bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers
Authors: van Schooneveld Eleni , Wouters Maartje CA , Van der Auwera Ilse , Peeters Dieter J , Wildiers Hans , Van Dam Peter A , Vergote Ignace , Vermeulen Peter B , Dirix Luc Y , Van Laere Steven J 
Published: May 2012

Abstract
Introduction
MicroRNAs (miRNAs) are a group of small noncoding RNAs involved in the regulation of gene expression. As such, they regulate a large number of cellular pathways, and deregulation or altered expression of miRNAs is associated with tumorigenesis. In the current study, we evaluated the feasibility and clinical utility of circulating miRNAs as biomarkers for the detection and staging of breast cancer.

Methods
miRNAs were extracted from a set of 84 tissue samples from patients with breast cancer and eight normal tissue samples obtained after breast-reductive surgery. After reverse transcription and preamplification, 768 miRNAs were profiled by using the TaqMan low-density arrays. After data normalization, unsupervised hierarchical cluster analysis (UHCA) was used to investigate global differences in miRNA expression between cancerous and normal samples. With fold-change analysis, the most discriminating miRNAs between both tissue types were selected, and their expression was analyzed on serum samples from 20 healthy volunteers and 75 patients with breast cancer, including 16 patients with untreated metastatic breast cancer. miRNAs were extracted from 200 μl of serum, reverse transcribed, and analyzed in duplicate by using polymerase chain reaction (qRT-PCR).

Results
UHCA showed major differences in miRNA expression between tissue samples from patients with breast cancer and tissue samples from breast-reductive surgery (P < 0.0001). Generally, miRNA expression in cancerous samples tends to be repressed when compared with miRNA expression in healthy controls (P = 0.0685). The four most discriminating miRNAs by fold-change (miR-215, miR-299-5p, miR-411, and miR-452) were selected for further analysis on serum samples. All miRNAs at least tended to be differentially expressed between serum samples from patients with cancer and serum samples from healthy controls (miR-215, P = 0.094; miR-299-5P, P = 0.019; miR-411, P = 0.002; and miR-452, P = 0.092). For all these miRNAs, except for miR-452, the greatest difference in expression was observed between serum samples from healthy volunteers and serum samples from untreated patients with metastatic breast cancer.

Conclusions
Our study provides a basis for the establishment of miRNAs as biomarkers for the detection and eventually staging of breast cancer through blood-borne testing. We identified and tested a set of putative biomarkers of breast cancer and demonstrated that altered levels of these miRNAs in serum from patients with breast cancer are particularly associated with the presence of metastatic disease.
Hyperandrogenism Sensitizes Leukocytes to Hyperglycemia to Promote Oxidative Stress in Lean Reproductive-Age Women
Authors: González Frank , Nair K. Sreekumaran , Daniels Janice K. , Basal Eati , Schimke Jill M. , Blair Hilary E. 
Published: May 2012

AbstractContext:Hyperandrogenism and oxidative stress are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate oxidative stress.Objective:The purpose of this study was to determine the effect of oral androgen administration on fasting and glucose-stimulated leukocytic reactive oxygen species (ROS) generation, reduced nicotinamide adenine dinucleotide phosphate oxidase p47phox subunit gene expression, and plasma thiobarbituric acid-reactive substances (TBARS) in lean healthy reproductive-age women.Participants, Design, and Setting:Sixteen lean healthy ovulatory reproductive-age women were treated with 130 mg dehydroepiandrosterone (DHEA) or placebo (n = 8 each) for 5 d in this randomized, controlled, double-blind study that was performed at an an academic medical center.Main Outcome Measures:Leukocytic ROS generation, p47phox gene expression, and plasma TBARS were quantified in the fasting state and 2 h after glucose ingestion, before and after treatment.Results:Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any prooxidant markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-sulfate, increased the percent change in glucose-challenged p47phox RNA content, and increased the percent change in fasting and glucose-challenged ROS generation from mononuclear cells and polymorphonuclear cells, p47phox protein content, and plasma TBARS.Conclusion:Elevation of circulating androgens comparable to what is present in PCOS increases leukocytic ROS generation, p47phox gene expression, and plasma TBARS to promote oxidative stress in lean healthy reproductive-age women. Thus, hyperandrogenemia activates and sensitizes leukocytes to glucose in this population.
The cystic fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3
Authors: He Liping , Skirkanich Jennifer , Moronetti Lorenza , Lewis Rosemary , Lamitina Todd 
Published: May 2012

