This study was performed to examine the feeding effects of Angelica keiskei Koidz (AK) and its processed products on serum, liver, and body fat content and the expression of antioxidant genes in rats fed a high fat diet. AK and its processed products were added at 3-5% to a high fat diet and fed to adult rats for 6 weeks. In experiment 1 (EXP 1), the rats were fed with one of six diets including a control diet (normal fat), high fat diet (HF), and HF + AK additives groups (four groups). In experiment 2 (EXP 2), the rats were separated into three groups of HF, HF + AK whole leaves, and HF + fermented juice (FS) + squeeze (SA). Body weight was not different among the groups in either experiment. The liver weight was lower in the FS and SA groups compared to that in the other groups (P < 0.05). Serum luteolin was higher in the AK and processed products groups compared to that in the HF group (P < 0.05). Gene expression of the antioxidative enzymes catalase and glutathione-s-reductase in the liver was higher in the AK processed products group than that in the other groups (P < 0.05). The results suggest that the intake of AK and its processed products increased the expression of antioxidant enzymes in animals fed a high fat diet, reduced hepatic cholesterol content, and increased the effective absorption of luteolin.

The purpose of this study was to evaluate the soft tissue and bone change around two adjacent implants in one-stage implant surgery.

Switchgrass (Panicum virgatum) has been identified as a promising cellulosic biofuel crop in the United States. Construction of a genetic linkage map is fundamental for switchgrass molecular breeding and the elucidation of its genetic mechanisms for economically important traits. In this study, a novel population consisting of 139 selfed progeny of a northern lowland genotype, NL 94 LYE 16X13, was used to construct a linkage map. A total of 2493 simple sequence repeat markers were screened for polymorphism. Of 506 polymorphic loci, 80.8% showed a goodness-of-fit of 1:2:1 segregation ratio. Among 469 linked loci on the framework map, 241 coupling vs. 228 repulsion phase linkages were detected that conformed to a 1:1 ratio, confirming disomic inheritance. A total of 499 loci were mapped to 18 linkage groups (LG), of which the cumulative length was 2085.2 cM, with an average marker interval of 4.2 cM. Nine homeologous LG pairs were identified based on multi-allele markers and comparative genomic analysis. Two clusters of segregation-distorted loci were identified on LG 5b and 9b, respectively. Comparative analysis indicated a one-to-one relationship between nine switchgrass homeologous groups and nine foxtail millet (Setaria italica) chromosomes, suggesting strong homology between the two species. The linkage map derived from selfing a heterozygous parent, instead of two separate maps usually constructed for a cross-fertilized species, provides a new genetic framework to facilitate genomics research, quantitative trait locus (QTL) mapping, and marker-assisted breeding.

Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression.

In the fruit fly, Drosophila melanogaster, serotonin functions both as a neurotransmitter to regulate larval feeding, and in the development of the stomatogastric feeding circuit. There is an inverse relationship between neuronal serotonin levels during late embryogenesis and the complexity of the serotonergic fibers projecting from the larval brain to the foregut, which correlate with perturbations in feeding, the functional output of the circuit. Dopamine does not modulate larval feeding, and dopaminergic fibers do not innervate the larval foregut. Since dopamine can function in central nervous system development, separate from its role as a neurotransmitter, the role of neuronal dopamine was assessed on the development, and mature function, of the 5-HT larval feeding circuit.

Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat number exceeds a critical threshold. In the case of FRDA, the repeat unit is the triplet GAA•TTC and the tandem array is located in the first intron of the frataxin (FXN) gene. Pathology arises because expanded alleles make lower than normal levels of mature FXN mRNA and thus reduced levels of frataxin, the FXN gene product. The repeats form a variety of unusual DNA structures that have the potential to affect gene expression in a number of ways. For example, triplex formation in vitro and in bacteria leads to the formation of persistent RNA:DNA hybrids that block transcription. In addition, these repeats have been shown to affect splicing in model systems. More recently, it has been shown that the region flanking the repeats in the FXN gene is enriched for epigenetic marks characteristic of transcriptionally repressed regions of the genome. However, exactly how repeats in an intron cause the FXN mRNA deficit in FRDA has been the subject of much debate. Identifying the mechanism or mechanisms responsible for the FXN mRNA deficit in FRDA is important for the development of treatments for this currently incurable disorder. This review discusses evidence for and against different models for the repeat-mediated mRNA deficit.

