bluuebunny/crossref_metadata_2025 huggingface dataset:
Tal1 Transgenic Expression Reveals Absence of B Lymphocytes
Authors: Palamarchuk Alexey , Zanesi Nicola , Aqeilan Rami I. , Efanov Alexey , Maximov Vadim , Santanam Urmila , Hagan John P. , Croce Carlo M. , Pekarsky Yuri
Published: June 2006

TAL1 oncogene encodes a helix-loop-helix transcription factor, Tal1, which is required for blood cell development, and its activation is a frequent event in T-cell acute lymphoblastic leukemia. Tal1 interacts and inhibits other helix-loop-helix factors such as E47 and HEB. To investigate the function of Tal1 in B cells, we generated Eμ-TAL1 transgenic mouse line, expressing Tal1 in mouse B-cell lineage. Fluorescence-activated cell sorting (FACS) analysis of lymphocytes isolated from spleens of five out of five founders reveals complete absence of IgM- or CD19-expressing cells. Only 2% to 3% of these cells were B220+ and 100% of B220+ cells were CD43+, indicating that these mice were able to make pro-B cells. Similarly, FACS analysis of bone marrow cells in Eμ-TAL1 mice revealed complete absence of B220+IgM+ and B220+CD19+ cells. Analysis of the recombination status of IgH genes revealed the presence of D-J but absence or drastic reduction of V-D-J rearrangements. Our results suggest that Tal1 overexpression in B cells results in a phenotype similar to that of B cells of E47/E2A knockout animals. This represents first in vivo evidence that Tal1 can completely inhibit E47/E2A function. (Cancer Res 2006; 66(12): 6014-7)
R-253 Disrupts Microtubule Networks in Multiple Tumor Cell Lines
Authors: Gururaja Tarikere L. , Goff Dane , Kinoshita Taisei , Goldstein Eileen , Yung Stephanie , McLaughlin John , Pali Erlina , Huang Jianing , Singh Rajinder , Daniel-Issakani Sarkiz , Hitoshi Yasumichi , Cooper R.D.G. , Payan Donald G.
Published: June 2006

Purpose: The design and development of synthetic small molecules to disrupt microtubule dynamics is an attractive therapeutic strategy for anticancer drug discovery research. Loss of clinical efficacy of many useful drugs due to drug resistance in tumor cells seems to be a major hurdle in this endeavor. Thus, a search for new chemical entities that bind tubulin, but neither are a substrate of efflux pump, P-glycoprotein 170/MDR1, nor cause undesired side effects, would potentially increase the therapeutic index in certain cancer treatments.

Experimental Design: A high-content cell-based screen of a compound library led to the identification of a new class of compounds belonging to a thienopyrimidine series, which exhibited significant antitumor activities. On structure-activity relationship analysis, R-253 [N-cyclopropyl-2-(6-(3,5-dimethylphenyl)thieno[3,2-d]pyrimidin-4-yl)hydrazine carbothioamide] emerged as a potent antiproliferative agent (average EC50, 20 nmol/L) when examined in a spectrum of tumor cell lines.

Results: R-253 is structurally unique and destabilizes microtubules both in vivo and in vitro. Standard fluorescence-activated cell sorting and Western analyses revealed that the effect of R-253 on cell growth was associated with cell cycle arrest in mitosis, increased select G2-M checkpoint proteins, and apoptosis. On-target activity of R-253 on microtubules was further substantiated by immunofluorescence studies and selected counter assays. R-253 competed with fluorescent-labeled colchicine for binding to tubulin, indicating that its binding site on tubulin could be similar to that of colchicine. R-253 neither is a substrate of P-glycoprotein 170/MDR1 nor is cytotoxic to nondividing human hepatocytes.

Conclusion: Both biochemical and cellular mechanistic studies indicate that R-253 could become a promising new tubulin-binding drug candidate for treating various malignancies.
Parthenolide Cooperates with NS398 to Inhibit Growth of Human Hepatocellular Carcinoma Cells through Effects on Apoptosis and G0-G1 Cell Cycle Arrest
Authors: Ralstin Matthew C. , Gage Earl A. , Yip-Schneider Michele T. , Klein Patrick J. , Wiebke Eric A. , Schmidt C. Max
Published: June 2006

Chemotherapy to date has not been effective in the treatment of human hepatocellular carcinoma. More effective treatment strategies may involve combinations of agents with activity against hepatocellular carcinoma. Parthenolide, a nuclear factor-κB (NF-κB) inhibitor, and NS398, a cyclooxygenase (COX)-2 inhibitor, have been shown to individually suppress the growth of hepatocellular carcinoma cells in vitro. To investigate their effects in combination, three human hepatocellular carcinoma lines (Hep3B, HepG2, and PLC) were treated with parthenolide and/or NS398. Parthenolide (0.1-10 μmol/L) and NS398 (1-100 μmol/L) each caused concentration-dependent growth inhibition in all cell lines. The addition of parthenolide to NS398 reduced the concentration of NS398 required to inhibit hepatocellular carcinoma growth. Because parthenolide and COX-2 inhibitors have been reported to influence NF-κB activity, the effects on this pathway were investigated. The combination of parthenolide/NS398 inhibited phosphorylation of the NF-κB-inhibitory protein IκBα and increased total IκBα levels. NF-κB DNA-binding and transcriptional activities were inhibited more by the combination than the single agents in Hep3B and HepG2 cells but not in PLC cells. The response of PLC cells to NS398 was augmented by p65 small interfering RNA to inhibit NF-κB p65 protein expression. The combination of parthenolide/NS398 increased apoptosis only in PLC cells, suggesting that the combination may decrease the apoptotic threshold in these cells. In Hep3B and HepG2 cells, combination treatment with NS398/parthenolide altered the cell cycle distribution resulting in more G0-G1 accumulation. Cyclin D1 levels were further decreased by combination treatment in all cell lines, correlating with the cell cycle alterations. Our results suggest that parthenolide may be effective in combination with COX-2 inhibitors for the treatment of hepatocellular carcinoma. (Mol Cancer Res 2006;4(6):387–400)
Oxytocin Induces Proliferation and Migration in Immortalized Human Dermal Microvascular Endothelial Cells and Human Breast Tumor-Derived Endothelial Cells
Authors: Cassoni Paola , Marrocco Tiziana , Bussolati Benedetta , Allia Elena , Munaron Luca , Sapino Anna , Bussolati Gianni
Published: June 2006

