bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive evolution and inherent tolerance to extreme thermal environments
Authors: Cox Jennifer , Schubert Alyxandria M , Travisano Michael , Putonti Catherine 
Published: March 2010

Abstract

Background
When introduced to novel environments, the ability for a species to survive and rapidly proliferate corresponds with its adaptive potential. Of the many factors that can yield an environment inhospitable to foreign species, phenotypic response to variation in the thermal climate has been observed within a wide variety of species. Experimental evolution studies using bacteriophage model systems have been able to elucidate mutations, which may correspond with the ability of phage to survive modest increases/decreases in the temperature of their environment.

Results
Phage ΦX174 was subjected to both elevated (50°C) and extreme (70°C+) temperatures for anywhere from a few hours to days. While no decline in the phage's fitness was detected when it was exposed to 50°C for a few hours, more extreme temperatures significantly impaired the phage; isolates that survived these heat treatments included the acquisition of several mutations within structural genes. As was expected, long-term treatment of elevated and extreme temperatures, ranging from 50-75°C, reduced the survival rate even more. Isolates which survived the initial treatment at 70°C for 24 or 48 hours exhibited a significantly greater tolerance to subsequent heat treatments.

Conclusions
Using the model organism ΦX174, we have been able to study adaptive evolution on the molecular level under extreme thermal changes in the environment, which to-date had yet to be thoroughly examined. Under both acute and extended thermal selection, we were able to observe mutations that occurred in response to excessive external pressures independent of concurrently evolving hosts. Even though its host cannot tolerate extreme temperatures such as the ones tested here, this study confirms that ΦX174 is capable of survival.
Pre-hospital ECG for acute coronary syndrome in urban India: A cost-effectiveness analysis
Authors: Schulman-Marcus Joshua , Prabhakaran Dorairaj , Gaziano Thomas A 
Published: March 2010

Abstract

Background
Patients with acute coronary syndrome (ACS) in India have increased pre-hospital delay and low rates of thrombolytic reperfusion. Use of ECG could reduce pre-hospital delay among patients who first present to a general practitioner (GP). We assessed whether performing ECG on patients with acute chest pain would improve long-term outcomes and be cost-effective.

Methods
We created a Markov model of urban Indian patients presenting to a GP with acute chest pain to compare a GP's performing an ECG versus not performing one. Variables describing the accuracy of a GP's referral decision in chest pain and ACS, ACS treatment patterns, the effectiveness of thrombolytic reperfusion, and costs were derived from Indian data where available and other developed world studies. The model was used to estimate the incremental cost-effectiveness ratio (ICER) of the intervention in 2007 US dollars per quality adjusted life years (QALY) gained.

Results
Under baseline assumptions, the ECG strategy cost an additional $12.65 per QALY gained compared to no ECG. Sensitivity analyses around the cost of the ECG, cost of thrombolytic, and referral accuracy of the GP yielded ICERs for the ECG strategy ranging between cost-saving and $1124/QALY. All results indicated the intervention is cost-effective under current World Health Organization recommendations.

Conclusions
While direct presentation to the hospital with acute chest pain is preferable, in urban Indian patients presenting first to a GP, an ECG performed by the GP is a cost-effective strategy to reduce disability and mortality. This strategy should be clinically studied and considered until improved emergency transport services are available.
Research protocol of the NeedYD-study (Needs in Young onset Dementia): a prospective cohort study on the needs and course of early onset dementia
Authors: van Vliet Deliane , Bakker Christian , Koopmans Raymond TCM , Vernooij-Dassen Myrra JFJ , Verhey Frans RJ , de Vugt Marjolein E 
Published: March 2010

Abstract

Background
Early onset dementia has serious consequences for patients and their family members. Although there has been growing attention for this patient group, health care services are still mainly targeted at the elderly. Specific knowledge of the needs of early onset dementia patients and their families is limited but necessary for the development of adequate health care services and specific guidelines. This research project is mainly targeted at delineating the course of early onset dementia, the functional characteristics and needs of early onset dementia patients and their caregivers, the risk factors for institutionalization and the interaction with the caring environment.

Methods/Design
The NeedYD-study (Needs in Young Onset Dementia) is a longitudinal observational study investigating early onset dementia patients and their caregivers (n = 217). Assessments are performed every six months over two years and consist of interviews and questionnaires with patients and caregivers. The main outcomes are (1) the needs of patients and caregivers, as measured by the Camberwell Assessment of Needs for the Elderly (CANE) and (2) neuropsychiatric symptoms, as measured by the NeuroPsychiatric Inventory (NPI). Qualitative analyses will be performed in order to obtain more in-depth information on the experiences of EOD patients and their family members. The results of this study will be compared with comparable data on late onset dementia from a historical cohort.

