Lead is an important heavy metal used worldwide in several applications, especially in industry. People exposed to lead can develop a wide range of symptoms associated with lead poisoning. Many effects of lead poisoning are reported in the literature, showing a compromising of whole body health, with symptoms related to cardiovascular, immune, bone, reproductive, hematological, renal, gastrointestinal, and nervous system. However, the molecular lead targets as well as the pathways affected by lead poisoning are not completely described. The aim of this study was to construct a map of metabolic pathways impaired in lead poisoning by evaluating which biomolecules are directly affected by lead. Through manual literature curation, we identified proteins which physically interact with lead and subsequently determined the metabolic pathways those proteins are involved with. At total, we identified 23 proteins involved with heme synthesis, calcium metabolism, neurotransmission, among other biological systems, which helps to understand the wide range of lead-poisoning symptoms.

Vitamin D (VD) deficiency is a growing problem, affecting a significant portion of the population in many countries. VD deficiency may be related to several diseases, including Alzheimer's disease (AD). This study aimed to review the relationship between VD deficiency and AD. We describe the proteins involved in AD pathogenesis and how those proteins can be influenced by VD deficiency. We also investigated a relationship between AD death rate and solar radiation and we found an increased AD death rate in countries with low sunlight. It was also observed that amyloid precursor protein, ryanodine receptor, mammalian target of rapamycin complex 1, and receptor for advanced glycation end products are associated with a worse prognosis in AD. While the Klotho protein, phosphatase and tensin homologue, and VD receptor are associated with a better prognosis in the disease. The literature suggests that decline in VD concentrations may be involved in the establishment and progression of AD. According to sunlight data, we can conclude that countries with low average sunlight have high AD death rate.

The emergence of open ocean global-scale studies provided important information about the genomics of oceanic microbial communities. Metagenomic analyses shed light on the structure of marine habitats, unraveling the biodiversity of different water masses. Many biological and environmental factors can contribute to marine organism composition, such as depth. However, much remains unknown about microbial communities’ taxonomic and functional features in different water layer depths. Here, we performed a metagenomic analysis of 76 publicly available samples from the Tara Ocean Project, distributed in 8 collection stations located in tropical or subtropical regions, and sampled from three layers of depth (surface water layer—SRF, deep chlorophyll maximum layer—DCM, and mesopelagic zone—MES). The SRF and DCM depth layers are similar in abundance and diversity, while the MES layer presents greater diversity than the other layers. Diversity clustering analysis shows differences regarding the taxonomic content of samples. At the domain level, bacteria prevail in most samples, and the MES layer presents the highest proportion of archaea among all samples. Taken together, our results indicate that the depth layer influences microbial sample composition and diversity.

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells’ ability to differentiate, therefore influencing ES-NP cells’ fate.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, accounting for approximately 20% of all childhood brain tumors. Despite recent advances, current treatments like surgery, radiation, and chemotherapy still lead to severe side effects and high morbidity. Limited knowledge exists regarding the regulatory mechanisms behind the MB transcriptional alterations in high-aggressive subgroups like Group 3 and Group 4, hindering the development of targeted therapies. Identifying key transcriptional regulators, known as master regulators (MRs), can elucidate the dysregulated pathways underlying MB progression and uncover potential treatment targets. In this study, we utilize primary MB gene expression samples to infer its regulatory network. Subsequently, we applied the Master Regulator Analysis identifying the transcription factors BHLHE41, RFX4, and NPAS3 as its main transcriptional regulators, showing tumor suppressor features. We also identified eight risk MRs highly associated with patient outcome: four regulators (MYC, REL, ZSCAN5 A, and ZFAT) with activities associated with poor prognosis, and four (PAX6, ARNT2, ZNF157, and HIVEP3) acting antagonistically, being associated with good outcome. Our results offer key insights into the molecular mechanisms driving these tumors and identify novel potential therapeutic targets, addressing the urgent need for more effective and less toxic treatments.