The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

A nucleotide binding rectification Brownian ratchet model for translocation of Y-family DNA polymerases

Y-family DNA polymerases are characterized by low-fidelity synthesis on undamaged DNA and ability to catalyze translesion synthesis over the damaged DNA. Their translocation along the DNA template is an important event during processive DNA synthesis. In this work we present a Brownian ratchet model for this translocation, where the directed translocation is rectified by the nucleotide binding to the polymerase. Using the model, different features of the available structures for Dpo4, Dbh and polymerase ι in binary and ternary forms can be easily explained. Other dynamic properties of the Y-family polymerases such as the fast translocation event upon dNTP binding for Dpo4 and the considerable variations of the processivity among the polymerases can also be well explained by using the model. In addition, some predicted results of the DNA synthesis rate versus the external force acting on Dpo4 and Dbh polymerases are presented. Moreover, we compare the effect of the external force on the DNA synthesis rate of the Y-family polymerase with that of the replicative DNA polymerase

Effects of Transcranial Direct Current Stimulation on Episodic Memory Related to Emotional Visual Stimuli

The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action

Nucleoporin98-96 Function Is Required for Transit Amplification Divisions in the Germ Line of Drosophila melanogaster

Production of specialized cells from precursors depends on a tightly regulated sequence of proliferation and differentiation steps. In the gonad of Drosophila melanogaster, the daughters of germ line stem cells (GSC) go through precisely four rounds of transit amplification divisions to produce clusters of 16 interconnected germ line cells before entering a stereotypic differentiation cascade. Here we show that animals harbouring a transposon insertion in the center of the complex nucleoporin98-96 (nup98-96) locus had severe defects in the early steps of this developmental program, ultimately leading to germ cell loss and sterility. A phenotypic analysis indicated that flies carrying the transposon insertion, designated nup98-962288, had dramatically reduced numbers of germ line cells. In contrast to controls, mutant testes contained many solitary germ line cells that had committed to differentiation as well as abnormally small clusters of two, four or eight differentiating germ line cells. This indicates that mutant GSCs rather differentiated than self-renewed, and that these GSCs and their daughters initiated the differentiation cascade after zero, or less than four rounds of amplification divisions. This phenotype remained unaffected by hyper-activation of signalling pathways that normally result in excessive proliferation of GSCs and their daughters. Expression of wildtype nup98-96 specifically in the germ line cells of mutant animals fully restored development of the GSC lineage, demonstrating that the effect of the mutation is cell-autonomous. Nucleoporins are the structural components of the nucleopore and have also been implicated in transcriptional regulation of specific target genes. The nuclear envelopes of germ cells and general nucleocytoplasmic transport in nup98-96 mutant animals appeared normal, leading us to propose that Drosophila nup98-96 mediates the transport or transcription of targets required for the developmental timing between amplification and differentiation

The Evolution of Social Orienting: Evidence from Chicks (Gallus gallus) and Human Newborns

Converging evidence from different species indicates that some newborn vertebrates, including humans, have visual predispositions to attend to the head region of animate creatures. It has been claimed that newborn preferences for faces are domain-relevant and similar in different species. One of the most common criticisms of the work supporting domain-relevant face biases in human newborns is that in most studies they already have several hours of visual experience when tested. This issue can be addressed by testing newly hatched face-na\uefve chicks (Gallus gallus) whose preferences can be assessed prior to any other visual experience with faces

D-Cycloserine as an augmentation strategy for cognitive behavioral therapy of anxiety disorders

The goal of this review is to examine the clinical studies on d-cycloserine, a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure procedures during cognitive behavioral therapy for anxiety disorders. Although cognitive behavioral therapy and anxiolytic medications are more effective than placebo for treating anxiety disorders, there is still considerable room for further improvement. Traditional combination strategies typically yield disappointing results. However, recent studies based on translational research have shown promise to augment the neural circuitry underlying fear extinction with pharmacological means. We discuss the current state of the literature, including inconsistencies of findings and issues concerning the drug mechanism, dosing, and dose timing. D-cycloserine is a promising combination strategy for cognitive behavioral therapy of anxiety disorders by augmenting extinction learning. However, there is also evidence to suggest that d-cycloserine can facilitate reconsolidation of fear memory when exposure procedures are unsuccessful

Integration of the β-Catenin-Dependent Wnt Pathway with Integrin Signaling through the Adaptor Molecule Grb2

