bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative diffusion-weighted magnetic resonance imaging of normal and diseased uterine zones
Authors: Kilickesmez O. , Bayramoglu S. , Inci E. , Cimilli T. , Kayhan A.
Published: February 2009

Background: Magnetic resonance (MR) imaging has been established as the best imaging modality for the detection, localization, and staging of uterine cancers. Recently, the usefulness of diffusion-weighted imaging (DWI) in the diagnosis of cancers has been reported in several studies.

Purpose: To calculate the apparent diffusion coefficient (ADC) values of normal uterine zones as well as benign and malignant uterine diseases, and to determine a cut-off ADC value for the quantitative detection of uterine malignancies with DWI.

Material and Methods: Eighty-seven patients (mean age 53 years) with 107 benign and malignant uterine pathologies and 50 healthy controls (mean age 38 years) were enrolled in the study. DWI was performed with b factors of 0, 500, and 1000 s/mm2.

Results: The ADC values of benign and malignant lesions were compared using Student's t test. The mean and the standard deviation of the ADC values of the control group were as follows: myometrium 1.76±0.19×10−3 mm2/s, junctional zone 0.99±0.18×10−3 mm2/s, endometrium 1.65±0.33×10−3 mm2/s, and cervix 1.71±0.17×10−3 mm2/s. There was a statistically significant difference among the ADC values of normal myometrium and leiomyomas (1.47±0.36×10−3 mm2/s; P<0.009), endometrium and endometrial carcinomas (0.86±0.13×10−3 mm2/s; P<0.001), myometrium-junctional zone and adenomyosis (1.24±0.20×10−3mm2/s; P<0.001), and cervix and cervical carcinomas (0.91±0.14×10−3 mm2/s; P<0.001). The ADC values differed significantly between malignant (0.88±0.11) and benign lesions (1.55±0.33; P<0.01). A cut-off value for malignant lesions of 1.05×10−3 mm2/s yielded a sensitivity, specificity, and accuracy of 95.83%, 94.55%, and 94.94%, respectively.

Conclusion: The present study shows that ADC measurements have the potential to quantitatively differentiate between normal and cancerous tissues of the uterine zones. We propose adding DWI as an adjunct sequence in the MR protocol for the assessment of uterine lesions.
Evaluation of possible prognostic factors of fulminant acute disseminated encephalomyelitis (ADEM) on magnetic resonance imaging with fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging
Authors: Donmez F. Y. , Aslan H. , Coskun M.
Published: February 2009

Background: Acute disseminated encephalomyelitis (ADEM) may be a rapidly progressive disease with different clinical outcomes.

Purpose: To investigate the radiological findings of fulminant ADEM on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images, and to correlate these findings with clinical outcome.

Material and Methods: Initial and follow-up magnetic resonance imaging (MRI) scans in eight patients were retrospectively evaluated for distribution of lesions on FLAIR images and presence of hemorrhage or contrast enhancement. DWI of the patients was evaluated as to cytotoxic versus vasogenic edema. The clinical records were analyzed, and MRI results and clinical outcome were correlated.

Results: Four of the eight patients died, three had full recovery, and one had residual cortical blindness. The distribution of the hyperintense lesions on FLAIR sequence was as follows: frontal (37.5%), parietal (50%), temporal (37.5%), occipital (62.5%), basal ganglia (50%), pons (37.5%), mesencephalon (37.5%), and cerebellum (50%). Three of the patients who died had brainstem involvement. Two patients had a cytotoxic edema, one of whom died, and the other developed cortical blindness. Six patients had vasogenic edema: three of these patients had a rapid progression to coma and died; three of them recovered.

Conclusion: DWI is not always helpful for evaluating the evolution or predicting the outcome of ADEM. However, extension of the lesions, particularly brainstem involvement, may have an influence on the prognosis.
Independent Regulation of Periarteriolar and Perivenular Nitric Oxide Mechanisms in the In Vivo Hamster Cheek Pouch Microvasculature
Authors: KIM DAVID D. , KANETAKA TAKEHITO , DURÁN RICARDO G. , SÁNCHEZ FABIOLA A. , BOHLEN H. GLENN , DURÁN WALTER N.
Published: February 2009

Objective: We tested the hypothesis that differential stimulation of nitric oxide (NO) production can be induced in pre‐ and postcapillary segments of the microcirculation in the hamster cheek pouch.

