Miracle-dz/UniFAR-FTUs huggingface dataset:
Knockdown of the zebrafish ortholog of the retinitis pigmentosa 2 (RP2) gene results in retinal degeneration.

PURPOSE The authors investigated the expression and function of the zebrafish ortholog of the retinitis pigmentosa 2 (RP2) gene. METHODS Zebrafish RP2 (ZFRP2) cDNA was isolated from adult eye mRNA by reverse transcription-polymerase chain reaction (RT-PCR). Gene expression was examined by RT-PCR. The deduced peptide sequence was aligned with RP2 orthologues from different species. Translational suppression (knockdown) of zebrafish RP2 was carried out by antisense morpholino-injection. The phenotype of ZFRP2 knockdown morphants was characterized by immunohistology and histology. Human wild-type and mutant RP2 mRNAs were coinjected with ZFRP2 morpholinos to test whether human RP2 mRNA could rescue ZFRP2 knockdown phenotypes. RESULTS ZFRP2 encodes a protein of 376 amino acids containing an N-terminal tubulin folding cofactor C-like domain and a C-terminal nucleoside diphosphate kinase-like domain. It shares 63% to 65% amino acid identity with human, mouse and bovine RP2. RP2 is expressed at the earliest stages of zebrafish development and persists into adulthood. Knockdown of RP2 in zebrafish causes a curved body axis and small eye phenotype, associated with increased cell death throughout the retina. Human wild-type RP2 mRNA could rescue the body curvature phenotype of ZFRP2 morphants, and the eye size of the resultant morphants was significantly increased over that of morphants in which ZFRP2 had been depleted. CONCLUSIONS Zebrafish RP2 is widely expressed throughout development. ZFRP2 knockdown caused retinal degeneration in zebrafish. Human RP2 could partially rescue the small eye phenotype of ZFRP2 morphants.
International Evidence for Return Predictability and the Implications for Long-Run Covariation of the G7 Stock Markets

Abstract Temporary fluctuations of the US consumption-wealth ratio do not only predict excess returns on the US but also international stock markets at the business cycle frequency. This finding is the reflection of a common, temporary component in national stock markets. Exposure to this common component explains up to 50% of the pairwise covariation among long-horizon returns on the G7 stock markets for the time period from 1970 to 2008. This latter finding is less pronounced in the post-1990s period.
Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study

Background Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking. Aims To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania. Method Eighteen patients with DSM–IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry. Results Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally. Conclusions Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research.
Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor

Purpose: To evaluate CD4+ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT). Experimental Design: To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4+ helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201–positive B16 melanoma that express TERT. Results: The presence of a high number of UCP-specific CD4+ T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4+ TH1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8+ T cells. Conclusions: Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers. Clin Cancer Res; 18(22); 6284–95. ©2012 AACR.
A Phenotype at Last: Essential Role for the Yersinia enterocolitica Ysa Type III Secretion System in a Drosophila melanogaster S2 Cell Model

ABSTRACT The highly pathogenic Yersinia enterocolitica strains have a chromosomally encoded type III secretion system (T3SS) that is expressed and functional in vitro only when the bacteria are cultured at 26°C. Mutations that render this system nonfunctional are slightly attenuated in the mouse model of infection only following an oral inoculation and only at early time points postinfection. The discrepancy between the temperature required for the Ysa gene expression and the physiological temperature required for mammalian model systems has made defining the role of this T3SS challenging. Therefore, we explored the use of Drosophila S2 cells as a model system for studying Ysa function. We show here that Y. enterocolitica is capable of infecting S2 cells and replicating intracellularly to high levels, an unusual feature of this pathogen. Importantly, we show that the Ysa T3SS is required for robust intracellular replication. A secretion-deficient mutant lacking the secretin gene, ysaC, is defective in replication within S2 cells, marking the first demonstration of a pronounced Ysa-dependent virulence phenotype. Establishment of S2 cells as a model for Y. enterocolitica infection provides a versatile tool to elucidate the role of the Ysa T3SS in the life cycle of this gastrointestinal pathogen.
The effect of McKenzie therapy as compared with that of intensive strengthening training for the treatment of patients with subacute or chronic low back pain: A randomized controlled trial.

