bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of peer victimization on later maladjustment: mediating and moderating effects of hostile and self‐blaming attributions
Authors: Perren Sonja , Ettekal Idean , Ladd Gary
Published: October 2012

Background:  Evidence indicates that being a victim of bullying or peer aggression has negative short‐ and long‐term consequences. In this study, we investigated the mediating and moderating role of two types of attributional mechanisms (hostile and self‐blaming attributions) on children’s maladjustment (externalizing and internalizing problems).

Methods:  In total, 478 children participated in this longitudinal study from grade 5 to grade 7. Children, parents, and teachers repeatedly completed questionnaires. Peer victimization was assessed through peer reports (T1). Attributions were assessed through self‐reports using hypothetical scenarios (T2). Parents and teachers reported on children’s maladjustment (T1 and T3).

Results:  Peer victimization predicted increases in externalizing and internalizing problems. Hostile attributions partially mediated the impact of victimization on increases in externalizing problems. Self‐blame was not associated with peer victimization. However, for children with higher levels of self‐blaming attributions, peer victimization was linked more strongly with increases in internalizing problems.

Conclusions:  Results imply that hostile attributions may operate as a potential mechanism through which negative experiences with peers lead to increases in children’s aggressive and delinquent behavior, whereas self‐blame exacerbates victimization’s effects on internalizing problems.
Histone deacetylase inhibitors preserve function in aging axons
Authors: Baltan Selva
Published: October 2012

Aging increases the vulnerability of aging white matter to ischemic injury. Histone deacetylase (HDAC) inhibitors preserve young adult white matter structure and function during ischemia by conserving ATP and reducing excitotoxicity. In isolated optic nerve from 12‐month‐old mice, deprived of oxygen and glucose, we show that pan‐ and Class I‐specific HDAC inhibitors promote functional recovery of axons. This protection correlates with preservation of axonal mitochondria. The cellular expression of HDAC 3 in the central nervous system (CNS), and HDAC 2 in optic nerve considerably changed with age, expanding to more cytoplasmic domains from nuclear compartments, suggesting that changes in glial cell protein acetylation may confer protection to aging axons. Our results indicate that manipulation of HDAC activities in glial cells may have a universal potential for stroke therapy across age groups.
Plasma 3‐nitrotyrosine estimates the reperfusion‐induced cerebrovascular stress, whereas matrix metalloproteinases mainly reflect plasma activity: a study in patients treated with thrombolysis or endovascular recanalization
Authors: Bas Demet Funda , Topcuoglu Mehmet Akif , Gursoy‐Ozdemir Yasemin , Saatci Isil , Bodur Ebru , Dalkara Turgay
Published: October 2012

Cerebral reperfusion injury may account for complications of thrombolysis and endovascular recanalization. Experimental studies have shown that brain matrix metalloproteinase (MMP) activity increases during reperfusion and is correlated with oxidative/nitrative stress. Increased plasma MMP levels have been reported in stroke, but no information is available for reperfusion‐induced plasma MMP and 3‐nitrotyrosine (3‐NT, a marker of oxidative/nitrative stress) changes immediately after recanalization. We obtained plasma from 29 patients undergoing endovascular recanalization, 12 patients treated with thrombolysis, and six control patients having diagnostic angiogram before and 1,3, and 24 h after treatment to investigate the effect of cerebral reperfusion on plasma MMP gelatinolytic activity and 3‐NT level. Hypoperfusion was shown distal to the stenotic artery in endovascular treatment patients. Presence of an occluded artery and recanalization was documented in thrombolysis patients. A significant increase was detected in plasma 3‐NT levels 3 and 24 h after stenting/angioplasty. Plasma MMP‐9 gelatinolytic activity rose more than 50% of the pre‐treatment level in 12 of 29 patients. However, this was not statistically significant and not correlated with any of the clinical or radiological correlates of reperfusion injury (e.g., hyperperfusion and hemorrhage). After thrombolysis, a significant increase in plasma MMP‐9 gelatinolytic activity at 3 and 24 h and the cleaved form of MMP‐9 were detected. 3‐NT levels increased by 44% and 62% at 3 and 24 h, which did not achieve statistical significance, but was highly correlated with admission NIH Stroke Scale (r = 0.930 p < 0.001). No change was detected in MMP‐2 in all groups. In conclusion, these data suggest that the increased plasma MMP‐9 levels is not a direct measure of MMP‐9 activity in the reperfused brain but rather a consequence of tissue plasminogen activator infusion, whereas plasma 3‐NT levels appear to originate from the reperfused brain vasculature. The changes in 3‐NT levels may therefore be useful to monitor oxygen/nitrogen radical formation during reperfusion with serial measurements.
Activation of immune responses to brain antigens after stroke
Authors: Becker Kyra J.
Published: October 2012

Infection is common after stroke and is independently associated with a worse outcome. The predisposition to infection following stroke is in part related to a sympathetically mediated suppression of the peripheral immune response. The teleological explanation for this immune dysfunction is that it serves to prevent autoimmune responses to brain antigens. We believe that the systemic immune response in patients who develop infection, however, thwarts this seemingly protective response and predisposes to central nervous system autoimmunity. These autoimmune responses may mediate, at least in part, the worse outcome associated with post‐stroke infection.
National interest versus the common good: The Presidency in European Council agenda setting
Authors: Alexandrova Petya , Timmermans Arco
Published: October 2012

