Efr3b is essential for social recognition by modulating the excitability of CA2 pyramidal neurons.

CA2 pyramidal neurons (PNs) are associated with social behaviors. The mechanisms, however, remain to be fully investigated. Here, we report that Efr3b, a protein essential for phospholipid metabolism at the plasma membrane, is widely expressed in the brain, especially in the hippocampal CA2/CA3 areas. To assess the functional significance of Efr3b in the brain, we generated Efr3bf/f mice and crossed them with Nestin-cre mice to delete Efr3b specifically in the brain. We find that Efr3b deficiency in the brain leads to deficits of social novelty recognition and hypoexcitability of CA2 PNs. We then knocked down the expression of Efr3b specifically in CA2 PNs of C57BL/6J mice, and our results showed that reducing Efr3b in CA2 PNs also resulted in deficits of social novelty recognition and hypoexcitability of CA2 PNs. More interestingly, restoring the expression of Efr3b in CA2 PNs enhances their excitability and improves social novelty recognition in Efr3b-deficient mice. Furthermore, direct activation of CA2 PNs with chemogenetics improves social behaviors in Efr3b-deficient mice. Together, our data suggest that Efr3b is essential for social novelty by modulating the excitability of CA2 PNs.

A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane.

Phosphatidylinositol 4-kinase IIIα (PI4KIIIα) is the major enzyme responsible for generating phosphatidylinositol (4)-phosphate [PI(4)P] at the plasma membrane. This lipid kinase forms two multicomponent complexes, both including a palmitoylated anchor, EFR3. Whereas both PI4KIIIα complexes support production of PI(4)P, the distinct functions of each complex and mechanisms underlying the interplay between them remain unknown. Here, we present roles for differential palmitoylation patterns within a tri-cysteine motif in EFR3B (Cys5, Cys7 and Cys8) in controlling the distribution of PI4KIIIα between these two complexes at the plasma membrane and corresponding functions in phosphoinositide homeostasis. Spacing of palmitoyl groups within three doubly palmitoylated EFR3B 'lipoforms' affects both interactions between EFR3B and TMEM150A, a transmembrane protein governing formation of a PI4KIIIα complex functioning in rapid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] resynthesis following phospholipase C signaling, and EFR3B partitioning within liquid-ordered and -disordered regions of the plasma membrane. This work identifies a palmitoylation code involved in controlling protein-protein and protein-lipid interactions that affect a plasma membrane-resident lipid biosynthetic pathway.

Engineered Agrobacterium improves transformation by mitigating plant immunity detection.

Agrobacterium tumefaciens microbe-associated molecular pattern elongation factor Tu (EF-Tu) is perceived by orthologs of the Arabidopsis immune receptor EFR activating pattern-triggered immunity (PTI) that causes reduced T-DNA-mediated transient expression. We altered EF-Tu in A. tumefaciens to reduce PTI and improved transformation efficiency. A robust computational pipeline was established to detect EF-Tu protein variation in a large set of plant bacterial species and identified EF-Tu variants from bacterial pathogen Pseudomonas syringae pv. tomato DC3000 that allow the pathogen to escape EFR perception. Agrobacterium tumefaciens strains were engineered to substitute EF-Tu with DC3000 variants and examined their transformation efficiency in plants. Elongation factor Tu variants with rarely occurred amino acid residues were identified within DC3000 EF-Tu that mitigates recognition by EFR. Agrobacterium tumefaciens strains were engineered by expressing DC3000 EF-Tu instead of native agrobacterial EF-Tu and resulted in decreased plant immunity detection. These engineered A. tumefaciens strains displayed an increased efficiency in transient expression in both Arabidopsis thaliana and Camelina sativa. The results support the potential application of these strains as improved vehicles to introduce transgenic alleles into members of the Brassicaceae family.

Causal Relationship between the Right Auditory Cortex and Speech-Evoked Envelope-Following Response: Evidence from Combined Transcranial Stimulation and Electroencephalography.