A coxsackievirus B4 induces acute pancreatitis with different outcomes. The study utilized a systems biology approach to identify molecular immune responses that differentiate between disease resolution and disease progression. The data establish a temporal pattern of host responses that differentiate the resolution of acute pancreatitis from the progression to chronic pancreatitis. A group of twenty-five genes exhibited characteristic expression profiles that were observed during the development of chronic pancreatitis but not during the resolution of disease. We postulate that the temporal dynamics of the twenty-five genes influence the development of pathogenic immune responses associated with chronic pancreatitis. Furthermore, a subset of eleven genes exhibited increased expression as viral titers waned. Of the eleven gene products, five are secreted molecules, TNF-α, IFN-γ, CXCL10, IL-10, and IL-22b, and represent novel potential therapeutic targets since they can be readily modulated with antibodies against the specific cytokine/chemokine or with antibodies against the corresponding receptors.

Ovarian reserve describes a woman's reproductive potential and there are a variety of tests for this. This reflects the lack of a gold standard and the lack of a single test that provides sufficient accuracy. Ovarian biopsy has been proposed as a potential tool for assessing the ovarian reserve and therefore the ability or inability for a woman to bear a child with or without treatment. The literature assessing the diagnostic accuracy of ovarian biopsy as a test of ovarian reserve for predicting fertility outcomes (live birth rate, ongoing pregnancy, clinical pregnancy, biochemical pregnancy, embryos available, oocytes retrieved or cancelled cycles) was systematically reviewed. There were no studies identified that assessed the diagnostic accuracy of ovarian biopsy for predicting fertility outcomes but a number of studies provided evidence that ovarian follicles are distributed unevenly and randomly throughout the ovarian cortex. This leads to sampling error when ovarian biopsy is used to sample the ovarian reserve. It is concluded that ovarian biopsy should not be used as a test of ovarian reserve. Every woman is born with a limited number of eggs, and as women age, their ability to have children eventually decreases to zero due to the loss of these eggs. Ovarian reserve is a term that describes the remaining pool of eggs. Testing for ovarian reserve enables one to predict the ability or inability of a woman to have a child and how long a woman may be able to defer having a child. This is of importance as social trends in developed countries are leading to increasing numbers of women who have children at later stages of their lives. One test of ovarian reserve is an ovarian biopsy, where a woman undergoes an operation to have a small piece of her ovary removed. The number of eggs in this removed piece is counted, and from this, the number of eggs in the whole ovary can be estimated and calculated. We reviewed the literature for all studies that examined the accuracy of ovarian biopsy to predict fertility outcomes but found no studies that answered this question. A number of studies have found that eggs are distributed unevenly and randomly in an ovary. As such, the number of eggs in an ovarian biopsy sample does not represent the actual number of eggs remaining in the ovary. Because of this and the risks inherent in the operation to perform this test, we believe that ovarian biopsy should not be used as a test of ovarian reserve.

The biological mechanisms responsible for the onset and exacerbation of asthma symptoms in children may involve the epigenetic regulation of inflammatory genes after environmental exposures. Using buccal cells, we hypothesized that DNA methylation in promoter regions of two asthma genes, inducible nitric oxide synthase (iNOS) and interferon γ (IFNγ), can vary over several days. Repeat buccal samples were collected 4 to 7 days apart from 34 children participating in the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study. Several field duplicates (sequential collection of two samples in the field) and replicates (one sample pyrosequenced twice) also were collected to ensure consistency with collection and laboratory procedures. DNA methylation was assessed by pyrosequencing a PCR of bisulfite-treated DNA. We found that replicate and field duplicate samples were correlated strongly (r = 0.86 to 0.99, P < 0.05), while repeat samples demonstrated low within-subject correlations (r = 0.19 to 0.56, P = 0.06 to 0.30). Our data reveal DNA methylation as a dynamic epigenetic mechanism that can be accessed safely and reproducibly in an inner city pediatric cohort using non-invasive buccal swabs and pyrosequencing technology.

