Biology subjects

Martins, G. C.

Publications and source records attributed to Martins, G. C..

3 recordsLinked to original sources

bioRxiv2025

FOXM1 Inhibition Promotes Polyploidization and Metabolic Maturation in Human iPSC-Derived Hepatocytes by Modulating the Wnt/β-Catenin Pathway

Human induced pluripotent stem cell (iPSCs)-derived hepatocytes are widely used in regenerative medicine and disease modeling. However, existing protocols mainly produce fetal-like cells, limiting accurate modeling of liver functionality. Topoisomerase II (TOP2) and its transcription factor, forkhead box M1 (FOXM1), are silenced during late liver embryonic development; however, their roles in hepatocyte differentiation remain unclear. Here, we examined the effects of TOP2 and FOXM1 inhibition on the terminal differentiation of hepatocytes. We found that subtoxic TOP2 inhibition reduced nuclear chromatin condensation without causing DNA damage. RNA-seq analysis showed that TOP2 inhibition induced cell cycle arrest in a TOP2A-selective manner, with FOXM1 downregulation. ATAC-seq validation demonstrated that TOP2A inhibition decreases chromatin accessibility and modulates the Wnt/{beta}-catenin pathway. Proteomic analysis revealed that FOXM1 inhibition modulated TOP2A expression, replicated TOP2A-mediated cell cycle arrest, and reduced the levels of fetal hepatocyte proteins (HBG1/2, UGT2B7, and AFP). Prolonged FOXM1 inhibition is correlated with increased hepatocyte polyploidization, enhanced CYP450 activity, and improved lipid metabolism, suggesting a potential role in these processes. Overall, our findings suggest that FOXM1 inhibition significantly promotes the terminal differentiation of human iPSC-derived hepatocytes, indicating a potential role for FOXM1 and TOP2A in liver development, regeneration, and disease.

cell biology↗

bioRxiv2025

EXPLORING SOCIAL COGNITION DECLINE ACROSS ALZHEIMER'S DISEASE SEVERITY: INSIGHTS FROM A COMPARATIVE ANALYSIS

The detection of subtle behavioral signs in early stages of Alzheimers Disease (AD) is of great importance to start clinical investigation. Memory and reasoning problems are usually more commonly reported by relatives than those associated with Social Cognition (SC). This study focusing on deficits in SC as a behavioral marker of Alzheimers Disease (AD) investigated: (1) selective impairments in SC domains according to stage of disease; (2) if impairments were better explained by nonsocial cognitive dysfunctions. Sixty-five elderly distributed into groups according to the Mini-Mental State Examination (Healthy, Mild cognitive impairment, Mild-AD, Moderate-AD) participated in the study. All underwent the Edinburgh Social Cognition Test (ESCoT), which investigates the cognitive and affective domains of Theory of Mind, as well as interpersonal and intrapersonal understanding of social norms. The nonsocial cognitive battery included traditional tests of episodic memory, executive functions, verbal fluency and language comprehension. Mediation analysis was performed to understand the influence of nonsocial cognitive skills in SC impairment among groups. Results revealed prominent losses in SC in moderate AD regardless of memory- skills. Theory of mind was a crucial link between social and nonsocial cognitive abilities. Executive functioning, verbal fluency and language comprehension mediated group-related cognitive declines effects on SC impairment. These findings underscore the complex interplay between cognitive domains in AD and suggest that selective impairments of SC highlight is as potential a marker for tracking the progression of the disease.

neuroscience↗

bioRxiv2019

Anthropogenic Soils Promote Biodiversity in Amazonian Rainforests

Amazonian Dark Earths (ADEs) are fertile anthropic soils found throughout Amazonia, resulting from long-term occupation by pre-Columbian societies. Although the chemistry of these soils is well known, their biodiversity, particularly soil invertebrate communities have been neglected. To address this, we characterised soil macroinvertebrate communities and their activities in ADEs, comparing them with adjacent reference soils under forests and agriculture, at nine archaeological sites. We found 667 morphospecies and a tenacious pre-Columbian biodiversity footprint, with 40% of species found exclusively in ADEs. Soil biological activity was higher in ADEs than in adjacent soils, and associated with higher biomass and richness of organisms known to engineer the ecosystem. We show that these habitats have unique species pools, but that contemporary land-use causes nutrient loss and threatens their diversity. Both past and present human activities alter biodiversity and its distribution in Amazonia, and further efforts are needed to recognize and preserve these ADEs and their biodiversity.

zoology↗