Suprathreshold length summation.

To investigate the mechanisms underlying elongated spatial summation with a pattern-masking paradigm, we measured the contrast detection thresholds for elongated Gabor targets situated at 3° eccentricity to either the left or right of the fixation and elongated along an arc of the same radius to access homogeneous retinal sensitivity. The mask was a ring with a Gabor envelope of the same 3° center radius containing either a concentric (iso-orientation mask) or a radial (orthogonal mask) modulation. The task of the observer was to indicate whether the target in each trial was on the left or the right of the fixation. With orthogonal or low contrast iso-orientation masks, target thresholds first decreased with size with slope -1 on log-log coordinates until the target length reached 45' (specified as the half-height full-width of the Gabor envelope) and then further decreased according to a slope of -1/2, the latter being the signature of an ideal summation process. When the contrast of the iso-orientation mask was sufficiently high, however, the target thresholds, while still showing a -1 slope up to ∼10', asymptoted up to about 50' length, suggesting that the presence of the mask eliminated the ideal summation regime. Beyond about 50', the data approximated another -1 slope decrease in threshold, suggesting the existence of an extra-long channel that is not revealed by the conventional spatial summation paradigm. The full results could be explained by a divisive inhibition model, in which second-order filters sum responses across local oriented channels, combined with a single extra-long filter at least 300' in extent. In this model, the local filter response is given by the linear excitation of the local channels raised to a power, and scaled by divisive inhibition from all channels in the neighborhood. With the high-contrast iso-orientation masks, such divisive inhibition swamps the response to eliminate the ideal summation regime until the stimulus is long enough to activate the extra-long filter.

Coarse-to-fine interaction on perceived depth in compound grating.

To encode binocular disparity, the visual system uses a pair of left eye and right eye bandpass filters with either a position or a phase offset between them. Such pairs are considered to exit at multiple scales to encode a wide range of disparity. However, local disparity measurements by bandpass mechanisms can be ambiguous, particularly when the actual disparity is larger than a half-cycle of the preferred spatial frequency of the filter, which often occurs in fine scales. In this study, we investigated whether the visual system uses a coarse-to-fine interaction to resolve this ambiguity at finer scales for depth estimation from disparity. The stimuli were stereo grating patches composed of a target and comparison patterns. The target patterns contained spatial frequencies of 1 and 4 cycles per degree (cpd). The phase disparity of the low-frequency component was 0° (at the horopter), -90° (uncrossed), or 90° (crossed), and that of the high-frequency components was changed independent of the low-frequency disparity, in the range between -90° (uncrossed) and 90° (crossed). The observers' task was to indicate whether the target appeared closer to the comparison pattern, which always shared the disparity with the low-frequency component of the target. Regardless of whether the comparison pattern was a 1-cpd + 4-cpd compound or a 1-cpd simple grating, the perceived depth order of the target and the comparison varied in accordance with the phase disparity of the high-frequency component of the target. This effect occurred not only when the low-frequency component was at the horopter, but also when it contained a large disparity corresponding to one cycle of the high-frequency component (±90°). Our findings suggest a coarse-to-fine interaction in multiscale disparity processing, in which the depth interpretation of the high-frequency changes based on the disparity of the low-frequency component.

Gestalt neurons and emergent properties in visual perception: A novel concept for the transformation from local to global processing.

Gestalten in visual perception are defined by emergent properties of the whole, which cannot be predicted from the sum of its parts; rather, they arise by virtue of inherent principles, the Laws of Seeing. This review attempts to assign neurophysiological correlates to select emergent properties in motion and contour perception and proposes parallels to the processing of local versus global attributes by classical versus contextual receptive fields. The aim is to identify Gestalt neurons in the visual system to account for the Laws of Seeing in causal terms and to explain "Why do things look as they do" (Koffka, 1935, p. 76).

A One-Size-Fits-All Approach to Pressure Ulcers: Whole-Buttock Fasciocutaneous Advancement Flap.

