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A cut-off of daily sedentary time and all-cause mortality in adults: a meta-regression analysis involving more than 1 million participants

(2018-05-25) Ku, Po-Wen; Steptoe, Andrew; Liao, Yung; Hsueh, Ming-Chun; Chen, Li-Jung

Abstract Background The appropriate limit to the amount of daily sedentary time (ST) required to minimize mortality is uncertain. This meta-analysis aimed to quantify the dose-response association between daily ST and all-cause mortality and to explore the cut-off point above which health is impaired in adults aged 18–64 years old. We also examined whether there are differences between studies using self-report ST and those with device-based ST. Methods Prospective cohort studies providing effect estimates of daily ST (exposure) on all-cause mortality (outcome) were identified via MEDLINE, PubMed, Scopus, Web of Science, and Google Scholar databases until January 2018. Dose-response relationships between daily ST and all-cause mortality were examined using random-effects meta-regression models. Results Based on the pooled data for more than 1 million participants from 19 studies, the results showed a log-linear dose-response association between daily ST and all-cause mortality. Overall, more time spent in sedentary behaviors is associated with increased mortality risks. However, the method of measuring ST moderated the association between daily ST and mortality risk (p < 0.05). The cut-off of daily ST in studies with self-report ST was 7 h/day in comparison with 9 h/day for those with device-based ST. Conclusions Higher amounts of daily ST are log-linearly associated with increased risk of all-cause mortality in adults. On the basis of a limited number of studies using device-based measures, the findings suggest that it may be appropriate to encourage adults to engage in less sedentary behaviors, with fewer than 9 h a day being relevant for all-cause mortality.

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A network approach to investigating the key microbes and stability of gut microbial communities in a mouse neuropathic pain model

(2020-09-30) Brandon-Mong, Guo-Jie; Shaw, Grace T; Chen, Wei-Hsin; Chen, Chien-Chang; Wang, Daryi

Abstract Background Neuropathic pain is an abnormally increased sensitivity to pain, especially from mechanical or thermal stimuli. To date, the current pharmacological treatments for neuropathic pain are still unsatisfactory. The gut microbiota reportedly plays important roles in inducing neuropathic pain, so probiotics have also been used to treat it. However, the underlying questions around the interactions in and stability of the gut microbiota in a spared nerve injury-induced neuropathic pain model and the key microbes (i.e., the microbes that play critical roles) involved have not been answered. We collected 66 fecal samples over 2 weeks (three mice and 11 time points in spared nerve injury-induced neuropathic pain and Sham groups). The 16S rRNA gene was polymerase chain reaction amplified, sequenced on a MiSeq platform, and analyzed using a MOTHUR- UPARSE pipeline. Results Here we show that spared nerve injury-induced neuropathic pain alters gut microbial diversity in mice. We successfully constructed reliable microbial interaction networks using the Metagenomic Microbial Interaction Simulator (MetaMIS) and analyzed these networks based on 177,147 simulations. Interestingly, at a higher resolution, our results showed that spared nerve injury-induced neuropathic pain altered both the stability of the microbial community and the key microbes in a gut micro-ecosystem. Oscillospira, which was classified as a low-abundance and core microbe, was identified as the key microbe in the Sham group, whereas Staphylococcus, classified as a rare and non-core microbe, was identified as the key microbe in the spared nerve injury-induced neuropathic pain group. Conclusions In summary, our results provide novel experimental evidence that spared nerve injury-induced neuropathic pain reshapes gut microbial diversity, and alters the stability and key microbes in the gut.

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A note on the almost-Schur lemma on smooth metric measure spaces

(2018-07-27) Chen, Jui-Tang

Abstract In this paper, we prove almost-Schur inequalities on closed smooth metric measure spaces, which implies the results of Cheng and De Lellis–Topping whenever the weighted function f is constant.