The European Council is an institution which brings together the Heads of State, or Governments of the European Union (EU) Member States. For the Presidency, preparing the agenda of European Council meetings involves a tension between loyalties. Existing research is divided over the question whether the Presidency pushes its domestic policy agenda on the EU level. Using empirical data on the Conclusions of European Council meetings, and national executive speeches presented annually in five Member States, this article investigates the relationship between the policy agendas of the EU and its constituent countries. It tests whether national issue attention of the Presidency holder dominates the European Council agenda. The findings suggest that having the Presidency does not provide a de facto institutional advantage for agenda setting power for any of the countries in the sample. The analysis points out that normative and political constrains limit the leeway of presiding Member States to push for domestic agenda preferences in the European Council.
Decreased Immunoreactivity of the Polypeptide Precursor Pro‐Opiomelanocortin (POMC) and the Prohormone Convertase PC1/3 After Chronic Ethanol Exposure in Sprague‐Dawley Rats
Authors: Navarro Montserrat , Cubero Inmaculada , Thiele Todd E.
Published: October 2012

Background

The melanocortin (MC) peptides and opioid peptide β‐endorphin are cleaved from the polypeptide precursor pro‐opiomelanocortin (POMC). POMC‐derived peptides are generated by extensive posttranslational processing that involves several enzymes including prohormone convertase 1/3 and 2 (PC1/3 and PC2). Because ethanol (EtOH) decreases POMC mRNA levels, we determined whether the exposure to an EtOH‐containing diet (ED) would significantly reduce central immunoreactivity (IR) of POMC, PC1/3, PC2, and β‐endorphin.

Methods

Male Sprague‐Dawley rats were given 18 days of access to a normal rodent chow or a control diet (CD), or short‐term (4 days) or long‐term (18 days) access to an ED. At the end of the study, rats were perfused with 4% paraformaldehyde, and their brains were sectioned into sets for processing with POMC, PC1/3, PC2, and β‐endorphin IR.

Results

Rats exposed to an ED for 18 days (ED18) exhibited significant reductions of POMC and PC1/3 IR in the arcuate nucleus of the hypothalamus (Arc) relative to rats pair‐fed a CD. On the other hand, rats exposed to an ED did not show any changes of central β‐endorphin or PC2 IR relative to rats pair‐fed a CD, regardless of length of exposure. Because there were no differences in body weights or caloric intake between the CD and ED groups, reductions of POMC and PC1/3 IR in ED‐treated rats are best explained by EtOH exposure rather than altered energy balance.

Conclusions

This study shows that EtOH site‐specifically reduces POMC and PC1/3 IR in rat brain. These observations are consistent with EtOH‐induced reductions of α‐melanocyte‐stimulating hormone (α‐MSH) and POMC IR that were previously reported. As MC agonists have been shown to blunt EtOH intake in rodents, exogenous MC receptor agonists, as well as targets that may increase the synthesis of endogenous α‐MSH (e.g., PC1/3), may have therapeutic value for treating alcohol abuse disorders and alcoholism.
Implementing Individual Producer Responsibility for Waste Electrical and Electronic Equipment through Improved Financing
Authors: Mayers Kieren , Lifset Reid , Bodenhoefer Karl , Van Wassenhove Luk N.
Published: October 2012

Under the European Union (EU) Waste Electrical and Electronics Equipment (WEEE) Directive, producers are responsible for financing the recycling of their products at end of life. A key intention of such extended producer responsibility (EPR) legislation is to provide economic incentives for producers to develop products that are easier to treat and recycle at end of life. Recent research has shown, however, that the implementation of EPR for WEEE has so far failed in this respect.

Current WEEE systems calculate their prices according to simple mass‐based allocation of costs to producers, based on broad collection categories containing a mixture of different product types and brands. This article outlines two alternative approaches, which instead calculate charges for products sold by producers by classifying them according to their eventual end‐of‐life treatment requirements and cost. Worked examples indicate that these methods provide both effective and efficient frameworks for financing WEEE, potentially delivering financial incentives to producers substantial enough to affect their potential profitability and, as a likely consequence, the decisions relating to the design of their products. In particular they fulfill three important criteria required by the WEEE Directive: they can financially reward improved design, allocate costs of historic waste proportionately (on the basis of tonnes of new products sold), and provide sufficient financial guarantees against future waste costs and liabilities. They are also relatively practical for implementation because they are based solely on cost allocation and financing. Further research and investigation would be worthwhile to test and verify this approach using real‐world data and under various scenarios.
Dermal Uptake of 18 Dilute Aqueous Chemicals: In Vivo Disappearance‐Method Measures Greatly Exceed In Vitro‐Based Predictions
Authors: Bogen Kenneth T.
Published: October 2012

Average rates of total dermal uptake (Kup) from short‐term (e.g., bathing) contact with dilute aqueous organic chemicals (DAOCs) are typically estimated from steady‐state in vitro diffusion‐cell measures of chemical permeability (Kp) through skin into receptor solution. Widely used (“PCR‐vitro”) methods estimate Kup by applying diffusion theory to increase Kp predictions made by a physico‐chemical regression (PCR) model that was fit to a large set of Kp measures. Here, Kup predictions for 18 DAOCs made by three PCR‐vitro models (EPA, NIOSH, and MH) were compared to previous in vivo measures obtained by methods unlikely to underestimate Kup. A new PCR model fit to all 18 measures is accurate to within approximately threefold (r = 0.91, p < 10−5), but the PCR‐vitro predictions (r > 0.63) all tend to underestimate the Kup measures by mean factors (UF, and p value for testing UF = 1) of 10 (EPA, p < 10−6), 11 (NIOSH, p < 10−8), and 6.2 (MH, p = 0.018). For all three PCR‐vitro models, log(UF) correlates negatively with molecular weight (r2 = 0.31 to 0.84, p = 0.017 to < 10−6) but not with log(vapor pressure) as an additional predictor (p > 0.05), so vapor pressure appears not to explain the significant in vivo/PCR‐vitro discrepancy. Until this discrepancy is explained, careful in vivo measures of Kup should be obtained for more chemicals, the expanded in vivo database should be compared to in vitro‐based predictions, and in vivo data should be considered in assessing aqueous dermal exposure and its uncertainty.
Update on Emergency Contraception
Authors: Murphy Patricia Aikins
Published: October 2012

