bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural requirements for calmodulin binding to membrane‐associated guanylate kinase homologs
Authors: Paarmann Ingo , Lye Ming F. , Lavie Arnon , Konrad Manfred 
Published: September 2008

AbstractEffector molecules such as calmodulin modulate the interactions of membrane‐associated guanylate kinase homologs (MAGUKs) and other scaffolding proteins of the membrane cytoskeleton by binding to the Src homology 3 (SH3) domain, the guanylate kinase (GK) domain, or the connecting HOOK region of MAGUKs. Using surface plasmon resonance, we studied the interaction of members of all four MAGUK subfamilies—synapse‐associated protein 97 (SAP97), calcium/calmodulin‐dependent serine protein kinase (CASK), membrane palmitoylated protein 2 (MPP2), and zona occludens (ZO) 1—and calmodulin to determine interaction affinities and localize the binding site. The SH3‐GK domains of the proteins and derivatives thereof were expressed in E. coli and purified. In all four proteins, high‐affinity calmodulin binding was identified. CASK was shown to contain a Ca2+‐dependent calmodulin binding site within the HOOK region, overlapping with a protein 4.1 binding site. In ZO1, a Ca2+‐dependent calmodulin binding site was detected within the GK domain. The equilibrium dissociation constants for MAGUK–calmodulin interaction were found to range from 50 nM to 180 nM. Sequence analyses suggest that binding sites for calmodulin have evolved independently in at least three subfamilies. For ZO1, pulldown of GST‐calmodulin was shown to occur in a calcium‐dependent manner; moreover, molecular modeling and sequence analyses predict conserved basic residues to be exposed on one side of a helix. Thus, calmodulin binding appears to be a common feature of MAGUKs, and Ca2+‐activated calmodulin may serve as a general regulator to affect the interactions of MAGUKs and various components of the cytoskeleton.
DCUN1D3, a novel UVC‐responsive gene that is involved in cell cycle progression and cell growth
Authors: Ma Teng , Shi Taiping , Huang Jing , Wu Lina , Hu Fanlei , He PengFei , Deng WeiWei , Gao Peng , Zhang Yingmei , Song Quansheng , Ma Dalong , Qiu Xiaoyan 
Published: September 2008

DCUN1D3 (DCN1, defective in cullin neddylation 1, domain containing 3) was found during the process of high throughput screening of novel human genes associated with serum response element (SRE) pathway activation. The DCUN1D3 gene is highly conserved among vertebrates. Human DCUN1D3 complementary DNA (cDNA) encodes 304 amino acids with an apparent molecular mass of 34 kDa. However, there has been no report about the function of DCUN1D3. This study detected that DCUN1D3 was broadly expressed in several tumor tissues and cultured cell lines; however, UVC irradiation of different doses significantly increased DCUN1D3 expression level in these cancer cell lines. Over‐expression of the DCUN1D3 inhibits cell growth in HeLa. When the DCUN1D3 gene was silenced by siRNA in UVC‐treated HeLa, the cell cycle in S phase was remarkably blocked; furthermore, the UVC‐induced cell death was inhibited. In addition, DCUN1D3 localized mainly in the cytoplasm and perinuclear, but after UVC treatment, the DCUN1D3 gradually entered the nucleus. All the results above indicate that DCUN1D3 is a novel UVC‐response gene involved in cell cycle regulation and cell survival. (Cancer Sci 2008; 99: 2128–2135)
Antitumor and antimetastatic actions of anthrone‐C‐glucoside, cassialoin isolated from Cassia garrettiana heartwood in colon 26‐bearing mice
Authors: Kimura Yoshiyuki , Sumiyoshi Maho , Taniguchi Masahiko , Baba Kimiye 
Published: September 2008