Speech-evoked envelope-following response (EFR) reflects brain encoding of speech periodicity that serves as a biomarker for pitch and speech perception and various auditory and language disorders. Although EFR is thought to originate from the subcortex, recent research illustrated a right-hemispheric cortical contribution to EFR. However, it is unclear whether this contribution is causal. This study aimed to establish this causality by combining transcranial direct current stimulation (tDCS) and measurement of EFR (pre- and post-tDCS) via scalp-recorded electroencephalography. We applied tDCS over the left and right auditory cortices in right-handed normal-hearing participants and examined whether altering cortical excitability via tDCS causes changes in EFR during monaural listening to speech syllables. We showed significant changes in EFR magnitude when tDCS was applied over the right auditory cortex compared with sham stimulation for the listening ear contralateral to the stimulation site. No such effect was found when tDCS was applied over the left auditory cortex. Crucially, we further observed a hemispheric laterality where aftereffect was significantly greater for tDCS applied over the right than the left auditory cortex in the contralateral ear condition. Our finding thus provides the first evidence that validates the causal relationship between the right auditory cortex and EFR.

EFR3A: a new raft domain organizing protein?

BACKGROUND: Membrane rafts play a crucial role in the regulation of many important biological processes. Our previous data suggest that specific interactions of flotillins with MPP1 are responsible for membrane raft domain organization and regulation in erythroid cells. Interaction of the flotillin-based protein network with specific membrane components underlies the mechanism of raft domain formation and regulation, including in cells with low expression of MPP1. METHODS: We sought to identify other flotillin partners via the immobilized recombinant flotillin-2-based affinity approach and mass spectrometry technique. The results were further confirmed via immunoblotting and via co-immunoprecipitation. In order to study the effect of the candidate protein on the physicochemical properties of the plasma membrane, the gene was knocked down via siRNA, and fluorescence lifetime imaging microscopy and spot-variation fluorescence correlation spectroscopy was employed. RESULTS: EFR3A was identified as a candidate protein that interacts with flotillin-2. Moreover, this newly discovered interaction was demonstrated via overlay assay using recombinant EFR3A and flotillin-2. EFR3A is a stable component of the detergent-resistant membrane fraction of HeLa cells, and its presence was sensitive to the removal of cholesterol. While silencing the EFR3A gene, we observed decreased order of the plasma membrane of living cells or giant plasma membrane vesicles derived from knocked down cells and altered mobility of the raft probe, as indicated via fluorescence lifetime imaging microscopy and spot-variation fluorescence correlation spectroscopy. Moreover, silencing of EFR3A expression was found to disturb epidermal growth factor receptor and phospholipase C gamma phosphorylation and affect epidermal growth factor-dependent cytosolic Ca2+ concentration. CONCLUSIONS: Altogether, our results suggest hitherto unreported flotillin-2-EFR3A interaction, which might be responsible for membrane raft organization and regulation. This implies participation of this interaction in the regulation of multiple cellular processes, including those connected with cell signaling which points to the possible role in human health, in particular human cancer biology.

Ethanol Extract of Rosa laevigata Michx. Fruit Inhibits Inflammatory Responses through NF-κB/MAPK Signaling Pathways via AMPK Activation in RAW 264.7 Macrophages.

The fruit of Rosa laevigata Michx. (FR), a traditional Chinese herb utilized for the treatment of a variety diseases, has notably diverse pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory effects. Despite ongoing research on illustrating the underlying anti-inflammatory mechanism of FR, the principal mechanism remained inadequately understood. In this study, we investigated in depth the molecular mechanism of the anti-inflammatory actions of the ethanol extract of FR (EFR) and its potential targets using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. We showed that EFR effectively ameliorated the overproduction of inflammatory mediators and cytokines, as well as the expression of related genes. It was further demonstrated that LPS-induced activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) were significantly inhibited by pretreatment with EFR, accompanied by a concomitant decrease in the nuclear translocation of the p65 subunit of NF-κB and activator protein 1 (AP-1). In addition, EFR pretreatment potently prevented LPS-induced decreased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Our data also revealed that the activation of AMPK and subsequent inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway was probably responsible for the inhibitory effect of EFR on LPS-induced inflammatory responses, evidenced by reverse changes observed under the condition of AMPK inactivation following co-treatment with the AMPK-specific inhibitor Compound C. Finally, the main components with an anti-inflammatory effect in EFR were identified as madecassic acid, ellagic acid, quinic acid, and procyanidin C1 by LC-MS and testified based on the inhibition of NO production and inflammatory mediator expression. Taken together, our results indicated that EFR was able to ameliorate inflammatory responses via the suppression of MAPKs/NF-κB signaling pathways following AMPK activation, suggesting the therapeutic potential of EFR for inflammatory diseases.

Xylella fastidiosa's relationships: the bacterium, the host plants, and the plant microbiome.