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A novel non-negative matrix factorization technique for decomposition of Chinese characters with application to secret sharing

(2019-08-14) Lin, Chih-Yang; Kang, Li-Wei; Huang, Tsung-Yi; Chang, Min-Kuan

Abstract The decomposition of Chinese characters is difficult and has been rarely investigated in the literature. In this paper, we propose a novel non-negative matrix factorization (NMF) technique to decompose a Chinese character into several graphical components without considering the strokes of the character or any semantic or phonetic properties of the components. Chinese characters can usually be represented as binary images. However, traditional NMF is only suitable for representing general gray-level or color images. To decompose a binary image using NMF, we force all of the elements of the two matrices (obtained by factorizing the binary image/matrix to be decomposed) as close to 0 or 1 as possible. As a result, a Chinese character can be efficiently decomposed into several components, where each component is semantically unreadable. Moreover, our NMF-based Chinese character decomposition method is suitable for applications in visual secret sharing by distributing the shares (different character components) among multiple parties, so that only when the parties are taken together with their respective shares can the secret (the original Chinese character(s)) be reconstructed. Experimental results have verified the decomposition performance and the feasibility of the proposed method.

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A reappraisal of lymph node dissection in colorectal cancer during primary surgical resection

(2020-05-17) Chen, Yen-Jen; Yeh, Shin-Ting; Kao, Ping-Sheng; Ou, Liang-Hung; Lin, Chen-Sung

Abstract Purpose Controversy exists regarding the extent to which lymph node dissection (LND) should be performed for operable colorectal cancers (CRCs) during primary surgical resection. We reappraised the role of LND in CRCs. Methods Seventy-three CRC patients (mean age, 65.3 years; 43 males) undergoing primary surgical resection at Taipei Hospital, Ministry of Health and Welfare, Taiwan, within a 3-year period were retrospectively analyzed. Their pathological T/N/M statuses and cancer stages were defined according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. The numbers of total dissected lymph nodes (TDLNs), positive dissected lymph nodes (PDLNs), and negative dissected lymph nodes (NDLNs) for each CRC patient were recorded in detail (TDLNs = PDLNs + NDLNs). Possible prognostic variables were evaluated. Results An advanced N status (N1/N2 vs. N0; HR, 5.749/17.677 vs. 1.000; p = 0.056/0.009) and M1 status (M1 vs. M0; HR, 7.517 vs. 1.000; p = 0.010) were independent variables for a poor prognosis. For all 73 CRC patients (p = 0.030), as well as T2 CRC patients (p = 0.061), those with > 15 TDLNs tended to have more PDLNs than those with ≤ 15 TDLNs. For 42 N(+) CRC patients (p = 0.007), as well as N2 CRC patients (p = 0.011), those with > 21 TDLNs tended to have more PDLNs than those with ≤ 21 TDLNs. Conclusion For CRC patients undergoing primary surgical resection, the number of TDLNs influences the accuracy of nodal staging. A minimum of 15 TDLNs is necessary for positive lymph nodes to be identified in CRC patients, and 21 TDLNs is sufficient for the severity of the N(+) status to be distinguished in N(+) CRC patients.

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A search for a correlation between time change in transfer functions and seismic energy release in northern Taiwan

(2006-09-16) Chen, Kuang-Jung; Chiu, Bonbbon; Lin, Cheng-Horng

Abstract The geomagnetic data of the Lunping Geomagnetic Observatory from 1988 to 2000 are utilized for computing daily geomagnetic transfer functions. The method of analysis is based on the power spectrum analysis developed by Everett and Hyndman. Monthly means are statistically obtained from these daily values of transfer functions. In order to compare these time changes with seismic activity (seismicity), the earthquakes occurring within 150 km from Lunping, with a magnitude ML greater than 4.0, are located. The related energy releases by those earthquakes, summed month by month, are correlated to the transfer functions. After removing the seasonal effect, we find that the time changes of magnitude of Au and Bu (real parts of the transfer function) for frequencies of 2, 3, 4, and 6 cycles/hour seem to be strongly related to the energy release within the whole study period. Two significant precursors were found from the A and B values, 40 and 20 months before high seismicities, respectively.