Gumiganghwal-tang (GGT, known as Kumi-Kyokatsu-to in Japanese) is a traditional herbal prescription made from nine different herbs that is used for the treatment of the common cold, pain, and inflammatory diseases.

Brain activity is inherently combinatorial and three-dimensional. Optical imaging techniques offer a suitable opportunity to record many activity foci simultaneously, but under conventional microscopy conditions, optical access is generally limited to the frontal part of the brain. Thus, even for cases in which optical recordings have delivered substantial data, our knowledge of deeper layers is deficient. Using the honeybee olfactory system as a test system, we report that by using a gold-sputtered cover slip as a minute mirror, it is possible to optically access and record from otherwise inaccessible brain areas. In insects, the first brain area to code for odors is the antennal lobe (comparable to the vertebrate olfactory bulb). Several previous studies have characterized glomerular odor response patterns of the frontal view, readily accessible when the head capsule of the bee is opened. However, until now, the back and the sides of the antennal lobe have remained utterly unexplored. This is particularly relevant because in the honeybee these two views coincide with two separate olfactory subsystems, related to two axonal tracts of second-order neurons: the lAPT and the mAPT. Combining wide-field microscopy, calcium imaging, and a minute mirror, we report the first glomerular odor responses from the side of the honeybee antennal lobe.

A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD.

We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis.

Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from JRA to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets can be defined using A1AT, MTHFR and APOE genotyping. Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes. These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to selective advantages: ICE phenotype and disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes.

TDP-43 pathology in motor neurons is a hallmark of ALS. In addition, the reduced expression of an RNA editing enzyme, adenosine deaminase acting on RNA 2 (ADAR2), increases the expression of GluA2 with an unedited Q/R site in the motor neurons of patients with sporadic ALS. As the occurrence of these two disease-specific abnormalities in the same motor neurons suggests a molecular link between them, we examined the effects of altered TDP-43 processing on ADAR2 activity in TetHeLaG2m and Neuro2a cells. We found that ADAR2 activity did not consistently change due to the overexpression or knockdown of TDP-43 or the expression of abnormal TDP-43, including caspase-3-cleaved fragments, truncated TDP-43 lacking either nuclear localization or export signals and ALS-linked TDP-43 mutants. These results suggest that the abnormal processing of TDP-43 is not an upstream event of inefficient GluA2 Q/R site editing in the motor neurons of sporadic ALS patients.

Attentional biases have been proposed to contribute to symptom maintenance in posttraumatic stress disorder (PTSD), although the neural correlates of these processes have not been well defined; this was the goal of the present study. We administered an attention bias task, the dot probe, to a sample of 37 (19 control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to controls, PTSD+ participants demonstrated increased activation in the dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In addition, attentional avoidance of threat corresponded with increased ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder.