Emergency contraception (EC) is any method used after sexual intercourse to prevent pregnancy. This article provides an overview of the history of EC methods and describes the current availability of oral and intrauterine EC. Oral forms include the Yuzpe regimen (combining ethinyl estradiol and levonorgestrel), levonorgestrel‐only pills, and ulipristal acetate, which is a new emergency contraceptive drug recently approved by the US Food and Drug Administration. The copper T‐380A intrauterine device can also be used for EC. Information about dosing, timing, access, and other considerations in the provision of EC is covered. Clinicians should be aware of all available options in order to counsel women in need of EC appropriately.
Neglecting uncertainty behind Allee effect estimation may generate false predictions of population extinction risk
Authors: Berec Luděk , Mrkvička Tomáš
Published: October 2012

Estimation of extinction thresholds arising from Allee effects (Allee thresholds) and related probabilities of population extinction is notoriously difficult. One way is to analyze adequately parameterized population models. Traditionally, a point estimate is substituted for the Allee effect strength in such models. However, each point estimate entails an underlying uncertainty. We explore how accounting for this uncertainty affects the probability of population extinction, and show that this probability decreases sigmoidally with increasing population density, even in the absence of any stochasticity. Deviations from when only a point estimate of the Allee effect strength is used can be significant, unless stochasticity is added and the stochastic noise intensity is high. Significant deviations from when only a point estimate is used also occur when the Allee threshold and the environmental carrying capacity of the species are close enough one to another. We also show that the impact of the uncertainty in the Allee effect strength estimate increases as the Allee effect strength itself increases and decreases as the species recovery potential increases. This is not a good news, since we would like to preferentially and efficiently manage slowly recovering populations prone to strong Allee effects. Still, there is a way to come up with relatively good Allee threshold estimates. Besides an obvious option of collecting as many data as possible, the impact of the uncertainty can be mitigated by diversifying Allee effect experiments such that we put more emphasis on larger size groups. This is somewhat surprising, given that frequent complaints on the (im)possibility of detecting Allee effects concern difficulties in locating, observing and experimenting on rare populations. Our results extend current theory surrounding Allee effects and have broad ramifications for applied ecology.
Listening to Uncertainty
Authors: Brown Ethan , Bearman Nick
Published: October 2012

As the world gets more complex, it is harder and harder to see what is going on. But we are failing to use all our faculties, say Ethan Brown and Nick Bearman. We should use our ears as well as our eyes, and make our data sing. This article was another of the runners-up in our Young Statisticians Group/Significance writing competition.
NMR structural studies of thymosin α1 and β‐thymosins
Authors: Volk David E. , Tuthill Cynthia W. , Elizondo‐Riojas Miguel‐Angel , Gorenstein David G.
Published: October 2012

Thymosin proteins, originally isolated from fractionation of thymus tissue, represent a class of compounds that we now know are present in numerous other tissues, are unrelated to each other in a genetic sense, and appear to have different functions within the cell. Thymosin α1 (generic drug name thymalfasin; trade name Zadaxin) is derived from a precursor molecule, prothymosin, by proteolytic cleavage, and stimulates the immune system. Although the peptide is natively unstructured in aqueous solution, the helical structure has been observed in the presence of trifluoroethanol or unilamellar vesicles, and these studies are consistent with the presence of a dynamic helical structure whose sides are not completely hydrophilic or hydrophobic. This helical structure may occur in circulation when the peptide comes into contact with membranes. In this report, we discuss the current knowledge of the thymosin α1 structure and similar properties of thymosin β4 and thymosin β9, in different environments.
Identification of interaction partners of β‐thymosins: application of thymosin β4 labeled by transglutaminase
Authors: App Christine , Knop Jana , Mannherz Hans Georg , Hannappel Ewald
Published: October 2012

In this review, we identify potential interaction partners of the β‐thymosin family. The proteins of this family are highly conserved peptides in mammals and yet only one intracellular (G‐actin) and one cell‐surface protein (β subunit of F1–F0 ATP synthase) were identified as interaction partners of thymosin β4. Cross‐linking experiments may be a possible approach to discover additional proteins that interact with the β‐thymosin family. It has previously been shown that thymosin β4 can be labeled at its glutaminyl residues with various cadaverines using tissue transglutaminase. Here, we illuminate recent results and give an outlook on upcoming work in the field.
Development of an analytical HPLC methodology to study the effects of thymosin β4 on actin in sputum of cystic fibrosis patients
Authors: Badamchian Mahnaz , Damavandy Ali A. , Goldstein Allan L.
Published: October 2012

