bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term Stability of Demethylation after Transient Exposure to 5-Aza-2′-Deoxycytidine Correlates with Sustained RNA Polymerase II Occupancy
Authors: Kagey Jacob D. , Kapoor-Vazirani Priya , McCabe Michael T. , Powell Doris R. , Vertino Paula M.
Published: June 2010

DNA methyltransferase inhibitors are currently the standard of care for myelodysplastic syndrome and are in clinical trials for leukemias and solid tumors. However, the molecular basis underlying their activity remains poorly understood. Here, we studied the induction and long-term stability of gene reactivation at three methylated tumor suppressor loci in response to the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-azaCdR) in human breast cancer cells. At the TMS1/ASC locus, treatment with 5-azaCdR resulted in partial DNA demethylation, the reengagement of RNA polymerase II (Pol II), and a shift from a repressive chromatin profile marked with H3K9me2 and H4K20me3 to an active profile enriched in H3ac and H3K4me2. Using a single-molecule approach coupling chromatin immunoprecipitation with bisulfite sequencing, we show that H3ac, H3K4me2, and Pol II selectively associated with the demethylated alleles, whereas H3K9me2 preferentially marked alleles resistant to demethylation. H4K20me3 was unaffected by DNA demethylation and associated with both unmethylated and methylated alleles. After drug removal, TMS1 underwent partial remethylation, yet a subset of alleles remained stably demethylated for over 3 months. These alleles remained selectively associated with H3K4me2, H3ac, and Pol II and correlated with a sustained low level of gene expression. TMS1 alleles reacquired H3K9me2 over time, and those alleles that became remethylated retained H3ac. In contrast, CDH1 and ESR1 were remethylated and completely silenced within ∼1 week of drug removal, and failed to maintain stably unmethylated alleles. Our data suggest that the ability to maintain Pol II occupancy is a critical factor in the long-term stability of drug-induced CpG island demethylation. Mol Cancer Res; 8(7); 1048–59. ©2010 AACR.
The Convective Instability Pathway to Warm Season Drought in Texas. Part I: The Role of Convective Inhibition and Its Modulation by Soil Moisture
Authors: Myoung Boksoon , Nielsen-Gammon John W.
Published: June 2010

This research is designed to investigate how convective instability influences monthly mean precipitation in Texas in the summertime and to examine the modulation of convective instability and precipitation by local and regional forcings. Since drought results from the accumulated effects of deficient precipitation over time, this study is expected to shed light on the physical and dynamical mechanisms of the initiation and maintenance of serious droughts as well. The focus in Part I of this two-part study is on identification of the controlling convective parameters and, in turn, the surface-based processes that cause variations in these parameters. NCEP–NCAR reanalysis data and observed precipitation data, correlation analysis, multiple linear regression analysis, and back-trajectory analysis are used to reveal the underlying dynamics of their linkage and causality.

Monthly mean precipitation is modified mainly by convective inhibition (CIN) rather than by convective available potential energy (CAPE) or by precipitable water. Excessive CIN is caused by surface dryness and warming at 700 hPa, leading to precipitation deficits on a monthly time scale. While the dewpoint temperature and thermodynamics at the surface are greatly affected by the soil moisture, the temperature at 700 hPa was found to be statistically independent of the surface dewpoint temperature since the 700-hPa temperature represents free-atmospheric processes. (These free-atmospheric processes are the focus of the companion paper.) Finally, the strong correlations among precipitation, soil moisture, and CIN, as well as their underlying physical processes, suggest that the tight linkage between precipitation and soil moisture is not only due to the impacts of precipitation on soil moisture but also to the feedbacks of soil moisture on precipitation by controlling CIN.
Fifty-Year Trends in Global Ocean Salinities and Their Relationship to Broad-Scale Warming
Authors: Durack Paul J. , Wijffels Susan E.
Published: June 2010

