bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of two distinct monopartite begomoviruses infecting tomato in india
Authors: Pandey Prerna , Mukhopadhya Subhra , Naqvi Afsar R , Mukherjee Sunil K , Shekhawat Gyan S , Choudhury Nirupam R
Published: November 2010

Background

Tomato leaf curl viruses, which are the members of the genus Begomovirus, have emerged as devastating pathogens worldwide causing huge economic losses and threatening production of crops like cassava, cotton, grain legumes and vegetables. Even though the ToLCV isolates from Northern India have been shown to possess bipartite genome (designated as DNA A and DNA B), those from Australia, Taiwan and Southern India have a single genomic component (DNA A). We describe here the genetic diversity of two isolates of monopartite Tomato leaf curl virus infecting tomato in two extreme regions (North and South) of Indian subcontinent.

Results

The rolling circle amplification (RCA) products obtained from symptomatic samples were digested, cloned and sequenced. The complete DNA sequence of two Tomato leaf curl virus isolates identified as ToLCV-CTM (India, New Delhi, 2005) and ToLCVK3/K5 (India, Kerala, 2008) are reported here. These isolates had the characteristic features of Begomovirus genome organization with six conserved open reading frames (ORFs). The ToLCV-K3 and ToLCV-K5 isolates may be the strains of the same virus since they show sequence homology of 97% over their entire genome. This, according to the guidelines established by the ICTV Geminiviridae Study-Group is higher than threshold (92%) for delineation of different viral variants and hence single, average value has been assigned for all their analyses presented here. The ToLCV-CTM and ToLCV-K3/K5 viruses were found to be monopartite, as neither DNA-B component nor betasatellite associated with begomovirus species, were detected. The complete nucleotide sequence of DNA-A genome of CTM exhibited highest sequence homology (88%) to Croton yellow vein mosaic virus (AJ507777), and of isolates K3/K5 (88.5%) to Tomato leaf curl Pakistan virus (DQ116884). This is less than the threshold value for demarcation of species in the genus Begomovirus.

Conclusion

K3/K5 and CTM are considered to be novel isolates of Tomato leaf curl virus. Sequence analyses and phylogenetic study indicate that these two ToLCV isolates might have evolved by recombination between viruses related to two or more viral ancestors. The existence of different ToLCV isolates having high genome diversity in India poses a threat to the tomato production in the Asian continent.
Hypofractionated radiotherapy after conservative surgery for breast cancer: analysis of acute and late toxicity
Authors: Deantonio Letizia , Gambaro Giuseppina , Beldì Debora , Masini Laura , Tunesi Sara , Magnani Corrado , Krengli Marco
Published: November 2010

Background

A variety of hypofractionated radiotherapy schedules has been proposed after breast conserving surgery in the attempt to shorten the overall treatment time. The aim of the present study is to assess acute and late toxicity of using daily fractionation of 2.25 Gy to a total dose of 45 Gy to the whole breast in a mono-institutional series.

Methods

Eighty-five women with early breast cancer were assigned to receive 45 Gy followed by a boost to the tumour bed. Early and late toxicity were scored according to the Radiation Therapy Oncology Group criteria. For comparison, a group of 70 patients with similar characteristics and treated with conventional fractionation of 2 Gy to a total dose of 50 Gy in 25 fractions followed by a boost, was retrospectively selected.

Results

Overall median treatment duration was 29 days for hypofractionated radiotherapy and 37 days for conventional radiotherapy. Early reactions were observed in 72/85 (85%) patients treated with hypofractionation and in 67/70 (96%) patients treated with conventional fractionation (p = 0.01). Late toxicity was observed in 8 patients (10%) in the hypofractionation group and in 10 patients (15%) in the conventional fractionation group, respectively (p = 0.4).

Conclusions

The hypofractionated schedule delivering 45 Gy in 20 fractions shortened the overall treatment time by 1 week with a reduction of skin acute toxicity and no increase of late effects compared to the conventional fractionation. Our results support the implementation of hypofractionated schedules in clinical practice.
Transarticular screw fixation for atlantoaxial instability - modified Magerl's technique in 38 patients
Authors: Bahadur Raj , Goyal Tarun , Dhatt Saravdeep S , Tripathy Sujit K
Published: November 2010

Background

Symptomatic atlantoaxial instability needs stabilization of the atlantoaxial joint. Among the various techniques described in literature for the fixation of atlantoaxial joint, Magerl's technique of transarticular screw fixation remains the gold standard. Traditionally this technique combines placement of transarticular screws and posterior wiring construct. The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability who were operated using transarticular screws and iliac crest bone graft, without the use of sublaminar wiring (a modification of Magerl's technique).

Methods

We evaluated retrospectively 38 subjects with atlantoaxial instability who were operated at our institute using transarticular screw fixation. The subjects were followed up for pain, fusion rates, neurological status and radiographic outcomes. Final outcome was graded both subjectively and objectively, using the scoring system given by Grob et al.

Results

Instability in 34 subjects was secondary to trauma, in 3 due to rheumatoid arthritis and 1 had tuberculosis. Neurological deficit was present in 17 subjects. Most common presenting symptom was neck pain, present in 35 of the 38 subjects.