STUDY DESIGN A randomized controlled comparative trial with an 8-month follow-up period was conducted. OBJECTIVE To compare the effect of the McKenzie treatment method with that of intensive dynamic strengthening training in patients with subacute or chronic low back pain. SUMMARY OF BACKGROUND DATA Randomized studies indicate that the efficacy of the McKenzie method in the treatment of patients with acute or subacute low back pain is debatable. Currently, no randomized studies examining the effects of this method for patients with chronic low back pain have been published. METHODS For this study, 260 consecutive patients with low back pain and at least 8 weeks duration of symptoms (85% of the patients had more than 3 months duration of symptoms) were randomized into two groups: Group A was treated with the McKenzie method (n = 132), and Group B was treated with intensive dynamic strengthening training (n = 128). The treatment period for both groups was 8 weeks at an outpatient clinic, followed by 2 months of self-training at home. Treatment results were recorded at the end of the treatment period at the clinic, then 2 and 8 months after. In both groups, 30% of the patients were lost to follow-up evaluation. An intention-to-treat analysis of the main effect variables, disability, and pain was performed for all the patients included in the study. A supplementary analysis of the 180 patients who completed the full treatment program also was undertaken. RESULTS Intention-to-treat analysis showed a tendency toward a difference in reduction of disability in favor of the McKenzie group at the 2-month follow-up assessment (P = 0.04), but no differences at the end of treatment and at the 8-month follow-up evaluation. No differences in reduction of pain were observed at any time between the groups. The supplementary analysis of the patients who had completed the full intervention showed a tendency toward a difference in favor of the McKenzie method in reduction of pain at the end of treatment (P = 0.02). This difference reached statistical significance at the 2-month follow-up assessment (P = 0.01), but no difference was found after 8 months. The supplementary analysis showed no differences between the groups with regard to reduction of disability. CONCLUSION The McKenzie method and intensive dynamic strengthening training seem to be equally effective in the treatment of patients with subacute or chronic low back pain.
Short-Term Monocular Deprivation Enhances Physiological Pupillary Oscillations

Short-term monocular deprivation alters visual perception in adult humans, increasing the dominance of the deprived eye, for example, as measured with binocular rivalry. This form of plasticity may depend upon the inhibition/excitation balance in the visual cortex. Recent work suggests that cortical excitability is reliably tracked by dilations and constrictions of the pupils of the eyes. Here, we ask whether monocular deprivation produces a systematic change of pupil behavior, as measured at rest, that is independent of the change of visual perception. During periods of minimal sensory stimulation (in the dark) and task requirements (minimizing body and gaze movements), slow pupil oscillations, “hippus,” spontaneously appear. We find that hippus amplitude increases after monocular deprivation, with larger hippus changes in participants showing larger ocular dominance changes (measured by binocular rivalry). This tight correlation suggests that a single latent variable explains both the change of ocular dominance and hippus. We speculate that the neurotransmitter norepinephrine may be implicated in this phenomenon, given its important role in both plasticity and pupil control. On the practical side, our results indicate that measuring the pupil hippus (a simple and short procedure) provides a sensitive index of the change of ocular dominance induced by short-term monocular deprivation, hence a proxy for plasticity.
Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein

Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.
Expression of interleukin‐8 gene in radical prostatectomy specimens is associated with advanced pathologic stage

We previously reported that relative expression of E‐cadherin, matrix metalloproteinases (MMPs)‐2 and ‐9, and vascular endothelial growth factor (VEGF)/vascular permeability factor in radical prostatectomy specimens (RP) can distinguish organ‐confined cancers from advanced prostate cancers. Here, we evaluate the expression of interleukin‐8 (IL‐8) and basic fibroblast growth factor (bFGF), two other genes involved in angiogenesis and metastasis, in RP specimens.
Optimal ALOHA-Like Random Access With Heterogeneous QoS Guarantees for Multi-Packet Reception Aided Visible Light Communications

