bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization and Preliminary Toxicity Assay of Nano‐Titanium Dioxide Additive in Sugar‐Coated Chewing Gum
Authors: Chen Xin‐Xin , Cheng Bin , Yang Yi‐Xin , Cao Aoneng , Liu Jia‐Hui , Du Li‐Jing , Liu Yuanfang , Zhao Yuliang , Wang Haifang
Published: October 2012

Nanotechnology shows great potential for producing food with higher quality and better taste through including new additives, improving nutrient delivery, and using better packaging. However, lack of investigations on safety issues of nanofood has resulted in public fears. How to characterize engineered nanomaterials in food and assess the toxicity and health impact of nanofood remains a big challenge. Herein, a facile and highly reliable separation method of TiO2 particles from food products (focusing on sugar‐coated chewing gum) is reported, and the first comprehensive characterization study on food nanoparticles by multiple qualitative and quantitative methods is provided. The detailed information on nanoparticles in gum includes chemical composition, morphology, size distribution, crystalline phase, particle and mass concentration, surface charge, and aggregation state. Surprisingly, the results show that the number of food products containing nano‐TiO2 (<200 nm) is much larger than known, and consumers have already often been exposed to engineered nanoparticles in daily life. Over 93% of TiO2 in gum is nano‐TiO2, and it is unexpectedly easy to come out and be swallowed by a person who chews gum. Preliminary cytotoxicity assays show that the gum nano‐TiO2 particles are relatively safe for gastrointestinal cells within 24 h even at a concentration of 200 μg mL−1. This comprehensive study demonstrates accurate physicochemical property, exposure, and cytotoxicity information on engineered nanoparticles in food, which is a prerequisite for the successful safety assessment of nanofood products.
Distinct effects of enriched environment on dopamine clearance in nucleus accumbens shell and core following systemic nicotine administration
Authors: Zhu Jun , Bardo Michael T. , Dwoskin Linda P.
Published: October 2012

Environmental enrichment during development may reduce drug abuse liability by modulating dopamine transporter (DAT) function. Nucleus accumbens (NAc) shell and core respond differentially to regulate the rewarding properties and locomotor stimulant effects of psychostimulants. The current study evaluated dopamine (DA) clearance (CLDA) in the NAc shell and core using in vivo voltammetry in rats raised in an enriched condition (EC) or an impoverished condition (IC) and determined the effect of nicotine (0.4 mg/kg) on CLDA. Baseline CLDA in NAc shell and core was not different between EC and IC rats. In the saline control group, CLDA in NAc shell was greater across time in IC when compared with EC rats, whereas CLDA in NAc core was greater in EC rats when compared with IC rats. Consistent with these findings, opposite effects of enrichment on DA clearance in shell and core were obtained following acute nicotine administration. In NAc shell, nicotine increased CLDA in EC rats, but not in IC rats. Conversely, in NAc core, nicotine increased CLDA in IC rats, but not in EC rats. The current results demonstrate that environmental enrichment differentially regulates the response to nicotine in NAc shell and core via alterations in DAT function, which may explain how environmental enrichment reduces the behavioral response to nicotine. Synapse, 2013. © 2012 Wiley Periodicals, Inc.
Hematologic profile of neonates with growth restriction is associated with rate and degree of prenatal Doppler deterioration
Authors: Baschat A. A. , Kush M. , Berg C. , Gembruch U. , Nicolaides K. H. , Harman C. R. , Turan O. M.
Published: October 2012

Objective

To examine the relationship between hematologic parameters at birth and prenatal progression of Doppler abnormalities in fetal growth restriction (FGR).

Methods

The study was a secondary analysis of FGR patients (abdominal circumference < 5th percentile and umbilical artery pulsatility index (UA‐PI) elevation) with at least three examinations prior to delivery. Prenatal progression was classified as rapid, moderate or slow based on the interval between diagnosis and delivery and the extent of UA, middle cerebral artery and ductus venosus Doppler abnormalities. Associations between diagnosis‐to‐delivery interval, Doppler Z‐scores, progression and hematologic parameters at birth were examined.

Results

Of 130 patients, 54 (41.5%) had rapid, 51 (39.2%) moderate and 25 (19.2%) slow deterioration, delivering within 4, 6 and 9 weeks of diagnosis, respectively. The strongest association of moderate and rapid deterioration was with a low platelet count (r2 = 0.37 and 0.70, respectively; P < 0.0001). In patients with moderate deterioration, platelet count correlated inversely with UA‐PI (ρ = −0.44, P = 0.001) and was lowest when end‐diastolic velocity was absent. With rapid progression, platelet count correlated inversely with nucleated red blood cell count (ρ = −0.51, P < 0.001) but no longer with UA‐PI.

