bluuebunny/crossref_metadata_2025 huggingface dataset:
Internal mammary lymph node recurrence: rare but characteristic metastasis site in breast cancer
Authors: Chen Lei , Gu Yajia , Leaw Shiangjiin , Wang Zhonghua , Wang Peihua , Hu Xichun , Chen Jiayi , Lu Jingsong , Shao Zhimin
Published: September 2010

Background

To assess the frequency of IMLN recurrence, its associated risk factors with disease-free interval (DFI) and its predicting factors on overall survival time.

Methods

133 cases of breast cancer IMLN recurrence were identified via the computerized CT reporting system between February 2003 and June 2008, during which chest CT for patients with breast cancer (n = 8867) were performed consecutively at Cancer Hospital, Fudan University, Shanghai, China. Patients' charts were retrieved and patients' characteristics, disease characteristics, and treatments after recurrence were collected for analysis. The frequency was 1.5% (133/8867).

Results

IMLN recurrence was presented as the first metastatic site in 121 (91%) patients while 88 (66.2%) had other concurrent metastases. Typical chest CT images included swelling of the IMLN at the ipsilateral side with local lump and sternal erosion located mostly between the second and third intercostal space. The median disease-free interval (DFI) of IMLN recurrence was 38 months. The independent factors that could delay the IMLN recurrence were small tumor size (HR 0.5 95%CI: 0.4 - 0.8; p = 0.002), and positive ER/PR disease (HR 0.6, 95% CI: 0.4 - 0.9; p = 0.006). The median survival time after IMLN recurrence was 42 months, with a 5-year survival rate of 30%. Univariate analysis showed four variables significantly influenced the survival time: DFI of IMLN recurrence (p = 0.001), no concurrent distant metastasis (p = 0.024), endocrine therapy for patients with positive ER/PR (p = 0.000), radiotherapy (p = 0.040). The independent factors that reduced the death risk were no concurrent distant metastases (HR: 0.7, 95% CI: 0.4 - 0.9; p = 0.031), endocrine therapy for patients with positive ER/PR status (HR: 0.2, 95% CI: 0.1 - 0.5; p = 0.001) and palliative radiotherapy (HR: 0.3, 95% CI: 0.1- 0.9; p = 0.026).

Conclusions

The risk of IMLN recurrence is low and there are certain characteristics features on CT images. ER/PR status is both a risk factor for DFI of IMLN recurrence and a prognostic factor for overall survival after IMLN recurrence. Patients with only IMLN recurrence and/or local lesion have a good prognosis.
Acetylcholinesterase Inhibitors (AChEI's) for the treatment of visual hallucinations in schizophrenia: A review of the literature
Authors: Patel Sachin S , Attard Azizah , Jacobsen Pamela , Shergill Sukhi
Published: September 2010

Background

Visual hallucinations occur in various neurological diseases, but are most prominent in Lewy body dementia, Parkinson's disease and schizophrenia. The lifetime prevalence of visual hallucinations in patients with schizophrenia is much more common than conventionally thought and ranges from 24% to 72%. Cortical acetylcholine (ACh) depletion has been associated with visual hallucinations; the level of depletion being related directly to the severity of the symptoms. Current understanding of neurobiological visual processing and research in diseases with reduced cholinergic function, suggests that AChEI's may prove beneficial in treating visual hallucinations. This offers the potential for targeted drug therapy of clinically symptomatic visual hallucinations in patients with schizophrenia using acetylcholinesterase inhibition.

Methods

A systematic review was carried out investigating the evidence for the effects of AChEI's in treating visual hallucinations in Schizophrenia.

Results

No evidence was found relating to the specific role of AChEI's in treating visual hallucinations in this patient group.

Discussion

Given the use of AChEI's in targeted, symptom specific treatment in other neuropsychiatric disorders, it is surprising to find no related literature in schizophrenia patients. The use of AChEI's in schizophrenia has investigated effects on cognition primarily with non cognitive effects measured more broadly.

Conclusions

We would suggest that more focused research into the effects of AChEI's on positive symptoms of schizophrenia, specifically visual hallucinations, is needed.
Sequencing bias: comparison of different protocols of MicroRNA library construction
Authors: Tian Geng , Yin XuYang , Luo Hong , Xu XiaoHong , Bolund Lars , Zhang XiuQing
Published: September 2010

Background

MicroRNAs(miRNAs) are 18-25 nt small RNAs playing critical roles in many biological processes. The majority of known miRNAs were discovered by conventional cloning and a Sanger sequencing approach. The next-generation sequencing (NGS) technologies enable in-depth characterization of the global repertoire of miRNAs, and different protocols for miRNA library construction have been developed. However, the possible bias between the relative expression levels and sequences introduced by different protocols of library preparation have rarely been explored.