THE COMPLEXITY OF WNT SIGNALING LIKELY STEMS FROM TWO SOURCES: multiple pathways emanating from frizzled receptors in response to wnt binding, and modulation of those pathways and target gene responsiveness by context-dependent signals downstream of growth factor and matrix receptors. Both rac1 and c-jun have recently been implicated in wnt signaling, however their upstream activators have not been identified.Here we identify the adapter protein Grb2, which is itself an integrator of multiple signaling pathways, as a modifier of beta-catenin-dependent wnt signaling. Grb2 synergizes with wnt3A, constitutively active (CA) LRP6, Dvl2 or CA-beta-catenin to drive a LEF/TCF-responsive reporter, and dominant negative (DN) Grb2 or siRNA to Grb2 block wnt3A-mediated reporter activity. MMP9 is a target of beta-catenin-dependent wnt signaling, and an MMP9 promoter reporter is also responsive to signals downstream of Grb2. Both a jnk inhibitor and DN-c-jun block transcriptional activation downstream of Dvl2 and Grb2, as does DN-rac1. Integrin ligation by collagen also synergizes with wnt signaling as does overexpression of Focal Adhesion Kinase (FAK), and this is blocked by DN-Grb2.These data suggest that integrin ligation and FAK activation synergize with wnt signaling through a Grb2-rac-jnk-c-jun pathway, providing a context-dependent mechanism for modulation of wnt signaling

Gene expression profile of cervical and skin tissues from human papillomavirus type 16 E6 transgenic mice

<p>Abstract</p> <p>Background</p> <p>Although K14E6 transgenic mice develop spontaneous tumors of the skin epithelium, no spontaneous reproductive tract malignancies arise, unless the transgenic mice were treated chronically with 17β-estradiol. These findings suggest that E6 performs critical functions in normal adult cervix and skin, highlighting the need to define E6-controlled transcriptional programs in these tissues.</p> <p>Methods</p> <p>We evaluated the expression profile of 14,000 genes in skin or cervix from young K14E6 transgenic mice compared with nontransgenic. To identify differentially expressed genes a linear model was implemented using R and the LIMMA package. Two criteria were used to select the set of relevant genes. First a set of genes with a Log-odds ≥ 3 were selected. Then, a hierarchical search of genes was based on Log Fold Changes.</p> <p>Results</p> <p>Microarray analysis identified a total of 676 and 1154 genes that were significantly up and down-regulated, respectively, in skin from K14E6 transgenic mice. On the other hand, in the cervix from K14E6 transgenic mice we found that only 97 and 252 genes were significantly up and down-regulated, respectively. One of the most affected processes in the skin from K14E6 transgenic mice was the cell cycle. We also found that skin from transgenic mice showed down-regulation of pro-apoptotic genes and genes related to the immune response. In the cervix of K14E6 transgenic mice, we could not find affected any gene related to the cell cycle and apoptosis pathways but did observe alterations in the expression of immune response genes. Pathways such as angiogenesis, cell junction and epidermis development, also were altered in their gene expression profiles in both tissues.</p> <p>Conclusion</p> <p>Expression of the HPV16 E6 oncoprotein in our model alters expression of genes that fell into several functional groups providing insights into pathways by which E6 deregulate cell cycle progression, apoptosis, the host resistance to infection and immune function, providing new opportunities for early diagnostic markers and therapeutic drug targets.</p

Effects of macromolecular crowding on intracellular diffusion from a single particle perspective

Compared to biochemical reactions taking place in relatively well-defined aqueous solutions in vitro, the corresponding reactions happening in vivo occur in extremely complex environments containing only 60–70% water by volume, with the remainder consisting of an undefined array of bio-molecules. In a biological setting, such extremely complex and volume-occupied solution environments are termed ‘crowded’. Through a range of intermolecular forces and pseudo-forces, this complex background environment may cause biochemical reactions to behave differently to their in vitro counterparts. In this review, we seek to highlight how the complex background environment of the cell can affect the diffusion of substances within it. Engaging the subject from the perspective of a single particle’s motion, we place the focus of our review on two areas: (1) experimental procedures for conducting single particle tracking experiments within cells along with methods for extracting information from these experiments; (2) theoretical factors affecting the translational diffusion of single molecules within crowded two-dimensional membrane and three-dimensional solution environments. We conclude by discussing a number of recent publications relating to intracellular diffusion in light of the reviewed material