bluuebunny/crossref_metadata_2025 huggingface dataset:
Late-Holocene palaeoecology of a polygonal peatland on the south shore of Hudson Strait, northern Québec, Canada
Authors: Ouzilleau Samson David , Bhiry Najat , Lavoie Martin
Published: March 2010

In order to document climate fluctuations during the late Holocene in Nunavik (in the Québec Arctic), a 182 cm peat core extracted from a polygonal peatland in the Salluit region was subjected to macrofossil and pollen analysis. Peat accumulation began around 4500 cal. BP in the peatland and 2340 cal. BP in the core site following the formation of frost cracks and ice wedges. Four distinct Holocene climatic changes were identified. Between 1910 and 1100 cal. BP, the climate was clement (similar to today’s climate), which favoured the growth of several species of Sphagnum (from poorly minerotrophic to ombrotrophic conditions). Colder and drier conditions starting around 1100 cal. BP are evidenced by the disappearance of Sphagnum and aeolian sedimentation. A short return to more clement conditions occurred around 870 cal. BP and lasted until 670 cal. BP. Subsequently, the climate once again became colder and drier, which induced significant aeolian activity. Late-Holocene local vegetation changes recorded in the peat core were probably induced by permafrost degradation and aggradation, associated with regional warming and a subsequent cooling trend.
The History of Legislation and Regulations Related to Children With Developmental Disabilities
Authors: Dang Michelle T.
Published: March 2010

A significant number of children in the United States have developmental disabilities. Historically, many children with developmental disabilities were institutionalized and rarely seen in public. Currently, children with developmental disabilities are entitled to education and health-related support services that permit them access to public education and community services. To understand current laws related to children with developmental disabilities, it is important to consider past legislation and landmark court cases that have significantly affected the lives of children with disabilities and school nursing practice. This article presents an overview of historical legislation and court cases as they pertain to children and individuals with developmental disabilities and of current issues that require further attention and inquiry.
Mothers, Domestic Violence, and Child Protection
Authors: Douglas Heather , Walsh Tamara
Published: March 2010

This article explores the relationship between understandings of domestic violence and the child protection response drawing on material gathered in focus groups with workers who support mothers dealing with both domestic violence and child protection issues. The interviewees expressed concern that the dynamics of domestic violence are often misunderstood and inappropriately responded to by child protection workers.This article critically examines the interviewees’ concerns and concludes that to properly protect children, it is crucial that child protection workers have a clear understanding of the dynamics of and issues related to domestic violence.
Does a common ingroup identity reduce intergroup threat?
Authors: Riek Blake M. , Mania Eric W. , Gaertner Samuel L. , McDonald Stacy A. , Lamoreaux Marika J.
Published: March 2010

Intergroup threat is regarded as a cause of negative outgroup attitudes; however, little research has attempted to examine ways of reducing intergroup threat. Two studies examine the effectiveness of a superordinate identity for reducing intergroup threat. It was predicted that when two groups were aware of a shared identity, intergroup threat would be lowered and attitudes would become more positive. In Study 1, perceptions of common identities among Black and White students were related to decreases in intergroup threat and increases in positive outgroup attitudes. In Study 2, when their shared identity as Americans was made salient, Democrats and Republicans experienced less threat and more positive outgroup attitudes compared to when political party identities alone were salient. In both studies, intergroup threat acted as a mediator of the relationship between common identity and outgroup attitudes, suggesting that a common identity increases positive outgroup attitudes by first reducing intergroup threat.
Intergroup bias in weight controllability attributions
Authors: Popan Jason R. , Kenworthy Jared B. , Barden Melisa A. , Griffiths Jenny
Published: March 2010

We examined weight controllability attributions for obese and non-obese targets who were either racial ingroup or outgroup members, predicting that attributions would be biased in favor of ingroup targets. In Experiment 1, white British participants attributed more controllability to obese than to non-obese targets overall, and this effect was more pronounced for black than for white targets. In Experiment 2, white and black American participants rated targets that were racial ingroup or outgroup members, fit or obese, and male or female. Again, the simple effect of target weight was stronger for racial outgroup than for racial ingroup targets. Consistent with past research on hierarchical category dominance for gender, the effects were stronger for same-gender targets than for opposite-gender targets.
Identifying needs, burden, and distress of carers of people with Frontotemporal dementia compared to Alzheimer’s disease
Authors: Nicolaou Paula L. , Egan Sarah J. , Gasson Natalie , Kane Robert T.
Published: March 2010

