Microenvironmental changes in familial adenomatous polyposis during colorectal cancer carcinogenesis.

Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8+ T cells became exhausted only in carcinoma, although the cytotoxicity of CD8+ T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.

Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer.

BACKGROUND: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. METHODS: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. RESULTS: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3- M-MDSCs and were abundant in treatment-resistant GC patients. CONCLUSIONS: The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

Effects of human depopulation and warming climate on bird populations in Japan.

Quantifying biodiversity trends in economically developed countries, where depopulation, associated secondary succession, and climate warming are ongoing, provides insights for global biodiversity conservation in the 21st century. However, few studies have assessed the impacts of secondary succession and climate warming on species' population trends at a national scale. We estimated the population trends of common breeding bird species in Japan and examined the associations between the overall population trend and species traits with the nationwide bird count data on 47 species collected from 2009 to 2020. The overall population trend varied among species. Four species populations increased moderately, 18 were stable, and 11 declined moderately. Population trends for 13 species were uncertain. The difference in overall trends among the species was associated with their habitat group and temperature niche. Species with relatively low-temperature niches experienced more pronounced declines. Multispecies indicators showed a moderate increase in forest specialists and moderate declines in forest generalists (species that use both forests and open habitats) and open-habitat specialists. Forest generalists and open-habitat specialists also declined more rapidly at sites with more abandoned farmland. All species groups showed an accelerated decline or decelerated increase after 2015. These results suggest that common breeding birds in Japan are facing deteriorating trends as a result of nationwide changes in land use and climate. Future land-use planning and policies should consider the benefits of passive rewilding for forest specialists and active restoration measures (e.g., low-intensive forestry and agriculture) for nonforest specialists to effectively conserve biodiversity in the era of human depopulation and climate warming.

Efectos de la despoblación humana y el calentamiento climático sobre las poblaciones de aves en Japón Resumen La cuantificación de las tendencias poblacionales en los países económicamente desarrollados, en donde la despoblación (asociada a la sucesión secundaria) y el cambio climático son continuos, proporciona información para la conservación mundial de la biodiversidad en el siglo XXI. Sin embargo, pocos estudios han evaluado el impacto de la sucesión secundaria y el calentamiento climático sobre las tendencias poblacionales a escala nacional. Usamos un conteo nacional de aves de 47 especies recolectado entre 2009 y 2020 para estimar las tendencias poblacionales de especies de aves en Japón y examinamos las asociaciones entre la tendencia poblacional general y las características de la especie. La tendencia poblacional general varió entre especies. Las poblaciones de cuatro especies incrementaron con moderación, 18 permanecieron estables y once declinaron con moderación. Las tendencias poblacionales para 13 especies no fueron claras. La diferencia entre las tendencias generales de las especies estuvo asociada con su grupo de hábitat y el nicho térmico. Las especies con un nicho térmico relativamente bajo experimentaron una declinación más pronunciada. Los indicadores multiespecie mostraron un incremento moderado en las especialistas de bosque y una declinación moderada en las generalistas de bosque (especies que usan los bosques y hábitats abiertos) y las especialistas de hábitat abierto. Las generalistas de bosque y las especialistas de hábitat abierto también declinaron con mayor rapidez en los sitios con más suelo agrícola abandonado. Todos los grupos de especies mostraron una declinación acelerada o un incremento desacelerado después de 2015. Estos resultados sugieren que las aves reproductoras comunes en Japón están sufriendo tendencias declinantes como resultado de los cambios en el uso de suelo y el clima a nivel nacional. Las políticas y planeaciones de uso de suelo deben considerar a futuro los beneficios de la recuperación pasiva para las especialistas de bosque y las medidas activas de restauración (como la silvicultura y agricultura de baja intensidad) para las especialistas que no son de bosque y así conservar de manera efectiva la biodiversidad en la era de despoblación humana y calentamiento climático.

Tertiary lymphoid structures correlate with enhancement of antitumor immunity in esophageal squamous cell carcinoma.