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A single sequence context cannot satisfy all non-AUG initiator codons in yeast†

(2010-07-09) Chang, Chia-Pei; Chen, Shun-Jia; Lin, Chen-Huan; Wang, Tzu-Ling; Wang, Chien-Chia

Abstract Background Previous studies in Saccharomyces cerevisiae showed that ALA1 (encoding alanyl-tRNA synthetase) and GRS1 (encoding glycyl-tRNA synthetase) respectively use ACG and TTG as their alternative translation initiator codons. To explore if any other non-ATG triplets can act as initiator codons in yeast, ALA1 was used as a reporter for screening. Results We show herein that except for AAG and AGG, all triplets that differ from ATG by a single nucleotide were able to serve as initiator codons in ALA1. Among these initiator codons, TTG, CTG, ACG, and ATT had ~50% initiating activities relative to that of ATG, while GTG, ATA, and ATC had ~20% initiating activities relative to that of ATG. Unexpectedly, these non-AUG initiator codons exhibited different preferences toward various sequence contexts. In particular, GTG was one of the most efficient non-ATG initiator codons, while ATA was essentially inactive in the context of GRS1. Conclusion This finding indicates that a sequence context that is favorable for a given non-ATG initiator codon might not be as favorable for another.

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Achieving per-flow and weighted fairness for uplink and downlink in IEEE 802.11 WLANs

(2012) Wang, Chiapin

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Adherence among HIV-positive injection drug users undergoing methadone treatment in Taiwan

(2020-07-02) Chao, En; Hung, Chia-Chun; Lin, Ching-Po; Ku, Yi-Chien J; Ain, Qurat U; Metzger, David S; Lee, Tony S

Abstract Aims The study aims were to investigate adherence to methadone maintenance treatment (MMT) and to identify associated clinical factors in patients who inject drugs diagnosed with human immunodeficiency virus (HIV) infection in Taiwan. Methods Data were from the National Health Surveillance System on HIV and the National Drug Treatment System on MMT. HIV-positive people who inject drugs (HIVPWID) were defined as the study population. Information obtained included age, sex, education, marital status, employment, methadone dose, and date of diagnosis of HIV infection. Adherence was defined as taking methadone for the past 90, 180 and 365 days, then categorized as high (> 90%), moderate (51 to 90%), or low (<=50%) adherent respectively. Results Of 1641 HIVPWID registered in the datasets from 2007 to 2012, 961 (58.56%) had received MMT. For HIVPWID evaluated at 90 days (n = 951), 271 (28.5%), 382 (40.2%), and 298 (31.3%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 180 days (n = 936), 190 (20.3%), 349 (37.3%), and 397 (42.4%) were classified as high, moderate, and low adherent respectively. For HIVPWID evaluated at 365 days (n = 919), 133 (14.5%), 271 (29.5%), and 515 (56.0%) were classified as high, moderate, and low adherent respectively. After controlling for sociodemographics, results showed that methadone dose, location of MMT clinic, and date of HIV diagnosis were significantly associated with MMT adherence. Conclusions Study findings underscore the importance to MMT adherence of methadone dosage, early diagnosis of patient’s HIV infection, and area of patient residence.

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An alternative approach for a distance inequality associated with the second-order cone and the circular cone

(2016-11-22) Miao, Xin-He; Lin, Yen-chi R; Chen, Jein-Shan

Abstract It is well known that the second-order cone and the circular cone have many analogous properties. In particular, there exists an important distance inequality associated with the second-order cone and the circular cone. The inequality indicates that the distances of arbitrary points to the second-order cone and the circular cone are equivalent, which is crucial in analyzing the tangent cone and normal cone for the circular cone. In this paper, we provide an alternative approach to achieve the aforementioned inequality. Although the proof is a bit longer than the existing one, the new approach offers a way to clarify when the equality holds. Such a clarification is helpful for further study of the relationship between the second-order cone programming problems and the circular cone programming problems.

