bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance
Authors: Ali H Raza , Dawson Sarah-Jane , Blows Fiona M , Provenzano Elena , Pharoah Paul D , Caldas Carlos 
Published: November 2011

Abstract
Introduction
The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC).

Methods
We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria.

Results
In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006).

Conclusions
Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs.
Arterial cerebrovascular complications in 94 adults with acute bacterial meningitis
Authors: Klein Matthias , Koedel Uwe , Pfefferkorn Thomas , Zeller Grete , Woehrl Bianca , Pfister Hans-Walter 
Published: November 2011

Abstract
Introduction
Intracranial vascular complications are an important complication of acute bacterial meningitis. Ischemic stroke in meningitis is reported as a result of vasculitis, vasospasm, endocarditis or intraarterial thrombosis. The aim of the study was to identify the value of measuring cerebral blood flow velocity (CBFv) on transracranial doppler (TCD) in the identification of patients at risk for meningitis-associated stroke.

Methods
We retrospectively studied patients with acute bacterial meningitis who were treated in our university hospital from 2000 to 2009. Data were analyzed with the main focus on the incidence of an increase of CBFv on TCD, defined as peak systolic values above 150 cm/s, and the development of stroke.

Results
In total, 114 patients with acute bacterial meningitis were treated, 94 of them received routine TCD studies during their hospital stay. 41/94 patients had elevated CBFv values. This increase was associated with an increased risk of stroke (odds ratio (95% confidence intervall) = 9.15 (1.96-42.67); p < 0.001) and unfavorable outcome (Glasgow Outcome Score < 4; odds ratio (95% confidence intervall) = 2.93 (1.23-6.98); p = 0.018). 11/32 (34.4%) patients with an increase of CBFv who received nimodipine and 2/9 (22.2%) patients with an increase of CBFv who did not receive nimodipine developed stroke (p = 0.69).

Conclusions
In summary, TCD was found to be a valuable bedside test to detect arterial alterations in patients with bacterial meningitis. These patients have an increased risk of stroke.
Genome sequence of the insect pathogenic fungus Cordyceps militaris, a valued traditional chinese medicine
Authors: Zheng Peng , Xia Yongliang , Xiao Guohua , Xiong Chenghui , Hu Xiao , Zhang Siwei , Zheng Huajun , Huang Yin , Zhou Yan , Wang Shengyue , Zhao Guo-Ping , Liu Xingzhong , St Leger Raymond J , Wang Chengshu 
Published: November 2011

Abstract
Background
Species in the ascomycete fungal genus Cordyceps have been proposed to be the teleomorphs of Metarhizium species. The latter have been widely used as insect biocontrol agents. Cordyceps species are highly prized for use in traditional Chinese medicines, but the genes responsible for biosynthesis of bioactive components, insect pathogenicity and the control of sexuality and fruiting have not been determined.

Results
Here, we report the genome sequence of the type species Cordyceps militaris. Phylogenomic analysis suggests that different species in the Cordyceps/Metarhizium genera have evolved into insect pathogens independently of each other, and that their similar large secretomes and gene family expansions are due to convergent evolution. However, relative to other fungi, including Metarhizium spp., many protein families are reduced in C. militaris, which suggests a more restricted ecology. Consistent with its long track record of safe usage as a medicine, the Cordyceps genome does not contain genes for known human mycotoxins. We establish that C. militaris is sexually heterothallic but, very unusually, fruiting can occur without an opposite mating-type partner. Transcriptional profiling indicates that fruiting involves induction of the Zn2Cys6-type transcription factors and MAPK pathway; unlike other fungi, however, the PKA pathway is not activated.

Conclusions
The data offer a better understanding of Cordyceps biology and will facilitate the exploitation of medicinal compounds produced by the fungus.
Heat shock factor binding in Alu repeats expands its involvement in stress through an antisense mechanism
Authors: Pandey Rajesh , Mandal Amit K , Jha Vineet , Mukerji Mitali 
Published: November 2011

Abstract
Background
Alu RNAs are present at elevated levels in stress conditions and, consequently, Alu repeats are increasingly being associated with the physiological stress response. Alu repeats are known to harbor transcription factor binding sites that modulate RNA pol II transcription and Alu RNAs act as transcriptional co-repressors through pol II binding in the promoter regions of heat shock responsive genes. An observation of a putative heat shock factor (HSF) binding site in Alu led us to explore whether, through HSF binding, these elements could further contribute to the heat shock response repertoire.