Oxytocin either increases or inhibits cell growth in different cell subtypes. We tested here the effect of oxytocin on cell proliferation and migration of human dermal microvascular endothelial cells (HMEC) and tumor-associated endothelial cells purified from human breast carcinomas (B-TEC). Oxytocin receptors were expressed in both cell subtypes at mRNA and protein levels. Through oxytocin receptor, oxytocin (1 nmol/L-1 μmol/L) significantly increased cell proliferation and migration in both HMEC and B-TEC, and addition of a selective oxytocin antagonist fully reverted these effects. To verify whether a different expression of adhesion molecule-related genes could be responsible for the oxytocin-induced cell migration, untreated and treated cells were compared applying a microarray technique. In HMEC, oxytocin induced the overexpression of the matrix metalloproteinase (MMP)-17, cathepsin D, and integrin β6 genes. In B-TEC, oxytocin significantly switched on the gene profile of some MMP (MMP-11 and MMP-26) and of integrin β6. The up-regulation of the integrin β6 gene could be involved in the oxytocin-induced cell growth, because this subunit is known to determine activation of mitogen-activated protein kinase-extracellular signal-regulated kinase 2, which is involved in the oxytocin mitogenic effect. In B-TEC, oxytocin also increased the expression of caveolin-1 at gene and protein levels. Because oxytocin receptor localization within caveolin-1-enriched membrane domains is necessary for activation of the proliferative (instead of the inhibitory) response to oxytocin, its enhanced expression can be involved in the oxytocin-induced B-TEC growth as well. Altogether, these data indicate that oxytocin contributes to cell motility and growth in HMEC and B-TEC. (Mol Cancer Res 2006;4(6):351–9)
Dynamics of Biweekly Oscillations in the Equatorial Indian Ocean*
Authors: Miyama Toru , McCreary Julian P. , Sengupta Debasis , Senan Retish
Published: June 2006

Variability of the wind field over the equatorial Indian Ocean is spread throughout the intraseasonal (10–60 day) band. In contrast, variability of the near-surface υ field in the eastern, equatorial ocean is concentrated at biweekly frequencies and is largely composed of Yanai waves. The excitation of this biweekly variability is investigated using an oceanic GCM and both analytic and numerical versions of a linear, continuously stratified (LCS) model in which solutions are represented as expansions in baroclinic modes. Solutions are forced by Quick Scatterometer (QuikSCAT) winds (the model control runs) and by idealized winds having the form of a propagating wave with frequency σ and wavenumber kw. The GCM and LCS control runs are remarkably similar in the biweekly band, indicating that the dynamics of biweekly variability are fundamentally linear and wind driven. The biweekly response is composed of local (nonradiating) and remote (Yanai wave) parts, with the former spread roughly uniformly along the equator and the latter strengthening to the east. Test runs to the numerical models separately forced by the τx and τy components of the QuikSCAT winds demonstrate that both forcings contribute to the biweekly signal, the response forced by τy being somewhat stronger. Without mixing, the analytic spectrum for Yanai waves forced by idealized winds has a narrowband (resonant) response for each baroclinic mode: Spectral peaks occur whenever the wavenumber of the Yanai wave for mode n is sufficiently close to kw and they shift from biweekly to lower frequencies with increasing modenumber n. With mixing, the higher-order modes are damped so that the largest ocean response is restricted to Yanai waves in the biweekly band. Thus, in the LCS model, resonance and mixing act together to account for the ocean's favoring the biweekly band. Because of the GCM's complexity, it cannot be confirmed that vertical mixing also damps its higher-order modes; other possible processes are nonlinear interactions with near-surface currents, and the model's low vertical resolution below the thermocline. Test runs to the LCS model show that Yanai waves from several modes superpose to form a beam (wave packet) that carries energy downward as well as eastward. Reflections of such beams from the near-surface pycnocline and bottom act to maintain near-surface energy levels, accounting for the eastward intensification of the near-surface, equatorial υ field in the control runs.
Numerical Investigation of Solitary Internal Wave-Induced Global Instability in Shallow Water Benthic Boundary Layers
Authors: Diamessis Peter J. , Redekopp Larry G.
Published: June 2006