Discussion
The study protocol of the NeedYD-study is presented here. To our knowledge, this study is the first prospective cohort study in this research area. Although some limitations exist, these do not outweigh the strong points of this study design.
Factors associated with persistent hypertension after puerperium among women with pre-eclampsia/eclampsia in Mulago hospital, Uganda
Authors: Ndayambagye Emmanuel B , Nakalembe Miriam , Kaye Dan K 
Published: March 2010

Abstract

Background
Women with severe pre-eclampsia/eclampsia are at risk of developing chronic hypertension in future. Chronic hypertension may manifest initially as persistent hypertension at the end of the puerperium. The objective was to determine the incidence and maternal biochemical, hematological and socio-demographic risk factors for persistent hypertension in patients with pre-eclampsia/eclampsia.

Methods
This was a prospective cohort study conducted from November 2008 to May 2009 at Mulago hospital labor ward and postnatal clinic. Participants were 200 women managed for pre-eclampsia/eclampsia and followed up to the end of the puerperium. Data was collected through using pre-coded interviewer-administered questionnaires, checking medical records and laboratory investigations. STATA (release 9) software was used for data analysis. At bivariate analysis, the relative risk of persistent hypertension was estimated at the 95% confidence level. Using multivariate logistic regression analysis, factors that were independently associated with persistent hypertension were evaluated.

Results
Fifty four (27.7%) out of the total 195 women had persistent hypertension after puerperium. Serum creatinine and the age of the patient were the only factors associated with persistence of hypertension after puerperium.

Conclusion
Nearly every one in four mothers with pre-eclampsia/eclampsia are at risk of persistent hypertension after the puerperium. Serum creatinine, serum uric acid and participants' age were the only factors independently associated with persistence of hypertension after the puerperium.
Determinants of public trust in complementary and alternative medicine
Authors: van der Schee Evelien , Groenewegen Peter P 
Published: March 2010

Abstract

Background
In the Netherlands, public trust in conventional medicine is relatively high. There is reason to believe that public trust in complementary and alternative medicine (CAM) is rated lower. The aim of this study is to gain insight into public trust in CAM and the determinants that lie at the root of it. We hypothesized that public trust in CAM is related to (perceived) institutional guarantees, media information on CAM, information from people's social network, personal experiences, the role of general practitioners (GPs) and trust in conventional medicine.

Methods
A postal questionnaire on public trust in CAM was mailed to 1358 members of the Health Care Consumer Panel. 65% of the questionnaires were returned. Data were analysed using frequencies, ANOVA, post hoc testing and linear regression analyses.

Results
In the total sample, the level of public trust in CAM was a 5.05 on average on a scale of 1-10. 40.7% was CAM user (current or past) and displayed significantly higher levels of trust toward CAM than CAM non users. In the total sample, public trust in CAM was related to institutional guarantees, negative media information, positive and negative information reported by their social network and people's personal experiences with CAM. For non users, trust is mostly associated with institutional guarantees. For users, personal experiences are most important. For both users and non users, trust levels in CAM are affected by negative media information. Public trust in CAM is for CAM users related to positive information and for non users to negative information from their network.

Conclusions
In the Netherlands, CAM is trusted less than conventional medicine. The hypotheses on institutional guarantees, media information, information from the network and people's personal experiences are confirmed by our study for the total sample, CAM non users and users. The other hypotheses are rejected.
Dynamics of pfcrt alleles CVMNK and CVIET in chloroquine-treated Sudanese patients infected with Plasmodium falciparum
Authors: Gadalla Nahla B , Elzaki Salah Eldin , Mukhtar Ebtihal , Warhurst David C , El-Sayed Badria , Sutherland Colin J 
Published: March 2010

Abstract

Background
Parasite resistance to the anti-malarial drug chloroquine is common in eastern Sudan. Dynamic within-host changes in the relative abundance of both sensitive and resistant Plasmodium falciparum parasites were examined in a cohort of chloroquine-treated patients presenting with uncomplicated falciparum malaria, using a novel allele-specific quantitative approach.

Methods
Treatment outcomes were determined for 93 patients of all ages in a per protocol cohort using a modified 14-day WHO protocol. Parasite DNA samples at days 0, 1, 2, 3, 7 and 14 following treatment were analysed using real-time quantitative PCR methods that distinguished resistant and sensitive genotypes at amino acids 72 - 76 of the pfcrt locus.

Results
Chloroquine treatment was not efficacious, and of 93 assessable patients, only 10 individuals (10.7%; 95% C.I. 4.34 - 17.2%) enjoyed an adequate clinical and parasitological response. Resistant parasites with the haplotype CVIET at codons 72-76 of the pfcrt locus were dominant in the starting population. Chloroquine sensitive parasites with the haplotype CVMNK were detected in 19 individuals prior to treatment (20.43%; 95% C.I. 5.14 - 18.5%). In these patients, CQ treatment rapidly selected CVIET parasites, and this haplotype overwhelmingly dominated the parasite population in each individual by day 2 after treatment.