Extracellular protein:protein interactions between secreted or membrane-tethered proteins are critical for both initiating intercellular communication and ensuring cohesion within multicellular organisms. Proteins predicted to form extracellular interactions are encoded by approximately a quarter of human genes, but despite their importance and abundance, the majority of these proteins have no documented binding partner. Primarily, this is due to their biochemical intractability: membrane-embedded proteins are difficult to solubilise in their native conformation and contain structurally-important posttranslational modifications. Also, the interaction affinities between receptor proteins are often characterised by extremely low interaction strengths (half-lives < 1 second) precluding their detection with many commonly-used high throughput methods. Here, we describe an assay, AVEXIS (AVidity-based EXtracellular Interaction Screen) that overcomes these technical challenges enabling the detection of very weak protein interactions (t(1/2) ≤ 0.1 sec) with a low false positive rate. The assay is usually implemented in a high throughput format to enable the systematic screening of many thousands of interactions in a convenient microtitre plate format (Fig. 1). It relies on the production of soluble recombinant protein libraries that contain the ectodomain fragments of cell surface receptors or secreted proteins within which to screen for interactions; therefore, this approach is suitable for type I, type II, GPI-linked cell surface receptors and secreted proteins but not for multipass membrane proteins such as ion channels or transporters. The recombinant protein libraries are produced using a convenient and high-level mammalian expression system, to ensure that important posttranslational modifications such as glycosylation and disulphide bonds are added. Expressed recombinant proteins are secreted into the medium and produced in two forms: a biotinylated bait which can be captured on a streptavidin-coated solid phase suitable for screening, and a pentamerised enzyme-tagged (β-lactamase) prey. The bait and prey proteins are presented to each other in a binary fashion to detect direct interactions between them, similar to a conventional ELISA (Fig. 1). The pentamerisation of the proteins in the prey is achieved through a peptide sequence from the cartilage oligomeric matrix protein (COMP) and increases the local concentration of the ectodomains thereby providing significant avidity gains to enable even very transient interactions to be detected. By normalising the activities of both the bait and prey to predetermined levels prior to screening, we have shown that interactions having monomeric half-lives of 0.1 sec can be detected with low false positive rates.

Behavioural and psychological symptoms in dementia, or BPSD, occur in the majority of Alzheimer's disease (AD) patients. They are associated with considerable patient morbidity and greater care-giver stress. There is some evidence suggesting that BPSD have a genetic component and a large number of studies have examined the association of candidate genes with these symptoms. This review provides a comprehensive summary of all the published studies investigating the association of candidate gene missense substitutions with BPSD. Missense substitutions could potentially alter protein function or render the protein non-functional, resulting in phenotypic consequences. More than 80 studies investigating the association of 8 missense substitutions in 7 genes with BPSD were identified. However, results of these studies are contradictory and do not provide firm support for these associations. Larger studies and more systematic approaches will delineate the association of missense substitutions with behavioural symptoms in AD.

Identification of regions of interest (ROIs) is a fundamental issue in brain network construction and analysis. Recent studies demonstrate that multimodal neuroimaging approaches and joint analysis strategies are crucial for accurate, reliable and individualized identification of brain ROIs. In this paper, we present a novel approach of visual analytics and its open-source software for ROI definition and brain network construction. By combining neuroscience knowledge and computational intelligence capabilities, visual analytics can generate accurate, reliable and individualized ROIs for brain networks via joint modeling of multimodal neuroimaging data and an intuitive and real-time visual analytics interface. Furthermore, it can be used as a functional ROI optimization and prediction solution when fMRI data is unavailable or inadequate. We have applied this approach to an operation span working memory fMRI/DTI dataset, a schizophrenia DTI/resting state fMRI (R-fMRI) dataset, and a mild cognitive impairment DTI/R-fMRI dataset, in order to demonstrate the effectiveness of visual analytics. Our experimental results are encouraging.

Pneumococcal meningitis can lead to death or serious neurological sequelae as a result of the host inflammatory response. We investigated the association between host response protein expression and outcome in patients with pneumococcal meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal controls. Candidate proteins were analyzed for an association with survival. Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P < 0.05). This C3 reduction was not associated with lower levels in serum, indicating a compartmentalized CSF response. Transferrin levels were significantly higher in CSF (but not serum) from nonsurvivors than in CSF from survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but there was no clear association between level of expression and clinical outcome. Increased blood-brain barrier permeability and complement C3 depletion may have a role in determining outcome from bacterial meningitis. Therapeutic use of citicoline or caspase inhibitors is unlikely to have beneficial effects in patients with meningitis.