Results
Alu density was significantly enriched in transcripts that are down-regulated following heat shock recovery in HeLa cells. ChIP analysis confirmed HSF binding to a consensus motif exhibiting positional conservation across various Alu subfamilies, and reporter constructs demonstrated a sequence-specific two-fold induction of these sites in response to heat shock. These motifs were over-represented in the genic regions of down-regulated transcripts in antisense oriented Alus. Affymetrix Exon arrays detected antisense signals in a significant fraction of the down-regulated transcripts, 50% of which harbored HSF sites within 5 kb. siRNA knockdown of the selected antisense transcripts led to the over-expression, following heat shock, of their corresponding down-regulated transcripts. The antisense transcripts were significantly enriched in processes related to RNA pol III transcription and the TFIIIC complex.

Conclusions
We demonstrate a non-random presence of Alu repeats harboring HSF sites in heat shock responsive transcripts. This presence underlies an antisense-mediated mechanism that represents a novel component of Alu and HSF involvement in the heat shock response.
Ablation of 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) in Vascular Endothelial Cells Enhances Insulin Sensitivity by Reducing Visceral Fat and Suppressing Angiogenesis
Authors: Tawaramoto Kazuhito , Kotani Ko , Hashiramoto Mitsuru , Kanda Yukiko , Nagare Tomoki , Sakaue Hiroshi , Ogawa Wataru , Emoto Noriaki , Yanagisawa Masashi , Noda Tetsuo , Kasuga Masato , Kaku Kohei 
Published: November 2011

Abstract
The phosphatidylinositol 3-kinase signaling pathway in vascular endothelial cells is important for systemic angiogenesis and glucose metabolism. In this study, we addressed the precise role of the 3-phosphoinositide-dependent protein kinase 1 (PDK1)-regulated signaling network in endothelial cells in vivo, using vascular endothelial PDK1 knockout (VEPDK1KO) mice. Surprisingly, VEPDK1KO mice manifested enhanced glucose tolerance and whole-body insulin sensitivity due to suppression of their hepatic glucose production with no change in either peripheral glucose disposal or even impaired vascular endothelial function at 6 months of age. When mice were fed a standard diet at 6 months of age and a high-fat diet at 3 months of age, hypertrophy of epididymal adipose tissues was inhibited, adiponectin mRNA was significantly increased, and mRNA of MCP1, leptin, and TNFα was decreased in the white adipose tissue of VEPDK1KO mice in comparison with controls. Consequently, both the circulating adiponectin levels and the activity of hepatic AMP-activated protein kinase were significantly increased, subsequently enhancing whole-body insulin sensitivity and energy expenditure with increased hepatic fatty acid oxidation in VEPDK1KO mice. These results provide the first in vivo evidence that lowered angiogenesis through the deletion of PDK1 signaling not only interferes with the growth of adipose tissue but also induces increased energy expenditure due to amelioration of the adipocytokine profile. This demonstrates an unexpected role of PDK1 signaling in endothelial cells on the maintenance of proper glucose homeostasis through the regulation of adipocyte development.
The role of vision in odor-plume tracking by walking and flying insects
Authors: Willis Mark A. , Avondet Jennifer L. , Zheng Elizabeth 
Published: November 2011

SUMMARY
The walking paths of male cockroaches, Periplaneta americana, tracking point-source plumes of female pheromone often appear similar in structure to those observed from flying male moths. Flying moths use visual-flow-field feedback of their movements to control steering and speed over the ground and to detect the wind speed and direction while tracking plumes of odors. Walking insects are also known to use flow field cues to steer their trajectories. Can the upwind steering we observe in plume-tracking walking male cockroaches be explained by visual-flow-field feedback, as in flying moths? To answer this question, we experimentally occluded the compound eyes and ocelli of virgin P. americana males, separately and in combination, and challenged them with different wind and odor environments in our laboratory wind tunnel. They were observed responding to: (1) still air and no odor, (2) wind and no odor, (3) a wind-borne point-source pheromone plume and (4) a wide pheromone plume in wind. If walking cockroaches require visual cues to control their steering with respect to their environment, we would expect their tracks to be less directed and more variable if they cannot see. Instead, we found few statistically significant differences among behaviors exhibited by intact control cockroaches or those with their eyes occluded, under any of our environmental conditions. Working towards our goal of a comprehensive understanding of chemo-orientation in insects, we then challenged flying and walking male moths to track pheromone plumes with and without visual feedback. Neither walking nor flying moths performed as well as walking cockroaches when there was no visual information available.
Damping in flapping flight and its implications for manoeuvring, scaling and evolution
Authors: Hedrick Tyson L. 
Published: November 2011

