bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining tissue transcriptomics and urine metabolomics for breast cancer biomarker identification
Authors: Nam Hojung , Chung Bong Chul , Kim Younghoon , Lee KiYoung , Lee Doheon
Published: September 2009

Motivation: For the early detection of cancer, highly sensitive and specific biomarkers are needed. Particularly, biomarkers in bio-fluids are relatively more useful because those can be used for non-biopsy tests. Although the altered metabolic activities of cancer cells have been observed in many studies, little is known about metabolic biomarkers for cancer screening. In this study, a systematic method is proposed for identifying metabolic biomarkers in urine samples by selecting candidate biomarkers from altered genome-wide gene expression signatures of cancer cells. Biomarkers identified by the present study have increased coherence and robustness because the significances of biomarkers are validated in both gene expression profiles and metabolic profiles.

Results: The proposed method was applied to the gene expression profiles and urine samples of 50 breast cancer patients and 50 normal persons. Nine altered metabolic pathways were identified from the breast cancer gene expression signatures. Among these altered metabolic pathways, four metabolic biomarkers (Homovanillate, 4-hydroxyphenylacetate, 5-hydroxyindoleacetate and urea) were identified to be different in cancer and normal subjects (p <0.05). In the case of the predictive performance, the identified biomarkers achieved area under the ROC curve values of 0.75, 0.79 and 0.79, according to a linear discriminate analysis, a random forest classifier and on a support vector machine, respectively. Finally, biomarkers which showed consistent significance in pathways' gene expression as well as urine samples were identified.

Contact:  dhlee@biosoft.kaist.ac.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
EasyMIFs and SiteHound: a toolkit for the identification of ligand-binding sites in protein structures
Authors: Ghersi Dario , Sanchez Roberto
Published: September 2009

Summary: SiteHound uses Molecular Interaction Fields (MIFs) produced by EasyMIFs to identify protein structure regions that show a high propensity for interaction with ligands. The type of binding site identified depends on the probe atom used in the MIF calculation. The input to EasyMIFs is a PDB file of a protein structure; the output MIF serves as input to SiteHound, which in turn produces a list of putative binding sites. Extensive testing of SiteHound for the detection of binding sites for drug-like molecules and phosphorylated ligands has been carried out.

Availability: EasyMIFs and SiteHound executables for Linux, Mac OS X, and MS Windows operating systems are freely available for download from http://sitehound.sanchezlab.org/download.html.

Contact:  roberto@sanchezlab.org or roberto.sanchez@mssm.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The accelerated post‐infarction progression of cardiac remodelling is associated with genetic changes in an untreated streptozotocin‐induced diabetic rat model
Authors: Song Guang‐Yuan , Wu Yong‐Jian , Yang Yue‐Jin , Li Jian‐Jun , Zhang Hong‐Liang , Pei Han‐Jun , Zhao Zhen‐Yan , Zeng Zeng‐Hua , Hui Ru‐Tai
Published: September 2009

Aims

The mechanism by which diabetes mellitus exacerbates myocardial injury and the incidence of heart failure after acute myocardial infarction (AMI), remains unclear. We studied the severity of cardiac dysfunction and time‐dependent gene expression in a hyperglycaemic rat model with AMI.

Methods and results

The diabetic model was produced by injection of streptozotocin in Sprague‐Dawley rats. Ten weeks after induction of diabetes, AMI was induced by ligation of the left anterior descending coronary artery. Cardiac function and left ventricular (LV) dimensions were evaluated using two‐dimensional echocardiography. Structural changes were assessed by histological examination. Gene expression profile was documented by using affymetrix genechip U230 2.0 array and real time‐PCR. During 56 days post‐AMI, lower survival rates, worse LV function, more severe fibrosis, and larger LV diameters were identified in diabetic rats compared with non‐diabetic rats. A total 1221 genes involved in processes, such as glucose metabolism, fatty acid metabolism, extracellular matrix, and apoptosis, were found to be differentially expressed between diabetic and non‐diabetic rats, of these 770 were up‐regulated and 451 down‐regulated. Up‐regulation of the genes was found 1–2 weeks earlier in diabetic rats than in non‐diabetic rats.

Conclusion

The present data suggest that hyperglycaemia up‐regulates remodelling‐related genes, which may be responsible for the worse outcomes in diabetics than in non‐diabetics after AMI.
Gender differences in survival in patients with severe left ventricular dysfunction despite similar extent of myocardial scar measured on cardiac magnetic resonance
Authors: Kwon Deborah H. , Halley Carmel M. , Popovic Zoran B. , Carrigan Thomas P. , Zysek Victoria , Setser Randolph , Schoenhagen Paul , Flamm Scott D. , Starling Randall C. , Desai Milind Y.
Published: September 2009

Aims

We sought to determine the association between myocardial scarring, gender, and survival in patients with significant coronary artery disease (CAD) and severe systolic left ventricular (LV) dysfunction using delayed hyper‐enhancement cardiac magnetic resonance imaging (DHE‐CMR).