Postoperatively residual neck and occipital pain was present in 8 subjects. Neurological deficit persisted in only 7 subjects. Vertebral artery injury was seen in 3 subjects. None of these subjects had any sign of neurological deficit or vertebral insufficiency. Three cases had nonunion. At the latest follow up, subjectively, 24 subjects had good result, 6 had fair and 8 had bad result. On objective grading, 24 had good result, 11 had fair and 3 had bad result. The mean follow up duration was 41 months.

Conclusions

Transarticular screw fixation is an excellent technique for fusion of the atlantoaxial complex. It provides highest fusion rates, and is particularly important in subjects at risk for nonunion. Omitting the posterior wiring construct that has been used along with the bone graft in the traditional Magerl' s technique achieves equally good fusion rates and is an important modification, thereby avoiding the complications of sublaminar wire passage.
Biodetoxification of toxins generated from lignocellulose pretreatment using a newly isolated fungus, Amorphotheca resinae ZN1, and the consequent ethanol fermentation
Authors: Zhang Jian , Zhu Zhinan , Wang Xiaofeng , Wang Nan , Wang Wei , Bao Jie
Published: November 2010

Background

Degradation of the toxic compounds generated in the harsh pretreatment of lignocellulose is an inevitable step in reducing the toxin level for conducting practical enzymatic hydrolysis and ethanol fermentation processes. Various detoxification methods have been tried and many negative outcomes were found using these methods, such as the massive freshwater usage and wastewater generation, loss of the fine lignocellulose particles and fermentative sugars and incomplete removal of inhibitors. An alternate method, biodetoxification, which degrades the toxins as part of their normal metabolism, was considered a promising option for the removal of toxins without causing the above problems.

Results

A kerosene fungus strain,Amorphotheca resinaeZN1, was isolated from the microbial community growing on the pretreated corn stover material. The degradation of the toxins as well as the lignocelluloses-derived sugars was characterized in different ways, and the results show thatA. resinaeZN1 utilized each of these toxins and sugars as the sole carbon sources efficiently and grew quickly on the toxins. It was found that the solid-state culture ofA. resinaeZN1 on various pretreated lignocellulose feedstocks such as corn stover, wheat straw, rice straw, cotton stalk and rape straw degraded all kinds of toxins quickly and efficiently. The consequent simultaneous saccharification and ethanol fermentation was performed at the 30% (wt/wt) solid loading of the detoxified lignocellulosic feedstocks without a sterilization step, and the ethanol titer in the fermentation broth reached above 40 g/L using food crop residues as feedstocks.

Conclusions

The advantages of the present biodetoxification byA. resinaeZN1 over the known detoxification methods include zero energy input, zero wastewater generation, complete toxin degradation, processing on solid pretreated material, no need for sterilization and a wide lignocellulose feedstock spectrum. These advantages make it possible for industrial applications with fast and efficient biodetoxification to remove toxins generated during intensive lignocellulose pretreatment.
Sox10- Venus mice: a new tool for real-time labeling of neural crest lineage cells and oligodendrocytes
Authors: Shibata Shinsuke , Yasuda Akimasa , Renault-Mihara Francois , Suyama Satoshi , Katoh Hiroyuki , Inoue Takayoshi , Inoue Yukiko U , Nagoshi Narihito , Sato Momoka , Nakamura Masaya , Akazawa Chihiro , Okano Hideyuki
Published: November 2010

Background

While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between humanSOX10mutations and neural crest cell pathogenesis led us to focus on theSox10gene, which is critical for neural crest development. We generatedSox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes.

Results

Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in theSox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues inSox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell levelin vivodue to the intense, focused Venus fluorescence. In the adultSox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury.

Conclusions

In the newly-developedSox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows forin vivoimaging of live cells at the single-cell level. ThisSox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes.
Targeted therapy in lymphoma
Authors: Johnston Patrick B , Yuan RuiRong , Cavalli Franco , Witzig Thomas E
Published: November 2010

Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.
Expression and clinicopathological significance of Mel-18 and Bmi-1 mRNA in gastric carcinoma
Authors: Lu You-Wei , Li Jin , Guo Wei-Jian
Published: November 2010

Background

The Polycomb group (PcG) genes are a class of regulators responsible for maintaining homeotic gene expression throughout cell division. PcG expression is deregulated in some types of human cancer. Both Bmi-1 and Mel-18 are of the key PcG proteins. We investigate the expression and clinicopathological roles of Mel-18 and Bmi-1 mRNA in gastric cancer.

Methods

The expression of Mel-18 and Bmi-1 in a series of 71 gastric cancer tissues and paired normal mucosal tissues distant from the tumorous lesion was assayed by quantitative real time RT-PCR. The correlation between Mel-18 and Bmi-1 mRNA expression, and between Mel-18 or Bmi-1 mRNA level and clinicopathological characteristics were analyzed.