Using over 1.6 million profiles of salinity, potential temperature, and neutral density from historical archives and the international Argo Program, this study develops the three-dimensional field of multidecadal linear change for ocean-state properties. The period of analysis extends from 1950 to 2008, taking care to minimize the aliasing associated with the seasonal and major global El Niño–Southern Oscillation modes. Large, robust, and spatially coherent multidecadal linear trends in salinity to 2000-dbar depth are found. Salinity increases at the sea surface are found in evaporation-dominated regions and freshening in precipitation-dominated regions, with the spatial pattern of change strongly resembling that of the mean salinity field, consistent with an amplification of the global hydrological cycle. Subsurface salinity changes on pressure surfaces are attributable to both isopycnal heave and real water-mass modification of the temperature–salinity relationship. Subduction and circulation by the ocean’s mean flow of surface salinity and temperature anomalies appear to account for most regional subsurface salinity changes on isopycnals. Broad-scale surface warming and the associated poleward migration of isopycnal outcrops drive a clear and repeating pattern of subsurface isopycnal salinity change in each independent ocean basin. Qualitatively, the observed global multidecadal salinity changes are thus consonant with both broad-scale surface warming and the amplification of the global hydrological cycle.
Why Is There a Gender Wage Gap According to Occupational Prestige?
Authors: Magnusson Charlotta
Published: June 2010

Studies have shown that women receive lower wage returns to attained occupational prestige than do men. In this article, I examine whether the gender difference in wage return for attained occupational prestige can be explained by men’s and women’s different family obligations, and whether gender differences in work characteristics, which are difficult to combine with family duties, account for some of the gender wage gap in returns for attained occupational prestige. If women’s family obligations were a major cause of women’s disadvantage, the negative interaction between women and occupational prestige with regard to wages would be larger for mothers and married/cohabiting women than for single women without children. Results show a gender wage gap between married/ cohabiting men and women with children that increases with occupational prestige. However, the interaction between gender and prestige is insignificant among single women and men and among married/cohabiting respondents without children. Furthermore, when controlling for time-consuming work, the gender wage gap for married/cohabiting respondents with children according to occupational prestige narrows, especially in occupations with high prestige.
Aiding and Abetting: Human Rights INGOs and Domestic Protest
Authors: Murdie Amanda , Bhasin Tavishi
Published: June 2010

This article studies the effects of human rights international nongovernmental organizations (INGOs) on domestic antigovernment protest. Unlike mainstream scholarship, the authors argue that human rights INGOs are not simply the magic bullet in orchestrating nonviolent protests; different types of human rights INGO activity have varying effects on protest. Moreover, some human rights INGO activities may lead to higher levels of violent protest. The empirical tests use new data on the activities of over 400 human rights INGOs and domestic nonviolent and violent protest globally from 1991 to 2004. The authors find that increases in human rights INGO activities reflecting a greater commitment to the domestic population are associated with higher levels of both violent and nonviolent protest.
The Effect of Text Translation on Perceived Musical Tension in Debussy’s Noël des enfants qui n’ont plus de maisons
Authors: Hackworth Rhonda S. , Fredrickson William E.
Published: June 2010

The primary focus of the present study was to investigate the effect participants’ ( N = 100) knowledge of a text translation may have on their perceived musical tension while listening to a piece of choral music sung in another language. When examining the graphs that show the group mean responses of the participants, control (without text translation) versus experimental (with text translation), it is clear that there are many similarities between the groups. Any differences that may be attributable to an understanding of the text while tracking tension in this musical selection are minimal and most likely individualized by participant. A secondary goal of the study was to observe the impact of having half the participants begin recording their responses with the dial pointer of the Continuous Response Digital Interface (CRDI) positioned either at the left of the tension curve-continuum or positioned at middial. Group data for participants’ who started with their dials on the left, versus those who started with dials in the middle, also showed similarities sufficient to call into the question the idea that starting at a different place on this scale would affect recording of perceptions significantly.
The effect of the building population and the number of floors on the vertical transportation design of low and medium rise buildings
Authors: Al-Sharif Lutfi , Seeley Christopher
Published: June 2010

The design of vertical transportation systems for buildings involves the selection of the number, speed and capacity of the lifts required. It also involves the selection of the most appropriate configuration in terms of zoning, group control algorithm and the use or otherwise of double deckers.

Interval is the classical performance criterion for vertical transportation design, while modern passenger centric performance criteria are now based on passenger waiting time and travelling time. Both types of performance parameters are used in this work.

This work identifies the two most influential demand factors that affect the design output for vertical transportation systems in low and medium rise buildings. These are the total building population and the number of floors served above the main terminal. These are then used to develop general guidelines to find the most optimum configuration for every pair of such parameters. This is then transformed into the form of a 2D chart that can visually aid the designer into using the best configuration for a building.

