bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico method for systematic analysis of feature importance in microRNA-mRNA interactions
Authors: Xiao Jiamin , Li Yizhou , Wang Kelong , Wen Zhining , Li Menglong , Zhang Lifang , Guang Xuanmin 
Published: December 2009

Abstract

Background
MicroRNA (miRNA), which is short non-coding RNA, plays a pivotal role in the regulation of many biological processes and affects the stability and/or translation of mRNA. Recently, machine learning algorithms were developed to predict potential miRNA targets. Most of these methods are robust but are not sensitive to redundant or irrelevant features. Despite their good performance, the relative importance of each feature is still unclear. With increasing experimental data becoming available, research interest has shifted from higher prediction performance to uncovering the mechanism of microRNA-mRNA interactions.

Results
Systematic analysis of sequence, structural and positional features was carried out for two different data sets. The dominant functional features were distinguished from uninformative features in single and hybrid feature sets. Models were developed using only statistically significant sequence, structural and positional features, resulting in area under the receiver operating curves (AUC) values of 0.919, 0.927 and 0.969 for one data set and of 0.926, 0.874 and 0.954 for another data set, respectively. Hybrid models were developed by combining various features and achieved AUC of 0.978 and 0.970 for two different data sets. Functional miRNA information is well reflected in these features, which are expected to be valuable in understanding the mechanism of microRNA-mRNA interactions and in designing experiments.

Conclusions
Differing from previous approaches, this study focused on systematic analysis of all types of features. Statistically significant features were identified and used to construct models that yield similar accuracy to previous studies in a shorter computation time.
Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population
Authors: Kim Eun Young , Lim Ju Eun , Jung Ji Ye , Son Ji Young , Lee Kyung Jong , Yoon Yoe Wun , Park Byung Hoon , Moon Jin Wook , Park Moo Suk , Kim Young Sam , Kim Se Kyu , Chang Joon , Kang Young Ae 
Published: December 2009

Abstract

Background
Interferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.

Methods
We conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.

Results
Of 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.

Conclusion
In immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.
Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme
Authors: Verhoeff Joost JC , van Tellingen Olaf , Claes An , Stalpers Lukas JA , van Linde Myra E , Richel Dirk J , Leenders William PJ , van Furth Wouter R 
Published: December 2009

Abstract

Background
The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect.

Discussion
GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients.
Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function.

Summary
Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM.
Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral) malaria from uncomplicated malaria
Authors: Conroy Andrea L , Lafferty Erin I , Lovegrove Fiona E , Krudsood Srivicha , Tangpukdee Noppadon , Liles W Conrad , Kain Kevin C 
Published: December 2009

Abstract

Background
Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG) levels as biomarkers of disease severity in Plasmodium falciparum malaria.

Methods
The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87) and severe (non-cerebral) malaria (SM; n = 36) from uncomplicated malaria (UM; n = 70). Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate). Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM), adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma.

Results
ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p < 0.001) and significant increases in ANG-2 (p < 0.001) levels and the ratio of ANG-2: ANG-1 (p < 0.001) observed in patients with SM and CM. This effect was independent of covariates (ethnicity, age, parasitaemia, sex). Further, there was a significant decrease in ANG-1 levels in patients with SM (non-cerebral) versus CM (p < 0.001). In participants with severe disease, ANG-2, but not ANG-1, levels correlated with cumulative organ injury scores; however, ANG-1 correlated with the presence of renal dysfunction and coma. Receiver operating characteristic curve analysis demonstrated that the level of ANG-1, the level of ANG-2 or the ratio of ANG-2: ANG-1 discriminated between individuals with UM and SM (area under the curve, p-value: ANG-2, 0.763, p < 0.001; ANG-1, 0.884, p < 0.001; Ratio, 0.857, p < 0.001) or UM and CM (area under the curve, p-value: ANG-2, 0.772, p < 0.001; ANG-1, 0.778, p < 0.001; Ratio, 0.820, p < 0.001).

Conclusions
These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.
Perceived body image in men and women with type 2 diabetes mellitus: correlation of body mass index with the figure rating scale
Authors: Bays Harold E , Bazata Debbra D , Fox Kathleen M , Grandy Susan , Gavin James R ,   SHIELD Study Group
Published: December 2009

Abstract

Background
Body mass index (BMI) is often used as an objective surrogate estimate of body fat. Increased BMI is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus (T2DM). The Stunkard Figure Rating Scale (FRS) is a subjective measure of body fat, and self-perceptions of body image conceivably impact the development and treatment of T2DM. This study examined the self-perception of body image to various levels of BMI among those with T2DM.