Materials and Methods: We applied acetylcholine (ACh) or platelet‐activating factor (PAF) topically and measured perivascular NO concentration ([NO]) with NO‐sensitive microelectrodes in arterioles and venules of the hamster cheek pouch. We also measured NO in cultured coronary endothelial cells (CVEC) after ACh or PAF.

Results: ACh increased periarteriolar [NO] significantly in a dose‐dependent manner. ACh at 1 μM increased [NO] from 438.1±43.4 nM at baseline to 647.9±66.3 nM, while 10 μM of ACh increased [NO] from baseline to 1,035.0±59.2 nM (P<0.05). Neither 1 nor 10 μM of ACh changed perivenular [NO] in the hamster cheek pouch. PAF, at 100 nM, increased perivenular [NO] from 326.6±50.8 to 622.8±41.5 nM. Importantly, 100 nM of PAF did not increase periarteriolar [NO]. PAF increased [NO] from 3.6±2.1 to 455.5±19.9 in CVEC, while ACh had no effect.

Conclusions: We conclude that NO production can be stimulated in a differential manner in pre‐ and postcapillary segments in the hamster cheek pouch. ACh selectively stimulates the production of NO only in arterioles, while PAF stimulates the production of NO only in venules.
Developing and Launching the Government Social Franchise Model of Reproductive Health Care Service Delivery in Vietnam
Authors: Ngo Anh D. , Alden Dana L. , Hang Nguyen , Dinh Nhuan
Published: February 2009

Social franchising, an effective social marketing business model, has increased the quality of health care services in developing and developed countries. Typically, private sector physicians and pharmacies are recruited by local or international nonprofit organizations into branded networks of clinics that benefit from economies of scale, a standardized business model, higher quality services, and sophisticated social marketing. While generally effective in the private sector, social franchising of public government operated clinics is very limited. As a result, the social franchise model is relatively untested as a means of enhancing the capacity and quality of public health care services for individuals with limited financial resources. Addressing the need for additional study, this case analysis traces development and launch of a social franchise network of reproductive health services through community public health clinics in two provinces in central Vietnam. Improvement of the clinic infrastructure, increased standardization of quality services, staff instruction on proactive relationship management, and promotion of a culturally relevant brand all appear to have contributed to the successful launch of the network in this case study. The decision to implement a standardized schedule of affordable service fees in one of the two provinces also appears to have improved perceived service quality. Implementation of planned staff incentives has proven to be the most challenging aspect of what is referred to as the government social franchise (GSF) model. Overall, initial evaluation suggests that significant improvement in reproductive health care service quality can be achieved through adaptation of the social franchise model to public sector context.
Integration of Social Marketing Elements in the Design of a Physical Activity Program for Preschoolers
Authors: Bellows Laura , Anderson Jennifer , Davies Patricia , Kennedy Catherine
Published: February 2009

As obesity rates in young children continue to rise, the need for innovative nutrition- and physical activity-focused programs is apparent. With limited preschool obesity prevention efforts, a physical activity program, Food Friends Get Movin' with Mighty Moves™, has been developed to compliment a successful nutrition social marketing campaign, Food Friends®. Building off formative research findings, this article focuses on two other stages of the social marketing process – the strategy development and program development – and how elements of the marketing framework were integrated into the design of Mighty Moves. Input from children, teachers, and early childhood specialists greatly contributed to strategy refinement, solidification of the exchange principle, and program development. This information increased the likelihood that the intervention would affect the desired behavior change or product. Superhero graphics were developed for the program as well as creative and engaging program concepts and materials.
Surveillance Cultures for Detection of Methicillin-Resistant Staphylococcus aureus: Diagnostic Yield of Anatomic Sites and Comparison of Provider- and Patient-Collected Samples
Authors: Lautenbach Ebbing , Nachamkin Irving , Hu Baofeng , Fishman Neil O. , Tolomeo Pam , Prasad Priya , Bilker Warren B. , Zaoutis Theoklis E.
Published: February 2009

We studied provider- and patient-collected samples from multiple anatomic sites to determine the yield for detection of methicillin-resistant Staphylococcus aureus (MRSA). Sampling of multiple sites was required to achieve a sensitivity of more than 90% for MRSA colonization. Groin and perineum samples yielded positive results significantly more often for community-onset MRSA than for hospital-onset MRSA. Agreement rates between provider- and patient-collected swab specimens were excellent.
PAnnBuilder: an R package for assembling proteomic annotation data
Authors: Li Hong , Ding Guohui , Xie Lu , Li Yixue
Published: February 2009

Summary: PAnnBuilder is an R package to automatically assemble protein annotation information from public resources to provide uniform annotation data for large-scale proteomic studies. Sixteen public databases have been parsed and 54 annotation packages have been constructed based on R environment or SQLite database. These ready-to-use packages cover most frequently needed protein annotation for three model species including human, mouse and rat. Several extended applications such as annotation based on protein sequence similarity are also provided. Sophisticated users can develop their own packages using PAnnBuilder. PAnnBuilder may become an important tool for proteomic research.