Results

Expression of Mel-18 and Bmi-1 genes was variably detected, but overexpression of Bmi-1 mRNA and decreased expression of Mel-18 mRNA were the most frequent alteration. In addition, the expression of Bmi-1 and Mel-18 mRNA inversely correlates in gastric tumors. Moreover, a significant positive correlation between Bmi-1 overexpression and tumor size, depth of invasion, or lymph node metastasis, and a significant negative correlation between Mel-18 low-expression with lymph node metastasis or the clinical stage were observed.

Conclusion

Our data suggest that Mel-18 and Bmi-1 may play crucial but opposite roles in gastric cancer. Decreased Mel-18 and increased Bmi-1 mRNA expression was associated with the carcinogenesis and progression of gastric cancer. It is possible to list Bmi-1 and Mel-18 as biomarkers for predicting the prognosis of gastric cancer.
Diagnosis of carotid arterial injury in major trauma using a modification of Memphis criteria
Authors: Ciapetti Marco , Circelli Alessandro , Zagli Giovanni , Migliaccio Maria Luisa , Spina Rosario , Alessi Alessandro , Acquafresca Manlio , Bartolini Marco , Peris Adriano
Published: November 2010

Background

Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury has been reported as 0.5-1% of all admissions for blunt trauma, with a high stroke and mortality rate. The purpose of this study is to evaluate if a modification of Memphis criteria could improve the rate of BCVI diagnosis.

Methods

Trauma patients consecutively admitted to Intensive Care Unit (ICU) from Jan 2008 to Oct 2009 were considered for the study. Memphis criteria comprehend: basilar skull fracture with involvement of the carotid canal, cervical spine fracture, neurological exam not explained by brain imaging, Horner's syndrome, LeFort II-III fractures, and neck soft tissue injury. As single criteria modification, we included all patients with petrous bone fracture, even without carotid canal involvement. In all patients at risk of BCVI, 64-slice angio-CT-scans was performed.

Results

During the study period, 266 patients were admitted to the ICU for blunt major trauma. Among them, 162 presented traumatic brain injury or cervical spine fracture. In accordance with the proposed modified-Memphis criteria, 53 patients showed risk factors for BCVI compared to 45 using the original Memphis criteria. Among the 53 patients, 6 resulted as having carotid lesions (2.2% of all blunt major traumas; one patient more than when using Memphis criteria). Anticoagulant therapy with low molecular weight heparin was administered in all patients. No stroke or hemorrhagic complications occurred. Clinical examination at 6-months showed no central neurological deficit.

Conclusion

A modification of a single criteria of Memphis screening protocol might permit the identification of a higher percentage of BCVI. Limited by sample size, this study needs to be validated.
A method to estimate the number of people in a country or region with HIV who are undiagnosed and in need of ART
Authors: Lodwick RK , Sabin CA , Phillips AN
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Immunological response among patients with undetectable viral load followed for 5 years
Authors: Piñeiro C , Santos AS , Cardoso S , Nuak J , Lucas R , Ferreira A , Xerinda S , Tavares M , Marques R , Sarmento A
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Sex differences in hypothalamic astrocyte response to estradiol stimulation
Authors: Kuo John , Hamid Naheed , Bondar Galyna , Dewing Phoebe , Clarkson Jenny , Micevych Paul
Published: November 2010

Background

Reproductive functions controlled by the hypothalamus are highly sexually differentiated. One of the most dramatic differences involves estrogen positive feedback, which leads to ovulation. A crucial feature of this positive feedback is the ability of estradiol to facilitate progesterone synthesis in female hypothalamic astrocytes. Conversely, estradiol fails to elevate hypothalamic progesterone levels in male rodents, which lack the estrogen positive feedback-induced luteinizing hormone (LH) surge. To determine whether hypothalamic astrocytes are sexually differentiated, we examined the cellular responses of female and male astrocytes to estradiol stimulation.

Methods

Primary adult hypothalamic astrocyte cultures were established from wild type rats and mice, estrogen receptor-α knockout (ERKO) mice, and four core genotype (FCG) mice, with the sex determining region of the Y chromosome (Sry) deleted and inserted into an autosome. Astrocytes were analyzed for Sry expression with reverse transcription PCR. Responses to estradiol stimulation were tested by measuring free cytoplasmic calcium concentration ([Ca2+]i) with fluo-4 AM, and progesterone synthesis with column chromatography and radioimmunoassay. Membrane estrogen receptor-α (mERα) levels were examined using surface biotinylation and western blotting.

Results

Estradiol stimulated both [Ca2+]i release and progesterone synthesis in hypothalamic astrocytes from adult female mice. Male astrocytes had a significantly elevated [Ca2+]i response but it was significantly lower than in females, and progesterone synthesis was not enhanced. Surface biotinylation demonstrated mERα in both female and male astrocytes, but only in female astrocytes did estradiol treatment increase insertion of the receptor into the membrane, a necessary step for maximal [Ca2+]i release. Regardless of the chromosomal sex, estradiol facilitated progesterone synthesis in astrocytes from mice with ovaries (XX and XY-), but not in mice with testes (XY-
Sry and XXSry).