BACKGROUND: Tertiary lymphoid structures (TLSs) are associated with a favorable prognosis in several cancers. However, the correlation between TLSs and outcomes of esophageal squamous cell carcinoma (ESCC) and the impact of TLSs on the tumor immune microenvironment (TIME) remain unknown. METHODS: We pathologically evaluated the significance of TLSs in ESCC focusing on TLS maturation using 180 ESCC specimens and performed single-cell RNA sequencing (scRNA-seq) using 14 ESCC tissues to investigate functional differences of immune cells according to TLS presence. RESULTS: TLS+ cases had better recurrence-free-survival (RFS) (p < 0.0001) and overall survival (OS) (p = 0.0016) compared with TLS- cases. Additionally, mature TLS+ cases had better RFS and OS compared with immature TLS+ cases (p = 0.019 and p = 0.015) and TLS- cases (p < 0.0001 and p = 0.0002). The scRNA-seq showed that CD8+ T cells in TLS+ tumors expressed high levels of cytotoxic signatures and antigen-presentation of dendritic cells (DCs) was enhanced in TLS+ tumors. Immunohistochemistry showed that the densities of tumor-infiltrating CD8+ T cells and DCs were significantly higher in TLS+ tumors than those in TLS- tumors. CONCLUSIONS: These data suggest the prognostic and functional significance of TLSs in ESCC and provides new insights into TLSs on the TIME.

Prediction of the Area under the Curve Using Limited-Point Blood Sampling in a Cocktail Study to Assess Multiple CYP Activities.

A cocktail study is an in vivo evaluation method to assess multiple CYP activities via a single trial and single administration of a cocktail drug that is a combination of multiple CYP substrates. However, multiple blood samples are required to evaluate the pharmacokinetics of a CYP probe drug. A limited-point sampling method is generally beneficial in clinical studies because of the simplified protocol and reduced participant burden. The aim of this study was to evaluate whether a limited-point plasma concentration analysis of CYP substrates in a cocktail drug could predict their area under the curve (AUC). We created prediction models of five CYP substrates (caffeine, losartan, omeprazole, dextromethorphan, and midazolam) using multiple linear regressions from the data of two cocktail studies, and then performed predictability analysis of these models using data derived from data in the co-administration with inducer (rifampicin) and inhibitors (fluvoxamine and cimetidine). For the administration of inhibitors, the AUC prediction accuracy (mean absolute error (MAE)) were <39.5% in Model 1 and <26.2% in Model 2 which were created using 1- and 4-point sampling data. MAE shows larger values in the administration of inducer in compared with the administration of inhibitors. The accuracy of the prediction in Model 2 could be acceptable for screening of inhibitions. MAE for caffeine, dextromethorphan, and midazolam were acceptable in the model that used 4 sampling points from all data. The use of this method could reduce the burden on the subject and make it possible to evaluate each AUC in a minimally invasive manner.

Verification of a cocktail approach for quantitative drug-drug interaction assessment: a comparative analysis between the results of a single drug and a cocktail drug.

A cocktail approach is a method to comprehensively evaluate the activity of cytochrome P450 enzymes (CYPs) by co-administering multiple CYP substrates. This is the first report that compares the results from a cocktail study to a single substrate separate administration study (single study) with concomitant administration of CYP inducers/inhibitors. The validity of a cocktail study for use as a quantitative drug-drug interactions (DDIs) assessment was evaluated.We administered a cocktail drug (caffeine, losartan, omeprazole, dextromethorphan, midazolam) with rifampicin, cimetidine or fluvoxamine. A comparative analysis was performed between the results of a cocktail study and single studies. The results of single studies were obtained from a literature review and the trials of single substrate separate administration.A strong positive correlation of the AUC ratio of all drugs between single studies and the cocktail study was obtained. The ratio of AUC change of 12 combinations converged to 0.82-1.09, and 2 combinations ranged between 0.74-1.32.The differences in the degree of interaction between the single studies and cocktail study are acceptable to evaluate DDIs for almost all combinations. Our results indicate that a cocktail study is an adequate and quantitative evaluation method for DDIs.

Clinical evaluation of drug-drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers.

AIMS: The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of ACT-333679, an active metabolite of selexipag, by 11-fold. Similarly to gemfibrozil, the CYP2C8 inhibitor clopidogrel increased ACT-333679 concentration by 1.9-fold after a single loading dose (300 mg once daily) and 2.7-fold after repeated treatment with the maintenance dose (75 mg once daily) in Europeans. However, the effects of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 have not been fully elucidated in the Japanese population. METHODS: We investigated the effect of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 in 14 healthy Japanese volunteers. RESULTS: The concomitant administration of clopidogrel with selexipag did not influence the maximum concentration and AUC0-∞ of selexipag, whereas it significantly increased AUC0-∞ of ACT-333679 by approximately 1.90-fold (90% confidence interval 1.69-2.14) without changing the maximum concentration. When selexipag was administered 1 day after clopidogrel was discontinued, the increase in AUC0-∞ of ACT-333679 was 1.37-fold (90% confidence interval 0.93-2.02), suggesting that, although the inhibitory effect of clopidogrel on CYP2C8 was reduced, it persisted for at least 1 day after withdrawal. CONCLUSION: Our results demonstrated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite and suggested that selexipag should be carefully prescribed with clopidogrel with dose adjustment or reducing the dosing frequency in Japanese clinical settings.