Practical applications: The importance of this article arises from the fact that it justifies the widely held view that single deck lifts in one group are limited to 20 floors and that the direct travel from ground approach is limited to around 60 floors (after which sky lobbies are needed). It shows that the two most important parameters that affect the design of a vertical transportation system are the total building population and the number of floors above the lobby.

The two dimensional chart included within the article as Figure 3 allows the system designer to immediately assess the most suitable vertical transportation zoning arrangement for the building, the preferred number of zones and the preference for using single decker or double decker lifts.
Spontaneous Malignant Mixed Müllerian Tumor in a Wistar Rat
Authors: van den Brink-Knol H. , van Esch E.
Published: June 2010

This report presents a rare, spontaneous, heterologous, malignant mixed Müllerian tumor observed in a 98-week-old untreated Wistar rat. At necropsy, the right uterine horn was dilated and contained a mass of approximately 10 × 15 mm. Histopathologically the mass consisted of 2 parts with different morphologic characteristics, a polypoid mass protruding into the uterine lumen and a more solid part that replaced the adjacent uterine wall. The solid part exhibited characteristics of a highly infiltrative adenocarcinoma, whereas the composition of the polypoid mass was heterogeneous, consisting of a variety of benign and malignant epithelial and mesenchymal elements. The epithelial components included well-differentiated endometrial and squamous epithelium juxtaposed to carcinosarcomatous areas. The mesenchymal components consisted of well-differentiated cartilage and bone along with chondrosarcomatous, rhabdomyomatous, and other mesenchymal elements. Immunohistochemical analysis further supported the diagnosis of malignant mixed Müllerian tumor.
DIAGNOSTIC EXERCISE
Authors: Gelberg H. B. , Valentine B. A.
Published: June 2010

Angiomatoid lesions in a lymph node associated with a thyroid carcinoma of a dog were restricted to the subcapsular and medullary sinuses. Lymphoid atrophy was present, but nodal architecture was not distorted and normal structures were not invaded. Immunohistochemical staining indicated that the vascular spaces formed by spindloid cells were lined by endothelium with a low mitotic index. The spindloid cells were positive for smooth muscle actin, vimentin, and desmin and thus were likely to be fibroblasts, myofibroblasts, smooth muscle cells, and/or pericytes. These features are comparable to vascular transformation of lymph node sinuses in humans (nodal angiomatosis), a nonneoplastic condition often associated with mechanical or functional blockage of efferent lymphatics and veins.
The Role of Visual Evoked Potentials in the Differential Diagnosis of Functional Visual Loss and Optic Neuritis in Children
Authors: Suppiej Agnese , Gaspa Giorgio , Cappellari Ambra , Toldo Irene , Battistella Pier Antonio
Published: June 2010

This study aims to determine whether visual evoked potentials can aid the diagnosis of functional visual loss and differentiate it from optic neuritis in children. The medical records and visual evoked potentials of 72 patients registered in the neurophysiological database of our Institution in the period 2000—2009, with diagnoses of functional visual loss or optic neuritis were reviewed retrospectively. In 61 children, visual evoked potentials confirmed the diagnosis: 49 functional visual loss and 12 optic neuritis. Visual evoked potentials were normal in all patients but 1 in the functional visual loss group, while all were abnormal in the optic neuritis group. Overlapping clinical features occurred between the 2 groups as well as prevalent severe visual loss, relative afferent pupillary defect, and papillitis in optic neuritis. Visual evoked potentials are of value in confirming clinical suspicion of functional visual loss, particularly when clinical overlap with optic neuritis occurs.
Domestic Violence and Longitudinal Associations With Children’s Physiological Regulation Abilities
Authors: Rigterink Tami , Fainsilber Katz Lynn , Hessler Danielle M.
Published: June 2010

The present study examined the impact of domestic violence (DV) on children’s emotion regulation abilities measured via baseline vagal tone (VT). Specifically, the authors examined the relationship between DV exposure and children’s regulatory functioning over time, investigating whether DV exposure was related to the trajectory of children’s physiological regulatory abilities from the preschool period to middle childhood. Covariates, including marital dissatisfaction and conduct-problem status, along with potential gender differences, were examined. Though all children increased in baseline VT from Time 1 to Time 2, children exposed to DV displayed less increase in baseline VT over time as compared to nonexposed children. Results in terms of the long-term outcomes of DV on children and implications for interventions were taken into consideration and discussed in the article.
Why Doesn’t He Leave? Relationship Continuity and Satisfaction Among Male Domestic Violence Offenders
Authors: Henning Kris , Connor-Smith Jennifer
Published: June 2010