Availability: PAnnBuilder and example annotation packages are freely available from http://www.biosino.org/PAnnBuilder/

Contact:  xielu@scbit.org; yxli@sibs.ac.cn
iMembrane: homology-based membrane-insertion of proteins
Authors: Kelm Sebastian , Shi Jiye , Deane Charlotte M.
Published: February 2009

Summary: iMembrane is a homology-based method, which predicts a membrane protein's position within a lipid bilayer. It projects the results of coarse-grained molecular dynamics simulations onto any membrane protein structure or sequence provided by the user. iMembrane is simple to use and is currently the only computational method allowing the rapid prediction of a membrane protein's lipid bilayer insertion. Bilayer insertion data are essential in the accurate structural modelling of membrane proteins or the design of drugs that target them.

Availability:  http://imembrane.info. iMembrane is available under a non-commercial open-source licence, upon request.

Contact:  kelm@stats.ox.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online and at http://www.stats.ox.ac.uk/proteins/resources.
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

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

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.
Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2
Authors: Katoh Takayuki , Sakaguchi Yuriko , Miyauchi Kenjyo , Suzuki Takeo , Kashiwabara Shin-ichi , Baba Tadashi , Suzuki Tsutomu
Published: February 2009

The steady-state levels of microRNAs (miRNAs) and their activities are regulated by the post-transcriptional processes. It is known that 3′ ends of several miRNAs undergo post-dicing adenylation or uridylation. We isolated the liver-specific miR-122 from human hepatocytes and mouse livers. Direct analysis by mass spectrometry revealed that one variant of miR-122 has a 3′-terminal adenosine that is introduced after processing by Dicer. We identified GLD-2, which is a regulatory cytoplasmic poly(A) polymerase, as responsible for the 3′-terminal adenylation of miR-122 after unwinding of the miR-122/miR-122* duplex. In livers from GLD-2-null mice, the steady-state level of the mature form of miR-122 was specifically lower than in heterozygous mice, whereas no reduction of pre-miR-122 was observed, demonstrating that 3′-terminal adenylation by GLD-2 is required for the selective stabilization of miR-122 in the liver.
F-box proteins regulate ethylene signaling and more
Authors: Wang Xuelu , Kong Hongzhi , Ma Hong
Published: February 2009

Ethylene regulates several aspects of plant development, such as fruit ripening. In this issue of Genes & Development, Qiao and colleagues (pp. 512–521) report that the stability of the ethylene signaling protein EIN2 is modulated by two F-box proteins ETP1/2, reminiscent of the finding that another regulator of ethylene response, EIN3, is also targeted by the F-box proteins EBF1/2. ETP1/2 and EBF1/2 show distinct phylogenetic patterns, suggesting that they have different evolutionary constraints.
Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information
Authors: Viosca Jose , Malleret Gaël , Bourtchouladze Rusiko , Benito Eva , Vronskava Svetlana , Kandel Eric R. , Barco Angel
Published: February 2009

The activation of cAMP-responsive element-binding protein (CREB)-dependent gene expression is thought to be critical for the formation of different types of long-term memory. To explore the consequences of chronic enhancement of CREB function on spatial memory in mammals, we examined spatial navigation in bitransgenic mice that express in a regulated and restricted manner a constitutively active form of CREB, VP16-CREB, in forebrain neurons. We found that chronic enhancement of CREB activity delayed the acquisition of an allocentric strategy to solve the hidden platform task. The ability to turn on and off transgene expression allowed us to dissect the role of CREB in dissociable memory processes. In mice in which transgene expression was turned on during memory acquisition, turning off the transgene re-established the access to the memory trace, whereas in mice in which transgene expression was turned off during acquisition, turning on the transgene impaired memory expression in a reversible manner, indicating that CREB enhancement specifically interfered with the retrieval of spatial information. The defects on spatial navigation in mice with chronic enhancement of CREB function were not corrected by conditions that increased further CREB-dependent activation of hippocampal memory systems, such as housing in an enriched environment. These results along with previous findings in CREB-deficient mutants indicate that the relationship of CREB-mediated plasticity to spatial memory is an inverted-U function, and that optimal learning in the water maze requires accurate regulation of this pathway.
Square-grid coordination networks of (5,10,15,20-tetra-4-pyridylporphyrinato)zinc(II) in its clathrate with two guest molecules of 1,2-dichlorobenzene: supramolecular isomerism of the porphyrin self-assembly
Authors: Koner Rajesh , Goldberg Israel
Published: February 2009