BACKGROUND: Buttock pressure injuries can be difficult to treat. There are many choices of flaps to reconstruct these wounds, but few are large, technically simple, and easily recycled. AIM AND OBJECTIVE: We are presenting our experience on surgical reconstruction of buttock pressure injuries using large whole-buttock fasciocutaneous flaps that are easily designed for ulcers regardless of location and size and are easily recycled for treatment of recurrences. MATERIAL AND METHODS: We conducted a retrospective review of all patients who received reconstruction with fasciocutaneous rotational flaps for buttock region pressure injuries from January 2013 to December 2018. The key steps of this one-size-fits-all flap include elevation of a large, oversized flap to achieve tension-free closure, avoiding fascial incisions over bony prominences, placing the V-Y type closure wound in the posteromedial thigh, and the use of closed incisional negative wound therapy postoperatively. RESULTS: Fifty patients underwent 54 flaps reconstruction for coverage of stage 4 gluteal pressure injuries between January 2013 and December 2018. Seventy-four percent healed without the need for further operation. The average size of the defect was 90 cm2 (maximum = 300 cm2). The average follow-up period was 31 months. Four of the 54 flaps were "recycled" flaps, 3 were performed for the coverage of recurrent ulcers and 1 flap was performed for treatment of a postoperative wound dehiscence. CONCLUSIONS: We recommend this simple, one-size-fits-all approach, whole-buttock fasciocutaneous flap when surgically treating gluteal pressure injuries for selected patients.

Biomechanical Evaluation and Factorial Analysis of the 3-Dimensional Printing Self-Designed Metallic Reconstruction Plate for Mandibular Segmental Defect.

PURPOSE: Reconstruction plates are frequently used to treat mandibular segmental defects. The aim of this study is to compare the biomechanical performance of a 3-dimensional-printed self-designed titanium alloy reconstruction plate with that of the traditional reconstruction plate in mandible reconstruction. The analyzed parameters of the self-designed reconstruction plate, including plate length (100 mm and 125 mm), plate thickness (2.1, 2.4, and 2.7 mm), and bone mass (100, 75, and 50%), were also evaluated. METHODS: An artificial mandible with anatomical geometry was used to develop the self-designed reconstructed plate. Both in vitro experiments and finite element simulations were performed for the biomechanical comparison of the self-designed and traditional reconstruction plates. In finite element analysis, 3 major muscle forces of mandible movement were set as the loading condition, and the displacement of the condyle was fixed in all directions as the boundary condition. RESULTS: The biomechanical performances (stresses in the plate and strains in bone) of the self-designed reconstruction plate were superior to those of the traditional plate. Factorial analysis indicated that plate length and thickness had significant effects on decreasing stresses of the plate and mandibular bone. CONCLUSIONS: The self-designed reconstruction plate might have a benefit to reduce the stresses/strains in plate itself and surrounding bone.

The role of color contrast gain control in global form perception.

A Glass pattern consists of randomly distributed dot pairs, or dipoles, whose orientation is determined by a geometric transform, which defines the global percept perceived by an observer. The perception of Glass patterns involves a local process that associates dot pairs into dipoles and a global process that groups the dipoles into a global structure. In the present study, we used a variant of Glass patterns, which was composed of randomly distributed tripoles instead of dipoles, to estimate the influence of color contrast on perceptual grouping. Each tripole contained an anchor dot and two context dots. Grouping the anchor dot with one of the context dots resulted in a global percept of a clockwise spiral, while grouping with the other dot, a counter-clockwise spiral. All dots in each pattern were modulated in the same color direction but different contrasts. Four colors were involved, namely, red, green, blue, and yellow. The observers were to determine whether the spiral in each trial was clockwise or counter-clockwise. The probability of a context dot being grouped with the anchoring dot increased with its color contrast to a certain level, then decreased when the contrast continued to increase. Such probability decreased as the contrast of the other context dot increased. Our result cannot be explained by existing models in the literature, but with a divisive inhibition model. The equiluminance contrast result observed here is similar to the inverted U-shaped function for luminance contrast result previously reported by us, except that the color contrast model comprises a weaker self-inhibition component.

The role of lateral modulation in orientation-specific adaptation effect.

