bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory ataxia associated with chronic organophosphate pesticide exposure
Authors: Little S. , Llewellyn H. , Clarke SFJ
Published: January 2010

Organophosphorus compounds are widely used in agriculture and industry. Although the immediate and delayed effects of acute exposure have been well described, the clinical sequelae of chronic, low-dose exposure are less certain. This paper describes the case of a farmer who had been exposed to a variety of organophosphate pesticides over a 30-year period, and developed sensory ataxia, which has not previously been described. She was found to have an abnormal cholinesterase phenotype. Mechanisms of possible increased sensitivity to these compounds are discussed which may, in future, allow certain occupational groups to be screened.
Micronucleus-centromere assay in workers occupationally exposed to low level of benzene
Authors: Yang Jee Kim  , Jun Yeol Choi  , Yoon Hee Cho  , Hae Dong Woo  , Hai Won Chung
Published: February 2010

Benzene is a well-known carcinogen that induces chromosomal instability, including chromosome aberration and aneuploidy. In order to assess aneugenic effect of low-level benzene, micronucleus-centromere assay using specific probes for chromosomes 7 and 9 was performed in workers occupationally exposed to low-dose benzene at a petroleum refinery. A micronucleus-centromere assay using a pan-centromeric probe was also performed to determine the origin of benzene-induced micronucleus (MN). Frequency of aneuploidy of chromosomes 7 and 9 was significantly higher among workers compared to the unexposed control group. Poisson regression analysis revealed that aneuploidy frequency of chromosome 7 or 9 was significantly associated with benzene level after adjusting for confounding variables such as age, smoking, alcohol intake, and duration of work (p = .042). Additionally, frequencies of MN and centromere-negative micronuclei (MNC—) were significantly higher in benzene-exposed workers compared to controls, while frequency of centromere-positive micronuclei (MNC+) was similar in both groups. In conclusion, aneuploidy of chromosomes 7 and 9 could be a useful biomarker to assess the effect of low-level benzene exposure, and benzene-induced MN originates from chromosome breaks rather than chromosome non-disjunction.
Families’ and Professional Caregivers’ Views of Using Advanced Technology to Track People With Dementia
Authors: Landau Ruth , Auslander Gail K. , Werner Shirli , Shoval Noam , Heinik Jeremia
Published: February 2010

in this study we examined the ethical aspects of the use of the Global Positioning Systems (GPS) to track people with dementia. The findings are based on qualitative data gathered from focus groups of family and professional caregivers. The most important theme was the need to balance patients’ need for safety with the need to preserve their autonomy and privacy. The main potential benefit of the use of GPS was related to the peace of mind of the caregivers themselves. The findings also suggest that caregivers’ views change according to the locus of responsibility of the caregivers for the safety of people with dementia. The caregivers give preference to patients’ safety more than autonomy when they are responsible for the patients. When the patients are under the responsibility of other caregivers, they give preference to patients’ autonomy more than their safety. Overall, the variety and the depth of the views of different stakeholders toward the use of electronic tracking for people with dementia presented in this article provide a meaningful contribution to the ethical debate on this topic.
Women’s Reporting of Sexual and Physical Assaults to Police in the National Violence Against Women Survey
Authors: Chen Yingyu , Ullman Sarah E.
Published: February 2010

Previous research has assumed that rape reporting is unique, but no study has systematically tested this assumption. The present study used a probability sample of female victims from the National Violence Against Women Survey to compare factors affecting rape and physical assault reporting using multinomial logit regression. Overall, results suggested that there was similarity in reporting decisions between rapes and physical assaults in terms of main effects. However, interactions suggested that age, marital status, and physical force each influenced reporting differently by assault type. Implications of these results are discussed and directions for future research are offered.
“Fathers’ Rights” and the Defense of Paternal Authority in Australia
Authors: Flood Michael
Published: February 2010

Feminism’s achievements regarding violence against women are a key target for the fathers’ rights movement. This article provides an overview of the impact of the fathers’ rights movement on men’s violence against women. It documents the ways in which fathers’ rights groups in Australia have influenced changes in family law, which privilege parental contact over safety, particularly through moves toward a presumption of children’s joint residence. They have attempted to discredit female victims of violence, to wind back the legal protections available to victims and the sanctions imposed on perpetrators, and to undermine services for the victims of men’s violence.
Adaptation of Models Versus Variations in Form: Classifying Structures of City Government
Authors: Nelson Kimberly L. , Svara James H.
Published: January 2010

A great deal of variability exists in American local government structures. It would be useful to analyze the differences in outcomes associated with different structures, but two factors stand in the way. First, there is no agreement about how to classify city governments. Second, many of the components used in existing classifications are inaccurately reported or missing in survey data. In this research note, a new classification system based on three easily determined components is developed and used to measure the current distribution of forms and variations in an expanded data set that includes almost all cities over 10,000 in population.
A Multiplex Theory of Urban Service Distribution: The Case of School Expenditures
Authors: Pallas Aaron M. , Jennings Jennifer L.
Published: January 2010

