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Lobo, J.

Publications and source records attributed to Lobo, J..

4 recordsLinked to original sources

Neural competition and probabilistic representations

Perception and action show tight links to the statistical structure of physical stimuli and likely rewards, but the underlying mechanisms are unknown. A simple, biologically plausible network model shows that probabilistic behavior emerges naturally in diverse scenarios, and arises from sampling of competing responses. Notably, it also provides a principled computational rationale for the prevalent finding of balanced excitation and inhibition in the brain. Recurrent connections within a population of excitatory neurons embed multiple attractor states, and coupling to a pool of inhibitory neurons enforces mutual exclusivity among the states. Upon concurrent stimulation, competing attractors alternate in activity. These global state transitions are caused by local, uncorrelated spiking noise and yet convey, over time, the relative strengths of attractors' support. The simplest probabilistic competitive recurrent networks (PCRNs) allow for closed-form analysis, shedding light on the neural basis of choice behavior under uncertainty. More complex systems of laterally connected PCRNs can collectively resolve the myriad local ambiguities pervasive in sensory stimuli, rapidly settling into globally-consistent configurations that match perceptual reports. Alternations are crucial in all cases, and occur only if a PCRN's inhibitory pool is strong enough to prevent attractors' activity from reaching saturation. A balance between excitation and inhibition is thus both a prerequisite and a hallmark of probabilistic sampling in cortical networks.

neuroscience↗

Deciphering the impact of cancer cells secretome and its derived-peptide VGF on breast cancer brain metastasis

Brain metastases (BM) are one of the most serious clinical problems in breast cancer (BC) progression, associated with lower survival rates and a lack of effective therapies. Thus, to dissect the early stages of the brain metastatic process, we have searched for a brain-tropic metastatic signature on BC cells secretome, as a promising source for the discovery of new biomarkers involved in brain metastatic progression. Therefore, six specifically deregulated peptides were found to be enriched in the secretome of brain organotropic BC cells. Importantly, these secretomes caused significant blood-brain barrier (BBB) disruption, as well as microglial activation, in vitro and in vivo. We identified the VGF nerve growth factor inducible as a brain-specific peptide, promoting BBB dysfunction similar to the secretome of brain organotropic BC cells. Concerning microglial activation, a slight increase was also observed upon VGF treatment. In a series of human breast tumors, VGF was found to be expressed in both cancer cells and in the adjacent stroma. VGF-positive tumors showed a significant worse prognosis and were associated with HER2 overexpression and triple-negative molecular signatures. Finally, in a cohort including primary breast tumors and their corresponding metastatic locations to the lung, bone, and brain, we found that VGF significantly correlates with the brain metastatic site. In conclusion, we found a specific BC brain metastatic signature, where VGF was identified as a key mediator in this process. Importantly, its expression was associated with poor prognosis for BC patients, probably due to its associated increased risk of developing BM.

cancer biology↗

Reconstructing deep-time paleoclimate legacies unveil the demise and turnover of the ancient (boreo)tropical flora

AimSince the Late Cretaceous, the Earth has gone through periods of climate change similar in scale and pace to the warming trend observed today in the Anthropocene. The impact of these ancient climatic events on the evolutionary trajectories of organisms provides clues on the organismal response to climate change, including extinction, migration or persistence. Here, we examine the evolutionary response to climate cooling/warming events of the clusioid families Calophyllaceae, Podostemaceae and Hypericaceae (CPH), and the genus Hypericum as test cases.\n\nLocationHolarctic.\n\nTime periodLate Cretaceous-Cenozoic\n\nMajor taxa studiedangiosperms\n\nMethodsWe use paleoclimate simulations, species distribution models and phylogenetic comparative approaches calibrated with fossils.\n\nResultsAncestral CPH lineages could have been distributed in the Holarctic 100 Ma, occupying tropical subhumid assemblages, a finding supported by the fossil record. Expansion to closed-canopy tropical rain forests occurred after 60 Ma, in the Cenozoic, in agreement with earlier ideas of a post-Cretaceous origin of current tropical rain forest. Cooling during this period triggered diversification declines on CPH tropical lineages, and was associated with a climatic shift towards temperate affinities in Hypericum. Hypericum subsequently migrated to tropical mountains where it encountered different temperate conditions than in the Holarctic.\n\nMain conclusionsWe hypothesize that most clusioid CPH lineages failed to adapt to temperate regimes during periods of Cenozoic climate change, and thus went extinct in the Holarctic. In contrast, boreotropical descendants including Hypericum that underwent niche evolution demonstrated selective advantages as climates became colder. Our results points toward macroevolutionary trajectories involving the altering fates of closely related clades that adapt to periods of global climate change versus those that do not. Moreover, they suggest the hypothesis that potentially many clades, particularly inhabitants of boreotropical floras, were likely extirpated from the Holarctic and persist today (if at all) in more southern tropical locations.

evolutionary biology↗

DNA Metabarcoding For High-Throughput Monitoring Of Estuarine Macrobenthic Communities

Benthic communities are key components of aquatic ecosystems biomonitoring. However, morphology-based species identifications remain a low-throughput, and sometimes ambiguous, approach. Despite metabarcoding methodologies have been applied for above-species taxa inventories in marine meiofaunal communities, a comprehensive approach providing species-level identifications for estuarine macrobenthic communities is still lacking. Here we report a combination of experimental and field studies demonstrating the aptitude of COI metabarcoding to provide robust species-level identifications within a framework of high-throughput monitoring of estuarine macrobenthic communities. To investigate the ability to recover DNA barcodes from all species present in a bulk DNA extract, we assembled 3 phylogenetically diverse communities, using 4 different primer pairs to generate PCR products of the COI barcode region. Between 78 and 83% of the species in the tested communities were recovered through HTS. Subsequently, we compared morphology and metabarcoding-based approaches to determine the species composition from four distinct sites of an estuary. Our results indicate that the species richness would be considerably underestimated if only morphological methods were used. Although further refinement is required for improving the efficiency and output of this approach, here we show the great aptitude of COI metabarcoding to provide high quality and auditable species identifications in macrobenthos monitoring.

genetics↗