Asymmetric Event-Related Potential Priming Effects Between English Letters and American Sign Language Fingerspelling Fonts

Letter recognition plays an important role in reading and follows different phases of processing, from early visual feature detection to the access of abstract letter representations. Deaf ASL–English bilinguals experience orthography in two forms: English letters and fingerspelling. However, the neurobiological nature of fingerspelling representations, and the relationship between the two orthographies, remains unexplored. We examined the temporal dynamics of single English letter and ASL fingerspelling font processing in an unmasked priming paradigm with centrally presented targets for 200 ms preceded by 100 ms primes. Event-related brain potentials were recorded while participants performed a probe detection task. Experiment 1 examined English letter-to-letter priming in deaf signers and hearing non-signers. We found that English letter recognition is similar for deaf and hearing readers, extending previous findings with hearing readers to unmasked presentations. Experiment 2 examined priming effects between English letters and ASL fingerspelling fonts in deaf signers only. We found that fingerspelling fonts primed both fingerspelling fonts and English letters, but English letters did not prime fingerspelling fonts, indicating a priming asymmetry between letters and fingerspelling fonts. We also found an N400-like priming effect when the primes were fingerspelling fonts which might reflect strategic access to the lexical names of letters. The studies suggest that deaf ASL–English bilinguals process English letters and ASL fingerspelling differently and that the two systems may have distinct neural representations. However, the fact that fingerspelling fonts can prime English letters suggests that the two orthographies may share abstract representations to some extent

Implicit Co-activation of American Sign Language in Deaf Readers: An ERP Study

In an implicit phonological priming paradigm, deaf bimodal bilinguals made semantic relatedness decisions for pairs of English words. Half of the semantically unrelated pairs had phonologically related translations in American Sign Language (ASL). As in previous studies with unimodal bilinguals, targets in pairs with phonologically related translations elicited smaller negativities than targets in pairs with phonologically unrelated translations within the N400 window. This suggests that the same lexicosemantic mechanism underlies implicit co-activation of a non-target language, irrespective of language modality. In contrast to unimodal bilingual studies that find no behavioral effects, we observed phonological interference, indicating that bimodal bilinguals may not suppress the non-target language as robustly. Further, there was a subset of bilinguals who were aware of the ASL manipulation (determined by debrief), and they exhibited an effect of ASL phonology in a later time window (700–900 ms). Overall, these results indicate modality-independent language co-activation that persists longer for bimodal bilinguals

The N170 ERP Component Differs in Laterality, Distribution, and Association with Continuous Reading Measures for Deaf and Hearing Readers

The temporo-occipitally distributed N170 ERP component is hypothesized to reflect print-tuning in skilled readers. This study investigated whether skilled deaf and hearing readers (matched on reading ability, but not phonological awareness) exhibit similar N170 patterns, given their distinct experiences learning to read. Thirty-two deaf and 32 hearing adults viewed words and symbol strings in a familiarity judgment task. In the N170 epoch (120–240 ms) hearing readers produced greater negativity for words than symbols at left hemisphere (LH) temporo-parietal and occipital sites, while deaf readers only showed this asymmetry at occipital sites. Linear mixed effects regression was used to examine the influence of continuous measures of reading, spelling, and phonological skills on the N170 (120–240 ms). For deaf readers, better reading ability was associated with a larger N170 over the right hemisphere (RH), but for hearing readers better reading ability was associated with a smaller RH N170. Better spelling ability was related to larger occipital N170s in deaf readers, but this relationship was weak in hearing readers. Better phonological awareness was associated with smaller N170s in the LH for hearing readers, but this association was weaker and in the RH for deaf readers. The results support the phonological mapping hypothesis for a left-lateralized temporo-parietal N170 in hearing readers and indicate that skilled reading is characterized by distinct patterns of neural tuning to print in deaf and hearing adults

Unique N170 Signatures to Words and Faces in Deaf ASL Signers Reflect Experience-Specific Adaptations During Early Visual Processing