The literature on urban service delivery has crystallized into two key theoretical perspectives, one emphasizing agency and interests and the other structure and bureaucracy. These perspectives typically do not allow for the possibility that explanations of the origins of variability in the distribution of urban services might differ from explanations of the persistence of such variability. In this article, the authors articulate a multiplex, longitudinal model of urban service distribution, emphasizing the contributions of multiplex funding streams and multiple layers of bureaucracy, bureaucratic discretion, and path dependency to the model. Drawing on data on school building—level expenditures in New York City over six years, the authors provide new evidence on the distribution of expenditures on public education in New York City. They find that there is substantial year-to-year stability in per-pupil expenditures, that expenditures are responsive to the social and economic characteristics of clients at varying levels of the education system, and that allocation decisions made at a given level of the system may either amplify or diminish the distributional consequences of allocation decisions made at a higher level of the system.
Native Sexual Inequalities: American Indian Cultural Conservative Homophobia and the Problem of Tradition
Authors: Gilley Brian Joseph
Published: February 2010

Two-Spirit men cite the common goal of eventually gaining social acceptance and restoring a place of honor within their individual tribal societies as their unifying factor. They set out to achieve this goal by actively engaging with American Indian cultural conservative values through ceremonial and social practices. By altering normalized gender practices they challenge their alienation while also solidifying their commitment to tribal communities. By proving themselves as culturally competent contributors to their tribal societies they publicly question mainstream Native attitudes toward sexuality and gender in the hope that their value to Native societies will eventually put an end to the ubiquitous homophobia that alienates them.
The Incredible Shrinking Lesbian World and other Queer Conundra
Authors: Stein Arlene
Published: February 2010

This is a reflection on the state of lesbian identity politics, focusing on claims that lesbian subcultures are shrinking and even dying. Current fears focus on the increasingly permeable boundaries between butch lesbians and female-to-male transgender individuals, but its history is much longer. What we are seeing, quite possibly, is the exhaustion of a particular historical construction: a group of individuals who are defined primarily on the basis of their sexuality, and the rise of more specific identities which combine sexual preference, gender presentation and other modes of identification. This was the first annual Sally Miller Gearhart Lecture in Lesbian Studies, sponsored by the Department of Women’s and Gender Studies at the University of Oregon, in May 2009
On the Possibility of Spectral Ethnography
Authors: Armstrong Justin
Published: January 2010

This article reflects on the possibility of engaging in a kind of ethnography of absence, an anthropology of people, and places and things that have been removed, deleted, and abandoned to the flows of time and space. Here, the author suggests a mode of ethnographic inquiry that performs an archaeology of the emptied present and of the vacant spaces of culture. Using recent ethnographic fieldwork in the North American High Plains as the basis of his analysis, the author seeks to reimagine his own ethnographic practices in the context of these hollowed-out and spectrally resonant spaces of culture. What significance can be drawn from the multiple layers of time and materiality that have accumulated in these places and what type of haunted narratives can emerge from the discarded remnants of human occupation? How can ethnography excavate the lives-once-lived from the space of abandonment?
Child and Parental Perception of Asthma Control
Authors: Carlton B. Gwen , Thompson Carol , Wan Jim Y. , Conboy-Ellis Kathleen , Coates Loretta
Published: January 2010

This investigation was conducted to determine if children with asthma and their parents had similar perceptions of asthma control. This retrospective chart review looked at the electronic medical records of 45 children with asthma, ages 4-11 years. The records were reviewed to determine age, gender, race, and medication management. The answers to the C-ACT were analyzed to determine if the child’s asthma was well controlled and to find out if the child and their parents had the same perception of the child’s level of asthma control. It revealed that 62% of the subjects had asthma that was not well controlled. When comparing the child’s weighted score to the parent score on the C-ACT using the signed rank test there was a significance of P <.04. Comparing mean difference in the two groups revealed that the children perceive their asthma to be less well controlled than their parents do. Asthma control was not achieved for the majority of subjects in investigation despite appropriate prescribing practices. Most importantly, the child with asthma may perceive his or her asthma to be less well controlled than their parent, therefore making it imperative for the health care provider to assess both the child and their parents with regard to asthma control.
Allergic Rhinitis
Authors: Hayden Mary Lou
Published: January 2010