We examined the antitumor and antimetastatic actions of 10‐hydroxy‐anthrone‐C‐glucoside cassialoin isolated from Cassia garrettiana heartwood in colon 26‐bearing mice. Cassialoin (5 and 10 mg/kg) inhibited tumor growth and metastasis to the abdomen and the expression of CD31 (angiogenesis marker) in the tumors, and it increased the numbers of the γ‐interferon (IFN‐γ)‐positive, CD8+ T and natural killer cells in the small intestine or spleen of colon 26‐bearing mice. Furthermore, cassialoin inhibited tumor‐induced angiogenesis in colon 26‐packed chamber‐bearing mice. We examined the metabolic activities in the blood, stomach and small intestine after p.o. administration of cassialoin to mice. These results suggest that cassialoin might be converted to chrysophanol through chrysophanol‐9‐anthrone and metabolized to aloe‐emodin from chrysophanol. Chrysophanol‐9‐anthrone inhibited vascular endothelial growth factor (VEGF) and matrix metallopeptidase‐9 expression in colon 26 cells at 5 and 10 µM, and it inhibited VEGF‐induced angiogenesis and migration in human umbilical vein endothelial cells (HUVEC) at 0.5–10 µM. Furthermore, chrysophanol‐9‐anthrone inhibited VEGF receptor (VEGFR)‐2 expression and VEGF‐induced VEGFR‐2 phosphorylation. Aloe‐emodin also inhibited the VEGF‐induced angiogenesis by HUVEC at 1–100 µM. Cassialoin, chrysophanol‐9‐anthrone and aloe‐emodin enhanced concanavalin A‐induced IFN‐γ production in splenocytes of colon 26‐bearing mice at a low concentration of 0.1 µM. From these results, it is suggested that the antitumor and antimetastatic actions of p.o. administered cassialoin may be partly due to cassialoin and its metabolites such as chrysophanol‐9‐anthrone and aloe‐emodin through their anti‐angiogenic activities and/or the modulation of the immune systems in the spleen and small intestine in tumor‐bearing mice. (Cancer Sci 2008; 99: 2336–2348)
Somatostatin receptor‐1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer
Authors: Li Min , Wang Xiaochi , Li Wei , Li Fei , Yang Hui , Wang Hao , Brunicardi F. Charles , Chen Changyi , Yao Qizhi , Fisher William E. 
Published: September 2008

Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR‐1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR‐1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR‐1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR‐1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR‐1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR‐1 caused cell cycle arrest at the G0/G1 growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR‐1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t‐test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t‐test), in Panc‐SSTR‐1 and MIA‐SSTR‐1 groups, respectively, indicating the potent inhibitory effect of SSTR‐1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR‐1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR‐1 may be a potential adjuvant treatment for pancreatic cancer. (Cancer Sci 2008; 99: 2218–2223)
TS‐1 enhances the effect of radiotherapy by suppressing radiation‐induced hypoxia‐inducible factor‐1 activation and inducing endothelial cell apoptosis
Authors: Zeng Lihua , Ou Guangfei , Itasaka Satoshi , Harada Hiroshi , Xie Xuejun , Shibuya Keiko , Kizaka‐Kondoh Shinae , Morinibu Akiyo , Shinomiya Kazumi , Hiraoka Masahiro 
Published: September 2008

The therapeutic effect of concurrent chemoradiotherapy with TS‐1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia‐inducible factor‐1 (HIF‐1) as one of the targets of TS‐1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non‐small‐cell lung carcinoma, H441, TS‐1 treatment enhanced the therapeutic effect of single γ‐ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58‐fold compared to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a HIF‐1‐dependent 5HRE‐luc reporter gene revealed that TS‐1 treatment suppressed radiation‐induced activation of HIF‐1 in the tumor xenografts. The suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density (P < 0.05; vs radiation therapy alone) and a significant increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in tumor xenografts. All of these results indicate that TS‐1 enhances radiation‐induced apoptosis of endothelial cells by suppressing HIF‐1 activity, resulting in an increase in radiosensitivity of the tumor cells. Our findings strengthen the importance of both HIF‐1 and its downstream gene, such as vascular endothelial cell growth factor, as therapeutic targets to enhance the effect of radiotherapy. (Cancer Sci 2008; 99: 2327–2335)
Frequent aberrant methylation of the promoter region of sterile α motif domain 14 in pulmonary adenocarcinoma
Authors: Sun Weihong , Iijima Tatsuo , Kano Junko , Kobayashi Hiromi , Li Dongping , Morishita Yukio , Okubo Chigusa , Anami Yoichi , Noguchi Masayuki 
Published: September 2008

Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of tumor‐suppressor and tumor‐related genes. In order to identify novel hypermethylated genes in early stage lung adenocarcinoma, we carried out methylated CpG island amplification, modified suppression subtractive hybridization, and methylation‐specific polymerase chain reaction to identify aberrant methylation of CpG islands in the A/J mouse lung adenoma model, which histologically mimics the early stage of human pulmonary adenocarcinoma. Through methylated CpG island amplification, suppression subtractive hybridization, and differential screening, we detected five genes, three of which have human homologs. Two of them showed downregulation of their expression in human lung adenocarcinoma. Of these two genes, we selected sterile α motif domain 14 (SAMD14) and further analyzed its methylation status and expression level by methylation‐specific polymerase chain reaction and quantitative real‐time polymerase chain reaction. Most of the lung adenocarcinoma cell lines showed suppressed expression of SAMD14 together with hypermethylation at the promoter region, although an immortalized bronchial epithelium cell line (PL16B) did not show hypermethylation and did express SAMD14. The expression of SAMD14 in A549 was rescued by treatment with the demethylation agent 5‐aza‐2′‐deoxycytidine. These data indicate that hypermethylation of the SAMD14 gene promoter region is associated with silencing of its expression. Hypermethylation at the CpG site of the SAMD14 promoter region was detected frequently in early invasive adenocarcinoma (8/24, 33.3%) but not in in situ adenocarcinoma (0/7, 0%) or normal lung tissue (0/31, 0%). Hypermethylation of the SAMD14 gene is a specific event in pulmonary adenocarcinogenesis and malignant progression. (Cancer Sci 2008; 99: 2177–2184)
Constitutive heterologous expression of avrXa27 in rice containing the R gene Xa27 confers enhanced resistance to compatible Xanthomonas oryzae strains
Authors: TIAN DONGSHENG , YIN ZHONGCHAO 
Published: September 2008

SUMMARYThe vascular pathogen Xanthomonas oryzae pv. oryzae (Xoo) and nonvascular pathogen Xanthomonas oryzae pv. oryzicola (Xoc) cause bacterial blight (BB) and bacterial leaf streak (BLS) diseases of rice, respectively. We have previously identified the avirulence gene avrXa27 from Xoo PXO99A, which specifically induces the expression of the rice resistance gene Xa27, ultimately leading to resistance against BB disease in rice. In this study, we have generated a transgenic rice line (L24) that expresses avrXa27 constitutively under the control of the PR1 promoter, and have examined its role in the host–pathogen interaction. L24 is not more susceptible to BB, indicating that avrXa27 does not contribute to virulence. AvrXa27 retains avirulence activity in L24 and, after crossing with a line containing Xa27, progeny display phenotypic changes including inhibition of tillering, delay in flowering, stiff leaves, early leaf senescence and activation of pathogenesis‐related (PR) genes. On challenge with a variety of compatible strains of Xoo and Xoc strain L8, lines with both avrXa27 and Xa27 also show enhanced resistance to bacterial infection. The induction of Xa27 and subsequent inhibition of Xoc growth in Xa27 plants are observed on inoculation with Xoc L8 harbouring avrXa27. Our results indicate that the heterologous expression of avrXa27 in rice containing Xa27 triggers R gene‐specific resistance and, at the same time, confers enhanced resistance to compatible strains of Xoo and Xoc. The expression of AvrXa27 and related proteins in plants has the potential to generate broad resistance in plants.
The effects of polymorphisms in the DGAT1, leptin and growth hormone receptor gene loci on body energy, blood metabolic and reproductive traits of Holstein cows
Authors: Oikonomou G. , Angelopoulou K. , Arsenos G. , Zygoyiannis D. , Banos G. 
Published: September 2008