Methods and results

We studied 339 patients (24% women, mean age 65 ± 11 years) referred for assessment of myocardial viability by DHE‐CMR. Scar was defined as myocardium with an intensity >2 SD above viable myocardium. Left ventricular scar (defined as a percentage of total LV myocardium), LV volumes, risk factors, cardiac transplantation (CTx), and all‐cause mortality were recorded. There were 84 deaths and five CTx over 3.7 ± 1.6 years (median 4 years, interquartile range 2.6–4.9 years). Left ventricular ejection fraction (LVEF) in men was only slightly different from women (23% ± 9 vs. 25% ± 10, P = 0.05), whereas mean scar % was similar in both groups (32 ± 21 vs. 29 ± 20, P = 0.3). On univariable survival analysis, age [hazard ratio, HR, 1.03 (1.01–1.05), P = 0.002], female gender [HR 2.02 (1.31–3.12), P = 0.001], and scar % [HR 1.01 (1.003–1.02), P = 0.009] predicted outcomes; and also on multivariable analysis (χ2 32, P < 0.0001). Women with scar % greater than the median had more events, compared with men with or without a high scar burden (log‐rank P < 0.001).

Conclusion

In patients with CAD and severely reduced LVEF, women have worse outcomes than men, irrespective of myocardial scar burden.
A randomized, double‐blind, placebo‐controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction
Authors: Parthasarathy Hari K. , Pieske Burkert , Weisskopf Marianne , Andrews Chris D. , Brunel Patrick , Struthers Allan D. , MacDonald Thomas M.
Published: September 2009

Aims

To determine whether valsartan improves treadmill exercise time, in patients with symptomatic heart failure with a preserved ejection fraction (HFPEF), compared with placebo.

Methods and results

In this multicentred, double‐blind, 14‐week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force‐titrated up to 320 mg. A total of 152 patients were randomized (V = 70, P = 82). Most patients had well‐controlled hypertension (V = 91.2%, P = 89.0%) (mean baseline systolic BP ~130 mmHg) and >50% were receiving an angiotensin‐converting enzyme inhibitor and/or beta‐blocker (V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group (n = 64) and 71.52% in the valsartan group (n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion‐related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quality‐of‐life scores. Valsartan significantly lowered peak exercise systolic BP (−13.1 mmHg vs. placebo; P < 0.001) and improved ratings of perceived exertion (Borg score) (−0.69 vs. placebo; P = 0.008).

Conclusion

In this population, which predominantly included patients with well‐controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well‐tolerated.
Left ventricular remodelling and torsional dynamics in dilated cardiomyopathy: reversed apical rotation as a marker of disease severity
Authors: Popescu Bogdan A. , Beladan Carmen C. , Călin Andreea , Muraru Denisa , Deleanu Dan , Roşca Monica , Ginghină Carmen
Published: September 2009

Aims

Decreased left ventricular (LV) rotation and torsion and even reversed systolic apical rotation have been described in patients with dilated cardiomyopathy (DCM). We sought to test in patients with DCM whether reversed apical rotation with loss of LV torsion is related to the extent of LV remodelling and to the severity of LV dysfunction.

Methods and results

Fifty consecutive patients with DCM (aged 49 ± 13 years) were enrolled prospectively. Forty‐seven healthy volunteers served as controls. All subjects underwent clinical examination, 12‐lead electrocardiography, and a comprehensive echocardiogram. Basal and apical LV rotation and LV torsion were quantified by speckle tracking echocardiography. Left ventricular systolic rotation and torsion were reduced in patients, compared with controls (P < 0.001). Normally directed (counterclockwise) apical rotation was found in 24 patients (group 1), whereas 26 had reversed (clockwise) apical rotation (group 2). Patients in group 2 had larger LV volume, increased LV sphericity (P ≤ 0.02), more severe systolic dysfunction (ejection fraction 26 ± 7 vs. 33 ± 12%), and higher filling pressures (E/E′ ratio 19 ± 10 vs. 14 ± 6; P < 0.05). The main correlates of LV apical rotation were LV volume, sphericity index, and QRS duration.

Conclusion

Reversed apical rotation and loss of LV torsion in patients with DCM is associated with significant LV remodelling, increased electrical dyssynchrony, reduced systolic function, and increased filling pressures, indicating a more advanced disease stage.
Intake of very long chain n‐3 fatty acids from fish and the incidence of heart failure: the Rotterdam Study
Authors: Dijkstra S. Coosje , Brouwer Ingeborg A. , van Rooij Frank J.A. , Hofman Albert , Witteman Jacqueline C.M. , Geleijnse Johanna M.
Published: September 2009

Aims

Evidence is accumulating for a cardioprotective effect of fish or its n‐3 fatty acids, eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). We examined EPA plus DHA and fish intake in relation to incident heart failure in the population‐based Rotterdam Study.

Methods and results

The analysis comprised 5299 subjects (41% men, age ~68 years) free from heart failure for whom dietary data were available. During 11.4 years of follow‐up, 669 subjects developed heart failure. The relative risk (RR) of heart failure in the top vs. bottom quintile of EPA plus DHA intake was 0.89 (95% CI 0.69–1.14), after adjustment for lifestyle and dietary factors. For fish intakes ≥20 g/day, the RR was 0.96 (0.78–1.18) compared with no fish intake. In sex‐specific analysis, a high EPA plus DHA intake tended to be protective in women (RR = 0.75, 0.54–1.04) but not in men (RR = 1.00, 0.73–1.36). An inverse association for EPA plus DHA was also observed in diabetics (RR = 0.58, 0.32–1.06), which was borderline statistically significant.