Allergic rhinitis (AR) is a common chronic disease that can lead to medical complications and is associated with asthma. For a number of reasons, including cost of health care, many patients self-diagnose and self-medicate rather than present for evaluation by a health care provider. While some effective medications are transitioning from prescription to over-the-counter status, patients are not receiving proper education regarding environmental triggers and the consequences of untreated or undertreated rhinitis. Patients rarely appreciate the role AR plays in asthma. Furthermore, uncontrolled AR can result in reduced quality of life with impaired work and school performance and social functioning. This article will discuss the relationship between AR and asthma, summarize signs and symptoms of rhinitis, differentiate allergic from nonallergic rhinitis, and present optimal pharmacologic and nonpharmacologic treatments of rhinitis.
Critical roles for c-Myb in lymphoid priming and early B-cell development
Authors: Greig Kylie T. , de Graaf Carolyn A. , Murphy James M. , Carpinelli Marina R. , Pang Swee Heng Milon , Frampton Jon , Kile Benjamin T. , Hilton Douglas J. , Nutt Stephen L.
Published: February 2010

c-Myb is a transcription factor with functions in many hematopoietic lineages. c-Myb–deficient mice display reduced numbers of B cells; however, it is unknown what role c-Myb plays in B lymphopoiesis because no critical target genes have been identified in the B-cell lineage. We demonstrate that conditional deletion of c-Myb in B-cell progenitors completely abolishes B-cell development. c-Myb is required for lymphoid progenitors to respond to the cytokines interleukin-7 and thymic stromal lymphopoietin; in the absence of sufficient c-Myb activity, mice display a B lymphopenia that closely resembles that observed in interleukin-7 receptor α–deficient animals. Analysis of the multipotent progenitor compartment indicates that c-Myb is also required for up-regulation of multiple lymphoid-associated genes, including Il7r, and for the subsequent development of the common lymphoid progenitor population. These data show that c-Myb plays a critical role in the regulatory pathways governing lymphoid specification and early B-cell differentiation.
Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors
Authors: Merchant Akil , Joseph Giselle , Wang Qiuju , Brennan Sarah , Matsui William
Published: January 2010

The Hedgehog (Hh) pathway is essential for normal embryonic development and tissue repair. The role of Hh signaling in hematopoiesis has been studied primarily by modulating the activity of Patched and Smoothened, but results have been conflicting. Some studies demonstrate a requirement for pathway activity in hematopoiesis, whereas others report that it is dispensable. Hh activity converges on the Gli transcription factors, but the specific role of these downstream effectors in hematopoiesis has not been reported. We have analyzed hematopoietic stem cell (HSC) and progenitor function in mice with a homozygous deletion of Gli1 (Gli1null). Gli1null mice have more long-term HSCs that are more quiescent and show increased engraftment after transplantation. In contrast, myeloid development is adversely affected with decreased in vitro colony formation, decreased in vivo response to granulocyte colony-stimulating factor (G-CSF), and impaired leukocyte recovery after chemotherapy. Levels of the proto-oncogene Cyclin D1 are reduced in Gli1null mice and may explain the loss of proliferation seen in HSCs and progenitor cells. These data demonstrate that Gli1 regulates normal and stress hematopoiesis. Moreover, they suggest that Gli1 and Smoothened may not be functionally redundant, and direct GLI1 inhibitors may be needed to effectively block HH/GLI1 activity in human disease.
Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo
Authors: Bertrand Julien Y. , Cisson Jennifer L. , Stachura David L. , Traver David
Published: January 2010

Recent studies have revealed that definitive hematopoiesis in vertebrates initiates through the formation of a non–self-renewing progenitor with limited multilineage differentiation potential termed the erythromyeloid progenitor (EMP). EMPs are specified before hematopoietic stem cells (HSCs), which self-renew and are capable of forming all mature adult blood lineages including lymphoid cells. Despite their differences, EMPs and HSCs share many phenotypic traits, making precise study of their respective functions difficult. Here, we examine whether embryonic specification of EMPs requires Notch signaling as has been shown for HSCs. In mindbomb mutants, which lack functional Notch ligands, we show that EMPs are specified normally: we detect no significant differences in cell number, gene expression, or differentiation capacity between EMPs purified from wild-type (WT) or mindbomb mutant embryos. Similarly N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), a chemical inhibitor of Notch receptor activation, has no effect on EMP specification. These studies establish that HSCs are the only hematopoietic precursor that requires Notch signaling and help to clarify the signaling events underlying the specification of the 2 distinct waves of definitive hematopoiesis.
Rapid determination of tricarboxylic acid cycle enzyme activities in biological samples
Authors: Goncalves Sergio , Paupe Vincent , Dassa Emmanuel P , Brière Jean-Jacques , Favier Judith , Gimenez-Roqueplo Anne-Paule , Bénit Paule , Rustin Pierre
Published: January 2010

Background

In the last ten years, deficiencies in tricarboxylic acid cycle (TCAC) enzymes have been shown to cause a wide spectrum of human diseases, including malignancies and neurological and cardiac diseases. A prerequisite to the identification of disease-causing TCAC enzyme deficiencies is the availability of effective enzyme assays.