Xylella fastidiosa is the causal agent of important crop diseases and is transmitted by xylem-sap-feeding insects. The bacterium colonizes xylem vessels and can persist with a commensal or pathogen lifestyle in more than 500 plant species. In the past decade, reports of X. fastidiosa across the globe have dramatically increased its known occurrence. This raises important questions: How does X. fastidiosa interact with the different host plants? How does the bacterium interact with the plant immune system? How does it influence the host's microbiome? We discuss recent strain genetic typing and plant transcriptome and microbiome analyses, which have advanced our understanding of factors that are important for X. fastidiosa plant infection.

Synaptopathy in the Aging Cochlea: Characterizing Early-Neural Deficits in Auditory Temporal Envelope Processing.

Aging listeners, even in the absence of overt hearing loss measured as changes in hearing thresholds, often experience impairments processing temporally complex sounds such as speech in noise. Recent evidence has shown that normal aging is accompanied by a progressive loss of synapses between inner hair cells and auditory nerve fibers. The role of this cochlear synaptopathy in degraded temporal processing with age is not yet understood. Here, we used population envelope following responses, along with other hair cell- and neural-based measures from an age-graded series of male and female CBA/CaJ mice to study changes in encoding stimulus envelopes. By comparing responses obtained before and after the application of the neurotoxin ouabain to the inner ear, we demonstrate that we can study changes in temporal processing on either side of the cochlear synapse. Results show that deficits in neural coding with age emerge at the earliest neural stages of auditory processing and are correlated with the degree of cochlear synaptopathy. These changes are seen before losses in neural thresholds and particularly affect the suprathreshold processing of sound. Responses obtained from more central sources show smaller differences with age, suggesting compensatory gain. These results show that progressive cochlear synaptopathy is accompanied by deficits in temporal coding at the earliest neural generators and contribute to the suprathreshold sound processing deficits observed with age.SIGNIFICANCE STATEMENT Aging listeners often experience difficulty hearing and understanding speech in noisy conditions. The results described here suggest that age-related loss of cochlear synapses may be a significant contributor to those performance declines. We observed aberrant neural coding of sounds in the early auditory pathway, which was accompanied by and correlated with an age-progressive loss of synapses between the inner hair cells and the auditory nerve. Deficits first appeared before changes in hearing thresholds and were largest at higher sound levels relevant to real world communication. The noninvasive tests described here may be adapted to detect cochlear synaptopathy in the clinical setting.

Direct Regulation of the EFR-Dependent Immune Response by Arabidopsis TCP Transcription Factors.

One layer of the innate immune system allows plants to recognize pathogen-associated molecular patterns (PAMPS), activating a defense response known as PAMP-triggered immunity (PTI). Maintaining an active immune response, however, comes at the cost of plant growth and development; accordingly, optimization of the balance between defense and development is critical to plant fitness. The TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor family consists of well-characterized transcriptional regulators of plant development and morphogenesis. The three closely related class I TCP transcription factors TCP8, TCP14, and TCP15 have also been implicated in the regulation of effector-triggered immunity, but there has been no previous characterization of PTI-related phenotypes. To identify TCP targets involved in PTI, we screened a PAMP-induced gene promoter library in a yeast one-hybrid assay and identified interactions of these three TCPs with the EF-Tu RECEPTOR (EFR) promoter. The direct interactions between TCP8 and EFR were confirmed to require an intact TCP binding site in planta. A tcp8 tcp14 tcp15 triple mutant was impaired in EFR-dependent PTI and exhibited reduced levels of PATHOGENESIS-RELATED PROTEIN 2 and induction of EFR expression after elicitation with elf18 but also increased production of reactive oxygen species relative to Col-0. Our data support an increasingly complex role for TCPs at the nexus of plant development and defense.

Clathrin-dependent endocytosis is required for immunity mediated by pattern recognition receptor kinases.