Results

We assessed three different miRNA library preparation protocols, SOLiD, Illumina versions 1 and 1.5, using cloning or SBS sequencing of total RNA samples extracted from skeletal muscles from Hu sheep and Dorper sheep, and then validated 9 miRNAs by qRT-PCR. Our results show that SBS sequencing data highly correlate with Illumina cloning data. The SOLiD data, when compared to Illumina's, indicate more dispersed distribution of length, higher frequency variation for nucleotides near the 3'- and 5'-ends, higher frequency occurrence for reads containing end secondary structure (ESS), and higher frequency for reads that do not map to known miRNAs. qRT-PCR results showed the best correlation with SOLiD cloning data. Fold difference of Hu sheep and Dorper sheep between qRT-PCR result and SBS sequencing data correlated well (r = 0.937), and fold difference of miR-1 and miR-206 among SOLiD cloning data, qRT-PCR and SBS sequencing data was similar.

Conclusions

The sequencing depth can influence the quantitative measurement of miRNA abundance, but the discrepancy caused by it was not statistically significant as high correlation was observed between Illumina cloning and SBS sequencing data. Bias of length distribution, sequence variation, and ESS was observed between data obtained with the different protocols. SOLiD cloning data differ from Illumina cloning data mainly because of distinct methods of adapter ligation. The good correlation between qRT-PCR result and SOLiD data might be due to the similarities of the hybridization-based methods. The fold difference analysis indicated that methods based on hybridization may be superior for quantitative measurement of miRNA abundance. Because of the genome sequence of the sheep is not available, our data may not explain how the entire miRNA bias in the natural miRNAs in sheep or other mammal miRNA expression, unbiased artificially synthesized miRNA will help on evaluating the methodology of miRNA library preparation.
Quantification of ETS exposure in hospitality workers who have never smoked
Authors: Kolb Stefanie , Brückner Ulrike , Nowak Dennis , Radon Katja
Published: September 2010

Background

Environmental Tobacco Smoke (ETS) was classified as human carcinogen (K1) by the German Research Council in 1998. According to epidemiological studies, the relative risk especially for lung cancer might be twice as high in persons who have never smoked but who are in the highest exposure category, for example hospitality workers. In order to implement these results in the German regulations on occupational illnesses, a valid method is needed to retrospectively assess the cumulative ETS exposure in the hospitality environment.

Methods

A literature-based review was carried out to locate a method that can be used for the German hospitality sector. Studies assessing ETS exposure using biological markers (for example urinary cotinine, DNA adducts) or questionnaires were excluded. Biological markers are not considered relevant as they assess exposure only over the last hours, weeks or months. Self-reported exposure based on questionnaires also does not seem adequate for medico-legal purposes. Therefore, retrospective exposure assessment should be based on mathematical models to approximate past exposure.

Results

For this purpose a validated model developed by Repace and Lowrey was considered appropriate. It offers the possibility of retrospectively assessing exposure with existing parameters (such as environmental dimensions, average number of smokers, ventilation characteristics and duration of exposure). The relative risk of lung cancer can then be estimated based on the individual cumulative exposure of the worker.

Conclusion

In conclusion, having adapted it to the German hospitality sector, an existing mathematical model appears to be capable of approximating the cumulative exposure. However, the level of uncertainty of these approximations has to be taken into account, especially for diseases with a long latency period such as lung cancer.
Reciprocal control of cell proliferation and migration
Authors: De Donatis Alina , Ranaldi Francesco , Cirri Paolo
Published: September 2010

In adult tissue the quiescent state of a single cell is maintained by the steady state conditions of its own microenvironment for what concern both cell-cell as well as cell-ECM interaction and soluble factors concentration. Physiological or pathological conditions can alter this quiescent state through an imbalance of both soluble and insoluble factors that can trigger a cellular phenotypic response. The kind of cellular response depends by many factors but one of the most important is the concentration of soluble cytokines sensed by the target cell. In addition, due to the intrinsic plasticity of many cellular types, every single cell is able, in response to the same stimulus, to rapidly switch phenotype supporting minimal changes of microenviromental cytokines concentration. Wound healing is a typical condition in which epithelial, endothelial as well as mesenchymal cells are firstly subjected to activation of their motility in order to repopulate the damaged region and then they show a strong proliferative response in order to successfully complete the wound repair process. This schema constitute the leitmotif of many other physiological or pathological conditions such as development vasculogenesis/angiogenesis as well as cancer outgrowth and metastasis.

