257 research outputs found

    Amygdala and fusiform gyrus temporal dynamics: Responses to negative facial expressions

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    <p>Abstract</p> <p>Background</p> <p>The amygdala habituates in response to repeated human facial expressions; however, it is unclear whether this brain region habituates to schematic faces (i.e., simple line drawings or caricatures of faces). Using an fMRI block design, 16 healthy participants passively viewed repeated presentations of schematic and human neutral and negative facial expressions. Percent signal changes within anatomic regions-of-interest (amygdala and fusiform gyrus) were calculated to examine the temporal dynamics of neural response and any response differences based on face type.</p> <p>Results</p> <p>The amygdala and fusiform gyrus had a within-run "U" response pattern of activity to facial expression blocks. The initial block within each run elicited the greatest activation (relative to baseline) and the final block elicited greater activation than the preceding block. No significant differences between schematic and human faces were detected in the amygdala or fusiform gyrus.</p> <p>Conclusion</p> <p>The "U" pattern of response in the amygdala and fusiform gyrus to facial expressions suggests an initial orienting, habituation, and activation recovery in these regions. Furthermore, this study is the first to directly compare brain responses to schematic and human facial expressions, and the similarity in brain responses suggest that schematic faces may be useful in studying amygdala activation.</p

    Substance Use and Mild Traumatic Brain Injury Risk Reduction and Prevention: A Novel Model for Treatment

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    Traumatic brain injury (TBI) and substance use disorders (SUDs) frequently co-occur. Individuals with histories of alcohol or other drug use are at greater risk for sustaining TBI, and individuals with TBI frequently misuse substances before and after injury. Further, a growing body of literature supports the relationship between comorbid histories of mild TBI (mTBI) and SUDs and negative outcomes. Alcohol and other drug use are strongly associated with risk taking. Disinhibition, impaired executive function, and/or impulsivity as a result of mTBI also contribute to an individual's proclivity towards risk-taking. Risk-taking behavior may therefore, be a direct result of SUD and/or history of mTBI, and risky behaviors may predispose individuals for subsequent injury or continued use of substances. Based on these findings, evaluation of risk-taking behavior associated with the co-occurrence of SUD and mTBI should be a standard clinical practice. Interventions aimed at reducing risky behavior among members of this population may assist in decreasing negative outcomes. A novel intervention (Substance Use and Traumatic Brain Injury Risk Reduction and Prevention (STRRP)) for reducing and preventing risky behaviors among individuals with co-occurring mTBI and SUD is presented. Areas for further research are discussed

    Amplified ambivalence: having a sibling with juvenile idiopathic arthritis

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    Despite increased awareness of family responses to chronic illness and disability, there is still a need to understand experiences of well siblings. We begin to address this by asking “What is it like to have a sibling with juvenile idiopathic arthritis?” (JIA).Eight families with an adolescent diagnosed with JIA participated. Four members of each family, including one healthy sibling, were interviewed and transcripts analyzed using grounded theory. Analysis suggests healthy siblings see their family as different to ‘normal’ families, forfeit time with peers, share vicariously adverse experiences of their ill sibling, and feel inadequately informed. Such experiences amplify the ambivalent nature of sibling relationships and are possibly felt most strongly during late childhood and early adolescence. Support from extended family can reduce these negative experiences and facilitate social and emotional adjustment which also occurs over time as the children mature. These findings have implications for healthcare professionals and voluntary organizations

    Next-Generation Probiotics Targeting \u3ci\u3eClostridium difficile\u3c/i\u3e through Precursor- Directed Antimicrobial Biosynthesis

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    Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials

    Emotional orientation, brain function and genetics in adults and children : implications for development, and psychopathology

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    The ability to attend or avoid emotional stimuli is important to our survival. Attending to potential threats can help us avoid danger; while attending to positive stimuli is important for our social function. For example, when we see a man with a knife it is important to run away, or avoid the threat so we are not harmed. Just as the knife warns us of the threatening stiuation, a smiling face indicates a friendly person. We are drawn to this cue to possibly receive a rewarding social interaction. Attention orientation to both negative and positive stimuli may be impacted by development, psychopathology and genetics. The dot probe task yields both behavioral and neural indices of attention biases towards or away from an emotional cue (angry or happy face). This thesis includes three studies to determine the effects of development, psychopathology, and genetics on attention orientating. In Study I, we examined age-related correlations in attention-orienting biases to negative and positive faces in a healthy sample using functional magnetic resonance imaging (fMRI) and a dot probe task. Behavioral response data indicated a positive correlation between age and attention bias towards happy faces, such that younger participants showed less bias towards happy, relative to neutral, faces, than older subjects. Attention bias towards angry faces did not correlate with age. Relative to older, younger participants demonstrated greater activation in the left cuneus and left caudate on the contrast of trials used to assess happy-face attention bias. In Study II, using the dot probe task in a home setting, we studied parents that were highly exposed to the attack on the World Trade Center in 2001 and their children. We found that psychiatrically healthy parents who experienced severe trauma showed greater attention bias towards threat than parents experiencing no such trauma, but trauma experienced by parents did was not predictive of attention bias in their children. In Study III, using an fMRI on 5-HTTLPR genotyped adults performing dot probe task; we compared amygdala response to threat bias contrasts. The 5- HTTLPR has been previously linked to amygdala reactivity and the amygdala has been implicated in the orienting of attention towards threat. Behavioral data indicated no difference between the two genotyped subject populations for the 5-HTTLPR polymorphism (l/l and s-carrier). However, fMRI data did reveal between-group differences in the amygdala activation. Specifically, relative to l/l, s-carriers showed greater right amygdala activation to trials with angry faces. Because similar levels of threat bias were found in the two genotype groups, these findings suggest that s-carriers exhibit a lower threshold for engaging the amygdala within the context of the task. In total, these three studies explore the effect of both the environment and genes on behavior and brain function. Studies I and II focus on environment, specifically, how their environment affects their emotional orientation. On the genetic side, Study III focuses on the effect of genetics on emotional orientation