Results

We developed three assays that measure the full set of TCAC enzymes. One assay relies on the sequential addition of reagents to measure succinyl-CoA ligase activity, followed by succinate dehydrogenase, fumarase and, finally, malate dehydrogenase. Another assay measures the activity of α-ketoglutarate dehydrogenase followed by aconitase and isocitrate dehydrogenase. The remaining assay measures citrate synthase activity using a standard procedure. We used these assays successfully on extracts of small numbers of human cells displaying various severe or partial TCAC deficiencies and on frozen heart homogenates from heterozygous mice harboring an SDHB gene deletion.

Conclusion

This set of assays is rapid and simple to use and can immediately detect even partial defects, as the activity of each enzyme can be readily compared with one or more other activities measured in the same sample.
Computational identification of rare codons of Escherichia coli based on codon pairs preference
Authors: Wu Xianming , Wu Songfeng , Li Dong , Zhang Jiyang , Hou Lin , Ma Jie , Liu Wanlin , Ren Daming , Zhu Yunping , He Fuchu
Published: January 2010

Background

Codon bias is believed to play an important role in the control of gene expression. In Escherichia coli, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in Escherichia coli.

Results

In Escherichia coli, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (Frare) was developed. Through comparison with the classical indices we found a significant negative correlation between Frare and the indices which depend on reference datasets.

Conclusions

Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (Frare) could be a useful index of codon bias regardless of the lack of expression abundance information.
Mechano-transduction in periodontal ligament cells identifies activated states of MAP-kinases p42/44 and p38-stress kinase as a mechanism for MMP-13 expression
Authors: Ziegler Nelli , Alonso Angel , Steinberg Thorsten , Woodnutt Dale , Kohl Annette , Müssig Eva , Schulz Simon , Tomakidi Pascal
Published: January 2010

Background

Mechano-transduction in periodontal ligament (PDL) cells is crucial for physiological and orthodontic tooth movement-associated periodontal remodelling. On the mechanistic level, molecules involved in this mechano-transduction process in PDL cells are not yet completely elucidated.

Results

In the present study we show by western blot (WB) analysis and/or indirect immunofluorescence (IIF) that mechanical strain modulates the amount of the matrix metalloproteinase MMP-13, and induces non-coherent modulation in the amount and activity of signal transducing molecules, such as FAK, MAP-kinases p42/44, and p38 stress kinase, suggesting their mechanistic role in mechano-transduction. Increase in the amount of FAK occurs concomitant with increased levels of the focal contact integrin subunits β3 and β1, as indicated by WB or optionally by IIF. By employing specific inhibitors, we further identified p42/44 and p38 in their activated, i.e. phosphorylated state responsible for the expression of MMP-13. This finding may point to the obedience in the expression of this MMP as extracellular matrix (ECM) remodelling executioner from the activation state of mechano-transducing molecules. mRNA analysis by pathway-specific RT-profiler arrays revealed up- and/or down-regulation of genes assigning to MAP-kinase signalling and cell cycle, ECM and integrins and growth factors. Up-regulated genes include for example focal contact integrin subunit α3, MMP-12, MAP-kinases and associated kinases, and the transcription factor c-fos, the latter as constituent of the AP1-complex addressing the MMP-13 promotor. Among others, genes down-regulated are those of COL-1 and COL-14, suggesting that strain-dependent mechano-transduction may transiently perturbate ECM homeostasis.

Conclusions

Strain-dependent mechano-/signal-transduction in PDL cells involves abundance and activity of FAK, MAP-kinases p42/44, and p38 stress kinase in conjunction with the amount of MMP-13, and integrin subunits β1 and β3. Identifying the activated state of p42/44 and p38 as critical for MMP-13 expression may indicate the mechanistic contribution of mechano-transducing molecules on executioners of ECM homeostasis.
Transcriptome analysis reveals absence of unintended effects in drought-tolerant transgenic plants overexpressing the transcription factor ABF3
Authors: Abdeen Ashraf , Schnell Jaimie , Miki Brian
Published: January 2010

Background

Plants engineered for abiotic stress tolerance may soon be commercialized. The engineering of these plants typically involves the manipulation of complex multigene networks and may therefore have a greater potential to introduce pleiotropic effects than the simple monogenic traits that currently dominate the plant biotechnology market. While research on unintended effects in transgenic plant systems has been instrumental in demonstrating the substantial equivalence of many transgenic plant systems, it is essential that such analyses be extended to transgenic plants engineered for stress tolerance. Drought-tolerant Arabidopsis thaliana were engineered through overexpression of the transcription factor ABF3 in order to investigate unintended pleiotropic effects. In order to eliminate position effects, the Cre/lox recombination system was used to create control plant lines that contain identical T-DNA insertion sites but with the ABF3 transgene excised. This additionally allowed us to determine if Cre recombinase can cause unintended effects that impact the transcriptome.

Results

Microarray analysis of control plant lines that underwent Cre-mediated excision of the ABF3 transgene revealed only two genes that were differentially expressed in more than one plant line, suggesting that the impact of Cre recombinase on the transcriptome was minimal. In the absence of drought stress, overexpression of ABF3 had no effect on the transcriptome, but following drought stress, differences were observed in the gene expression patterns of plants overexpressing ABF3 relative to control plants. Examination of the functional distribution of the differentially expressed genes revealed strong similarity indicating that unintended pathways were not activated.