Summary
Membrane proteins comprise ~30% of the proteome. During the early stages of maturation, this class of proteins can experience localized misfolding in distinct cellular compartments, such as the cytoplasm, endoplasmic reticulum (ER) lumen, and ER membrane. ER quality control (ERQC) mechanisms monitor folding and determine whether a membrane protein is appropriately folded or is misfolded and warrants degradation. ERQC plays critical roles in human diseases, such as cystic fibrosis, where deletion of a single amino acid (F508) results in the misfolding and degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Cl- channel. We introduced the ΔF508 mutation into C. elegans PGP-3, a 12 transmembrane ABC transporter with 15% identity to CFTR. When expressed in intestinal epithelial cells, PGP-3wt was stable and efficiently trafficked to the apical plasma membrane through a COPII-dependent mechanism. However, PGP-3ΔF508 was post-transcriptionally destabilized, resulting in reduced total and apical membrane protein levels. Genetic or physiological activation of the osmotic stress response pathway, which causes accumulation of the chemical chaperone glycerol, stabilized PGP-3ΔF508. Efficient degradation of PGP-3ΔF508 required the function of several C. elegans endoplasmic reticulum-associated degradation (ERAD) homologs, suggesting that destabilization occurs through an ERAD-type mechanism. Our studies show that the ΔF508 mutation causes post-transcriptional destabilization and degradation of PGP-3 in C. elegans epithelial cells. This model, combined with the power of C. elegans genetics, provides a new opportunity to genetically dissect metazoan ERQC.
Aerobic and anaerobic metabolism in oxygen minimum layer fishes: the role of alcohol dehydrogenase
Authors: Torres Joseph J. , Grigsby Michelle D. , Clarke M. Elizabeth 
Published: May 2012

SUMMARYZones of minimum oxygen form at intermediate depth in all the world’s oceans as a result of global circulation patterns that keep the water at oceanic mid-depths out of contact with the atmosphere for hundreds of years. In areas where primary production is very high, the microbial oxidation of sinking organic matter results in very low oxygen concentrations at mid-depths. Such is the case with the Arabian Sea, with O2 concentrations reaching zero at 200 m and remaining very low (&lt;0.1 ml O2 l–1) for hundreds of meters below this depth, and in the California borderland, where oxygen levels reach 0.2 ml O2 l–1 at 700 m with severely hypoxic (&lt;1.0 ml O2 l–1) waters at depths 300 m above and below that. Despite the very low oxygen, mesopelagic fishes (primarily lanternfishes: Mytophidae) inhabiting the Arabian Sea and California borderland perform a daily vertical migration into the low-oxygen layer, spending daylight hours in the oxygen minimum zone and migrating upward into normoxic waters at night. To find out how fishes were able to survive their daily sojourns into the minimum zone, we tested the activity of four enzymes, one (lactate dehydrogenase, LDH) that served as a proxy for anaerobic glycolysis with a conventional lactate endpoint, a second (citrate synthase, CS) that is indicative of aerobic metabolism, a third (malate dehydrogenase) that functions in the Krebs’ cycle and as a bridge linking mitochondrion and cytosol, and a fourth (alcohol dehydrogenase, ADH) that catalyzes the final reaction in a pathway where pyruvate is reduced to ethanol. Ethanol is a metabolic product easily excreted by fish, preventing lactate accumulation. The ADH pathway is rarely very active in vertebrate muscle; activity has previously been seen only in goldfish and other cyprinids capable of prolonged anaerobiosis. Activity of the enzyme suite in Arabian Sea and California fishes was compared with that of ecological analogs in the same family and with the same lifestyle but living in systems with much higher oxygen concentrations: the Gulf of Mexico and the Southern Ocean. ADH activities in the Arabian Sea fishes were similar to those of goldfish, far higher than those of confamilials from the less severe minimum in the Gulf of Mexico, suggesting that the Arabian Sea fishes are capable of exploiting the novel ethanol endpoint to become competent anaerobes. In turn, the fishes of California exhibited a higher ADH activity than their Antarctic relatives. It was concluded that ADH activity is more widespread in fishes than previously believed and that it may play a role in allowing vertically migrating fishes to exploit the safe haven afforded by severe oxygen minima.
Muscular strategy shift in human running: dependence of running speed on hip and ankle muscle performance
Authors: Dorn Tim W. , Schache Anthony G. , Pandy Marcus G. 
Published: May 2012