SummaryThe objective of this study was to examine the impact of polymorphisms in the acyl‐CoA:diacylglycerol acyltransferase (DGAT1), leptin and growth hormone receptor genes on body energy (body condition score, total body energy content and cumulative effective energy balance) and blood metabolic traits (levels of β‐hydroxybutyrate, glucose and non‐esterified fatty acids), measured once before the first calving and then repeatedly throughout first lactation in 497 Holstein cows. The influence of the same polymorphisms on cow reproductive performance and health during the first and second lactations was also assessed. Several reproductive traits were considered including interval, conception and insemination traits, as well as incidence of metritis and reproductive problems. Genotyping was performed using PCR‐RFLP (DGAT1, leptin) or allele‐specific PCR (growth hormone receptor). For each locus, the effect of allele substitution on body energy and blood metabolic traits was estimated using random regression models. The same effect on reproductive traits was assessed with single‐trait mixed linear models. Significant (P < 0.05) effects on specific reproductive traits were observed. DGAT1 and growth hormone receptor alleles responsible for significant increases in milk production were found to have an adverse effect on reproduction, while the leptin allele responsible for significant increase in milk production was linked to marginally increased metritis frequency. Furthermore, the three studied loci were also found to significantly (P < 0.05) affect certain body energy and blood metabolic traits. Several associations are published for the first time, but these should be confirmed by other investigators before the polymorphisms are used in gene‐assisted selection.
Relationship between body size and homing ability in the genus Osmia (Hymenoptera; Megachilidae)
Authors: GUÉDOT CHRISTELLE , BOSCH JORDI , KEMP WILLIAM P. 
Published: September 2008

Abstract 1. The maximum homing ability of female bees, that is, their capacity to return to the nest after being displaced a certain distance, is considered to be an estimate of their maximum foraging distance.2. The present study provides data on homing ability and body weight for Osmia lignaria and combines them with data for five other congenerics, O. rufa, O. cornuta, O. pedicornis, O. cornifrons, and O. emarginata for analysis. These species are important pollinators of spring‐flowering plants, and some have been developed as commercial crop pollinators.3. It is shown that homing ability is positively and linearly related to body weight (r2 = 0.81; P = 0.01).4. These results should be of use in selecting Osmia species as potential crop pollinators and establishing adequate buffer distances around genetically modified crops.
Wounding‐mediated gene expression and accelerated viviparous reproduction of the pea aphid Acyrthosiphon pisum
Authors: Altincicek B. , Gross J. , Vilcinskas A. 
Published: September 2008

AbstractMost insects mount a potent antimicrobial defence upon contact with microbes or microbe‐associated pattern molecules. Using a combined set of methods for analysis of insect innate immunity, we report here that piercing of the pea aphid Acyrthosiphon pisum with a bacteria‐contaminated needle elicits lysozyme‐like activity in the haemolymph but no detectable activities against live bacteria. Confirming these results, we found no homologues of known antimicrobial peptides in our cDNA library generated by using the suppression subtractive hybridization method or in over 90 000 public expressed sequence tag (EST) sequences, but lysozyme genes have recently been described in A. pisum. Interestingly, we discovered that production of viviparous offspring was significantly accelerated upon wounding. Therefore, we postulate that aphids may increase terminal reproductive investment and limit antibacterial defence in response to a threat to their survival.
Exploring the Afromontane centre of endemism: Kniphofia Moench (Asphodelaceae) as a floristic indicator
Authors: Ramdhani Syd , Barker Nigel P. , Baijnath Himansu 
Published: September 2008

