bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different subcellular localizations and functions of Arabidopsis myosin VIII
Authors: Golomb Lior , Abu-Abied Mohamad , Belausov Eduard , Sadot Einat 
Published: January 2008

Abstract

Background
Myosins are actin-activated ATPases that use energy to generate force and move along actin filaments, dragging with their tails different cargos. Plant myosins belong to the group of unconventional myosins and Arabidopsis myosin VIII gene family contains four members: ATM1, ATM2, myosin VIIIA and myosin VIIIB.

Results
In transgenic plants expressing GFP fusions with ATM1 (IQ-tail truncation, lacking the head domain), fluorescence was differentially distributed: while in epidermis cells at the root cap GFP-ATM1 equally distributed all over the cell, in epidermal cells right above this region it accumulated in dots. Further up, in cells of the elongation zone, GFP-ATM1 was preferentially positioned at the sides of transversal cell walls. Interestingly, the punctate pattern was insensitive to brefeldin A (BFA) while in some cells closer to the root cap, ATM1 was found in BFA bodies. With the use of different markers and transient expression in Nicotiana benthamiana leaves, it was found that myosin VIII co-localized to the plasmodesmata and ER, colocalized with internalized FM4-64, and partially overlapped with the endosomal markers ARA6, and rarely with ARA7 and FYVE. Motility of ARA6 labeled organelles was inhibited whenever associated with truncated ATM1 but motility of FYVE labeled organelles was inhibited only when associated with large excess of ATM1. Furthermore, GFP-ATM1 and RFP-ATM2 (IQ-tail domain) co-localized to the same spots on the plasma membrane, indicating a specific composition at these sites for myosin binding.

Conclusion
Taken together, our data suggest that myosin VIII functions differently in different root cells and can be involved in different steps of endocytosis, BFA-sensitive and insensitive pathways, ER tethering and plasmodesmatal activity.
Risk factors for house-entry by malaria vectors in a rural town and satellite villages in The Gambia
Authors: Kirby Matthew J , Green Clare , Milligan Paul M , Sismanidis Charalambos , Jasseh Momadou , Conway David J , Lindsay Steven W 
Published: January 2008

Abstract

Background
In the pre-intervention year of a randomized controlled trial investigating the protective effects of house screening against malaria-transmitting vectors, a multi-factorial risk factor analysis study was used to identify factors that influence mosquito house entry.

Methods
Mosquitoes were sampled using CDC light traps in 976 houses, each on one night, in Farafenni town and surrounding villages during the malaria-transmission season in The Gambia. Catches from individual houses were both (a) left unadjusted and (b) adjusted relative to the number of mosquitoes caught in four sentinel houses that were operated nightly throughout the period, to allow for night-to-night variation. Houses were characterized by location, architecture, human occupancy and their mosquito control activities, and the number and type of domestic animals within the compound.

Results
106,536 mosquitoes were caught, of which 55% were Anopheles gambiae sensu lato, the major malaria vectors in the region. There were seven fold higher numbers of An. gambiae s.l. in the villages (geometric mean per trap night = 43.7, 95% confidence intervals, CIs = 39.5–48.4) than in Farafenni town (6.3, 5.7–7.2) and significant variation between residential blocks (p < 0.001). A negative binomial multivariate model performed equally well using unadjusted or adjusted trap data. Using the unadjusted data the presence of nuisance mosquitoes was reduced if the house was located in the town (odds ratio, OR = 0.11, 95% CIs = 0.09–0.13), the eaves were closed (OR = 0.71, 0.60–0.85), a horse was tethered near the house (OR = 0.77, 0.73–0.82), and churai, a local incense, was burned in the room at night (OR = 0.56, 0.47–0.66). Mosquito numbers increased per additional person in the house (OR = 1.04, 1.02–1.06) or trapping room (OR = 1.19, 1.13–1.25) and when the walls were made of mud blocks compared with concrete (OR = 1.44, 1.10–1.87).

Conclusion
This study demonstrates that the risk of malaria transmission is greatest in rural areas, where large numbers of people sleep in houses made of mud blocks, where the eaves are open, horses are not tethered nearby and where churai is not burnt at night. These factors need to be considered in the design and analysis of intervention studies designed to reduce malaria transmission in The Gambia and other parts of sub-Saharan Africa.
Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic therapy? Preclinical modeling in ovarian cancer
Authors: Holtz David O , Krafty Robert T , Mohamed-Hadley Alisha , Zhang Lin , Alagkiozidis Ioannis , Leiby Benjamin , Guo Wensheng , Gimotty Phyllis A , Coukos George 
Published: January 2008