In contrast to the extensive literature on women’s decisions to leave violent relationships, there is little research examining relationship continuity from the offending male’s perspective. Similarly, research exploring relationship satisfaction in men arrested for intimate partner violence (IPV) is lacking, despite the fact that dissatisfaction appears to increase risk for future IPV. The present study explored these issues using a large sample of men who were recently convicted of violence toward a female intimate partner ( N = 1,130). More than half of the men (59%) reported that they were continuing or planning to continue their relationship. Factors associated with relationship continuity included older age, being married to the victim, having children together, attributing less blame to the victim for the recent offense, and having a childhood history of family violence. Among men who were continuing their relationship, low relationship satisfaction was predicted by having children, expressing hostile attitudes toward women, being jealous, blaming the victim for the arrest incident, and describing the victim as aggressive. Implications of the findings for clinical practice and research are discussed.
The Prevalence of the Middle-Eastern Extreme Ideologies Among Some Canadians
Authors: Loza Wagdy
Published: June 2010

A total of 183 Canadian participants of different religious backgrounds completed the Belief Diversity Scale (BDS). The BDS is an 80-item, 6-subscale instrument designed to quantitatively measure the religious attitudes, beliefs, and ideologies of Middle-Eastern extremists’ on risk areas that are reported in the literature. The results demonstrated the reliability and validity of the BDS as well as indicated the prevalence of Middle-Eastern extremists’ ideologies among Muslim Canadians. Results were similar to those obtained from similar study completed on South African participants. These findings suggested that the BDS has the potential to be used as an objective tool to measure Middle-Eastern religious extremism.
The Meaning of Collective Terrorist Threat: Understanding the Subjective Causes of Terrorism Reduces Its Negative Psychological Impact
Authors: Fischer Peter , Postmes Tom , Koeppl Julia , Conway Lianne , Fredriksson Tom
Published: June 2010

This article hypothesized that the possibility to construct intellectual meaning of a terrorist attack (i.e., whether participants can cognitively understand why the perpetrators did their crime) reduces the negative psychological consequences typically associated with increased terrorist threat. Concretely, the authors investigated the effect of intellectual meaning (induced by providing additional information about potential economic, cultural, and historical reasons for the terrorist attack) on perceived terrorist threat and associated emotional well-being. Study 1 revealed that pictures of terrorist attacks elicited less experienced terrorist threat when they were presented with background information about the terrorists’ motives (meaning provided) rather than without additional background information (no meaning provided). Study 2 replicated this effect with a different manipulation of terrorist threat (i.e., newspaper article) and clarified the underlying psychological process: Participants in the high terror salience condition with meaning provided experienced less terrorist threat and thus more emotional well-being in the face of crisis than participants in the high terror salience condition without meaning provided. Theoretical and practical implications in the context of psychological health and mass media effects are discussed.
Victim Resistance in Child Sexual Abuse: A Look Into the Efficacy of Self-Protection Strategies Based on the Offender’s Experience
Authors: Leclerc Benoit , Wortley Richard , Smallbone Stephen
Published: June 2010

This study examines the efficacy, as experienced by offenders with their victim, of self-protection strategies used in child sexual abuse cases. It also investigates whether the efficacy of self-protection varies according to victim characteristics. The sample consists of 94 adult offenders who sexually abused a single child and who agreed to provide confidential self-report data on the efficacy of self-protection strategies used by their victim. Strategies taken into account are: (1) yelling or screaming, (2) fighting back, (3) saying no, (4) saying they didn’t want to, (5) crying, (6) telling someone else about the abuse, (7) saying they were scared, (8) demanding to be left alone, (9) saying they would tell someone, (10) saying that people are not supposed to touch their private parts, (11) trying to get away, and (12) yelling for help. Saying that they do not want to have sexual contact and saying “no” to the offender are the most effective strategies. Because they are more likely to use self-protection initially, younger girls are also more likely to prevent episodes of abuse than older girls.
Size-dependent Probabilistic Micromechanical Damage Mechanics for Particle-reinforced Metal Matrix Composites
Authors: Ju J.W. , Yanase K.
Published: June 2010

