Biology subjects

Borges, H.

Publications and source records attributed to Borges, H..

8 recordsLinked to original sources

bioRxiv2026

Spoken Recall Reveals Lexical and Mnemonic Function Differences in Temporal Lobe Epilepsy Patients

Background and Objectives: Word-finding difficulty is common in healthy aging and in neurologic disorders, including temporal lobe epilepsy (TLE) and early Alzheimer disease. Standard language measures have limited sensitivity for detecting subtle or longitudinal changes in spontaneous speech. We examined whether natural language processing and acoustic analysis of spoken biographical recall could identify lexical and temporal speech features associated with language and memory performance in TLE. Methods: We conducted a cross-sectional observational study of spoken recall during a Famous Faces biographical memory task. Adults with TLE and healthy controls (HCs) viewed 20 famous faces and spontaneously recalled biographical details. Speech was transcribed and diarized using automated tools. Lexical measures included word counts and lexical index (ratio of rare to common words). Acoustic measures included utterance and pause duration and pause frequency. Features were compared between groups and correlated with neuropsychological measures, including Montreal Cognitive Assessment (MoCA), Boston Naming Test (BNT), delayed recall, education, and biographical recall accuracy Results: Eighty-one adults participated (51 TLE, 30 HCs). Lexical measures did not differ between groups. In TLE, lexical index correlated with BNT performance (rs=0.62) and MoCA score (rs=0.35). Compared with HCs, participants with TLE produced shorter utterances (5.54 {+/-} 2.50 vs. 6.59 {+/-} 2.63; Cohen's d=0.41, 95% CI -0.05 to 0.86, p=0.041), shorter pauses (0.61 {+/-} 0.21 vs 0.67 {+/-} 0.22, Cohen's d=0.29, 95% CI -0.16 to 0.74, p=0.043), and more frequent pauses (10.81 {+/-} 3.30 vs 9.29 {+/-} 3.59, Cohen's d=-0.45, 95% CI -0.90 to 0.01, p=0.036). Higher education was associated with longer utterances, longer pauses, and lower pause frequency, without evidence of a diagnosis-by-education interaction. Faster utterance rate was associated with better biographical recall in both groups, while higher pause rate was associated with worse recall in TLE. Discussion: Speech-derived lexical and temporal features from naturalistic recall capture clinically relevant variation in language and memory-related performance. Although lexical output did not distinguish TLE from HCs, lexical richness tracked naming and global cognition in TLE, while temporal speech features related to recall performance. These findings support the potential of automated speech analysis as a digital behavioral biomarker for word-finding difficulty in neurologic populations.

neuroscience↗

bioRxiv2026

Modulation of Oncogenic KRAS Signaling by Branched Actin-driven Cell Membrane Protrusions

For over three decades, we have known that oncogenic RAS alters the actin cytoskeleton organization and cell surface morphology1,2. RAS activates the GTPase RAC1, which triggers the growth of branched actin networks to promote cell membrane protrusions3,4. In melanoma, the hyperactive RAC1 mutant, Rac1P29S, was recently shown to drive extended lamellipodia, which then empower cell proliferation through sequestration and localized inhibition of the merlin tumor suppressor5. This discovery illustrates cell morphological programs not only as outputs but also as regulators of human oncogenic signals. Hence, we wondered whether the pronounced branched actin-driven membrane protrusions (BAMPs) downstream of oncogenic RAS are not mere outputs of RAS signaling but rather an active component in mediating the oncogenic penetrance of RAS mutants. We used volumetric light sheet microscopy and biochemical approaches to investigate the role of BAMPs in regulating the molecular signaling of oncogenic KRAS in pancreatic and lung cancer models. We found that elevated BAMP formation regulated the interaction of oncogenic KRAS with downstream effectors, specifically with the RAC1 GEF TIAM1. This implies that BAMPs amplify their own upstream regulators in a positive feedback. This meritorious cycle upregulates cyclin D1 expression by inactivating the merlin tumor suppressor, independently of the mitogen activated protein kinase pathway (MAPK). In the absence of BAMPs, cells carrying oncogenic KRAS mutations are unable to attain their full penetrance in proliferation. Overall, this work unveils the long-overlooked role of branched actin-driven cell morphology in the functionalization of KRAS mutants as potent oncogenes.