The title compound, (5,10,15,20-tetra-4-pyridylporphyrinato)zinc(II) 1,2-dichlorobenzene disolvate, [Zn(C40H24N8)]·2C6H4Cl2, contains a clathrate-type structure. It is composed of two-dimensional square-grid coordination networks of the self-assembled porphyrin moiety, which are stacked one on top of the other in a parallel manner. The interporphyrin cavities of the overlapping networks combine into channel voids accommodated by the dichlorobenzene solvent. Molecules of the porphyrin complex are located on crystallographic inversion centres. The observed two-dimensional assembly mode of the porphyrin units represents a supramolecular isomer of the unique three-dimensional coordination frameworks of the same porphyrin building block observed earlier. The significance of this study lies in the discovery of an additional supramolecular isomer of the rarely observed structures of metalloporphyrins self-assembled directly into extended coordination polymers without the use of external ligand or metal ion auxiliaries.
Colouring cryo-cooled crystals: online microspectrophotometry
Authors: McGeehan John , Ravelli Raimond B. G. , Murray James W. , Owen Robin Leslie , Cipriani Florent , McSweeney Sean , Weik Martin , Garman Elspeth F.
Published: February 2009

X-rays can produce a high concentration of radicals within cryo-cooled macromolecular crystals. Some radicals have large extinction coefficients in the visible (VIS) range of the electromagnetic spectrum, and can be observed optically and spectrally. An online microspectrophotometer with high temporal resolution has been constructed that is capable of measuring UV/VIS absorption spectra (200–1100 nm) during X-ray data collection. The typical X-ray-induced blue colour that is characteristic of a wide range of cryo-conditions has been identified as trapped solvated electrons. Disulphide-containing proteins are shown to form disulphide radicals at millimolar concentrations, with absorption maxima around 400 nm. The solvated electrons and the disulphide radicals seem to have a lifetime in the range of seconds up to minutes at 100 K. The temperature dependence of the kinetics of X-ray-induced radical formation is different for the solvated electrons compared with the disulphide radicals. The online microspectrophotometer provides a technique complementary to X-ray diffraction for analysing and characterizing intermediates and redox states of proteins and enzymes.
Can soaked-in scavengers protect metalloprotein active sites from reduction during data collection?
Authors: Macedo Sofia , Pechlaner Maria , Schmid Walther , Weik Martin , Sato Katsuko , Dennison Christopher , Djinović-Carugo Kristina
Published: February 2009

One of the first events taking place when a crystal of a metalloprotein is exposed to X-ray radiation is photoreduction of the metal centres. The oxidation state of a metal cannot always be determined from routine X-ray diffraction experiments alone, but it may have a crucial impact on the metal's environment and on the analysis of the structural data when considering the functional mechanism of a metalloenzyme. Here, UV–Vis microspectrophotometry is used to test the efficacy of selected scavengers in reducing the undesirable photoreduction of the iron and copper centres in myoglobin and azurin, respectively, and X-ray crystallography to assess their capacity of mitigating global and specific radiation damage effects. UV–Vis absorption spectra of native crystals, as well as those soaked in 18 different radioprotectants, show dramatic metal reduction occurring in the first 60 s of irradiation with an X-ray beam from a third-generation synchrotron source. Among the tested radioprotectants only potassium hexacyanoferrate(III) seems to be capable of partially mitigating the rate of metal photoreduction at the concentrations used, but not to a sufficient extent that would allow a complete data set to be recorded from a fully oxidized crystal. On the other hand, analysis of the X-ray crystallographic data confirms ascorbate as an efficient protecting agent against radiation damage, other than metal centre reduction, and suggests further testing of HEPES and 2,3-dichloro-1,4-naphtoquinone as potential scavengers.
Radiation damage in protein crystals examined under various conditions by different methods
Authors: Garman Elspeth F. , Nave Colin
Published: February 2009