Conclusion

Our observations suggest a relationship between prenatal clinical progression of FGR and hematologic abnormalities at birth. Accelerating cardiovascular deterioration is associated with decreased platelet count, which can be explained by placental consumption or dysfunctional erythropoiesis and thrombopoiesis. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Norms governing urban African American adolescents' sexual and substance‐using behavior
Authors: Dolcini M. Margaret , Catania Joseph A. , Harper Gary W. , Watson Susan E. , Ellen Jonathan M. , Towner Senna L.
Published: October 2012

Using a probability‐based neighborhood sample of urban African American youth and a sample of their close friends (N = 202), we conducted a one‐year longitudinal study to examine key questions regarding sexual and drug using norms. The results provide validation of social norms governing sexual behavior, condom use, and substance use among friendship groups. These norms had strong to moderate homogeneity; and both normative strength and homogeneity were relatively stable over a one‐year period independent of changes in group membership. The data further suggest that sex and substance using norms may operate as a normative set. Similar to studies of adults, we identified three distinct “norm‐based” social strata in our sample. Together, our findings suggest that the norms investigated are valid targets for health promotion efforts, and such efforts may benefit from tailoring programs to the normative sets that make up the different social strata in a given adolescent community.
The structure of the corpus callosum in obsessive compulsive disorder
Authors: Di Paola M. , Luders E. , Rubino I.A. , Siracusano A. , Manfredi G. , Girardi P. , Martinotti G. , Thompson P.M. , Chou Y.-Y. , Toga A.W. , Caltagirone C. , Spalletta G.
Published: October 2012

Abnormal brain connectivity has recently been reported in obsessive compulsive disorder (OCD). However, structural differences in the corpus callosum (CC), the primary structure connecting the two hemispheres, have not been extensively studied. In this case-control study, we recruited 30 patients with OCD and 30 healthy control subjects carefully matched for age, sex and handedness. Combining surface-based mesh-modeling and voxel-based morphometry (VBM), we compared callosal thickness and white matter (WM) density in patients and controls. We investigated associations between callosal structure and cortical gray matter (GM) density, and we related CC measures to neuropsychological performance in OCD. OCD patients showed small anterior and posterior callosal regions compared to healthy control subjects. In the OCD group, anterior callosal thickness was positively correlated with GM density of the right mid-dorso-lateral prefrontal (BA 9/46) area, while posterior callosal thickness was positively correlated with GM density in the left supramarginal gyrus (BA 40). Moreover, posterior callosal WM density was positively correlated with verbal memory, visuo-spatial memory, verbal fluency, and visuo-spatial reasoning performances. Callosal attributes were related to GM density in cortical areas innervated by the CC, and were also related to performance in cognitive domains impaired in the disorder. The CC may therefore be integrally involved in OCD.
Localisation of a family of complex‐forming β‐barrels in the T. vaginalis hydrogenosomal membrane
Authors: Kay Christopher , Lawler Karen , Self Tim J. , Dyall Sabrina D. , Kerr Ian D.
Published: October 2012

Crucial to organellogenesis was the development of membrane translocases responsible for delivering proteins to new cellular compartments. This investigation examines the Trichomonas vaginalis hydrogenosome, a mitochondrially derived organelle. We identify an expanded family of putative β‐barrel proteins (THOM A–I) comprising nine related sequences. Sub‐cellular localisation by immunofluorescence and biochemical fractionation is consistent with THOMs being localised to the hydrogenosomal membrane. Native gel electrophoresis and chemical cross‐linking support the ability of THOM proteins to be components of membrane‐bound oligomeric protein complexes, consistent with a role in protein translocation.
Munc13 genotype regulates secretory amyloid precursor protein processing via postsynaptic glutamate receptors
Authors: Hartlage‐Rübsamen Maike , Waniek Alexander , Roßner Steffen
Published: October 2012