cancer biology↗

bioRxiv2026

Film Recall Reveals Intact Event Memory but Impaired Sequence Memory in Temporal Lobe Epilepsy Patients

BACKGROUND AND OBJECTIVESPatients with epilepsy (PWE), especially temporal lobe epilepsy (TLE), experience impaired memory for personally experienced events. However, current assessments of episodic memory are limited in their ecological validity with a potential to miss detection of subtle cognitive decline. We conducted an exploratory study to determine whether a naturalistic film-viewing task with open-ended spoken recall could detect memory differences between TLE patients and healthy controls (HCs). METHODSTLE patients (ages 18-60, fluent in English, not legally blind) were recruited from a Level 4 Epilepsy Center (2018-2024). TLE diagnosis was based on seizure semiology, MRI Brain, and EEG. TLE patients scored [≥]22/30 on the Montreal Cognitive Assessment (MOCA); HCs scored [≥]26/30. Subjects watched 6 short films and then freely recalled film details. Spoken responses were recorded, transcribed, segmented, and scored for film- and event-level recall. Recall order was assessed using the Damerau-Levenshtein distance. Semantic and causal centrality were quantified using sentence embeddings and rater-identified causal links, respectively. Beta regression with cluster-robust standard errors assessed group and centrality effects on recall probability. Beta regression evaluated the influence of age, MOCA, and testing platform on sequence recall error. RESULTSWe recruited 51 subjects (27 TLEs; 24 HCs, 70.1% F, mean 29.9 {+/-}8.3 years). TLE patients and HCs showed similar recall of films (HC 89% {+/-}11% vs TLE 88% {+/-}18%, p = 0.54), coarse events (HC 50% {+/-}16% vs TLE 44% {+/-}18%, p = 0.19) and fine events (HC 25%{+/-}10% vs. TLE 22%{+/-}12%, p=0.17). Both groups recalled high causal centrality events better. For coarse event sequence recall, TLE patients showed a numerical trend toward greater sequence errors compared to HCs (HC 10.8% {+/-} 10.5% vs. TLE 19.5% {+/-} 18%, p = 0.06), although this difference did not reach statistical significance. However, TLE patients showed significantly greater fine event sequence errors at recall than HCs (HC 15% {+/-}13% vs 23% {+/-}18%, p = 0.02, Hedges g = 0.85, Cliffs {delta} = 0.51), with RTLE demonstrating more sequence errors than HCs (15%{+/-}13 vs. 29%{+/-}21% p = 0.021) Age, education, MOCA, and performance on standard verbal and visual memory tasks were unrelated to film, event, and sequence recall performance. DISCUSSIONWe demonstrate that a short film task with spontaneous spoken recall can identify sequence memory impairment in TLE patients despite intact film- and event-level recall. Sequence memory may represent a subtle manifestation of memory impairment that is not detected by standard cognitive testing. Key PointsO_LIWe asked whether a naturalistic film recall task could detect episodic memory impairment in a temporal lobe epilepsy cohort. C_LIO_LIPatients with temporal lobe epilepsy showed comparable film and event recall compared to healthy controls but were found to have impaired sequence memory. C_LIO_LISequential memory for temporal order is an overlooked aspect of episodic memory that may detect subtle memory decline. C_LI

neuroscience↗

bioRxiv2026

In vivo evidence for bleb-induced survival signaling in metastatic melanoma

Bleb signaling is a cellular process in which pressure-driven plasma membrane protrusions generate localized micron-scale membrane curvature that recruits cytosolic septin complexes, assembling signaling hubs that promote cell survival1. Our prior work showed that this morphology-encoded signaling pathway is necessary to sustain anchorage-independent survival of BRAF and NRAS mutant melanoma cells in vitro. However, whether bleb-induced signaling occurs in vivo and contributes to cancer progression is unclear. Here, we develop complementary in vivo and ex vivo assays spanning human patient samples and mouse xenograft models to mechanistically interrogate bleb signaling directly in physiologic contexts. We observe that bleb-associated septin hubs are exclusively formed in poorly adherent amoeboid tumor cells at the invasive margin, within malignant effusions, and at distant metastatic sites, while well-adhered cells in the tumor interior show no signs of septin hub formation. Accordingly, pharmacological pathway disruption specifically kills disseminated tumor cells within these low-adhesion microenvironments while having no appreciable effect on adhered cells in the tumor interior, resulting in reduced metastatic burden and delayed disease recurrence in vivo. This work confirms septin-mediated bleb signaling as a previously unrecognized vulnerability of disseminated cancer cells and demonstrates that this morphology-encoded pathway operates in vivo to support disease progression, preserving cancer cell viability under conditions in which cell survival signals from the environment are muted. These findings suggest novel opportunities to target survival signaling in micrometastatic disseminated cancer cells. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/697601v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1770384org.highwire.dtl.DTLVardef@87e567org.highwire.dtl.DTLVardef@1e5d6b2org.highwire.dtl.DTLVardef@724c5f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