The time-dependent boundary layer induced by a weakly nonlinear solitary internal wave in shallow water is examined through direct numerical simulation. Waves of depression and elevation are both considered. The mean density field corresponds to that typical of the coastal ocean and lakes where the lower fraction of the water column is subject to the stabilizing effect of a diffuse stratification. Sufficient resolution of the “inviscid” dynamics of the boundary layer is ensured through use of a Legendre spectral multidomain discretization scheme in the vertical direction. At higher Reynolds numbers, where the simulations become underresolved, because of restrictions in available computational resources, spectral accuracy and numerical stability at the scales of physical interest are preserved through use of a penalty scheme in the vertical and explicit spectral filtering. Thus, a highly accurate description of the qualitative dynamics of the wave-induced global instability is possible and finescale physical mechanisms critical to the appearance of this instability are not smeared out by the high artificial dissipation inherent in lower-order finite-difference schemes. Results indicate that, for a wave amplitude exceeding a critical value, the global instability occurs in regions near the bottom boundary where the wave induces an adverse pressure gradient. The structure of the associated separation bubble is modified through the establishment of coherent and synchronous dynamics, characterized by elevated levels of bottom shear stress and a periodic shedding of coherent vortex structures. Although details of the vortex shedding depend on the particular wave forcing involved, these vortical structures always ascend high into the water column. All findings suggest that this global instability is a potent mechanism for benthic turbulence, mixing, and possible sediment resuspension in shallow waters, presumably even more intense than the nominal turbulent boundary layer.
A Modeling Study of the Impact of Tropical Instability Waves on the Heat Budget of the Eastern Equatorial Pacific
Authors: Menkes Christophe E. R. , Vialard Jérôme G. , Kennan Sean C. , Boulanger Jean-Philippe , Madec Gurvan V.
Published: June 2006

A numerical simulation is used to investigate the mixed layer heat balance of the tropical Pacific Ocean including the equatorial cold tongue and the region of vortices associated with tropical instability waves (TIWs). The study is motivated by a need to quantify the effects that TIWs have on the climatological heat budget of the cold tongue mixed layer; there has been some discrepancy between observations indicating very large equatorward heat transport by TIWs and models that disagree on the full three-dimensional budget. Validation of the model reveals that the TIW-induced circulation patterns are realistic but may have amplitudes about 15% weaker than those in the observations. The SST budget within tropical instabilities is first examined in a frame of reference moving with the associated tropical instability vortices (TIVs). Zonal advection of temperature anomalies and meridional advection of temperature by current anomalies dominate horizontal advection. These effects strongly heat the cold cusps and slightly cool the downwelling areas located at the leading edge of the vortices. Cooling by vertical mixing is structured at the vortex scale and almost compensates for horizontal advective heating in the cold cusps. In contrast to some previous studies, TIW-induced vertical advection is found to be negligible in the SST budget. Cooling by this term is only significant below the mixed layer. The effect of TIWs on the climatological heat budget is then investigated for the region bounded by 2°S–6°N, 160°–90°W, where instabilities are most active. TIW-induced horizontal advection leads to a warming of 0.84°C month−1, which is of the same order as the 0.77°C month−1 warming effect of atmospheric fluxes, while the mean currents and vertical mixing cool the upper ocean by −0.59°C month−1 and −1.06°C month−1, respectively. The cooling effect of TIW-induced vertical advection is also negligible in the long-term surface layer heat budget and only becomes significant below the mixed layer. The results above, and in particular the absence of cancellation between horizontal and vertical TIW-induced eddy advection, are robust in three other sensitivity experiments involving different mixing parameterizations and increased vertical resolution.
When a Favela Dared to Become a Gated Condominium
Authors: Vargas João H. Costa
Published: June 2006

An analysis of the key political events that led to the installation of gates and cameras around Jacarezinho, the second-largest favela in Rio de Janeiro, in July 2001 and the reaction to them by the news media is here framed by ethnographic data gathered since June 2001 among Afro-Brazilian activists in Rio de Janeiro. Study of the newspaper coverage of the creation of the “favela-condominium” and the public debate that followed shows that such discourses, albeit often tacitly, dehumanized Afro-Brazilians by linking them to crime and corruption and depicted the favelas as likely to produce future generations of dangerous blacks who would continue to terrorize the imagination and lives of nonfavela people. Attention to the way race and urban space intersect is necessary if scholarship on Brazilian cities intends to understand and dialogue with favela activists, who have no choice but to confront their continued dehumanization.
Neoliberal Global Remedies: From Speculative-Led Growth to IMF-Led Crisis in Turkey
Authors: Yeldan Erinc
Published: June 2006

Turkey experienced a severe economic and political crisis in November 2000, and again in February 2001. The IMF has been involved with the macro management of the Turkish economy both prior to and after the crisis, and provided financial assistance of $20.4 billion, net, between 1999 and 2003. The official stance is that the crisis was the result of the failure of the public sector to maintain the austerity targets and the failure to fully implement the free market rationale of globalization. I argue in this article, however, that contrary to the official wisdom, the current economic and political crisis is not the end result of a set of technical errors or administrative mismanagement unique to Turkey, but is the result of a series of pressures emanating from the process of integration with the global capital markets. I document the fragility indicators of the Turkish financial and fiscal system, and show that the IMF program led to an increase in vulnerability of the financial system throughout 2000-2001. I further argue that the recent wave of structural reforms destined for stability and credibility serve, in fact, mainly the interests of foreign finance capital, and primarily aim at securing the debt obligations of the Turkish arbiters.
The Adverse Effects of Morphine: A Prospective Survey of Common Symptoms During Repeated Dosing for Chronic Cancer Pain
Authors: Glare Paul , Walsh Declan , Sheehan Denice
Published: June 2006