The literature on carers of people with Frontotemporal dementia (FTD) is negligible compared to the vast literature on carers of people with Alzheimer’s disease (AD), and little research has compared the two groups. Research has mainly focused on identifying the behavioural characteristics of people with FTD or AD. The impact of these behaviours on the psychological well-being of carers of people with FTD is relatively unexplored. This study investigated the needs, burden, and extent of depression and anxiety in carers of people with FTD ( n = 30) compared to carers of people with AD ( n = 30). Findings indicated that needs of carers of people with FTD were significantly higher than those of the carers of people with AD. The elevated needs were related to the younger onset of FTD, financial dissatisfaction, typical FTD characteristics, and access to appropriate services, information and support. Results also suggested that female carers were more likely to report a greater severity and impact of disruptive symptoms associated with FTD. No significant differences were found between the two groups on carers’ levels of burden, depression or anxiety. In order to address the needs of carers of people with FTD, we recommend specific educational and support programs, raising community awareness and understanding, and tailoring existing domiciliary services and activities for people with FTD.
Supporting persons with Down syndrome and advanced dementia
Authors: McCarron Mary , McCallion Philip , Fahey-McCarthy Elizabeth , Connaire Kevin , Dunn-Lane Jean
Published: March 2010

Aim: To understand staff perceptions of critical issues in caring for persons with intellectual disability (ID) and advanced dementia. Background: There has been growing interest in addressing resource, training, and service redesign issues including an increase in collaborative practices in response to the growing incidence of dementia among persons with ID. Most recently this has included consideration of the specific issues in advanced dementia.

Method: Thirteen focus group interviews were held involving staff in six ID services and one specialist palliative care provider in Ireland. A qualitative descriptive approach was taken to analysis.

Results: Staff identified three key themes: (1) readiness to respond to end of life needs, (2) the fear of swallowing difficulties, and (3) environmental concerns and ageing in place.

Discussion: Four underlying issues that emerged in this study offer clues to solutions: (a) differences in staff preparation associated with settings, (b) lack of understanding and lack of collaboration with palliative care services, (c) uncertainties about the ability to transfer existing palliative care models to persons with ID and dementia and (d) the need to develop training on end stage dementia and related care approaches.
Mealtimes and being connected in the community-based dementia context
Authors: Keller Heather H. , Schindel Martin Lori , Dupuis Sherry , Genoe Rebecca , Gayle Edward H. , Cassolato Carly
Published: March 2010

Mealtimes provide an opportunity for social activity and emotional connection. This grounded theory study focused on the meaning and experience of mealtimes in families living with dementia in the community; 28 partners in care and 27 persons with dementia were interviewed together and separately. Team analysis resulted in the development of a substantive theory which explains how eating together ‘mirrors the way we are’ and reveals the essence of what it is to be human while living with dementia. Mealtimes reflect how these families were being connected, honouring identity and adapting to an evolving life. This article focuses on three ways in which Being Connected occurs at mealtimes: being face to face, participating psychologically, and getting and giving support. Understanding the role that mealtimes play in promoting improved connections and thus relationships within the dementia context has important implications for both formal and family care partners.
Structural Health Management in the NAVY
Authors: Perez Ignacio , DiUlio Michael , Maley Scott , Phan Nam
Published: March 2010

There is a critical need for integrated system health management (ISHM) approaches to asset maintenance. Ideally, ISHM methodologies would track the system usage and the associated loads, monitor the system degradation and materials state, monitor relevant environmental parameters and their effects on system degradation, detect insipient system damage, diagnose failure mode, predict future system performance, and recommend maintenance actions. Even though there has been considerable progress in many subareas of ISHM over the past years, there is still ample room for future improvements in all technological aspects affecting ISHM. In fact, progress in ISHM has not been uniform. Some subsystems have experienced a far greater degree of development than others. For example, engine and machinery health monitoring and diagnostics, due to its criticality, has evolved at a faster pace than structural health monitoring. This article will review some of the aspects that need to be addressed in order to make structural health monitoring (SHM) of military systems a reality in the near future.
Structural Health Monitoring, In-service Experience, Benefit and Way Ahead
Authors: Stolz Christian , Neumair Manfred
Published: March 2010

The structural health monitoring (SHM) is an important requirement to handle military aircraft safety. In contrast with civil aircraft, the missions, configurations and environments are changing frequently and therefore also the load spectra, which lead to a various life consumption. To ensure the structural integrity of the airframe and structural systems by SHM systems the following four functions are essential: Event and fatigue monitoring, including remaining life assessment and damage detection monitoring. This is the basis for an economic and safety in-service operation of a flying weapon system.