Conclusions

Astrocytes are sexually differentiated, and in adulthood reflect the actions of sex steroids during development. The response of hypothalamic astrocytes to estradiol stimulation was determined by the presence or absence of ovaries, regardless of chromosomal sex. The trafficking of mERα in female, but not male, astrocytes further suggests that cell signaling mechanisms are sexually differentiated.
Increased prevalence of vulnerable atherosclerotic plaques and low levels of natural IgM antibodies against phosphorylcholine in patients with systemic lupus erythematosus
Authors: Anania Cristina , Gustafsson Thomas , Hua Xiang , Su Jun , Vikström Max , de Faire Ulf , Heimbürger Mikael , Jogestrand Tomas , Frostegård Johan
Published: November 2010

Introduction

The risk of cardiovascular disease (CVD) and atherosclerosis is reported to be increased in systemic lupus erythematosus (SLE). We recently reported a negative association between natural IgM-antibodies against phosphorylcholine (anti-PC) in the general population, high anti-PC levels leading to decreased atherosclerosis development and low levels to increased risk of CVD. Potential mechanisms include anti-inflammatory properties and inhibition of uptake of oxidized low density lipoprotein (LDL) in macrophages. The objective herein was to study atherosclerosis in SLE in detail and in relation to traditional and non-traditional risk factors.

Methods

A total of 114 patients with SLE were compared with 122 age- and sex-matched population-based controls. Common carotid intima-media thickness (IMT), calculated intima-media area (cIMa) and plaque occurrence were determined by B-mode ultrasound as a surrogate measure of atherosclerosis. Plaques were graded according to echogenicity and grouped as 1 to 4, with 1 being echoluscent, and considered most vulnerable. Anti-PC was studied by ELISA.

Results

Hypertension, triglycerides and insulin resistance (determined by homeostasis model assessment of insulin resistance) and C-reactive protein (CRP) were increased in SLE (P < 0.01) while smoking, LDL, high density lipoprotein (HDL) did not differ between groups. Low levels of anti-PC IgM (lowest tertile) were more common in SLE patients than in controls (P = 0.0022). IMT and cIMa did not differ significantly between groups. However, plaques were more often found in SLE patients (P = 0.029). Age, LDL and IgM anti-PC (lowest tertile) were independently associated with plaque occurrence in SLE. Further, in the left carotid arteries echoluscent plaques (grade 1) were more prevalent in SLE as compared to controls (P < 0.016).

Conclusions

Plaque occurrence in the carotid arteries is increased in SLE and is independently associated with age, LDL and low anti-PC levels. Vulnerable plaques were more common in SLE. Anti-PC could be a novel risk marker also with a therapeutic potential in SLE.
Cross-comparison of cardiac output trending accuracy of LiDCO, PiCCO, FloTrac and pulmonary artery catheters
Authors: Hadian Mehrnaz , Kim Hyung Kook , Severyn Donald A , Pinsky Michael R
Published: November 2010

Introduction

Although less invasive than pulmonary artery catheters (PACs), arterial pulse pressure analysis techniques for estimating cardiac output (CO) have not been simultaneously compared to PAC bolus thermodilution CO (COtd) or continuous CO (CCO) devices.

Methods

We compared the accuracy, bias and trending ability of LiDCO™, PiCCO™ and FloTrac™ with PACs (COtd, CCO) to simultaneously track CO in a prospective observational study in 17 postoperative cardiac surgery patients for the first 4 hours following intensive care unit admission. Fifty-five paired simultaneous quadruple CO measurements were made before and after therapeutic interventions (volume, vasopressor/dilator, and inotrope).

Results

Mean CO values for PAC, LiDCO, PiCCO and FloTrac were similar (5.6 ± 1.5, 5.4 ± 1.6, 5.4 ± 1.5 and 6.1 ± 1.9 L/min, respectively). The mean CO bias by each paired method was -0.18 (PAC-LiDCO), 0.24 (PAC-PiCCO), -0.43 (PAC-FloTrac), 0.06 (LiDCO-PiCCO), -0.63 (LiDCO-FloTrac) and -0.67 L/min (PiCCO-FloTrac), with limits of agreement (1.96 standard deviation, 95% confidence interval) of ± 1.56, ± 2.22, ± 3.37, ± 2.03, ± 2.97 and ± 3.44 L/min, respectively. The instantaneous directional changes between any paired CO measurements displayed 74% (PAC-LiDCO), 72% (PAC-PiCCO), 59% (PAC-FloTrac), 70% (LiDCO-PiCCO), 71% (LiDCO-FloTrac) and 63% (PiCCO-FloTrac) concordance, but poor correlation (r2 = 0.36, 0.11, 0.08, 0.20, 0.23 and 0.11, respectively). For mean CO < 5 L/min measured by each paired devices, the bias decreased slightly.