Our review focuses on the molecular mechanisms that control the starting and, eventually, the switching of cellular phenotypic outcome in response to changes in the symmetry of the extracellular environment.
Eotaxin and FGF enhance signaling through an Extracellular signal-related kinase (ERK)-dependent pathway in the pathogenesis of Eosinophilic Esophagitis
Authors: Huang Jennifer J , Joh Jae Won , Fuentebella Judy , Patel Anup , Nguyen Tammie , Seki Scott , Hoyte Lisa , Reshamwala Neha , Nguyen Christine , Quiros Anthony , Bass Dorsey , Sibley Eric , Berquist William , Cox Kenneth , Kerner John , Nadeau Kari C
Published: September 2010

Background

Eosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.

Method

Real-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8).

Result

Of the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.

Conclusion

We describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.
Molluscicidal efficacies of different formulations of niclosamide: result of meta-analysis of Chinese literature
Authors: Yang Guo-Jing , Li Wei , Sun Le-Ping , Wu Feng , Yang Kun , Huang Yi-Xin , Zhou Xiao-Nong
Published: September 2010

The control efforts on Oncomelania hupensis, the intermediate snail host of Schistosoma japonicum, cannot be easily excluded from the integrated approach of schistosomiasis control in China. Application of chemical compounds, molluscicides, in snail habitats is a common method for snail control in addition to environmental modification. We conducted a systematic review and meta-analysis to assess the molluscicidal effects of the currently recommended 50% niclosamide ethanolamine salt wettable powder and a new 4% niclosamide ethanolamine salt powder developed by Chinese researchers. Literature was searched from three Chinese databases, i.e. Chinese Biomedical Database, VIP Database and Wanfang Database, on field mollusciciding trials of niclosamide in China (from January 1, 1990 to April 1, 2010). Molluscicidal effects on reduction of snail population of the 50% or 4% niclosamide formulations in field trial were evaluated 3 days, 7 days or 15 days post-application. Out of 90 publications, 20 papers were eventually selected for analysis. Publication bias and heterogeneity tests indicated that no publication bias existed but heterogeneity between studies was present. Meta-analysis in a random effect model showed that the snail mortality of 3, 7 and 15 days after spraying the 50% niclosamide ethanolamine salt wettable powder were 77% [95%CI: 0.68-0.86], 83% [95%CI: 0.77-0.89], and 88% [95%CI: 0.82-0.92], respectively. For the 4% niclosamide ethanolamine salt powder, the snail mortality after 3, 7 and 15 days were 81% [95%CI: 0.65-0.93], 90% [95%CI: 0.83-0.95] and 94% [95%CI: 0.91-0.97], respectively. Both are good enough to be used as molluscicides integrated with a schistosomiasis control programme. The 4% niclosamide ethanolamine salt powder can be applied in the field without water supply as the surrogate of the current widely used 50% niclosamide ethanolamine salt wettable powder. However, to consolidate the schistosomiasis control achievement gained, it is necessary to continuously perform mollusciciding more than twice annually in the field.
Elevated c-Src and c-Yes expression in malignant skin cancers
Authors: Lee Jang Hyun , Pyon Jae-Kyung , Kim Dong Wook , Lee Sang Han , Nam Hae Seon , Kim Chul Han , Kang Sang Gue , Lee Yoon Jin , Park Mi Youn , Jeong Dong Jun , Cho Moon Kyun
Published: September 2010

Abstracts

Background

Src family kinases (SFKs) play an important role in cancer proliferation, survival, motility, invasiveness, metastasis, and angiogenesis. Among the SFKs, c-Src and c-Yes are particularly over-expressed or hyper-activated in many human epithelial cancers. However, only a few studies have attempted to define the expression and role of c-Src and c-Yes in cutaneous carcinomas.

Objectives

To investigate the expression of c-Src and c-Yes in cutaneous carcinomas to include malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).

Methods

We examined 6 normal skin tissues and 18 malignant skin tumor tissues using western blotting for the expression of c-Src and c-Yes. In another set, 16 specimens of MM, 16 SCCs and 16 BCCs were analyzed for the expression of c-Src and c-Yes using immunohistochemical staining.

Results

Western blotting showed that c-Src was expressed in all malignant skin tumors, but not in normal skin, while c-Yes was expressed in MM and SCC, but not in BCC and normal skin. Immunohistochemical staining results of c-Src and c-Yes in MM, SCC, and BCC mirrored those of the western blot analysis.