AbstractAim  The genus Kniphofia contains 71 species with an African–Malagasy distribution, including one species from Yemen. The genus has a general Afromontane distribution. Here we explore whether Kniphofia is a floristic indicator of the Afromontane centre of endemism and diversity. The South Africa Centre of diversity and endemism was explored in greater detail to understand biogeographical patterns.Location  Africa, Afromontane Region, southern Africa, Madagascar and Yemen.Methods  Diversity and endemism for the genus were examined at the continental scale using a chorological approach. Biogeographical patterns and endemism in the South Africa Centre were examined in greater detail using chorology, phenetics, parsimony analysis of endemicity (PAE) and mapping of range‐restricted taxa.Results  Six centres of diversity were recovered, five of which are also centres of endemism. Eight subcentres of diversity are proposed, of which only two are considered subcentres of endemism. The South Africa Centre is the most species‐rich region and the largest centre of endemism for Kniphofia. The phenetic analysis of the South Africa Centre at the full degree square scale recovered three biogeographical areas that correspond with the subcentres obtained from the chorological analysis. The PAE (at the full degree square scale) and the mapping of range‐restricted taxa recovered two and six areas of endemism (AOEs), respectively. These latter two approaches produced results of limited value, possibly as a result of inadequate collecting of Kniphofia species. Only two AOEs were identified by PAE and these are embedded within two of the six AOEs recovered by the mapping of range‐restricted taxa. All the above AOEs are within the three subcentres found by chorological and phenetic analysis (at the full degree square scale) for the South Africa Centre.Main conclusions  The centres for Kniphofia broadly correspond to the Afromontane regional mountain systems, but with some notable differences. We regard Kniphofia as a floristic indicator of the Afromontane Region sensu lato. In southern Africa, the phenetic approach at the full‐degree scale retrieved areas that correlate well with those obtained by the chorological approach.
Panmixia: an example from Dawson's burrowing bee (Amegilla dawsoni) (Hymenoptera: Anthophorini)
Authors: BEVERIDGE MAXINE , SIMMONS LEIGH W. 
Published: September 2008

AbstractDawson's burrowing bee is a large, fast‐flying solitary nesting bee endemic to the arid zone of Western Australia. In this study the population structure of the species was examined with molecular markers. Using eight microsatellite loci, we genotyped 531 adult female bees collected from 13 populations of Dawson's burrowing bee, Amegilla dawsoni, across the species range. The mean number of alleles per locus ranged from 4 to 38 and expected heterozygosity was uniformly high with a mean of 0.602. Pairwise comparisons of FST among all 13 populations ranged from 0.0071 to 0.0122 with only one significant estimate and an overall FST of 0.001. The entire sample collection was in Hardy–Weinberg equilibrium and there was no evidence of inbreeding with a mean FIS of 0.010. The mating and nesting behaviour of this bee suggests that gene flow would be limited by monandry and the fact that almost 90% of females mate immediately on emergence. Nevertheless there is obviously sufficient gene flow to maintain panmixia, and we suggest that this results from infrequent and unreliable rainfall in the species range, which causes the bees to congregate at limited food resources, allowing a small number of unmated females from one emergence site to come into contact with males from another population. In addition, when drought eliminates food resources near an emergence site, the whole population may move elsewhere, increasing gene flow across the species range.
Genetic variation in MHC class II expression and interactions with MHC sequence polymorphism in three‐spined sticklebacks
Authors: WEGNER K. M. , KALBE M. , RAUCH G. , KURTZ J. , SCHASCHL H. , REUSCH T. B. H. 
Published: September 2008

AbstractGenes of the major histocompatibility complex (MHC) have been studied for several decades because of their pronounced allelic polymorphism. Structural allelic polymorphism is, however, not the only source of variability subjected to natural selection. Genetic variation may also exist in gene expression patterns. Here, we show that in a natural population of three‐spined sticklebacks (Gasterosteus aculeatus) the expression of MHC class IIB genes was positively correlated with parasite load, which indicates increased immune activation of the MHC when infections are frequent. To experimentally study MHC expression, we used laboratory‐bred sticklebacks that were exposed to three naturally occurring species of parasite. We found strong differences in MHC class IIB expression patterns among fish families, which were consistent over two generations, thus demonstrating a genetic component. The average number of MHC class IIB sequence variants within families was negatively correlated to the MHC expression level suggesting compensatory up‐regulation in fish with a low (i.e. suboptimal) MHC sequence variability. The observed differences among families and the negative correlation with individual sequence diversity imply that MHC expression is evolutionary relevant for the onset and control of the immune response in natural populations.