Infant-directed speech facilitates word learning through attentional mechanisms: An fNIRS study of toddlers.

The speech register that adults especially caregivers use when interacting with infants and toddlers, that is, infant-directed speech (IDS) or baby talk, has been reported to facilitate language development throughout the early years. However, the neural mechanisms as well as why IDS results in such a developmental faciliatory effect remain to be investigated. The current study uses functional near-infrared spectroscopy (fNIRS) to evaluate two alternative hypotheses of such a facilitative effect, that IDS serves to enhance linguistic contrastiveness or to attract the child's attention. Behavioral and fNIRS data were acquired from twenty-seven Cantonese-learning toddlers 15-20 months of age when their parents spoke to them in either an IDS or adult-directed speech (ADS) register in a naturalistic task in which the child learned four disyllabic pseudowords. fNIRS results showed significantly greater neural responses to IDS than ADS register in the left dorsolateral prefrontal cortex (L-dlPFC), but opposite response patterns in the bilateral inferior frontal gyrus (IFG). The differences in fNIRS responses to IDS and to ADS in the L-dlPFC and the left parietal cortex (L-PC) showed significantly positive correlations with the differences in the behavioral word-learning performance of toddlers. The same fNIRS measures in the L-dlPFC and right PC (R-PC) of toddlers were significantly correlated with pitch range differences of parents between the two speech conditions. Together, our results suggest that the dynamic prosody in IDS increased toddlers' attention through greater involvement of the left frontoparietal network that facilitated word learning, compared to ADS. RESEARCH HIGHLIGHTS: This study for the first time examined the neural mechanisms of how infant-directed speech (IDS) facilitates word learning in toddlers. Using fNIRS, we identified the cortical regions that were directly involved in IDS processing. Our results suggest that IDS facilitates word learning by engaging a right-lateralized prosody processing and top-down attentional mechanisms in the left frontoparietal networks. The language network including the inferior frontal gyrus and temporal cortex was not directly involved in IDS processing to support word learning.

Lexical and Prosodic Pitch Modifications in Cantonese Infant-directed Speech.

The functions of acoustic-phonetic modifications in infant-directed speech (IDS) remain a question: do they specifically serve to facilitate language learning via enhanced phonemic contrasts (the hyperarticulation hypothesis) or primarily to improve communication via prosodic exaggeration (the prosodic hypothesis)? The study of lexical tones provides a unique opportunity to shed light on this, as lexical tones are phonemically contrastive, yet their primary cue, pitch, is also a prosodic cue. This study investigated Cantonese IDS and found increased intra-talker variation of lexical tones, which more likely posed a challenge to rather than facilitated phonetic learning. Although tonal space was expanded which could facilitate phonetic learning, its expansion was a function of overall intonational modifications. Similar findings were observed in speech to pets who should not benefit from larger phonemic distinction. We conclude that lexical-tone adjustments in IDS mainly serve to broadly enhance communication rather than specifically increase phonemic contrast for learners.

The Progress of Platelets in Breast Cancer.

Breast cancer is the most common female cancer and the sixth leading cause of death, seriously affecting the quality of life of women. Platelets, one of the fragments derived from megakaryocytes, are being increasingly investigated by tumor researchers because of their anticoagulant function. According to relevant studies, platelets, as the key source of circulating angiogenesis-related factors, can regulate tumor angiogenesis and vascular integrity, and they can also affect the tumor microenvironment, thereby facilitating the proliferation and differentiation of tumor cells. By covering or transferring normal MHC I molecules to tumor cells, platelets can protect tumor cells from being killed by the immune system and facilitate tumor cell metastasis. However, details on the mechanisms involved have remained elusive. This paper reviews and analyzes studies of the role of platelets in tumorigenesis, tumor cell proliferation, tumor metastasis, and cancer treatment to provide readers with a better understanding of the relevant studies.

Identification and panoramic analysis of drug response-related genes in triple negative breast cancer using as an example NVP-BEZ235.

Taking NVP-BEZ235 (BEZ235) as an example to screen drug response-related genes (DRRGs) and explore their potential value in triple-negative breast cancer (TNBC). Through high-throughput technique, multidimensional transcriptome expression data (mRNA, miRNA and lncRNA) of BEZ235-treated and -untreated MDA-MB-468 cell lines were obtained. Combined with transcriptome data of the MDA-MB-468 cells and TCGA-TNBC tissues, differential gene expression analysis and WGCNA were performed to identify DRRGs associated with tumor trait by simulating the drug response microenvironment (DRM) of BEZ235-treated patients. Based on DRRGs, we constructed a ceRNA network and verified the expression levels of three key molecules by RT-qPCR, which not only demonstrated the successful construction of a BEZ235-treated cell line model but also explained the antitumor mechanism of BEZ235. Four molecular subtypes related to the DRM with survival difference were proposed using cluster analysis, namely glycolysis subtype, proliferation depression subtype, immune-suppressed subtype, and immune-activated subtype. A novel prognostic signature consisting of four DRRGs was established by Lasso-Cox analysis, which exhibited outstanding performance in predicting overall survival compared with several excellent reported signatures. The high- and low-risk groups were characterized by enrichment of metabolism-related pathways and immune-related pathways, respectively. Of note, the low-risk group had a better response to immune checkpoint blockade. Besides, pRRophetic analysis found that patients in the low-risk group were more sensitive to methotrexate and cisplation, whereas more resistant to BEZ235, docetaxel and paclitaxel. In conclusion, the DRRGs exemplified by BEZ235 are potential biomarkers for TNBC molecular typing, prognosis prediction and targeted therapy. The novel DRRGs-guided strategy for predicting the subtype, survival and therapy efficacy, might be also applied to more cancers and drugs other than TNBC and BEZ235.

OLA1 regulates protein synthesis and integrated stress response by inhibiting eIF2 ternary complex formation.

Translation is a fundamental cellular process, and its dysregulation can contribute to human diseases such as cancer. During translation initiation the eukaryotic initiation factor 2 (eIF2) forms a ternary complex (TC) with GTP and the initiator methionyl-tRNA (tRNAi), mediating ribosomal recruitment of tRNAi. Limiting TC availability is a central mechanism for triggering the integrated stress response (ISR), which suppresses global translation in response to various cellular stresses, but induces specific proteins such as ATF4. This study shows that OLA1, a member of the ancient Obg family of GTPases, is an eIF2-regulatory protein that inhibits protein synthesis and promotes ISR by binding eIF2, hydrolyzing GTP, and interfering with TC formation. OLA1 thus represents a novel mechanism of translational control affecting de novo TC formation, different from the traditional model in which phosphorylation of eIF2α blocks the regeneration of TC. Depletion of OLA1 caused a hypoactive ISR and greater survival in stressed cells. In vivo, OLA1-knockdown rendered cancer cells deficient in ISR and the downstream proapoptotic effector, CHOP, promoting tumor growth and metastasis. Our work suggests that OLA1 is a novel translational GTPase and plays a suppressive role in translation and cell survival, as well as cancer growth and progression.