Conclusions

c-Src, rather than c-Yes, plays a key role in the proliferation and progression of malignant skin cancers.
Expression and clinical significance of multidrug resistance proteins in brain tumors
Authors: Guo Zhenhua , Zhu Jin , Zhao Lihua , Luo Qing , Jin Xianqing
Published: September 2010

Background

To investigate the mechanisms of multidrug resistance of brain tumors, to identify the site of cellular expression of P-gp in human brains in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1.

Methods

Immunohistochemistry was used to detect the expression and location of P-glycoprotein (P-gp), Multidrug resistance-associated protein (MDR), Lung resistance-related protein (LRP), Topoisomerase II (Topo II) and Glutathione-S-π (GST-π) in 30 patient tumor tissues and 5 normal brain tissues. The sections were subjected to double labeling for P-gp (TRITC labeled) and caveolin-1 (FITC labeled). The location and characteristics of expression of the two proteins in the blood brain barrier(BBB) was observed using a laser scanning microscope.

Results

High expression of P-gp was detected in vessel walls and the tissue surrounding the vessels. However, expression of P-gp was low in tumor cells. The expression of the other 4 multidrug resistance proteins was not observed in the vessel walls. Laser scanning microscopy showed P-gp and caveolin-1 co-expression: the two proteins co-localized either in the luminal endothelial compartment or at the border of the luminal/abluminal compartments.

Conclusion

Chemotherapeutics drugs are interrupted in the end-feet of neuroepithelial cells of the BBB by P-gp, which weakens the chemotherapeutic effect. P-gp marks the BBB, and the transporter is localized in the luminal endothelial compartment where it co-localizes with caveolin-1.
Nonstationary phase estimation: A tool for seismic interpretation?
Authors: van der Baan Mirko , Fomel Sergey , Perz Mike
Published: September 2010

Spectral decomposition is a standard tool in seismic interpretation to highlight variations in layer thicknesses (e.g., in sand channels and turbidites). This is done by examining changes in peak frequencies in extracted horizon slices (Partyka et al., 1999). Variations in peak frequencies occur due to constructive interference between reflections from the top and bottom of a layer, with lower peak frequencies indicating thicker layers.
Seismic texture analysis for reservoir prediction and characterization
Authors: Yenugu Malleswar (Moe) , Marfurt Kurt J. , Matson Shane
Published: September 2010

A plethora of seismic attributes are currently in use for reservoir prediction and characterization. Some are useful in understanding subsurface stratigraphy (like channels) while others are useful for structural interpretation (anticlines, faults/fractures etc). Volumetric computation of seismic attributes is helpful to interpreters for 3D seismic visualization and interpretation. In addition to the time of a seismic reflection (resulting in a time-structure map), the more commonly used seismic attributes are rms amplitude, frequency, coherence, AVO, and impedance. These attributes are based on clearly established morphological or petrophysical models with some attributes sensitive to rock types, some to fluid saturation, some to porosity and some to minor faults or fractures within the reservoir. Our case study of a diagenetically altered Mississippian limestone resulting in complex paleo topography defies simple analysis. Even with adequate well control and good ties to 3D seismic data, uncertainty in the attribute expression of different reservoir architecture may result in the failure to identify sweet spots for drilling.
Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non–Small-Cell Lung Cancer
Authors: Zhu Chang-Qi , Ding Keyue , Strumpf Dan , Weir Barbara A. , Meyerson Matthew , Pennell Nathan , Thomas Roman K. , Naoki Katsuhiko , Ladd-Acosta Christine , Liu Ni , Pintilie Melania , Der Sandy , Seymour Lesley , Jurisica Igor , Shepherd Frances A. , Tsao Ming-Sound
Published: September 2010

Purpose

The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non–small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.

Patients and Methods

Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR).

Results

A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001; stage II HR, 13.47; P < .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n = 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P < .001). Significant interaction between risk groups and ACT was verified by qPCR.

Conclusion

This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
Survival Benefit With Proapoptotic Molecular and Pathologic Responses From Dual Targeting of Mammalian Target of Rapamycin and Epidermal Growth Factor Receptor in a Preclinical Model of Pancreatic Neuroendocrine Carcinogenesis
Authors: Chiu Christopher W. , Nozawa Hiroaki , Hanahan Douglas
Published: September 2010

Purpose

Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET.

Materials and Methods

Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics.

Results

Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy.

