlands of western Japan, was examined using partial sequence data of mitochondrial DNA (mtDNA). Molecular phylogenetic analysis revealed that the populations of the western Kyushu region were markedly differentiated from all eastern populations, such that the groups would be comparable to different species; their divergence was inferred to have occurred in the Late Miocene–Pliocene. Also, a largely divergent mtDNA group (with divergence in the early Pleistocene) was found in the Sanyo and northeastern Shikoku regions, forming a secondary contact zone in the western Kinki with the eastern mtDNA group. To date, these aspects of the population structure of H. rasborella appear to be unique among lowland fishes in western Japan. Deeper understanding of the formation processes of freshwater faunas in western Japan will require further comparisons of the phylogeographic patterns and ecological traits of constituent species.

A model network comprising climate models, a hydrological model, a catchment-scale model for phosphorus biogeochemistry, and a lake thermodynamics and plankton dynamics model was used to simulate phosphorus loadings, total phosphorus and chlorophyll concentrations in Lake Vansjø, Southern Norway. The model network was automatically calibrated against time series of hydrological, chemical and biological observations in the inflowing river and in the lake itself using a Markov Chain Monte-Carlo (MCMC) algorithm. Climate projections from three global climate models (GCM: HadRM3, ECHAM5r3 and BCM) were used. The GCM model HadRM3 predicted the highest increase in temperature and precipitation and yielded the highest increase in total phosphorus and chlorophyll concentrations in the lake basin over the scenario period of 2031–2060. Despite the significant impact of climate change on these aspects of water quality, it is minimal when compared to the much larger effect of changes in land-use. The results suggest that implementing realistic abatement measures will remain a viable approach to improving water quality in the context of climate change.

Interstitial deletions of chromosome 3 are rare, and only one patient with a microdeletion of 3p21.31 has been reported to date. We identified two additional cases of patients with microdeletions of 3p21.31. The characteristic clinical features of developmental delay and distinctive facial features (including arched eyebrows, hypertelorism, epicanthus, and micrognathia) were seen both in the previously reported patient and in the two newly identified patients. In these two new cases, additional features, including elevated serum creatine kinase levels and characteristic neuroradiological features with white matter involvement, were seen. These features had not been described in the previous case in which the patient was examined during infancy, suggesting an age-dependent mechanism. The shortest region of overlap among the three deletions narrowed down the candidate genes that may be responsible for the common neurological features to the bassoon (presynaptic cytomatrix protein) gene (BSN), which has an important function in neuronal synapses. In this study, we confirmed common phenotypic features in the patients with microdeletions of 3p21.31 and identified additional features that have not been reported previously. Because the constellation of such characteristic features is quite unique, clinical manifestations of the patients with microdeletions of 3p21.31 would be clinically recognizable as a contiguous gene deletion syndrome. © 2013 Wiley Periodicals, Inc.