    Computational modeling of threat learning reveals links with anxiety and neuroanatomy in humans

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    Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain anatomy, and anxiety severity. Results indicate that greater anxiety severity related specifically to slower safety learning and slower extinction of response to safe stimuli. Nucleus accumbens gray-matter volume moderated learning-anxiety associations. Using a modeling approach, we identify computational mechanisms linking threat learning and anxiety severity and their neuroanatomical substrates

    PALM-3000 high-order adaptive optics system for Palomar Observatory

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    Deployed as a multi-user shared facility on the 5.1 meter Hale Telescope at Palomar Observatory, the PALM-3000 highorder upgrade to the successful Palomar Adaptive Optics System will deliver extreme AO correction in the near-infrared, and diffraction-limited images down to visible wavelengths, using both natural and sodium laser guide stars. Wavefront control will be provided by two deformable mirrors, a 3368 active actuator woofer and 349 active actuator tweeter, controlled at up to 3 kHz using an innovative wavefront processor based on a cluster of 17 graphics processing units. A Shack-Hartmann wavefront sensor with selectable pupil sampling will provide high-order wavefront sensing, while an infrared tip/tilt sensor and visible truth wavefront sensor will provide low-order LGS control. Four back-end instruments are planned at first light: the PHARO near-infrared camera/spectrograph, the SWIFT visible light integral field spectrograph, Project 1640, a near-infrared coronagraphic integral field spectrograph, and 888Cam, a high-resolution visible light imager

    The Association Between Women’s Perceptions of Professional Support and Problems Experienced on Breastfeeding Cessation: A Western Australian Study

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    A cross-sectional survey was used to determine the association among women’s breastfeeding problems, their perceptions of support from midwives and child health nurses, and breastfeeding cessation in the first 10 weeks postbirth in a sample of Western Australian women (N = 2669). Primiparous women (75.8%) experienced significantly more problems that multiparous women (52.6%). Although 78.8% of all women agreed or strongly agreed that staff were helpful with feeding, 53.4% confirmed that different midwives offered different feeding advice; however, receiving different advice from midwives around feeding was not associated with breastfeeding cessation. Differences in breastfeeding cessation were associated with parity. Primiparous women’s cessation was associated with experiencing any breastfeeding problems, unhelpful hospital midwives, and unhelpful information from child health nurses, whereas for multiparous women, this included 2 or more breastfeeding problems, not being able to choose when to feed, and unhelpful information from child health nurses

    Removal and Reconstitution of the Carotenoid Antenna of Xanthorhodopsin

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    Salinixanthin, a C40-carotenoid acyl glycoside, serves as a light-harvesting antenna in the retinal-based proton pump xanthorhodopsin of Salinibacter ruber. In the crystallographic structure of this protein, the conjugated chain of salinixanthin is located at the protein–lipid boundary and interacts with residues of helices E and F. Its ring, with a 4-keto group, is rotated relative to the plane of the π-system of the carotenoid polyene chain and immobilized in a binding site near the β-ionone retinal ring. We show here that the carotenoid can be removed by oxidation with ammonium persulfate, with little effect on the other chromophore, retinal. The characteristic CD bands attributed to bound salinixanthin are now absent. The kinetics of the photocycle is only slightly perturbed, showing a 1.5-fold decrease in the overall turnover rate. The carotenoid-free protein can be reconstituted with salinixanthin extracted from the cell membrane of S. ruber. Reconstitution is accompanied by restoration of the characteristic vibronic structure of the absorption spectrum of the antenna carotenoid, its chirality, and the excited-state energy transfer to the retinal. Minor modification of salinixanthin, by reducing the carbonyl C=O double bond in the ring to a C-OH, suppresses its binding to the protein and eliminates the antenna function. This indicates that the presence of the 4-keto group is critical for carotenoid binding and efficient energy transfer

    Genotype, haplotype and copy-number variation in worldwide human populations

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    Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd
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