SummaryFlying animals exhibit remarkable degrees of both stability and manoeuvrability. Our understanding of these capabilities has recently been improved by the identification of a source of passive damping specific to flapping flight. Examining how this damping effect scales among different species and how it affects active manoeuvres as well as recovery from perturbations provides general insights into the flight of insects, birds and bats. These new damping models offer a means to predict manoeuvrability and stability for a wide variety of flying animals using prior reports of the morphology and flapping motions of these species. Furthermore, the presence of passive damping is likely to have facilitated the evolution of powered flight in animals by providing a stability benefit associated with flapping.
Potentially adaptive effects of maternal nutrition during gestation on offspring phenotype of a viviparous reptile
Authors: Cadby Chloé D. , Jones Susan M. , Wapstra Erik 
Published: November 2011

SUMMARY
Viviparous reptiles have been used as model species for many studies that seek to explain the evolution of viviparity. The vast majority of such studies have focused on the advantage viviparity provides with regards to maternal control of embryonic developmental temperature. However, viviparity may also allow increased control of nutrient transfer, such that mothers adaptively manipulate offspring phenotype through varying maternal nutritional support. Because maternal nutritional transfer is temperature dependent, maternal nutritional strategies may vary between climatically distinct populations. In this study we used an orthogonal experimental design in which mothers and offspring from climatically distinct populations of a viviparous skink (Niveoscincus ocellatus) were allocated randomly to either a protein-rich or a protein-poor diet. Our results suggest that N. ocellatus mothers are able to compensate for sub-optimal nutritional conditions and can adaptively manipulate offspring phenotype to best fit the postnatal nutritional environment. Furthermore, maternal nutritional strategies appear to vary between climatically distinct populations. These results suggest that in viviparous reptiles, matrotrophy provides a means of producing an adaptive offspring phenotype, in addition to maternal control of developmental temperature.
Negative correlation between milk production and brown adipose tissue gene expression in lactating mice
Authors: Król Elzbieta , Martin Samuel A. M. , Huhtaniemi Ilpo T. , Douglas Alex , Speakman John R. 
Published: November 2011

SUMMARYIt has been proposed that the performance of lactating animals is limited by the capacity of the female to dissipate body heat – the heat dissipation limit (HDL) theory. This theory predicts that milk production might be constrained not by intrinsic properties of the mammary glands but rather by competitive heat production such as thermogenesis in brown adipose tissue (BAT). To test this prediction, we measured the expression of genes linked to thermogenesis in BAT of lactating laboratory mice. The applicability of BAT gene expression to reflect thermogenic activity of BAT was confirmed by a positive relationship between expression levels of several BAT genes (summarised by the first principal component following principal component analysis) and daily energy expenditure in virgin mice. Milk production at peak lactation was strongly and negatively associated with the expression of thermogenic genes in BAT. Downregulation of these genes during lactation was correlated with low levels of circulating leptin and high levels of circulating prolactin. Our results are consistent with the HDL theory. However, we cannot discount the converse interpretation that milk production may reduce BAT activity. If the reduction in BAT activity does facilitate increased milk production, then reducing the heat generated by competitive processes may be a more productive route to increase lactational performance than attempts to improve mammary gland performance in isolation from the other body systems.
Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron dipeptidyl peptidase III is a regulatory residue for enzyme activity
Authors: Vukelić Bojana , Salopek-Sondi Branka , Špoljarić Jasminka , Sabljić Igor , Meštrović Nevenka , Agić Dejan , Abramić Marija 
Published: November 2011

AbstractDipeptidyl peptidase III (DPP III), a member of the metallopeptidase family M49, was considered as an exclusively eukaryotic enzyme involved in intracellular peptide cata­bolism and pain modulation. In 2003, new data on genome sequences revealed the first prokaryotic orthologs, which showed low sequence similarity to eukaryotic ones and a cysteine (Cys) residue in the zinc-binding motif HEXXGH. Here we report the cloning and heterologous expression of DPP III from the human gut symbiontBacteroides thetaiotaomicron. The catalytic efficiency of bacterial DPP III for preferred synthetic substrate hydrolysis was very similar to that of the human host enzyme. Substitution of Cys450from the active-site motif by serine did not substantially change the enzymatic activity. However, this residue was wholly responsible for the inactivation effect of sulfhydryl reagents. Molecular modeling indicated seven basic amino acid residues in the local environment of Cys450as a possible cause for its high reactivity. Sequence analysis of 81 bacterial M49 peptidases showed conservation of the HECLGH motif in 68 primary structures with the majority of proteins lacking an active-site Cys originated from aerobic bacteria. Data obtained suggest that Cys450ofB. thetaiotaomicronDPP III is a regulatory residue for the enzyme activity.
Proteome analysis of protein partners to nucleosomes containing canonical H2A or the variant histones H2A.Z or H2A.X
Authors: Fujimoto Satoru , Seebart Corrine , Guastafierro Tiziana , Prenni Jessica , Caiafa Paola , Zlatanova Jordanka 
Published: November 2011