Conclusion

Our findings do not support a major role for fish intake in the prevention of heart failure. The potentially protective effect of EPA plus DHA in diabetic patients, however, warrants further investigation.
Emergency Legal Preparedness Among Select US Local Governments
Authors: Anderson Evan D. , Hodge James G.
Published: September 2009

Legal preparedness is an essential component of effective public health emergency response, evinced recently by the numerous emergency declarations issued at the federal, state, and local levels to address the 2009 H1N1 influenza outbreak. Although the impact of these emergency laws at the federal and state levels has been studied extensively, the scope and role of local emergency laws have not been similarly assessed. In this article, we examine key issues of emergency laws among select US localities in the context of the recent H1N1 outbreak and their application to volunteer health professionals, who are often needed to meet patient surge capacity during local emergencies.

Localities represent the front line of emergency preparedness and must address an array of legal challenges before and during declared emergencies. Local legal preparedness differs based on overarching restrictions such as the degree of home rule provided to localities under state law. Some localities take innovative legal approaches to address emergency preparedness. Although beneficial in many respects, these variations add additional complexity to legal preparedness and intensify the need for predisaster planning, exercises, and coordination. (Disaster Med Public Health Preparedness. 2009;3(Suppl 2):S176–S184)
A Comparison of Endovascular Repair versus Open Repair of Abdominal Aortic Aneurysms in a Community Setting
Authors: Karmy-Jones Riyad , Bloch Robert , Nicholls Stephen
Published: September 2009

Objective

To compare outcomes between endovascular versus surgical repair of abdominal aortic aneurysms (AAA) in a community hospital setting.

Methods

A retrospective analysis of all patients undergoing repair of AAA during 2007. Inclusion criteria included stability and anatomic suitability for endovascular repair (EVAR). Data analyzed included comorbidity, length of stay, complications, and cost to the hospital.

Results

Thirty-one endovascular and 12 open cases fit criteria. There were no significant differences in mortality risk, size of aneurysm, or age between the groups (endovascular 71.6 ± 8 years vs. open 66.7 ± 9 years, P = 0.07). The endovascular group included three patients with contained retroperitoneal rupture, one of whom died secondary to visceral embolization and thrombosis (the only mortality). EVAR was performed with local anesthesia in three and spinal in three cases. Twenty-three cases were performed completely percutaneously. There were no deaths in the surgical group, but four patients experienced major complications. There was no difference between groups in terms of “contribution” costs, but EVAR had significantly greater cost/benefit when measuring “fully loaded” costs (endovascular 4436 ± 7418$ vs. open −1418 ± 6756$, P = 0.02). Endovascular was associated with significantly shorter intensive care unit stay (1.3 ± 0.7 days vs. 2.8 ± 2.1 days, P = 0.001) and overall stay (2.5 ± 2.1 days vs. 7.2 ± 1.6 days, P = 0.001).

Conclusions

Endovascular of AAA seems to be at least equivalent to open repair in terms of acute outcomes, with much improved cost/benefit predominantly linked to reduced length of stay.
Do genetic recombination and gene density shape the pattern of DNA elimination in rice long terminal repeat retrotransposons?
Authors: Tian Zhixi , Rizzon Carene , Du Jianchang , Zhu Liucun , Bennetzen Jeffrey L. , Jackson Scott A. , Gaut Brandon S. , Ma Jianxin
Published: September 2009

In flowering plants, the accumulation of small deletions through unequal homologous recombination (UR) and illegitimate recombination (IR) is proposed to be the major process counteracting genome expansion, which is caused primarily by the periodic amplification of long terminal repeat retrotransposons (LTR-RTs). However, the full suite of evolutionary forces that govern the gain or loss of transposable elements (TEs) and their distribution within a genome remains unclear. Here, we investigated the distribution and structural variation of LTR-RTs in relation to the rates of local genetic recombination (GR) and gene densities in the rice (Oryza sativa) genome. Our data revealed a positive correlation between GR rates and gene densities and negative correlations between LTR-RT densities and both GR and gene densities. The data also indicate a tendency for LTR-RT elements and fragments to be shorter in regions with higher GR rates; the size reduction of LTR-RTs appears to be achieved primarily through solo LTR formation by UR. Comparison of indica and japonica rice revealed patterns and frequencies of LTR-RT gain and loss within different evolutionary timeframes. Different LTR-RT families exhibited variable distribution patterns and structural changes, but overall LTR-RT compositions and genes were organized according to the GR gradients of the genome. Further investigation of non-LTR-RTs and DNA transposons revealed a negative correlation between gene densities and the abundance of DNA transposons and a weak correlation between GR rates and the abundance of long interspersed nuclear elements (LINEs)/short interspersed nuclear elements (SINEs). Together, these observations suggest that GR and gene density play important roles in shaping the dynamic structure of the rice genome.
Epigenetic Regulation of Gene Programs by EMF1 and EMF2 in Arabidopsis
Authors: Kim Sang Yeol , Zhu T. , Sung Z. Renee
Published: September 2009