AbstractBecause of its low toxicity, low-dose (LD) chemotherapy is ideally suited for combination with antiangiogenic drugs. We investigated the impact of tumor vascular endothelial growth factor A (VEGF-A) expression on the efficacy of LD paclitaxel chemotherapy and its interactions with the tyrosine kinase inhibitor SU5416 in the ID8 and ID8-Vegf models of ovarian cancer. Functional linear models using weighted penalized least squares were utilized to identify interactions between Vegf, LD paclitaxel and antiangiogenic therapy. LD paclitaxel yielded additive effects with antiangiogenic therapy against tumors with low Vegf expression, while it exhibited antagonism to antiangiogenic therapy in tumors with high Vegf expression. This is the first preclinical study that models interactions of LD paclitaxel chemotherapy with antiangiogenic therapy and tumor VEGF expression and offers important lessons for the rational design of clinical trials.
The ubiquitin E3 ligase activity of BRCA1 and its biological functions
Authors: Wu Wenwen , Koike Ayaka , Takeshita Takashi , Ohta Tomohiko 
Published: January 2008

Abstract
The basal-like breast cancer, a new category of breast cancer associated with poor prognosis and possibly unique chemosensitivity, is a current topic in the breast cancer field. Evidence from multiple sources strongly indicate that impairment of BRCA1 pathways is responsible for this phenotype, implying the importance of BRCA1 not only in familial breast cancers but also in sporadic cancers. BRCA1 acts as a hub protein that coordinates a diverse range of cellular pathways to maintain genomic stability. BRCA1 participates in multiple cellular supercomplexes to execute its tasks and, in most of the complexes, BRCA1 exists as a RING heterodimer with BARD1 to provide ubiquitin E3 ligase activity that is required for its tumor suppressor function. It was revealed recently that the BRCA1 RING finger is capable of catalyzing multiple types of ubiquitination depending upon the interacting E2, the ubiquitin carrier protein. BRCA1 may catalyze distinct ubiquitination on different substrates as the situation demands. On the other hand, in response to DNA double-strand breaks where BRCA1 plays its major role for homologous recombination repair, recent evidence showed that ubiquitination is a critical step to recruit BRCA1 to the damaged site through UIM (ubiquitin interacting motif) containing protein RAP80. Thus, ubiquitin and BRCA1 likely affect each other in many ways to perform cellular functions. Elucidation of this mechanism in relation to cell survival is now much anticipated because it could be a key to predict chemosensitivity of basal-like breast cancer.
Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the hypofractionated treatment of high-risk prostate cancer
Authors: Yuen Jasper , Rodrigues George , Trenka Kristina , Coad Terry , Yartsev Slav , D'Souza David , Lock Michael , Bauman Glenn 
Published: January 2008

Abstract

Background
To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated high-risk prostate cancer treatment.

Methods
3DCRT and dIMRT/Helical Tomotherapy(HT) planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate) and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets) in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes) and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures) were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests.

Results
When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p < 0.001), similar nodal coverage (8/8 t-test comparisons; p = ns), higher and more homogenous pelvic tissue dose (6/6 t-test comparisons; p < 0.03), at the cost of slightly higher critical structure dose (Ddose, 1–3 Gy over 5/10 dose points; p < 0.03). The dIMRT/HT approaches were superior to 3DCRT in sparing organs at risk (22/24 t-test comparisons; p < 0.05).

Conclusion
dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies.
Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients
Authors: Sassen Andrea , Rochon Justine , Wild Peter , Hartmann Arndt , Hofstaedter Ferdinand , Schwarz Stephan , Brockhoff Gero 
Published: January 2008

Abstract
Introduction
The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intracellular signal transduction pathways resulting in receptor interaction and cross-activation. The most famous family member is HER2, which is a target in Herceptin™ therapy in metastatic status and also in adjuvant therapy of breast cancer in the event of dysregulation as a result of gene amplification and resulting protein overexpression. The HER2-related HER receptors have been shown to interact directly with HER2 receptors and thereby mutually affect their activity and subsequent malignant growth potential. However, the clinical outcome with regard to total HER receptor state remains largely unknown.

Methods
We investigated HER1–HER4, at both the DNA and the protein level, using fluorescence in situ hybridisation (FISH) probes targeted to all four receptor loci and also immunohistochemistry in tissue microarrays derived from 278 breast cancer patients.

Results
We retrospectively found HER3 gene amplification with a univariate negative impact on disease-free survival (hazard ratio 2.35, 95% confidence interval 1.08 to 5.11, p = 0.031), whereas HER4 amplification showed a positive trend in overall and disease-free survival. Protein expression revealed no additional information.