This article shows the way from a simple monitoring system to a state-of-the-art support system based on examples from the German Air Force (GAF). From a military aircraft manufacturer’s point of view, the pro and contra of these systems based on in-service experience of various aircraft types are listed. Referring to this experience the benefit of the modernization of SHM-System will be presented and the requirements on a modern SHM-System especially for the ground support system and the logistic and in addition for new monitoring areas will be worked out. The approach for hot spot monitoring for damage detection is explained. A special view will be given on the possible integration of modern damage detection methods in existing and new SHM-Systems. Furthermore the combination of damage detection system and existing usage monitoring systems opens the way for enhanced monitoring systems.
Lactic acid levels in patients with chronic obstructive pulmonary disease accomplishing unsupported arm exercises
Authors: de Souza Gérson F , Castro Antonio AM , Velloso Marcelo , Silva Camille R , Jardim José R
Published: March 2010

Patients with chronic obstructive pulmonary disease (COPD) may suffer dyspnea when performing unsupported arm exercises (UAE). However, some factors related to the tolerance of the upper limbs during these exercises are not well understood. Our investigation was to determine if an unsupported arm exercise test in patients with COPD accomplishing diagonal movements increases lactic acid levels; also, we assessed the metabolic, ventilatory and cardiovascular responses obtained from the unsupported arm exercise test. The study used results of maximal symptom limited tests with unsupported arms and legs performed on 16 patients with COPD. In order to do the test, some metabolic, respiratory and cardiovascular parameters such as oxygen uptake (VO2), carbon dioxide production (VCO2), respiratory rate (RR), pulmonary ventilation (VE), heart rate (HR) and blood pressure (BP) were measured during the exercise tests. Furthermore, blood lactate concentration was measured during the arm test. We detected a significant increase in the mean blood lactate concentration, VO2, VCO 2, VE and RR from the resting to the peak phase of the UAE test. The mean values of VO2, VCO2 and VE obtained at the peak of the UAE test corresponded to 52.5%, 50.0% and 61.2%, respectively, of the maximal values obtained at the peak of the leg exercise test. In comparison, the mean heart rate and systolic arterial blood pressure were significantly lower at the peak of the UAE test than at the peak leg exercise test and corresponded to 76.2% and 83.0%, respectively. Unsupported incremental arm exercises in patients with COPD increases blood lactic acid levels.
Long-term outcome of division of the C8 nerve root for spasticity of the hand in cerebral palsy
Authors: Lin H. , Hou C. , Chen A. , Xu Z.
Published: March 2010

Division of the C8 nerve root results in short-term relief of spasticity in the hands of cerebral palsy patients. In the present study, we assessed the long-term outcome of C8 nerve root division. Between March 1997 and January 2002, this procedure was done in 13 patients. All received consistent postoperative functional rehabilitation training. The hands were assessed before operation and at follow-up using the Lazareff grading system. The average follow-up time was 8.6 years. Two hands showed excellent improvement, three limbs showed good improvement and eight hands showed no improvement. No long-term complications occurred in any patient. These results indicate that the long-term outcome of C8 nerve root rhizotomy for the treatment of hand spasticity in CP is generally poor.
Review: Anti-tumor necrosis factor therapy and influenza: keeping it in perspective
Authors: Shale Matt , Czub Markus , Kaplan Gilaad G. , Panaccione Remo , Ghosh Subrata
Published: March 2010

The association of opportunistic infections in the context of anti-tumor necrosis factor (TNF) antibody therapies have attracted widespread attention. The recent H1N1 influenza pandemic brought this into sharp focus with numerous patient queries and physician anxieties. The following short review gives a scientific perspective to this issue including the role of vaccination.
Safety and efficacy of weekly 5-fluorouracil/ folinic acid/oxaliplatin/irinotecan in the first-line treatment of gastrointestinal cancer
Authors: Peinert Stefan , Grothe Wilfried , Stein Alexander , Müller Lutz P. , Ruessel Joern , Voigt Wieland , Schmoll Hans-Joachim , Arnold Dirk
Published: March 2010

Background: Standard chemotherapy for patients with metastatic colorectal cancer (mCRC) or gastric cancer (GC) consists of two-drug, usually fluoropyrimidine-based, combinations, with or without the addition of biological agents. Studies of triple-drug regimens combining 5-fluorouracil (5-FU)/folinic acid (FA) with both oxaliplatin and irinotecan have shown promising efficacy in studies of patients with mCRC or GC. However, improved efficacy has often been achieved at the expense of high rates of grade 3 or 4 toxicities such as neutropenia and diarrhoea, occasionally even resulting in toxic deaths.

Objective/Methods: We performed a phase II study of previously untreated patients with mCRC or GC to assess the safety and efficacy of our 5-fluorouracil/folinic acid/oxaliplatin/irinotecan (FUFOXIRI) regimen with weekly administration of irinotecan 70 mg/m 2, oxaliplatin 50 mg/m2, FA 500 mg/m2 and 5-FU 2000 mg/m2 on days 1, 8, 15 and 22, repeated from day 36.

