Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Castration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.</p> <p>Methods</p> <p>We investigated these two pathways together using <it>in vitro </it>models of androgen-dependent (AD) and androgen-independent (AI) PC. We measured cellular levels, activity and surface expression of Neutral Endopeptidase (NEP), levels of secreted Endothelin-1 (ET-1), levels, sub-cellular localisation and DNA binding ability of NFκB, and proteasomal activity in human native PC cell lines (LnCaP and PC-3) modelling AD and AI states.</p> <p>Results</p> <p>At baseline, AD cells were found to have high NEP expression and activity and low secreted ET-1. In contrast, they exhibited a low-level activation of the NFκB pathway associated with comparatively low 20S proteasome activity. The AI cells showed the exact mirror image, namely increased proteasomal activity resulting in a canonical pathway-mediated NFκB activation, and minimal NEP activity with increased levels of secreted ET-1.</p> <p>Conclusions</p> <p>Our results seem to support evidence for divergent patterns of expression of the NFκB/proteasome pathway with relation to components of the NEP/neuropeptide axis in PC cells of different level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFκB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.</p

Immaturity of the Oculomotor Saccade and Vergence Interaction in Dyslexic Children: Evidence from a Reading and Visual Search Study

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction

Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2′,2′-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

Using experimental approaches to study translation the what and how

In the last few years, the study of the cognitive processes that underlie the translating act is well under way in the field of translation studies (TS). Yet considering the potential of this research area, translation behaviour and how it is affected and modulated by linguistic and psycholinguistic factors is still underinvestigated. The main culprit of this holdback appears to be fuzziness over what experimental methods are expected to deliver and how sometimes they are actually used. The present discussion article outlines these aspects, draws attention to methodological issues commonly encountered when an experimental approach is adopted, and suggests ways to overcome the challenges posed by this promising line of research. © 2021 Translation, Cognition and Behavior. All rights reserved

Metaphor comprehension in L2: Meaning, images and emotions

Non-linguistic components of metaphor understanding, emotions and mental images, have recently received attention within neurolinguistics and cognitive pragmatics, suggesting a role in differential representation and processing of language: metaphors are considered richer in affective connotations than their lexical or sentential non-emotional counterparts and images may be used in the recovery of propositional meaning. Assuming that the above characteristics of metaphors can trigger inferential processing, we explored the impact of their modulation on metaphor understanding in a second language (L2). We thus manipulated the nature of prime sentences in relation to the original target metaphors (e.g. Obama presided over a topic of discussion of epochal proportions) and created less emotional literal paraphrases (synonymous; historic proportions) which we compared against emotionally loaded counterparts (implicatures; amazing proportions), and examined the performance of seventy-four Greek-English bilinguals on a reading comprehension and a meaning-matching task. The results showed that both experimental conditions elicited fewer errors in comparison to the control condition but did not differ between them in accuracy or in reaction time (RT). We discuss these findings in view of the role of emotions and mental imagery in the understanding of metaphorical meaning, especially in the context of English as a Foreign Language (EFL). © 2019 Elsevier B.V

The way you say it, the way I feel it: Emotional word processing in accented speech

The present study examined whether processing words with affective connotations in a listener&apos;s native language may be modulated by accented speech. To address this question, we used the Event Related Potential (ERP) technique and recorded the cerebral activity of Spanish native listeners, who performed a semantic categorization task, while listening to positive, negative and neutral words produced in standard Spanish or in four foreign accents. The behavioral results yielded longer latencies for emotional than for neutral words in both native and foreign-accented speech, with no difference between positive and negative words. The electrophysiological results replicated previous findings from the emotional language literature, with the amplitude of the Late Positive Complex (LPC), associated with emotional language processing, being larger (more positive) for emotional than for neutral words at posterior scalp sites. Interestingly, foreign-accented speech was found to interfere with the processing of positive valence and go along with a negativity bias, possibly suggesting heightened attention to negative words. The manipulation employed in the present study provides an interesting perspective on the effects of accented speech on processing affective-laden information. It shows that higher order semantic processes that involve emotion-related aspects are sensitive to a speaker&apos;s accent. © 2015 Hatzidaki, Baus and Costa

ERP indexes of number attraction and word order during correct verb agreement production

Successful subject-verb agreement production requires retrieving the verbal forms that agree with the features of the subject head noun and not of other nouns in the sentence. We investigate, for the first time, the electrophysiological indexes of number attraction and word order during agreement production. Twenty-four Basque native speakers were tested while producing auxiliary verbs during sentence completion of transitive sentence preambles involving singular subjects and singular or plural objects in canonical (SOV) and non-canonical (OSV) structures. ERP results yielded a larger production P2 (pP2) amplitude for mismatching than matching objects in SOV sentences, and larger negativity for OSV than SOV in number matching condition. We explain these results in terms of distinct contributions of number and word order during correct agreement production, with the pP2 indexing morphosyntactic retrieval difficulty of agreement-inflection, and the frontal negativity reflecting word order effects during monitoring the correctness of the selected verbal form. © 2020 The Author

Is language interference (when it occurs) a graded or an all-or-none effect? Evidence from bilingual reported speech production

Do cross-lingual interactions occur even with structures of different word order in different languages of bilinguals? Or could the latter provide immunity to interference of the contrasting characteristics of the other language? To answer this question, we examined the reported speech production (utterances reporting what just happened; e.g., Holly asked what Eric ate) of two groups of proficient, unbalanced bilinguals with varying similarity between their native (L1-Spanish/L1-Dutch) and second language (L2-English). The results showed that both groups of bilinguals produced word order errors when formulating indirect What-questions in L2, regardless of how similar the L1 was to the L2 in that respect. Our findings suggest that in the case of reported speech production in the examined bilingual groups, cross-linguistic syntactic differences by themselves suffice to induce language interference, and that the degree of similarity between the L1 and the L2 does not seem to modulate the magnitude of this effect. © 2018 Cambridge University Press