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Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining colorectal tumors in vivo

(2013) Huang, Kai-Wen; Chieh, Jen-Jie; Lin, In-Tsang; Horng, Herng-Er; Yang, Hong-Chang; Hong, Chin-Yih

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Antioxidant, cell-protective, and anti-melanogenic activities of leaf extracts from wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) cultivars

(2014-12-10) Tsai, Tsung-Hsien; Huang, Ching-Jang; Wu, Wen-Huey; Huang, Wen-Cheng; Chyuan, Jong-Ho; Tsai, Po-Jung

Abstract Background Several wild bitter melon (WBM; Momordica charantia Linn. var. abbreviata Ser.) cultivars were developed in Taiwan. However, little information is available regarding biological function of WBM leaf. Therefore, the objectives of this study were to investigate the nutrient content, antioxidant, cell protection and anti-melanogenic properties of wild bitter melon leaf. Results Methanolic leaf extracts were prepared from a variety and two cultivars of WBM. All extracts exerted potent nitric oxide and hydroxyl radical scavenging capacities. Furthermore, all extracts effectively reduce the production of reactive oxygen species and prevent cell death in UVB-irradiated HaCaT keratinocytes. The cell protective effect of leaf extract was also investigated by the prevention of HaCaT cells from sodium nitroprusside or menadione-induced toxicity, and significant cyto-protective activities were observed for all of them. Additionally, all extracts significantly suppressed tyrosinase activity and melanin levels in B16-F10 melanocytes. Conclusions WBM leaf extract showed significant antioxidant, cyto-protective and anti-melanogenic activities. These findings suggested that WBM leaves may be beneficial for preventing the photo-oxidative damage and melanogenesis of skin.

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Anxiety symptoms and preventive measures during the COVID-19 outbreak in Taiwan

(2020-07-16) Wong, Li P; Hung, Chia-Chun; Alias, Haridah; Lee, Tony S

Abstract Background It is hypothesized that anxiety and behavioral responses are intense at the beginning of an epidemic. The objective of this study was to investigate anxiety symptoms and use of preventive measures against COVID-19. The study also compared the association between preventive measures and anxiety symptoms during the week immediately preceding the study and those symptoms and measures at the beginning of the outbreak. Methods A cross-sectional population survey using an online questionnaire commenced on 14 February 2020. The study participants were residents of Taiwan ages 20 to 70 years. The 6-item state version of the State–Trait Anxiety Inventory (STAI-6) was used to assess anxiety symptoms. The questions about preventive measures asked participants about their personal protection, cough etiquette, contact precautions, voluntary quarantine, and prompt reporting. Multivariable logistic regression was used to determine the factors influencing an increase in the preventive measures scores. Results Of a total of 3555 completed responses, a total of 52.1% (95% confidence interval [CI] 50.4–53.7) of the respondents reported moderate to severe levels of anxiety symptoms in the past week, whereas 48.8% (95%CI 47.2–50.5) reported moderate to severe anxiety symptoms at the beginning of the outbreak. With a higher score indicating greater anxiety, the median scores for anxiety symptoms in the past week and at the beginning of the outbreak were 46.7 (IQR [interquartile range] 36.7–53.3) and 43.3 (IQR 36.7–53.3), respectively. The median scores for the preventive measures taken in the past week and at the beginning of the outbreak were 26.0 (IQR 21.0–30.0) and 24.0 (IQR 19.0–28.0), respectively, out of a maximum score of 36. In the multivariable analysis, an increased anxiety symptom score from the beginning of the outbreak to the past week (adjusted OR = 7.38, 95%CI 6.28–8.66) was a strongly significant determinant of an increased preventive measures score in the past week compared with the score at the beginning of the outbreak. Conclusions Anxiety and preventive measures scores were high and increased with the epidemic rate. Higher anxiety was associated with an increased use of preventive measures against COVID-19.

