bluuebunny/crossref_metadata_2025_split huggingface dataset:
A neural network model for constructing endophenotypes of common complex diseases: an application to male young-onset hypertension microarray data
Authors: Lynn Ke-Shiuan , Li Li-Lan , Lin Yen-Ju , Wang Chiuen-Huei , Sheng Shu-Hui , Lin Ju-Hwa , Liao Wayne , Hsu Wen-Lian , Pan Wen-Harn 
Published: February 2009

Abstract
Motivation: Identification of disease-related genes using high-throughput microarray data is more difficult for complex diseases as compared with monogenic ones. We hypothesized that an endophenotype derived from transcriptional data is associated with a set of genes corresponding to a pathway cluster. We assumed that a complex disease is associated with multiple endophenotypes and can be induced by their up/downregulated gene expression patterns. Thus, a neural network model was adopted to simulate the gene–endophenotype–disease relationship in which endophenotypes were represented by hidden nodes.
Results: We successfully constructed a three-endophenotype model for Taiwanese hypertensive males with high identification accuracy. Of the three endophenotypes, one is strongly protective, another is weakly protective and the third is highly correlated with developing young-onset male hypertension. Sixteen of the involved 101 genes were highly and consistently influential to the endophenotypes. Identification of SLC4A5, SLC5A10 and LDOC1 indicated that sodium/bicarbonate transport, sodium/glucose transport and cell-proliferation regulation may play important upstream roles and identification of BNIP1, APOBEC3F and LDOC1 suggested that apoptosis, innate immune response and cell-proliferation regulation may play important downstream roles in hypertension. The involved genes not only provide insights into the mechanism of hypertension but should also be considered in future gene mapping endeavors.
Availability: Microarray data and test program are available at http://ms.iis.sinica.edu.tw/microarray/index.htm
Contact: pan@ibms.sinica.edu.tw or hsu@iis.sinica.edu.tw
Supplementary information: Supplementary data are available at Bioinformatics online.
Surviving a sea-change: survival of southern rock lobster (Jasus edwardsii) translocated to a site of fast growth
Authors: Green Bridget S. , Gardner Caleb 
Published: February 2009

Abstract
Green, B. S., and Gardner, C. 2009. Surviving a sea-change: survival of southern rock lobster (Jasus edwardsii) translocated to a site of fast growth. – ICES Journal of Marine Science, 66: 656–664. In an experiment aimed at increasing the yield and value of the fishery for southern rock lobster (Jasus edwardsii), 1998 pale and slow-growing lobsters were translocated to sites where lobsters grow faster naturally and develop higher value market traits. Survival of lobsters in their new habitat was critical to the viability of this experiment. To estimate survival, the release site was surveyed every 1–3 months for 2 years. Apparent survival of translocated lobsters was compared with survival of resident lobsters tagged in a similar period using Cormack–Jolly–Seber modelling on mark–recapture data. Lobster survival was not influenced by size, gender, or origin (translocated or resident) alone. The four most parsimonious models suggested slightly lower apparent survival in translocated lobsters immediately after release compared with all other lobsters, but support for these models was weak (∑QAICc weights 62%). The differences in apparent survival were not likely to be significant because of large variance when averaged over all the models. Apparent survival of newly released translocated lobsters was 92% (72–98, 95% CI) compared with 97% (95–98, 95% CI) for all other lobsters. Potential sources of differences in survival are movement from the release site or greater predation on pale lobsters. Losses of lobster through release mortality were low and unlikely to influence the feasibility of translocation as a tool to enhance the value of the fishery, although it would be prudent to include 5% mortality of translocated lobsters in future models of translocation feasibility.
Species delimitation and evolution of metal bioaccumulation in the lichenized Acarospora smaragdula (Ascomycota, Fungi) complex
Authors: Wedin Mats , Westberg Martin , Crewe Anna T. , Tehler Anders , Purvis O. William 
Published: February 2009