The amyloid precursor protein (APP) can be proteolytically degraded via non‐amyloidogenic α‐secretase and amyloidogenic β‐secretase pathways. Previously, we have identified the presynaptic protein Munc13‐1 as a diacylglycerol/phorbolester (DAG/PE) receptor that contributes to secretory, non‐amyloidogenic APP processing after PE stimulation. Here, we used organotypic brain slice cultures from wild‐type mice and from Munc13‐1 knock‐out (KO), Munc13‐2 KO and Munc13‐1/2 double KO (DKO) mice for pharmacological stimulation experiments. First, we demonstrate that neuronal populations and synaptic components important for secretory APP processing develop normally in organotypic brain slice cultures of all genotypes analyzed. Blockade of voltage‐gated Na+ channels by tetrodotoxin reduced the PE‐stimulated secretory APP processing, whereas depolarization by high extracellular K+ concentration evoked APP secretion. Additionally, the PE‐stimulated APP secretion from Munc13‐1 KO brain slices was significantly lower than that from wild‐type brain slices. This effect was not observed in brain slices from Munc13‐2 KO mice, which is consistent with the lower abundance and subpopulation‐specific distribution of Munc13‐2 in presynaptic elements. In Munc13‐1/2 DKO brain slices, the deficiency of Munc13‐1 dominated the effect of APP processing. The Munc13‐1 KO effect on APP processing could be rescued by the stimulation of postsynaptic glutamatergic receptors. This indicates that lack of postsynaptic glutamate receptor stimulation in Munc13‐1 KO brain slice cultures but not presynaptic mechanisms account for compromised APP processing. We conclude that organotypic brain slices cultures are a valuable tool for studying APP processing pathways in intact neuronal circuits and that neuronal activity is important for maintenance of the non‐amyloidogenic APP processing.
Hepatocellular carcinoma cells cause different responses in expressions of cancer‐promoting genes in different cancer‐associated fibroblasts
Authors: Lin Zu‐Yau , Chuang Wan‐Long
Published: October 2012

Cancer‐associated fibroblast (CAF) is one of the most crucial components of the tumor microenvironment to promote the invasiveness of cancer cells. The interactions between cancer cells and CAFs are bidirectional. Our recent study showed that up‐regulations of chemokine (C‐C motif) ligand 2 (CCL2), chemokine (C‐C motif) ligand 26 (CCL26), interleukin 6 (IL6), and lysyl oxidase‐like 2 (LOXL2) genes in cancer cells were parts of the common effects of CAFs on hepatocellular carcinoma (HCC) cells to promote proliferation, migration and invasion of cancer cells. However, the subject of how HCC cells to influence the gene expressions of CAFs still needs to be clarified. The purpose of this study was to investigate this issue. Two human HCC (HCC24/KMUH, HCC38/KMUH) and two human CAF cell lines (F26/KMUH, F28/KMUH) were studied. Influence of HCC38/KMUH cancer cells on differential expressions of genes in F28/KMUH CAFs was detected by microarray to select target genes for further analysis. Both HCC cell lines increased proliferation (all p < 0.005) and migration (all p < 0.0001) of two CAF cell lines. HCC24/KMUH cancer cells had stronger ability to promote migration of F26/KMUH CAFs than HCC38/KMUH cancer cells did (p < 0.0001). Eleven up‐regulated cancer‐promoting genes, including apelin (APLN), CCL2, CCL26, fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), IL6, mucin 1 (MUC1), LOXL2, platelet‐derived growth factor alpha polypeptide (PDGFA), phosphoglycerate kinase 1 (PGK1), and vascular endothelial growth factor A (VEGFA) detected by microarray showed good correlation with results of quantitative reverse transcriptase‐polymerase chain reaction study. Among these genes, HCC24/KMUH cancer cells had same tendency of effects on differential expressions of genes in F28/KMUH CAFs as HCC38/KMUH cancer cells did. However, the responses of F26/KMUH CAFs to different HCC cell lines were variable. Only PGK1 gene was consistently up‐regulated and PDGFA gene was consistently down‐regulated caused by both HCC cell lines in F26/KMUH CAFs. Besides PGK1 gene, HCC38/KMUH cancer cells only up‐regulated APLN, LOXL2, and VEGFA genes and HCC24/KMUH cancer cells only up‐regulated FGF2 gene in F26/KMUH CAFs. In conclusion, HCC cells can promote proliferation and migration of CAFs. However, the impact of HCC cells on differential expressions of cancer‐promoting genes in CAFs is influenced by the characteristics of CAFs. This implies that blocking single or several particular cancer‐promoting genes in CAFs is unable to become a common stratagem for the treatment of HCC.
Dexmedetomidine did not reduce the effects of tourniquet‐induced ischemia‐reperfusion injury during general anesthesia
Authors: Bostankolu Evrim , Ayoglu Hilal , Yurtlu Serhan , Okyay Rahsan Dilek , Erdogan Gülay , Deniz Yeliz , Hanci Volkan , Can Murat , Turan Isil Ozkocak
Published: October 2012