The EMBRYONIC FLOWER (EMF) genes are required to maintain vegetative development in Arabidopsis (Arabidopsis thaliana). Loss-of-function emf mutants skip the vegetative phase, flower upon germination, and display pleiotropic phenotypes. EMF1 encodes a putative transcriptional regulator, while EMF2 encodes a Polycomb group (PcG) protein. PcG proteins form protein complexes that maintain gene silencing via histone modification. They are known to function as master regulators repressing multiple gene programs. Both EMF1 and EMF2 participate in PcG-mediated silencing of the flower homeotic genes AGAMOUS, PISTILLATA, and APETALA3. Full-genome expression pattern analysis of emf mutants showed that both EMF proteins regulate additional gene programs, including photosynthesis, seed development, hormone, stress, and cold signaling. Chromatin immunoprecipitation was carried out to investigate whether EMF regulates these genes directly. It was determined that EMF1 and EMF2 interact with genes encoding the transcription factors ABSCISIC ACID INSENSITIVE3, LONG VEGETATIVE PHASE1, and FLOWERING LOCUS C, which control seed development, stress and cold signaling, and flowering, respectively. Our results suggest that the two EMFs repress the regulatory genes of individual gene programs to effectively silence the genetic pathways necessary for vegetative development and stress response. A model of the regulatory network mediated by EMF is proposed.
MAP KINASE PHOSPHATASE1 and PROTEIN TYROSINE PHOSPHATASE1 Are Repressors of Salicylic Acid Synthesis and SNC1-Mediated Responses inArabidopsis
Authors: Bartels Sebastian , Anderson Jeffrey C. , González Besteiro Marina A. , Carreri Alessandro , Hirt Heribert , Buchala Antony , Métraux Jean-Pierre , Peck Scott C. , Ulm Roman
Published: September 2009

Mitogen-activated protein (MAP) kinase phosphatases are important negative regulators of the levels and kinetics of MAP kinase activation that modulate cellular responses. The dual-specificity phosphatase MAP KINASE PHOSPHATASE1 (MKP1) was previously shown to regulate MAP KINASE6 (MPK6) activation levels and abiotic stress responses in Arabidopsis thaliana. Here, we report that the mkp1 null mutation in the Columbia (Col) accession results in growth defects and constitutive biotic defense responses, including elevated levels of salicylic acid, camalexin, PR gene expression, and resistance to the bacterial pathogen Pseudomonas syringae. PROTEIN TYROSINE PHOSPHATASE1 (PTP1) also interacts with MPK6, but the ptp1 null mutant shows no aberrant growth phenotype. However, the pronounced constitutive defense response of the mkp1 ptp1 double mutant reveals that MKP1 and PTP1 repress defense responses in a coordinated fashion. Moreover, mutations in MPK3 and MPK6 distinctly suppress mkp1 and mkp1 ptp1 phenotypes, indicating that MKP1 and PTP1 act as repressors of inappropriate MPK3/MPK6-dependent stress signaling. Finally, we provide evidence that the natural modifier of mkp1 in Col is largely the disease resistance gene homolog SUPPRESSOR OF npr1-1, CONSTITUTIVE 1 (SNC1) that is absent in the Wassilewskija accession. Our data thus indicate a major role of MKP1 and PTP1 in repressing salicylic acid biosynthesis in the autoimmune-like response caused by SNC1.
Evolutionarily Conserved Regulatory Motifs in the Promoter of the Arabidopsis Clock Gene LATE ELONGATED HYPOCOTYL
Authors: Spensley Mark , Kim Jae-Yean , Picot Emma , Reid John , Ott Sascha , Helliwell Chris , Carré Isabelle A.
Published: September 2009

The transcriptional regulation of the LATE ELONGATED HYPOCOTYL (LHY) gene is key to the structure of the circadian oscillator, integrating information from multiple regulatory pathways. We identified a minimal region of the LHY promoter that was sufficient for rhythmic expression. Another upstream sequence was also required for appropriate waveform of transcription and for maximum amplitude of oscillations under both diurnal and free-running conditions. We showed that two classes of protein complexes interact with a G-box and with novel 5A motifs; mutation of these sites reduced the amplitude of oscillation and broadened the peak of expression. A genome-wide bioinformatic analysis showed that these sites were enriched in phase-specific clusters of rhythmically expressed genes. Comparative genomic analyses showed that these motifs were conserved in orthologous promoters from several species. A position-specific scoring matrix for the 5A sites suggested similarity to CArG boxes, which are recognized by MADS box transcription factors. In support of this, the FLOWERING LOCUS C (FLC) protein was shown to interact with the LHY promoter in planta. This suggests a mechanism by which FLC might affect circadian period.
Overexpression and involvement of special AT‐rich sequence binding protein 1 in multidrug resistance in human breast carcinoma cells
Authors: Li Qing‐Quan , Chen Zhong‐Qing , Xu Jing‐Da , Cao Xi‐Xi , Chen Qi , Liu Xiu‐Ping , Xu Zu‐De
Published: September 2009

Special AT‐rich sequence binding protein (SATB) 1 has been proposed to act as a determinant for the acquisition of metastatic activity by controlling expression of a specific set of genes that promote metastatic activity. Here we found that SATB1 expression is upregulated in multidrug‐resistant breast cancer cells that exhibit higher invasive potential than the parental cells. Apart from accelerating metastasis and inducing epithelial–mesenchymal transition, SATB1 was demonstrated to confer resistance to both P‐glycoprotein‐related and P‐glycoprotein‐non‐related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1‐overexpressing transfectants. SATB1 depletion could partially reverse the multidrug resistance (MDR) phenotype of MCF7/ADR in vitro and in vivo. The SATB1‐induced P‐glycoprotein‐mediated MDR could be reversed by treatment with anti‐P‐glycoprotein mAb. Moreover, SATB1 plays an important role in anti‐apoptotic activity in MCF7/ADR cells in response to adriamycin treatment, which suggests another mechanism contributing to SATB1‐related MDR of breast cancers. These data provide new insights into the mode by which breast tumors acquire the MDR phenotype and also imply a role for SATB1 in this process. (Cancer Sci 2009)
Molecular mechanism underlying the synergistic interaction between trifluorothymidine and the epidermal growth factor receptor inhibitor erlotinib in human colorectal cancer cell lines
Authors: Bijnsdorp Irene V. , Kruyt Frank A. E. , Fukushima Masakazu , Smid Kees , Gokoel Shanti , Peters Godefridus J.
Published: September 2009