Little information is available about the incidence, prevalence, or severity of morphine side effects during repeated individualized dosing for chronic cancer pain, although it has been widely used in this way for more than 30 years. The authors’ aim was to describe the prevalence of symptoms possibly attributable to morphine side effects in a convenience sample of patients with pain due to advanced cancer. They used a prospective survey of inpatients and outpatients on regularly dosed morphine, with a questionnaire administered weekly for 4 weeks. Forty-two of 56 eligible patients completed at least the first questionnaire, with 30 completing all 4. Dry mouth was the most common symptom reported (point prevalence, 95%); this was often moderate to severe in intensity (57%) and was the most persistent symptom (period prevalence, 20%). Sedation and constipation were frequent (point prevalence, 88%) and was often moderate or severe at some point (55% and 62%, respectively) but had low period prevalence. Nausea was reported by less than half the patients. Myoclonus was common (point prevalence, 83%) but was usually mild and not persistent. Total daily morphine dose had little impact on side-effect patterns. Constipation, dysphoria, myoclonus, nausea, and sedation were more likely to be severe following dose increases. In conclusion, although constipation, nausea, and sedation are well described as side effects of morphine administration, others such as dry mouth and myoclonus appear to be underestimated. Validated patient-based measures of opioid side effects are needed.
Quality of Life of Caregivers of Patients With Advanced-Stage Cancer
Authors: Clark Matthew M. , Rummans Teresa A. , Sloan Jeff A. , Jensen Andrus , Atherton Pamela J. , Frost Marlene H. , Richardson Jarrett W. , Bostwick J. Michael , Johnson Mary E. , Hanson Jean M. , Brown Paul D.
Published: June 2006

There has been much research documenting the impact of having a loved one diagnosed with advanced cancer, but little is known about how to reduce care-giver burden. In this randomized controlled trial, the authors examined the potential relationship of an advanced cancer patient’s participation in an 8-session, structured, multidisciplinary intervention on the care-giver’s burden and quality of life (QOL). Although the patients randomly assigned to the intervention (n = 54) demonstrated improved QOL compared to the control condition (n = 49) participants ( P < .05), there was no evidence that improving the patient’s QOL made an impact on the caregiver’s level of burden or the care-giver’s QOL. Further investigation is warranted in this area, including interventions specifically designed and targeted to both reduce caregiver burden and to improve caregiver QOL.
What Palliative Care Volunteers Would Like to Know About the Patients They Are Being Asked to Support
Authors: Claxton-Oldfield Stephen , MacDonald Jessica , Claxton-Oldfield Jane
Published: June 2006

A study was conducted to determine the kind of information palliative care volunteers would like to know about the patients they are being asked to support before they actually meet with them for the first time. Thirty-one palliative care volunteers responded to a brief questionnaire, developed for this study. At least half of the volunteers indicated that their coordinator provided them with the following patient information: (1) the patient’s support system/family circumstances (eg, if there is any family),(2) the patient’s diagnosis/disease, (3) the patient’s age, and (4) the patient’s location (address/room number). Overall, the volunteers were very satisfied with the information their coordinators passed along to them. Volunteers rated medical information (eg, the patient’s diagnosis) and relationship information (eg, the patient’s marital status) as being more important to them than personal information (eg, the patient’s interests and hobbies). The 3 most important sources of patient information, mentioned by at least half of the volunteers, were (1) their coordinator, (2) the patient’s family members, and (3) the patient himself or herself. Only a few volunteers described issues around confidentiality that had arisen in their work (eg, being a volunteer in a small town, where people know what you are doing).
Advance Directive Communication: Nurses’ and Social Workers’ Perceptions of Roles
Authors: Black Kathy
Published: June 2006

As a facet of advance care planning for future health care, advance directive communication represents an important aspect of professional health care practice with older patients. Nurses and social workers routinely discuss advance directives in acute care settings; however, communication practices by discipline are not well understood. This qualitative study explored differences in advance directive communication practices by comparing and contrasting nurses’ and social workers’ perceptions of their roles. Focus group interviews were conducted with nurses (n = 6) and social workers (n = 5). Five key themes emerged from the data. Findings suggest that both professions perceive primary educational roles, though their informational practices differed in content. The professionals reported differential pathways that led to their practices with patients. Both disciplines identified advocacy roles with families and providers. The practitioners reported distinct roles with families. There was mutual recognition of interdisciplinary roles. The findings suggest that nurses and social workers engage in both parallel and complementary advance care planning practices with their patients.
Charity at the Deathbed: Impacts of Public Funding Changes on Hospice Care
Authors: Pietroburgo Julie
Published: June 2006

A core hospice value is caring for dying individuals regardless of their ability to pay. Historically, a stable source of government funding has provided the financial cushion necessary to extend care to indigent patients. Recently however, 2 factors have challenged the charitable-care value. First, financial reserves have been constrained by regulatory actions limiting admissions, lengths of stay, and reimbursement levels. Second, the number of uninsured individuals has increased. This study of hospices in 17 states found that hospices (1) remain committed to indigent care despite deep concerns about inadequate financial resources, (2) are encountering increased demand for services from indigent patients, (3) are currently covering indigent-care costs, but are pessimistic about their future ability to do so, and (4) are pursuing alternative funding with mixed results.
Reasons for Intimate Partner Violence Perpetration Among Arrested Women
Authors: Stuart Gregory L. , Moore Todd M. , Hellmuth Julianne C. , Ramsey Susan E. , Kahler Christopher W.
Published: June 2006