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Asarum pubitessellatum, sp. nov. (sect. Heterotropa, Aristolochiaceae) from Taiwan based on morphological and palynological evidence

(2013) Lu, Chang-Tse; Chiou, Wen-Liang; Wang, Jenn-Che

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Assaying Carcinoembryonic Antigens by Normalized Saturation Magnetization

(2015-07-03) Huang, Kai-Wen; Chieh, Jen-Jie; Shi, Jin-Cheng; Chiang, Ming-Hsien

Abstract Biofunctionalized magnetic nanoparticles (BMNs) that provide unique advantages have been extensively used to develop immunoassay methods. However, these developed magnetic methods have been used only for specific immunoassays and not in studies of magnetic characteristics of materials. In this study, a common vibration sample magnetometer (VSM) was used for the measurement of the hysteresis loop for different carcinoembryonic antigens (CEA) concentrations (Φ CEA) based on the synthesized BMNs with anti-CEA coating. Additionally, magnetic parameters such as magnetization (M), remanent magnetization (M R), saturation magnetization (M S), and normalized parameters (ΔM R/M R and ΔM S/M S) were studied. Here, ΔM R and ΔM s were defined as the difference between any ΦCEA and zero Φ CEA. The parameters M, ΔM R, and ΔM S increased with Φ CEA, and ΔM S showed the largest increase. Magnetic clusters produced by the conjugation of the BMNs to CEAs showed a ΔM S greater than that of BMNs. Furthermore, the relationship between ΔM S/M S and Φ CEA could be described by a characteristic logistic function, which was appropriate for assaying the amount of CEAs. This analytic ΔM S/M S and the BMNs used in general magnetic immunoassays can be used for upgrading the functions of the VSM and for studying the magnetic characteristics of materials.

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Assembling contigs in draft genomes using reversals and block-interchanges

(2013-04-10) Li, Chi-Long; Chen, Kun-Tze; Lu, Chin L

Abstract The techniques of next generation sequencing allow an increasing number of draft genomes to be produced rapidly in a decreasing cost. However, these draft genomes usually are just partially sequenced as collections of unassembled contigs, which cannot be used directly by currently existing algorithms for studying their genome rearrangements and phylogeny reconstruction. In this work, we study the one-sided block (or contig) ordering problem with weighted reversal and block-interchange distance. Given a partially assembled genome π and a completely assembled genome σ, the problem is to find an optimal ordering to assemble (i.e., order and orient) the contigs of π such that the rearrangement distance measured by reversals and block-interchanges (also called generalized transpositions) with the weight ratio 1:2 between the assembled contigs of π and σ is minimized. In addition to genome rearrangements and phylogeny reconstruction, the one-sided block ordering problem particularly has a useful application in genome resequencing, because its algorithms can be used to assemble the contigs of a draft genome π based on a reference genome σ. By using permutation groups, we design an efficient algorithm to solve this one-sided block ordering problem in O δ n time, where n is the number of genes or markers and δ is the number of used reversals and block-interchanges. We also show that the assembly of the partially assembled genome can be done in O n time and its weighted rearrangement distance from the completely assembled genome can be calculated in advance in O n time. Finally, we have implemented our algorithm into a program and used some simulated datasets to compare its accuracy performance to a currently existing similar tool, called SIS that was implemented by a heuristic algorithm that considers only reversals, on assembling the contigs in draft genomes based on their reference genomes. Our experimental results have shown that the accuracy performance of our program is better than that of SIS, when the number of reversals and transpositions involved in the rearrangement events between the complete genomes of π and σ is increased. In particular, if there are more transpositions involved in the rearrangement events, then the gap of accuracy performance between our program and SIS is increasing.