A size-dependent micromechanical framework is proposed to predict the deformation responses of particle-reinforced metal matrix composites by incorporating the essential features of the dislocation plasticity. Within the framework of probabilistic micromechanical formulation, the damage caused by the manufacturing process and by the external mechanical loading in the presence of thermal residual stresses is considered. The effective elastic moduli of four-phase composites, consisting of a ductile matrix and randomly located spherical intact or damaged particles are derived. Subsequently, the size-dependent plastic deformation behavior of particle-reinforced metal matrix composites is predicted with a dislocation theory. Specifically, the density of dislocations due to the thermal contraction misfit and the plastic deformation misfit is taken into consideration within the micromechanical methodology to account for the dislocation strengthening. To predict the overall elastoplastic damage behavior of composites, a size-dependent hybrid effective yield function is presented on the basis of the ensemble-volume averaging and the modified matrix yield strength. The comparisons between our predictions and available experimental data illustrate the potential capability of the proposed framework. Numerical simulations are also performed to exhibit the salient features of the proposed methodology.
Global Warming Coverage in the Media: Trends in a Mexico City Newspaper
Authors: Gordon Joye C. , Deines Tina , Havice Jacqueline
Published: June 2010

This study examined newspaper coverage, intensity of stories (how intensely the issue of global warming is presented), and the presence of frames, solutions, and conflicts surrounding the global warming issue in 144 articles appearing from 2004 through 2006 in the Mexico City—based newspaper, Reforma. The ecology/science frame and consequences frames were the most intensely reported frames. Scientific conflict and U.S. conflict are present, but in low frequencies and near the end of stories. International relations were the most frequently presented solution to global warming, and story frequencies peaked during international conferences. Consistent with previous findings, this study found that foreign media tend to emphasize international relations and de-emphasize conflicts and controversies.
Factors Related to Family Caregivers’ Satisfaction With Home Care for Mental Illness in Taiwan
Authors: Tung Wei-Chen , Jie Hu
Published: June 2010

In Taiwan, family caregivers play a significant role in the treatment of mentally ill patients at home because of cultural obligations. This descriptive, cross-sectional study explored factors affecting family caregivers’ satisfaction with home care services for the mentally ill and assessed the possibility of continuous use of home care and recommendation of home care to others based on the level of satisfaction of family caregivers. Data were collected using a questionnaire completed by a convenience sample of 75 primary family caregivers of mentally ill patients. Family caregiver satisfaction was significantly associated with caregiver age, marital status, support from family members to assist the caregiver during weekdays and weekends, the amount of time spent in caregiving per week, and feelings about having a mentally ill family member at home. Caregivers who had a higher level of satisfaction with home care were twice as likely as those with lower satisfaction to use the services again when needed. Home care nurses should pay close attention to the variables that support use of home care.
Increasing social responsiveness in a child with autism
Authors: Finnigan Emily , Starr Elizabeth
Published: June 2010

This study sought to determine the effects of using music and non-music interventions on the social responsive and avoidant behaviours of a preschool child with autism. A single-subject alternating treatment design was used in which two interventions were presented in a similar fashion except for the addition of music during the music condition. Four phases took place: baseline (Phase A), alternating treatments (Phase B), a second treatment phase (Phase C) using the condition that proved to be more effective in Phase B, and follow-up (Phase D). Data were collected over a total of 12 treatment sessions for various social responsive and avoidant behaviours. Results indicated that the music intervention was more effective than the non-music intervention in increasing all three social responsive behaviours in both Phases B and C. Furthermore, no avoidant behaviours were observed during the music condition. It is suggested that the music condition was more motivating for the participant than the non-music condition, resulting in more social responsive behaviours.
Nostalgia and identity: Jules Simon’s La Femme du Vingtième Siècle
Authors: Brown Kathryn
Published: June 2010

This article analyses Jules Simon’s nostalgic view of 17th-century femininity as part of his vision of French social reform during the 1890s. Simon’s enthusiasm for the past is located in the context of late 19th-century social criticism that prized a domestic role for women and used such a role to symbolize the re-establishment of boundaries between public and private life. Simon’s vision of female life underpins a form of social organization that sought to neutralize the ongoing effects of France’s defeat in the Franco-Prussian war and the violence of France’s revolutionary past. I distinguish Simon’s nostalgic strategy from Jules and Edmond de Goncourt’s enthusiasm for the ancien régime and argue that Simon re-animates aspects of the past in order to temper progress in the new century. Nostalgia secures a preferred image of national identity and shapes an ideal narrative of both past and future.
Remembering lost paintings: Vanessa Bell’s The Nursery
Authors: Stevens Bethan
Published: June 2010