There are limited empirical data regarding the reasons or motives for the perpetration of intimate partner violence among women arrested for domestic violence and court referred to violence intervention programs. The present study examined arrested women’s self-report reasons for partner violence perpetration and investigated whether women who were victims of severe intimate partner violence were more likely than were women who were victims of minor partner violence to report self-defense as a reason for their behavior. In all, 87 women in violence intervention programs completed a measure of violence perpetration and victimization and a questionnaire assessing 29 reasons for violence perpetration. Self-defense, poor emotion regulation, provocation by the partner, and retaliation for past abuse were the most common reasons for violence perpetration. Victims of severe partner violence were significantly more likely than were victims of minor partner violence to report self-defense as a reason for their violence perpetration. The clinical implications of these findings are discussed.
Alcohol and Domestic Violence
Authors: Galvani Sarah
Published: June 2006

Alcohol’s role in men’s violence to women is a controversial issue. In the United Kingdom, little research has been conducted on the link between the two, and no in-depth studies have sought the views of the women who suffer such violence. This article reports on in-depth research with 20 women that aimed to hear their views on the role of alcohol in men’s violence to them. The results of the research show that women do not blame alcohol for their partner’s violence; they hold the men, not their alcohol consumption, responsible for their actions.
Effect of smoking cessation on cough reflex sensitivity
Authors: Dicpinigaitis P. V. , Sitkauskiene B. , Stravinskaite K. , Appel D. W. , Negassa A. , Sakalauskas R.
Published: June 2006

Recent studies have shown that cigarette smokers have diminished cough reflex sensitivity compared with nonsmokers. The current authors proposed a mechanism of chronic cigarette smoke-induced desensitisation of airway cough receptors.

To investigate this hypothesis, cough sensitivity to inhaled capsaicin (C5) in chronic smokers was measured both while they were actively smoking and 2, 6, 12 and 24 weeks after smoking cessation.

In total, 29 subjects underwent baseline capsaicin challenge while smoking and 2 weeks after smoking cessation. Mean±semlog C5fell from 1.86±0.12 to 1.60±0.12, demonstrating significant enhancement of cough reflex sensitivity. Of the total, 20, 18 and 14 subjects successfully abstained from smoking for 6, 12 and 24 weeks, respectively. Mean log C5values after 12 and 24 weeks of smoking cessation were significantly diminished from baseline. In a control group of smokers, mean log C5did not decrease from baseline after 6, 12 and 24 weeks. Overall, the log C5profile of the smoking cessation group showed a clear, linearly decreasing trend over time compared with the control group.

Even after many years of smoking, cough sensitivity is enhanced as early as 2 weeks after smoking cessation. Given the importance of an intact cough reflex, these changes may provide clinical benefit.
Transcriptome analysis of Deinagkistrodon acutus venomous gland focusing on cellular structure and functional aspects using expressed sequence tags
Authors: Zhang Bing , Liu Qinghua , Yin Wei , Zhang Xiaowei , Huang Yijun , Luo Yingfeng , Qiu Pengxin , Su Xingwen , Yu Jun , Hu Songnian , Yan Guangmei
Published: June 2006

Background

The snake venom gland is a specialized organ, which synthesizes and secretes the complex and abundant toxin proteins. Though gene expression in the snake venom gland has been extensively studied, the focus has been on the components of the venom. As far as the molecular mechanism of toxin secretion and metabolism is concerned, we still knew a little. Therefore, a fundamental question being arisen is what genes are expressed in the snake venom glands besides many toxin components?

Results

To examine extensively the transcripts expressed in the venom gland of Deinagkistrodon acutus and unveil the potential of its products on cellular structure and functional aspects, we generated 8696 expressed sequence tags (ESTs) from a non-normalized cDNA library. All ESTs were clustered into 3416 clusters, of which 40.16% of total ESTs belong to recognized toxin-coding sequences; 39.85% are similar to cellular transcripts; and 20.00% have no significant similarity to any known sequences. By analyzing cellular functional transcripts, we found high expression of some venom related genes and gland-specific genes, such as calglandulin EF-hand protein gene and protein disulfide isomerase gene. The transcripts of creatine kinase and NADH dehydrogenase were also identified at high level. Moreover, abundant cellular structural proteins similar to mammalian muscle tissues were also identified. The phylogenetic analysis of two snake venom toxin families of group III metalloproteinase and serine protease in suborder Colubroidea showed an early single recruitment event in the viperids evolutionary process.

Conclusion

Gene cataloguing and profiling of the venom gland of Deinagkistrodon acutus is an essential requisite to provide molecular reagents for functional genomic studies needed for elucidating mechanisms of action of toxins and surveying physiological events taking place in the very specialized secretory tissue. So this study provides a first global view of the genetic programs for the venom gland of Deinagkistrodon acutus described so far and an insight into molecular mechanism of toxin secreting.

All sequences data reported in this paper have been submitted into the public database [GenBank: DV556511-DV565206].
Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]
Authors: Apostolopoulos Vasso , Pietersz Geoffrey A , Tsibanis Anastasios , Tsikkinis Annivas , Drakaki Heleni , Loveland Bruce E , Piddlesden Sara J , Plebanski Magdalena , Pouniotis Dodie S , Alexis Michael N , McKenzie Ian F , Vassilaros Stamatis
Published: June 2006

Introduction

Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1.