Conclusions
Such rapid intra-host selection of particular genotypes after the introduction of drug will cause frequent misidentification of parasite genotypes present in the starting population. This will have a potentially serious confounding effect on clinical trials which employ PCR-corrected estimates of treatment failure, as resistant parasites below the detection threshold in the pre-treatment sample can be erroneously classified as "new" infections during follow-up, over-estimating drug efficacy.
GCN5-dependent acetylation of HIV-1 integrase enhances viral integration
Authors: Terreni Mariaelena , Valentini Paola , Liverani Vania , Gutierrez Maria Ines , Di Primio Cristina , Di Fenza Armida , Tozzini Valentina , Allouch Awatef , Albanese Alberto , Giacca Mauro , Cereseto Anna 
Published: March 2010

Abstract

Background
An essential event during the replication cycle of HIV-1 is the integration of the reverse transcribed viral DNA into the host cellular genome. Our former report revealed that HIV-1 integrase (IN), the enzyme that catalyzes the integration reaction, is positively regulated by acetylation mediated by the histone acetyltransferase (HAT) p300.

Results
In this study we demonstrate that another cellular HAT, GCN5, acetylates IN leading to enhanced 3'-end processing and strand transfer activities. GCN5 participates in the integration step of HIV-1 replication cycle as demonstrated by the reduced infectivity, due to inefficient provirus formation, in GCN5 knockdown cells. Within the C-terminal domain of IN, four lysines (K258, K264, K266, and K273) are targeted by GCN5 acetylation, three of which (K264, K266, and K273) are also modified by p300. Replication analysis of HIV-1 clones carrying substitutions at the IN lysines acetylated by both GCN5 and p300, or exclusively by GCN5, demonstrated that these residues are required for efficient viral integration. In addition, a comparative analysis of the replication efficiencies of the IN triple- and quadruple-mutant viruses revealed that even though the lysines targeted by both GCN5 and p300 are required for efficient virus integration, the residue exclusively modified by GCN5 (K258) does not affect this process.

Conclusions
The results presented here further demonstrate the relevance of IN post-translational modification by acetylation, which results from the catalytic activities of multiple HATs during the viral replication cycle. Finally, this study contributes to clarifying the recent debate raised on the role of IN acetylated lysines during HIV-1 infection.
Rapid expression of transgenes driven by seed-specific constructs in leaf tissue: DHA production
Authors: Petrie James R , Shrestha Pushkar , Liu Qing , Mansour Maged P , Wood Craig C , Zhou Xue-Rong , Nichols Peter D , Green Allan G , Singh Surinder P 
Published: March 2010

Abstract

Background
Metabolic engineering of seed biosynthetic pathways to diversify and improve crop product quality is a highly active research area. The validation of genes driven by seed-specific promoters is time-consuming since the transformed plants must be grown to maturity before the gene function can be analysed.

Results
In this study we demonstrate that genes driven by seed-specific promoters contained within complex constructs can be transiently-expressed in the Nicotiana benthamiana leaf-assay system by co-infiltrating the Arabidopsis thaliana LEAFY COTYLEDON2 (LEC2) gene. A real-world case study is described in which we first assembled an efficient transgenic DHA synthesis pathway using a traditional N. benthamiana Cauliflower Mosaic Virus (CaMV) 35S-driven leaf assay before using the LEC2-extended assay to rapidly validate a complex seed-specific construct containing the same genes before stable transformation in Arabidopsis.

Conclusions
The LEC2-extended N. benthamiana assay allows the transient activation of seed-specific promoters in leaf tissue. In this study we have used the assay as a rapid preliminary screen of a complex seed-specific transgenic construct prior to stable transformation, a feature that will become increasingly useful as genetic engineering moves from the manipulation of single genes to the engineering of complex pathways. We propose that the assay will prove useful for other applications wherein rapid expression of transgenes driven by seed-specific constructs in leaf tissue are sought.
Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers
Authors: Song Chang Hoon , Park So Yeon , Eom Keun-Yong , Kim Jee Hyun , Kim Sung-Won , Kim Jae Sung , Kim In Ah 
Published: March 2010

Abstract
Introduction
Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse.

Methods
Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed.

Results
Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases.