Conclusion

Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.
A genetic cascade involving klumpfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNS
Authors: Benito-Sipos Jonathan , Estacio-Gómez Alicia , Moris-Sanz Marta , Baumgardt Magnus , Thor Stefan , Díaz-Benjumea Fernando J.
Published: September 2010

Identification of the genetic mechanisms underlying the specification of large numbers of different neuronal cell fates from limited numbers of progenitor cells is at the forefront of developmental neurobiology. In Drosophila, the identities of the different neuronal progenitor cells, the neuroblasts, are specified by a combination of spatial cues. These cues are integrated with temporal competence transitions within each neuroblast to give rise to a specific repertoire of cell types within each lineage. However, the nature of this integration is poorly understood. To begin addressing this issue, we analyze the specification of a small set of peptidergic cells: the abdominal leucokinergic neurons. We identify the progenitors of these neurons, the temporal window in which they are specified and the influence of the Notch signaling pathway on their specification. We also show that the products of the genes klumpfuss, nab and castor play important roles in their specification via a genetic cascade.
Plasma membrane-bound AGC3 kinases phosphorylate PIN auxin carriers at TPRXS(N/S) motifs to direct apical PIN recycling
Authors: Dhonukshe Pankaj , Huang Fang , Galvan-Ampudia Carlos S. , Mähönen Ari Pekka , Kleine-Vehn Jurgen , Xu Jian , Quint Ab , Prasad Kalika , Friml Jiří , Scheres Ben , Offringa Remko
Published: September 2010

Polar membrane cargo delivery is crucial for establishing cell polarity and for directional transport processes. In plants, polar trafficking mediates the dynamic asymmetric distribution of PIN FORMED (PIN) carriers, which drive polar cell-to-cell transport of the hormone auxin, thereby generating auxin maxima and minima that control development. The Arabidopsis PINOID (PID) protein kinase instructs apical PIN localization by phosphorylating PINs. Here, we identified the PID homologs WAG1 and WAG2 as new PIN polarity regulators. We show that the AGC3 kinases PID, WAG1 and WAG2, and not other plant AGC kinases, instruct recruitment of PINs into the apical recycling pathway by phosphorylating the middle serine in three conserved TPRXS(N/S) motifs within the PIN central hydrophilic loop. Our results put forward a model by which apolarly localized PID, WAG1 and WAG2 phosphorylate PINs at the plasma membrane after default non-polar PIN secretion, and trigger endocytosis-dependent apical PIN recycling. This phosphorylation-triggered apical PIN recycling competes with ARF-GEF GNOM-dependent basal recycling to promote apical PIN localization. In planta, expression domains of PID, WAG1 and WAG2 correlate with apical localization of PINs in those cell types, indicating the importance of these kinases for apical PIN localization. Our data show that by directing polar PIN localization and PIN-mediated polar auxin transport, the three AGC3 kinases redundantly regulate cotyledon development, root meristem size and gravitropic response, indicating their involvement in both programmed and adaptive plant development.
Integrin-linked kinase regulates p38 MAPK-dependent cell cycle arrest in ureteric bud development
Authors: Smeeton Joanna , Zhang Xi , Bulus Nada , Mernaugh Glenda , Lange Anika , Karner Courtney M. , Carroll Thomas J. , Fässler Reinhard , Pozzi Ambra , Rosenblum Norman D. , Zent Roy
Published: September 2010

The integrin-linked kinase (ILK), pinch and parvin ternary complex connects the cytoplasmic tails of β1 integrins to the actin cytoskeleton. We recently showed that constitutive expression of ILK and alpha parvin in both the ureteric bud and the metanephric mesenchyme of the kidney is required for kidney development. In this study, we define the selective role of ILK in the ureteric bud of the mouse kidney in renal development by deleting it in the ureteric cell lineage before the onset of branching morphogenesis (E10.5). Although deleting ILK resulted in only a moderate decrease in branching, the mice died at 8 weeks of age from obstruction due to the unprecedented finding of intraluminal collecting duct cellular proliferation. ILK deletion in the ureteric bud resulted in the inability of collecting duct cells to undergo contact inhibition and to activate p38 mitogen-activated protein kinase (MAPK) in vivo and in vitro. p38 MAPK activation was not dependent on the kinase activity of ILK. Thus, we conclude that ILK plays a crucial role in activating p38 MAPK, which regulates cell cycle arrest of epithelial cells in renal tubulogenesis.
Do women consult more than men? A review of gender and consultation for back pain and headache
Authors: Hunt Kate , Adamson Joy , Hewitt Catherine , Nazareth Irwin
Published: September 2010

Objectives:

Because women consult their general practitioners more frequently on average than men, it is commonly assumed that they consult more for all symptoms and conditions. This assumption is reinforced by qualitative studies reporting a widespread reluctance to consult by men. However, few studies directly compare consultation in men and women experiencing similar symptoms or conditions.