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Association of TNF-α gene with spontaneous deep intracerebral hemorrhage in the Taiwan population: a case control study

(2010-06-10) Chen, Yi-Chun; Hu, Fen-Ju; Chen, Phoebe; Wu, Yih-Ru; Wu, Hsiu-Chuan; Chen, Sien-Tsong; Lee-Chen, Guey-Jen; Chen, Chiung-Mei

Abstract Background Genetic factors may play a role in susceptibility to spontaneous deep intracerebral hemorrhage (SDICH). Previous studies have shown that TNF-α gene variation was associated with risks of subarachnoid hemorrhage in multiple ethnicities. The present case-control study tested the hypothesis that genetic variations of the TNF-α gene may affect the risk of Taiwanese SDICH. We examined the association of SDICH risks with four single nucleotide polymorphisms (SNPs) within the TNF-α gene promoter, namely T-1031C, C-863A, C-857T, and G-308A. Methods Genotyping was determined by PCR-based restriction and electrophoresis assay for 260 SDICH patients and 368 controls. Associations were tested by logistic regression or general linear models with adjusting for multiple covariables in each gender group, and then in combined. Multiplicative terms of gender and each of the four SNPs were applied to detect the interaction effects on SDICH risks. To account for the multiple testing, permutation testing of 1,000 replicates was performed for empirical estimates. Results In an additive model, SDICH risks were positively associated with the minor alleles -1031C and -308A in men (OR = 1.9, 95% CI 1.1 to 3.4, p = 0.03 and OR = 2.6, 95% CI 1.3 to 5.3, p = 0.005, respectively) but inversely associated with -863A in females (OR = 0.5, 95% CI 0.2 to 0.9, p = 0.03). There were significant interaction effects between gender and SNP on SDICH risks regarding SNPs T-1031C, C-863A, and G-308A (p = 0.005, 0.005, and 0.007, respectively). Hemorrhage size was inversely associated with -857T in males (p = 0.04). Conclusions In the Taiwan population, the associations of genetic variations in the TNF-α gene promoter with SDICH risks are gender-dependent.

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Associations of neighbourhood walkability indices with weight gain

(2018-04-03) Koohsari, Mohammad J; Oka, Koichiro; Shibata, Ai; Liao, Yung; Hanibuchi, Tomoya; Owen, Neville; Sugiyama, Takemi

Abstract Background Inconsistent associations of neighbourhood walkability with adults’ body weight have been reported. Most studies examining the relationships of walkability and adiposity are cross-sectional in design. We examined the longitudinal relationships of two walkability indices – conventional walkability and space syntax walkability, and their individual components, with weight change among adults over four years. Methods Data were from the Physical Activity in Localities and Community study in Adelaide, Australia. In 2003–2004, 2650 adults living in 154 Census Collection Districts (CCDs) returned baseline questionnaires; in 2007–2008, the follow-up survey was completed by 1098. Participants reported their weight at baseline and at follow-up. Neighbourhood walkability indices were calculated using geographic information systems and space syntax software. Linear marginal models using generalized estimating equations with robust standard errors were fitted to examine associations of the two walkability indices and their individual components with the weight at follow-up, adjusting for baseline weight, socio-demographic variables, and spatial clustering at the level of CCD. Results The overall mean weight gain over four years was 1.5 kg. The two walkability indices were closely correlated (r = 0.76, p < 0.01). No significant associations were found between the overall neighbourhood walkability indices and weight change. Among walkability components, there was a marginally significant negative association between space syntax measure of street integration and weight change: one standard deviation increment in street integration was associated with 0.31 kg less weight gain (p = 0.09). Conclusions Using a prospective study design and a novel space-syntax based measure of walkability, we were not able to identify relationships between neighbourhood walkability with weight gain. This is consistent with other inconclusive findings on the built environment and obesity. Research on the built environment and adults’ weight gain may need to consider not just local environments but also a larger scale environment within a city or workplace environment in order to capture multiple behaviours relevant to weight gain.