The pyrimidine trifluorothymidine (TFT) inhibits thymidylate synthase (TS) and can be incorporated into the DNA. TFT, as part of TAS‐102, is clinically evaluated in phase II studies as an oral chemotherapeutic agent. Erlotinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that is often deregulated in colorectal cancer. This study investigated molecular mechanisms underlying the cytotoxic actions of the combination of an EGFR−tyrosine kinase inhibitor with TFT in colorectal cancer cells Caco2, WiDR, Lovo92, and Colo320. Drug interactions were examined by the sulforhodamine B assay and subsequent combination index (CI) analyses, cell cycle effects by FACS analysis of propidium iodide stained cells, Akt, MAPK and EGFR phosphorylation and expression levels by Western blotting and TS activity by the TS in situ assay. All combination schedules were synergistic in wt‐EGFR expressing (but with mutated downstream pathways) WiDR and Lovo92 (CI 0.4–0.8) and very synergistic in Caco2 cells (with wt‐EGFR and functional downstream pathways; CI 0.1–0.3), but in EGFR‐lacking Colo320 cells, no additional activity was found (CI 1.0–1.2). Synergism was mostly related to the induction of cell cycle arrest and an erlotinib‐mediated inhibition of the pro‐survival signaling through Akt and MAPK that was activated (phosphorylated) by TFT. Erlotinib inhibited TS activity in EGFR‐expressing cell lines, probably due to cell cycle arrest in the G1 phase. TS activity was slightly lower in the combinations, probably due to cell cycle interference. Taken together, the combination of erlotinib with TFT seems to present a potential strategy in the field of molecular therapeutics. (Cancer Sci 2009)
Modulation of innate immunity system by Epstein–Barr virus‐encoded non‐coding RNA and oncogenesis
Authors: Samanta Mrinal , Takada Kenzo
Published: September 2009

Epstein–Barr virus (EBV)‐encoded small RNAs (EBERs) are polyA–, non‐coding RNAs that are expressed abundantly in all forms of cells latently infected with EBV. EBERs (EBER1 and EBER2) contribute to the clonal proliferation of EBV‐negative Burkitt’s lymphoma (BL) cells in soft agar, tumorigenicity in SCID mice, up‐regulation of the bcl‐2 oncoprotein, resistance to apoptosis, and maintenance of malignant phenotypes in BL cells. EBERs induce the expression of interleukin (IL)‐10 in BL cells, insulin‐like growth factor 1 (IGF‐I) in gastric and nasopharyngeal carcinoma cells, IL‐9 in T cells, and IL‐6 in lymphoblastoid cell lines. Additionally, each of these cytokines acts as an autocrine growth factor. In BL cells, EBERs bind the double‐stranded RNA‐activated protein kinase PKR, inhibit its phosphorylation, and thereby prevent IFN‐α‐mediated apoptosis. In epithelial cells, EBERs confer resistance to Fas‐mediated apoptosis by blocking PKR activity. EBERs form complexes with PKR, ribosomal protein L22, lupus erythematosis‐associated antigen (La), and retinoic acid‐inducible gene I (RIG‐I). In BL cells, EBERs activate RIG‐I signaling and induce the expression of type‐I IFNs and interferon stimulated genes (ISGs) through the activation of RIG‐I substrates, nuclear factor‐kappa B (NF‐κB), and IFN regulatory factor 3 (IRF‐3), and anti‐inflamatory cytokine IL‐10 through IRF‐3 but not NF‐κB signaling. EBERs also play critical roles in the growth transformation of B lymphocytes. Although EBER1 and EBER2 exhibit similarities in their primary (54%) and secondary structures, recent findings have shown that recombinant EBVs carrying only the EBER2 gene play a greater role in the growth transformation of B lymphocytes than EBVs carrying only the EBER1 gene. Thus, EBERs play multiple roles in various cell types, and we present a model that highlights the functions of EBERs in EBV‐mediated oncogenesis in BL cells. (Cancer Sci 2009)
Duiker demography and dispersal under hunting in Northern Congo
Authors: Mockrin Miranda H.
Published: September 2009