Conclusions

The action of ABF3 is tightly controlled in Arabidopsis. In the absence of drought stress, ectopic activation of drought response pathways does not occur. In response to drought stress, overexpression of ABF3 results in a reprogramming of the drought response, which is characterized by changes in the timing or strength of expression of some drought response genes, without activating any unexpected gene networks. These results illustrate that important gene networks are highly regulated in Arabidopsis and that engineering stress tolerance may not necessarily cause extensive changes to the transcriptome.
An evolved ribosome-inactivating protein targets and kills human melanoma cells in vitro and in vivo
Authors: Cheung Melissa C , Revers Leigh , Perampalam Subodini , Wei Xin , Kiarash Reza , Green David E , Abdul-Wahid Aws , Gariépy Jean
Published: February 2010

Background

Few treatment options exist for patients with metastatic melanoma, resulting in poor prognosis. One standard treatment, dacarbazine (DTIC), shows low response rates ranging from 15 to 25 percent with an 8-month median survival time. The development of targeted therapeutics with novel mechanisms of action may improve patient outcome. Ribosome-inactivating proteins (RIPs) such as Shiga-like Toxin 1 (SLT-1) represent powerful scaffolds for developing selective anticancer agents. Here we report the discovery and properties of a single chain ribosome-inactivating protein (scRIP) derived from the cytotoxic A subunit of SLT-1 (SLT-1A), harboring the 7-amino acid peptide insertion IYSNKLM (termed SLT-1AIYSNKLM) allowing the toxin variant to selectively target and kill human melanoma cells.

Results

SLT-1AIYSNKLM was able to kill 7 of 8 human melanoma cell lines. This scRIP binds to 518-A2 human melanoma cells with a dissociation constant of 18 nM, resulting in the blockage of protein synthesis and apoptosis in such cells. Biodistribution and imaging studies of radiolabeled SLT-1AIYSNKLM administered intravenously into SCID mice bearing a human melanoma xenograft indicate that SLT-1AIYSNKLM readily accumulates at the tumor site as opposed to non-target tissues. Furthermore, the co-administration of SLT-1AIYSNKLM with DTIC resulted in tumor regression and greatly increased survival in this mouse xenograft model in comparison to DTIC or SLT-1AIYSNKLM treatment alone (115 day median survival versus 46 and 47 days respectively; P values < 0.001). SLT-1AIYSNKLM is stable in serum and its intravenous administration resulted in modest immune responses following repeated injections in CD1 mice.

Conclusions

These results demonstrate that the evolution of a scRIP template can lead to the discovery of novel cancer cell-targeted compounds and in the case of SLT-1AIYSNKLM can specifically kill human melanoma cells in vitro and in vivo.
Polysaccharide from Fuzi (FPS) Prevents Hypercholesterolemia in Rats
Authors: Huang Xiongqing , Tang Juan , Zhou Qin , Lu Hanping , Wu Yiling , Wu Weikang
Published: January 2010

Background and aim

Polysaccharide from fuzi (FPS), a Chinese herbal medicine extract, has been demonstrated to exert lipid lowering affects. In this study we examined potential mechanisms underlying this affect, specifically alterations in expression of the LDL-receptor (LDL-R), 3-hydroxy-3-methyl glutaryl (HMG)-CoA reductase and cytochrome P450 7α-1 (CYP7α-1), using a rat model of hypercholesterolemia.

Methods and results

Male rats were fed either a normal or high cholesterol (HC) diet for two-weeks. Half of the rats on the HC diet were orally gavaged with FPS (224 mg/kg, 448 mg/kg or 896 mg/kg diet) daily. Serum lipid levels were quantified at end of the study period as were liver levels of LDL-R protein and mRNA expression of CYP7α-1 and HMG-CoA. Serum cholesterol and LDL-C concentrations were significantly elevated from control in HC rats, but not in those treated with FPS (P < 0.05). LDL-R expression was significantly decreased in the HC group compared to control (P < 0.05), but significantly increased in the FPS group (P < 0.05). HMG-CoA mRNA levels were significantly increased in the HC group compared both other groups (P < 0.05), while CYP7α-1 expression was significantly higher in the FPS group compared to both other groups (P < 0.05).