Center-surround modulation in visual processing reflects a normalization process of contrast gain control in the responsive neurons. Prior adaptation to a clockwise (CW) tilted grating, for example, leads to the percept of counterclockwise tilt in a vertical grating, referred to as the tilt-aftereffect (TAE). We previously reported that the magnitude of the TAE is modulated by adding a same-orientation annular surround to an adapter, suggesting inhibitory lateral modulation. To further examine the property of this lateral modulation effect on the perception of a central target, we here used center-surround sinusoidal patterns as adapters and varied the adapter surround and center orientations independently. The target had the same spatial extent as the adapter center with no physical overlap with the adapter surround. Participants were asked to judge the target orientation as tilted either CW or counterclockwise from vertical after adaptation. Results showed that, when the surround orientation was held constant, the TAE magnitude was determined by the adapter center, peaking between 10° and 20° of tilt. More important, the adapter surround orientation modulated the adaptation effect such that the TAE magnitude first decreased and then increased as the surround orientation became increasingly more different from that of the center, suggesting that the surround modulation effect was indeed orientation specific. Our data can be accounted for by a divisive inhibition model, in which (1) the adaptation effect is represented by increasing the normalizing constant and (2) the surround modulation is captured by two multiplicative sensitivity parameters determined by the adapter surround orientation.

Microtube Array Membrane Encapsulated Cell Therapy: A Novel Platform Technology Solution for Treatment of Alzheimer's Disease.

Alzheimer's disease is the most frequent form of dementia in aging population and is presently the world's sixth largest cause of mortality. With the advancement of therapies, several solutions have been developed such as passive immunotherapy against these misfolded proteins, thereby resulting in the clearance. Within this segment, encapsulated cell therapy (ECT) solutions that utilize antibody releasing cells have been proposed with a multitude of techniques under development. Hence, in this study, we utilized our novel and patented Microtube Array Membranes (MTAMs) as an encapsulating platform system with anti-pTau antibody-secreting hybridoma cells to study the impact of it on Alzheimer's disease. In vivo results revealed that in the water maze, the mice implanted with hybridoma cell MTAMs intracranially (IN) and subcutaneously (SC) showed improvement in the time spent the goal quadrant and escape latency. In passive avoidance, hybridoma cell loaded MTAMs (IN and SC) performed significantly well in step-through latency. At the end of treatment, animals with hybridoma cell loaded MTAMs had lower phosphorylated tau (pTau) expression than empty MTAMs had. Combining both experimental results unveiled that the clearance of phosphorylated tau might rescue the cognitive impairment associated with AD.

Involvement of Aquaporins in the Intense Pulsed Light-Enhanced Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVES: We previously demonstrated that intense pulsed light (IPL) irradiation prior to wounding improved the wound healing in rats with diabetes mellitus (DM). Also, we found that IPL upregulated the expression of aquaporin 3 (AQP3), a protein that is crucial for wound healing, in normal rats. This present study aimed to examine the involvement of AQPs in the IPL-enhanced wound healing in diabetic rats. STUDY DESIGN/MATERIALS AND METHODS: Streptozotocin was used to induce diabetes in Sprague-Dawley rats. Animals were divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL irradiation and wounding (DM + IPL-Con group). Wounds were created on the dorsal skin of rats. The expressions of AQP1, 3, 4, 7, and 9 in the pre-injured skin, periwound, and wound were determined. RESULTS: Among all the AQPs analyzed, only the expressions of AQP3 and AQP7 were significantly altered. Unirradiated diabetic rats showed much higher expression level of AQP3 in the regenerating skin compared with normal rats. IPL pretreatment, but not concurrent treatment, attenuated the expression toward the level detected in the normal wounds. In contrast, a lower expression level of AQP7 was noted in the regenerating skin of DM only rats and IPL pretreatment upregulated the expression to a level similar to that in the normal rats. CONCLUSION: The beneficial effect of IPL pretreatment on the wound healing in diabetic rats might involve a mechanism by which the expression of AQPs is regulated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. RESULTS: There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. CONCLUSION: Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

Lateral modulation of orientation perception in center-surround sinusoidal stimuli: Divisive inhibition in perceptual filling-in.

The perception of a target stimulus may be altered by its context. Perceptual filling-in is thought to be one example of lateral modulation, in which the percept of a central blank area is replaced by that of the surround. We investigated the mechanisms in eccentric vision underlying filling-in by selectively adapting the center (pedestal adapter), surround (annulus adapter), or both (disk adapter) in a sinusoidal grating and observed how the adaptation influences the orientation percept of a subsequently presented Gabor target, located at the same position as the adapter center. In a binary choice task, observers were to judge the orientation (clockwise or counterclockwise) of the target after adaptation. The tilt aftereffect (TAE), corresponding to an illusory tilt of a physically vertical Gabor target, depended both on the adapter orientation and the adapter type. The TAE, peaked between 10 degrees and 20 degrees adapter orientation, was strongest in the pedestal, followed by the disk, and weakest in the annulus adapter conditions. The difference between the disk and pedestal conditions implies lateral inhibition from the surround. Lacking physical overlap with the target, the annulus adapter nonetheless induced a small but significant TAE in the central area. The effect of filling-in on the TAE was estimated by comparing the results from trials with and without subjectively reported filling-in during adaptation to the annulus adapter. The TAE was greater when filling-in occurred during adaptation, suggesting a stronger lateral modulation effect on trials where filling-in was induced. The data were fit by a variant of a divisive inhibition model, in which the adaptation effect is captured by the increase of an additive constant in the denominator of the response function, whereas the surround modulation in the adapter is modeled by an excitatory sensitivity in the numerator.

Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways.

Extrapituitary prolactin (Prl) is produced in humans and rodents; however, little is known about its in vivo regulation or physiological function. We now report that autocrine prolactin is required for terminal mammary epithelial differentiation during pregnancy and that its production is regulated by the Pten-PI3K-Akt pathway. Conditional activation of the PI3K-Akt pathway in the mammary glands of virgin mice by either Akt1 expression or Pten deletion rapidly induced terminal mammary epithelial differentiation accompanied by the synthesis of milk despite the absence of lobuloalveolar development. Surprisingly, we found that mammary differentiation was due to the PI3K-Akt-dependent synthesis and secretion of autocrine prolactin and downstream activation of the prolactin receptor (Prlr)-Jak-Stat5 pathway. Consistent with this, Akt-induced mammary differentiation was abrogated in Prl(-/-), Prlr(-/-), and Stat5(-/-) mice. Furthermore, cells treated with conditioned medium from mammary glands in which Akt had been activated underwent rapid Stat5 phosphorylation in a manner that was blocked by inhibition of Jak2, treatment with an anti-Prl antibody, or deletion of the prolactin gene. Demonstrating a physiological requirement for autocrine prolactin, mammary glands from lactation-defective Akt1(-/-);Akt2(+/-) mice failed to express autocrine prolactin or activate Stat5 during late pregnancy despite normal levels of circulating serum prolactin and pituitary prolactin production. Our findings reveal that PI3K-Akt pathway activation is necessary and sufficient to induce autocrine prolactin production in the mammary gland, Stat5 activation, and terminal mammary epithelial differentiation, even in the absence of the normal developmental program that prepares the mammary gland for lactation. Together, these findings identify a function for autocrine prolactin during normal development and demonstrate its endogenous regulation by the PI3K-Akt pathway.

Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice.

Oxytocin (OXT) receptors (OXTRs) are prominently expressed in hippocampal CA2 and CA3 pyramidal neurons, but little is known about its physiological function. As the functional necessity of hippocampal CA2 for social memory processing, we tested whether CA2 OXTRs may contribute to long-term social recognition memory (SRM) formation. Here, we found that conditional deletion of Oxtr from forebrain (Oxtr-/-) or CA2/CA3a-restricted excitatory neurons in adult male mice impaired the persistence of long-term SRM but had no effect on sociability and preference for social novelty. Conditional deletion of CA2/CA3a Oxtr showed no changes in anxiety-like behavior assessed using the open-field, elevated plus maze and novelty-suppressed feeding tests. Application of a highly selective OXTR agonist [Thr4,Gly7]-OXT to hippocampal slices resulted in an acute and lasting potentiation of excitatory synaptic responses in CA2 pyramidal neurons that relied on N-methyl-d-aspartate receptor activation and calcium/calmodulin-dependent protein kinase II activity. In addition, Oxtr-/- mice displayed a defect in the induction of long-term potentiation, but not long-term depression, at the synapses between the entorhinal cortex and CA2 pyramidal neurons. Furthermore, Oxtr deletion led to a reduced complexity of basal dendritic arbors of CA2 pyramidal neurons, but caused no alteration in the density of apical dendritic spines. Considering that the methodologies we have used to delete Oxtr do not rule out targeting the neighboring CA3a region, these findings suggest that OXTR signaling in the CA2/CA3a is crucial for the persistence of long-term SRM.SIGNIFICANCE STATEMENT Oxytocin receptors (OXTRs) are abundantly expressed in hippocampal CA2 and CA3 regions, but there are little known about their physiological function. Taking advantage of the conditional Oxtr knock-out mice, the present study highlights the importance of OXTR signaling in the induction of long-term potentiation at the synapses between the entorhinal cortex and CA2 pyramidal neurons and the persistence of long-term social recognition memory. Thus, OXTRs in the CA2/CA3a may provide a new target for therapeutic approaches to the treatment of social cognition deficits, which are often observed in patients with neuropsychiatric disorders.