Previous studies with deaf adults reported reduced N170 waveform asymmetry to visual words, a finding attributed to reduced phonological mapping in left-hemisphere temporal regions compared to hearing adults. An open question remains whether this pattern indeed results from reduced phonological processing or from general neurobiological adaptations in visual processing of deaf individuals. Deaf ASL signers and hearing nonsigners performed a same-different discrimination task with visually presented words, faces, or cars, while scalp EEG time-locked to the onset of the first item in each pair was recorded. For word recognition, the typical left-lateralized N170 in hearing participants and reduced left-sided asymmetry in deaf participants were replicated. The groups did not differ on word discrimination but better orthographic skill was associated with larger N170 in the right hemisphere only for deaf participants. Face recognition was characterized by unique N170 signatures for both groups, and deaf individuals exhibited superior face discrimination performance. Laterality or discrimination performance effects did not generalize to the N170 responses to cars, confirming that deaf signers are not inherently less lateralized in their electrophysiological responses to words and critically, giving support to the phonological mapping hypothesis. P1 was attenuated for deaf participants compared to the hearing, but in both groups, P1 selectively discriminated between highly learned familiar objects – words and faces versus less familiar objects – cars. The distinct electrophysiological signatures to words and faces reflected experience-driven adaptations to words and faces that do not generalize to object recognition

Propagation Failure in Excitable Media

We study a mechanism of pulse propagation failure in excitable media where stable traveling pulse solutions appear via a subcritical pitchfork bifurcation. The bifurcation plays a key role in that mechanism. Small perturbations, externally applied or from internal instabilities, may cause pulse propagation failure (wave breakup) provided the system is close enough to the bifurcation point. We derive relations showing how the pitchfork bifurcation is unfolded by weak curvature or advective field perturbations and use them to demonstrate wave breakup. We suggest that the recent observations of wave breakup in the Belousov-Zhabotinsky reaction induced either by an electric field or a transverse instability are manifestations of this mechanism.Comment: 8 pages. Aric Hagberg: http://cnls.lanl.gov/~aric; Ehud Meron:http://www.bgu.ac.il/BIDR/research/staff/meron.htm

The dpsA Gene of Streptomyces coelicolor: Induction of Expression from a Single Promoter in Response to Environmental Stress or during Development

The DpsA protein plays a dual role in Streptomyces coelicolor, both as part of the stress response and contributing to nucleoid condensation during sporulation. Promoter mapping experiments indicated that dpsA is transcribed from a single, sigB-like dependent promoter. Expression studies implicate SigH and SigB as the sigma factors responsible for dpsA expression while the contribution of other SigB-like factors is indirect by means of controlling sigH expression. The promoter is massively induced in response to osmotic stress, in part due to its sensitivity to changes in DNA supercoiling. In addition, we determined that WhiB is required for dpsA expression, particularly during development. Gel retardation experiments revealed direct interaction between apoWhiB and the dpsA promoter region, providing the first evidence for a direct WhiB target in S. coelicolor

Beyond the marrow:insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.</p

Receptor Tyrosine Kinases Activate Canonical WNT/β-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct β-Catenin Phosphorylation

Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate β-catenin at Tyr142, which is known to increase cytoplasmic β-catenin concentration via release of β-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct β-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling

The SsgA-like proteins in actinomycetes: small proteins up to a big task

Several unique protein families have been identified that play a role in the control of developmental cell division in streptomycetes. The SsgA-like proteins or SALPs, of which streptomycetes typically have at least five paralogues, control specific steps of sporulation-specific cell division in streptomycetes, affecting cell wall-related events such as septum localization and synthesis, thickening of the spore wall and autolytic spore separation. The expression level of SsgA, the best studied SALP, has a rather dramatic effect on septation and on hyphal morphology, which is not only of relevance for our understanding of (developmental) cell division but has also been succesfully applied in industrial fermentation, to improve growth and production of filamentous actinomycetes. Recent observations suggest that SsgB most likely is the archetypal SALP, with only SsgB orthologues occurring in all morphologically complex actinomycetes. Here we review 10 years of research on the SsgA-like proteins in actinomycetes and discuss the most interesting regulatory, functional, phylogenetic and applied aspects of this relatively unknown protein family