Method

In a randomized, double-blind study, 31 patients with stage II breast cancer and with no evidence of disease received subcutaneous injections of either placebo or oxidized mannan-MUC1, to immunize against MUC1 and prevent cancer reoccurrence/metastases. Twenty-eight patients received the full course of injections of either oxidized mannan-MUC1 or placebo. Survival and immunological assays were assessed.

Results

After more than 5.5 years had elapsed since the last patient began treatment (8.5 years from the start of treatment of the first patient), the recurrence rate in patients receiving the placebo was 27% (4/15; the expected rate of recurrence in stage II breast cancer); those receiving immunotherapy had no recurrences (0/16), and this finding was statistically significant (P = 0.0292). Of the patients receiving oxidized mannan-MUC1, nine out of 13 had measurable antibodies to MUC1 and four out of 10 had MUC1-specific T cell responses; none of the placebo-treated patients exhibited an immune response to MUC1.

Conclusion

The results suggest that, in early breast cancer, MUC1 immunotherapy is beneficial, and that a larger phase III study should be undertaken.
Maternal control of vertebrate dorsoventral axis formation and epiboly by the POU domain protein Spg/Pou2/Oct4
Authors: Reim Gerlinde , Brand Michael
Published: June 2006

Dorsoventral (DV) axis formation of the vertebrate embryo is controlled by the maternal genome and is subsequently refined zygotically. In the zygote,repression of ventralizing Bmp activity on the dorsal side through chordin and noggin is crucial for establishment of a dorsally located organizer. This interplay generates a zygotic Bmp activity gradient that defines distinct positional values along the DV axis. The maternal processes that control expression of the zygotic genes implicated in DV patterning are largely unknown. spiel-ohne-grenzen (spg/pou2) is a maternally and zygotically expressed zebrafish gene that encodes the POU domain transcription factor Pou2, an ortholog of mammalian Oct4/Pou5f1. We show that embryos that are genetically depleted of both maternal and zygotic pou2 function(MZspg) exhibit extreme DV patterning defects and, independently, a blastoderm-specific arrest of epiboly. Dorsal tissues expand to the ventral side at the expense of ventrolateral tissue in MZspg embryos. Dorsally expressed Bmp-antagonists, such as Chd and Nog1, and Gsc are ectopically activated at ventral levels in MZspg. Lack of ventral specification is apparent very early, suggesting that maternal processes are affected in MZspg. Indeed, maternal pou2 function is necessary to initiate zygotic expression of ventrally expressed genes such as bmp2b and bmp4, and for proper activation of bmp7, vox,vent and eve1. A constitutively active Alk8-TGFβ-receptor can ectopically induce bmp2b and bmp4 and rescues the dorsalization of MZspg. This indicates that pou2 acts upstream of Alk8, a maternally provided receptor implicated in the activation of zygotic bmp2b and bmp4 transcription. Consistent with this possibility, Bmp gene misexpression can rescue MZspg embryos,indicating that TGFβ-mediated signal transduction itself is intact in absence of Pou2. Inhibition of Fgf signaling, another pathway with early dorsalizing activity, can also restore and even ventralize MZspgembryos. The requirement for pou2 to initiate bmp2bexpression can therefore be bypassed by releasing the repressive function of Fgf signaling upon bmp2b transcription. In transplantation experiments, we find that dorsalized cells from prospective ventrolateral regions of MZspg embryos are non cell-autonomously respecified to a ventral fate within wild-type host embryos. Analysis of pou2 mRNA injected MZspg embryos shows that pou2 is required on the ventral side of cleavage stage embryos. Based on the maternal requirement for pou2 in ventral specification, we propose that ventral specification employs an active, pou2-dependent maternal induction step, rather than a default ventralizing program.
Cskdifferentially regulatesSrc64during distinct morphological events inDrosophilagerm cells
Authors: O'Reilly Alana M. , Ballew Anna C. , Miyazawa Byron , Stocker Hugo , Hafen Ernst , Simon Michael A.
Published: June 2006

The Src family protein tyrosine kinases (SFKs) are crucial regulators of cellular morphology. In Drosophila, Src64 controls complex morphological events that occur during oogenesis. Recent studies have identified key Src64-dependent mechanisms that regulate actin cytoskeletal dynamics during the growth of actin-rich ring canals, which act as intercellular bridges between germ cells. By contrast, the molecular mechanisms that regulate Src64 activity levels and potential roles for Src64 in additional morphological events in the ovary have not been defined. In this report, we demonstrate that regulation of Src64 by DrosophilaC-terminal-Src Kinase (Csk) contributes to the packaging of germline cysts by overlying somatic follicle cells during egg chamber formation. These results uncover novel roles for both Csk and Src64 in a dynamic event that involves adhesion, communication between cell types and control of cell motility. Strikingly, Src64 and Csk function in the germline to control packaging, not in migrating follicle cells, suggesting novel functions for this signaling cassette in regulating dynamic adhesion. In contrast to the role played by Csk in the regulation of Src64 activity during packaging, Csk is dispensable for ring canal growth control, indicating that distinct mechanisms control Src64 activity during different morphological events.
Analysis of mouse EphA knockins and knockouts suggests that retinal axons programme target cells to form ordered retinotopic maps
Authors: Willshaw David
Published: June 2006