Results: A total of 22 patients were enrolled, 11 each with mCRC and GC receiving a median of four cycles per patient. The FUFOXIRI regimen was generally well tolerated with no toxic deaths, neutropenic fever or grade 4 toxicities. Most common grade 3 side effects were diarrhoea and neutropenia each affecting 24% of patients. Dose reductions due to toxicity were performed in 48% of all and 60% of patients having received at least two cycles of FUFOXIRI. The overall response rate was 46% (all partial responses), 55% and 36% for patients with mCRC and GC, respectively. Median progression-free survival for all patients, mCRC and GC patients was 9.5, 10.0 and 8.0 months, respectively. The median overall survival for all patients was 16.5, 18.0 and 15.0 months for patients with mCRC and GC, respectively.

Conclusion: These data show excellent tolerance and efficacy of the FUFOXIRI regimen in both mCRC and GC. Therefore, FUFOXIRI is a promising backbone for future studies incorporating biologic ‘targeted’ agents for the treatment of gastrointestinal cancers.
Microfracture
Authors: Steadman J. Richard , Rodkey William G. , Briggs Karen K.
Published: March 2010

Development and implementation of the microfracture technique began in the early 1980s. The surgical goal was to produce “microfractures” in the subchondral bone perpendicular to the surface and to be able to reach all areas of the joint with the instruments. The microfracture technique has been demonstrated to be an effective arthroscopic treatment for full-thickness chondral lesions and joints with degenerative lesions. This technique is cost effective, technically not complicated, has an extremely low rate of associated patient morbidity, and leaves options for further treatment. Patient compliance with rehabilitation, knee alignment, and the depth of the cartilage rim surrounding the lesion are a few of the factors that can affect the outcomes following microfracture.
CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells
Authors: Guo Yong-Mei , Ishii Keiko , Hirokawa Makoto , Tagawa Hiroyuki , Ohyagi Hideaki , Michishita Yoshihiro , Ubukawa Kumi , Yamashita Junsuke , Ohteki Toshiaki , Onai Nobuyuki , Kawakami Kazuyoshi , Xiao Weiguo , Sawada Kenichi
Published: March 2010

Recent studies have shown that anemia is commonly observed after exposure to pathogens or pathogen-derived products, which are recognized via Toll-like receptor 9 (TLR9). In the current study, we demonstrate that CpG oligodeoxynucleotide-2006, a TLR9 ligand with phosphodiester (PO; 2006-PO) but not with the phosphorothioate backbone, selectively inhibits the erythroid growth derived from human CD34+ cells. The 2006-PO was internalized by the erythroid progenitors within 30 minutes; however, expression of TLR9 mRNA was not detected in these cells. The 2006-PO directly inhibited burst-forming unit-erythroid growth, resulted in the accumulation of cells in S and G2/M phases, and increased cell size and frequency of apoptotic cells. These features were similar to those observed in erythroid progenitors infected with human parvovirus B19 that causes pure red cell aplasia. The consensus sequence of 2006-PO was defined as 5′-GTTTTGT-3′, which was located in the P6-promoter region of B19 and inhibited erythroid growth in a sequence-specific manner and down-regulated expression of erythropoietin receptor (EPOR) mRNA and EPOR. B19 genome extracted from serum also inhibited erythroid growth and down-regulated expression of EPOR on glycophorin A+ cells. These results provide a possible insight into our understanding of the mechanisms of human parvovirus B19-mediated inhibition of erythropoiesis.
Long-term study of indolent adult T-cell leukemia-lymphoma
Authors: Takasaki Yumi , Iwanaga Masako , Imaizumi Yoshitaka , Tawara Masayuki , Joh Tatsuro , Kohno Tomoko , Yamada Yasuaki , Kamihira Shimeru , Ikeda Schuichi , Miyazaki Yasushi , Tomonaga Masao , Tsukasaki Kunihiro
Published: March 2010

The long-term prognosis of indolent adult T-cell leukemia-lymphoma (ATL) is not clearly elucidated. From 1974 to 2003, newly diagnosed indolent ATL in 90 patients (65 chronic type and 25 smoldering type) was analyzed. The median survival time was 4.1 years; 12 patients remained alive for more than 10 years, 44 progressed to acute ATL, and 63 patients died. The estimated 5-, 10-, and 15-year survival rates were 47.2%, 25.4%, and 14.1%, respectively, with no plateau in the survival curve. Although most patients were treated with watchful waiting, 12 patients were treated with chemotherapy. Kaplan-Meier analyses showed that advanced performance status (PS), neutrophilia, high concentration of lactate dehydrogenase, more than 3 extranodal lesions, more than 4 total involved lesions, and receiving chemotherapy were unfavorable prognostic factors for survival. Multivariate Cox analysis showed that advanced PS was a borderline significant independent factor in poor survival (hazard ratio, 2.1, 95% confidence interval, 1.0-4.6; P = .06), but it was not a factor when analysis was limited to patients who had not received chemotherapy. The prognosis of indolent ATL in this study was poorer than expected. These findings suggest that even patients with indolent ATL should be carefully observed in clinical practice. Further studies are required to develop treatments for indolent ATL.
The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma
Authors: Spagnuolo Paul A. , Hu Jiayi , Hurren Rose , Wang Xiaoming , Gronda Marcela , Sukhai Mahadeo A. , Di Meo Ashley , Boss Jonathan , Ashali Iman , Beheshti Zavareh Reza , Fine Noah , Simpson Craig D. , Sharmeen Sumaiya , Rottapel Rob , Schimmer Aaron D.
Published: March 2010

