Biology subjects

Machado, F.

Publications and source records attributed to Machado, F..

6 recordsLinked to original sources

bioRxiv2026

A novel phylogenetic comparative model reveals strong signals for early high disparity in ichthyosaurs

Early high disparity, where clades reach maximum morphological diversity early in their history, is often observed in the fossil record. Since there are currently no suitable methods to model these Early High Disparity (EHD) processes accurately, we introduce a new phylogenetic comparative method (PCM) to address this gap by combining two evolutionary modes--Ornstein-Uhlenbeck (OU) and Early Burst (EB)--leading to an initial surge in disparity until an early maximum, driven by the EB component, after which disparity declines due to OU constraints. We tested the EHD model on ichthyosaur skull length data and found it to be the best fit in nearly all cases compared to other modes. The median time of peak disparity (TEHD) is about 231.1 million years ago, during the Triassic, roughly 12.4% into the ichthyosaur lineage. To explore how environmental and geological factors might influence peak disparity, we performed changepoint analyses on sea level, sea surface temperature, rock area, and sedimentary sequence ages. While changepoints in temperature at 237.2 Ma and sequence boundaries at 238 Ma were closest to TEHD, no significant changepoints appeared to match TEHD.

paleontology↗

bioRxiv2024

Lead as a toxic environmental toxicant in models of synucleinopathies

Lead, a toxic heavy metal, is prevalent in various industrial applications, contributing to environmental contamination and significant health concerns. Lead affects various body systems, especially the brain, causing long-lasting cognitive and behavioral changes. While most studies have focused on continuous lead exposure, intermittent exposure, such as that caused by migration or relocations, has received less attention. Importantly, lead exposure intensifies the severity of Parkinsons disease (PD) and dementia with Lewy bodies, diseases involving the accumulation of alpha-synuclein (aSyn) in the brain and in the gut. Although, the precise mechanisms underlying these observations remain unclear, oxidative stress and mitochondrial dysfunction likely play a role. Here, we investigated how two different profiles of lead exposure - continuous and intermittent - affect models of synucleinopathies. We found that lead exposure enhances the formation of aSyn inclusions, resulting in an increase in both their number and size in cell models. In addition, we found that animals injected with aSyn pre-formed fibrils display serine 129-phosphorylated aSyn inclusions and a reduction in astrocytes in the substantia nigra. These animals also display neuronal damage and alterations in locomotor activity, exploratory behavior, anxiety, memory impairments and hypertension. Our results suggest a mechanistic link between environmental lead exposure and the onset and progression of diseases associated with aSyn pathology. Understanding the molecular and cellular interactions between lead and aSyn is crucial for shaping public health policies and may provide novel insight into strategies for mitigating the impact of environmental toxins on neurodegenerative processes involved in Parkinsons disease and related synucleinopathies. Key points summaryO_LILead exposure increases the number and size of alpha-synuclein (aSyn) inclusions in cell models.[~] C_LIO_LIAnimals exposed to aSyn fibrils and lead show increased phosphorylation of aSyn, neuronal damage and reduced astrogliosis in the substantia nigra. C_LIO_LILead-exposed animals exhibit impaired locomotion, anxiety, memory deficits, hypertension and chemoreceptor reflex hypersensitivity. C_LIO_LIThe study suggests a mechanistic link between environmental lead exposure and the progression of diseases involving aSyn pathology, such as Parkinsons disease. C_LI

physiology↗

bioRxiv2024

Simultaneous circulation and coinfection of Dengue clades and serotypes in Southern Brazil

Dengue is an arthropod-borne virus with worldwide urban transmission mediated by anthropophilic vectors of the genus Aedes. Currently, there is a substantial genotype diversity that belongs to at least four known serotypes. Tropical regions, where several serotypes cocirculate in the population, are hyperendemic, driving multiple outbreaks with variable disease manifestations. Notably, the Dengue virus burden is increasing in subtropical and temperate regions of the globe due to climatic changes associated with new outbreaks in naive and previously unaffected human populations. The introduction and endemic transmission of different clades and serotypes in these regions is highly concerning due to the known and still unknown consequences of Dengue infection on populations with diverse genetic backgrounds. Here, we characterized the coinfection of different Dengue clades and serotypes in Rio Grande do Sul, Brazils southernmost and subtropical state, by combining serotype-specific RT-PCR and deep sequencing. We found five coinfected patients in four municipalities where these clades and serotypes circulated simultaneously. Our data suggests that coinfection events account for a minority of total cases, but these findings may reflect the early transmission phases of some Dengue clades. Hence, close monitoring is warranted to evaluate coinfection rates and associated clinical consequences as clade prevalence changes.