Ignoring non-English-language studies may bias ecological meta-analyses.

Meta-analysis plays a crucial role in syntheses of quantitative evidence in ecology and biodiversity conservation. The reliability of estimates in meta-analyses strongly depends on unbiased sampling of primary studies. Although earlier studies have explored potential biases in ecological meta-analyses, biases in reported statistical results and associated study characteristics published in different languages have never been tested in environmental sciences. We address this knowledge gap by systematically searching published meta-analyses and comparing effect-size estimates between English- and Japanese-language studies included in existing meta-analyses. Of the 40 published ecological meta-analysis articles authored by those affiliated to Japanese institutions, we find that three meta-analysis articles searched for studies in the two languages and involved sufficient numbers of English- and Japanese-language studies, resulting in four eligible meta-analyses (i.e., four meta-analyses conducted in the three meta-analysis articles). In two of the four, effect sizes differ significantly between the English- and Japanese-language studies included in the meta-analyses, causing considerable changes in overall mean effect sizes and even their direction when Japanese-language studies are excluded. The observed differences in effect sizes are likely attributable to systematic differences in reported statistical results and associated study characteristics, particularly taxa and ecosystems, between English- and Japanese-language studies. Despite being based on a small sample size, our findings suggest that ignoring non-English-language studies may bias outcomes of ecological meta-analyses, due to systematic differences in study characteristics and effect-size estimates between English- and non-English languages. We provide a list of actions that meta-analysts could take in the future to reduce the risk of language bias.

La méta­analyse joue un rôle essentiel dans les synthèses de preuves quantitatives en écologie et en conservation de la biodiversité. La fiabilité des estimations dans les méta­analyses dépend fortement d'un échantillonnage non biaisé des études primaires. Bien que des études antérieures aient examiné les biais potentiels dans les méta­analyses écologiques, les biais n'ont jamais été mis à l'épreuve dans les sciences de l'environnement lors de publications dans différentes langues de résultats statistiques enregistrés et de caractéristiques des études associées. Nous abordons cette lacune dans les connaissances en recherchant de manière systématique des méta­analyses publiées et en comparant les estimations d'ampleur de l'effet entre des études en anglais et en japonais figurant dans les méta­analyses existantes. Sur 40 articles publiés de méta­analyse écologique dont les auteurs sont affiliés à des institutions japonaises, nous trouvons que trois articles de méta­analyse ont recherché des études dans les deux langues et ont mis en jeu des nombres suffisants d'études en anglais et en japonais, avec pour résultat quatre méta­analyses admissibles (c.­à­d. quatre méta­analyses effectuées dans les trois articles de méta­analyse). Dans deux de ces quatre cas, les ampleurs de l'effet diffèrent de façon significative entre les études en japonais et en anglais comprises dans les méta­analyses, ce qui provoque des changements considérables dans les ampleurs moyennes globales de l'effet et même dans leur direction lorsque les études en japonais sont exclues. On peut probablement attribuer les différences observées dans les ampleurs de l'effet entre les études en japonais et en anglais, en particulier en ce qui concerne les taxons et les écosystèmes, aux différences systématiques dans les résultats statistiques enregistrés, de même que dans les caractéristiques des études associées. Bien que basés sur un échantillon de petite taille, nos résultats suggèrent que le fait d'ignorer les études non anglophones peut biaiser les résultats de méta­analyses écologiques en raison des différences systématiques dans les caractéristiques d'étude et les estimations d'ampleur de l'effet entre langue anglaise et langues non anglophones. Nous proposons une liste de mesures qui pourraient être adoptées à l'avenir dans les méta­analyses pour réduire le risque de biais linguistique.