SUMMARY
Humans run faster by increasing a combination of stride length and stride frequency. In slow and medium-paced running, stride length is increased by exerting larger support forces during ground contact, whereas in fast running and sprinting, stride frequency is increased by swinging the legs more rapidly through the air. Many studies have investigated the mechanics of human running, yet little is known about how the individual leg muscles accelerate the joints and centre of mass during this task. The aim of this study was to describe and explain the synergistic actions of the individual leg muscles over a wide range of running speeds, from slow running to maximal sprinting. Experimental gait data from nine subjects were combined with a detailed computer model of the musculoskeletal system to determine the forces developed by the leg muscles at different running speeds. For speeds up to 7 m s–1, the ankle plantarflexors, soleus and gastrocnemius, contributed most significantly to vertical support forces and hence increases in stride length. At speeds greater than 7 m s–1, these muscles shortened at relatively high velocities and had less time to generate the forces needed for support. Thus, above 7 m s–1, the strategy used to increase running speed shifted to the goal of increasing stride frequency. The hip muscles, primarily the iliopsoas, gluteus maximus and hamstrings, achieved this goal by accelerating the hip and knee joints more vigorously during swing. These findings provide insight into the strategies used by the leg muscles to maximise running performance and have implications for the design of athletic training programs.
An experimental exploration of the incorporation of hydrogen isotopes from dietary sources into avian tissues
Authors: Wolf Nathan , Newsome Seth D. , Fogel Marilyn L. , del Rio Carlos Martínez 
Published: May 2012

SUMMARY
The analysis of hydrogen stable isotopes (∂D) is a potentially powerful tool for studying animal ecology. Unlike other stable isotopes used in ecological research, however, we are less familiar with the physiological processes that influence the incorporation of hydrogen isotopes from dietary resources to animal tissues. Here we present the results of a controlled feeding experiment utilizing Japanese quail (Cortunix japonica) that was designed to: (1) estimate the relative contributions of diet to the ∂D signatures of blood plasma, red blood cells, intestine, liver, muscle and feathers; (2) investigate possible differences among these same tissues in diet to tissue discrimination; and (3) explore the differences in incorporation dynamics between deuterium (2H) and a well-studied isotope, 13C, for blood plasma solids and red blood cells. Tissues differed in both the relative contribution of diet to tissue ∂D and diet to tissue discrimination. The average residence time of both hydrogen and carbon was significantly lower in plasma solids than in red blood cells. The average residence time of hydrogen was significantly lower than that of carbon in plasma solids, but not in red blood cells. Although the average residence times of hydrogen and carbon were positively correlated, the correlation was weak. Hence the incorporation of carbon seems to be a poor predictor of that of hydrogen.
A vitellogenin polyserine cleavage site: highly disordered conformation protected from proteolysis by phosphorylation
Authors: Havukainen Heli , Underhaug Jarl , Wolschin Florian , Amdam Gro , Halskau Øyvind 
Published: May 2012