genomics↗

bioRxiv2020

Double-layer flexible neuronal probe with closely spaced electrodes for high-density in vivo brain recordings

Flexible probes for brain activity recordings are an attractive emerging approach that reduces mechanical mismatch between probe and neuronal tissue, thus minimizing the risk of brain damage or glial scaring. Although promising, flexible probes still present some technical challenges namely: i) how to overcome probe buckling during brain insertion given its intrinsically low mechanical rigidity; ii) how to fabricate closely spaced electrode configurations for high density recordings by standard lithography techniques in the flexible substrate. Here, we present a new flexible probe based solely on standard and low-cost lithography processes, which has closely spaced 10 m diameter gold electrode sites on a polyimide substrate with inter-site distances of only 5 m. By using a double-layer design and fabrication approach we were able to accommodate closely spaced electrode sites at two different depths from probe surface while also providing additional stiffening, just sufficient to prevent probe buckling during brain insertion. Detailed probe characterization through metrology of structural and electrical properties and chemical composition analysis, as well as functional assessment through in vivo high-density recordings of neuronal activity in the mouse cortex, confirmed the viability of this new fabrication approach and that this probe can be used for obtaining high quality brain recordings with excellent signal-to-noise ratio (SNR).

bioengineering↗

bioRxiv2020

Linked deterioration of early visual perception, function and structure in healthy human aging

Low-level visual perception deteriorates during healthy aging. We hypothesized that age-related retinal and cortical structure deteriorations affect perception through specific disruptions of neural function. We measured perceptual visual acuity in fifty healthy adults aged 20-80 years. We then measured these participants early visual field map (V1, V2 and V3) functional population receptive field (pRF) sizes and structural surface areas using fMRI, and their retinal structure using high-definition optical coherence tomography. With increasing age visual acuity decreased, pRF sizes increased, visual field maps surface areas decreased, and retinal thickness decreased. Among these measures, only functional pRF sizes predicted perceptual visual acuity. PRF sizes were in turn predicted by cortical structure only (surface areas), which were only predicted by retinal structure (thickness). We propose that age-related retinal structural deterioration disrupts cortical structure, thereby disrupting cortical functional neural interactions that normally sharpen visual position selectivity: the resulting functional disruption underlies age-related perceptual deterioration.

neuroscience↗

bioRxiv2020

A versatile and modular tetrode-based device for single-unit recordings in rodent ex vivo and in vivo acute preparations

The demand for affordable tools for recording extracellular activity and successfully isolating single units from different brain preparations has pushed researchers and companies to invest in developing and fabricating new recording devices. However, depending on the brain region of interest, experimental question or type of preparations, different devices are required thus adding substantial financial burden to laboratories. We have developed a simple and affordable tetrode-based device that allows interchangeable extracellular recordings of neural activity between in vivo and ex vivo preparations and can be easily implemented in all wet-bench laboratories. Spontaneous activity from several putative single neurons could be easily recorded and isolated by lowering the device into ex vivo cerebellum brain slices. The same device was also used in vivo, lowered into primary auditory cortex of adult anesthetized transgenic mice expressing channelrhodopsin in cortical neurons. Acoustic stimulation of the contralateral ear or direct laser optogenetic stimulation successfully evoked cortical activity at the recording site. Several isolated putative single neurons presented time-locked activity response to the different stimuli. In summary, we developed an affordable, versatile and modular device to facilitate tetrode extracellular recordings interchangeably between in vivo anaesthetized animals and ex vivo brain slice recordings. HighlightsDeveloped a versatile and modular device to facilitate tetrode acute brain recordings interchangeably between in vivo and ex vivo preparations. Conducted ex vivo extracellular recordings in acute cerebellar slices. Conducted in vivo extracellular recordings in auditory cortex of anaesthetized mice. Recorded and isolated multiple single units in both acute slices and anaesthetized mice recordings using the same device. Device can be easily extended to accommodate optic fiber and cannula.

neuroscience↗