Conclusion

These findings suggest that the cholesterol lowering effect of FPS in hypercholesteremic rats is caused at least in part by increased hepatic LDL-R and CYP7α-1 expression and decreased HMG-CoA expression. Further study is needed to determine precisely where and how FPS exerts these effects. FPS offers potential as a therapeutic agent for the treatment of hypercholesterolemia.
Solitary adrenal metastasis from invasive ductal breast cancer: an uncommon finding
Authors: Liu Xiao-Jiao , Shen Peng , Wang Xin-Feng , Sun Ke , Sun Fei-Fei
Published: January 2010

Background

Invasive ductal carcinoma (IDC) of the breast usually metastasizes to the lungs, liver, bones and brain. Solitary adrenal metastasis is extremely rare. Due to the rarity of this condition, the optimal treatment is unclear. We report the first case of IDC of the breast metastasizing solely to the adrenal gland after a modified radical mastectomy but having a long-term disease-free survival while treated merely by a left adrenalectomy.

Case presentation

A 64-year-old woman was found a left adrenal mass on a follow- up visit two years after taking a right modified radical mastectomy for the breast cancer. She was subsequently given a left adrenalectomy. Postoperative histopathology findings were compatible with invasive ductal carcinoma (IDC) of the breast. Due to the patient's refusal, no further treatments were offered after the adrenalectomy. The patient now is still alive and has no sign of relapse. Survival time after taking the right modified radical mastectomy and the left adrenalectomy is more than five years and three years, respectively.

Conclusion

This is the first case of a patient with solitary, metachronous adrenal metastasis from IDC of the breast to be reported. For patients in this condition, complete removal of metastasized organ may translate into survival benefit.
Behavioral and Anatomical Characterization of the Bilateral Sciatic Nerve Chronic Constriction (bCCI) Injury: Correlation of Anatomic Changes and Responses to Cold Stimuli
Authors: Datta Sukdeb , Chatterjee Koel , Kline Robert H , Wiley Ronald G
Published: January 2010

Background:

Unilateral constrictive sciatic nerve injury (uCCI) is a common neuropathic pain model. However, the bilateral constrictive injury (bCCI) model is less well studied, and shows unique characteristics. In the present study, we sought to correlate effects of bCCI on nocifensive responses to cold and mechanical stimuli with selected dorsal horn anatomic markers. bCCI or sham ligation of both rat sciatic nerves were followed up to 90 days of behavioural testing. Additional rats sacrificed at 15, 30 and 90 days were used for anatomic analyses. Behavioural tests included hindpaw withdrawal responses to topical acetone, cold plate testing, an operant thermal preference task and hindpaw withdrawal thresholds to mechanical probing.

Results:

All nocifensive responses to cold increased and remained enhanced for >45 days. Mechanical withdrawal thresholds decreased for 25 days only. Densitometric analyses of immunoperoxidase staining in the superficial dorsal horn at L4–5 revealed decreased cholecystokinin (CCK) staining at all times after bCCI, decreased mu opiate receptor (MOR) staining, maximal at 15 days, increased neuropeptide Y (NPY) staining only at days 15 and 30, and increased neurokinin-1 receptor (NK-1R) staining at all time points, maximal at 15 days. Correlation analyses at 45 days post-bCCI, were significant for individual rat nocifensive responses in each cold test and CCK and NK-1R, but not for MOR or NPY.

Conclusions:

These results confirm the usefulness of cold testing in bCCI rats, a new approach using CCI to model neuropathic pain, and suggest a potential value of studying the roles of dorsal horn CCK and substance P in chronic neuropathic pain. Compared to human subjects with neuropathic pain, responses to cold stimuli in rats with bCCI may be a useful model of neuropathic pain.
Improving calculation, interpretation and communication of familial colorectal cancer risk: Protocol for a randomized controlled trial
Authors: Dekker Nicky , Hermens Rosella PMG , Elwyn Glyn , van der Weijden Trudy , Nagengast Fokko M , van Duijvendijk Peter , Salemink Simone , Adang Eddy , van Krieken J Han JM , Ligtenberg Marjolijn JL , Hoogerbrugge Nicoline
Published: January 2010

Background

Individuals with multiple relatives with colorectal cancer (CRC) and/or a relative with early-onset CRC have an increased risk of developing CRC. They are eligible for preventive measures, such as surveillance by regular colonoscopy and/or genetic counselling. Currently, most at-risk individuals do not follow the indicated follow-up policy. In a new guideline on familial and hereditary CRC, clinicians have new tasks in calculating, interpreting, and communicating familial CRC risk. This will lead to better recognition of individuals at an increased familial CRC risk, enabling them to take effective preventive measures. This trial compares two implementation strategies (a common versus an intensive implementation strategy), focussing on clinicians' risk calculation, interpretation, and communication, as well as patients' uptake of the indicated follow-up policy.

Methods

A clustered randomized controlled trial including an effect, process, and cost evaluation will be conducted in eighteen hospitals. Nine hospitals in the control group will receive the common implementation strategy (i.e., dissemination of the guideline). In the intervention group, an intensive implementation strategy will be introduced. Clinicians will receive education and tools for risk calculation, interpretation, and communication. Patients will also receive these tools, in addition to patient decision aids. The effect evaluation includes assessment of the number of patients for whom risk calculation, interpretation, and communication is performed correctly, and the number of patients following the indicated follow-up policy. The actual exposure to the implementation strategies and users' experiences will be assessed in the process evaluation. In a cost evaluation, the costs of the implementation strategies will be determined.