Investigation of radiation damage in protein crystals has progressed in several directions over the past couple of years. There have been improvements in the basic procedures such as calibration of the incident X-ray intensity and calculation of the dose likely to be deposited in a crystal of known size and composition with this intensity. There has been increased emphasis on using additional techniques such as optical, Raman or X-ray spectroscopy to complement X-ray diffraction. Apparent discrepancies between the results of different techniques can be explained by the fact that they are sensitive to different length scales or to changes in the electronic state rather than to movement of atoms. Investigations have been carried out at room temperature as well as cryo-temperatures and, in both cases, with the introduction of potential scavenger molecules. These and other studies are leading to an overall description of the changes which can occur when a protein crystal is irradiated with X-rays at both cryo- and room temperatures. Results from crystallographic and spectroscopic radiation-damage experiments can be reconciled with other studies in the field of radiation physics and chemistry.
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

The 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

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

Studies 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

Objective:  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

Objectives:  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

Background  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

Background  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

Objective  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

Background  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.
Translational Mini-Review Series on Immunology of Vascular Disease: Inflammation, infections and Toll-like receptors in cardiovascular disease
Authors: Ward J R , Wilson H L , Francis S E , Crossman D C , Sabroe I
Published: February 2009

Cardiovascular disease, in which atherosclerosis is the major underlying cause, is currently the largest cause of death in the world. Atherosclerosis is an inflammatory disease characterized by the formation of arterial lesions over a period of several decades at sites of endothelial cell dysfunction. These lesions are composed of endothelial cells, vascular smooth muscle cells, monocytes/macrophages and T lymphocytes (CD4+). As the lesions progress some can become unstable and prone to disruption, resulting in thrombus formation and possibly a myocardial infarction or stroke depending upon the location. Although the exact triggers for plaque disruption remain unknown, much recent evidence has shown a link between the incidence of myocardial infarction and stroke and a recent respiratory tract infection. Interestingly, many reports have also shown a link between a family of pattern recognition receptors, the Toll-like receptors, and the progression of atherosclerosis, suggesting that infections may play a role in both the progression of atherosclerosis and in inducing the more severe complications associated with the disease.
Translational Mini-Review Series on Immunology of Vascular Disease: Mechanisms of vascular inflammation and remodelling in systemic vasculitis
Authors: Maugeri N , Rovere-Querini P , Baldini M , Sabbadini M G , Manfredi A A
Published: February 2009

Vessel walls are the primary inflammatory sites in systemic vasculitides. In most cases the initiating event is unknown, and a self-sustaining circuit attracts and activates inflammatory leucocytes in the wall of vessels of various size and anatomical characteristics. Recent studies have revealed homeostatic roles of vascular inflammation and have identified the action of humoral innate immunity, in particular injury-associated signals and acute phase proteins, on the activation of circulating leucocytes, platelets and endothelial cells. These advances have provided clues to the molecular mechanisms underlying the vicious circle that maintains and amplifies vessel and tissue injury.
Undersampling bias: the null hypothesis for singleton species in tropical arthropod surveys
Authors: Coddington Jonathan A. , Agnarsson Ingi , Miller Jeremy A. , Kuntner Matjaž , Hormiga Gustavo
Published: February 2009

Frequency of singletons – species represented by single individuals – is anomalously high in most large tropical arthropod surveys (average, 32%).

We sampled 5965 adult spiders of 352 species (29% singletons) from 1 ha of lowland tropical moist forest in Guyana.

Four common hypotheses (small body size, male‐biased sex ratio, cryptic habits, clumped distributions) failed to explain singleton frequency. Singletons are larger than other species, not gender‐biased, share no particular lifestyle, and are not clumped at 0·25–1 ha scales.

Monte Carlo simulation of the best‐fit lognormal community shows that the observed data fit a random sample from a community of ~700 species and 1–2 million individuals, implying approximately 4% true singleton frequency.

Undersampling causes systematic negative bias of species richness, and should be the default null hypothesis for singleton frequencies.

Drastically greater sampling intensity in tropical arthropod inventory studies is required to yield realistic species richness estimates.

The lognormal distribution deserves greater consideration as a richness estimator when undersampling bias is severe.