Conclusions
The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers.
Silencing of threeAmblyomma americanum(L.) insulin-like growth factor binding protein-related proteins prevents ticks from feeding to repletion
Authors: Mulenga Albert , Khumthong Rabuesak 
Published: March 2010

SUMMARYThe insulin-like growth factor (IGF) binding proteins (IGFBP) family is the regulatory arm of the IGF signaling system that control mitogenic and anabolic actions of IGF peptide hormones. This study describes cloning and biological characterization of three Amblyomma americanum (L.) (Aam) proteins that show amino-terminal sequence and secondary structure similarity to the IGFBP superfamily. The three molecules here provisionally identified as AamIGFBP-rP1 and short (S) and long (L) AamIGFBP-rP6 are expressed in multiple tick organs and are responsive to tick feeding activity with the former being upregulated and the latter being downregulated. We show that they regulate tick physiological functions that may be related to A. americanum tick feeding success as revealed by RNAi-mediated dual silencing of AamIGFBP-rP6S and AamIGFBP-rP6L or AamIGFBP-rP1 alone, which caused a reduction in blood meal size compared to the controls. Additionally, in the case of AamIGFBP-rP1 silencing, 47% of ticks died while attempting to feed and those that did survive and spontaneously detached from the host failed to lay eggs. Although AamIGFBP-rP6S and AamIGFBP-rP6L show overall identities of 49% and 59%, respectively, to Rhipicephalus microplus C protein, the identity level jumps to ~84% when the comparison is restricted to first 70 amino acids of the mature protein. Similarly, the AamIGFBP-rP1 mature protein is ~72%, 87%, 88% and 92% identical to that of Ixodes scapularis S, R. microplus, R. appendiculatus N and A. variegatum F, respectively. The observed across-tick-species conservation suggests that the three molecules (AamIGFBP-rP1, AamIGFBP-rP6S and AamIGFBP-rP6L) represent target for development of vaccines to protect animals against multiple tick species. The data are discussed with reference to advances in tick molecular biology and the potential of the three proteins as targets for immunizing animals against tick feeding.
Collagen type XI α1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.)
Authors: Wargelius A. , Fjelldal P. G. , Nordgarden U. , Grini A. , Krossøy C. , Grotmol S. , Totland G. K. , Hansen T. 
Published: March 2010

SUMMARY
Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity in structure, osteoid secretion and mineralization in response to photoperiod. Other properties of the vertebral bone, such as mineral content and mechanical strength, are also associated with common malformations in farmed Atlantic salmon. The biological mechanisms that underlie these changes in bone physiology are unknown, and in order to elucidate which factors might be involved in this process, microarray assays were performed on vertebral bone of Atlantic salmon reared under natural or continuous light. Eight genes were upregulated in response to continuous light treatment, whereas only one of them was upregulated in a duplicate experiment. The transcriptionally regulated gene was predicted to code for collagen type XI α1, a protein known to be involved in controlling the diameter of fibrillar collagens in mammals. Furthermore, the gene was highly expressed in the vertebrae, where spatial expression was found in trabecular and compact bone osteoblasts and in the chordoblasts of the notochordal sheath. When we measured the expression level of the gene in the tissue compartments of the vertebrae, the collagen turned out to be 150 and 25 times more highly expressed in the notochord and compact bone respectively, relative to the expression in the trabecular bone. Gene expression was induced in response to continuous light, and reduced in compressed vertebrae. The downregulation in compressed vertebrae was due to reduced expression in the compact bone, while expression in the trabecular bone and the notochord was unaffected. These data support the hypothesis that this gene codes for a presumptive collagen type XI α1, which may be involved in the regulatory pathway leading to structural adaptation of the vertebral architecture.
The relationship of head movements to semicircular canal size in cetaceans
Authors: Kandel Benjamin M. , Hullar Timothy E. 
Published: March 2010

SUMMARYThe semicircular canals measure head rotations, providing information critical for maintaining equilibrium. The canals of cetaceans (including whales, dolphins and porpoises) are extraordinarily small, making them unique exceptions to the allometric relationship shared by all other vertebrates between canal size and animal mass. Most modern cetaceans have shorter and less flexible necks than those of their ancestors, an adaptation hypothesized to have led to exaggerated head movements during locomotion. These movements are thought to have necessitated a decrease in the size and sensitivity of the canals, increasing their operating range to accommodate increased head motion. We tested whether the size of the semicircular canals in cetaceans is related to their head movements by comparing the rotational head velocities, frequencies and accelerations of the bottlenose dolphin (Tursiops truncatus) and a terrestrial relative, cattle (Bos taurus), using an array of three orthogonal head-fixed miniaturized rotational ratemeters. We collected data during typical locomotion (swimming; trotting) and during behaviors with enhanced head movements (rapid spiraling underwater; bucking). Cattle head movements always exceeded those of dolphins. Maximum head velocities were 528 deg. s−1 in dolphins and 534 deg. s−1 in cattle; maximum head frequencies were 2.86 Hz in dolphins and 3.45 Hz in cattle; and maximum head accelerations were 5253 deg. s−2 in dolphins and 10,880 deg. s−2 in cattle. These results indicate that accentuated head movements cannot explain the reduced size and sensitivity of cetacean semicircular canals. The evolutionary cause for their reduced canal size remains uncertain.