Length summation in noise.

To investigate the effect of background noise on visual summation, we measured the contrast detection thresholds for targets with or without a white noise mask in luminance contrast. The targets were Gabor patterns placed at 3° eccentricity to either the left or right of the fixation and elongated along an arc of the same radius to ensure equidistance from fixation for every point along the long axis. The task was a spatial two-alternative forced-choice (2AFC) paradigm in which the observer had to indicate whether the target was on the left or the right of the fixation. The threshold was measured at 75% accuracy with a staircase procedure. The detection threshold decreased with target length with slope -1/2 on log-log coordinates for target lengths between 30' and 300' half-height full-width (HHFW), defining a range of ideal matched-filter summation extending up to about 200' (or about 16× the center width of the Gabor targets). The summation curves for different noise contrasts were shifted copies of each other. For the threshold versus mask contrast (TvN) functions, the target threshold was constant for noise levels up to about -22 dB, then increased with noise contrast to a linear asymptote on log-log coordinates. Since the "elbow" of the target threshold versus noise function is an index of the level of the equivalent noise experienced by the visual system during target detection, our results suggest that the signal-to-noise ratio was invariant with target length. We further show that a linear-nonlinear-linear gain-control model can fully account for these results with far fewer parameters than a matched-filter model.

Spatial configuration processing in visual word form perception and reading abilities in Chinese.

The analysis of spatial relations among components of a character is important in identifying visual word forms. We investigated such spatial configuration processing for Chinese characters in dyslexic children (aged 9-12 years) and two groups of typically developing children, matched according to chronological age or reading level. In this study, we used real characters and noncharacters to manipulate the spatial configuration between character components while preserving their local features. Both characters were displayed either in an upright or inverted position. Participants were asked to quickly determine whether the two presented stimuli were identical. A significant interaction between character type and character orientation showed children's matching performance was better in upright real characters than in the inverted version, but such effect was absent in noncharacters. This indicated that regardless of reading skills, children developed the ability to use local configuration information to visually identify words. Dyslexic children performed poorly in both real-character and noncharacter conditions. Furthermore, compared with control groups, dyslexic children performed worse in real-character conditions, which were close to the noncharacter performance of other groups. This reflected an impairment of global visual word-form processing (i.e., spatial configuration between components) in dyslexia.

A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.

Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S. epidermidis. We demonstrate that the application of the encapsulation of S. epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C. acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S. epidermidis in the presence of glycerol. The application of S. epidermidis-encapsulated PST MTAM plus glycerol onto the C. acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.

MiR-148a and miR-152 reduce tamoxifen resistance in ER+ breast cancer via downregulating ALCAM.

Activated leukocyte cell adhesion molecule (ALCAM), also called CD166 is a 105-kDa transmembrane glycoprotein of the immunoglobin superfamily. In this study, we studied the association between ALCAM expression and tamoxifen resistance in ER + breast cancer and further investigated how ALCAM is regulated in the cancer cells. IHC staining data showed that the tumor tissues from non-responders (N = 20) generally had significantly stronger ALCAM staining than that from tamoxifen responders (N = 16). In vitro cell assay also confirmed ALCAM upregulation in tamoxifen resistant (TamR) MCF-7 cells than in tamoxifen sensitive (TamS) MCF-7 cells. ALCAM overexpression significantly alleviated 4-Hydroxytestosterone (4-OHT) induced cell viability inhibition and cell apoptosis in TamS MCF-7 cells, while ALCAM knockdown remarkably enhanced 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. Demethylation reagent treatment significantly restored miR-148a and miR-152 expression in TamR MCF-7 cells. MiR-148a and miR-152 can directly target ALCAM 3'UTR and decrease ALCAM expression. MiR-148a overexpression had similar effect as ALCAM siRNA on enhancing 4-OHT induced cell viability inhibition and cell apoptosis in TamR MCF-7 cells. MiR-152 overexpression alone caused growth inhibition and increased cell apoptosis in TamR MCF-7 cells. It also enhanced the effect of 4-OHT. Simultaneous inhibition of miR-148a and miR-152 significantly protected TamS MCF-7 cells from 4-OHT induced cell viability inhibition and cell apoptosis. Based on these findings, we infer that MiR-148a and miR-152 can sensitize TamR MCF-7 cells to tamoxifen at least via downregulating ALCAM.