Sensing of potential pathogenic bacteria is of critical importance for immunity. In plants, this involves plasma membrane-resident pattern recognition receptors, one of which is the FLAGELLIN SENSING 2 (FLS2) receptor kinase. Ligand-activated FLS2 receptors are internalized into endosomes. However, the extent to which these spatiotemporal dynamics are generally present among pattern recognition receptors (PRRs) and their regulation remain elusive. Using live-cell imaging, we show that at least three other receptor kinases associated with plant immunity, PEP RECEPTOR 1/2 (PEPR1/2) and EF-TU RECEPTOR (EFR), internalize in a ligand-specific manner. In all cases, endocytosis requires the coreceptor BRI1-ASSOCIATED KINASE 1 (BAK1), and thus depends on receptor activation status. We also show the internalization of liganded FLS2, suggesting the transport of signaling competent receptors. Trafficking of activated PRRs requires clathrin and converges onto the same endosomal vesicles that are also shared with the hormone receptor BRASSINOSTERIOD INSENSITIVE 1 (BRI1). Importantly, clathrin-dependent endocytosis participates in plant defense against bacterial infection involving FLS2-mediated stomatal closure and callose deposition, but is uncoupled from activation of the flagellin-induced oxidative burst and MAP kinase signaling. In conclusion, immunity mediated by pattern recognition receptors depends on clathrin, a critical component for the endocytosis of signaling competent receptors into a common endosomal pathway.

Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3af/f mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Moreover, the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway was significantly enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF, TrkB, and the downstream molecules, including phospho-MAPK and phospho-Akt. Furthermore, the number of TUNEL+ cells was decreased in the subgranular zone of dentate gyrus in Efr3a-deficient mice compared with that of control mice. Our data suggest that brain-specific deletion of Efr3a could promote adult hippocampal neurogenesis, presumably by upregulating the expression of BDNF and its receptor, TrkB, and therefore provide new insight into the roles of Efr3 in the brain.-Qian, Q., Liu, Q., Zhou, D., Pan, H., Liu, Z., He, F., Ji, S., Wang, D., Bao, W., Liu, X., Liu, Z., Zhang, H., Zhang, X., Zhang, L., Wang, M., Xu, Y., Huang, F., Luo, B., Sun B. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

EFR3s are palmitoylated plasma membrane proteins that control responsiveness to G-protein-coupled receptors.

The yeast Efr3p protein is a main regulator of the Stt4p phosphatidylinositol 4-kinase at contact sites between the endoplasmic reticulum and the plasma membrane. A mutation in its fly homologue Rbo, leads to diminished light responses in the eye attributed to progressively impaired PLC signaling. Here, we find that Efr3s plays a role in maintaining responsiveness to the type-I angiotensin II (AngII) receptors. siRNA-mediated depletion of EFR3A and EFR3B impaired the sustained phase of cytosolic Ca(2+) response to high concentration of AngII in HEK293 cells that express wild type but not truncated AGTR1 (AT1a receptor), missing the phosphorylation sites. Efr3 depletion had minimal effect on the recovery of plasma membrane phosphoinositides during stimulation, and AT1 receptors still underwent ligand-induced internalization. A higher level of basal receptor phosphorylation and a larger response was observed after stimulation. Moreover, Gq activation more rapidly desensitized after AngII stimulation in Efr3 downregulated cells. A similar but less pronounced effect of EFR3 depletion was observed on the desensitization of the cAMP response after stimulation with isoproterenol. These data suggest that mammalian Efr3s contribute to the control of the phosphorylation state and, hence, desensitization of AT1a receptors, and could affect responsiveness of G-protein-coupled receptors in higher eukaryotes.

Comparative validity and repeatability of a single question, a twenty-eight-item FFQ and estimated food records to assess takeaway meal intake.

A single question (SQ) and a twenty-eight-item FFQ to measure takeaway meal intake were compared with two 7-d estimated food records (EFR; reference method). Test methods were completed after the reference period and repeated 6-8 d later for repeatability. The SQ asked about intake of high-SFA takeaway meals. FFQ items included low- and high-SFA meals. Test methods were compared with EFR for sensitivity, specificity, and positive and negative predictive values, using a goal of ≤1 high-SFA weekly takeaway meals. Bland-Altman analyses were used to check agreement between measurement approaches, the κ coefficient was used to summarise the observed level of agreement, and Spearman's correlation was used to assess the degree to which instruments ranked individuals. Young adults were recruited from two universities, and 109 participants (61 % female) completed the study. The mean age was 24·4 (sd 4·9) years, and the mean BMI was 23·5 (sd 3·7) kg/m2. The SQ and the FFQ had a sensitivity of 97 and 83 % and a specificity of 46 and 92 %, respectively. Both methods exhibited moderate correlation for measuring total and high-SFA takeaway meal intakes (r s ranging from 0·64 to 0·80). Neither instrument could measure precise, absolute intake at the group or individual level. Test methods ranged from fair (κ w =0·24) to moderate agreement (κ w =0·59). The repeatability for all was acceptable. The FFQ identified excessive high-SFA takeaway meal intake and measured individuals' category for total and high-SFA takeaway intakes. Both methods are suitable for ranking individuals for total or high-SFA takeaway meal intakes.