I present a novel analysis of abnormal retinocollicular maps in mice in which the distribution of EphA receptors over the retina has been modified by knockin and/or knockout of these receptor types. My analysis shows that in all these cases, whereas the maps themselves are discontinuous, the graded distribution of EphA over the nasotemporal axis of the retina is recreated within the pattern of axonal terminations across rostrocaudal colliculus. This suggests that the guiding principle behind the formation of ordered maps of nerve connections between vertebrate retina and superior colliculus, or optic tectum, is that axons carrying similar amounts of Eph receptor terminate near to one another on the target structure. I show how the previously proposed marker induction model embodies this principle and predicts these results. I then describe a new version of the model in which the properties of the markers, or labels, are based on those of the Eph receptors and their associated ligands, the ephrins. I present new simulation results, showing the development of maps between two-dimensional structures, exploring the role of counter-gradients of labels across the target and confirming that the model reproduces the retinocollicular maps found in EphA knockin/knockout mice. I predict that abnormal distributions of label within the retina lead to abnormal distributions of label over the target, so that in each of the types of knockin/knockout mice analysed, there will be a different distribution of labels over the target structure. This mechanism could be responsible for the flexibility with which neurons reorganise their connections during development and the degree of precision in the final map. Activity-based mechanisms would play a role only at a later stage of development to remove the overlap between individual retinal projection fields, such as in the development of patterns of ocular dominance stripes.
Cation Effects on Infrared Reflection Absorption Spectra of Cyanide Adsorbed on Pt(111) Electrode in Electrolyte Solutions
Authors: Inukai Junji , Morioka Yukiko , Kim Youn-Geun , Yau Shueh-Lin , Itaya Kingo
Published: June 2006

In-situ infrared reflection absorption spectroscopy was applied to the investigation of cation effects on the C–N stretching frequency of cyanide ions on Pt(111) electrode in electrolyte solutions. Only a single absorption peak was observed at ca. 2100 cm−1 in solutions containing H3O+, Li+, Na+, K+, or Cs+. In a KClO4 solution (pH = 9.5), a change in slope was observed in the peak frequency–potential curve at ca. −0.5 V vs. the saturated calomel electrode. It was concluded that in the cathodic region in the KClO4 solution, H3O+ dominates the outer Helmholtz plane as a result of cation exchange. In alkaline solutions, the slope for the frequency shift is dependent on the cations in the order K+ > Na+ > Li+ ≈ Cs+. In HClO4, a change in slope was also observed in the peak frequency-potential curve. In a Mg(ClO4)2 solution, three peaks were observed for CN on Pt(111), indicating that factors other than the simple electrochemical Stark effect must be considered for interpreting the influence of this strongly adsorbed cation.
Quantum Yields of Intramolecular Hydrogen Abstraction Induced by Laser Flash Photolysis of Arene/Cl π-Complexes
Authors: Wu Feng , Shindo Toshihiko , Sawamura Sadashi , Sumiyoshi Takashi
Published: June 2006

Arene/chlorine atom π-complexes were generated by pulse radiolysis of a wide variety of substituted benzenes in carbon tetrachloride at room temperature. Upon laser flash photolysis of the π-complexes, intramolecular hydrogen abstraction was observed in times much shorter than the flash time (6 ns), with quantum yields between 0.05 and 0.18 depending on the sort and the number of the substituents but not on their positions. The effects of substituents on the photochemistry of arene/chlorine atom π-complexes were discussed in connection with the bond dissociation energy of the related atoms and with the structure of the π-complexes.
Dinaionic Ligand Complexes, K2[CuLn] and K2[NiLn] (n = 1, 2; H4L1 = 1,2-Bis(2-hydroxybenzamido)ethane, H4L2 = 1,2-Bis(2-hydroxybenzamido)benzene), and Their Dinuclear Cu(II)–Cu(II) and Ni(II)–Cu(II) Complexes
Authors: Sunatsuki Yukinari , Nakamura Masaaki , Matsumoto Naohide , Kai Fumiaki
Published: June 2006

Copper(II) and nickel(II) complexes with tetraanionic quadridentate ligands, K2[CuLn] and K2[NiLn] (n = 1, 2), have been prepared. We examined whether or not they can function as “ligand complexes”, where H4L1 = 1,2-bis(2-hydroxybenzamido)ethane and H4L2 = 1,2-bis(2-hydroxybenzamido)benzene. One of the ligand complexes, K2[NiL1]·2dmf·2H2O, crystallizes in the monoclinic space group P21/n with the cell dimensions of a = 15.34(8), b = 18.99(8), c = 18.86(5) Å, β = 100.2(3), V = 5406 Å3, and Z = 8. The ligand complex assumes a unique one-dimensional structure consisting of {[KO3][K(NiL1)O]}n as the repeating unit, where each K+ ion is surrounded octahedrally by six oxygen atoms with the distances of 2.672(2)—2.866(9) Å and all the oxygen atoms act as bridging group to K+ ion. Each of the precursor complexes can function as an electrically dianionic bidentate “ligand complex” and reacts with Cu(II) ion and terminal capping ligand (cap) such as 2,2′-bipyridine (bpy), 1,10-phenanthroline (phen), ethylenediamine (en), and 1,3-diaminopropane (tn) to give di-μ-phenoxo-bridged dinuclear Cu(II)–Cu(II) and Ni(II)–Cu(II) complexes with the general formula of [(Cu or Ni)LnCu(cap)]. The molar electrical conductivities of the dinuclear complexes measured in the DMF or DMSO solutions are essentially zero, indicating that the dinuclear structures are preserved in the solutions. The electrochemical measurements for a series of [CuL2Cu(cap)] (cap = bpy, phen, tn) demonstrated that the Cu(II/III) redox process of the {CuL2} site exhibits more positive potential (−0.04 — −0.09 V) than that of the mononuclear precursor complex (−0.288 V). One of the dinuclear complexes, [CuL2Cu(phen)(DMSO)], crystallizes in the orthorhombic space group Pna21 with the cell dimensions of a = 19.702(3), b = 15.847(3), c = 9.652(2) Å, V = 3013 Å3, and Z = 4. The complex consists of a discrete di-μ-phenoxo-bridged dinuclear structure, in which two copper(II) ions assume a square planar and square pyramidal coordination geometry and the bridging core of Cu2O2 is unequivalent, as found in the distances of Cu(1)–O(1) = 1.924(4) Å, Cu(1)–O(2) = 1.908(4) Å, Cu(2)–O(2) = 1.964(4) Å and Cu(2)–O(1) = 2.249(4) Å. The magnetic susceptibility is well reproduced with the antiferromagnetic coupling parameter of J = −82 cm−1 by the Bleaney–Boweres equation.
Synthesis and Properties of Tris(octaethylporphyrin)s Connected with Vinylene Groups
Authors: Higuchi Hiroyuki , Shimizu Kenji , Takeuchi Makoto , Ojima Juro , Sugiura Ken-ichi , Sakata Yoshiteru
Published: June 2006