On-patent and off-patent drugs with previously unrecognized anticancer activity could be rapidly repurposed for this new indication given their prior toxicity testing. To identify such compounds, we conducted chemical screens and identified the antihelmintic flubendazole. Flubendazole induced cell death in leukemia and myeloma cell lines and primary patient samples at nanomolar concentrations. Moreover, it delayed tumor growth in leukemia and myeloma xenografts without evidence of toxicity. Mechanistically, flubendazole inhibited tubulin polymerization by binding tubulin at a site distinct from vinblastine. In addition, cells resistant to vinblastine because of overexpression of P-glycoprotein remained fully sensitive to flubendazole, indicating that flubendazole can overcome some forms of vinblastine resistance. Given the different mechanisms of action, we evaluated the combination of flubendazole and vinblastine in vitro and in vivo. Flubendazole synergized with vinblastine to reduce the viability of OCI-AML2 cells. In addition, combinations of flubendazole with vinblastine or vincristine in a leukemia xenograft model delayed tumor growth more than either drug alone. Therefore, flubendazole is a novel microtubule inhibitor that displays preclinical activity in leukemia and myeloma.
Age-dependent vulnerability to endotoxemia is associated with reduction of anticoagulant factors activated protein C and thrombomodulin
Authors: Starr Marlene E. , Ueda Junji , Takahashi Hitoshi , Weiler Hartmut , Esmon Charles T. , Evers B. Mark , Saito Hiroshi
Published: March 2010

The protein C (PC) pathway is an important anticoagulant mechanism that prevents thrombosis during the systemic inflammatory response. Thrombomodulin (TM), an endothelial cell membrane receptor, accelerates the conversion of PC to activated protein C (APC), which leads to the down-regulation of thrombin production and fibrin formation. Induction of acute endotoxemia in young and aged mice with a low dose of bacterial endotoxin lipopolysaccharide (LPS, 2.5 mg/kg) caused a high mortality rate in aged (80%) but not young (0%) mice. After injection with this dose of LPS, fibrin formation was significantly elevated only in aged mice, plasma APC levels were increased only in young mice, and TM expression was profoundly depressed in the aged. The increased thrombosis, suppressed APC level, and decreased TM expression were not observed in young mice receiving a higher dose of LPS (20 mg/kg), which resulted in a mortality rate (78%) equivalent to that seen in aged mice with the low-dose LPS. Mutant mice with reduced TM showed significantly less plasma APC and increased fibrin formation compared with wild-type mice after LPS. These results demonstrate that PC pathway activation is suppressed with aging and is partly responsible for age-associated thrombosis and high mortality during endotoxemia.
Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor
Authors: Zhu Donghui , Wang Yaoming , Singh Itender , Bell Robert D. , Deane Rashid , Zhong Zhihui , Sagare Abhay , Winkler Ethan A. , Zlokovic Berislav V.
Published: March 2010

The anticoagulant factor protein S (PS) has direct cellular activities. Lack of PS in mice causes lethal coagulopathy, ischemic/thrombotic injuries, vascular dysgenesis, and blood-brain barrier (BBB) disruption with intracerebral hemorrhages. Thus, we hypothesized that PS maintains and/or enhances the BBB integrity. Using a BBB model with human brain endothelial cells, we show PS inhibits time- and dose-dependently (half maximal effective concentration [EC50] = 27 ± 3 nM) oxygen/glucose deprivation-induced BBB breakdown, as demonstrated by measurements of the transmonolayer electrical resistance, permeability of endothelial monolayers to dextran (40 kDa), and rearrangement of F-actin toward the cortical cytoskeletal ring. Using Tyro-3, Axl, and Mer (TAM) receptor, tyrosine kinase silencing through RNA interference, specific N-terminus–blocking antibodies, Tyro3 phosphorylation, and Tyro3-, Axl- and Mer-deficient mouse brain endothelial cells, we show that Tyro3 mediates PS vasculoprotection. After Tyro3 ligation, PS activated sphingosine 1-phosphate receptor (S1P1), resulting in Rac1-dependent BBB protection. Using 2-photon in vivo imaging, we show that PS blocks postischemic BBB disruption in Tyro3+/+, Axl−/−, and Mer−/− mice, but not in Tyro3−/− mice or Tyro3+/+ mice receiving low-dose W146, a S1P1-specific antagonist. Our findings indicate that PS protects the BBB integrity via Tyro3 and S1P1, suggesting potentially novel treatments for neurovascular dysfunction resulting from hypoxic/ischemic BBB damage.
Complexity of cis-regulatory organization of six3aduring forebrain and eye development in zebrafish
Authors: Chao Chung-Hao , Wang Horng-Dar , Yuh Chiou-Hwa
Published: March 2010

Background

Six3a belongs to the SIX family of homeodomain proteins and is expressed in the most anterior neural plate at the beginning of neurogenesis in various species. Though the function of Six3a as a crucial regulator of eye and forebrain development has been thoroughly investigated, the transcriptional regulation of six3a is not well understood.