Duikers are the most heavily hunted species across forested Central and West Africa. Although these species form a vital food resource for people, little is known about their ecology and demography. The information available to date was collected from populations protected from hunting. However, hunting can profoundly alter demography and behaviour, such as dispersal, which in turn determine the sustainability of harvest. To address this research gap, I used radiotelemetry to examine duiker demography under hunting in Congo‐Brazzaville. Among blue duikers (Philantoba monticola, n = 17) I found annual survival rates (0.94), immature dispersal rates (0.25), and average home ranges (5.5 ha) that largely coincided with previous research from unhunted regions. Neighbouring animals all showed some home range overlap, in contrast to previous studies which found blue duikers to be strictly territorial. Although limited by sample size, immature animals’ dispersal distances were relatively high (1.5 km, n = 2). Animals’ dispersal rates do not appear to be greatly increased by hunting pressure, although source‐sink theory depends upon high rates of dispersal to maintain the elevated and localized hunting offtakes observed around settlements. Building a fuller understanding of duiker demography under hunting, including dispersal, will be essential for conservation and management efforts.
The ranging patterns of elephants in Marsabit protected area, Kenya: the use of satellite‐linked GPS collars
Authors: Ngene Shadrack M. , Van Gils Hein , Van Wieren Sipke E. , Rasmussen Henrik , Skidmore Andrew K. , Prins Herbert H. T. , Toxopeus Albertus G. , Omondi Patrick , Douglas‐Hamilton Iain
Published: September 2009

We investigated the ranging patterns of elephants in the Marsabit protected area, north eastern Kenya, to ascertain the range of bachelor and female family herds in different seasons, and to identify corridor and noncorridor areas. Data were acquired for five bachelor and four female family herds equipped with satellite‐linked geographical positioning system collars, and monitored from December 2005 to December 2007. Distinct dry (about 260 km2) and wet seasons (about 910 km2) ranges were observed, with connecting corridors (north‐eastern corridor: about 90 km long, about 2‐7 km wide; southern corridors: about 10‐20 km long, about 2‐3 km wide). The dry season range corresponded with Marsabit evergreen forest, while the wet season range matched with dry deciduous lowland shrubs. The ranging elephants moved at speed of about 0.2‐20 kmh−1. Bachelor herds moved faster than female family herds. Elephants moved fast during the intermediate and wet seasons than during the dry season. The speed of ranging elephants was over 1 kmh−1in the corridor areas and about 0.2 to less than 1 kmh−1in the non‐corridor areas. Expansion of settlements towards corridor areas needs to be controlled to avoid future blocking of connectivity between wet and dry season elephant ranges.
Spiders as potential indicators of elephant‐induced habitat changes in endemic sand forest, Maputaland, South Africa
Authors: Haddad Charles R. , Honiball Allet S. , Dippenaar‐Schoeman Anna S. , Slotow Rob , Van Rensburg Berndt J.
Published: September 2009

Elephant impacts on spider assemblages, and the potential use of spiders as indicators of habitat changes was assessed in central Maputaland, South Africa. Three habitats, namely undisturbed sand forest, elephant disturbed sand forest and mixed woodland, were sampled. To ensure a thorough representation of all spider guilds, spiders were collected by tree beating, sweep netting, active searching, leaf litter sifting and pitfall traps. In total, 2808 individual spiders, representing 36 families, 144 determined genera and 251 species were collected. Spider abundance was highest in the undisturbed sand forest (n = 1129, S = 179), followed by elephant disturbed sand forest (n = 1006, S = 165) and mixed woodland (n = 673, S = 171). Assemblages of the two sand forests were more similar than to the mixed woodland assemblage. Active hunting species were indicators of the more open vegetation of elephant disturbed sand forest (six active hunters, no web‐builders) and mixed woodland (ten active hunters, one web‐builder), whereas web‐builders are indicators of the dense, complex vegetation structure of undisturbed sand forest (six web‐builders, three active hunters). Elephant‐induced changes to the vegetation structure in this high diversity, high endemism region result in changes in the composition of spider assemblages, and may need to be mitigated by management intervention.
Impacts of traditional land uses on biodiversity outside conservation areas: effects on dung beetle communities of Vaalbos National Park
Authors: Simelane Thokozani S.
Published: September 2009

Grazing is one of the key processes in terrestrial ecosystems and this can be provided by both indigenous and domestic ungulates. However, a question remains whether or not traditional forms of land use such as the grazing of domestic animals support the maintenance of biodiversity. If it does not, then the second question becomes to what extent does grazing of domestic animals alter the systems and processes that support biodiversity? This study demonstrates that in attempting to answer this question, small organisms like dung beetles are ideal indicators that can be used to express significant differences between conserved (indigenous) and non‐conserved (domestic) land. As a general trend, studies that investigated these differences displayed differences through analysis of the diversity indices. This method has in most cases demonstrated a lack of contrast between conserved and non‐conserved land. In the existence of such uncertainty this study has demonstrated that in such cases, where the analysis of biodiversity indices fail to demonstrate significant differences a closer examination of actual species such as guilds and functional groups could confirm significant differences between conserved and non‐conserved land. These apparently conflicting findings reflect the need to consider the actual elements of biodiversity (e.g. species) when assessing conservation issues rather than just the statistical measures of biodiversity.
Reproductive life history of Thornicroft’s giraffe in Zambia
Authors: Bercovitch Fred B. , Berry Philip S. M.
Published: September 2009

Knowledge of the reproductive life history of giraffe in the wild is sparse. Giraffe have two fairly unusual reproductive patterns among large mammals: they can become pregnant while lactating, and calf mortality is extremely high. Longitudinal records are largely absent, so tracking reproductive parameters tends to combine information from captive and field studies. In this study, we examine longitudinal data obtained over a 33‐year period in one population of Thornicroft’s giraffe in order to chart their reproductive careers. We found that age at first parturition was 6.4 years, or slightly later than in captivity. Giraffe bred throughout the year, with cows producing offspring on average every 677.7 days. About half of the calves died before one year of age, but death of a calf did not reduce interbirth interval. We conclude that the lifetime reproductive success of giraffe is more dependent on longevity and calf survivorship than on reproductive rate.
Conservation planning and viability: problems associated with identifying priority sites in Swaziland using species list data
Authors: Smith Robert J. , Monadjem Ara , Magagula Cebisile N. , Mahlaba Themba A.M.
Published: September 2009