A metanálise desempenha um papel crucial na síntese de evidências quantitativas na ecologia e conservação da biodiversidade. A confiabilidade das estimativas nas metanálises depende fortemente da amostragem imparcial de estudos primários. Embora estudos anteriores tenham explorado possíveis vieses em metanálises ecológicas, os vieses nos resultados estatísticos relatados e características de estudos associados publicados em diferentes idiomas nunca foram testados em ciências ambientais. Abordamos essa lacuna de conhecimento pesquisando sistematicamente metanálises publicadas e comparando estimativas de tamanho de efeito entre os estudos em inglês e japonês incluídos nas metanálises existentes. Dos 40 artigos de metanálise ecológica publicados por autores filiados a instituições japonesas, descobrimos que três artigos de metanálise pesquisaram estudos nos dois idiomas e envolveram um número suficiente de estudos em inglês e japonês, resultando em quatro metanálises elegíveis (ou seja, quatro metanálises realizadas nos três artigos de metanálise). Em duas das quatro metanálises, os tamanhos de efeito diferem significativamente entre os estudos em inglês e japonês incluídos nas metanálises, causando mudanças consideráveis nos tamanhos de efeito médios em geral e até mesmo na sua direção quando os estudos em japonês são excluídos. As diferenças observadas nos tamanhos de efeito provavelmente são atribuíveis a diferenças sistemáticas nos resultados estatísticos relatados, bem como às características de estudos associados, particularmente táxons e ecossistemas, entre estudos em inglês e japonês. Embora baseados em um pequeno tamanho amostral, nossos resultados sugerem que ignorar estudos que não sejam em inglês pode influenciar os resultados de metanálises ecológicas, devido a diferenças sistemáticas nas características dos estudos e estimativas de tamanho de efeito entre o idioma inglês e o não­inglês. Fornecemos uma lista de medidas que metanalistas podem adotar no futuro para reduzir o risco de viés de idioma.

El meta­análisis juega un papel crucial en la síntesis de evidencia cuantitativa en ecología y conservación de la biodiversidad. La fiabilidad de las estimaciones en los meta­análisis depende en gran medida del muestreo imparcial de los estudios primarios. A pesar de que estudios previos han explorado posibles sesgos en meta­análisis ecológicos, sesgos en resultados estadísticos y características asociadas al estudio publicados en diferentes idiomas nunca han sido comprobados en ciencias ambientales. Abordamos esta brecha de conocimiento buscando sistemáticamente los meta­análisis publicados y comparando las estimaciones del tamaño del efecto entre los estudios en inglés y japonés incluidos en los meta­análisis existentes. De los 40 artículos de meta­análisis ecológicos publicados por aquellos afiliados a instituciones japonesas, encontramos que tres artículos de meta­análisis buscaron estudios en dos idiomas e involucraron un número suficiente de estudios en inglés y japonés, lo que resultó en cuatro meta­análisis elegibles (i.e., cuatro meta­análisis realizados en tres artículos de meta­análisis). En dos de los cuatro, los tamaños de los efectos difieren significativamente entre los estudios en inglés y japonés incluidos en los meta­análisis, lo que provoca cambios considerables en los tamaños de efectos medios generales e incluso su dirección cuando se excluyen los estudios en japonés. Las diferencias observadas en los tamaños de los efectos son probablemente atribuibles a las diferencias sistemáticas en los resultados estadísticos informados, así como a las características de los estudios asociados, particularmente los taxones y los ecosistemas, entre los estudios en inglés y japonés. A pesar de estar basados ​​en un tamaño de muestra pequeño, nuestros hallazgos sugieren que ignorar los estudios que no están en inglés puede sesgar los resultados de los meta­análisis ecológicos, debido a las diferencias sistemáticas en las características del estudio y a las estimaciones del tamaño del efecto entre el idioma inglés y el no inglés. Proporcionamos una lista de acciones que los meta­analistas podrían tomar en el futuro para reducir el riesgo de sesgo lingüístico.

Transient Laterality of Cerebral Oxygenation Changes in Response to Head-of-Bed Manipulation in Acute Ischemic Stroke.