Conclusions

Although PAC (COTD/CCO), FloTrac, LiDCO and PiCCO display similar mean CO values, they often trend differently in response to therapy and show different interdevice agreement. In the clinically relevant low CO range (< 5 L/min), agreement improved slightly. Thus, utility and validation studies using only one CO device may potentially not be extrapolated to equivalency of using another similar device.
Activity of Sorafenib in Recurrent Ovarian Cancer and Primary Peritoneal Carcinomatosis: A Gynecologic Oncology Group Trial
Authors: Matei Daniela , Sill Michael W. , Lankes Heather A. , DeGeest Koen , Bristow Robert E. , Mutch David , Yamada S. Diane , Cohn David , Calvert Valerie , Farley John , Petricoin Emanuel F. , Birrer Michael J.
Published: November 2010

Purpose

Sorafenib is a kinase inhibitor targeting Raf and other kinases (ie, vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], Flt3, and c-KIT). This study assessed its activity and tolerability in patients with recurrent ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC).

Methods

This open-label, multi-institutional, phase II study used a two-stage design. Eligible patients had persistent or recurrent OC/PPC after one to two prior cytotoxic regimens, and they experienced progression within 12 months of platinum-based therapy. Treatment consisted of sorafenib 400 mg orally twice per day. Primary end points were progression-free survival (PFS) at 6 months and toxicity by National Cancer Institute criteria. Secondary end points were tumor response and duration of PFS and overall survival. Biomarker analyses included measurement of ERK and b-Raf expression in tumors and phosphorylation of ERK (pERK) in peripheral-blood lymphocytes (PBLs) before and after 1 month of treatment.

Results

Seventy-three patients were enrolled, of which 71 were eligible. Fifty-nine eligible patients (83%) had measurable disease, and 12 (17%) had detectable disease. Significant grade 3 or 4 toxicities included the following: rash (n = 7), hand-foot syndrome (n = 9), metabolic (n = 10), GI (n = 3), cardiovascular (n = 2), and pulmonary (n = 2). Only patients with measurable disease were used to assess efficacy. Fourteen survived progression free for at least 6 months (24%; 90% CI, 15% to 35%). Two patients had partial responses (3.4%; 90% CI, 1% to 10%); 20 had stable disease; 30 had progressive disease; and seven could not have their tumor assessed. ERK and b-Raf were expressed in all tumors. Exploratory analyses indicated that pERK in post-treatment PBL specimens was associated with PFS.

Conclusion

Sorafenib has modest antitumor activity in patients with recurrent OC, but the activity was at the expense of substantial toxicity.
Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children's Oncology Group Study
Authors: Henderson Tara O. , Bhatia Smita , Pinto Navin , London Wendy B. , McGrady Patrick , Crotty Catherine , Sun Can-Lan , Cohn Susan L.
Published: November 2010

Purpose

Although health disparities are well-described for many cancers, little is known about racial and ethnic disparities in neuroblastoma. To evaluate differences in disease presentation and survival by race and ethnicity, data from the Children's Oncology Group (COG) were analyzed.

Patients and Methods

The racial/ethnic differences in clinical and biologic risk factors, and outcome of patients with neuroblastoma enrolled on COG ANBL00B1 between 2001 and 2009 were investigated.

Results

A total of 3,539 patients (white, 72%; black, 12%; Hispanic, 12%; Asian, 4%; and Native American, < 1%) with neuroblastoma were included. The 5-year event-free survival (EFS) rates were 67% for whites (95% CI, 65% to 69%), 69% for Hispanics (95% CI, 63% to 74%), 62% for Asians (95% CI, 51% to 71%), 56% for blacks (95% CI, 50% to 62%), and 37% for Native American (95% CI, 17% to 58%). Blacks (P < .001) and Native Americans (P = .04) had a higher prevalence of high-risk disease than whites, and significantly worse EFS (P = .01 and P = .002, respectively). Adjustment for risk group abrogated these differences. However, closer examination of the EFS among high-risk patients who remained event free for 2 years or longer, revealed a higher prevalence of late-occurring events among blacks compared with whites (hazard ratio, 1.5; 95% CI, 1.0 to 2.3; P = .04).

Conclusion

Black and Native American patients with neuroblastoma have a higher prevalence of high-risk disease, accounting for their worse EFS when compared with whites. The higher prevalence of late-occurring events among blacks with high-risk disease suggests that this population may be more resistant to chemotherapy. Studies focused on delineating the genetic basis for the racial disparities observed in this study are planned.
Impact of Comorbidity on Chemotherapy Use and Outcomes in Solid Tumors: A Systematic Review
Authors: Lee Linda , Cheung Winson Y. , Atkinson Esther , Krzyzanowska Monika K.
Published: November 2010

Background

The treatment of cancer in patients with comorbidities can be challenging as these individuals are underrepresented in clinical trials. We conducted a systematic review to determine the impact of comorbidity on chemotherapy use, delivery, tolerability, and survival among patients with solid tumors to summarize current data and provide recommendations for future research.

Methods

All English-language articles from 1990 to 2009 that explored the association between comorbidity and chemotherapy were identified from MEDLINE and EMBASE. Abstracts were reviewed for eligibility, and data on study design and results were extracted.

Results

Thirty-four articles met the inclusion criteria. Study populations and design were heterogeneous, and the quality of reporting was generally poor. Most studies were retrospective (76%), were based on a cancer registry linked with administrative data (47%), and assessed the overall effect of comorbidity using an index score (76%). Sixteen studies (47%) investigated chemotherapy use, and 29 (85%) addressed survival. The majority reported decreased chemotherapy use (75%) and inferior survival (69%) for patients with comorbidities compared to those without. In 11 of 14 studies, inferior survival was independent of treatment. Of the few studies that addressed chemotherapy tolerability, seven of 10 reported an increased rate of severe toxicity, and three of five reported increased treatment delays for patients with comorbidity.