A high‐performance liquid chromatography (HPLC) methodology is presented. Using bovine and rabbit F‐ and G‐actin, this methodology results in both fractions as being well‐resolved peaks, which were confirmed by dot blot immunoassay and fluorescence microscopy. F‐ and G‐actin were incubated with thymosin β4 (Tβ4) and DNase and then analyzed by HPLC, which indicated that Tβ4 and DNase inhibit G‐actin polymerization and that Tβ4 depolymerizes F‐actin in a dose‐ and time‐dependent manner. The F‐ and G‐actin content in sputum from healthy controls and cystic fibrosis (CF) patients were measured by HPLC before and after incubation with Tβ4, DNase, and gelsolin. These data demonstrate higher quantities of F‐actin in the sputum of CF patients compared to healthy individuals, and also demonstrate a significantly increased F/G‐actin ratio in CF sputum. Further, Tβ4, DNase, and gelsolin each increase the depolymerization of F‐actin in CF sputum in a dose‐dependent fashion that is additive when these agents are combined.
Thymosin α1 continues to show promise as an enhancer for vaccine response
Authors: Tuthill Cynthia , Rios Israel , De Rosa Alfonso , Camerini Roberto
Published: October 2012

Thymosin α1 (Tα1) is an immune‐modulating peptide that can be expected to improve response to vaccinations, as stimulated dendritic cells and T cells can act in concert to increase antibody production along with an improved cytotoxic response from the T cells themselves. Tα1 demonstrated efficacy in preclinical studies; subsequently, it was shown to enhance response to vaccinations in difficult‐to‐treat populations, including individuals immune suppressed due to age or hemodialysis, and leading to a decrease in later infections. During the 2009 pandemic outbreak of H1N1 influenza, mouse and ferret studies confirmed that the use of higher doses of Tα1 allowed for fewer injections than those used in the previous clinical studies. In addition, a clinical study with Focetria™ MF59‐adjuvanted monovalent H1N1 vaccine showed that treatment with Tα1 twice provided an earlier and greater response to the vaccine (P < 0.01).
Thymosin β4: a potential novel dry eye therapy
Authors: Sosne Gabriel , Qiu Ping , Ousler 3rd George W. , Dunn Steven P. , Crockford David
Published: October 2012

The purpose of this manuscript is to review the clinical entity of dry eye syndrome (DES) and to provide a scientific basis and rationale for the usage of thymosin beta 4 (Tβ4) as a novel therapy for DES. DES is a common disorder affecting an estimated 25–30 million people in the United States alone and is characterized by inflammation of the ocular surface. Consequently, patients can suffer from burning, irritation, severe discomfort, foreign body sensation, and blurry and decreased vision. Recent animal studies of DES demonstrate that Tβ4 eye drops significantly reduce corneal fluorescein staining, indicating improved wound healing. Based on previous studies, there is clear support for further clinical investigation and development of Tβ4 as a novel, safe, and effective agent to treat dry eye. Herein, we discuss the scientific and clinical rationales that make Tβ4 a potential ideal candidate therapeutic for DES.
Cardiac repair with thymosin β4 and cardiac reprogramming factors
Authors: Srivastava Deepak , Ieda Masaki , Fu Jidong , Qian Li
Published: October 2012

Heart disease is a leading cause of death in newborns and in adults. We previously reported that the G‐actin–sequestering peptide thymosin β4 promotes myocardial survival in hypoxia and promotes neoangiogenesis, resulting in cardiac repair after injury. More recently, we showed that reprogramming of cardiac fibroblasts to cardiomyocyte‐like cells in vivo after coronary artery ligation using three cardiac transcription factors (Gata4/Mef2c/Tbx5) offers an alternative approach to regenerate heart muscle. We have combined the delivery of thymosin β4 and the cardiac reprogramming factors to further enhance the degree of cardiac repair and improvement in cardiac function after myocardial infarction. These findings suggest that thymosin β4 and cardiac reprogramming technology may synergistically limit damage to the heart and promote cardiac regeneration through the stimulation of endogenous cells within the heart.
Inositol polyphosphate multikinase signaling in the regulation of metabolism
Authors: Lee Joo‐Young , Kim Young‐ran , Park Jina , Kim Seyun
Published: October 2012

Inositol phosphates (IPs) act as signaling messengers to regulate various cellular processes such as growth. Inositol polyphosphate multikinase (IPMK) generates inositol tetrakis‐ and pentakisphosphates (IP4 and IP5), acting as a key enzyme for inositol polyphosphate biosynthesis. IPMK was initially discovered as an essential subunit of the arginine‐sensing transcription complex in budding yeast. In mammals, IPMK is also known as a physiologically important phosphatidylinositol 3 kinase (PI3K) that forms phosphatidylinositol 3,4,5‐trisphosphate (PIP3), which activates Akt/PKB and stimulates its signaling. Acting in a catalytically independent fashion, IPMK mediates the activation of mammalian target of rapamycin (mTOR) in response to essential amino acids. In addition, IPMK binds and modulates AMP‐activated protein kinase (AMPK) signaling pathways, including those involved in hypothalamic control of food intake. These recent findings strongly suggest that IPMK is a versatile player in insulin‐, nutrient‐, and energy‐mediated metabolism signaling networks. Agents that control IPMK functions may provide novel therapeutics in metabolic syndromes such as obesity and diabetes.
Molecular determinants of ovarian cancer chemoresistance: new insights into an old conundrum
Authors: Ali Ahmed Y. , Farrand Lee , Kim Ji Young , Byun Sanguine , Suh Jeong‐Yong , Lee Hyong Joo , Tsang Benjamin K.
Published: October 2012