Abstract
Although the existence of histone variants has been known for quite some time, only recently are we grasping the breadth and diversity of the cellular processes in which they are involved. Of particular interest are the two variants of histone H2A, H2A.Z and H2A.X because of their roles in regulation of gene expression and in DNA double-strand break repair, respectively. We hypothesize that nucleosomes containing these variants may perform their distinct functions by interacting with different sets of proteins. Here, we present our proteome analysis aimed at identifying protein partners that interact with nucleosomes containing H2A.Z, H2A.X or their canonical H2A counterpart. Our development of a nucleosome-pull down assay and analysis of the recovered nucleosome-interacting proteins by mass spectrometry allowed us to directly compare nuclear partners of these variant-containing nucleosomes to those containing canonical H2A. To our knowledge, our data represent the first systematic analysis of the H2A.Z and H2A.X interactome in the context of nucleosome structure.
Whatever Happened to the Farm Problem?
Authors: Hillman Jimmye S. 
Published: November 2011

The “farm problem” was a phrase that appeared on the scene in the 1930s after a continued inability of the market to absorb what farmers were producing. Actually, there had always been a farm problem, mostly one of overproduction, and lack of rural employment. Short-term crises were treated with short-term remedies. Banking “panics” came and went; tariff policy was a principal worry for farmers, and land policy (the public domain) had affected farmers since the time of Thomas Jefferson.
It was not until the Great Depression that the federal government intervened directly in the market place to affect prices and incomes. The government also intervened in labor markets and foreign trade to benefit the farm sector. Government has never been able to extract itself. The farm problem is that too many resources being committed to agriculture, and farmers and the rural sector are unable to adjust. Ultimately, the issue became political: how much (or how little) money should be spent on agriculture, and in what way should it be spent? So long as the agricultural budget dominated the federal budget there was “war.”
Today, agriculture has a smaller share of the budget but the farm problem remains. Henry Wallace, US Secretary of Agriculture under FDR, would be astounded!
Comparison of biosensors based on gold and nanocomposite electrodes for monitoring of malic acid in wine
Authors: Monošík Rastislav , Streďanský Miroslav , Greif Gabriel , Šturdík Ernest 
Published: November 2011

Abstract
Amperometric biosensors based on a gold planar electrode and on two types of nanocomposite electrodes consisting of multi-walled carbon nanotubes for the determination of L-malic acid designed for wine-makers were developed. The biosensors designed for wine-makers were constructed by immobilization of L-malate dehydrogenase and diaphorase within chitosan layers on the surface of the electrodes. The coenzyme NAD+ and the electrochemical mediator ferricyanide were present in the measuring solution. The current resulting from re-oxidation of produced ferrocyanide was measured at a working potential of +300 mV against an Ag/AgCl reference electrode. The biosensor based on a gold electrode showed linearity over the range 10–520 µM with a detection limit of 5.41 µM. Calibration curves for biosensors utilizing nanocomposites were obtained both with the linear range of 10 to 610 µM. The detection limits were 1.57 and 1.77 µM, respectively. The biosensors showed satisfactory operational stability (no loss of sensitivity after 30 consecutive measurements) and storage stability (90% of the initial sensitivity after one year of storage at room temperature). The results obtained from measurements of wine samples were in a good correlation with the standard HPLC method. Satisfactory biosensor sensitivity, specificity and stability allowed their successful commercialization.
Detection of NADH and ethanol at a graphite electrode modified with titania sol-gel/Meldola’s Blue/MWCNT/Nafion nanocomposite film
Authors: Kochana Jolanta , Adamski Juliusz 
Published: November 2011

Abstract
For electrocatalytic determination of NADH, a graphite electrode modified with titania sol-gel/Meldola’s Blue/MWCNT/Nafion nanocomposite was proposed. The composition of the matrix film was optimised in terms of the content of carbon nanotubes and Nafion. Incorporation of a redox mediator, Meldola’s Blue, into the nanocomposite film enabled electrocatalytic determination of NADH at a low potential, −50 mV. For determination of ethanol, alcohol dehydrogenase (ADH) was immobilized into the matrix layer. Experimental conditions affecting the biosensor response were examined, including enzyme loading, temperature of measurement and pH of background electrolyte. Assessments of the analytical characteristics of the biosensor were performed with respect to sensitivity, limit of detection, operational stability, repeatability and reproducibility. The proposed biosensor showed electrocatalytic activity toward oxidation of ethanol with sensitivity of 2.24 µA L mmol−1, linear range from 0.05 to 1.1 mmol L−1, and limit of detection of 25 µmol L−1. The apparent Michaelis-Menten constant was 1.24 mmol L−1, indicating a high biological affinity of ADH/titania sol-gel/Meldola’s Blue/MWCNT/Nafion electrode for ethanol. The developed biosensor was tested in determinations of ethanol content in alcoholic beverages.