There is a paucity of random access protocols designed for alleviating collisions in visible light communication (VLC) systems, where carrier sensing is hard to achieve due to the directionality of light. To resolve the problem of collisions, we adopt the successive interference cancellation (SIC) algorithm to enable the coordinator to simultaneously communicate with multiple devices, which is referred to as the multi-packet reception (MPR) capability. However, the MPR capability could be fully utilized only when random access algorithms are properly designed. Considering the characteristics of the SIC aided random access VLC system, we propose a novel effective capacity (EC)-based ALOHA-like distributed random access algorithm for MPR-aided uplink VLC systems having heterogeneous quality-of-service (QoS) guarantees. First, we model the VLC network as a conflict graph and derive the EC for each device. Then, we formulate the VLC QoS-guaranteed random access problem as a saturation throughput maximization problem subject to multiple statistical QoS constraints. Finally, the resultant non-concave optimization problem is solved by a memetic search algorithm relying on invasive weed optimization and differential evolution. We demonstrate that our derived EC expression matches the Monte Carlo simulation results accurately, and the performance of our proposed algorithms is competitive.
Mechanisms on Boron-Induced Alleviation of Aluminum-Toxicity in Citrus grandis Seedlings at a Transcriptional Level Revealed by cDNA-AFLP Analysis

The physiological and biochemical mechanisms on boron (B)-induced alleviation of aluminum (B)-toxicity in plants have been examined in some details, but our understanding of the molecular mechanisms underlying these processes is very limited. In this study, we first used the cDNA-AFLP to investigate the gene expression patterns in Citrus grandis roots responsive to B and Al interactions, and isolated 100 differentially expressed genes. Results showed that genes related to detoxification of reactive oxygen species (ROS) and aldehydes (i.e., glutathione S-transferase zeta class-like isoform X1, thioredoxin M-type 4, and 2-alkenal reductase (NADP+-dependent)-like), metabolism (i.e., carboxylesterases and lecithin-cholesterol acyltransferase-like 4-like, nicotianamine aminotransferase A-like isoform X3, thiosulfate sulfurtransferase 18-like isoform X1, and FNR, root isozyme 2), cell transport (i.e., non-specific lipid-transfer protein-like protein At2g13820-like and major facilitator superfamily protein), Ca signal and hormone (i.e., calcium-binding protein CML19-like and IAA-amino acid hydrolase ILR1-like 4-like), gene regulation (i.e., Gag-pol polyprotein) and cell wall modification (i.e., glycosyl hydrolase family 10 protein) might play a role in B-induced alleviation of Al-toxicity. Our results are useful not only for our understanding of molecular processes associated with B-induced alleviation of Al-toxicity, but also for obtaining key molecular genes to enhance Al-tolerance of plants in the future.
Engagement in gender normative versus nonnormative forms of aggression: links to social-psychological adjustment.

Although many important advances have been made in our understanding of childhood aggression in recent years, a significant limitation of prior studies has been the lack of attention to the possible moderating role of gender in the links between aggression and social-psychological adjustment. To address this issue, the author evaluated the adjustment status associated with engagement in gender normative versus gender nonnormative forms of aggression for both boys and girls. Indexes of social-psychological adjustment assessed included teacher and self-reports of internalizing and externalizing difficulties (N = 1.166 children 9-12 years old). Results showed that children who engaged in gender nonnormative forms of aggression (i.e., overtly aggressive girls and relationally aggressive boys) were significantly more maladjusted than children who engaged in gender normative forms of aggression and children who were nonaggressive.
Enriching document representation via translation for improved monolingual information retrieval