An Effective Cell Coculture Platform Based on the Electrospun Microtube Array Membrane for Nerve Regeneration.

Recently, a novel substrate known as an electrospun polylactic acid (PLLA) microtube array membrane (MTAM) was successfully developed as a cell coculture platform. Structurally, this substrate is made up of one-to-one connected, ultrathin, submicron scale fibers that are arranged in an arrayed formation. Its unique structure confers several key advantages which are beneficial in a cell coculture system. In this study, the interaction between rat fetal neural stem cells (NSC) and astrocytes was examined by comparing the outcome of a typical Transwell-based coculture system and that of an electrospun PLLA MTAM-based coculture system. Compared to tissue culture polystyrene (TCP) and Transwell coculture inserts, a superior cell viability of NSC was observed when cultured in lumens of electrospun PLLA MTAM (with supportive immunostaining images). Reverse transcription polymerase chain reaction revealed a strong interaction between astrocytes and NSC through a higher expression of doublecortin and a lower expression of nestin. These data demonstrate that MTAM is clearly a better coculture platform than the traditional Transwell system.

Contrast gain control determines global form percept in tripole Glass patterns.

A Glass pattern consists of randomly distributed dot pairs, or dipoles, whose orientation is determined by a geometric transform that defines the global percept for this pattern. The perception of Glass patterns involves a local process to associate paired dots into dipoles and a global process to group the dipoles into a global structure. We used a variant of Glass patterns consisting of tripoles instead of dipoles to estimate the effect of luminance contrast on the global form percept. In each tripole, an anchor dot and two context dots formed the vertices of an equilateral triangle with the anchor dot pointing toward the center of the display. Grouping the anchor dot with one context dot would result in a global percept of a clockwise (CW) spiral and grouping with the other dot a counterclockwise (CCW) spiral. We manipulated the contrast of the context dots and measured the probability of a participant judging the patterns as a CW spiral. The CW spiral judging probability first increased then decreased with the contrast of the CW context dots, resulting in an inverted U shape. The peak also shifted to the right as the contrast of the competing CCW context dots increased. Our result cannot be explained by the existing models for Glass pattern perception. Instead, the data was well fit by a divisive inhibition model, in which the response of a global pattern is the excitation raised by a power and divided by the inhibition from all global patterns plus an additive constant.

Alleviating Bone Cancer-induced Mechanical Hypersensitivity by Inhibiting Neuronal Activity in the Anterior Cingulate Cortex.

BACKGROUND: The anterior cingulate cortex (ACC) is a brain region that has been critically implicated in the processing of pain perception and modulation. While much evidence has pointed to an increased activity of the ACC under chronic pain states, less is known about whether pain can be alleviated by inhibiting ACC neuronal activity. METHODS: The authors used pharmacologic, chemogenetic, and optogenetic approaches in concert with viral tracing technique to address this issue in a mouse model of bone cancer-induced mechanical hypersensitivity by intratibia implantation of osteolytic fibrosarcoma cells. RESULTS: Bilateral intra-ACC microinjections of γ-aminobutyric acid receptor type A receptor agonist muscimol decreased mechanical hypersensitivity in tumor-bearing mice (n =10). Using adenoviral-mediated expression of engineered Gi/o-coupled human M4 (hM4Di) receptors, we observed that activation of Gi/o-coupled human M4 receptors with clozapine-N-oxide reduced ACC neuronal activity and mechanical hypersensitivity in tumor-bearing mice (n = 11). In addition, unilateral optogenetic silencing of ACC excitatory neurons with halorhodopsin significantly decreased mechanical hypersensitivity in tumor-bearing mice (n = 4 to 9), and conversely, optogenetic activation of these neurons with channelrhodopsin-2 was sufficient to provoke mechanical hypersensitivity in sham-operated mice (n = 5 to 9). Furthermore, we found that excitatory neurons in the ACC send direct descending projections to the contralateral dorsal horn of the lumbar spinal cord via the dorsal corticospinal tract. CONCLUSIONS: The findings of this study indicate that enhanced neuronal activity in the ACC contributes to maintain bone cancer-induced mechanical hypersensitivity and suggest that the ACC may serve as a potential therapeutic target for treating bone cancer pain.