Application of clips assisted with foreign body forceps in defect closure after endoscopic full-thickness resection.

BACKGROUND: This study was designed to evaluate the feasibility and efficacy of metallic clips assisted with foreign body forceps closing the gastric wall defect after endoscopic full-thickness resection (EFR) for gastric submucosal tumors (SMTs). METHODS: Eighteen patients with gastric SMTs originated from the muscularis propria were treated by EFR between September 2012 and June 2014. Twelve patients underwent endoscopic closure of the gastric wall defects after EFR with endoloop and metallic clips (endoloop string suture method, ESSM), and six patients with clips and foreign body forceps (clips assisted with foreign body forceps clip method, CFCM). RESULTS: No significant differences existed between the two groups in terms of demographics, clinical characteristics, and the size of the gastric wall defects. The average time spent in closing the gastric wall defects (14.83 ± 1.94 min for the CFCM group and 22.42 ± 5.73 min for the ESSM group) and hospitalization fees of the CFCM group were significantly lower than those of the ESSM group. The average hospitalization time of the two groups had no statistical significance. No single case had surgical intervention or complications, such as gastric bleeding, perforation, peritonitis, or abdominal abscess. CONCLUSION: The CFCM and the ESSM are safe and effective techniques for gastric defect closure after EFR for gastric SMTs. Because of the "chopsticks effect," the CFCM more suitable for the lesions located at the gastric fundus, the greater curvature or anterior wall of the gastric body and gastric antrum.

On the Interplay Between Cochlear Gain Loss and Temporal Envelope Coding Deficits.

Hearing impairment is characterized by two potentially coexisting sensorineural components: (i) cochlear gain loss that yields wider auditory filters, elevated hearing thresholds and compression loss, and (ii) cochlear neuropathy, a noise-induced component of hearing loss that may impact temporal coding fidelity of supra-threshold sound. This study uses a psychoacoustic amplitude modulation (AM) detection task in quiet and multiple noise backgrounds to test whether these aspects of hearing loss can be isolated in listeners with normal to mildly impaired hearing ability. Psychoacoustic results were compared to distortion-product otoacoustic emission (DPOAE) thresholds and envelope-following response (EFR) measures. AM thresholds to pure-tone carriers (4 kHz) in normal-hearing listeners depended on temporal coding fidelity. AM thresholds in hearing-impaired listeners were normal, indicating that reduced cochlear gain may counteract how reduced temporal coding fidelity degrades AM thresholds. The amount with which a 1-octave wide masking noise worsened AM detection was inversely correlated to DPOAE thresholds. The narrowband noise masker was shown to impact the hearing-impaired listeners more so than the normal hearing listeners, suggesting that this masker may be targeting a temporal coding deficit. This study offers a window into how psychoacoustic difference measures can be adopted in the differential diagnostics of hearing deficits in listeners with mixed forms of sensorineural hearing loss.

S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signaling.

Plant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signaling molecules. Receptor kinases are regulated by numerous post-translational modifications.1,2,3 Here, using the immune receptor kinases FLS24 and EFR,5 we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biochemical properties and behavior within the membrane environment.6 We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following the perception of its ligand, flg22, in a BAK1 co-receptor and PUB12/13 ubiquitin ligase-dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signaling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR suppressed elf18-triggered signaling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents, and native membrane DIBMA nanodiscs indicates that S-acylation stabilizes, and promotes retention of, activated receptor kinase complexes at the plasma membrane to increase signaling efficiency.

Responses at Individual Gamma Frequencies Are Related to the Processing Speed but Not the Inhibitory Control.

The link between the state of networks underlying the generation of periodic responses at gamma ranges and cognitive outcomes is still poorly understood. In this study, we tested the idea that the individual differences in the ability to generate responses to auditory stimulation at gamma frequencies may underlie the individual differences in the inhibitory control. We focused on the processing speed and accuracy in the Bivalent Shape Task (a cognitive inhibition task assessing attentional interference) and explored the relationship with responses at 40 Hz and at individual gamma frequencies (IGFs, assessed utilizing auditory envelope-following responses in 30-60 Hz range). In a sample of 70 subjects, we show that individual measures (phase-locking index and event-related spectral perturbation) of the ability to generate gamma-range activity are not related to the individual differences in inhibitory control but rather reflect basic information processing speed in healthy young subjects. With the individualized approach (at IGFs), the observed associations were found to be somewhat stronger. These findings have important implications for the interpretation of gamma activity in neuropsychiatric disorders.

RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a.

Various RNA-binding proteins (RBPs) are key components in RNA metabolism and contribute to several neurodevelop-mental disorders. To date, only a few of such RBPs have been characterized for their roles in neocortex development. Here, we show that the RBP, Rbms1, is required for radial migration, polarization and differentiation of neuronal progenitors to neurons in the neocortex development. Rbms1 expression is highest in the early development in the developing cortex, with its expression gradually diminishing from embryonic day 13.5 (E13.5) to postnatal day 0 (P0). From in utero electroporation (IUE) experiments when Rbms1 levels are knocked down in neuronal progenitors, their transition from multipolar to bipolar state is delayed and this is accompanied by a delay in radial migration of these cells. Reduced Rbms1 levels in vivo also reduces differentiation as evidenced by a decrease in levels of several differentiation markers, meanwhile having no significant effects on proliferation and cell cycle rates of these cells. As an RNA binding protein, we profiled the RNA binders of Rbms1 by a cross-linked-RIP sequencing assay, followed by quantitative real-time polymerase chain reaction verification and showed that Rbms1 binds and stabilizes the mRNA for Efr3a, a signaling adapter protein. We also demonstrate that ectopic Efr3a can recover the cells from the migration defects due to loss of Rbms1, both in vivo and in vitro migration assays with cultured cells. These imply that one of the functions of Rbms1 involves the stabilization of Efr3a RNA message, required for migration and maturation of neuronal progenitors in radial migration in the developing neocortex.

Methodological considerations when measuring and analyzing auditory steady-state responses with multi-channel EEG.

The auditory steady-state response (ASSR) has been traditionally recorded with few electrodes and is often measured as the voltage difference between mastoid and vertex electrodes (vertical montage). As high-density EEG recording systems have gained popularity, multi-channel analysis methods have been developed to integrate the ASSR signal across channels. The phases of ASSR across electrodes can be affected by factors including the stimulus modulation rate and re-referencing strategy, which will in turn affect the estimated ASSR strength. To explore the relationship between the classical vertical-montage ASSR and whole-scalp ASSR, we applied these two techniques to the same data to estimate the strength of ASSRs evoked by tones with sinusoidal amplitude modulation rates of around 40, 100, and 200 Hz. The whole-scalp methods evaluated in our study, with either linked-mastoid or common-average reference, included ones that assume equal phase across all channels, as well as ones that allow for different phase relationships. The performance of simple averaging was compared to that of more complex methods involving principal component analysis. Overall, the root-mean-square of the phase locking values (PLVs) across all channels provided the most efficient method to detect ASSR across the range of modulation rates tested here.

The Relative and Combined Effects of Noise Exposure and Aging on Auditory Peripheral Neural Deafferentation: A Narrative Review.

Animal studies have shown that noise exposure and aging cause a reduction in the number of synapses between low and medium spontaneous rate auditory nerve fibers and inner hair cells before outer hair cell deterioration. This noise-induced and age-related cochlear synaptopathy (CS) is hypothesized to compromise speech recognition at moderate-to-high suprathreshold levels in humans. This paper evaluates the evidence on the relative and combined effects of noise exposure and aging on CS, in both animals and humans, using histopathological and proxy measures. In animal studies, noise exposure seems to result in a higher proportion of CS (up to 70% synapse loss) compared to aging (up to 48% synapse loss). Following noise exposure, older animals, depending on their species, seem to either exhibit significant or little further synapse loss compared to their younger counterparts. In humans, temporal bone studies suggest a possible age- and noise-related auditory nerve fiber loss. Based on the animal data obtained from different species, we predict that noise exposure may accelerate age-related CS to at least some extent in humans. In animals, noise-induced and age-related CS in separation have been consistently associated with a decreased amplitude of wave 1 of the auditory brainstem response, reduced middle ear muscle reflex strength, and degraded temporal processing as demonstrated by lower amplitudes of the envelope following response. In humans, the individual effects of noise exposure and aging do not seem to translate clearly into deficits in electrophysiological, middle ear muscle reflex, and behavioral measures of CS. Moreover, the evidence on the combined effects of noise exposure and aging on peripheral neural deafferentation in humans using electrophysiological and behavioral measures is even more sparse and inconclusive. Further research is necessary to establish the individual and combined effects of CS in humans using temporal bone, objective, and behavioral measures.