CURATING CURIOSITY: THE EVOLUTION OF MUSEOLOGICAL THEORY IN THE LATE SEVENTEENTH CENTURY AT THE BIBLIOTHÈQUE DE SAINTE-GENEVIÈVE

The evolution of museological theory at the Bibliotheque de Sainte-Genevieve marks a transition in the history of collecting during the early modern period. Although the contents of the collection remained largely unchanged from earlier Wunderkammern, the acquisition, display, and organization of artifacts within the cabinet had evolved tremendously by the end of the 17th century and one can begin to see the collection as a predecessor of modern museological methodologies

Subtypes of Attentional Bias within Social Anxiety Disorder: Evaluating Changes following Cognitive Behavioral Therapy

Prominent theories of social anxiety disorder (SAD) describe the role of attentional bias in the disorder\u27s etiology and maintenance; some models implicate bias toward social threats (e.g., Rapee & Heimberg, 1997) and others implicate bias to avoid them (e.g., Clark & Wells, 1995). The present investigation examined: 1) whether a clinical sample of individuals with SAD comprises two distinct groups based on attention bias for social threat (vigilant, avoidant), and 2) group-specific changes in attention bias following cognitive behavioral therapy (CBT) for SAD. Consistent with predictions, results yielded evidence of two pre-treatment groups (vigilant and avoidant). After eight weeks of treatment, the direction of change in attention bias differed between groups, such that the vigilant group became less vigilant, and the avoidant group became less avoidant, with the avoidant group showing a significant change in attention bias from pre- to post-treatment. These findings provide preliminary support for the hypothesis that SAD comprises subgroups with both threat vigilant and threat avoidant attentional styles and change in different directions following treatment. Implications for how individuals who exhibit one attentional bias or the other may differentially respond to treatment are discussed

Does engagement with exposure yield better outcomes?: Components of presence as a predictor of treatment response for virtual reality exposure therapy for social phobia

Virtual reality exposure (VRE) has been shown to be effective for treating a variety of anxiety disorders, including social phobia. Presence, or the level of connection an individual feels with the virtual environment, is widely discussed as a critical construct both for the experience of anxiety within a virtual environment and for a successful response to VRE. Two published studies show that whereas generalized presence relates to fear ratings during VRE, it does not relate to treatment response. However, presence has been conceptualized as multidimensional, with three primary factors (spatial presence, involvement, and realness). These factors can be linked to other research on the facilitation of fear during exposure, inhibitors of treatment response (e.g., distraction), and more recent theoretical discussions of the mechanisms of exposure therapy, such as Bouton’s (2004) description of expectancy violation. As such, one or more of these components of presence may be more strongly associated with the experience of fear during VRE and treatment response than the overarching construct. The current study (N=41) evaluated relations between three theorized components of presence, fear ratings during VRE, and treatment response for VRE for social phobia. Results suggest that total presence and realness subscale scores were related to in-session peak fear ratings. However, only scores on the involvement subscale significantly predicted treatment response. Implications of these findings are discussed

Natural and Induced Mitochondrial Phosphate Carrier Loss: DIFFERENTIAL DEPENDENCE OF MITOCHONDRIAL METABOLISM AND DYNAMICS AND CELL SURVIVAL ON THE EXTENT OF DEPLETION.

The relevance of mitochondrial phosphate carrier (PiC), encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3 First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the fifth matrix loop is incompatible with survival on non-fermentable substrate, whereas the L200W variant is functionally neutral. Next, using skin fibroblasts from an individual expressing these variants and HeLa cells with varying degrees of PiC depletion, PiC loss of ∼60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos), whereas lower maximal oxphos was evident at ∼85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete medium; however, proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1 or MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (\u3e85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss of function may be independent of phosphate limitation when ATP requirements are not high

Natural and induced mitochondrial phosphate carrier loss: differential dependence of mitochondrial metabolism and dynamics, and cell survival, on the extent of depletion