Conclusion

Chemotherapy use and outcomes among cancer patients with comorbidities are generally inferior, but the existing evidence is limited and of insufficient quality to determine the relationship between decreased use and inferior survival. Further studies that are prospective and site and stage specific are warranted.
Developmental origins of precocial forelimbs in marsupial neonates
Authors: Keyte Anna L. , Smith Kathleen K.
Published: November 2010

Marsupial mammals are born in an embryonic state, as compared with their eutherian counterparts, yet certain features are accelerated. The most conspicuous of these features are the precocial forelimbs, which the newborns use to climb unaided from the opening of the birth canal to the teat. The developmental mechanisms that produce this acceleration are unknown. Here we show that heterochronic and heterotopic changes early in limb development contribute to forelimb acceleration. Using Tbx5 and Tbx4 as fore- and hindlimb field markers, respectively, we have found that, compared with mouse, both limb fields arise notably early during opossum development. Patterning of the forelimb buds is also accelerated, as Shh expression appears early relative to the outgrowth of the bud itself. In addition, the forelimb fields and forelimb myocyte allocation are increased in size and number, respectively, and migration of the spinal nerves into the forelimb bud has been modified. This shift in the extent of the forelimb field is accompanied by shifts in Hox gene expression along the anterior-posterior axis. Furthermore, we found that both fore- and hindlimb fields arise gradually during gastrulation and extension of the embryonic axis, in contrast to the appearance of the limb fields in their entirety in all other known cases. Our results show a surprising evolutionary flexibility in the early limb development program of amniotes and rule out the induction of the limb fields by mature structures such as the somites or mesonephros.
Epithelial dynamics of pancreatic branching morphogenesis
Authors: Villasenor Alethia , Chong Diana C. , Henkemeyer Mark , Cleaver Ondine
Published: November 2010

The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ.
Initiation of trophectoderm lineage specification in mouse embryos is independent of Cdx2
Authors: Wu Guangming , Gentile Luca , Fuchikami Takuya , Sutter Julien , Psathaki Katherina , Esteves Telma C. , Araúzo-Bravo Marcos J. , Ortmeier Claudia , Verberk Gaby , Abe Kuniya , Schöler Hans R.
Published: November 2010

The separation of the first two lineages – trophectoderm (TE) and inner cell mass (ICM) – is a crucial event in the development of the early embryo. The ICM, which constitutes the pluripotent founder cell population, develops into the embryo proper, whereas the TE, which comprises the surrounding outer layer, supports the development of the ICM before and after implantation. Cdx2, the first transcription factor expressed specifically in the developing TE, is crucial for the differentiation of cells into the TE, as lack of zygotic Cdx2 expression leads to a failure of embryos to hatch and implant into the uterus. However, speculation exists as to whether maternal Cdx2 is required for initiation of TE lineage separation. Here, we show that effective elimination of both maternal and zygotic Cdx2 transcripts by an RNA interference approach resulted in failure of embryo hatching and implantation, but the developing blastocysts exhibited normal gross morphology, indicating that TE differentiation had been initiated. Expression of keratin 8, a marker for differentiated TE, further confirmed the identity of the TE lineage in Cdx2-deficient embryos. However, these embryos exhibited low mitochondrial activity and abnormal ultrastructure, indicating that Cdx2 plays a key role in the regulation of TE function. Furthermore, we found that embryonic compaction does not act as a `switch' regulator to turn on Cdx2 expression. Our results clearly demonstrate that neither maternal nor zygotic Cdx2 transcripts direct the initiation of ICM/TE lineage separation.
The receptor-like kinase KLAVIER mediates systemic regulation of nodulation and non-symbiotic shoot development in Lotus japonicus
Authors: Miyazawa Hikota , Oka-Kira Erika , Sato Naoto , Takahashi Hirokazu , Wu Guo-Jiang , Sato Shusei , Hayashi Masaki , Betsuyaku Shigeyuki , Nakazono Mikio , Tabata Satoshi , Harada Kyuya , Sawa Shinichiro , Fukuda Hiroo , Kawaguchi Masayoshi
Published: November 2010