Ischemia reperfusion injury causes the release of free oxygen radicals. Free oxygen radicals initiate the production of toxic metabolites, such as malondialdehyde (MDA), through the lipid peroxidation of cellular membranes. Following lipid peroxidation, the antioxidant enzyme system is activated against reactive oxygen species (ROS) and attempts to protect cells from oxidative damage. There is a balance between the scavenging capacity of antioxidant enzymes and ROS. Because of this balance, the total antioxidant capacity (TAC) measurement is a sensitive indicator of the overall protective effects of the antioxidants. Alpha2 receptor agonists are effective in preventing hemodynamic reactions during extremity surgeries by preventing the release of catecholamines secondary to tourniquet application. They have also been shown to possess preventive effects in various ischemia‐reperfusion injury models. In our study, we examined the effects of dexmedetomidine on tourniquet‐induced ischemia‐reperfusion injury in lower extremity surgeries performed under general anesthesia. The effects of dexmedetomidine were measured with serum MDA and TAC levels. We studied 60 adult American Society of Anesthesiologists (ASA) physical status I or II patients undergoing one‐sided lower extremity surgery with tourniquet. The patients were randomly divided into two groups. Group D was administered a dexmedetomidine infusion at a rate of 0.1 μg/kg/minute−1 for 10 minutes prior to induction and then at 0.7 μg/kg/hour−1 until 10 minutes before the end of the operation. The control group (Group C) received a saline infusion of the same amount and for the same period of time. General anesthesia was induced with thiopental, fentanyl, and rocuronium and maintained with nitrous oxide and sevoflurane in both groups. Venous blood samples were obtained before the administration of the study drugs (basal) at 1 minute before tourniquet release and at 5 and 20 minutes after tourniquet release (ATR). In both groups, MDA levels decreased at 5 and 20 minutes ATR when compared with the basal values (p < 0.05). TAC levels decreased at 1 and 5 minutes ATR and then returned to basal values at 20 minutes ATR (p < 0.05). In reference to the prevention of lipid peroxidation in tourniquet‐induced ischemia‐reperfusion injury, the results from the two groups in our study showed that dexmedetomidine did not have an additional protective role during routine general anesthesia.
A case of cutaneous malignant fibrous histiocytoma with multiple organ metastases
Authors: Suzuki Shuji , Watanabe Shoichi , Kato Hiroshi , Inagaki Hiroshi , Hattori Hideo , Morita Akimichi
Published: October 2012

Malignant fibrous histiocytoma is a soft tissue sarcoma that most commonly occurs in the extremities and rarely metastasizes cutaneously. A 79‐year‐old male patient consulted a dermatologist 11 months after recognizing an intractable ulcer on the right mandible. Punch biopsy revealed eosinophilic tumor cells in the dermal area and proliferation of rich spindle cells. Malignant fibrous histiocytoma or atypical fibroxanthoma was suspected and he was referred to our hospital. Red plaque tumors on the right mandible and right temple were 30 mm and 15 mm in size, respectively. The right mandible lesion was ulcerated. Immunohistochemically, the lesions were positive for CD10, CD74 and alpha‐smooth muscle actin. Radiological analysis revealed multiple organ metastases, including bone, liver, lung and skin on the right temple. The patient was diagnosed with malignant fibrous histiocytoma, stage IV and died 8 weeks after the first visit due to respiratory failure. Cutaneous malignant fibrous histiocytoma has a poor prognosis resulting in death.
MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib
Authors: Huang Ming-Hung , Lee Jih-Hsiang , Chang Ya-Ju , Tsai Hsin-Hui , Lin Yu-Lin , Lin Anya Maan-Yuh , Yang James Chih-Hsin
Published: October 2012

Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs), including gefitinib. Acquired resistance to EGFR‐TKIs develops after prolonged treatments. The study was prompt to explore effective strategies against resistance to EGFR‐TKIs. We established gefitinib resistant PC‐9 cells which harbor EGFR exon 19 deletion. Known mechanisms for intrinsic or acquired EGFR‐TKI resistance, including KRAS mutation, HER2 mutation, EGFR T790M mutation and MET gene amplification, were studied, and we did not observe any known mechanisms for intrinsic or acquired resistance to EGFR‐TKIs in the resistant cells. In the parental PC‐9 cells, labeled as PC‐9/wt, gefitinib completely inhibited EGF‐induced phosphorylation of EGFR, AKT and ERK. Gefitinib inhibited EGFR phosphorylation, but was unable to block EGF‐induced phosphorylation of ERK in resistant cells, labeled as PC‐9/gef cells, including PC‐9/gefB4, PC‐9/gefE3, and PC‐9/gefE7 subclones. We detected NRAS Q61K mutation in the PC‐9/gef cells but not the PC‐9/wt cells. MEK inhibitors, either AZD6244 or CI1040, inhibited ERK phosphorylation and sensitized gefitinib‐induced cytotoxicity in PC‐9/gef cells. Whereas MEK inhibitors or gefitinib alone did not activate caspases in PC‐9/gef cells, combination of gefitinib and AZD6244 or CI1040 induced apoptosis. Our in vivo studies showed that gefitinib inhibited growth of PC‐9/wt xenografts but not PC‐9/gef xenografts. Furthermore, combination of a MEK inhibitor and gefitinib inhibited growth of both PC‐9/wt xenografts and PC‐9/gefB4 xenografts. To conclude, persistent activation of ERK pathway contributes to the acquired gefitinib‐resistance. Combined treatment of gefitinib and MEK inhibitors may be therapeutically useful for acquired gefitinib‐resistance lung adenocarcinoma cells harboring EGFR mutations.
Insulin gene therapy from design to beta cell generation
Authors: Sanlioglu Ahter D. , Altunbas Hasan Ali , Balci Mustafa Kemal , Griffith Thomas S. , Sanlioglu Salih
Published: October 2012