SUMMARY
Vitellogenin (Vg) is an egg-yolk precursor protein in most oviparous species. In honeybee (Apis mellifera), the protein (AmVg) also affects social behavior and life-span plasticity. Despite its manifold functions, the AmVg molecule remains poorly understood. The subject of our structure-oriented AmVg study is its polyserine tract — a little-investigated repetitive protein segment mostly found in insects. We previously reported that AmVg is tissue specifically cleaved in the vicinity of this tract. Here, we show that, despite its potential for an open, disordered structure, AmVg is unexpectedly resistant to trypsin/chymotrypsin digestion at the tract. Our findings suggest that multiple phosphorylation plays a role in this resilience. Sequence variation is highly pronounced at the polyserine region in insect Vgs. We demonstrate that sequence differences in this region can lead to structural variation, as NMR and circular dichroism (CD) evidence assign different conformational propensities to polyserine peptides from the honeybee and the jewel wasp Nasonia vitripennis; the former is extended and disordered and the latter more compact and helical. CD analysis of the polyserine region of bumblebee Bombus ignitus and wasp Pimpla nipponica supports a random coil structure in these species. The spectroscopic results strengthen our model of the AmVg polyserine tract as a flexible domain linker shielded by phosphorylation.
Thermal games in crayfish depend on establishment of social hierarchies
Authors: Tattersall Glenn J. , Luebbert Joshua P. , LePine Olivia K. , Ormerod Kiel G. , Mercier A. Joffre 
Published: May 2012

SUMMARY
An unequal resource distribution is commonly seen in dominance hierarchies, in which the individual with the higher status is more successful in obtaining the resource. One possible resource is preferred temperature. When situations allow, ectotherms regulate their body temperature by behaviourally selecting different environmental conditions, achieving, when possible, a preferred temperature. Using a shuttlebox, the preferred temperature for Procambarus clarkii was determined to be 23.9°C with upper and lower voluntary escape temperatures of 25.9 and 21.8°C, respectively. If this preferred temperature zone (21.8–25.9°C) was valued as a resource, given the choice between a preferred temperature and a non-preferred temperature, crayfish should compete over the preferred temperature, with the dominant individual of dyadic pairs achieving the preferred temperature more often than the subordinate. Using a dual-choice experimental tank, competition over a binary temperature choice between rank-established paired crayfish was determined under both warm and cold challenge conditions (warm vs preferred temperature and cold vs preferred temperature, respectively). In naive pairings, similar levels of competition over the preferred temperature occurred in both warm and cold challenge trials, as predicted by game theory. In established pairings, however, dominant crayfish gained significantly greater access to preferred temperature in both warm and cold challenge conditions. These results demonstrate that crayfish engage in a cost–benefit assessment during their initial agonistic contests over temperature, but as hierarchies mature, these thermal games are decided by the dominant animal gaining primary access to the temperature resource.
The visual control of landing and obstacle avoidance in the fruit flyDrosophila melanogaster
Authors: van Breugel Floris , Dickinson Michael H. 
Published: May 2012

SUMMARYLanding behavior is one of the most critical, yet least studied, aspects of insect flight. In order to land safely, an insect must recognize a visual feature, navigate towards it, decelerate, and extend its legs in preparation for touchdown. Although previous studies have focused on the visual stimuli that trigger these different components, the complete sequence has not been systematically studied in a free-flying animal. Using a real-time 3D tracking system in conjunction with high speed digital imaging, we were able to capture the landing sequences of fruit flies (Drosophila melanogaster) from the moment they first steered toward a visual target, to the point of touchdown. This analysis was made possible by a custom-built feedback system that actively maintained the fly in the focus of the high speed camera. The results suggest that landing is composed of three distinct behavioral modules. First, a fly actively turns towards a stationary target via a directed body saccade. Next, it begins to decelerate at a point determined by both the size of the visual target and its rate of expansion on the retina. Finally, the fly extends its legs when the visual target reaches a threshold retinal size of approximately 60 deg. Our data also let us compare landing sequences with flight trajectories that, although initially directed toward a visual target, did not result in landing. In these ‘fly-by’ trajectories, flies steer toward the target but then exhibit a targeted aversive saccade when the target subtends a retinal size of approximately 33 deg. Collectively, the results provide insight into the organization of sensorimotor modules that underlie the landing and search behaviors of insects.
The formation and functional consequences of heterogeneous mitochondrial distributions in skeletal muscle
Authors: Pathi B. , Kinsey S. T. , Howdeshell M. E. , Priester C. , McNeill R. S. , Locke B. R. 
Published: May 2012