Word ambiguity and vocabulary mismatch are critical problems in information retrieval. To deal with these problems, this paper proposes the use of translated words to enrich document representation, going beyond the words in the original source language to represent a document. In our approach, each original document is automatically translated into an auxiliary language, and the resulting translated document serves as a semantically enhanced representation for supplementing the original bag of words. The core of our translation representation is the expected term frequency of a word in a translated document, which is calculated by averaging the term frequencies over all possible translations, rather than focusing on the 1-best translation only. To achieve better efficiency of translation, we do not rely on full-fledged machine translation, but instead use monotonic translation by removing the time-consuming reordering component. Experiments carried out on standard TREC test collections show that our proposed translation representation leads to statistically significant improvements over using only the original language of the document collection.
A Reformulation of Rule 2 of Centering Theory

The standard preference ordering on the well-known centering transitions Continue, Retain, Shift is argued to be unmotivated: a partial, context-dependent ordering emerges from the interaction between principles dubbed cohesion (maintaining the same center of attention) and salience (realizing the center of attention as the most prominent NP). A new formulation of Rule 2 of centering theory is proposed that incorporates these principles as well as a streamlined version of Strube and Hahn's (1999) notion of cheapness. It is argued that this formulation provides a natural way to handle topic switches that appear to violate the canonical preference ordering.
Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004.

BACKGROUND Widespread use of pneumococcal conjugate vaccine (PCV7) resulted in decreases in invasive disease among children and elderly persons. The benefits may be offset by increases in disease due to serotypes not included in the vaccine (hereafter, "nonvaccine serotypes"). We evaluated the effect of PCV7 on incidence of disease due to nonvaccine serotypes. METHODS Cases of invasive disease were identified in 8 geographic areas through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Serotyping and susceptibility testing of isolates were performed. We calculated the incidence of disease for children aged <5 years and adults aged > or =65 years. We compared rates of serotype-specific disease before and after PCV7 was licensed for use. RESULTS The annual incidence of disease due to nonvaccine serotypes increased from an average of 16.3 cases/100,000 population during prevaccine years (1998-1999) to 19.9 cases/100,000 population in 2004 for children aged <5 years (P=.01) and from 27.0 cases/100,000 population during prevaccine years to 29.8 cases/100,000 population in 2004 for adults aged > or =65 years (P=.05). Significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period (P<.05 for each serotype); serotype 19A has become the predominant cause of invasive disease in children. The incidence of disease due to these serotypes also increased among elderly persons. CONCLUSIONS The incidence of pneumococcal disease caused by nonvaccine serotypes is increasing. Ongoing surveillance is needed to monitor the magnitude of disease caused by nonvaccine serotypes, to ensure that future vaccines target the appropriate serotypes.
To move or not to move: a comparison between steerable versus fixed focus region paradigms in multi-resolution tabletop display systems

Previous studies have outlined the advantages of multi-resolution large-area displays over their fixed-resolution counterparts, however the mobility of the focus region has up until the present time received little attention. To study this phenomenon further, we have developed a multi-resolution tabletop display system with a steerable high resolution focus region to compare the performance between steerable and fixed focus region systems under different working scenarios. We have classified these scenarios according to region of interest (ROI) with analogies to different eye movement types (fixed, saccadic, and pursuit ROI). Empirical data gathered during the course of a multi-faceted user study demonstrates that the steerable focus region system significantly outperforms the fixed focus region system. The former is shown to provide enhanced display manipulation and proves especially advantageous in cases where the user must maintain spatial awareness of the display content as is the case in which, within a single session, several regions of the display are to be visited.
Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca2+]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K+ (IKs) channel is a cardiac K+ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating IKs channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human IKs channel activity by expressing human IKs channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the IKs channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the IKs channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the IKs channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca2+]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on IKs channel. However, gintonin had no effect on hERG K+ channel activity. These results show that gintonin-mediated enhancement of IKs channel currents is achieved through binding of the [Ca2+]i/CaM complex to the C terminus of KCNQ1 subunit.