Ovarian cancer is the most lethal gynecological malignancy. Cisplatin and its derivatives are first‐line chemotherapeutics, and their resistance is a major hurdle in successful ovarian cancer treatment. Understanding the molecular dysregulation underlying chemoresistance is important for enhancing therapeutic outcome. Here, we review two established pathways in cancer chemoresistance. p53 is a major tumor suppressor regulating proliferation and apoptosis, and its mutation is a frequent event in human malignancies. The PI3K/Akt axis is a key oncogenic pathway regulating survival and tumorigenesis by controlling several tumor suppressors, including p53. The interplay between these pathways is well established, although the oncogenic phosphatase PPM1D adds a new layer to this intricate relationship and provides new insights into the processes determining cell fate. Inhibition of the PI3K/Akt pathway by functional food compounds as an adjunct to chemotherapeutics may tip the balance in favor of apoptosis rather than survival, enhancing therapeutic efficacy, and reducing side effects.
Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development
Authors: Bazer Fuller W. , Kim Jingyoung , Song Gwonhwa , Ka Hakhyun , Tekwe Carmen D. , Wu Guoyao
Published: October 2012

Interferon tau (IFNT), a novel multifunctional type I interferon secreted by trophectoderm, is the pregnancy recognition signal in ruminants that also has antiviral, antiproliferative, and immunomodulatory bioactivities. IFNT, with progesterone, affects availability of the metabolic substrate in the uterine lumen by inducing expression of genes for transport of select nutrients into the uterine lumen that activate mammalian target of rapamycin (mTOR) cell signaling responsible for proliferation, migration, and protein synthesis by conceptus trophectoderm. As an immunomodulatory protein, IFNT induces an anti‐inflammatory state affecting metabolic events that decrease adiposity and glutamine:fructose‐6‐phosphate amidotransferase 1 activity, while increasing insulin sensitivity, nitric oxide production by endothelial cells, and brown adipose tissue in rats. This short review focuses on effects of IFNT and progesterone affecting transport of select nutrients into the uterine lumen to stimulate mTOR cell signaling required for conceptus development, as well as effects of IFNT on the immune system and adiposity in rats with respect to its potential therapeutic value in reducing obesity.
Molecular mechanisms of garlic‐derived allyl sulfides in the inhibition of skin cancer progression
Authors: Wang Hsiao‐Chi , Pao Jung , Lin Shuw‐Yuan , Sheen Lee‐Yan
Published: October 2012

Skin cancer is a serious concern whose incidence is increasing at an alarming rate. Allyl sulfides—i.e., sulfur metabolites in garlic oil—have been demonstrated to have anticancer activity against several cancer types, although the mechanisms underlying these effects remain enigmatic. Our previous study showed that diallyl trisulfide (DATS) is more potent than mono‐ and disulfides against skin cancer. DATS inhibits cell growth of human melanoma A375 cells and basal cell carcinoma (BCC) cells by increasing the levels of intracellular reactive oxygen species (ROS) and DNA damage and by inducing G2/M arrest, endoplasmic reticulum (ER) stress, and mitochondria‐mediated apoptosis, including the caspase‐dependent and ‐independent pathways. This short review focuses on the molecular mechanisms of garlic‐derived allyl sulfides on skin cancer prevention.
MicroRNA–target interactions: new insights from genome‐wide approaches
Authors: Lee Dooyoung , Shin Chanseok
Published: October 2012

MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression involved in diverse biological pathways in bilateral animals and plants. The key to understanding the biological function of a miRNA is to identify its regulatory targets. Although a few miRNA targets have been identified genetically, the rapidly expanding list of miRNAs has necessitated genome‐wide tools for identifying target mRNAs, and a number of computational and experimental approaches have consequently emerged. Some of these approaches have also provided insights into the mechanistic aspects of miRNA‐mediated regulation, another intensely debated area in the miRNA field. Here, we review several emerging features of miRNA–target interactions in animals and genome‐wide approaches for probing those interactions.
Determination of Ortho‐ and Retronasal Detection Thresholds and Odor Impact of 2,5‐Dimethyl‐3‐Methoxypyrazine in Wine
Authors: Botezatu Andreea , Pickering Gary J.
Published: October 2012

Abstract:  2,5‐Dimethyl‐3‐methoxypyrazine (DMMP) has been recently identified in both Coccinellidae‐tainted (by either Coccinella septempunctata or Harmonia axyridis beetles) and untainted wines; however, little is known regarding its impact on wine aroma and flavor. The aims of this study were to obtain an accurate estimate of both the ortho‐ and retronasal detection thresholds of DMMP in red wine and to understand how DMMP contributes to the aroma profile of red wine. In the first study, thresholds were determined for 21 individuals using the ASTM E679 ascending forced choice method of limits. The orthonasal group best estimate threshold (BET) was 31 ng/L and the retronasal group BET was 70 ng/L. A moderate variation in individual thresholds was observed for the orthonasal modality (standard deviation (SD) = 19.8) and a larger variation was noted for retronasal thresholds (SD = 111.8). In the second study, a panel of 8 assessors performed descriptive sensory analysis on 3 red wines containing various concentrations of added DMMP (0, 50, and 120 ng/L). Results show significant changes in aroma characteristics in the 120 ng/L wine and smaller effects at the 50 ng/L level. Overall, wines spiked with DMMP generated lower intensity ratings for cherry and red berry descriptors and higher ratings for earthy/musty and green/vegetal descriptors. When considered with other recent results on DMMP concentrations found in wine, DMMP can be considered a hitherto undescribed impact odorant in some wine styles.
Kinetic Study of Sasa veitchii Extract as a Radical Scavenger and an Antioxidant
Authors: Okada Youji , Okajima Haruo , Takeshita Kazuo , Kanamori Masato
Published: October 2012