BACKGROUND: Cerebral oxygenation monitoring provides important information for optimizing individualized management in patients with acute ischemic stroke (AIS). Although changes in cerebral oxygenation are known to occur in response to head-of-bed (HOB) elevation within 72 h after onset, changes in cerebral oxygenation during stroke recovery are unclear. We compared changes in total- (tHb), oxygenated- (HbO2), and deoxygenated-hemoglobin (deoxyHb) concentrations in response to HOB manipulation between the timeframes within 72 h and 7-10 days after AIS onset. METHODS: We measured forehead ΔtHb, ΔHbO2, and ΔdeoxyHb in response to HOB elevation (30°) within 72 h (first measurement) and 7-10 days (second measurement) after AIS onset using time-resolved near-infrared spectroscopy. RESULTS: We enrolled 30 participants (mean age 72.8 ± 11.3 years; 13 women) with a first AIS. There were no significant differences in ΔtHb, ΔHbO2, or ΔdeoxyHb measurements on the infarct or contra-infarct side. At the first measurement, ΔtHb, ΔHbO2, and ΔdeoxyHb measured on the contra-infarct side did not correlate with those measured on the infarct side: ΔtHb (r = 0.114, p = 0.539); ΔHbO2 (r = 0.143, p = 0.440); ΔdeoxyHb (r = 0.227, p = 0.221). Notably, at the second measurement, correlation coefficients of ΔtHb and ΔHbO2 between the contra-infarct and infarct sides were statistically significant: ΔtHb (r = 0.491, p = 0.008); ΔHbO2 (r = 0.479, p = 0.010); ΔdeoxyHb (r = 0.358, p = 0.054). CONCLUSION: Although changes in cerebral oxygenation in response to HOB elevation had a laterality difference between hemispheres within 72 h of AIS onset, the difference had decreased, at least partially, 7-10 days after AIS onset.

Meta-analysis of the effects of rice-field abandonment on biodiversity in Japan.

Farmland abandonment is increasing worldwide. Concurrently, some conservationists view this as an opportunity for biodiversity restoration (i.e., rewilding). Due to a lack of data, however, it remains unclear whether farmland abandonment increases biodiversity in different farmland types and surrounding environments. Information is particularly scarce for Asia, home to one-third of identified biodiversity hotspots and where dominant farmlands (i.e., rice fields) are often viewed as substitutes for natural wetlands. We conducted the first meta-analysis of the impacts of rice-field abandonment on biodiversity, in which we considered multiscale factors, such as taxon surveyed, landscape context, and climate. Species richness and abundance after abandonment decreased to 56-72%. This reduced biodiversity was unlikely to recover, at least for plant species richness, even after 10-15 years. These results suggest rewilding will not necessarily be achieved by rice-field abandonment. Moreover, there was a pronounced biodiversity decline under dry conditions (e.g., low precipitation), especially for organisms closely associated with aquatic environment, such as amphibians and fish. Biodiversity reduction was least pronounced for birds and mammals. Such context dependency may suggest that impacts of farmland abandonment can be predicted by considering biological features of organisms and their associations with human-modified environments.

Responses of macroinvertebrate communities to pesticide application in irrigated rice fields.

The ability to recover to original states after disturbances makes macroinvertebrates useful tools for assessing the impacts of pesticides. Many studies showed that direct exposure to pesticides decreases macroinvertebrate richness and alters their composition. The main objective of this study was to assess recovery patterns in macroinvertebrate communities after pesticide application in irrigated rice fields. We analyzed short-term temporal dynamics of macroinvertebrate communities after application of the herbicides bispyribac-sodium and clomazone and the insecticide chlorantraniliprole, over the rice-growing season in southern Brazil. We selected three conventional rice fields and the recovery of macroinvertebrate communities was also compared with three adjacent natural ponds. The study was developed from November 2011 to February 2012 (rice-growing season). Five macroinvertebrate collections were carried out 3, 7, 14, 38, and 60 days after pesticide application (November 25). Rice fields showed lower richness and abundance than ponds in the period immediately after pesticide application, and recovery rates in the richness of macroinvertebrate communities were more conspicuous as pesticide residuals dissipated from the fields. Macroinvertebrate community structure in rice fields also became more similar to natural ponds as pesticide traces were scarcer. However, macroinvertebrate abundance patterns were not related to pesticide concentrations in the fields. Our results supported the general hypothesis on the negative effects of pesticide application on macroinvertebrate community in irrigated rice fields, although other environmental features (e.g., length of the flooded period) also contributed to explain temporal dynamics in the macroinvertebrate communities from irrigated rice fields.

Bird diversity and abundance in organic and conventional apple orchards in northern Japan.