Conservation planning assessments based on species atlas data are known to select planning units containing ecotones because these areas are relatively species‐rich. However, this richness is often dependent on the presence of adjoining core habitat, so populations within these ecotones might not be viable. This suggests that atlas data may also fail to distinguish between planning units that are highly transformed by agriculture or urbanization with those from neighbouring untransformed units. These highly transformed units could also be identified as priority sites, based solely on the presence of species that require adjoining habitat patches to persist. This potential problem was investigated using bird and mammal atlas data from Swaziland and a landcover map and found that: (i) there was no correlation between planning unit species richness and proportion of natural landcover for both taxa; (ii) the priority areas that were identified for both birds and mammals were no less transformed than if the units had been chosen at random and (iii) an approach that aimed to meet conservation targets and minimize transformation levels failed to identify more viable priority areas. This third result probably arose because 4.8% of the bird species and 22% of the mammal species were recorded in only one planning unit, reducing the opportunity to choose between units when aiming to represent each species. Therefore, it is suggested that using species lists to design protected area networks at a fine spatial scale may not conserve species effectively unless population viability data are explicitly included in the analysis.
16α-Bromoepiandrosterone (HE2000) limits non-productive inflammation and stimulates immunity in lungs
Authors: Nicoletti F , Conrad D , Wang A , Pieters R , Mangano K , Van Heeckeren A , White S K , Frincke J , Reading C L , Auci D L , Stickney D
Published: September 2009

16α-Bromoepiandrosterone (HE2000) is a synthetic steroid that limits non-productive inflammation, enhances protective immunity and improves survival in clinical studies of patients with human immunodeficiency virus (HIV), malaria and tuberculosis infections. We now show that HE2000 decreased nitric oxide production by lipopolysaccharide (LPS)-stimulated RAW264·7 cells. Treatment with HE2000 also reduced non-productive inflammation associated with carrageenan-induced pleurisy and LPS-induced lung injury in mice. In the hapten-carrier reporter antigen popliteal lymph node assay, HE2000 increased absolute numbers of lymphocytes, antigen-presenting cells, hapten-specific immunoglobulin (Ig)M antibody-forming cells and shifted the interferon (IFN)-γ/interleukin (IL)-4 balance towards IFN-γ production. In the cystic fibrosis transmembrane conductance regulator (CFTR−/−) mouse model of acute Pseudomonas aeruginosa infection, treatment with HE2000 consistently reduced bacterial burden in lungs. All HE2000 effects were dose-dependent. In H1N1 infection in mice, HE2000 was safe but not effective as a monotherapy, as treatment did not effect survival. HE2000 reduced mortality related to excessive inflammation and opportunistic lung infections in animals and patients, and this might extend to those with H1N1 influenza infection.
A long‐standing Pleistocene refugium in southern Africa and a mosaic of refugia in East Africa: insights from mtDNA and the common eland antelope
Authors: Lorenzen Eline D. , Masembe Charles , Arctander Peter , Siegismund Hans R.
Published: September 2009

Aim Previous genetic studies of African savanna ungulates have indicated Pleistocene refugial areas in East and southern Africa, and recent palynological, palaeovegetation and fossil studies have suggested the presence of a long‐standing refugium in the south and a mosaic of refugia in the east. Phylogeographic analysis of the common eland antelope,Taurotragus oryx(Bovidae), was used to assess these hypotheses and the existence of genetic signatures of Pleistocene climate change.

Location The sub‐Saharan savanna biome of East and southern Africa.

Methods Mitochondrial DNA control‐region fragments (414 bp) from 122 individuals of common eland were analysed to elucidate the phylogeography, genetic diversity, spatial population structuring, historical migration and demographic history of the species. The phylogeographic split among major genetic lineages was dated using Bayesian coalescent‐based methods and a calibrated fossil root of 1.6 Ma for the split between the common eland and the giant eland,Taurotragus derbianus.

Results Two major phylogeographic lineages comprising East and southern African localities, respectively, were separated by a net nucleotide distance of 4.7%. A third intermediate lineage comprised only three haplotypes, from Zimbabwe in southern Africa. The estimated mutation rate of 0.097 Myr−1revealed a more recent common ancestor for the eastern lineage (0.21 Ma; 0.07–0.37) than for the southern lineage (0.35 Ma; 0.10–0.62). Compared with the latter, the eastern lineage showed pronounced geographic structuring, lower overall nucleotide diversity, higher population differentiation, and isolation‐by‐distance among populations.