Despite the fact that insulin injection can protect diabetic patients from developing diabetes-related complications, recent meta-analyses indicate that rapid and long-acting insulin analogues only provide a limited benefit compared with conventional insulin regarding glycemic control. As insulin deficiency is the main sequel of type-1 diabetes (T1D), transfer of the insulin gene-by-gene therapy is becoming an attractive treatment modality even though T1D is not caused by a single genetic defect. In contrast to human insulin and insulin analogues, insulin gene therapy targets to supplement patients not only with insulin but also with C-peptide. So far, insulin gene therapy has had limited success because of delayed and/or transient gene expression. Sustained insulin gene expression is now feasible using current gene-therapy vectors providing patients with basal insulin coverage, but management of postprandial hyperglycaemia is still difficult to accomplish because of the inability to properly control insulin secretion. Enteroendocrine cells of the gastrointestinal track (K cells and L cells) may be ideal targets for insulin gene therapy, but cell-targeting difficulties have limited practical implementation of insulin gene therapy for diabetes treatment. Therefore, recent gene transfer technologies developed to generate authentic beta cells through transdifferentiation are also highlighted in this review.
Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life
Authors: Nielsen M. O. , Kongsted A. H. , Thygesen M. P. , Strathe A. B. , Caddy S. , Quistorff B. , Jørgensen W. , Christensen V. G. , Husted S. , Chwalibog A. , Sejrsen K. , Purup S. , Svalastoga E. , McEvoy F. J. , Johnsen L.
Published: October 2012

We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50 % of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate–high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORM-HCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P< 0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P< 0·05), increased neonatal appetite for fat-(P= 0·004) rather than carbohydrate-rich feeds (P< 0·001) and reduced deposition of subcutaneous fat in both sexes (P< 0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P< 0·001). Postnatal overfeeding (HCHF) resulted in obesity (>30 % fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre- and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.
MARITAL FERTILITY AND INCOME: MODERATING EFFECTS OF THE CHURCH OF JESUS CHRIST OF LATTER-DAY SAINTS RELIGION IN UTAH
Authors: STANFORD JOSEPH B. , SMITH KEN R.
Published: October 2012

Utah has the highest total fertility of any state in the United States and also the highest proportion of population affiliated with the Church of Jesus Christ of Latter-day Saints (the LDS or Mormon Church). Data were used from the 1996 Utah Health Status Survey to investigate how annual household income, education and affiliation with the LDS Church affect fertility (children ever born) for married women in Utah. Younger age and higher education were negatively correlated with fertility in the sample as a whole and among non-LDS respondents. Income was negatively associated with fertility among non-LDS respondents. However, income was positively correlated with fertility among LDS respondents. This association persisted when instrumental variables were used to address the potential simultaneous equations bias arising from the potential endogeneity of income and fertility. The LDS religion's pronatalist stance probably encourages childbearing among those with higher income.
Do parasites adopt different strategies in different intermediate hosts? Host size, not host species, influencesCoitocaecum parvum(Trematoda) life history strategy, size and egg production
Authors: DANIELS R. RUIZ , BELTRAN S. , POULIN R. , LAGRUE C.
Published: October 2012

Host exploitation induces host defence responses and competition between parasites, resulting in individual parasites facing highly variable environments. Alternative life strategies may thus be expressed in context-dependent ways, depending on which host species is used and intra-host competition between parasites.Coitocaecum parvum(Trematode) can use facultative progenesis in amphipod intermediate hosts,Paracalliope fluviatilis, to abbreviate its life cycle in response to such environmental factors.Coitocaecum parvumalso uses another amphipod host,Paracorophium excavatum, a species widely different in size and ecology fromP. fluviatilis. In this study, parasite infection levels and strategies in the two amphipod species were compared to determine whether the adoption of progenesis byC. parvumvaried between these two hosts. Potential differences in size and/or egg production betweenC. parvumindividuals according to amphipod host species were also investigated. Results show thatC. parvumlife strategy was not influenced by host species. In contrast, host size significantly affectedC. parvumstrategy, size and egg production. Since intra-host interactions between co-infecting parasites also influencedC. parvumstrategy, size and fecundity, it is highly likely that within-host resource limitations affectC. parvumlife strategy and overall fitness regardless of host species.
Food combinations for cholesterol lowering
Authors: Harland Janice I.
Published: October 2012

Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3–9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten ‘portfolio diet’ studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22–30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into ‘portfolio diets’ increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.
Bringing a developmental perspective to anxiety genetics
Authors: McGrath Lauren M. , Weill Sydney , Robinson Elise B. , Macrae Rebecca , Smoller Jordan W.
Published: October 2012

Despite substantial recent advancements in psychiatric genetic research, progress in identifying the genetic basis of anxiety disorders has been limited. We review the candidate gene and genome-wide literatures in anxiety, which have made limited progress to date. We discuss several reasons for this hindered progress, including small samples sizes, heterogeneity, complicated comorbidity profiles, and blurred lines between normative and pathological anxiety. To address many of these challenges, we suggest a developmental, multivariate framework that can inform and enhance anxiety phenotypes for genetic research. We review the psychiatric and genetic epidemiological evidence that supports such a framework, including the early onset and chronic course of anxiety disorders, shared genetic risk factors among disorders both within and across time, and developmentally dynamic genetic influences. We propose three strategies for developmentally sensitive phenotyping: examination of early temperamental risk factors, use of latent factors to model underlying anxiety liability, and use of developmental trajectories as phenotypes. Expanding the range of phenotypic approaches will be important for advancing studies of the genetic architecture of anxiety disorders.
Confluence of genes, environment, development, and behavior in a post Genome-Wide Association Study world
Authors: Vrieze Scott I. , Iacono William G. , McGue Matt
Published: October 2012

This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoffs. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention in the history of psychology and is informed by psychometrics, whereas the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene–environment correlation). Genetically informed designs, which are no longer limited to twin and adoption studies thanks to ever-cheaper genotyping, are required to understand environmental influences. Finally, we outline the vast amount of individual difference in structural genomic variation, most of which remains to be leveraged in genetic association tests. Although the genetic data can be massive and burdensome (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research but with less confusion and more payoff than candidate gene research has to date.
The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: Moderation by FK506 binding protein 5 haplotype
Authors: Dackis Melissa N. , Rogosch Fred A. , Oshri Assaf , Cicchetti Dante
Published: October 2012

Childhood maltreatment is associated with lasting changes in neuroendocrine regulation, alterations in brain structure and function, and symptoms of “limbic irritability.” Limbic irritability symptoms include somatic, sensory, and behavioral phenomena and may stem from increased excitatory neurotransmission following maltreatment. We tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability and that variation within the FK506 binding protein 5 gene (FKBP5), a gene involved in glucorticoid receptor functioning, moderates these effects. The sample consisted of high-risk, low-income women (N= 236) living in an inner-city environment. Child maltreatment, limbic irritability, and symptoms of depression and dissociation were measured cross-sectionally using self-report assessments. Haplotype analyses were conducted across fourFKBP5single nucleotide polymorphisms:rs3800373,rs9296158,rs1360870, andrs9470080. Path analysis using bootstrapping procedures was performed to test hypotheses regarding indirect and conditional indirect effects. We found significant indirect effects of maltreatment on depression (β = 0.088,p< .01) and dissociation (β = 0.105,p< .01) via limbic irritability. In addition, variation withinFKBP5moderated these significant indirect effects. For individuals with one to two copies of the CATT haplotype, the indirect effects of maltreatment on depression (β = 0.137,p <.01) and dissociation (β = 0.132,p< .01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: β = 0.037,p >.05; dissociation: β = 0.002,p> .05). These results add to the growing evidence that child maltreatment may lead to symptoms of internalizing psychopathology through its impact on the limbic system. In addition, this study revealed a potential role ofFKBP5gene variants in contributing to risk for limbic system dysfunction.
Evocative gene–parenting correlations and academic performance at first grade: An exploratory study
Authors: Propper Cathi B. , Shanahan Michael J. , Russo Rosemary , Mills-Koonce W. Roger
Published: October 2012

Academic performance during the first years of school lays the groundwork for subsequent trajectories of academic success throughout childhood and adolescence. The current study tests a model according to which a gene–parenting correlation in the first 3 years of life is associated with subsequent psychosocial adjustment and then academic performance in the first grade (as indicated by teachers' assessment of academic behavior and two subscales of the Woodcock–Johnson Test of Achievement, Third Edition). Drawing on multiple waves of data from the Durham Child Health and Development Study, we find that risk alleles for dopamine receptor genes (dopamine receptor D4 for girls, dopamine receptor D2 for boys) are associated with less sensitive parenting. For girls, parenting mediates the link between dopamine receptor D4 and all academic outcomes. There is some indication that parenting also influences girls' withdrawn behavior in the classroom, which in turn influences teachers' assessments of academic performance. For boys, some evidence suggests that parenting is associated with emotion regulation, which is associated with teachers' assessments of academic behavior and both subscales of the Woodcock–Johnson. Replications of this exploratory study are necessary, but these findings provide a first step in understanding how evocative correlations in the home may predict indicators of psychosocial adjustment that in turn influence performance and achievement at school.
Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways
Authors: Monk Catherine , Spicer Julie , Champagne Frances A.
Published: October 2012