In legumes, the number of symbiotic root nodules is controlled by long-distance communication between the shoot and the root. Mutants defective in this feedback mechanism exhibit a hypernodulating phenotype. Here, we report the identification of a novel leucine-rich repeat receptor-like kinase (LRR-RLK), KLAVIER (KLV), which mediates the systemic negative regulation of nodulation in Lotus japonicus. In leaf, KLV is predominantly expressed in the vascular tissues, as with another LRR-RLK gene, HAR1, which also regulates nodule number. A double-mutant analysis indicated that KLV and HAR1 function in the same genetic pathway that governs the negative regulation of nodulation. LjCLE-RS1 and LjCLE-RS2 represent potential root-derived mobile signals for the HAR1-mediated systemic regulation of nodulation. Overexpression of LjCLE-RS1 or LjCLE-RS2 did not suppress the hypernodulation phenotype of the klv mutant, indicating that KLV is required and acts downstream of LjCLE-RS1 and LjCLE-RS2. In addition to the role of KLV in symbiosis, complementation tests and expression analyses indicated that KLV plays multiple roles in shoot development, including maintenance of shoot apical meristem, vascular continuity, shoot growth and promotion of flowering. Biochemical analyses using transient expression in Nicotiana benthamiana revealed that KLV has the ability to interact with HAR1 and with itself. Together, these results suggest that the potential KLV-HAR1 receptor complex regulates symbiotic nodule development and that KLV is also a key component in other signal transduction pathways that mediate non-symbiotic shoot development.
An interview with Patrick Tam
Authors: Senior Kathryn
Published: November 2010

Patrick Tam's research is focused on the cellular and molecular mechanisms of body patterning during mouse development. He agreed to be interviewed by Development to talk about his interest in mouse development, new concepts in gastrulation, X-linked diseases and his dream of an African safari.
The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration
Authors: Karpowicz Phillip , Perez Jessica , Perrimon Norbert
Published: November 2010

Identification of the signaling pathways that control the proliferation of stem cells (SCs), and whether they act in a cell or non-cell autonomous manner, is key to our understanding of tissue homeostasis and cancer. In the adult Drosophila midgut, the Jun N-Terminal Kinase (JNK) pathway is activated in damaged enterocyte cells (ECs) following injury. This leads to the production of Upd cytokines from ECs, which in turn activate the Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) pathway in Intestinal SCs (ISCs), stimulating their proliferation. In addition, the Hippo pathway has been recently implicated in the regulation of Upd production from the ECs. Here, we show that the Hippo pathway target, Yorkie (Yki), also plays a crucial and cell-autonomous role in ISCs. Activation of Yki in ISCs is sufficient to increase ISC proliferation, a process involving Yki target genes that promote division, survival and the Upd cytokines. We further show that prior to injury, Yki activity is constitutively repressed by the upstream Hippo pathway members Fat and Dachsous (Ds). These findings demonstrate a cell-autonomous role for the Hippo pathway in SCs, and have implications for understanding the role of this pathway in tumorigenesis and cancer stem cells.
SIMON: A Decade of Physiological Data Research and Development in Trauma Intensive Care
Authors: Norris Patrick R. , Riordan William P. , Dawant Benoit M. , Kleymeer Christopher J. , Jenkins Judith M. , Prestwich Anna E. , Morris John A.
Published: November 2010

SIMON (Signal Interpretation and MONitoring) continuously collects and processes bedside medical device data. As of December 2009, SIMON has monitored over 7,630 trauma intensive care unit (TICU) patients, representing approximately 731,000 hours of continuous monitoring, and is currently operational on all TICU beds at Vanderbilt University Medical Center. Parameters captured include heart rate, blood pressures, oxygen saturations, cardiac function variables, intracranial and cerebral perfusion pressures, and EKG waveforms. This repository supports research to identify “new vital signs” based on features of patient physiology observable through dense data capture and analysis, with the goal of improving predictions of patient status. SIMON′s alerting and reporting capabilities include web display, sentinel event notification, and daily summary reports of traditional and new vital sign statistics. This allows discoveries to be rapidly tested and implemented in a working clinical environment. The work details SIMON′s technology and corresponding design requirements to realize the value of dense physiologic data in critical care.
Heuristic RNA pseudoknot prediction including intramolecular kissing hairpins
Authors: Sperschneider Jana , Datta Amitava , Wise Michael J.
Published: November 2010

Pseudoknots are an essential feature of RNA tertiary structures. Simple H-type pseudoknots have been studied extensively in terms of biological functions, computational prediction, and energy models. Intramolecular kissing hairpins are a more complex and biologically important type of pseudoknot in which two hairpin loops form base pairs. They are hard to predict using free energy minimization due to high computational requirements. Heuristic methods that allow arbitrary pseudoknots strongly depend on the quality of energy parameters, which are not yet available for complex pseudoknots. We present an extension of the heuristic pseudoknot prediction algorithm DotKnot, which covers H-type pseudoknots and intramolecular kissing hairpins. Our framework allows for easy integration of advanced H-type pseudoknot energy models. For a test set of RNA sequences containing kissing hairpins and other types of pseudoknot structures, DotKnot outperforms competing methods from the literature. DotKnot is available as a web server under http://dotknot.csse.uwa.edu.au.
DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in catalytic steps
Authors: Tseng Chi-Kang , Liu Hsueh-Lien , Cheng Soo-Chen
Published: November 2010