Methods:

A systematic review of the evidence on gender and consultation for two common symptoms, back pain and headache. Extensive electronic searches identified 15 papers reporting the relationship between gender and help-seeking for back pain and 11 papers for headache. Two independent reviewers assessed articles for inclusion and extracted data from eligible studies.

Results:

Few studies compared consultation patterns for these symptoms among men and women known to have experienced the symptom. The quality of the studies was variable. Overall, evidence for greater consultation by women with back pain was weak and inconsistent. Among those with back pain, the odds ratios for women seeking help, compared with men, ranged from 0.6 (95% confidence intervals 0.3, 1.2, adjusted only for age) to 2.17 (95% confidence intervals 1.35, 3.57, unadjusted), although none of the reported odds ratio, below 1.00 was statistically significant. The evidence for women being more likely to consult for headache was a little stronger. Five studies showed a statistically elevated odds ratio, and none suggested that men with headache symptoms were more likely to consult than women with headache symptoms. Limitations to the studies are discussed.

Conclusion:

Given the strength of assumptions that women consult more readily for common symptoms, the evidence for greater consultation amongst women for two common symptoms, headache and back pain, was surprisingly weak and inconsistent, especially with respect to back pain.
RNA duplexes in transcriptional regulation
Authors: Swaminathan Sanjay , Hood Chantelle L. , Suzuki Kazuo , Kelleher Anthony D.
Published: September 2010

Transcriptional regulation by small RNA molecules, including small interfering RNA and microRNA, has emerged as an important gene expression modulator. The regulatory pathways controlling gene expression, post-transcriptional gene silencing and transcriptional gene silencing (TGS) have been demonstrated in yeast, plants and more recently in human cells. In this review, we discuss the currents models of transcriptional regulation and the main components of the RNA-induced silencing complex and RNA-induced transcriptional silencing complex machinery, as well as confounding off-target effects and gene activation. We also discuss RNA-mediated TGS within the NF-κB motif of the human immunodeficiency virus type 1 5′ long tandem repeat promoter region and the associated epigenetic modifications. Finally, we outline the current RNA interference (RNAi) delivery methods and describe the current status of human trials investigating potential RNAi therapeutics for several human diseases.
Zur Problematik des Mitteleuropabegriffs in der Literaturwissenschaft: Einige methodologische Überlegungen
Authors: Ohme Andreas
Published: September 2010

In the course of the so-called cultural turn the construction of identities has become a central field of research in literary criticism. In describing an area with a supposed specific cultural tradition the concept of Central Europe in this context achieved a certain prominence within Slavonic Studies. This paper therefore discusses the consequences of this research interest for the self-concept of Slavonic Studies as an academic subject. Demonstrating that the concept of Central Europe cannot claim any plausible heuristic value for the exploration of literary works of art the conclusion is drawn that this concept, as with the preoccupation with the construction of cultural identities in general, does not make any contribution to subject-specific knowledge. Thus this research interest tends to undermine the legitimacy of literary criticism as an independent academic subject.
„Das Paradies des Herzens“ des Jan Amos Komenský
Authors: Ebeling Jana
Published: September 2010

This article is an interpretation of the second part of the famous “Labyrint svĕta a ráj srdce” of Jan Amos Komenský. This text was written in the early 17th century and is in most beautiful Czech telling the story of a pilgrim who finds God by returning from his way through the sinful world (this part of the journey is described in the “Labyrint svĕta”) to his inner self. There he meets Jesus Christ in the chamber of his heart, from where he is again sent out to explore what life in the service of God can be like, if he only decides to fully believe. Komenský hereby presents his own vision of the right way of life.
Reduced Endothelial Progenitor Cells in Children With Hemodialysis but Not Predialysis Chronic Kidney Disease
Authors: Jie Kim E. , Lilien Marc R. , Goossens Michèle H. J. , Westerweel Peter E. , Ing Mark Klein , Verhaar Marianne C.
Published: September 2010

In adults with chronic kidney disease (CKD), reduced levels of vasculoprotective endothelial progenitor cells (EPCs) may contribute to their increased risk of cardiovascular disease. Children with CKD also show signs of cardiovascular disease. However, to our knowledge, there have been no studies on circulating EPC levels in pediatric patients with CKD. We investigated CD34+KDR+ EPC numbers by using flow cytometry in 15 children with predialysis CKD, 13 children on hemodialysis, and 18 age-matched healthy controls. Children on hemodialysis showed 47% reduced EPC levels compared with controls, whereas no significant difference was found for patients with predialysis CKD. Lower EPC levels were found in patients with higher levels of inflammatory marker high-sensitivity C-reactive protein. Our data show, for the first time, that children on hemodialysis have reduced CD34+KDR+ EPC levels, which potentially contributes to their increased cardiovascular risk. In children with predialysis CKD, a decline in renal function was not associated with reduced EPC levels, which may reflect a capacity for preservation of the endogenous repair system during relatively moderate disturbances of the systemic environment.
Spirometry Use Among Pediatric Primary Care Physicians
Authors: Dombkowski Kevin J. , Hassan Fauziya , Wasilevich Elizabeth A. , Clark Sarah J.
Published: September 2010

OBJECTIVE:

This study explores the use of spirometry in primary care settings.

