Biology subjects

Abrantes, M.

Publications and source records attributed to Abrantes, M..

7 recordsLinked to original sources

bioRxiv2026

BOWIe: Wireless Headstage for Optical Stimulation in Closed-Loop Optogenetics Experiments in Freely-moving Rodents

Optogenetics is an invaluable technique in neuroscience to study brain circuits, but conventional optogenetic systems use tethered approaches to deliver light to the brain which can hinder natural behavior. Optoelectronic advances led to the development of wireless optical stimulators for optogenetics experiments, but most reported devices have low widespread use due to complex builds and reduced versatility, which has also limited their integration in closed-loop systems. Here, we developed BOWIe, a battery-powered, low-weight, wireless headstage for photostimulation in optogenetics experiments with rodents, especially designed for simple integration in multiple behavioral setups, including those requiring closed-loop operation. BOWIe is based on a Bluetooth-Low Energy system-on-a-chip that allows simultaneous control and communication capabilities with a reduced number of components, and can be paired with an Arduino-based transmitter for simple integration in any behavioral paradigm using analogue or digital triggers. Two modes of optical stimulation are possible, either with ferrule-coupled optical fibers or LED neural probes, which permit adapting the headstage according to material availability or experimental demands. A user-friendly app was also developed to simplify headstage pairing, definition of stimulation parameters, and protocol design. BOWIe was validated in two behavioral paradigms, including in a closed-loop experiment using computer vision, Bonsai RX, and Deeplabcut Live to track behavioral parameters online and remotely trigger photostimulation upon detected events. BOWIe's modular design and flexible integration with behavioral setups make it a practical tool for in vivo experiments with optogenetics.

bioengineering↗

bioRxiv2026

Transcriptional rewiring of NF-κB by HBZ and Fra-2 drives inflammatory chemoresistance in Tax-negative adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive HTLV-1-associated malignancy with poor responses to chemotherapy. Although constitutive NF-kB activation is a hallmark of ATL, its persistence in tax-negative (Type I) ATL, where Tax is irreversibly silenced, remains unresolved. Here, we identify Fra-2 as a coactivator of NF-kB p65 that redirects p65's transcriptional activity toward inflammatory genes. Mechanistically, Fra-2 interacts with the Rel homology domain of p65 via its bZIP domain, enhancing p65 DNA-binding activity without altering nuclear localization. The HTLV-1 antisense protein HBZ disrupts Fra-2/JunD AP-1 complexes while stabilizing Fra-2/p65, as shown by co-immunoprecipitation, BiFC, and PICO assays. This rewiring selectively enhances NF-kB-dependent transcription of IL-1b, which is elevated in ATL patient sera and cells independently of proviral load. Chromatin immunoprecipitation revealed Fra-2 recruitment to NF-kB response elements in the IL1b promoter, an effect amplified by HBZ. Pharmacological inhibition of IL-1 signaling with anakinra or anti-IL-1b antibodies restored doxorubicin sensitivity in primary ATL cells. Together, these findings establish the Fra-2-NF-kB-IL-1b axis as a driver of chemoresistance in tax-negative ATL and a therapeutically targetable vulnerability.

cancer biology↗

bioRxiv2025

Ultrasensitive graphene FET aptasensor for direct attomolar detection of glutamate in human clinical samples

Glutamate, the principal excitatory neurotransmitter in the brain, is crucial for cognition and memory, and its dysregulation is implicated in several neurological disorders, including Alzheimers Disease and epilepsy. However, precise and high-throughput quantification of glutamate in physiological samples remains challenging. Here, we report an ultrasensitive and highly specific glutamate aptamer-based biosensor, or aptasensor, developed through in silico design and microfabrication, followed by in vitro and clinical validation. The biosensor consists of arrays of graphene field-effect transistors functionalized with a novel DNA aptamer, NG-Apt-Glu, designed and characterized computationally and biochemically, revealing two putative glutamate binding sites. The aptasensor detects glutamate in artificial cerebrospinal fluid with a 1 aM detection limit, a wide linear range (1 aM-10 pM), and 24 mV/decade sensitivity, showing strong selectivity against GABA, glutamine, dopamine, and serotonin. To evaluate clinical applicability, glutamate levels were measured in cerebrospinal fluid from patients with Alzheimers Disease, showing a significant increase relative to controls and correlating with neurofilament light chain concentrations, a biomarker of neuronal death. These findings underscore glutamates involvement in Alzheimers pathophysiology and its potential as a biomarker for neurodegeneration. This ultrasensitive graphene-based aptasensor enables point-of-care monitoring, paving the way for early diagnosis and the development of novel therapeutic strategies.