Prenatal exposure to maternal stress, anxiety, and depression can have lasting effects on infant development with risk of psychopathology. Although the impact of prenatal maternal distress has been well documented, the potential mechanisms through which maternal psychosocial variables shape development have yet to be fully elucidated. Advances in molecular biology have highlighted the role of epigenetic mechanisms in regulating gene activity, neurobiology, and behavior and the potential role of environmentally induced epigenetic variation in linking early life exposures to long-term biobehavioral outcomes. In this article, we discuss evidence illustrating the association between maternal prenatal distress and both fetal and infant developmental trajectories and the potential role of epigenetic mechanisms in mediating these effects. Postnatal experiences may have a critical moderating influence on prenatal effects, and we review findings illustrating prenatal–postnatal interplay and the developmental and epigenetic consequences of postnatal mother–infant interactions. The in utero environment is regulated by placental function and there is emerging evidence that the placenta is highly susceptible to maternal distress and a target of epigenetic dysregulation. Integrating studies of prenatal exposures, placental function, and postnatal maternal care with the exploration of epigenetic mechanisms may provide novel insights into the pathophysiology induced by maternal distress.
The epigenetics of maternal cigarette smoking during pregnancy and effects on child development
Authors: Knopik Valerie S. , Maccani Matthew A. , Francazio Sarah , McGeary John E.
Published: October 2012

The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures can influence the growth and development of the fetus as well as the child's future postnatal health and behavior. Maternal cigarette smoking during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. Previous studies have associated prenatal smoke exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders later in life. Researchers are now learning that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper fetal growth and development are epigenetic in nature. Maternal cigarette smoking during pregnancy has been associated with altered DNA methylation and dysregulated expression of microRNA, but a deeper understanding of the epigenetics of maternal cigarette smoking during pregnancy as well as how these epigenetic changes may affect later health and behavior remain to be elucidated. This article seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assess how such changes may have consequences for both fetal growth and development, as well as later child health, behavior, and well-being. We also outline future directions for this new and exciting field of research.
The serotonin transporter gene is a substrate for age and stress dependent epigenetic regulation in rhesus macaque brain: Potential roles in genetic selection and Gene × Environment interactions
Authors: Lindell Stephen G. , Yuan Qiaoping , Zhou Zhifeng , Goldman David , Thompson Robert C. , Lopez Juan F. , Suomi Stephen J. , Higley J. Dee , Barr Christina S.
Published: October 2012

In humans, it has been demonstrated that the serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates risk in the face of adversity. One mechanism by which stress could interact with genotype is via epigenetic modifications. We wanted to examine whether stress interacted with genotype to predict binding of a histone 3 protein trimethylated at lysine 3 (H3K4me3) that marks active promoters. The brains (N= 61) of male rhesus macaques that had been reared in the presence or absence of stress were archived and the hippocampusi dissected. Chromatin immunoprecipitation was performed with an antibody againstH3K4me3followed by sequencing on a SolexaG2A. The effects of age, genotype (5-HTTLPRlong/long vs. short), and stress exposure (peer-reared vs. mother-reared) on levels ofH3K4me3binding were determined. We found effects of age and stress exposure. There was a decline inH3K4me3from preadolescence to postadolescence and lower levels in peer-reared monkeys and no effects of genotype. When we controlled for age, however, we found that there were effects of5-HTTLPRgenotype and rearing condition onH3K4me3binding. In a larger sample, we observed that cerebrospinal fluid 5-hydroxyindoleacetic acid levels were subject to interactive effects among age, rearing history, and genotype. Genes containing both genetic selection and epigenetic regulation may be particularly important in stress adaptation and development. We find evidence for selection at the solute carrier family C6 member 4 gene and observe epigenetic reorganization according to genotype, stress, and age. These data suggest that developmental stage may moderate effects of stress and serotonin transporter genotype in the emergence of alternative adaptation strategies and in the vulnerability to developmental or psychiatric disorders.
Leaking methane reservoirs offshore Svalbard
Authors: Minshull T. A. , Westbrook G. K. , Weitemeyer K. A. , Sinha M. C. , Goswami B. K. , Marsset B.
Published: October 2012

