Biology subjects

Santos, B. F.

Publications and source records attributed to Santos, B. F..

7 recordsLinked to original sources

bioRxiv2026

First record of the subfamily Eucerotinae (Hymenoptera: Ichneumonidae) from the mainland Afrotropics, with a description of a new species

The ichneumonid subfamily Eucerotinae has been thought to be almost absent from the tropics, with the only known Afrotropical species found in Madagascar. We report the subfamily to be present in the mainland Afrotropics, and describe a new species, Euceros species 1 from Uganda and Cameroon (name not yet shown in preprint). The subfamily had likely not been observed in the mainland Afrotropics before due to low abundances and insufficient sampling. More Eucerotinae likely remain to be discovered in tropical Africa and Asia, although tropical America may genuinely have few eucerotine species. Much more extensive sampling will be needed before it is possible to make confident estimates of how eucerotine diversity is distributed globally.

zoology↗

bioRxiv2025

Weak and inverse latitudinal diversity gradients in the 10 most abundant and diverse flying insect clades

Latitudinal diversity gradients are a key concept in biodiversity science, but the available data are skewed towards large-bodied, charismatic taxa. To address this bias, we analyzed DNA barcode data for 1.35 million specimens of flying insects collected using 101 Malaise traps in 27 countries across six continents. We identify those ten families that consistently contribute more than half of all specimens and species across climates, habitats, and continents. Contrary to canonical expectations, five families have inverse or non-significant latitudinal gradients while the remaining five exhibit only weak to average gradients compared to 470 other terrestrial datasets. Furthermore, precipitation seasonality, rather than temperature, emerged as the strongest climatic correlate. Overall, we thus not only reveal a surprising convergence in the globally dominant insect clades but also illustrate that key textbook concepts in macroecology need testing for poorly studied invertebrate taxa that contribute most of Earths animal biodiversity and may behave unexpectedly.

ecology↗

bioRxiv2025

Combined expression of FOXO and Tribbles proteins predicts survival of glioma patients

BackgroundGliomas, particularly high-grade variants such as glioblastoma, remain therapeutically challenging with poor survival outcomes. Current biomarkers inadequately stratify patients for therapy selection, monitoring, and early detection of progression. The FOXO transcription factors and Tribbles pseudokinases, key regulators of the PI3K/AKT pathway, have been implicated in cancer progression but their prognostic value in gliomas is unclear. The aim of this study was to determine whether transcriptional profiles of FOXO and Tribbles family members predict survival in glioma patients better than established biomarkers. MethodsUsing RNA-seq data from The Cancer Genome Atlas (TCGA, n = 705) and Chinese Glioma Genome Atlas (CGGA, n = 1018), along with microarray datasets (REMBRANDT, n = 552; Gravendeel, n = 268), we analyzed mRNA levels of FOXO1/3/4/6 and TRIB1/2/3. Survival analysis was performed via Kaplan-Meier curves, log-rank tests, and concordance indices. Gene expression differences across tumor grades and molecular subgroups were assessed using Students t-test. ResultsHigh FOXO1 and low FOXO3/4 mRNA levels, combined with elevated TRIB1/2/3 expression, formed a signature significantly associated with worse survival across all cohorts. This signature stratifies grade 4 gliomas, with a median survival difference of 4.5 months. Grade 4 tumors exhibited elevated FOXO1 and TRIB1/2/3 but reduced FOXO3/4 levels compared to lower-grade gliomas. ConclusionsThe FOXO/Tribbles transcriptional signature robustly predicts survival in glioma patients. These findings highlight its potential as a biomarker for patient stratification and a therapeutic target for high-grade gliomas. Key PointsO_LIFOXO/Tribbles mRNA signature predicts glioma survival status. Our analysis identifies a distinct transcriptional signature - characterized by high FOXO1 and TRIB1/2/3 levels along with low FOXO3 and FOXO4 - that consistently predicts poor prognosis across glioma cohorts. This FOXO/Tribbles signature demonstrates great prognostic power, particularly in grade 4 gliomas, providing an improved tool for risk stratification and clinical decision-making. C_LIO_LIHigh FOXO1 and Tribbles levels mark aggressive glioblastoma tumors. We show that elevated expression of FOXO1 and Tribbles pseudokinases is enriched in glioblastoma (GB) and grade 4 astrocytomas. These tumors, known for their aggressiveness and therapy resistance, are consistently associated with this unfavorable mRNA profile. This suggests a functional role for FOXO1 and Tribbles in glioma progression and highlights them as promising biomarkers and therapeutic targets. C_LIO_LIMulti-cohort validation (TCGA, CGGA) confirms prognostic robustness. The predictive FOXO/Tribbles expression pattern was validated across four large and independent datasets (TCGA, CGGA, REMBRANDT, and Gravendeel), demonstrating consistency despite differences in platform and population. This multi-cohort validation reinforces the robustness and generalizability of this transcriptional signature for predicting survival outcomes in glioma patients. C_LI Importance of the StudyGlioblastoma and high-grade gliomas have dismal prognoses, yet current biomarkers fail to adequately guide therapy. This study identifies a novel transcriptional signature - combining FOXO transcription factors and Tribbles pseudokinases - that robustly predicts survival in glioma patients stratifying aggressive tumors. Using multi-cohort validation (TCGA, CGGA, REMBRANDT), we demonstrate that elevated FOXO1 and Tribbles (TRIB1/2/3) levels, coupled with reduced FOXO3/4, correlate with poor outcomes in grade 4 gliomas. This signature is enriched in glioblastomas, highlighting its link to therapy resistance. Unlike prior studies focusing on individual proteins, our integrated analysis reveals their collective prognostic power, offering a pathway-specific biomarker for patient stratification. These findings provide a translational framework for targeting FOXO/Tribbles in precision oncology, addressing an urgent need for improved therapeutic strategies in neuro-oncology.