SUMMARYDiffusion plays a prominent role in governing both rates of aerobic metabolic fluxes and mitochondrial organization in muscle fibers. However, there is no mechanism to explain how the non-homogeneous mitochondrial distributions that are prevalent in skeletal muscle arise. We propose that spatially variable degradation with dependence on O2 concentration, and spatially uniform signals for biogenesis, can account for observed distributions of mitochondria in a diversity of skeletal muscle. We used light and transmission electron microscopy and stereology to examine fiber size, capillarity and mitochondrial distribution in fish red and white muscle, fish white muscle that undergoes extreme hypertrophic growth, and four fiber types in mouse muscle. The observed distributions were compared with those generated using a coupled reaction-diffusion/cellular automata (CA) mathematical model of mitochondrial function. Reaction-diffusion analysis of metabolites such as oxygen, ATP, ADP and PCr involved in energy metabolism and mitochondrial function were considered. Coupled to the reaction-diffusion approach was a CA approach governing mitochondrial life cycles in response to the metabolic state of the fiber. The model results were consistent with the experimental observations and showed higher mitochondrial densities near the capillaries because of the sometimes steep gradients in oxygen. The present study found that selective removal of mitochondria in the presence of low prevailing local oxygen concentrations is likely the primary factor dictating the spatial heterogeneity of mitochondria in a diversity of fibers. The model results also suggest decreased diffusional constraints corresponding to the heterogeneous mitochondrial distribution assessed using the effectiveness factor, defined as the ratio of the reaction rate in the system with finite rates of diffusion to that in the absence of any diffusion limitation. Thus, the non-uniform distribution benefits the muscle fiber by increasing the energy status and increasing sustainable metabolic rates.
How well do muscle biomechanics predict whole-animal locomotor performance? The role of Ca2+ handling
Authors: Seebacher Frank , Pollard Samuel R. , James Rob S. 
Published: May 2012

SUMMARY
It is important to determine the enabling mechanisms that underlie locomotor performance to explain the evolutionary patterns and ecological success of animals. Our aim was to determine the extent to which calcium (Ca2+) handling dynamics modulate the contractile properties of isolated skeletal muscle, and whether the effects of changing Ca2+ handling dynamics in skeletal muscle are paralleled by changes in whole-animal sprint and sustained swimming performance. Carp (Cyprinus carpio) increased swimming speed by concomitant increases in tail-beat amplitude and frequency. Reducing Ca2+ release from the sarcoplasmic reticulum (SR) by blocking ryanodine receptors with dantrolene decreased isolated peak muscle force and was paralleled by a decrease in tail-beat frequency and whole-animal sprint performance. An increase in fatigue resistance following dantrolene treatment may reflect the reduced depletion of Ca2+ stores in the SR associated with lower ryanodine receptor (RyR) activity. Blocking RyRs may be detrimental by reducing force production and beneficial by reducing SR Ca2+ depletion so that there was no net effect on critical sustained swimming speed (Ucrit). In isolated muscle, there was no negative effect on force production of blocking Ca2+ release via dihydropyridine receptors (DHPRs) with nifedipine. Nifedipine decreased fatigue resistance of isolated muscle, which was paralleled by decreases in tail-beat frequency and Ucrit. However, sprint performance also decreased with DHPR inhibition, which may indicate a role in muscle contraction of the Ca2+ released by DHPR into the myocyte. Inhibiting sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity with thapsigargin decreased fatigue resistance, suggesting that SERCA activity is important in avoiding Ca2+ store depletion and fatigue. We have shown that different molecular mechanisms modulate the same muscle and whole-animal traits, which provides an explanatory model for the observed variations in locomotor performance within and between species.