Abstract:  We examined the free radical scavenging activity of Sasa veitchii extract (Hoshi's Striped Bamboo Extract®, HSBE), well known in folk medicine as an efficient drug and antioxidant in detail. To evaluate the free radical scavenging activity of HSBE, its reactivity as hydrogen atom donor toward the 1, 1‐diphenyl‐2‐picrylhydrazyl has been measured using stopped‐flow spectrophotometry. It was found that the second‐order rate constant, k2, obtained at 25 °C was 1.4 (g/L)−1s−1 for HSBE. To compare different chain‐breaking antioxidants quantitatively, we obtained the second‐order rate constant, k2′, on the molar basis of active hydroxyl groups in the tested substances. As a result, the k2′ values for HSBE, 6‐hydroxy‐2, 5, 7, 8‐tetramethylchroman‐2‐carboxylic acid (Trolox), caffeic acid, and (+)‐catechin were 2.6 × 103, 2.0 × 103, 2.3 × 102, and 6.0 × 102 M−1s−1, respectively. These results show that HSBE and Trolox exerted the same free radical scavenging activity under these conditions. In addition, HSBE significantly inhibited the oxidation of methyl linoleate micelles in aqueous dispersions at 30 °C and its antioxidant activity (kinh) was more effective than those of caffeic acid and (+)‐catechin. This is the first study on bamboo extracts in the context of radical scavenging activity that reports kinetic results.

Practical Application:  We determined the stoichiometric number and the rate constants of bamboo extracts using the method that was devised in determining the antioxidant activity of mixtures. This is the first study of bamboo extracts as an antioxidant that reports the stoichiometric and kinetic results.
Study on Mitigation of Acrylamide Formation in Cookies by 5 Antioxidants
Authors: Li Dong , Chen Yaqi , Zhang Yu , Lu Baiyi , Jin Cheng , Wu Xiaoqin , Zhang Ying
Published: October 2012

Abstract:  This study investigated the capacity of various antioxidants in reducing the formation of acrylamide during cookie processing. Five antioxidants, antioxidants of bamboo leaves (AOB), sodium erythorbate (SE), tea polyphenols (TP), vitamin E (VE), and tert‐butyl hydroquinone (TBHQ), were individually added into cookie formulas, and acrylamide content was determined by liquid chromatography tandem mass spectrometry (LC‐MS/MS). Cookie quality indexes, including flavor, brittleness, and water activity, were also evaluated. Results showed that the maximum inhibitory rate of acrylamide by AOB was achieved with addition of 0.2 g/kg AOB. Addition of AOB (0.2 g/kg), TP (0.1 g/kg), VE (0.1 g/kg), SE (0.1 g/kg), and TBHQ (0.2 g/kg) mitigated the formation of acrylamide by 63.9%, 43.0%, 71.2%, 49.6%, and 54.1%, respectively. Sensory evaluation showed that the color, texture, and flavor of cookies processed with either AOB (0.2 g/kg) or VE (0.1 g/kg) had no significant difference compared to control cookies (P > 0.05). The present study indicated that AOB (0.2 g/kg) and VE (0.1 g/kg) could not only effectively mitigate the formation of acrylamide, but also retain acceptable sensory attributes of cookies. This work shows the potential effectiveness of antioxidants in food processing to decrease acrylamide formation.

Practical Application:  There is an urgent need for reducing the level of acrylamide produced during food processing. This study found that certain antioxidants (antioxidant of bamboo leaves and vitamin E) could effectively inhibit acrylamide formation in cookie processing without affecting sensory properties. The results suggested that the application of antioxidants could be an effective method to decrease acrylamide formation.
Two Challenges in Cognitive Musicology
Authors: Huron David
Published: October 2012

Two themes in music cognition research are highlighted—inspired by the contributions in this volume: (a) statistical learning and (b) evolutionary theorizing. Our ability to test alternatives to statistical learning is threatened by the rapidly diminishing opportunities for cross‐cultural studies unconfounded by bimusicalism. Our ability to infer possible evolutionary origins for music is confounded by the “hedonic plenitude” of modern music‐making—where multiple pleasure channels are activated simultaneously. Cognitively inspired music research will benefit by studying a wider range of musical cultures. Evolutionary theorizing will benefit by further work involving comparative animal behavior.
Music Cognition and the Cognitive Sciences
Authors: Pearce Marcus , Rohrmeier Martin
Published: October 2012

Why should music be of interest to cognitive scientists, and what role does it play in human cognition? We review three factors that make music an important topic for cognitive scientific research. First, music is a universal human trait fulfilling crucial roles in everyday life. Second, music has an important part to play in ontogenetic development and human evolution. Third, appreciating and producing music simultaneously engage many complex perceptual, cognitive, and emotional processes, rendering music an ideal object for studying the mind. We propose an integrated status for music cognition in the Cognitive Sciences and conclude by reviewing challenges and big questions in the field and the way in which these reflect recent developments.
Lifestyle Educational Program Strongly Increases Compliance to Nonpharmacologic Intervention in Hypertensive Patients: A 2‐Year Follow‐Up Study
Authors: Ferrara Aldo L. , Pacioni Delia , Di Fronzo Valentina , Russo Barbara F. , Staiano Laura , Speranza Enza , Gente Rosaria , Gargiulo Francesco , Ferrara Fabio
Published: October 2012

J Clin Hypertens (Greenwich). 2012;14:767–772. ©2012 Wiley Periodicals, Inc.