Methods
Respondents (n = 13,887) to the US
S
tudy to
H
elp
I
mprove
E
arly evaluation and management of risk factors
L
eading to
D
iabetes (SHIELD) 2006 survey self-reported their weight and height for BMI calculation. On the gender-specific Stunkard FRS, respondents selected the figure most closely resembling their body image. Spearman correlation was computed between perceived body image and BMI for men and women separately. Student's t-test analysis compared the mean BMI differences between respondents with and without T2DM.

Results
Men with T2DM did not significantly differ from men without diabetes mellitus in mean BMI per body image figure except at the extremes in body figures. Women with T2DM had a significantly higher BMI for the same body figure compared with women without diabetes mellitus for most figures (p < 0.05).

Conclusions
Individuals, particularly women, with T2DM may differ in their perception of body image compared with those without diabetes mellitus. It is unclear if these perceived differences increase the risk of T2DM, or if the diagnosis of T2DM alters body image perceptions.
RNA interference as a gene silencing therapy for mutant MYOC protein in primary open angle glaucoma
Authors: Li Mao , Xu Jianjiang , Chen Xueli , Sun Xinghuai 
Published: December 2009

Abstract

Background
Primary open-angle glaucoma (POAG) is the most common form of glaucoma which is an irreversible blind leading disease and lacks effective remedies. In recent years, POAG has been linked to the gene MYOC encoding myocilin that has been identified to harbor causal mutations. A variety of studies show that the mutant myocilin acts by gain of function. The mutant MYOC protein induces endoplasmic reticulum (ER) stress and the resultant unfolded protein response (UPR) induces apoptosis in the trabecular meshwork cells, which then leads to an increase in resistance to aqueous humor outflow, elevated intraocular pressure (IOP), and, ultimately, glaucoma. Culturing human trabecular meshwork (HTM) cells at a condition facilitating protein folding promotes secretion of mutant myocilin, normalizes cell morphology and reverses cell lethality.

Presentation of the Hypothesis
We speculate that a complete elimination of mutant myocilin expression in trabecular meshwork cells is safe and that gives the possibility of avoiding the POAG phenotype.

Testing the Hypothesis
We propose RNA interference (RNAi) as a gene silencing therapy to eliminate the mutant myocilin proteins in the trabecular meshwork cells, either in a mutation-dependent or mutation-independent way due to the different engineering of the small interfering (si) RNA.

Implications of the Hypothesis
The RNAi strategy can reverse the pathological process of trabecular meshwork cells and thus treat the POAG caused by myocilin gene mutation. This strategy can also be applicable to many protein-misfolding diseases caused by gain-of-function mutant proteins.
Sustained Activity of the EGF Receptor Is an Absolute Requisite for LH-Induced Oocyte Maturation and Cumulus Expansion
Authors: Reizel Yitzhak , Elbaz Judith , Dekel Nava 
Published: December 2009

AbstractMammalian reproduction depends on the release of a mature oocyte from the ovarian follicle. Maturation of the oocyte and rupture of the follicle wall constitute part of the responses to the preovulatory surge of LH, which also include cumulus expansion and granulosa cell luteinization. It was previously shown that the epidermal growth factor receptor (EGFR) mediates the ovulatory response to LH in the ovarian follicle. We hypothesized that it is a sustained activity of the EGFR that generates oocyte maturation and cumulus expansion. We demonstrated that, whereas a transient exposure of rat isolated, intact, preovulatory follicles to either LH or forskolin was sufficient to induce oocyte maturation and cumulus expansion, these LH-induced responses were only generated upon a prolonged activity of the EGFR. In addition, the continuous activity of the EGFR is essential for the chronic phosphorylation of the ERK1/2 downstream signaling molecules, which were shown to be essential for oocyte maturation and cumulus expansion. Interestingly, EGFR-sustained activity was also necessary to maintain the up-regulation of Ptgs2, a gene essential for cumulus expansion. The unusual prolonged duration of ERK1/2 activity may possibly be attributed to the late induction of the ERK-specific phosphatase 3, demonstrated herein. These new data shed light on the unique characteristics of EGFR-ERK1/2 activity in the ovarian follicle and emphasize the fact that the ovulatory process involves a nonclassical activation of this pathway.
Epigenetics and transgenerational transfer: a physiological perspective
Authors: Ho D. H. , Burggren W. W. 
Published: December 2009