The relevance of PiC, encoded by SLC25A3, in bioenergetics is well accepted. However, little is known about the mechanisms mediating the cellular impairments induced by pathological SLC25A3 variants. To this end, we investigated the pathogenicity of a novel compound heterozygous mutation in SLC25A3. First, each variant was modeled in yeast, revealing that substituting GSSAS for QIP within the 5th matrix loop is incompatible with survival on non-fermentable substrate whereas the L200W variant is functionally neutral. Next, using skin fibroblasts from an individual expressing these variants, and HeLa cells with varying degrees of PiC depletion, PiC loss of ~60% was still compatible with uncompromised maximal oxidative phosphorylation (oxphos) whereas lower maximal oxphos was evident at ~85% PiC depletion. Furthermore, intact mutant fibroblasts displayed suppressed mitochondrial bioenergetics consistent with a lower substrate availability rather than phosphate limitation. This was accompanied by slowed proliferation in glucose-replete media, however proliferation ceased when only mitochondrial substrate was provided. Both mutant fibroblasts and HeLa cells with 60% PiC loss showed a less interconnected mitochondrial network and a mitochondrial fusion defect that is not explained by altered abundance of OPA1, MFN1/2 or relative amount of different OPA1 forms. Altogether these results indicate that PiC depletion may need to be profound (>85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss-of-function may be independent of phosphate limitation when ATP requirements are not high

Altered Gating of K\u3csub\u3ev\u3c/sub\u3e1.4 in the Nucleus Accumbens Suppresses Motivation for Reward

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine signaling genes. Functionally, motivation was inversely related to excitability of NAc principal neurons. Furthermore, neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, Kv1.4. These results raise the prospect of targeting Kv1.4 gating in psychiatric conditions associated with motivational dysfunction

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Sex-Biased Gene Flow Among Elk in the Greater Yellowstone Ecosystem

We quantified patterns of population genetic structure to help understand gene flow among elk populations across the Greater Yellowstone Ecosystem. We sequenced 596 base pairs of the mitochondrial control region of 380 elk from eight populations. Analysis revealed high mitochondrial DNA variation within populations, averaging 13.0 haplotypes with high mean gene diversity (0.85). The genetic differentiation among populations for mitochondrial DNA was relatively high (FST = 0.161; P = 0.001) compared to genetic differentiation for nuclear microsatellite data (FST = 0.002; P = 0.332), which suggested relatively low female gene flow among populations. The estimated ratio of male to female gene flow (mm/mf = 46) was among the highest we have seen reported for large mammals. Genetic distance (for mitochondrial DNA pairwise FST) was not significantly correlated with geographic (Euclidean) distance between populations (Mantel’s r = 0.274, P = 0.168). Large mitochondrial DNA genetic distances (e.g., FST . 0.2) between some of the geographically closest populations (,65 km) suggested behavioral factors and/or landscape features might shape female gene flow patterns. Given the strong sex-biased gene flow, future research and conservation efforts should consider the sexes separately when modeling corridors of gene flow or predicting spread of maternally transmitted diseases. The growing availability of genetic data to compare male vs. female gene flow provides many exciting opportunities to explore the magnitude, causes, and implications of sex-biased gene flow likely to occur in many species

Abnormal lateralization of functional connectivity between language and default mode regions in autism

Background: Lateralization of brain structure and function occurs in typical development, and abnormal lateralization is present in various neuropsychiatric disorders. Autism is characterized by a lack of left lateralization in structure and function of regions involved in language, such as Broca and Wernicke areas. Methods: Using functional connectivity magnetic resonance imaging from a large publicly available sample (n = 964), we tested whether abnormal functional lateralization in autism exists preferentially in language regions or in a more diffuse pattern across networks of lateralized brain regions. Results: The autism group exhibited significantly reduced left lateralization in a few connections involving language regions and regions from the default mode network, but results were not significant throughout left- and right-lateralized networks. There is a trend that suggests the lack of left lateralization in a connection involving Wernicke area and the posterior cingulate cortex associates with more severe autism. Conclusions: Abnormal language lateralization in autism may be due to abnormal language development rather than to a deficit in hemispheric specialization of the entire brain