Conclusion
Overall, the simultaneous quantification of HER3 and HER4 receptor genes by means of FISH might enable the rendering of a more precise stratification of breast cancer patients by providing additional prognostic information. The continuation of explorative and prospective studies on all HER receptors will be required for an evaluation of their potential use for specific therapeutic targeting with respect to individualised therapy.
Horizontal gene transfer and the evolution of transcriptional regulation in Escherichia coli
Authors: Price Morgan N , Dehal Paramvir S , Arkin Adam P 
Published: January 2008

Abstract
Background
Most bacterial genes were acquired by horizontal gene transfer from other bacteria instead of being inherited by continuous vertical descent from an ancient ancestor. To understand how the regulation of these acquired genes evolved, we examined the evolutionary histories of transcription factors and of regulatory interactions from the model bacterium Escherichia coli K12.

Results
Although most transcription factors have paralogs, these usually arose by horizontal gene transfer rather than by duplication within the E. coli lineage, as previously believed. In general, most neighbor regulators - regulators that are adjacent to genes that they regulate - were acquired by horizontal gene transfer, whereas most global regulators evolved vertically within the γ-Proteobacteria. Neighbor regulators were often acquired together with the adjacent operon that they regulate, and so the proximity might be maintained by repeated transfers (like 'selfish operons'). Many of the as yet uncharacterized (putative) regulators have also been acquired together with adjacent genes, and so we predict that these are neighbor regulators as well. When we analyzed the histories of regulatory interactions, we found that the evolution of regulation by duplication was rare, and surprisingly, many of the regulatory interactions that are shared between paralogs result from convergent evolution. Another surprise was that horizontally transferred genes are more likely than other genes to be regulated by multiple regulators, and most of this complex regulation probably evolved after the transfer.

Conclusion
Our findings highlight the rapid evolution of niche-specific gene regulation in bacteria.
Tumor Angiogenic and Hypoxic Profiles Predict Radiographic Response and Survival in Malignant Astrocytoma Patients Treated With Bevacizumab and Irinotecan
Authors: Sathornsumetee Sith , Cao Yiting , Marcello Jennifer E. , Herndon James E. , McLendon Roger E. , Desjardins Annick , Friedman Henry S. , Dewhirst Mark W. , Vredenburgh James J. , Rich Jeremy N. 
Published: January 2008

Purpose The combination of a vascular endothelial growth factor (VEGF) –neutralizing antibody, bevacizumab, and irinotecan is associated with high radiographic response rates and improved survival outcomes in patients with recurrent malignant gliomas. The aim of these retrospective studies was to evaluate tumor vascularity and expression of components of the VEGF pathway and hypoxic responses as predictive markers for radiographic response and survival benefit from the bevacizumab and irinotecan therapy. Patients and Methods In a phase II trial, 60 patients with recurrent malignant astrocytomas were treated with bevacizumab and irinotecan. Tumor specimens collected at the time of diagnosis were available for further pathologic studies in 45 patients (75%). VEGF, VEGF receptor-2, CD31, hypoxia-inducible carbonic anhydrase 9 (CA9), and hypoxia-inducible factor-2α were semiquantitatively assessed by immunohistochemistry. Radiographic response and survival outcomes were correlated with these angiogenic and hypoxic markers. Results Of 45 patients, 27 patients had glioblastoma multiforme, and 18 patients had anaplastic astrocytoma. Twenty-six patients (58%) had at least partial radiographic response. High VEGF expression was associated with increased likelihood of radiographic response (P = .024) but not survival benefit. Survival analysis revealed that high CA9 expression was associated with poor survival outcome (P = .016). Conclusion In this patient cohort, tumor expression levels of VEGF, the molecular target of bevacizumab, were associated with radiographic response, and the upstream promoter of angiogenesis, hypoxia, determined survival outcome, as measured from treatment initiation. Validation in a larger clinical trial is warranted.
Health Planning in the United States: An Old Idea with a New Significance
Authors: Atkisson Arthur A. , Grimes Richard M. 
Published: January 2008

This paper examines major features of the National Health Planning and Resources Development Act of 1974 (P.L. 93-641), a piece of legislation that would radically restructure the health planning system of the United States. The Act combines several, previously uncoordinated, health planning and health resources development agencies into one coordinated program. The program is to consist of a statutorily restricted federal agency which will generally oversee the operation of the program, a state program directed by a consumer-dominated board and a series of locally based, generally private, nonprofit, consumerdominated corporations (“Health Systems Agencies”) which will carry the bulk of the planning functions.
The resource development portion of the act grants funds for a variety of programs. These include both grants and loans (at very favorable interest rates) for medical facilities. In addition there are funds available for innovative projects which hold the prospect of improving health services and environmental conditions within the community.
The act also provides the states and local organizations with substantial power over a large portion of the allocations made under the Public Health Act and specifies the process by which health planning must be carried out. Each local planning agency must design a long range health plan for its community and prepare a one-year plan for carrying out portions of the health system plan. These two documents then are used to create State Health plans, plans for construction, modernization or conversion of health facilities and criteria for judging the appropriateness of health services offered in the local areas and in each state.
The act seems to create a mechanism whereby the health industry could be quickly converted into a heavily regulated industry. This regulatory process could be implemented in conjunction with national health insurance or by itself.
The Geriatric Long-Stay Hospital Patient: A Canadian Case Study
Authors: Shapiro Evelyn , Roos Noralou P. 
Published: January 2008