Results

To elucidate the transcriptional regulation of six3a, we performed an in vivo reporter assay. Alignment of the 21-kb region surrounding the zebrafish six3a gene with the analogous region from different species identified several conserved non-coding modules. Transgenesis in zebrafish identified two enhancer elements and one suppressor. The D module drives the GFP reporter in the forebrain and eyes at an early stage, while the A module is responsible for the later expression. The A module also works as a repressor suppressing ectopic expression from the D module. Mutational analysis further minimized the A module to four highly conserved elements and the D module to three elements. Using electrophoresis mobility shift assays, we also provided evidence for the presence of DNA-binding proteins in embryonic nuclear extracts. The transcription factors that may occupy those highly conserved elements were also predicted.

Conclusion

This study provides a comprehensive view of six3a transcription regulation during brain and eye development and offers an opportunity to establish the gene regulatory networks underlying neurogenesis in zebrafish.
The Mediterranean Sea as a barrier to gene flow: evidence from variation in and around the F7 and F12 genomic regions
Authors: Athanasiadis Georgios , González-Pérez Emili , Esteban Esther , Dugoujon Jean-Michel , Stoneking Mark , Moral Pedro
Published: March 2010

Background

The Mediterranean has a long history of interactions among different peoples. In this study, we investigate the genetic relationships among thirteen population samples from the broader Mediterranean region together with three other groups from the Ivory Coast and Bolivia with a particular focus on the genetic structure between North Africa and South Europe. Analyses were carried out on a diverse set of neutral and functional polymorphisms located in and around the coagulation factor VII and XII genomic regions (F7 and F12).

Results

Principal component analysis revealed a significant clustering of the Mediterranean samples into North African and South European groups consistent with the results from the hierarchical AMOVA, which showed a low but significant differentiation between groups from the two shores. For the same range of geographic distances, populations from each side of the Mediterranean were found to differ genetically more than populations within the same side. To further investigate this differentiation, we carried out haplotype analyses, which provided partial evidence that sub-Saharan gene flow was higher towards North Africa than South Europe.

Conclusions

As there is no consensus between the two genomic regions regarding gene flow through the Sahara, it is hard to reach a solid conclusion about its role in the differentiation between the two Mediterranean shores and more data are necessary to reach a definite conclusion. However our data suggest that the Mediterranean Sea was at least partially a barrier to gene flow between the two shores.
Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland
Authors: Mitterhuemer Simone , Petzl Wolfram , Krebs Stefan , Mehne Daniel , Klanner Andrea , Wolf Eckhard , Zerbe Holm , Blum Helmut
Published: March 2010

Background

Coliform bacteria are the most common etiologic agents in severe mastitis of cows.Escherichia coliinfections are mostly restricted to a single udder quarter whereas neighboring quarters stay clinically inapparent, implicating the presence of a systemic defense reaction. To address its underlying mechanism, we performed a transcriptome study of mammary tissue from udder quarters inoculated withE. coli(6 h and 24 h post infection), from neighboring quarters of the same animals, and from untreated control animals.

Results

After 6 h 13 probe sets of differentially expressed genes (DEG) were detected in infected quarters versus control animals. Eighteen hours later 2154 and 476 DEG were found in infected and in neighboring quarters vs. control animals. Cluster analysis revealed DEG found only in infected quarters (local response) and DEG detected in both infected and neighboring quarters (systemic response). The first group includes genes mainly involved in immune response and inflammation, while the systemic reaction comprises antigen processing and presentation, cytokines, protein degradation and apoptosis. Enhanced expression of antimicrobial genes (S100A8,S100A9,S100A12,CXCL2,GNLY), acute phase genes (LBP,SAA3,CP,BF, C6,C4BPA,IF), and indicators of oxidative stress (GPX3,MT1A,MT2A,SOD2) point to an active defense reaction in infected and neighboring healthy quarters. Its early onset is indicated by increased transcription ofNFIL3at 6 h. NFIL3 is a predicted regulator of many genes of the systemic response at 24 h. The significance of our transcriptome study was evidenced by some recent findings with candidate gene based approaches.