The authors investigated the efficacy of a lifestyle educational program, organized in small group meetings, in improving the outcome of a nonpharmacologic intervention. One hundred and eighty‐eight hypertensive patients with stable blood pressure (BP) levels and drug therapy in the previous 6 months were randomly divided into educational care (EC) and usual care (UC) groups. They were followed at 3‐month intervals up to 2 years. In addition to the visits in an outpatient clinic, patients in the EC program participated in small group meetings in order to improve their knowledge of the disease and reinforce their motivation for treatment. At baseline, EC and UC groups were similar for age, sex, body mass index (BMI), blood pressure (BP) levels, and pharmacologic treatment. Patients in the EC group had significantly reduced total energy, total and saturated fats, and sodium intake. Physical activity was significantly increased in the EC group as well. At the end of the 1‐year follow‐up, BMI (P<.001), visceral fat (P<.001), and BP (P<.001) were significantly lower in the EC group compared with the UC group. Pharmacologic treatment during the study was similar for all classes of drugs apart from diuretics whose dose was higher in the UC group at the end of the study.
Practitioner Review: Do performance‐based measures and ratings of executive function assess the same construct?
Authors: Toplak Maggie E. , West Richard F. , Stanovich Keith E.
Published: October 2012

Background: Both performance‐based and rating measures are commonly used to index executive function in clinical and neuropsychological assessments. They are intended to index the same broad underlying mental construct of executive function. The association between these two types of measures was investigated in the current article.

Method and Results: We examined the association between performance‐based and rating measures of executive function in 20 studies. These studies included 13 child and 7 adult samples, which were derived from 7 clinical, 2 nonclinical, and 11 combined clinical and nonclinical samples. Only 68 (24%) of the 286 relevant correlations reported in these studies were statistically significant, and the overall median correlation was only .19.

Conclusions: It was concluded that performance‐based and rating measures of executive function assess different underlying mental constructs. We discuss how these two types of measures appear to capture different levels of cognition, namely, the efficiency of cognitive abilities and success in goal pursuit. Clinical implications of using performance‐based and rating measures of executive function are discussed, including the use of these measures in assessing ADHD.
Voxel‐Based Morphometric Analysis in Hypothyroidism Using Diffeomorphic Anatomic Registration via an Exponentiated Lie Algebra Algorithm Approach
Authors: Singh S. , Modi S. , Bagga D. , Kaur P. , Shankar L. R. , Khushu S.
Published: October 2012

The present study aimed to investigate whether brain morphological differences exist between adult hypothyroid subjects and age‐matched controls using voxel‐based morphometry (VBM) with diffeomorphic anatomic registration via an exponentiated lie algebra algorithm (DARTEL) approach. High‐resolution structural magnetic resonance images were taken in ten healthy controls and ten hypothyroid subjects. The analysis was conducted using statistical parametric mapping. The VBM study revealed a reduction in grey matter volume in the left postcentral gyrus and cerebellum of hypothyroid subjects compared to controls. A significant reduction in white matter volume was also found in the cerebellum, right inferior and middle frontal gyrus, right precentral gyrus, right inferior occipital gyrus and right temporal gyrus of hypothyroid patients compared to healthy controls. Moreover, no meaningful cluster for greater grey or white matter volume was obtained in hypothyroid subjects compared to controls. Our study is the first VBM study of hypothyroidism in an adult population and suggests that, compared to controls, this disorder is associated with differences in brain morphology in areas corresponding to known functional deficits in attention, language, motor speed, visuospatial processing and memory in hypothyroidism.
Excessive Wnt/β‐catenin signaling disturbs tooth‐root formation
Authors: Bae C. H. , Lee J. Y. , Kim T. H. , Baek J. A. , Lee J. C. , Yang X. , Taketo M. M. , Jiang R. , Cho E. S.
Published: October 2012

Background and Objective

Wingless‐type MMTV integration site family (Wnt)/β‐catenin signaling plays an essential role in cellular differentiation and matrix formation during skeletal development. However, little is known about its role in tooth‐root formation. In a previous study, we found excessive formation of dentin and cementum in mice with constitutive β‐catenin stabilization in the dental mesenchyme. In the present study we analyzed the molar roots of these mice to investigate the role of Wnt/β‐catenin signaling in root formation in more detail.

Material and Methods

We generated OC‐Cre:Catnb+/lox(ex3) mice by intercrossing Catnb+/lox(ex3) and OC‐Cre mice, and we analyzed their mandibular molars using radiography, histomorphometry and immunohistochemistry.

Results

OC‐Cre:Catnb+/lox(ex3) mice showed impaired root formation. At the beginning of root formation in mutant molars, dental papilla cells did not show normal differentiation into odontoblasts; rather, they were prematurely differentiated and had a disorganized arrangement. Interestingly, SMAD family member 4 was upregulated in premature odontoblasts. In 4‐wk‐old mutant mice, molar roots were about half the length of those in their wild‐type littermates. In contrast to excessively formed dentin in crown, root dentin was thin and hypomineralized in mutant mice. Biglycan and dentin sialophosphoprotein were downregulated in root dentin of mutant mice, whereas dentin matrix protein 1 and Dickkopf‐related protein 1 were upregulated. Additionally, ectonucleotide pyrophosphatase/phosphodiesterase 1 was significantly downregulated in the cementoblasts of mutant molars. Finally, in the cementum of mutant mice, bone sialoprotein was downregulated but Dickkopf‐related protein 2 was upregulated.