Tris(octaethylporphyrin)s, in which two octaethylporphyrin (OEP) rings are connected with vinylene groups at α,γ- and α,β-meso positions of the central OEP ring, were synthesized. The tris(OEP)s have similar conformational and configurational structures to the corresponding vinylene group-connected bis(OEP). Examination of both 1H NMR and electronic absorption spectra of the tris(OEP)s showed the behavior reflecting the highly symmetrical structure and the mutual interaction between the three OEP rings through the vinylene linkages.
A Chemical Scale for Evaluating the Electron Transfer Ability of Alkylcopper Reagents
Authors: Chounan Yukiyasu , Horino Hiroshi , Ibuka Toshiro , Yamamoto Yoshinori
Published: June 2006

In order to evaluate the electron transfer ability of organocopper reagents, the reactions of appropriate Michael acceptors with methyl- and butylcopper reagents were investigated. The reaction of trimethyl ethylene-1,1,2-tricarboxylate (1a) with methylcopper reagents gave a mixture of the conjugate adduct 2a and reduction product 3a in good to high yields. The ratio of 2a and 3a varied with the copper species and decreased in the following order: MeCu(CN)Li > MeCu > Me2Cu(CN)Li2 >> Me2CuLi > Me3CuLi2. It was confirmed by 13C NMR studies and oxidation experiments of the intermediate copper species that the reduction product 3a was produced via an electron transfer process and that the conjugate adduct 2a was afforded through a nucleophilic attack of MeCuILn. Consequently, the electron transfer ability of methylcopper reagents is in the following order: Me3CuLi2 > Me2CuLi >> Me2Cu(CN)Li2 > MeCu > MeCu(CN)Li. By similar experiments using 3-cyclopropyl-2-methoxycarbonyl-3-phenyl-2-propenoate (9) as a Michael acceptor, we concluded that the electron transfer ability of butylcopper reagents is in the order of Bu2CuLi > BuCu(CN)Li ≈ Bu2Cu(CN)Li2 > BuCu, and that its ability of butylcopper reagents is higher than that of the corresponding methylcopper reagents.
Synthesis of 2-Polyprenyl-Substituted Polyprenols and Their Conversion into Phosphates
Authors: Nagano Hajime , Nagasawa Tomoko , Sakuma Masako
Published: June 2006

Highly Branched polyprenols, {(6E)-2-[(2E)-3,7-dimethyl-2,6-octadienyl]-7,11-dimethyl-3-methylene-6,10-dodecadien-1-ol and (6E,10E)-2-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrienyl]-7,11,15-trimethyl-3-methylene-6,10,14-hexadecatrien-1-ol}, were synthesized (1) from diethyl malate, geranyl bromide, and homogeranyl iodide, and (2) from ethyl acetoacetate and geranyl (or farnesyl) bromide. These alcohols were transformed into disodium phosphates, which have been postulated to be primitive lipids in the evolution of membranes.
Synthesis of Nano-Dimensional Iron–Cobalt Spinel Mixed Oxides from Layered-Type Carbonate Hydroxide Precursors
Authors: Uzunova Elly L , Mitov Ivan G , Klissurski Dimitar G
Published: June 2006

Pyroaurite-like carbonate hydroxide precursors Co1−xFex(CO3)x/2(OH)2·nH2O, where x varies in the range 0.25 ≤ x ≤ 0.75, yield cation deficient mixed oxides with particle dimensions in the nano-scale range. The thermal decomposition and spinel structure formation processes have been studied by thermal analysis and IR spectroscopy, revealing an intermediate of hydroxide oxide type. Mesoporous mixed oxides with cubic spinel structure were synthesised at 300—400 °C with significant contribution of small pores of radii <200 Å. Oxygen desorption from cobalt ferrite, synthesised at 350 °C, suggests the existence of a high content of extraframework oxygen. The temperature-programmed reduction (TPR) with hydrogen occurs in one stage for all cobalt/iron compositions. The peak maxima shift to higher temperatures and a broadening is observed with increasing the iron content. Partly inverse cation distributions of the spinel ferrites are deduced from the Moessbauer spectra.