cancer biology↗

bioRxiv2024

The Role of Alpha Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria ER Membranes

The protein alpha-synuclein (Syn) plays a critical role in the pathogenesis of synucleinopathy, which includes Parkinsons disease and multiple system atrophy, and mounting evidence suggests that lipid dyshomeostasis is a critical phenotype in these neurodegenerative conditions. Previously, we identified that Syn localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs), temporary functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we have analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinsons disease and controls, as well as three less affected brain regions of Parkinsons donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data show region-and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinsons disease. Some of these alterations, albeit to a lesser degree, are also observed multiples system atrophy. Using induced pluripotent stem cell-derived neurons, we show that Syn contributes to regulating phosphatidylserine metabolism at MAM domains, and that Syn dosage parallels the perturbation in phosphatidylserine levels. Our results support the notion that Syn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications. Significance StatementSynucleinopathy is a complex group of neurodegenerative disorders whose causes and underlying mechanisms remain unknown. In this work, we examined synucleinopathy postmortem brain samples and patient-derived neuron models and identified the functional impairment of the mitochondrial-associated endoplasmic reticulum membrane (MAM) domain, which facilitates lipid regulation. The protein alpha-synuclein is associated with synucleinopathy and increasing levels result in the mislocalization of this protein and the disruption of MAM domains, which, in turn, results in lipid and membrane composition alterations. Specifically, we report that increased alpha-synuclein expression impairs the regulation of phosphatidylserine synthase 2 and the levels of phosphatidylserine in cellular membranes from affected cells. Our study offers mechanistic insight tying alpha-synuclein pathology and lipid dysregulation as seminal factors in synucleinopathy, which may have pathogenic and therapeutic implications.

neuroscience↗

bioRxiv2020

Gene-corrected Parkinson's disease neurons show the A30P alpha-synuclein point mutation leads to reduced neuronal branching and function

Parkinsons disease is characterised by the degeneration of A9 dopaminergic neurons and the pathological accumulation of alpha-synuclein. In a patient-derived stem cell model, we have generated dopaminergic neurons from an individual harbouring the p.A30P SNCA mutation and compared those neurons against gene-corrected isogenic control cell lines. We have used confocal microscopy to assess the neuronal network, specifically segmenting dopaminergic neurons and have identified image-based phenotypes showing axonal impairment and reduced neurite branching. We show using multi-electrode array (MEA) technology that the neurons carrying the endogenous p.A30P alpha-synuclein mutation are functionally impaired and identified mitochondrial dysfunction as a pathogenic cellular phenotype. We report that against gene-corrected isogenic control cell lines the neurons carrying the p.A30P SNCA mutation have a deficit and are susceptible to the mitochondrial toxin and environmental pesticide Rotenone. Our data supports the use of isogenic cell lines in identifying image-based pathological phenotypes that can serve as an entry point for future disease modifying compound screenings and drug discovery strategies.

