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Given that multiple senses are often stimulated at the same time, perceptual awareness is most likely to take place in multisensory situations. However, theories of awareness are based on studies and models established for a single sense (mostly vision). Here, we consider the methodological and theoretical challenges raised by taking a multisensory perspective on perceptual awareness. First, we consider how well tasks designed to study unisensory awareness perform when used in multisensory settings, stressing that studies using binocular rivalry, bistable figure perception, continuous flash suppression, the attentional blink, repetition blindness and backward masking can demonstrate multisensory influences on unisensory awareness, but fall short of tackling multisensory awareness directly. Studies interested in the latter phenomenon rely on a method of subjective contrast and can, at best, delineate conditions under which individuals report experiencing a multisensory object or two unisensory objects. As there is not a perfect match between these conditions and those in which multisensory integration and binding occur, the link between awareness and binding advocated for visual information processing needs to be revised for multisensory cases. These challenges point at the need to question the very idea of multisensory awareness. [ABSTRACT FROM AUTHOR]

Coinfection with Candida and Staphylococcus results in higher mortality in animal studies. However, the pathogenesis and interplay between C. albicans and S. aureus in bloodstream infections (BSIs) is unclear. This study determines the clinical features and outcomes of mixed C. albicans/S. aureus (CA/SA) BSIs and biofilm formation on pathogenesis during coinfection. Demographics and outcomes for mixed BSIs and monomicrobial candidemia were compared. Compared to 115 monomicrobial C. albicans BSIs, 22 patients with mixed CA/SA BSIs exhibited a significantly higher mortality rate and shorter survival time. In vitro and in vivo biofilm analysis showed that C. albicans accounted for the main biofilm architecture, and S. aureus increased its amount. Antibiotic tolerance in S. aureus, which adhered to Candida hyphae observed by scanning electron microscope, was demonstrated by the presence of wild-type C. albicans co-biofilm. Upregulation in exotoxin genes of S. aureus was evidenced by quantitative RT-PCR when a co-biofilm was formed with C. albicans. Mixed CA/SA BSIs result in a higher mortality rate in patients and in vivo surrogate models experiments. This study demonstrates that the virulence enhancement of C. albicans and S. aureus during co-biofilm formation contributes to the high mortality rate.

The time-course of cross-modal semantic interactions between pictures and either naturalistic sounds or spoken words was compared. Participants performed a speeded picture categorization task while hearing a task-irrelevant auditory stimulus presented at various stimulus onset asynchronies (SOAs) with respect to the visual picture. Both naturalistic sounds and spoken words gave rise to cross-modal semantic congruency effects (i.e., facilitation by semantically congruent sounds and inhibition by semantically incongruent sounds, as compared to a baseline noise condition) when the onset of the sound led that of the picture by 240 ms or more. Both naturalistic sounds and spoken words also gave rise to inhibition irrespective of their semantic congruency when presented within 106 ms of the onset of the picture. The peak of this cross-modal inhibitory effect occurred earlier for spoken words than for naturalistic sounds. These results therefore demonstrate that the semantic priming of visual picture categorization by auditory stimuli only occurs when the onset of the sound precedes that of the visual stimulus. The different time-courses observed for naturalistic sounds and spoken words likely reflect the different processing pathways to access the relevant semantic representations. [ABSTRACT FROM AUTHOR]

We report a series of experiments designed to demonstrate that the presentation of a sound can facilitate the identification of a concomitantly presented visual target letter in the backward masking paradigm. Two visual letters, serving as the target and its mask, were presented successively at various interstimulus intervals (ISis). The results demonstrate that the crossmodal facilitation of participants' visual identification performance elicited by the presentation of a simultaneous sound occurs over a very narrow range of ISis. This critical time-window lies just beyond the interval needed for participants to differentiate the target and mask as constituting two distinct perceptual events (Experiment 1) and can be dissociated from any facilitation elicited by making the visual target physically brighter (Experiment 2). When the sound is presented at the same time as the mask, a facilitatory, rather than an inhibitory effect on visual target identification performance is still observed (Experiment 3). We further demonstrate that the crossmodal facilitation of the visual target by the sound depends on the establishment of a reliable temporally coincident relationship between the two stimuli (Experiment 4); however, by contrast, spatial coincidence is not necessary (Experiment 5). We suggest that when visual and auditory stimuli are always presented synchronously, a better-consolidated object representation is likely to be constructed (than that resulting from unimodal visual stimulation). [ABSTRACT FROM AUTHOR]