During 1930—1932, Vanessa Bell worked on a large-scale, ambitious painting called The Nursery, a nostalgic delineation of childhood and motherhood. The subsequent loss of the painting has tended to curtail rather than to colour interpretation; in contrast, my reading interrogates The Nursery’s status as a piece of lost art. The work survives hauntingly through a multiplicity of related visual and textual objects, including contemporary photographs, personal correspondence, criticism and fiction. I analyse these as memorials, questioning the kind of nostalgia required to see the lost Nursery , and setting up an interaction between two sites of nostalgia in operation here: within the lost painting, and around it.
Phototherapy for allergic rhinitis: a prospective, randomized, single-blind, placebo-controlled study
Authors: Cingi Cemal , Cakli Hamdi , Yaz Aytekin , Songu Murat , Bal Cengiz
Published: June 2010

Background: Phototherapy has a profound immunosuppressive effect, and phototherapeutic methods using both ultraviolet (UV) and visible light are therefore widely used for the therapy of various inflammatory skin diseases. It is also proposed that phototherapy, using a combination of UV-A (25%), UV-B (5%) and visible light (70%), may represent a therapeutic alternative in patients with allergic rhinitis.

Method: Seventy-nine patients were randomly assigned to receive either a combination of UV-A (25%), UV-B (5%) and visible light (70%), in the phototherapy group, or low-intensity visible light, in the control group. The efficacy of treatment was assessed by means of total nasal symptom score before treatment and 1 month after the end of treatment.

Results: Total nasal scores decreased in both groups but the decrease was highly significant in the active treatment group when compared with the placebo (p < 0.001).

Conclusions: This study demonstrates that phototherapy may be an effective modality in the treatment of allergic rhinitis especially in cases of which commonly used drugs either are contraindicated and/or have insufficient efficacy.
Therapeutic advances in the treatment of nicotine addiction: present and future
Authors: Casella Giuseppina , Caponnetto Pasquale , Polosa Riccardo
Published: June 2010

While the proportion of the adult population that smokes has declined steadily in several westernized societies, the rate of successful quit attempts is still low. This is because smokers develop nicotine dependence, a powerful addiction that may require multiple attempts and long-term treatment to achieve enduring abstinence. Currently available first-line agents for smoking cessation therapy include nicotine replacement therapy (available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge), bupropion (an atypical antidepressant), and varenicline (a partial agonist of the α4β2 nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy). Second-line agents are nortriptyline (a tricyclic antidepressant agent) and the antihypertensive agent clonidine. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. The adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. However, the currently marketed smoking cessation drugs reportedly lack high levels of efficacy, particularly in real-life settings. New medications and vaccines with significant clinical advantage are now in the advanced stage of development and offer promise. These include nicotine vaccines and monoamine type B inhibitors. In this review article we discuss current and emerging pharmacotherapies for tobacco dependence focusing on their mechanisms of action, efficacy and adverse event profiles.
Nanoparticle-induced vascular blockade in human prostate cancer
Authors: Agemy Lilach , Sugahara Kazuki N. , Kotamraju Venkata Ramana , Gujraty Kunal , Girard Olivier M. , Kono Yuko , Mattrey Robert F. , Park Ji-Ho , Sailor Michael J. , Jimenez Ana I. , Cativiela Carlos , Zanuy David , Sayago Francisco J. , Aleman Carlos , Nussinov Ruth , Ruoslahti Erkki
Published: June 2010

The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.
Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain
Authors: Tseng Hsiao-Chun , Lyu Ping-Chiang , Lin Wen-chang
Published: June 2010

Background

Several receptor tyrosine kinases (RTKs) such as EGFR, FGFR, TRK, and VEGFR are capable of localizing in the cell nucleus in addition to their usual plasma membrane localization. Recent reports also demonstrate that nuclear-localized RTKs have important cellular functions such as transcriptional activation. On the basis of preliminary bioinformatic analysis, additional RTKs, including receptor tyrosine kinase-like orphan receptor 1 (Ror1) were predicted to have the potential for nuclear subcellular localization. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system. Because the nuclear localization capability of the Ror1 cytoplasmic domain has not been reported, we examined the cellular expression distribution of this region.