Conclusions

The discovery and holistic analysis of an extensive systemic reaction in the mammary gland significantly expands the knowledge of host-pathogen interactions in mastitis which may be relevant for the development of novel therapies and for genetic selection towards mastitis resistance.
Study of the functionality of the Helicobacter pylori trans-translation components SmpB and SsrA in an heterologous system
Authors: Thibonnier Marie , Aubert Sylvie , Ecobichon Chantal , De Reuse Hilde
Published: March 2010

Background

Trans-translation is a ubiquitous bacterial quality control-mechanism for both transcription and translation. With its two major partners, SsrA a small stable RNA and the SmpB protein, it promotes the release of ribosomes stalled on defective mRNAs and directs the corresponding truncated proteins to degradation pathways. We have recently shown that trans-translation is an essential function in the gastric pathogen Helicobacter pylori. Our results suggested that some properties of the H. pylori trans-translation machinery distinguishes it from the well known system in E. coli. Therefore, we decided to test the functionality of the SmpB and SsrA molecules of H. pylori in the E. coli heterologous system using two established phenotypic tests.

Results

H. pylori SmpB protein was found to successfully restore the E. coli ΔsmpB mutant growth defect and its capacity to propagate λimm
P22 phage. We showed that in E. coli, H. pylori SsrA (Hp-SsrA) was stably expressed and maturated and that this molecule could restore wild type growth to the E. coli ΔssrA mutant. Hp-SsrA mutants affected in the ribosome rescue function were not able to restore normal growth to E. coli ΔssrA supporting a major role of ribosome rescue in this phenotype. Surprisingly, Hp-SsrA did not restore the phage λimm
P22 propagation capacity to the E. coli ΔssrA mutant.

Conclusions

These data suggest an additional role of the tag sequence that presents specific features in Hp-SsrA. Our interpretation is that a secondary role of protein tagging in phage propagation is revealed by heterologous complementation because ribosome rescue is less efficient. In conclusion, tm RNAs present in all eubacteria, have coevolved with the translational machinery of their host and possess specific determinants that can be revealed by heterologous complementation studies.
The four hexamerin genes in the honey bee: structure, molecular evolution and function deduced from expression patterns in queens, workers and drones
Authors: Martins Juliana R , Nunes Francis MF , Cristino Alexandre S , Simões Zilá LP , Bitondi Márcia MG
Published: March 2010

Background

Hexamerins are hemocyanin-derived proteins that have lost the ability to bind copper ions and transport oxygen; instead, they became storage proteins. The current study aimed to broaden our knowledge on the hexamerin genes found in the honey bee genome by exploring their structural characteristics, expression profiles, evolution, and functions in the life cycle of workers, drones and queens.

Results

The hexamerin genes of the honey bee (hex 70a, hex 70b, hex 70c and hex 110) diverge considerably in structure, so that the overall amino acid identity shared among their deduced protein subunits varies from 30 to 42%. Bioinformatics search for motifs in the respective upstream control regions (UCRs) revealed six overrepresented motifs including a potential binding site for Ultraspiracle (Usp), a target of juvenile hormone (JH). The expression of these genes was induced by topical application of JH on worker larvae. The four genes are highly transcribed by the larval fat body, although with significant differences in transcript levels, but only hex 110 and hex 70a are re-induced in the adult fat body in a caste- and sex-specific fashion, workers showing the highest expression. Transcripts for hex 110, hex 70a and hex70b were detected in developing ovaries and testes, and hex 110 was highly transcribed in the ovaries of egg-laying queens. A phylogenetic analysis revealed that HEX 110 is located at the most basal position among the holometabola hexamerins, and like HEX 70a and HEX 70c, it shares potential orthology relationship with hexamerins from other hymenopteran species.

Conclusions

Striking differences were found in the structure and developmental expression of the four hexamerin genes in the honey bee. The presence of a potential binding site for Usp in the respective 5' UCRs, and the results of experiments on JH level manipulation in vivo support the hypothesis of regulation by JH. Transcript levels and patterns in the fat body and gonads suggest that, in addition to their primary role in supplying amino acids for metamorphosis, hexamerins serve as storage proteins for gonad development, egg production, and to support foraging activity. A phylogenetic analysis including the four deduced hexamerins and related proteins revealed a complex pattern of evolution, with independent radiation in insect orders.
Efficacy of capillary pattern type IIIA/IIIB by magnifying narrow band imaging for estimating depth of invasion of early colorectal neoplasms
Authors: Ikematsu Hiroaki , Matsuda Takahisa , Emura Fabian , Saito Yutaka , Uraoka Toshio , Fu Kuang-I , Kaneko Kazuhiro , Ochiai Atsushi , Fujimori Takahiro , Sano Yasushi
Published: March 2010

Background

Capillary patterns (CP) observed by magnifying Narrow Band Imaging (NBI) are useful for differentiating non-adenomatous from adenomatous colorectal polyps. However, there are few studies concerning the effectiveness of magnifying NBI for determining the depth of invasion in early colorectal neoplasms. We aimed to determine whether CP type IIIA/IIIB identified by magnifying NBI is effective for estimating the depth of invasion in early colorectal neoplasms.