SummaryEpigenetics, the transgenerational transfer of phenotypic characters without modification of gene sequence, is a burgeoning area of study in many disciplines of biology. However, the potential impact of this phenomenon on the physiology of animals is not yet broadly appreciated, in part because the phenomenon of epigenetics is not typically part of the design of physiological investigations. Still enigmatic and somewhat ill defined is the relationship between the overarching concept of epigenetics and interesting transgenerational phenomena (e.g. ‘maternal/parental effects’) that alter the physiological phenotype of subsequent generations. The lingering effect on subsequent generations of an initial environmental disturbance in parent animals can be profound, with genes continuing to be variously silenced or expressed without an associated change in gene sequence for many generations. Known epigenetic mechanisms involved in this phenomenon include chromatin remodeling (DNA methylation and histone modification), RNA-mediated modifications (non-coding RNA and microRNA), as well as other less well studied mechanisms such as self-sustaining loops and structural inheritance. In this review we: (1) discuss how the concepts of epigenetics and maternal effects both overlap with, and are distinct from, each other; (2) analyze examples of existing animal physiological studies based on these concepts; and (3) offer a construct by which to integrate these concepts into the design of future investigations in animal physiology.
On the role of form and kinematics on the hydrodynamics of self-propelled body/caudal fin swimming
Authors: Borazjani I. , Sotiropoulos F. 
Published: December 2009

SUMMARY
We carry out fluid–structure interaction simulations of self-propelled virtual swimmers to investigate the effects of body shape (form) and kinematics on the hydrodynamics of undulatory swimming. To separate the effects of form and kinematics, we employ four different virtual swimmers: a carangiform swimmer (i.e. a mackerel swimming like mackerel do in nature); an anguilliform swimmer (i.e. a lamprey swimming like lampreys do in nature); a hybrid swimmer with anguilliform kinematics but carangiform body shape (a mackerel swimming like a lamprey); and another hybrid swimmer with carangiform kinematics but anguilliform body shape (a lamprey swimming like a mackerel). By comparing the performance of swimmers with different kinematics but similar body shapes we study the effects of kinematics whereas by comparing swimmers with similar kinematics but different body shapes we study the effects of form. We show that the anguilliform kinematics not only reaches higher velocities but is also more efficient in the viscous (Re∼102) and transitional (Re∼103) regimes. However, in the inertial regime (Re=∞) carangiform kinematics achieves higher velocities and is also more efficient than the anguilliform kinematics. The mackerel body achieves higher swimming speeds in all cases but is more efficient in the inertial regime only whereas the lamprey body is more efficient in the transitional regime. We also show that form and kinematics have little overall effect on the 3-D structure of the wake (i.e. single vs double row vortex streets), which mainly depends on the Strouhal number. Nevertheless, body shape is found to somewhat affect the small-scale features and complexity of the vortex rings shed by the various swimmers.
Individual variation and repeatability in aerobic and anaerobic swimming performance of European sea bass,Dicentrarchus labrax
Authors: Marras S. , Claireaux G. , McKenzie D. J. , Nelson J. A. 
Published: December 2009