Conclusion

These results suggest that temporospatial regulation of Wnt/β‐catenin signaling plays an important role in cell differentiation and matrix formation during root and cementum formation.
Pathological bacterial translocation in cirrhosis: pathophysiology, diagnosis and clinical implications
Authors: Bellot Pablo , Francés Rubén , Such Jose
Published: October 2012

Bacterial translocation (BT) is defined by the passage of viable indigenous bacteria from the intestinal lumen to mesenteric lymph nodes (MLNs) and other territories, and its diagnostic criteria rely on the isolation of viable bacteria in MLNs. Small intestinal overgrowth, increased intestinal permeability and immunological alterations are the main factors involved in its pathogenesis. BT is obviously difficult to identify in patients with cirrhosis, and alternative methods have been proposed instead. Bacterial DNA detection and species identification in serum or ascitic fluid has been proposed as a reliable marker of BT. Bacterial products, such as endotoxin, or bacterial DNA can translocate to extra‐intestinal sites and promote an immunological response similar to that produced by viable bacteria. Therefore, pathological BT plays an important role in the pathogenesis of the complications of cirrhosis, not only in infections, but by exerting a profound inflammatory state and exacerbating the haemodynamic derangement. This may promote in turn the development of hepatorenal syndrome, hepatic encephalopathy and other portal hypertension‐related complications. Therapeutic approaches for the prevention of BT in experimental and human cirrhosis are summarized. Finally, new investigations are needed to better understand the pathogenesis and consequences of translocation by viable bacteria (able to grow in culture), or non‐viable BT (detection of bacterial fragments with negative culture) and open new therapeutic avenues in patients with cirrhosis.
Cow's milk associated rectal bleeding: a population based prospective study
Authors: Elizur Arnon , Cohen Michal , Goldberg Michael R. , Rajuan Nelly , Cohen Adi , Leshno Moshe , Katz Yitzhak
Published: October 2012

Background

Isolated rectal bleeding in infants is often attributed to the consumption of cow's milk. However, the prevalence of this condition has not been described, and its preferred diagnostic methods and management are controversial.

Methods

In a prospective population‐based study following 13,019 children from birth, 21 infants with isolated rectal bleeding attributed to cow's milk protein consumption were identified. Following evaluation, parents were encouraged to resume cow's milk protein and infants were followed for reappearance of symptoms and thereafter for 6 yr. In addition, infants with rectal bleeding were compared to a control group of healthy infants.

Results

The prevalence of isolated rectal bleeding attributed to cow's milk consumption was 0.16%. All infants were asymptomatic within days of dietary modifications. Eleven of the 14 infants (78.5%) whose parents reintroduced cow's milk protein to their diet following our evaluation tolerated it with no adverse effects. Those 11 infants were significantly younger at initial consumption of cow's milk protein (6.7 ± 1.6 months) compared to those who continued elimination diet (17.7 ± 9.2 months), (p = 0.002) while their 1‐yr hemoglobin levels were comparable (p = 0.98). No risk factors for rectal bleeding were identified.

Conclusions

The prevalence of isolated rectal bleeding attributed to cow' milk is low. The condition is generally benign and resolves quickly with elimination diet. Reintroduction of cow's milk following resolution of symptoms is often well tolerated and is recommended for confirming the diagnosis and avoiding prolonged unnecessary elimination diets.
A randomized trial of Lactobacillus plantarum CJLP133 for the treatment of atopic dermatitis
Authors: Han Youngshin , Kim Bongjoon , Ban Jeongsook , Lee Jeongok , Kim Beom Joon , Choi Byung Sun , Hwang Sehee , Ahn Kangmo , Kim Jihyun
Published: October 2012

Background

There have been considerable disagreements regarding the therapeutic effects of probiotics in atopic dermatitis (AD). We performed this study to examine whether the oral administration of Lactobacillus plantarum CJLP133 improves pediatric AD.

Methods

In a randomized, double‐blind, placebo‐controlled study, either L. plantarum CJLP133 at a dosage of 0.5 × 1010 colony‐forming units or placebo in children aged 12 months to 13 yr was given twice a day for 12 wk. SCOring of Atopic Dermatitis (SCORAD) scores, eosinophil counts, serum total IgE, and cytokines were evaluated.

Results

Forty‐four of 58 patients in the probiotic group and 39 of 60 patients in the placebo group completed the study. The SCORAD score at week 14 was lower in the probiotic group than in the placebo group (p = 0.044). The mean change in the SCORAD score from weeks 2 to 14 was 9.1 in the probiotic group, which was greater than the mean change of 1.8 in the placebo group (p = 0.004). No statistical differences in the total use of topical corticosteroids were found between two groups (p = 0.815). In the probiotic group, the total eosinophil count was significantly lower at the end of the intervention compared to the baseline measurements (p = 0.023). Logarithmic IFN‐γ and IL‐4 were significantly decreased by the end of the intervention compared to baseline measurements in the probiotic group (p < 0.001 and 0.049).

Conclusions

Our results suggest that supplementation with probiotic L. plantarum CJLP133 is beneficial in the treatment of pediatric AD.