navigate: an open-source platform for smart light-sheet microscopy.

navigate is a turnkey, open-source software solution designed to enhance light-sheet fluorescence microscopy (LSFM) by integrating smart microscopy techniques into a user-friendly framework. It enables automated, intelligent imaging with a Python-based control system that supports GUI-reconfigurable acquisition routines and the integration of diverse hardware sets. As a comprehensive package, navigate democratizes access to advanced LSFM capabilities, facilitating the development and implementation of smart microscopy workflows without requiring deep programming knowledge or specialized expertise in light-sheet microscopy.

biophysics↗

bioRxiv2023

Age and obesity-driven changes in the extracellular matrix of the primary tumor and metastatic site influence tumor invasion and metastatic outgrowth

Younger age and obesity increase the incidence and metastasis of triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. The extracellular matrix (ECM) promotes tumor invasion and metastasis. We characterized the effect of age and obesity on the ECM of mammary fat pads, lungs, and liver using a diet-induced obesity (DIO) model. At 4 week intervals, we either injected the mammary fat pads with allograft tumor cells to characterize tumor growth and metastasis or isolated the mammary fat pads and livers to characterize the ECM. Age had no effect on tumor growth but increased lung and liver metastasis after 16 weeks. Obesity increased tumor growth starting at 12 weeks, increased liver metastasis only at 4 weeks, and weight gain correlated to increased lung but not liver metastasis. Utilizing whole decellularized ECM coupled with proteomics, we found that early stages of obesity were sufficient to induce changes in the ECM composition and invasive potential of mammary fat pads with increased abundance of pro-invasive ECM proteins Collagen IV and Collagen VI. We identified cells of stromal vascular fraction and adipose stem and progenitor cells as primarily responsible for secreting Collagen IV and VI, not adipocytes. We characterized the changes in ECM in the lungs and liver, and determined that older age decreases the metastatic potential of lung and liver ECM while later-stage obesity increases the metastatic potential. These data implicate ECM changes in the primary tumor and metastatic microenvironment as mechanisms by which age and obesity contribute to breast cancer progression. SignificanceYounger age and obesity increase the incidence and metastasis of triple-negative breast cancer. Our data suggest that changes in the breast, lung and liver ECM are driving some of these effects.

cancer biology↗

bioRxiv2023

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

BackgroundMetastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis. MethodsWe evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell lines cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines. ResultsWe identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo. ConclusionsOur results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.

cancer biology↗

bioRxiv2020

Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing

We describe the spatiotemporal course of cortical high-gamma activity (HGA), hippocampal ripple activity and interictal epileptiform discharges (IEDs) during an associative memory task in 15 epilepsy patients undergoing invasive electroencephalography. Successful encoding trials manifested significantly greater HGA in hippocampus and frontal regions. Successful cued recall trials manifested sustained HGA in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. IEDs during encoding were associated with 15% decreased odds of remembering in hippocampus (95% CI 6-23%). Hippocampal IEDs during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if IEDs occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal IEDs were followed by a transient decrease in ripple rate. We hypothesize that IEDs impair associative memory in a regionally and temporally specific manner by decreasing physiologic hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological IED events competing with physiological ripples, IEDs represent a promising therapeutic target for memory remediation in patients with epilepsy. SummaryHippocampal interictal epileptiform discharges in hippocampus acutely impair declarative memory, potentially by hijacking physiological processes essential for encoding and recall.

neuroscience↗