Main conclusions The data support the hypothesis of Pleistocene refugia occurring in East and southern Africa. In agreement with palynological, palaeovegetation and fossil studies, our data strongly support the presence of a longer‐standing population in the south and a mosaic of Pleistocene refugia in the east, verifying the efficacy of genetic tools in addressing such questions. The more recent origin of the common eland inhabiting East Africa could result from colonization following extinction from the region. Only two other dated African ungulate phylogenies have been published, applying different methods, and the similarity of dates obtained from the three distinct approaches indicates a significant eventc. 200 ka, which left a strong genetic signature across a range of ungulate taxa.
Biogeography of the Australian monsoon tropics
Authors: Bowman D. M. J. S. , Brown G. K. , Braby M. F. , Brown J. R. , Cook L. G. , Crisp M. D. , Ford F. , Haberle S. , Hughes J. , Isagi Y. , Joseph L. , McBride J. , Nelson G. , Ladiges P. Y.
Published: September 2009

Aim  This paper reviews the biogeography of the Australian monsoon tropical biome to highlight general patterns in the distribution of a range of organisms and their environmental correlates and evolutionary history, as well as to identify knowledge gaps.

Location  Northern Australia, Australian Monsoon Tropics (AMT). The AMT is defined by areas that receive more than 85% of rainfall between November and April.

Methods  Literature is summarized, including the origin of the monsoon climate, present‐day environment, biota and habitat types, and phylogenetic and geographical relationships of selected organisms.

Results  Some species are widespread throughout the AMT while others are narrow‐range endemics. Such contrasting distributions correspond to present‐day climates, hydrologies (particularly floodplains), geological features (such as sandstone plateaux), fire regimes, and vegetation types (ranging from rain forest to savanna). Biogeographical and phylogenetic studies of terrestrial plants (e.g. eucalypts) and animals (vertebrates and invertebrates) suggest that distinct bioregions within the AMT reflect the aggregated effects of landscape and environmental history, although more research is required to determine and refine the boundaries of biogeographical zones within the AMT. Phylogenetic analyses of aquatic organisms (fishes and prawns) suggest histories of associations with drainage systems, dispersal barriers, links to New Guinea, and the existence of Lake Carpentaria, now submerged by the Gulf of Carpentaria. Complex adaptations to the landscape and climate in the AMT are illustrated by a number of species.

Main conclusions  The Australian monsoon is a component of a single global climate system, characterized by a dominant equator‐spanning Hadley cell. Evidence of hot, seasonally moist climates dates back to the Late Eocene, implying that certain endemic elements of the AMT biota have a long history. Vicariant differentiation is inferred to have separated the Kimberley and Arnhem Land bioregions from Cape York Peninsula/northern Queensland. Such older patterns are overlaid by younger events, including dispersal from Southeast Asia, and range expansions and contractions. Future palaeoecological and phylogenetic investigations will illuminate the evolution of the AMT biome. Understanding the biogeography of the AMT is essential to provide a framework for ecological studies and the sustainable development of the region.
Breeding systems and phylogenetic diversity of seed plants along a large‐scale elevational gradient
Authors: Vamosi Steven M. , Queenborough Simon A.
Published: September 2009

Aim  The factors affecting the distribution of dioecious species have received surprisingly little attention and, as a consequence, are poorly understood. For example, there is a well‐documented negative association between dioecy and latitude, for which we have no candidate mechanisms. Conversely, it has been suggested that the relative proportion of dioecious species should be positively correlated with changes in elevation.

Location  Costa Rica, Central America.

Methods  We made use of data on the distribution of 175 seed plant species from a series of plots along a transect in Costa Rica that ranged from 30 to 2600 m a.s.l. to test the prediction that dioecy is correlated with elevation. Specifically, we examined relationships between the proportion of dioecy, at the species and individual levels, and the elevation, species richness, number of individuals, and phylogenetic diversity (PD) of plots. For comparison, we repeated all analyses with monoecious species, which also have unisexual flowers but do not suffer from reduced mate assurance and the seed shadow effect that may be the outcomes of having spatially separated sexes.

Results  The relative proportions of dioecious species and individuals displayed a unimodal relationship with elevation, both peaking at 750 m a.s.l. In contrast, the relative proportions of monoecious species and individuals displayed negative associations with elevation. In addition, the proportion of dioecious species was significantly positively associated with species richness and with the PD of plots. The proportion of monoecious species was not associated with species richness and was weakly positively associated with the PD of plots.

Main conclusions  Our results suggest that the selection pressure of elevation on the pollinators and life‐history strategy of dioecious species is much less than expected, and is overshadowed by the as‐yet unexplained correlation of dioecy with species richness. Additional studies of the ecology of cosexual and unisexual (i.e. dioecious and monoecious) species along large environmental gradients are needed.
Choosing a measure of support need: implications for research and policy
Authors: Brown H. K. , Ouellette‐Kuntz H. , Bielska I. , Elliott D.
Published: September 2009

Background  The paradigm surrounding the delivery of care for individuals with intellectual disabilities (ID) is shifting from a deficit‐based approach to a support‐based approach. However, it is unclear whether measures of support act as a proxy for adaptive functioning.

Methods  A sample of 40 staff or family members of individuals with ID completed the Supports Intensity Scale and the Scales of Independent Behavior‐Revised, Short Form. Correlations were used to examine the relationship between these scales.

Results  The subscales of the Supports Intensity Scale as well as the overall support needs index were highly correlated with both the Broad Independence W score and the support score (which reflects both maladaptive and adaptive behaviours) of the Scales of Independent Behavior‐Revised.

Conclusions  The strong correlations between these two scales confirm previous findings that current measures of support and measures of adaptive behaviour tap into the same underlying construct. These findings have implications for the development, use and interpretation of research and planning tools.