Results

The Ror1 cytoplasmic region was amplified and cloned into reporter constructs with fluorescent tags. Following transfection, the nuclear distribution patterns of transiently expressed fusion proteins were observed. Serial deletion constructs were then used to map the juxtamembrane domain of Ror1 (aa_471-513) for this nuclear translocation activity. Further site-directed mutagenesis suggested that a KxxK-16 aa-KxxK sequence at residues 486-509 is responsible for the nuclear translocation interaction. Subsequent immunofluorescence analysis by cotransfection of Ran and Ror1 implied that the nuclear translocation event of Ror1 might be mediated through the Ran pathway.

Conclusions

We have predicted several RTKs that contain the nuclear localization signals. This is the first report to suggest that the juxtamembrane domain of the Ror1 cytoplasmic region mediates the translocation event. Ran GTPase is also implicated in this event. Our study might be beneficial in future research to understand the Ror1 biological signaling pathway.
Pituitary hCG production and cerebral tuberculosis mimicking disease progression during chemotherapy for an advanced ovarian germ cell tumour
Authors: Rakha Serena , Bayliss Clare , Sanderson Frances , Smith Richard , Seckl Michael , Savage Philip
Published: June 2010

Background

Ovarian germ cell tumours (OGCT) are rare but are usually curable with chemotherapy, even when presenting with advanced disease. The majority of OGCT produce the tumour markers, hCG and/or AFP which can be helpful in the diagnosis and monitoring the response to treatment.

Case Presentation

In this case of a 36 year old woman, the elevated hCG level at presentation was helpful in making a clinical diagnosis of OGCT in a patient too unwell to permit a tissue diagnosis.

Cisplatin based combination chemotherapy produced an initial normalisation of the hCG level, but later in treatment the patient developed new cerebral lesions and a rising serum hCG suggestive of disease progression.

Further investigations suggested that the CNS lesions were cerebral TB and that the low levels of hCG elevations was likely to be pituitary in origin. Chemotherapy treatment was continued along with anti-tuberculous therapy and 24 months after successful completion of therapy the patient remains disease free.

Conclusions

In the treatment of cancer patients it may be helpful to consider the potential non-malignant causes of new CNS lesions and that low hCG elevations may result from physiology rather than pathology in selected cases.
Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance
Authors: El Mesallamy Hala O , El-Demerdash Ebtehal , Hammad Lamiaa N , El Magdoub Hekmat M
Published: June 2010

Background

High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin.

Methods

Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in maleWistarrats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days.

Results

Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration.

Conclusion

Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic abnormalities induced by this diet model except for HHcy.
Tripping for tests: psychostimulant misuse among university students - extra
Authors: Hickman Richard A.
Published: June 2010

Throughout my years so far of medical school, caffeine has supplied that extra energy needed to get me through the late nights before deadlines and exams. There is also another well-recognised group of students, well-recognised at least in the USA - those who illegitimately acquire drugs, such as Adderall, in the run up to, and even during, exams. A study published in the Journal of Attention Disorders identified that 56% of student patients with attention-deficit hyperactivity disorder (ADHD) had been approached by other students to acquire their ADHD medications; just under half of these ADHD patients complied. Of course, these stimulants can also be obtained with a simple internet search of symptoms to then present to the physician. Evidence demonstrates that these drugs can significantly bolster the score of an exam and so we ask, is it wrong for students to use these drugs for enhancing their grade?
Insights into schizophrenia using positron emission tomography: building the evidence and refining the focus
Authors: Vyas Nora S. , Patel Neva H. , Nijran Kuldip S. , Al-Nahhas Adil , Puri Basant K.
Published: June 2010

Schizophrenia involves dysregulation in dopaminergic transmission. Studies show heightened presynaptic striatal dopaminergic function and elevated striatal D2/D3 receptor density in the brain. Cognitive impairments result from hypostimulation of D1 receptors and are associated with dysfunction in the prefrontal cortex. Here we discuss relevant positron emissions tomography (PET) studies and provide future directions.
The Fair Deal campaign: a call to arms
Authors: Deahl Martin P.
Published: June 2010

The UK healthcare economy is facing an unprecedented downturn, mental health services being particularly vulnerable. The Royal College of Psychiatrists' Fair Deal campaign is a potentially important tool to help protect services. However, like the College itself, it is only as strong as the membership, and requires individual commitment and involvement if it is to be effective.
The Mental Capacity Act 2005: review of mental capacity assessment in people with proximal femoral fracture
Authors: Guyver P. , Hindle P. , Harrison J. , Jain N. , Brinsden M.
Published: June 2010

Aims and method

To ascertain whether patients with proximal femoral fractures were being correctly assessed in line with the Mental Capacity Act 2005. Fifty people admitted with proximal femoral fractures were audited to assess whether they had given consent to treatment in accordance with the Act. A Mental Capacity Act 2005 guidance and assessment form was then introduced accompanied by staff training. A re-audit was undertaken to assess the impact.