Discussion

The results of this study will help determine the most effective method as well as the costs of improving the recognition of individuals at an increased familial CRC risk. It will provide insight into the experiences of both patients and clinicians with these strategies.

The knowledge gathered in this study can be used to improve the recognition of familial and hereditary CRC at both the national and international level, and will serve as an example to improve care for patients and their relatives worldwide. Our results may also be useful in improving healthcare in other diseases.

Trial registration

ClinicalTrials.gov NCT00929097
Towards a genome-scale kinetic model of cellular metabolism
Authors: Smallbone Kieran , Simeonidis Evangelos , Swainston Neil , Mendes Pedro
Published: January 2010

Background

Advances in bioinformatic techniques and analyses have led to the availability of genome-scale metabolic reconstructions. The size and complexity of such networks often means that their potential behaviour can only be analysed with constraint-based methods. Whilst requiring minimal experimental data, such methods are unable to give insight into cellular substrate concentrations. Instead, the long-term goal of systems biology is to use kinetic modelling to characterize fully the mechanics of each enzymatic reaction, and to combine such knowledge to predict system behaviour.

Results

We describe a method for building a parameterized genome-scale kinetic model of a metabolic network. Simplified linlog kinetics are used and the parameters are extracted from a kinetic model repository. We demonstrate our methodology by applying it to yeast metabolism. The resultant model has 956 metabolic reactions involving 820 metabolites, and, whilst approximative, has considerably broader remit than any existing models of its type. Control analysis is used to identify key steps within the system.

Conclusions

Our modelling framework may be considered a stepping-stone toward the long-term goal of a fully-parameterized model of yeast metabolism. The model is available in SBML format from the BioModels database (BioModels ID: MODEL1001200000) and at http://www.mcisb.org/resources/genomescale/.
Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents
Authors: Tan Jiahuai , Cang Shundong , Ma Yuehua , Petrillo Richard L , Liu Delong
Published: February 2010

Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.
Expressed Alu repeats as a novel, reliable tool for normalization of real-time quantitative RT-PCR data
Authors: Marullo Manuela , Zuccato Chiara , Mariotti Caterina , Lahiri Nayana , Tabrizi Sarah J , Di Donato Stefano , Cattaneo Elena
Published: January 2010

We describe a novel strategy for mRNA normalization in quantitative real-time PCR that is based on expressed Alu repeat amplification as a measure for the mRNA fraction. We show that expressed Alu repeat amplification is a fast, accurate normalization tool that can be successfully used for quantification of selected mRNA in the human transcriptome. This result is particularly important for clinical diagnosis and biomarker validation studies based on mRNA detection in human blood.
Aldosterone Production and Insulin Resistance in Healthy Adults
Authors: Garg Rajesh , Hurwitz Shelley , Williams Gordon H. , Hopkins Paul N. , Adler Gail K.
Published: February 2010

Context: Aldosterone production is associated with insulin resistance in obese and hypertensive subjects. However, its effect on insulin sensitivity in healthy subjects is not clear.

Objective: The objective of this study was to test the hypothesis that increased aldosterone production is associated with lower insulin sensitivity in healthy subjects.

Design: This is an analysis of data previously collected during studies conducted as part of the International Hypertensive Pathotype Consortium.

Participants and Interventions: Eighty-four subjects free of any medical or psychiatric illness were included in this study. They were studied after 7 d of a standardized high-sodium diet confirmed by 24-h urine sodium above 200 mEq. Insulin sensitivity index (ISI) was calculated after a 75-g oral glucose load with glucose and insulin measurements at 0, 30, 60, and 120 min. Serum aldosterone levels were measured after 45 min of angiotensin II (3 ng/kg/min) infusion.

Results: There were significant negative correlations between ISI and age, body mass index (BMI), diastolic blood pressure, and angiotensin II-stimulated aldosterone level (P < 0.01). On multivariate regression analysis, stimulated aldosterone level was an independent predictor of ISI after adjusting for age, BMI, and diastolic blood pressure. Stimulated aldosterone level predicted 8% of the variance in ISI (P = 0.003) with age, BMI, and diastolic blood pressure together predicting 23% of the variance in ISI. Thus, the final regression model predicted 31% of the variance in ISI (P < 0.0001).