neuroscience↗

bioRxiv2020

IPSC-derived midbrain astrocytes from Parkinson's disease patients carrying pathogenic SNCA mutations exhibit alpha-synuclein aggregation, mitochondrial fragmentation and excess calcium release

Parkinsons disease (PD) is characterized by the loss of A9 midbrain dopaminergic neurons and the accumulation of alpha-synuclein aggregates in remaining neurons. Many studies of the molecular and cellular basis of neurodegeneration in PD have made use of iPSC-derived neurons from patients with familial PD mutations. However, approximately half of the cells in the brain are glia, and their role facilitating neurodegeneration is unclear. We developed a novel serum-free protocol to generate midbrain astrocytes from patient-derived iPSCs harbouring the pathogenic p.A30P, p.A53T mutations in SNCA, as well as duplication and triplication of the SNCA locus. In our cellular model, aggregates of alpha-synuclein occurred only within the GFAP+ astrocytes carrying the pathogenic SNCA mutations. Assessment of spontaneous cytosolic calcium (Ca2+) release using Fluo4 revealed that SNCA mutant astrocytes released excess Ca2+ compared to controls. Unbiased evaluation of 3D mitochondrial morphometric parameters showed that these SNCA mutant astrocytes had increased mitochondrial fragmentation and decreased mitochondrial connectivity compared to controls, and reduced mitochondrial bioenergetic function. This comprehensive assessment of different pathogenic SNCA mutations derived from PD patients using the same cellular model enabled assessment of the mutation effect, showing that p.A53T and triplication astrocytes were the most severely affected. Together, our results indicate that astrocytes harbouring the familial PD mutations in SNCA are dysfunctional, suggesting a contributory role for dysfunctional astrocytes in the disease mechanism and pathogenesis of PD. Table of Contents Image O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/053470v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@974d72org.highwire.dtl.DTLVardef@15d9da0org.highwire.dtl.DTLVardef@1177d4eorg.highwire.dtl.DTLVardef@123c0c2_HPS_FORMAT_FIGEXP M_FIG C_FIG Main PointsO_LIWe used a novel serum-free protocol to generate midbrain-specific functional astrocytes from Parkinsons disease patients carrying pathological mutations in SNCA C_LIO_LIPatient-derived astrocytes show morphological and functional impairments C_LI

neuroscience↗

bioRxiv2019

Conserved and specific genomic features of endogenous polydnaviruses revealed by whole genome sequencing of two ichneumonid wasps

Polydnaviruses (PDVs) are mutualistic endogenous viruses associated with some lineages of parasitoid wasps that allow successful development of the wasps within their hosts. PDVs include two taxa resulting from independent virus acquisitions in braconid (bracoviruses) and ichneumonid wasps (ichnoviruses). PDV genomes are fully incorporated into the wasp genomes and comprise (1) virulence genes located on proviral segments that are packaged into the viral particle, and (2) genes involved in the production of the viral particles, which are not encapsidated. Whereas the genomic organization of bracoviruses within the wasp genome is relatively well known, the architecture of endogenous ichnoviruses remains poorly understood. We sequenced the genome of two ichnovirus-carrying wasp species, Hyposoter didymator and Campoletis sonorensis. Complete assemblies with long scaffold sizes allowed identification of the integrated ichnovirus, highlighting an extreme dispersion within the wasp genomes of the viral loci, i.e. isolated proviral segments and clusters of replication genes. Comparing the two wasp species, proviral segments harbor distinct gene content and variable genomic environment, whereas viral machinery clusters show conserved gene content and order, and can be inserted in collinear wasp genomic regions. This distinct architecture is consistent with the biological properties of the two viral elements: proviral segments producing virulence proteins allowing parasitism success are fine-tuned to the host physiology, while an ancestral viral architecture was likely maintained for the genes involved in virus particle production. Finding a distinct genomic architecture of ichnoviruses and bracoviruses highlights different evolutionary trajectories leading to virus domestication in the two wasp lineages.

genomics↗