This article examines the use of acute beds by the elderly in Manitoba over the five-year period, 1972-1976. The analysis reveals that transfers of long-stay (greater than 90 day) elderly to long-term care facilities took longer in 1976 than in 1972 despite major provincial initiatives which included construction of additional long-term treatment beds, expansion of home care resources, and extension of universal insurance coverage to long-term institutional and home care.
Analyses of means to reduce long hospital stays prior to transfer suggests that building more long-term beds may be the least desirable policy alternative.
Occupational Regulation in the States: A Causal Model
Authors: Begun James W. , Crowe Edward W. , Feldman Roger 
Published: January 2008

Occupational regulation in the United States is mainly carried out by state licensing boards whose regulatory actions frequently are described as “anticompetitive.” Despite the social, political, and economic importance of these board policies, little empirical research has been conducted on the process by which regulations are developed by occupational associations and state legislatures.
This issue is addressed through analysis of data on state regulation of optometry. The regulatory power of optometry in each state is explained by characteristics of interest groups, the political system, and the socioeconomic setting. Independent variables in the analysis include the urbanization and per capita income of each state, interparty competition, legislative turnover, and innovativeness in policymaking. In addition, three measures of occupational interest group strength are employed: the percent of optometrists belonging to their state occupational associations, the ratio of optometrists to ophthalmologists and opticians, and whether or not the state optometric association employed a legislative lobbyist. The dependent variable, degree of regulation of optometry, is an index composed of four practice standard regulations which govern price advertising, branch offices, commercial practice, and continuing education.
The independent variables explain about one-third of the variance in regulatory policy across states. We find that relative interest group strength enhances optometry's ability to achieve regulation, while interparty competition and state policy innovativeness are inversely related to the level of that profession's control.
The causal analysis of state regulatory policy supports the argument that regulation is actively sought by professionalizing occupations. These groups enter the political arena to secure their regulatory objectives, and their success in obtaining these goals depends on organizational resources and the political environment in the states. The findings help to explain why state regulatory policies often appear to benefit the regulated occupations.
The Hospital Power Equilibrium: An Alternative View of the Cost Containment Dilemma
Authors: Saltman Richard B. , Young David W. 
Published: January 2008

In-patient hospital costs have grown at an annual rate of 15 percent for the last fifteen years, and the cumulative impact of these increases has created tremendous political pressures to contain this growth. Yet despite numerous attempts to pinpoint the causes of this inflation–and nearly as many recommended policy approaches–the outlines of an effective cost containment program still elude us.
Previous approaches to cost containment have tended to emphasize the mechanics of how hospital costs are incurred rather than seeking to explain the underlying causal factors that generate these costs. This analytic focus appears to reflect the lack of a political theory of the hospital which can comprehend the unique character of the hospital's internal decision-making process.
One suitable basis for such a theory is Crozier's model of a “conflictive equilibrium.” In this model, the hospital's decision-making authority is lodged in a complex power relationship which reflects the respective intra- and extra-institutional resources of its occupational groups, and particularly of physicians and administrators. This analysis of hospital behavior can both explain the hospital's reaction to present cost containment programs as well as predict its response to other likely policy approaches. It also may enable us to begin to design more effective programs through which to control the financial consequences of hospital decisions.
Social, Economic, and Health Aspects of Mandatory Retirement
Authors: Somers Anne R. 
Published: January 2008

The issue of mandatory retirement could grow into one of the major domestic conflicts of the next few decades. It cannot be divorced from the availability and adequacy of pensions. Major arguments advanced in favor of mandatory retirement include: easier personnel management, advantages to younger and minority workers, economy for employers, greater productivity, and, in certain industries, greater public safety. Major arguments against include: adverse effect on physical and mental health of many employees, inordinate cost to society–both in terms of pensions and loss of productive labor–and the general positive value of individual performance evaluation.
In the effort to resolve the conflict, three principles are suggested as a basis for future policy. (1) the individual benefits more from activity–physical and mental–than inactivity; (2) society benefits from the maximum feasible productive employment of the adult population; (3) management requires adequate flexibility in the deployment of personnel, and a balance between youth and maturity and the values associated with each age group. Based on these principles, eight specific recommendations are suggested.