Methods

A series of 127 consecutive patients with 130 colorectal lesions were evaluated from October 2005 to October 2007 at the National Cancer Center Hospital East, Chiba, Japan. Lesions were classified as CP type IIIA or type IIIB according to the NBI CP classification. Lesions were histopathologically evaluated. Inter and intraobserver variabilities were assessed by three colonoscopists experienced in NBI.

Results

There were 15 adenomas, 66 intramucosal cancers (pM) and 49 submucosal cancers (pSM): 16 pSM superficial (pSM1) and 33 pSM deep cancers (pSM2-3). Among lesions diagnosed as CP IIIA 86 out of 91 (94.5%) were adenomas, pM-ca, or pSM1; among lesions diagnosed as CP IIIB 28 out of 39 (72%) were pSM2-3. Sensitivity, specificity and diagnostic accuracy of the CP type III for differentiating pM-ca or pSM1 (<1000 μm) from pSM2-3 (≥1000 μm) were 84.8%, 88.7 % and 87.7%, respectively. Interobserver variability: κ = 0.68, 0.67, 0.72. Intraobserver agreement: κ = 0.79, 0.76, 0.75

Conclusion

Identification of CP type IIIA/IIIB by magnifying NBI is useful for estimating the depth of invasion of early colorectal neoplasms.
Geriatric rehabilitation of stroke patients in nursing homes: a study protocol
Authors: Spruit-van Eijk Monica , Buijck Bianca I , Zuidema Sytse U , Voncken Frans LM , Geurts Alexander CH , Koopmans Raymond TCM
Published: March 2010

Background

Geriatric patients are typically underrepresented in studies on the functional outcome of rehabilitation after stroke. Moreover, most geriatric stroke patients do probably not participate in intensive rehabilitation programs as offered by rehabilitation centers. As a result, very few studies have described the successfulness of geriatric stroke rehabilitation in nursing home patients, although it appears that the majority of these patients are being discharged back to the community, rather than being transferred to residential care. Nevertheless, factors associated with the successfulness of stroke rehabilitation in nursing homes or skilled nursing facilities are largely unknown. The primary goal of this study is, therefore, to assess the factors that uniquely contribute to the successfulness of rehabilitation in geriatric stroke patients that undergo rehabilitation in nursing homes. A secondary goal is to investigate whether these factors are similar to those associated with the outcome of stroke rehabilitation in the literature.

Methods/Design

This study is part of the Geriatric Rehabilitation in AMPutation and Stroke (GRAMPS) study in the Netherlands. It is a longitudinal, observational, multicenter study in 15 nursing homes in the Southern part of the Netherlands that aims to include at least 200 patients. All participating nursing homes are selected based on the existence of a specialized rehabilitation unit and the provision of dedicated multidisciplinary care. Patient characteristics, disease characteristics, functional status, cognition, behavior, and caregiver information, are collected within two weeks after admission to the nursing home. The first follow-up is at discharge from the nursing home or one year after inclusion, and focuses on functional status and behavior. Successful rehabilitation is defined as discharge from the nursing home to an independent living situation within one year after admission. The second follow-up is three months after discharge in patients who rehabilitated successfully, and assesses functional status, behavior, and quality of life. All instruments used in this study have shown to be valid and reliable in rehabilitation research or are recommended by the Netherlands Heart Foundation guidelines for stroke rehabilitation.

Data will be analyzed using SPSS 16.0. Besides descriptive analyses, both univariate and multivariate analyses will be performed with the purpose of identifying associated factors as well as their unique contribution to determining successful rehabilitation.

Discussion

This study will provide more information about geriatric stroke rehabilitation in Dutch nursing homes. To our knowledge, this is the first large study that focuses on the determinants of success of geriatric stroke rehabilitation in nursing home patients.
Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome
Authors: Li Gui-Sen , Chen Xiu-Ling , Zhang Yuan , He Qiang , Wang Fang , Hong Da-Qing , Zhang Ping , Pu Lei , Zhang Yue , Yang Xiu-Chuan , Wang Li
Published: March 2010

Background

Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake.

Methods

One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-α were measured and compared between Group E and 18 patients from Group C.

Results

The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment.

Conclusions

Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.
High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity
Authors: van den Berg Sjoerd AA , Guigas Bruno , Bijland Silvia , Ouwens Margriet , Voshol Peter J , Frants Rune R , Havekes Louis M , Romijn Johannes A , van Dijk Ko Willems
Published: March 2010

Background

Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat) on whole body energy metabolism and tissue specific insulin sensitivity.

Methods

C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet), for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5.

Results

Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle.

Conclusion

In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin resistance. These results indicate that dietary fatty acid composition per sé rather than dietary fat content determines insulin sensitivity in liver of high fat fed C57Bl/6 mice.