METHODS:

A 4-page survey was mailed to a national, random sample of office-based family physicians and pediatricians. Survey items addressed knowledge, attitudes, and practices regarding spirometry and standardized clinical vignettes. Data were analyzed by using χ2 tests and multivariate logistic regression.

RESULTS:

Among the 360 respondents who provided care to children with asthma, 52% used spirometry in clinical practice, whereas 80% used peak flow meters and 10% used no lung function tests. Only 21% routinely used spirometry for all guideline-recommended clinical situations. More family physicians than pediatricians reported using spirometry (75% vs 35%; P < .0001), and family physicians were more comfortable in interpreting spirometric results (50% vs 25%; P < .0001). Only one-half of respondents interpreted correctly the spirometric results in a standardized clinical vignette, and the frequency of underrating asthma severity increased with the inclusion of spirometric results. The most common barriers to the use of spirometry, that is, time and training, were cited more often by physicians who did not use spirometry. Two-thirds of respondents agreed that they would want additional training regarding implementing spirometry in their clinical practices.

CONCLUSIONS:

The use of spirometry in primary care settings for children with asthma does not conform to national guidelines. Widespread implementation of national asthma guidelines likely would require a major educational initiative to address deficiencies in spirometry interpretation and other barriers.
Introduction to papers on Women’s Leadership Roles in Therav?da Buddhist Traditions
Authors: Anderson Carol S. , Salgado Nirmala S.
Published: September 2010

These papers were presented at a panel, organized by us and chaired by Liz Wilson, on ‘Women’s Leadership and Monastic Organizations in Therav?da Buddhist Traditions’, at the 2008 American Academy of Religion meeting, Chicago. Here, we bring together articles that examine the roots of the teachings on nuns in P?li literature with others which investigate issues relating to contemporary Therav?da nuns, as well as an analysis of relevant debates in ancient China. The objective of these papers is to contribute to discussion of the multiple ways in which professionally celibate women are represented, organized and empowered in the textual and contemporary traditions of P?li and Therav?da Buddhism, to study how representations of female monasticism are related to organizational structures of leadership and agency, and explore how debates over the need for ‘dual ordination’ have occurred in traditions other than the Therav?da.
The Agency of Buddhist Nuns
Authors: Anderson Carol S
Published: September 2010

This article examines how Buddhist literatures construct the agency of Buddhist nuns. The first section explores the Vinaya collections of different schools, and examines the differences between the Bhikkhun?-vibha?ga and the Bhikkhu-vibha?ga on how nuns are expected to act. The second section explores material on the faculties (indriyas) in the P?li Abhidhamma-pi?aka and its commentaries so as to better understand how the abhidhamma analyses of ‘women’s nature’ and ‘men’s nature’ informed conceptions of agency. This article suggests that even though the abhidhamma literature uses such terms as ‘women’s nature’, there is little basis for concluding, as some scholars have done, that Buddhist literature reflects an essentialist view of gender. The fact that the abhidhamma analyses of gender distinguish between ‘male faculties’ and ‘female faculties’ does not appear to make a difference in the agency accorded to nuns: nuns, like monks, are expected to behave in certain ways independent of the fact that they have ‘female faculties’ and thus are inclined toward certain kinds of stereotypically female behaviour.
Reinterpretation of the Miocene Sea-Snake Egg Moniopterus Japonicus as a Boring of Rock-Boring Bivalve Lithophaga (Mytilidae: Mollusca)
Authors: Haga Takuma , Kurihara Yukito , Kase Tomoki
Published: September 2010