AbstractThe crustose lichenized fungi in the Acarosporaceae are splendid examples of organisms managing to survive in extremely harsh environments, such as highly mineralized rocks and low‐pH habitats. Some representatives of the Acarospora smaragdula complex are known to accumulate substantial amounts of potentially toxic metals including iron and copper, resulting in populations with highly divergent coloration and morphology. These populations have often been treated as distinct species by lichen taxonomists. Parsimony and parsimony jackknifing analyses of β‐tubulin, nuclear ITS rDNA, and mtSSU rDNA sequence data sets was used to investigate the evolution of iron and copper accumulation and the production of the secondary compound norstictic acid in populations within the A. smaragdula species complex in Sweden, with additional samples mainly from Norway and the UK. Phylogenetic species recognition (concordance of single‐gene phylogenies) was used to investigate species delimitations. Seven species are recognized in the complex. Atypically green, copper‐accumulating samples, often given species rank, do not form a distinct group but are nested within A. smaragdula s. str., indicating that this ability is widespread in this species. Rust‐coloured, iron‐accumulating samples form two well supported separate groups, indicating that two morphologically distinct, obligate, iron‐accumulating species are present, but facultatively iron‐accumulating populations occur in at least one additional species. Norstictic acid, sometimes claimed to characterize the whole A. smaragdula complex, is only present in A. smaragdula s. str. The evolutionary significance of metal accumulation in Acarospora is discussed, as is the significance of our results for the application of phylogenetic species recognition/gene tree concordance‐based species recognition, and DNA barcoding.  © The Willi Hennig Society 2009.
Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells
Authors: Kobune Masayoshi , Takimoto Rishu , Murase Kazuyuki , Iyama Satoshi , Sato Tsutomu , Kikuchi Shohei , Kawano Yutaka , Miyanishi Kohji , Sato Yasushi , Niitsu Yoshiro , Kato Junji 
Published: February 2009

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers and in cancer stem cells. However, the contribution of Hh signaling to leukemic cell regulation has remained unclear. In this study, we assessed the possibility that Hh pathway activation contributes to the survival and drug resistance of cluster of differentiation (CD)34+ leukemia cells. Hh signaling in leukemic cell lines and primary leukemic cells was screened by reverse transcription – polymerase chain reaction (RT‐PCR) and a Hh signaling reporter assay. We found that Hh signaling is active in several human acute myeloid leukemia (AML) cells, especially primary CD34+ leukemic cells and cytokine‐responsive CD34+ cell lines such as Kasumi‐1, Kasumi‐3 and TF‐1. These CD34+ cells express the downstream effectors glioma‐associated oncogene homolog (GLI)1 or GLI2, indicative of active Hh signaling. Moreover, inhibition of Hh signaling with the naturally derived Smoothened antagonist cyclopamine, endogenous Hh inhibitor hedgehog‐interacting protein or anti‐hedgehog neutralizing antibody induced apoptosis after 48 h of exposure, although these CD34+ cell lines exhibited resistance to cytarabine (Ara‐C). In contrast, cyclopamine failed to affect growth or survival in U937 and HL‐60 cell lines that lack expression of Hh receptor components, confirming that the effect of Hh inhibition is specific. Furthermore, combination with 10 µM cyclopamine significantly reduced drug resistance of CD34+ cell lines and primary CD34+ leukemic cells to Ara‐C. These results suggest that aberrant Hh pathway activation is a feature of some CD34+ myeloid leukemic cells and Hh inhibitors may have a therapeutic role in the treatment of AML. (Cancer Sci 2009; 100: 948–955)
Combination immunotherapy with radiation and CpG‐based tumor vaccination for the eradication of radio‐ and immuno‐resistant lung carcinoma cells
Authors: Chamoto Kenji , Takeshima Tsuguhide , Wakita Daiko , Ohkuri Takayuki , Ashino Shigeru , Omatsu Tokuhiko , Shirato Hiroki , Kitamura Hidemitsu , Togashi Yuji , Nishimura Takashi 
Published: February 2009