Conclusions: Aldosterone production is associated with insulin resistance in normotensive healthy subjects independent of traditional risk factors.
Partially Deglycosylated Equine LH Preferentially Activates β-Arrestin-Dependent Signaling at the Follicle-Stimulating Hormone Receptor
Authors: Wehbi Vanessa , Tranchant Thibaud , Durand Guillaume , Musnier Astrid , Decourtye Jérémy , Piketty Vincent , Butnev Vladimir Y. , Bousfield George R. , Crépieux Pascale , Maurel Marie-Christine , Reiter Eric
Published: January 2010

Deglycosylated FSH is known to trigger poor Gαs coupling while efficiently binding its receptor. In the present study, we tested the possibility that a deglycosylated equine LH (eLHdg) might be able to selectively activate β-arrestin-dependent signaling. We compared native eLH to an eLH derivative [i.e. truncated eLHβ (Δ121-149) combined with asparagine56-deglycosylated eLHα (eLHdg)] previously reported as an antagonist of cAMP accumulation at the FSH receptor (FSH-R). We confirmed that, when used in conjunction with FSH, eLHdg acted as an antagonist for cAMP accumulation in HEK-293 cells stably expressing the FSH-R. Furthermore, when used alone at concentrations up to 1 nm, eLHdg had no detectable agonistic activity on cAMP accumulation, protein kinase A activity or cAMP-responsive element-dependent transcriptional activity. At higher concentrations, however, a weak agonistic action was observed with eLHdg, whereas eLH led to robust responses whatever the concentration. Both eLH and eLHdg triggered receptor internalization and led to β-arrestin recruitment. Both eLH and eLHdg triggered ERK and ribosomal protein (rp) S6 phosphorylation at 1 nm. The depletion of endogenous β-arrestins had only a partial effect on eLH-induced ERK and rpS6 phosphorylation. In contrast, ERK and rpS6 phosphorylation was completely abolished at all time points in β-arrestin-depleted cells. Together, these results show that eLHdg has the ability to preferentially activate β-arrestin-dependent signaling at the FSH-R. This finding provides a new conceptual and experimental framework to revisit the physiological meaning of gonadotropin structural heterogeneity. Importantly, it also opens a field of possibilities for the development of selective modulators of gonadotropin receptors.
Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation
Authors: Fu Ming , Sato Yoshiharu , Lyons-Warren Ariel , Zhang Bin , Kane Maureen A. , Napoli Joseph L. , Heuckeroth Robert O.
Published: January 2010

Hirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinol-binding-protein-deficient (Rbp4–/–) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4–/– animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition.
The auxin influx carriers AUX1 and LAX3 are involved in auxin-ethylene interactions during apical hook development inArabidopsis thalianaseedlings
Authors: Vandenbussche Filip , Petrášek Jan , Žádníková Petra , Hoyerová Klára , Pešek Bedřich , Raz Vered , Swarup Ranjan , Bennett Malcolm , Zažímalová Eva , Benková Eva , Van Der Straeten Dominique
Published: January 2010

Dark-grown dicotyledonous seedlings form a hook-like structure at the top of the hypocotyl, which is controlled by the hormones auxin and ethylene. Hook formation is dependent on an auxin signal gradient, whereas hook exaggeration is part of the triple response provoked by ethylene in dark-grown Arabidopsis seedlings. Several other hormones and light are also known to be involved in hook development, but the molecular mechanisms that lead to the initial installation of an auxin gradient are still poorly understood. In this study, we aimed to unravel the cross-talk between auxin and ethylene in the apical hook. Auxin measurements, the expression pattern of the auxin reporter DR5::GUS and the localization of auxin biosynthesis enzymes and influx carriers collectively indicate the necessity for auxin biosynthesis and efficient auxin translocation from the cotyledons and meristem into the hypocotyl in order to support proper hook development. Auxin accumulation in the meristem and cotyledons and in the hypocotyl is increased ∼2-fold upon treatment with ethylene. In addition, a strong ethylene signal leads to enhanced auxin biosynthesis at the inner side of the hook. Finally, mutant analysis demonstrates that the auxin influx carrier LAX3 is indispensable for proper hook formation, whereas the auxin influx carrier AUX1 is involved in the hook exaggeration phenotype induced by ethylene.
Crumbs is required to achieve proper organ size control duringDrosophilahead development
Authors: Richardson Emily C. N. , Pichaud Franck
Published: January 2010

Crumbs (Crb) is a conserved apical polarity determinant required for zonula adherens specification and remodelling during Drosophila development. Interestingly, crb function in maintaining apicobasal polarity appears largely dispensable in primary epithelia such as the imaginal discs. Here, we show that crb function is not required for maintaining epithelial integrity during the morphogenesis of the Drosophila head and eye. However, although crb mutant heads are properly developed, they are also significantly larger than their wild-type counterparts. We demonstrate that in the eye, this is caused by an increase in cell proliferation that can be attributed to an increase in ligand-dependent Notch (N) signalling. Moreover, we show that in crb mutant cells, ectopic N activity correlates with an increase in N and Delta endocytosis. These data indicate a role for Crb in modulating endocytosis at the apical epithelial plasma membrane, which we demonstrate is independent of Crb function in apicobasal polarity. Overall, our work reveals a novel function for Crb in limiting ligand-dependent transactivation of the N receptor at the epithelial cell membrane.