Many studies have investigated the benefits of agri-environmental schemes, such as organic farming, on biodiversity conservation in annual systems, but their effectiveness in perennial systems is less well understood, particularly in bird communities in temperate regions of Asia. This study examined the effects of organic farming practices on species richness and abundance of breeding birds in apple orchards in northern Japan. Bird counts were conducted in six pairs of organic and conventional orchards during the breeding season in April and May 2015. The total species richness of birds, estimated by sample- and coverage-based rarefaction and extrapolation curves, was greater in organic orchards than in conventional orchards. Among the three dietary guilds (insectivore, granivore, and omnivore), only insectivorous species were more abundant in organic orchards than in conventional ones. This study offers the first quantitative evidence that organic farming can be beneficial for enhancing the diversity of birds, particularly of insectivores, in fruit orchards in Japan.

Landscape heterogeneity-biodiversity relationship: effect of range size.

The importance of landscape heterogeneity to biodiversity may depend on the size of the geographic range of species, which in turn can reflect species traits (such as habitat generalization) and the effects of historical and contemporary land covers. We used nationwide bird survey data from Japan, where heterogeneous landscapes predominate, to test the hypothesis that wide-ranging species are positively associated with landscape heterogeneity in terms of species richness and abundance, whereas narrow-ranging species are positively associated with landscape homogeneity in the form of either open or forest habitats. We used simultaneous autoregressive models to explore the effects of climate, evapotranspiration, and landscape heterogeneity on the richness and abundance of breeding land-bird species. The richness of wide-ranging species and the total species richness were highest in heterogeneous landscapes, where many wide-ranging species showed the highest abundance. In contrast, the richness of narrow-ranging species was not highest in heterogeneous landscapes; most of those species were abundant in either open or forest landscapes. Moreover, in open landscapes, narrow-ranging species increased their species richness with decreasing temperature. These results indicate that heterogeneous landscapes are associated with rich bird diversity but that most narrow-ranging species prefer homogeneous landscapes--particularly open habitats in colder regions, where grasslands have historically predominated. There is a need to reassess the generality of the heterogeneity-biodiversity relationship, with attention to the characteristics of species assemblages determined by environments at large spatiotemporal scales.

Hierarchical movement decisions in predators: effects of foraging experience at more than one spatial and temporal scale.

Animal movements in heterogeneous environments play a crucial role in a variety of ecological processes. Although a hierarchical structure to the scale of movements has been observed in many animal species, few studies to date have revealed what causes such multi-spatial scale movements within the framework of optimal theories. Using detailed information on movement paths and prey captures by Intermediate Egrets in rice fields, this study explored the effects of individual experience at multi-temporal scales on subsequent movement parameters. The results supported three predictions based on optimal foraging theories: (1) movement distances at small and large spatial scales are determined by past foraging experiences over short (one minute) and long (seven to eight minutes) temporal scales, respectively; (2) responses to prey encounters vary between temporal scales, e.g., prey attacks in the previous one minute caused egrets to walk away (i.e., area-avoided search), whereas those in the preceding eight minutes caused egrets to stay around (i.e., area-restricted search); and (3) the probability of patch departure by flying increases with decreasing intake rates in the previous seven minutes, and the quitting intake rate is mostly lower than the long-term average, not including travel time. These results suggest that egrets make different adaptive decisions at different spatial scales: in response to a clumped prey distribution at a large spatial scale, and to a dispersed distribution or behavioral depression of prey at a small spatial scale. This study showed that the framework of optimal foraging theories is useful for comprehensively explaining the different movement modes in animals. It should also be emphasized that considering both area-avoided and restricted searches at multi-temporal scales is important for understanding movement decisions, particularly in organisms searching for hierarchically distributed resources.

Age-related increase of insoluble, phosphorylated small heat shock proteins in human skeletal muscle.

Among mammalian heat shock proteins (Hsps), small Hsps (sHsps) are constitutively expressed in skeletal muscles. We investigated age-related changes of phosphorylation and cellular distribution of representative sHsps (Hsp27 and alphaB-crystallin) in human vastus lateralis muscle under resting conditions. We also examined upstream kinases which may be responsible for phosphorylation of sHsps, namely p38 mitogen-activated protein kinase (MAPK), MAPK-activated protein kinase-2, and extracellular signal-regulated kinase-1/2. The study groups consisted of nine young (15-38 years old) and nine aged (51-79 years old) patients who underwent orthopedic surgery. sHsps protein levels were higher in the insoluble fraction of aged muscles. The phosphorylated states of sHsps were enhanced in both the soluble and insoluble fraction of aged patients. The phosphorylated form of each upstream kinase was elevated in aged patients. Ubiquitinated proteins accumulated in the insoluble fractions of aged muscles. Aging mechanisms may affect the activation process of MAPKs, and the phosphorylation and accumulation of sHsps.