Unmethylated cytosine‐phosphorothioate‐guanine containing oligodeoxynucleotides (CpG‐ODN) is known as a ligand of toll‐like receptor 9 (TLR9), which selectively activates type‐1 immunity. We have already reported that the vaccination of tumor‐bearing mice with liposome‐CpG coencapsulated with model‐tumor antigen, ovalbumin (OVA) (CpG + OVA‐liposome) caused complete cure of the mice bearing OVA‐expressing EG‐7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)‐OVA‐carcinoma. To overcome the refractoriness of LLC‐OVA, we tried the combination therapy of radiation with CpG‐based tumor vaccination. When LLC‐OVA‐carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7–8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA‐liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA‐liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA‐liposome allowed the augmented induction of OVA‐tetramer+ LLC‐OVA‐specific cytotoxic T lymphocyte (CTL) in DLN of tumor‐bearing mice. These results indicate that the combined therapy of radiation with CpG‐based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934–939)
Quantitative trait loci meta‐analysis of Plum pox virus resistance in apricot (Prunus armeniaca L.): new insights on the organization and the identification of genomic resistance factors
Authors: MARANDEL GRÉGOIRE , SALAVA JAROSLAV , ABBOTT ALBERT , CANDRESSE THIERRY , DECROOCQ VÉRONIQUE 
Published: February 2009

SUMMARY Plum pox virus (PPV) is responsible for sharka disease, one of the most detrimental stone fruit diseases affecting Prunus trees worldwide. Only a few apricot cultivars have been described as resistant, most originating from North American breeding programmes. Several PPV resistance quantitative trait loci (QTLs) have been mapped in various progenies, consistently highlighting the contribution to the resistance of the upper part of linkage group 1 (LG1). However, to date, no consensus has been reached on the precise number of QTLs linked to the resistance to PPV in apricot and P. davidiana or on their accurate position on the genetic linkage map. In the present study, the quantitative resistance of cultivar ‘Harlayne’ was analysed over five growth periods in a large F1 population. Four QTLs were identified, three mapping on LG1, explaining between 5% and 39% of the observed phenotypic variance. In an effort to further this analysis of PPV resistance in apricot, these results were merged in a single QTL meta‐analysis with those of five other PPV resistance analyses available in the literature. Three consensus QTL regions were identified on LG1 and a putative fourth region on LG3. QTL meta‐analysis also revealed the contribution of each resistant cultivar to metaQTLs, providing interesting comparative data on the resistance factors shared between the resistance sources used in the various studies. Finally, it was shown that one of the metaQTLs co‐localizes with the eukaryotic translation initiation factor eIF4E, thus providing new hypotheses on the mechanisms of PPV resistance in apricot.
Levels of aloe mortality with and without elephants in the Thicket Biome of South Africa
Authors: Parker D. M. , Bernard R. T. F. 
Published: February 2009

AbstractStudies concerning the influence of African elephants (Loxodonta africana) on vegetation have produced contradictory results; some show minimal or no effect while others report significant elephant‐induced effects. Elephants are generalist megaherbivores but will selectively feed from preferred plant species. We investigated the mortality of aloe plants (highly preferred food items for elephants) at five sites with elephants (treatment) and five paired sites without elephants (control) in the Eastern Cape Province of South Africa. A significantly higher proportion of aloes were dead at treatment sites and significantly more aloes that had lost their crown (headless) were found at treatment sites compared with controls. We conclude that although the proportions of dead aloes at treatment sites were significantly higher, it remains unclear whether there is a need to be concerned with the potential small‐scale extinction of aloes from parts of the Eastern Cape Province. The observed mortality may merely be an artefact of the loss of large herbivores through disease (e.g. rinderpest) and hunting in the past.
Involvement of tazarotene‐induced gene 1 in proliferation and differentiation of human adipose tissue‐derived mesenchymal stem cells
Authors: Ohnishi S. , Okabe K. , Obata H. , Otani K. , Ishikane S. , Ogino H. , Kitamura S. , Nagaya N. 
Published: February 2009