SUMMARYStudies of inter-individual variation in fish swimming performance may provide insight into how selection has influenced diversity in phenotypic traits. We investigated individual variation and short-term repeatability of individual swimming performance by wild European sea bass in a constant acceleration test (CAT). Fish were challenged with four consecutive CATs with 5 min rest between trials. We measured maximum anaerobic speed at exhaustion (UCAT), gait transition speed from steady aerobic to unsteady anaerobic swimming (Ugt), routine metabolic rate (RMR), post-CAT maximum metabolic rate (MMR), aerobic scope and recovery time from the CATs. Fish achieved significantly higher speeds during the first CAT (UCAT=170 cm s–1), and had much more inter-individual variation in performance (coefficient of variation, CV=18.43%) than in the subsequent three tests (UCAT=134 cm s–1; CV=7.3%), which were very repeatable among individuals. The individual variation in UCAT in the first trial could be accounted for almost exclusively by variation in anaerobic burst-and-coast performance beyond Ugt. The Ugt itself varied substantially between individuals (CV=11.4%), but was significantly repeatable across all four trials. Individual RMR and MMR varied considerably, but the rank order of post-CAT MMR was highly repeatable. Recovery rate from the four CATs was highly variable and correlated positively with the first UCAT (longer recovery for higher speeds) but negatively with RMR and aerobic scope (shorter recovery for higher RMR and aerobic scope). This large variation in individual performance coupled with the strong correlations between some of the studied variables may reflect divergent selection favouring alternative strategies for foraging and avoiding predation.
Variation of the neurofilament medium KSP repeat sub-domain across mammalian species: implications for altering axonal structure
Authors: Barry D. M. , Carpenter C. , Yager C. , Golik B. , Barry K. J. , Shen H. , Mikse O. , Eggert L. S. , Schulz D. J. , Garcia M. L. 
Published: December 2009

SUMMARY
The evolution of larger mammals resulted in a corresponding increase in peripheral nerve length. To ensure optimal nervous system functionality and survival, nerve conduction velocities were likely to have increased to maintain the rate of signal propagation. Increases of conduction velocities may have required alterations in one of the two predominant properties that affect the speed of neuronal transmission: myelination or axonal diameter. A plausible mechanism to explain faster conduction velocities was a concomitant increase in axonal diameter with evolving axonal length. The carboxy terminal tail domain of the neurofilament medium subunit is a determinant of axonal diameter in large caliber myelinated axons. Sequence analysis of mammalian orthologs indicates that the neurofilament medium carboxy terminal tail contains a variable lysine–serine–proline (KSP) repeat sub-domain flanked by two highly conserved sub-domains. The number of KSP repeats within this region of neurofilament medium varies among species. Interestingly, the number of repeats does not change within a species, suggesting that selective pressure conserved the number of repeats within a species. Mapping KSP repeat numbers onto consensus phylogenetic trees reveals independent KSP expansion events across several mammalian clades. Linear regression analyses identified three subsets of mammals, one of which shows a positive correlation in the number of repeats with head–body length. For this subset of mammals, we hypothesize that variations in the number of KSP repeats within neurofilament medium carboxy terminal tail may have contributed to an increase in axonal caliber, increasing nerve conduction velocity as larger mammals evolved.
Prioritizing blood flow: cardiovascular performance in response to the competing demands of locomotion and digestion for the Burmese python,Python molurus
Authors: Secor Stephen M. , White Scott E. 
Published: December 2009

SUMMARYIndividually, the metabolic demands of digestion or movement can be fully supported by elevations in cardiovascular performance, but when occurring simultaneously, vascular perfusion may have to be prioritized to either the gut or skeletal muscles. Burmese pythons (Python molurus) experience similar increases in metabolic rate during the digestion of a meal as they do while crawling, hence each would have an equal demand for vascular supply when these two actions are combined. To determine, for the Burmese python, whether blood flow is prioritized when snakes are digesting and moving, we examined changes in cardiac performance and blood flow in response to digestion, movement, and the combination of digestion and movement. We used perivascular blood flow probes to measure blood flow through the left carotid artery, dorsal aorta, superior mesenteric artery and hepatic portal vein, and to calculate cardiac output, heart rate and stroke volume. Fasted pythons while crawling experienced a 2.7- and 3.3-fold increase, respectively, in heart rate and cardiac output, and a 66% decrease in superior mesenteric flow. During the digestion of a rodent meal equaling in mass to 24.7% of the snake's body mass, heart rate and cardiac output increased by 3.3- and 4.4-fold, respectively. Digestion also resulted in respective 11.6- and 14.1-fold increases in superior mesenteric and hepatic portal flow. When crawling while digesting, cardiac output and dorsal aorta flow increased by only 21% and 9%, respectively, a modest increase compared with that when they start to crawl on an empty stomach. Crawling did triggered a significant reduction in blood flow to the digesting gut, decreasing superior mesenteric and hepatic portal flow by 81% and 47%, respectively. When faced with the dual demands of digestion and crawling, Burmese pythons prioritize blood flow, apparently diverting visceral supply to the axial muscles.