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Bigger doesn’t mean bolder: behavioral variation of four wild rodent species to novelty and predation risk following a fast-slow continuum

(2020-09-21) Best, Ian N; Shaner, Pei-Jen L; Lo, Hsuan-Yi; Pei, Kurtis J; Kuo, Chi-Chien

Abstract Background Understanding how wild species respond to novel situations with associated risk can provide valuable insights for inter-specific behavioral variation and associations with pace-of-life (POL). Rodents, a globally distributed and diverse taxonomic group, have been the subjects of countless studies emulating risky situations. Controlled laboratory experiments with a focus on wild-caught species provide the opportunity to test fine-scale behavioral responses to contexts of risk with ecological implications. For example, assessing the importance of predator cues eliciting antipredator responses, as well as whether wild rodents embody behavioral plasticity and repertoires, illustrated by habituation and variation in behavioral traits, respectively. Results In this comparative study, we examined multiple behavioral responses of four rodent species in eastern Taiwan (three native species Mus caroli, Apodemus agrarius, Rattus losea, and one invasive, Rattus exulans) exposed to an unfamiliar microenvironment and novel cue from an allopatric predator, the leopard cat (Prionailurus bengalensis). All wild-caught animals were subjected to two consecutive nights of experimental trials in a laboratory setting. Behavioral responses to a novel situation during the first trial differed between species; smaller species investing more time in non-defensive behaviors compared to the larger species. More specifically, the smaller species M. caroli and A. agrarius allocated more time to exploration and foraging, whereas the larger rat species R. exulans and R. losea spent more time motionless or concealing. During the second trial, the addition of leopard cat cues did not elicit antipredator behaviors, but rather, rodents were found to exhibit increased non-defensive behaviors, specifically foraging efforts. Conclusions Our results suggest that these four species do largely follow a behavioral fast-slow continuum with the two smaller mice species demonstrating increased boldness in a novel context compared to the larger rat species. Also, the wild populations of rodents in eastern Taiwan may be naïve to leopard cats. Finally, the rodents in our study demonstrated habituation to the microenvironment, indicating they possess adaptive capacity.

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Brain functioning under acute hypothermic stress supported by dynamic monocarboxylate utilization and transport in ectothermic fish

(2014-08-08) Tseng, Yung-Che; Liu, Sian-Tai; Hu, Marian Y; Chen, Ruo-Dong; Lee, Jay-Ron; Hwang, Pung-Pung

Abstract Background The vertebrate brain is a highly energy consuming organ that requires continuous energy provision. Energy metabolism of ectothermic organisms is directly affected by environmental temperature changes and has been demonstrated to affect brain energy balance in fish. Fish were hypothesized to metabolize lactate as an additional energy substrate during acute exposure to energy demanding environmental abiotic fluctuations to support brain functionality. However, to date the pathways of lactate mobilization and transport in the fish brain are not well understood, and may represent a critical physiological feature in ectotherms during acclimation to low temperature. Results We found depressed routine metabolic rates in zebrafish during acute exposure to hypothermic (18°C) conditions accompanied by decreased lactate concentrations in brain tissues. No changes in brain glucose content were observed. Acute cold stress increased protein concentrations of lactate dehydrogenase 1 (LDH1) and citrate synthase (CS) in brain by 1.8- and- 2.5-fold, paralleled by an increased pyruvate to acetyl-CoA transformation. To test the involvement of monocarboxylate transporters (MCTs) under acute cold stress in zebrafish, we cloned and sequenced seven MCT1-4 homologues in zebrafish. All drMCT1-4 are expressed in brain tissues and in response to cold stress drmct2a and drmct4a transcripts were up-regulated 5- and 3-fold, respectively. On the contrary, mRNA levels of drmct1a, -1b and -4b in zebrafish brain responded with a down regulation in response to cold stress. By expressing drMCTs in Xenopus oocytes we could provide functional evidence that hypothermic stress leads to a 2-fold increase in lactate transport in drMCT4b expressing oocytes. Lactate transport of other paralogues expressed in oocytes was unaffected, or even decreased during cold stress. Conclusion The present work provides evidence that lactate utilization and transport pathways represent an important energy homeostatic feature to maintain vital functions of brain cells during acute cold stress in ectotherms.

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