Methane hydrate—a solid substance in which methane is trapped within ice‐like crystals—is stable at low temperatures and high pressures and may be destabilized by ocean warming on both geological and human time scales. Methane is a powerful greenhouse gas, and methane released from hydrate provides a potential positive feedback mechanism in global climate change [e.g., Archer and Buffett, 2005]—in theory, the more methane is released by the hydrates, the warmer the climate gets, causing the ocean to warm and release more methane. However, methane escaping from the seabed is oxidized and dissolved in the ocean, and insufficient methane may reach the atmosphere to affect the climate significantly. Its importance for climate change therefore depends on whether the flux from the seabed is great enough to overcome solution in the ocean and perturb atmospheric concentrations over sufficiently long time scales.
Honors
Authors: Anonymous
Published: October 2012

Two AGU members are among the 23 new MacArthur fellows for 2012, the John D. and Catherine T. MacArthur Foundation announced on 2 October. Geochemist Terry Plank, a professor in Columbia University's Department of Earth and Environmental Sciences, was cited for “probing the usually invisible but remarkably powerful thermal and chemical forces deep below the Earth's crust that drive the motion of tectonic plate collisions.” The MacArthur Foundation cited marine ecologist Nancy Rabalais, executive director and professor at the Louisiana Universities Marine Consortium, for “documenting the environmental and economic consequences of hypoxic zones in the Gulf of Mexico and informing strategies for restoring the degraded waters of the Gulf and the Mississippi River basin.” Each fellow will each receive $500,000 in no‐strings‐attached support over the next 5 years.
Breaking the ice: Theorizing the mechanisms of Arctic thaw
Authors: Rennermalm Asa K. , Mioduszewski John , Moustafa Samiah
Published: October 2012

Breaking the Ice: Theorizing the Arctic Thaw;New Brunswick, New Jersey, 12–14 April 2012 Some of the most striking contemporary environmental changes are the warming of the Arctic region and increased mass loss from the Greenland ice sheet. For example, areas of summer melt atop Greenland's massive ice sheet continue to expand, sending large volumes of ice and meltwater into surrounding seas and oceans. This may have profound implications for regional hydrology and marine biogeochemical cycles, as well as global sea level rise. While these trends are readily observable, urgent questions regarding how the Greenland ice sheet will respond to future climate change remain unanswered.
AGU governance's decision‐making process advances strategic plan
Authors: McPhaden Michael , Finn Carol , McEntee Chris
Published: October 2012

A lot has happened in a little more than 2 years, and we want give AGU members an update on how things are working under AGU's strategic plan and governance model. AGU is an organization committed to its strategic plan (http://www.agu.org/about/strategic_plan.shtml), and if you have not read the plan lately, we encourage you to do so. AGU's vision is to be an organization that “galvanizes a community of Earth and space scientists that collaboratively advances and communicates science and its power to ensure a sustainable future.” We are excited about the progress we have made under this plan and the future course we have set for the Union. Everything the Board of Directors, Council, and committees put on their agendas is intended to advance AGU's strategic goals and objectives. Together with headquarters staff, these bodies are working in an integrated, effective manner to carry out this plan. The best way to demonstrate the progress made and each group's role is to walk through a recent example: the creation of a new Union‐level award (see Figure 1).
Low frequency earthquakes below southern Vancouver Island
Authors: Bostock M. G. , Royer A. A. , Hearn E. H. , Peacock S. M.
Published: October 2012

The nature and distribution of low frequency earthquakes (LFEs) in subduction zones provide insight into plate boundary deformation downdip of the locked seismogenic zone. We employ network autocorrelation detection to identify LFE families beneath southern Vancouver Island and environs. An initial suite of 5775 LFEs detected in 2004 and 2005 at a select set of 7 stations is grouped into 140 families using waveform cluster analysis. These families are used as templates within an iterative network cross correlation scheme to detect LFEs across different tremor episodes, incorporate new stations, and improve LFE template signal‐to‐noise ratio. As in southwest Japan, representative LFE locations define a relatively tight, dipping surface several km above the locus of intraslab seismicity, within a prominent, dipping low‐velocity zone (LVZ). LFE polarizations for near‐vertical source‐receiver geometries possess a remarkably uniform dipolar signature indicative of point‐source, double‐couple excitation. Focal mechanisms determined fromP‐wave first motions are characterized by a combination of strike‐slip and thrust faulting. We suggest that LFEs and regular intraslab seismicity occur in distinct structural and stress regimes. The LVZ, inferred to represent weak, overpressured, porous and mylonitized metabasalts of oceanic crustal Layer 2, separates LFEs manifesting deformation within a plate boundary shear zone from intraslab earthquakes generated by tensional stresses and dehydration embrittlement within a more competent lower oceanic crustal Layer 3 and underlying mantle.