The enigmatic fossil Moniopterus japonicus Hatai et al., 1974 from the early Middle Miocene Moniwa Formation of northern Japan has been described as the only known example of fossil sea-snake eggs and also as fossilized pupal chambers of a coleopteran insect. A reexamination of the holotype provides no evidence in support of these previous interpretations. Scanning electronic microscopy and computed tomography observations on the holotype reveal that the calcareous lining, previously interpreted as eggshell, is instead composed of irregular spherulitic prisms, thin in the middle and becoming thicker toward both ends. In addition to the elongate oval shape and the presence of an opening at the more pointed end, these observations strongly suggest that M. japonicus is a boring of the mytilid boring bivalve Lithophaga isolated from the host rock. This reinterpretation is further supported by the occurrence of similar isolated and in situ borings with Lithophaga shells within the type and a nearby locality. Regarding this fossil as an ichnofossil makes the generic name Moniopterus a junior synonym of Gastrochaenolites Leymerie, 1842 and the species name japonicus is a senior synonym of Gastrochaenolites torpedo Kelly and Bromley, 1984. G. torpedo should thus be replaced with Gastrochaenolites japonicus (Hatai et al., 1974).
Distinguishing Agromyzidae (Diptera) Leaf Mines in the Fossil Record: New Taxa from the Paleogene of North America and Germany and Their Evolutionary Implications
Authors: Winkler Isaac S. , Labandeira Conrad C. , Wappler Torsten , Wilf Peter
Published: September 2010

Fossilized leaf mines and other traces of phytophagous insects provide a unique window into ecological and evolutionary associations of the past. Leaf-mining flies (Diptera: Agromyzidae) are an important component of the recent leaf-mining fauna, but their fossil record is sparse compared to other mining insect lineages; many putative agromyzid body fossils and traces are dubiously assigned. Agromyzid leaf mines often can be distinguished from those of other insects by the presence of an intermittent, fluidized frass trail that may alternate between the sides of the mine. Here, we describe two new Paleogene leaf mine fossils,Phytomyzites biliapchaensisWinkler, Labandeira and Wilfn. sp.from the early Paleocene of southeastern Montana, USA, occurring in leaves ofPlatanus raynoldsii(Platanaceae); andPhytomyzites schaarschmidtiWapplern. sp., from the middle Eocene of Messel, Germany, occurring in leaves ofToddalia ovata(Rutaceae). These fossils both exhibit frass trails indicative of an agromyzid origin, andP. biliapchaensisalso exhibits associated stereotypical marks identical to damage caused by feeding punctures of extant adult female Agromyzidae prior to oviposition.Phytomyzites biliapchaensisrepresents the earliest confirmed record of Agromyzidae, and one of the earliest records for the large dipteran clade Schizophora. Plant hosts of both species belong to genera that are no longer hosts of leaf-mining Agromyzidae, suggesting a complex and dynamic history of early host-plant associations and, for the early Paleocene example, an evolutionary, possibly opportunistic colonization in the midst of the ecological chaos following the end-Cretaceous event in North America.
Suppressor of cytokine signaling 3 knockdown in the mediobasal hypothalamus: counterintuitive effects on energy balance
Authors: de Backer M W A , Brans M A D , van Rozen A J , van der Zwaal E M , Luijendijk M C M , Garner K G , de Krom M , van Beekum O , la Fleur S E , Adan R A H
Published: September 2010

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.
Species dispersal rates alter diversity and ecosystem stability in pond metacommunities
Authors: Howeth Jennifer G. , Leibold Mathew A.
Published: September 2010

Metacommunity theory suggests that relationships between diversity and ecosystem stability can be determined by the rate of species dispersal among local communities. The predicted relationships, however, may depend upon the relative strength of local environmental processes and disturbance. Here we evaluate the role of dispersal frequency and local predation perturbations in affecting patterns of diversity and stability in pond plankton metacommunities. Pond metacommunities were composed of three mesocosm communities: one of the three communities maintained constant “press” predation from a selective predator, bluegill sunfish (Lepomis macrochirus); the second community maintained “press” conditions without predation; and the third community experienced recurrent “pulsed” predation from bluegill sunfish. The triads of pond communities were connected at either no, low (0.7%/d), or high (20%/d) planktonic dispersal. Richness and composition of zooplankton and stability of plankton biomass and ecosystem productivity were measured at local and regional spatial scales. Dispersal significantly affected diversity such that local and regional biotas at the low dispersal rate maintained the greatest number of species. The unimodal local dispersal–diversity relationship was predator‐dependent, however, as selective press predation excluded species regardless of dispersal. Further, there was no effect of dispersal on beta diversity because predation generated local conditions that selected for distinct community assemblages. Spatial and temporal ecosystem stability responded to dispersal frequency but not predation. Low dispersal destabilized the spatial stability of producer biomass but stabilized temporal ecosystem productivity. The results indicate that selective predation can prevent species augmentation from mass effects but has no apparent influence on stability. Dispersal rates, in contrast, can have significant effects on both species diversity and ecosystem stability at multiple spatial scales in metacommunities.