Results

The initial audit showed that only one person (2%) had been properly assessed. The re-audit demonstrated that the use of the Mental Capacity Act 2005 assessment form ensured correct assessment.

Clinical implications

Our findings suggest the form is a useful tool in the documentation and assessment of an individual's capacity under the Mental Capacity Act.
Btk-dependent Rac activation and actin rearrangement following FcεRI aggregation promotes enhanced chemotactic responses of mast cells
Authors: Kuehn Hye Sun , Rådinger Madeleine , Brown Jared M. , Ali Khaled , Vanhaesebroeck Bart , Beaven Michael A. , Metcalfe Dean D. , Gilfillan Alasdair M.
Published: June 2010

Mast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E2, is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (FcεRI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)Cγ-mediated Ca2+ mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF, adenosine and PGE2 were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk−/− mice. There were corresponding decreases in the PLCγ-mediated Ca2+ signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses.
Synthesis and Structure of Boron Compounds Bearing Tridentate Ligands with 1,3-Bicarbonylbenzene Skeleton
Authors: Nakatsuji Jun-ya , Yamamoto Yohsuke
Published: June 2010

In order to examine differences in structure due to the electronic nature of the oxygen ligand, several organoboron compounds bearing ester 8a–8c and amide 13a and 13b ligands were prepared and crystallographically analyzed. In the ester ligand systems, the pinacolato derivative 8a and catecholato derivative 8b took a pentacoordinate structure, while fluorenyl derivative 8c took a tetracoordinate structure instead of pentacoordinate due to the strong electrophilic nature of the boron atom. In contrast to the ester ligand systems, no pentacoordinate species were found in the amide ligand systems. The pinacolato derivative 13a is tricoordinated, and catecholato derivative 13b is tetracoordinated. These results could be due to the steric effect of the diisopropylamide ligand together with the electronic effects. The VT NMR study and the DFT calculations reveal that the energy difference between the tetracoordinate and pentacoordinate structure in 8c is very small, and indicated that the electronic nature and steric effects of the ligand greatly affect the coordination state of the boron atom.
Synthesis and Structures of Lithium Salts of Stannole Anions
Authors: Saito Masaichi , Kuwabara Takuya , Ishimura Kazuya , Nagase Shigeru
Published: June 2010

1-Lithio-1-phenyl- and 1-lithio-1-trimethylsilylstannoles were synthesized and the corresponding lithium salts of stannole anions were characterized by X-ray diffraction analysis. The five-membered rings of the two lithium salts are planar with remarkable alternation of the C–C bonds, suggesting that they are both non-aromatic. Theoretical calculations are also carried out to discuss their electronic nature.
A review of hyperprolactinaemia and severe mental illness: Are there implications for clinical biochemistry?
Authors: Bushe Chris J , Bradley Andrew , Pendlebury John
Published: June 2010

Hyperprolactinaemia is a common adverse event reported in association with treatments used in schizophrenia and bipolar disorder. Recent data are suggestive that hyperprolactinaemia may have a range of significant short-and long-term clinical consequences. The objective of this review is to examine the causes, frequency and clinical consequences of hyperprolactinaemia in the severely mentally ill (SMI) with a focus on patients taking antipsychotic medications. A Medline search was carried out to identify relevant publications. Reference lists from previous review articles were also examined to search for additional data. Hyperprolactinaemia may be one of the most common adverse events associated with some antipsychotic medications. Precise rates with individual drugs had however until recently been poorly categorized. The relationship between hyperprolactinaemia and adverse outcomes in the SMI population appears similar to that in the general population. Adverse outcomes (such as sexual dysfunction) can occur acutely and in the longer term (bone fractures and possibly breast cancer), but the precise link between degree and length of hyperprolactinaemia and adverse outcome remains to be established. In conclusion, hyperprolactinaemia is a common treatment-emergent adverse event of some antipsychotic medications and may have clinical consequences. Physicians must balance the benefits and risks of treatment when determining appropriate therapy for individual patients.