Effects of Hunger on Visual Perception in Binocular Rivalry

The effect of hunger on visual perception is largely absent from contemporary vision science. Using a well-established visual phenomenon termed binocular rivalry, this study was carried out to investigate the effects of hunger on visual perception. A within-subject design was applied in which participants attended two sessions before and after their lunch or dinner, i.e., a hunger state and a satiated state. In Experiment 1, we found that the mean dominance times to food-related pictures were larger in the hungry condition than that in the satiated condition, while the mean dominance time to the non-food stimuli were unaffected. In Experiment 2, we found the times to break through continuous flash suppression (b-CFS) for both food-related and non-food-related pictures were not affected by hunger. In Experiment 3, a probe-detection task was conducted to address possible response-biases. Our findings provide evidence that hunger biases the dynamic process of binocular rivalry to unsuppressed and visible food stimuli, while processing suppressed and invisible food-related was unaffected. Our results support the notion that the top-down modulation by hunger on food-related visual perception is limited to visible stimuli

Targeting of N-Type Calcium Channels via GABAB-Receptor Activation by α-Conotoxin Vc1.1 Variants Displaying Improved Analgesic Activity

α-Conotoxins exhibiting analgesic activity, such as Vc1.1, have been shown to inhibit α9α10 nicotinic acetylcholine receptors (nAChRs) and GABAB-receptor (GABABR) coupled N-type (CaV2.2) calcium channels. Here, we report two Vc1.1 variants, Vc1.1[N9R] and benzoyl-Vc1.1[N9R], that selectively inhibit CaV2.2 channels via GABABR activation but exhibit reduced inhibitory activity at α9α10 and other neuronal nAChR subtypes compared with Vc1.1. Surprisingly, the analgesic activity of Vc1.1[N9R] and benzoyl-Vc1.1[N9R] was more potent than that of Vc1.1 when tested in partial sciatic nerve ligation injury and chronic constriction injury models. Vc1.1[N9R] and benzoyl-Vc1.1[N9R] exhibited either similar or tenfold higher activity of GABABR-mediated CaV2.2 inhibition but no activity at CaV2.2 alone; however, the mechanism of increased analgesic activity is unknown. The effects on analgesic activity and α9α10 nAChR of other Vc1.1 variations at position 9 and the N-terminus were also determined. Our findings provide new insights for designing potent inhibitors for GABABR-coupled N-type (CaV2.2) calcium channels

Racial Bias in Neural Response for Pain Is Modulated by Minimal Group

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group

FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling

<div><p>Most cartilaginous tumors are formed during skeletal development in locations adjacent to growth plates, suggesting that they arise from disordered endochondral bone growth. Fibroblast growth factor receptor (FGFR)3 signaling plays essential roles in this process; however, the role of FGFR3 in cartilaginous tumorigenesis is not known. In this study, we found that postnatal chondrocyte-specific <i>Fgfr3</i> deletion induced multiple chondroma-like lesions, including enchondromas and osteochondromas, adjacent to disordered growth plates. The lesions showed decreased extracellular signal-regulated kinase (ERK) activity and increased Indian hedgehog (IHH) expression. The same was observed in <i>Fgfr3</i>-deficient primary chondrocytes, in which treatment with a mitogen-activated protein kinase (MEK) inhibitor increased <i>Ihh</i> expression. Importantly, treatment with an inhibitor of IHH signaling reduced the occurrence of chondroma-like lesions in <i>Fgfr3</i>-deficient mice. This is the first study reporting that the loss of <i>Fgfr3</i> function leads to the formation of chondroma-like lesions via downregulation of MEK/ERK signaling and upregulation of IHH, suggesting that FGFR3 has a tumor suppressor-like function in chondrogenesis.</p></div

Histological assessment of the knee and wrist in <i>Fgfr3</i> cKO mice.

<p>(<b>A</b>–<b>P</b>) Fast green/Safranin O- and H & E-stained sagittal sections of the proximal tibia of Cre-negative and <i>Fgfr3</i> cKO mice. (<b>A</b>–<b>D</b>) Images of multiple osteochondroma- and enchondroma-like lesions around disordered growth plates of the tibia in <i>Fgfr3</i> cKO but not in Cre-negative mice. Higher magnification views of areas shown in boxes in E–P. (<b>E</b>–<b>H</b>) Expansion of the region occupied by hypertrophic chondrocytes in <i>Fgfr3</i> cKO growth plates. (<b>I–L</b>) Images of enchondroma-like lesions attached to lamellar bone trabeculae in <i>Fgfr3</i> cKO mice. (<b>M–P</b>) Structure of the cartilaginous cap in <i>Fgfr3</i> cKO mice resembling growth plate cartilage. (<b>Q</b>–<b>X</b>) Fast Green/Safranin O- and H & E-stained coronal sections of the ulna and radius of Cre-negative and <i>Fgfr3</i> cKO mice. Higher magnification views of areas shown in boxes in U–X. (<b>U</b>–<b>X</b>) Images of enchondroma- (U, V) and osteochondroma-like (W, X) lesions in the ulna and radius of <i>Fgfr3</i> cKO mice. Scale bar: 1 mm (A–D, Q–T), 200 μm (E–P, U–X).</p

Loss of <i>Fgfr3</i> suppresses ERK activation but enhances IHH expression.

<p>(<b>A</b>) IHH protein expression in growth plates was enhanced in <i>Fgfr3</i> cKO relative to Cre-negative mice, and was abundant in chondroma-like lesions of mutants, as determined by immunohistochemistry. (<b>B</b>) Phospho-ERK expression was reduced in growth plates of <i>Fgfr3</i> cKO mice. (<b>C</b>) ERK activity in response to FGF18 was impaired in <i>Fgfr3</i>-deficient chondrocytes, as determined by western blotting. (<b>D</b>) Control chondrocytes, chondrocytes treated with MEK inhibitor (250 nM U0126 or 10 nM PD98059), and <i>Fgfr3</i>-deficient chondrocytes were evaluated for <i>Ihh</i> and <i>Pthrp</i> expression by qRT-PCR. Data are expressed as the percent expression relative to controls. Values represent mean ± SD. *p < 0.05 vs. controls. Scale bars: 200 μm.</p

Gross morphology and radiographic assessment of skeletal phenotypes in <i>Fgfr3</i> cKO mice.

<p>(<b>A</b>) Gross morphology of 12-week-old <i>Fgfr3</i> cKO mice with large stature. Femur and tibia lengths were determined from X-ray images; their lengths were increased in <i>Fgfr3</i> cKO as compared to Cre-negative mice. Values represent mean ± SD. ***p < 0.001, **p < 0.01 (n = 10). (<b>B</b>) X-ray and Micro-CT images showing subluxation/dislocation of the radial head (asterisks) and arch-like deformation of the radius (arrowheads) in <i>Fgfr3</i> cKO mice. Bony lesions (arrows) in mutants were attached to the distal ulna and radius. (<b>C</b>) Gross morphology and X-ray/micro-CT images of the knee joint of 12-week-old <i>Fgfr3</i> cKO mice after skin removal showing a bony lesion (arrows) contiguous with the proximal tibia affected by knee joint deformity (arrowheads). (<b>D, E</b>) Rib bones showing aberrant radiographic density (D, arrows) and an irregular costal cartilage surface (E, arrows) were observed by X-ray and micro-CT in <i>Fgfr3</i> cKO mice.</p