AbstractObjective:  Mesenchymal stem cells (MSC) have both self‐renewal and multilineage differentiation potential, and bone marrow‐derived MSC have been applied for tissue regeneration and repair. Although adipose tissue‐derived MSC (ASC) have emerged as an alternative cell source, little information is available regarding the biologic difference between ASC derived from visceral and subcutaneous fat. Therefore, we aimed to compare the proliferation and gene expression profile of cultured human visceral ASC (VASC) and subcutaneous ASC (SASC), and to identify a novel gene involved in proliferation and differentiation of ASC.Materials and methods:  We performed microarray analysis of cultured VASC and SASC, and investigated the role of tazarotene‐induced gene 1 (TIG1), a most differentially expressed gene, in the proliferation and differentiation of ASC.Results:  SASC proliferated faster than VASC for over 10 passages, and TIG1 expression was consistently up‐regulated in VASC of humans, rats and mice. Overexpression of the TIG1 gene in human SASC inhibited cell proliferation, whereas knockdown of TIG1 expression by siRNA promoted cell proliferation. In addition, overexpression of the TIG1 gene in SASC enhanced their differentiation into adipocytes, and promoted up‐regulation of peroxisome proliferators‐activated receptor γ and CCAAT/enhancer binding protein α. On the other hand, TIG1 overexpression in SASC inhibited their differentiation into osteocytes and the expression of osteocalcin.Conclusion:  TIG1 plays an important role in regulating proliferation and differentiation of ASC.
Fibroblastic response to treatment with different preparations rich in growth factors
Authors: Anitua E. , Sánchez M. , Zalduendo M. M. , De La Fuente M. , Prado R. , Orive G. , Andía I. 
Published: February 2009

AbstractObjectives:  Preparations rich in growth factors (PRGF) release them plus bioactive proteins at localized sites, with the aim of triggering healing and regenerative processes. The prevailing paradigm suggests that their influence on proliferation, angiogenesis and the extracellular matrix synthesis is minimal. However, variations in their composition and impact on different cell phenotypes have not been examined.Materials and methods:  Sixteen fibroblast cultures obtained from three different anatomical sites (skin, synovium and tendon) of 16 donors were exposed to the molecular pool released from PRGF scaffolds, with increasing amounts of platelets. We evaluated cell proliferation, secretion of angiogenic growth factors (VEGF and HGF), synthesis of type I collagen and hyaluronic acid (HA), considering platelet dose and anatomical origin of the cells. Activity of transforming growth factor‐beta (TGF‐β) in type I procollagen and HA synthesis was examined by adding exogenous TGF‐β to plasma preparations.Results:  All plasma preparations induced a significant proliferative response compared to non‐stimulated cells (P < 0.05). Maximum proliferation rate was obtained with PRGF with 2‐fold or 4‐fold platelet concentration. Exposure to PRGF stimulated VEGF synthesis exclusively in tendon cells (P < 0.05), which also exhibited a different pattern of HGF production (P < 0.05). PRGF enhanced HA synthesis (P < 0.05), but did not alter collagen I production. Platelet‐secreted TGF‐β may be involved in HA, but not in type I procollagen synthesis.Conclusions:  Optimizing composition and use of platelet‐rich products is crucial to enhancing the therapeutic potential of this technology. Our data show that the biological effects of PRGF may depend on concentration of platelets and on the anatomical source of the cells.
Developing policy in the provision of parenting programmes: integrating a review of reviews with the perspectives of both parents and professionals
Authors: Law J. , Plunkett C. , Taylor J. , Gunning M. 
Published: February 2009

AbstractBackground  Parenting programmes are a key component of the delivery of children's services, but evidence‐based policy has often proved difficult to implement.Methods  The present review addressed this issue by integrating a review of systematic reviews of parenting programmes and a series of focus groups with parents and professionals involved in parenting across three agencies in a regional area (health, education and social work). The review summarizes parenting interventions targeting infant mental health, emotional and behavioural difficulties, autism spectrum disorder and attention deficit hyperactivity disorder, abuse/neglect, alcohol/substance abuse and ‘vulnerable’ parents. The focus groups discussed topics such as the range of parenting services across the three agencies, accessibility, gaps in the service and future directions.Results and conclusions  Twenty systematic reviews were summarized. These reviews demonstrated that there is a wide range of parenting programmes available that have the potential to benefit families who are affected by problems ranging from emotional and behavioural difficulties to adolescent substance abuse. However, the findings of the focus groups reveal that the success of these programmes will depend in part on how they can be tailored to meet the social context of the families targeted. These integrated findings are discussed in terms of their implications for policy and practice.
Cognitive evaluation in children and adolescents with Möbius sequence
Authors: Briegel W. , Schimek M. , Knapp D. , Holderbach R. , Wenzel P. , Knapp E.‐M. 
Published: February 2009