We propose a multisensory framework based on Glaser and Glaser's (1989) general reading-naming interference model to account for the semantic priming effect by naturalistic sounds and spoken words on visual picture sensitivity. Four experiments were designed to investigate two key issues: First, can auditory stimuli enhance visual sensitivity when the sound leads the picture as well as when they are presented simultaneously? And, second, do naturalistic sounds (e.g., a dog's "woofing") and spoken words (e.g.,/dƆg/) elicit similar semantic priming effects? Here, we estimated participants' sensitivity and response criterion using signal detection theory in a picture detection task. The results demonstrate that naturalistic sounds enhanced visual sensitivity when the onset of the sounds led that of the picture by 346 ms (but not when the sounds led the pictures by 173 ms, nor when they were presented simultaneously, Experiments 1-3A). At the same SOA, however, spoken words did not induce semantic priming effects on visual detection sensitivity (Experiments 3B and 4A). When using a dual picture detection/identification task, both kinds of auditory stimulus induced a similar semantic priming effect (Experiment 4B). Therefore, we suggest that there needs to be sufficient processing time for the auditory stimulus to access its associated meaning to modulate visual perception. Besides, the interactions between pictures and the two types of sounds depend not only on their processing route to access semantic representations, but also on the response to be made to fulfill the requirements of the task. [ABSTRACT FROM AUTHOR]

Nanocrystalline ZnO particles were synthesized from an aqueous solution composed of zinc acetate dihydrate (Zn(CH3COO)2·2H2O) and urea (H2NCONH2). A precipitating precursor, basic zinc carbonate (Zn5(CO3)2(OH)6), was first formed by hydrothermally treating the solution at 120 °C for 2–4 h. Nanocrystalline ZnO particles were then obtained by calcining the precursors at 350–650 °C for 0.5–2 h. The synthesis products were characterized using thermogravimetry–differential scanning calorimetry–mass spectrometry, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and photoluminescence techniques. Based on the experimental results, a possible reaction mechanism for the ZnO formation was proposed. The effects of experimental parameters (namely, the hydrothermal treatment time, the calcination time, and the calcination temperature) on the characteristics of the resulting ZnO products (i.e., the crystalline size and the photoluminescence properties) were analyzed by the Taguchi method to attain the optimum synthesis conditions. By using the appropriate parameters derived from this method, we verified that the optimized synthesis provided a yield of ~70% and that the resulting ZnO particles possessed the characteristics of a ~25 nm crystalline size and a satisfactory photoluminescence property. [ABSTRACT FROM AUTHOR]

Repetition blindness (RB) is a visual deficit, wherein observers fail to perceive the second occurrence of a repeated item in a rapid serial visual presentation stream. Chen and Yeh (Psychon Bull Rev 15:404–408, 2008) recently observed a reduction of the RB effect when the repeated items were accompanied by two sounds. The current study further manipulated the pitch of the two sounds (same versus different) in order to examine whether this cross-modal facilitation effect is caused by the multisensory enhancement of the visual event by sound, or multisensory Gestalt (perceptual grouping) of a new representation formed by combining the visual and auditory inputs. The results showed robust facilitatory effects of sound on RB regardless of the pitch of the sounds (Experiment 1), despite an effort to further increase the difference in pitch (Experiment 2). Experiment 3 revealed a close link between participants’ awareness of pitch and the effect of pitch on the RB effect. We conclude that the facilitatory effect of sound on RB results from multisensory enhancement of the perception of visual events by auditory signals. [ABSTRACT FROM AUTHOR]

Repetition blindness (RB; Kanwisher, 1987) is the term used to describe people's failure to detect or report an item that is repeated in a rapid serial visual presentation (RSVP) stream. Although RB is, by definition, a visual deficit, whether it is affected by an auditory signal remains unknown. In the present study, we added two sounds before, simultaneous with, or after the onset of the two critical visual items during RSVP to examine the effect of sound on RB. The results show that the addition of the sounds effectively reduced RB when they appeared at, or around, the critical items. These results indicate that it is easier to perceive an event containing multisensory information than unisensory ones. Possible mechanisms of how visual and auditory information interact are discussed. [ABSTRACT FROM AUTHOR]

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants. Metformin inhibited pronephric cyst formation by 42–61% compared with the untreated controls. Metformin also reduced the number of proliferating cells in the pronephric ducts, the degree of dorsal body curvature, and the infiltration of leukocytes surrounding the pronephros. Moreover, metformin treatment increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and enhanced autophagy in the pronephros. Our data suggest that metformin reduces cyst formation through activation of the AMPK pathway and modulation of defective cellular events such as proliferation and autophagy. These results also imply that metformin could have therapeutic potential for ADPKD treatment.

