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Romeo, F.

Publications and source records attributed to Romeo, F..

2 recordsLinked to original sources

Challenging the right-hemisphere assumption in post-stroke pragmatics: largely comparable impairment profiles across lesion sides

Traditional views assume that pragmatic deficits after stroke, which compromise the interpretation of communicative intentions and non-literal meanings, follow damage to the right hemisphere (RHD), with left-hemisphere damage (LHD) primarily linked to aphasia and structural language impairment. To examine hemispheric contributions to post-stroke pragmatic profiles, we assessed 99 stroke patients (40 LHD, including 14 with aphasia of minimal-to-moderate severity; 59 RHD) and 60 healthy controls with the Assessment of Pragmatic Abilities and Cognitive Substrates (APACS). While stroke patients overall performed worse than controls, LHD and RHD profiles were largely comparable across three converging analyses: (1) permutation tests revealed no hemispheric differences except on the two tasks requiring expressive components (Interview and Figurative Language 2), which in turn lowered the composites (APACS Production and Total); (2) equivalence testing established equivalence for most measures, with only these same tasks and composites remaining inconclusive; and (3) unsupervised clustering did not group patients by lesion side. Theory of Mind was robustly associated with pragmatic performance in both groups, whereas structural language abilities related specifically to LHD performance and general cognition only to RHD. Excluding aphasic LHD patients strengthened the evidence for comparable profiles, indicating that aphasic LHD patients largely drove the residual differences. In conclusion, primary pragmatic impairment, especially in the receptive domain, emerged comparably after LHD and RHD, with the only residual LHD disadvantage limited to tasks demanding open verbal output. These findings challenge the assumption of right-hemispheric specialization for pragmatics, stressing the need for pragmatic assessment in all post-stroke patients.

neuroscience↗

Loss of the tumor suppressor NUMB drives aggressive bladder cancer through hyperactivation of a RhoA/ROCK/YAP signaling circuitry

Bladder cancer (BCa) is one of the most challenging and costly cancers to treat, yet little progress has been made on the development of predictive biomarkers and targeted therapies. Here, we uncover a critical function of Numb as a tumor suppressor in the bladder, identifying loss of Numb expression as a causal alteration in BCa that underlies biological aggressiveness and disease progression. Through retrospective cohort studies, we established that a Numb-deficient tumor status correlates with worse overall survival in post-cystectomy muscle-invasive bladder cancer (MIBC) patients and increased risk of MIBC progression in non-muscle-invasive bladder cancer (NMIBC) patients. The prognostic value of Numb loss can be attributed to its crucial role as a determinant of aggressive bladder tumorigenesis, as demonstrated in mouse and human models. Targeted Numb ablation in the basal layer of the urothelium was alone sufficient to trigger spontaneous bladder tumorigenesis and drive progression from preneoplastic to preinvasive and, ultimately, overtly invasive tumors. Additionally, Numb ablation sensitized the urothelium to other oncogenic insults, accelerating tumor onset and progression. Using 3D-Matrigel organoid cultures to recapitulate bladder tumorigenesis in vitro, we found that Numb loss heightens the proliferative and invasive potential of both mouse and human BCa cells. Integrative transcriptomic and functional analyses revealed that downregulation of the canonical Hippo pathway, resulting in enhanced YAP transcriptional activity, underlies the biological aggressiveness of Numb-deficient BCa. These molecular events are dependent on the activation of RhoA/ROCK signaling subsequent to Numb loss. Thus, a dysfunctional Numb-RhoA/ROCK-Hippo/YAP regulatory network is at play in aggressive Numb-deficient BCa and represents a therapeutic vulnerability. A 27-gene prognostic signature capable of identifying high-risk Numb-deficient patients could provide the basis of a clinical tool to stratify patients for innovative RhoA/ROCK/YAP targeted therapies. One Sentence SummaryNumb loss-directed hyperactivation of RhoA/ROCK/YAP underlies aggressive bladder cancer biology.

cancer biology↗