AbstractBackground  Möbius sequence is a rare condition usually defined as uni‐ or bilateral congenital facial weakness with impairment of ocular abduction. Mental retardation is estimated to occur in 10–15% of cases, but at present there have been no studies focusing on the intellectual capacities of children and adolescents with Möbius sequence.Methods  Twenty‐three children and adolescents aged 6–16 years could be recruited following a request of the German Möbius foundation. The primary caregivers of all subjects filled out a special questionnaire to compile personal, somatic and psychosocial history of the probands. All subjects had a physical examination. To assess intellectual capacities, the German version of the Wechsler Intelligence Test‐III (WISC‐III) was administered. In case of a severe mental retardation, the Vineland Adaptive Behavior Rating Form was used as an alternative.Results  Twenty‐two subjects [12 males, 10 females; mean age: 11.3 (6–16) years] could be included; 21 could be examined with the WISC‐III. Compared with the normative sample, Full Scale IQ (mean: 92.05; standard deviation: 14.84) was significantly lower (P = 0.023) which was the consequence of a very low Performance IQ (mean: 80.48; standard deviation: 15.84). Compared with the normative sample, the results of all performance subtests were significantly lower (P = 0.033–0.000), whereas verbal subtest scores did not differ or were even higher [‘Similarities’ (P = 0.026) and ‘Vocabulary’ (P = 0.019)]. Verbal IQ (mean: 106.24; standard deviation: 15.31) was not significantly different from the normative sample. Two boys met ICD‐10 criteria for mental retardation. Full Scale IQ was not predictive for academic success.Conclusions  The WISC‐III is not an adequate predictor for academic success in Möbius patients; intelligence tests which are less dependant on time constraints should be preferred for subjects with Möbius sequence.
The use of the Impact on Sibling scale with families of children with chronic illness and developmental disability
Authors: Kao B. , Plante W. , Lobato D. 
Published: February 2009

AbstractObjective  This study evaluated the Impact on Sibling scale, a six‐item measure of parents' perception of the effects of a child's illness on healthy siblings.Methods  Participants were 122 parents of a child with chronic illness, developmental disability, or autism spectrum disorder, and a well sibling aged 4–13 years. Parents completed the Impact on Sibling scale and the Child Behavior Checklist about the sibling, and completed the revised Impact on Family scale and the Brief Symptom Inventory about themselves.Results  The Impact on Sibling score was correlated with measures of sibling, parent and family functioning. The internal consistency of the Impact on Sibling scale was higher for families with children with chronic illness compared with the other two diagnostic groups.Conclusion  The Impact on Sibling scale is a brief set of items that can help identify siblings who are negatively affected by a brother/sister's illness. Findings support further research on the Impact on Sibling scale, particularly with families of children with chronic illnesses.
Long‐term behavioural outcomes of pre‐school mild traumatic brain injury
Authors: McKinlay A. , Grace R. C. , Horwood L. J. , Fergusson D. M. , MacFarlane M. R. 
Published: February 2009

AbstractBackground  Mild traumatic brain injury (MTBI) is a leading cause of injury for children during their pre‐school years. However, there is little information regarding the long‐term outcomes of these injuries.Method  We used fully prospective data from an epidemiological study of a birth cohort to examine behavioural effects associated with MTBI during the pre‐school years. Cases of confirmed MTBI were divided into two groups, those that had received outpatient medical attention, and those that had been admitted to hospital for a brief period of observation (inpatient cases). The remainder of the cohort served as a reference control group.Results  Mother/teacher ratings for behaviours associated with attention deficit/hyperactivity disorder and oppositional defiant/conduct disorder, obtained yearly from age 7 to 13, revealed evidence of deficits after inpatient MTBI (n = 21), relative to more minor outpatient injury MTBI (n = 55) and the reference control group (n = 852). For the inpatient group there was evidence of increasing deficits over years 7–13.Conclusions  More severe pre‐school MTBI may be associated with persistent negative effects in terms of psychosocial development. The vulnerability of pre‐school children to MTBI signals a pressing need to identify high‐risk cases that may benefit from monitoring and early intervention.