MicroRNAs (miRs) downregulate or upregulate the mRNA level by binding to the 3′-untranslated region (3′UTR) of target gene. Dysregulated miR levels can be used as biomarkers of Parkinson’s disease (PD) and could participate in the etiology of PD. In the present study, 45 brain-enriched miRs were evaluated in serum samples from 50 normal subjects and 50 sporadic PD patients. The level of miR-204-5p was upregulated in serum samples from PD patients. An upregulated level of miR-204-5p was also observed in the serum and substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Expression of miR-204-5p increased the level of α-synuclein (α-Syn), phosphorylated (phospho)-α-Syn, tau, or phospho-tau protein and resulted in the activation of endoplasmic reticulum (ER) stress in SH-SY5Y dopaminergic cells. Expression of miR-204-5p caused autophagy impairment and activation of c-Jun N-terminal kinase (JNK)-mediated apoptotic cascade in SH-SY5Y dopaminergic cells. Our study using the bioinformatic method and dual-luciferase reporter analysis suggests that miR-204-5p positively regulates mRNA expression of dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) by directly interacting with 3′UTR of DYRK1A. The mRNA and protein levels of DYRK1A were increased in SH-SY5Y dopaminergic cells expressing miR-204-5p and SN of MPTP-induced PD mouse model. Knockdown of DYRK1A expression or treatment of the DYRK1A inhibitor harmine attenuated miR-204-5p-induced increase in protein expression of phospho-α-Syn or phospho-tau, ER stress, autophagy impairment, and activation of JNK-mediated apoptotic pathway in SH-SY5Y dopaminergic cells or primary cultured dopaminergic neurons. Our results suggest that upregulated expression of miR-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated ER stress and apoptotic signaling cascade.

Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish (Danio rerio) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish prmt8 were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount in situ hybridization revealed ubiquitous prmt8 expression pattern during early embryonic stages, similar to that of prmt1. Knockdown of prmt8 with antisense morpholino oligonucleotide phenocopied prmt1-knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive prmt8 failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length prmt8 but not prmt1 cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the prmt8 morphants. In contrast, N-terminus- deleted but not full-length prmt8 cRNA can rescue the prmt1 morphants as efficiently as prmt1 cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon prmt8 knockdown confirm the critical roles of prmt8 in neural development. In summery, our study is the first report showing the expression and function of prmt8 in early zebrafish embryogenesis. Our results indicate that prmt8 may play important roles non-overlapping with prmt1 in embryonic and neural development depending on its specific N-terminus.

Akt1 is well known for its role in regulating cell proliferation, differentiation, and apoptosis and is implicated in tumors and several neurological disorders. However, the role of Akt1 in neural development has not been well defined. We have isolated zebrafish akt1 and shown that this gene is primarily transcribed in the developing nervous system, and its spatiotemporal expression pattern suggests a role in neural differentiation. Injection of akt1 morpholinos resulted in loss of neuronal precursors with a concomitant increase in post-mitotic neurons, indicating that knockdown of Akt1 is sufficient to cause premature differentiation of neurons. A similar phenotype was observed in embryos deficient for Notch signaling. Both the ligand (deltaA) and the downstream target of Notch (her8a) were downregulated in akt1 morphants, indicating that Akt1 is required for Delta-Notch signaling. Furthermore, akt1 expression was downregulated in Delta-Notch signaling-deficient embryos and could be induced by constitutive activation of Notch signaling. In addition, knockdown of Akt1 was able to nullify the inhibition of neuronal differentiation caused by constitutive activation of Notch signaling. Taken together, these results provide in vivo evidence that Akt1 interacts with Notch signaling reciprocally and provide an explanation of why Akt1 is essential for the inhibition of neuronal differentiation.

Understanding how diversity of neural cells is generated is one of the main tasks of developmental biology. The Hairy/E(spl) family members are potential targets of Notch signaling, which has been shown to be fundamental to neural cell maintenance, cell fate decisions, and compartment boundary formation. However, their response to Notch signaling and their roles in neurogenesis are still not fully understood. In the present study, we isolated a zebrafish homologue of hairy/E(spl), her8a, and showed this gene is specifically expressed in the developing nervous system. her8a is positively regulated by Su(H)-dependent Notch signaling as revealed by a Notch-defective mutant and injection of variants of the Notch intracellular regulator, Su(H). Morpholino knockdown of Her8a resulted in upregulation of proneural and post-mitotic neuronal markers, indicating that Her8a is essential for the inhibition of neurogenesis. In addition, markers for glial precursors and mature glial cells were down-regulated in Her8a morphants, suggesting Her8a is required for gliogenesis. The role of Her8a and its response to Notch signaling is thus similar to mammalian HES1, however this is the converse of what is seen for the more closely related mammalian family member, HES6. This study not only provides further understanding of how the fundamental signaling pathway, Notch signaling, and its downstream genes mediate neural development and differentiation, but also reveals evolutionary diversity in the role of H/E(spl) genes.