The assembly of the spliceosome involves dynamic rearrangements of interactions between snRNAs, protein components, and the pre-mRNA substrate. DExD/H-box ATPases are required to mediate structural changes of the spliceosome, utilizing the energy of ATP hydrolysis. Two DExD/H-box ATPases are required for the catalytic steps of the splicing pathway, Prp2 for the first step and Prp16 for the second step, both belonging to the DEAH subgroup of the protein family. The detailed mechanism of their action was not well understood until recently, when Prp2 was shown to be required for the release of U2 components SF3a and SF3b, presumably to allow the binding of Cwc25 to promote the first transesterification reaction. We show here that Cwc25 and Yju2 are released after the reaction in Prp16- and ATP-dependent manners, possibly to allow for the binding of Prp22, Prp18, and Slu7 to promote the second catalytic reaction. The binding of Cwc25 to the spliceosome is destabilized by mutations at the branchpoint sequence, suggesting that Cwc25 may bind to the branch site. We also show that Prp16 has an ATP-independent role in the first catalytic step, in addition to its known role in the second step. In the absence of ATP, Prp16 stabilizes the binding of Cwc25 to the spliceosome formed with branchpoint mutated pre-mRNAs to facilitate their splicing. Our results uncovered novel functions of Prp16 in both catalytic steps, and provide mechanistic insights into splicing catalysis.
Solubility of tetravalent actinides in alkaline CaCl2solutions and formation of Ca4[An(OH)8]4+complexes: A study of Np(IV) and Pu(IV) under reducing conditions and the systematic trend in the An(IV) series
Authors: Fellhauer D. , Neck Volker , Altmaier Marcus , Lützenkirchen Johannes , Fanghänel Thomas
Published: November 2010

The solubility of Np(IV) and Pu(IV) hydrous oxides was studied at 22±2 °C under reducing conditions in alkaline CaCl2solutions. Redox conditions were adjusted either with 2 mM Na2S2O4or additions of iron powder. In 2.0 and 4.5 M CaCl2and pHc=11–12, the neptunium and plutonium concentrations increase with a slope of +4 (log[An]vs. pHc) as expected for the formation of the complex Ca4[An(OH)8]4+recently identified for Th(IV). At CaCl2concentrations ≤1.0 M this effect is negligible for both Np(IV) and Pu(IV). The conditional equilibrium constants log*Ks,(4,1,8)for the reaction

An(OH)4(am) + 4 H2O + 4 Ca2+⇔ Ca4[An(OH)8]4++ 4 H+

are evaluated with the SIT and Pitzer model using the parameters derived from analogous data for Th(IV) in 0.5–4.5 M CaCl2. The log*K°s,(4,1,8)values and the complex formation constants logβ°(4,1,8)follow systematic trends in the series Th(IV), Np(IV) and Pu(IV) which allows the estimation of the corresponding data for U(IV).
Solubility of triuranyl diphosphate tetrahydrate (TDT) and Na autunite at 23 and 50 °C
Authors: Armstrong Christopher R. , Felmy Andrew R. , Clark Sue B.
Published: November 2010

In this report we present experimental solubility data for well-characterized triuranyl diphosphate tetrahydrate (TDT: (UO2)3(PO4)2·4H2O) and Na autunite (Na[UO2PO4]· x H2O) at 23 and 50 °C in NaClO4-HClO4 solutions at pCH+
=2. Duplicate samples of TDT in 0.1, 0.5, 1.0, 2.0 and 5.0 m solutions were equilibrated at 23 and 50 °C. TDT solid was synthesized and characterized with ICP-OES, ATR-IR and powder XRD before and after solubility experiments. The pH of the suspensions were monitored throughout the experiments. Equilibrium was achieved from undersaturation with respect to TDT and oversaturation for Na autunite. Steady-state conditions were achieved in all cases within 82 d. TDT was unstable at ionic strengths above 0.1 m, where its complete conversion to Na autunite was observed. The ion-interaction model was used to interpret the experimental solubility data. The solubility product, logߙK
sp, for TDT was determined to be −49.7 and −51.3 at 23 and 50 °C respectively. logߙK
sp for Na autunite was determined to be −24.4 (23 °C) and −24.1±0.2 (50 °C).
Complexation of Nd(III) with tetraborate ion and its effect on actinide(III) solubility in WIPP brine
Authors: Borkowski Marian , Richmann Michael , Reed Donald T. , Xiong Yongliang
Published: November 2010

The potential importance of tetraborate complexation on lanthanide(III) and actinide(III) solubility is recognized in the literature but a systematic study of f-element complexation has not been performed. In neodymium solubility studies in WIPP brines, the carbonate complexation effect is not observed since tetraborate ions form a moderately strong complex with neodymium(III). The existence of these tetraborate complexes was established for low and high ionic strength solutions. Changes in neodymium(III) concentrations in undersaturation experiments were used to determine the neodymium with tetraborate stability constants as a function of NaCl ionic strength. As very low Nd(III) concentrations have to be measured, it was necessary to use an extraction pre-concentration step combined with ICP-MS analysis to extend the detection limit by a factor of 50.

The determined Nd(III) with borate stability constants at infinite dilution and 25 °C are equal to logβ1=4.55±0.06 using the SIT approach, equal to logβ1=4.99±0.30 using the Pitzer approach, with an apparent logβ1=4.06±0.15 (in molal units) at I=5.6 m NaCl. Pitzer ion-interaction parameters for neodymium with tetraborate and SIT interaction coefficients were also determined and reported.