bioengineering↗

bioRxiv2025

HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy

AbstractHIV-1 and Mycobacterium tuberculosis (Mtb) coinfections are a major public health problem but are not well characterized. HIV-1 Tat is secreted by infected cells, generating nanomolar concentrations of Tat in the sera of people living with HIV. Circulating Tat enters cells, binds to PI(4,5)P2 then undergoes palmitoylation, thereby becoming resident on this phosphoinositide. Here, we found that Tat favors the multiplication of Mtb in macrophages. Moreover, Tat renders zebrafish larvae more sensitive to mycobacterial infection. We found that Tat binding to PI(4,5)P2 and palmitoylation enable Tat to inhibit the recruitment of the AP-2 adaptor, thereby inhibiting clathrin-mediated endocytosis and in turn autophagy. This inhibition prevents the degradation of intracellular pathogens such as Mtb and opsonized Toxoplasma gondii, but also of lipid droplets, thereby facilitating the access of these pathogens to lipids. We thus identified a mechanism enabling HIV Tat to favor the multiplication of intracellular pathogens such as Mtb.

microbiology↗

bioRxiv2024

Small form factor implantable neural probe with efficient flip chip micro LED for in vivo optogenetics

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (LEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate LEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip LEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm2 but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm2. Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 {o}C. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.

bioengineering↗

bioRxiv2022

Ultrasensitive Dopamine Detection with Graphene Aptasensor Multitransistor Arrays

Dopamine is a neurotransmitter with critical roles in the human brain and body, and abnormal dopamine levels underlie brain disorders such as Parkinsons Disease, Alzheimers Disease, and substance addiction. Herein, we present a novel high-throughput biosensor based on graphene multitransistor arrays (gMTAs) functionalized with a selective aptamer for robust ultrasensitive dopamine detection. The miniaturized biosensor integrates multiple electrolyte-gated graphene field-effect transistors (EG-gFETs) in an array configuration, fabricated by high-yield reproducible and scalable methodologies optimized at the wafer level. With these gMTA aptasensors, we reliably detected ultra-low dopamine concentrations in physiological buffers, including undiluted phosphate-buffered saline (PBS), artificial cerebral spinal fluid (aCSF), and high ionic strength complex biological samples. We report a record limit-of-detection (LOD) of 1 aM (10-18) for dopamine in both PBS, and dopamine-depleted brain homogenate samples spiked with dopamine. The gMTAs also display wide sensing ranges across all media, up to 100 M (10-8), with a 22 mV/decade peak sensitivity in aCSF. Furthermore, we show that the gMTAs can detect minimal changes in dopamine concentrations in small working volume biological CSF samples obtained from a mouse model of Parkinsons Disease.

bioengineering↗

bioRxiv2019

Genetic characterization of a recombinant myxoma virus leap into the Iberian hare (Lepus granatensis)

Myxomatosis is a lethal disease of wild European and domestic rabbits (Oryctolagus cuniculus) caused by a Myxoma virus (MYXV) infection, a leporipoxvirus that is found naturally in some Sylvilagus rabbit species in South America and California. The introduction of MYXV in the early 1950s into feral European rabbit populations in Australia and Europe demonstrate the best documented field example of host-virus coevolution following a cross-species transmission. Recently, a new cross-species jump of MYXV has been suggested in both Great Britain and Spain, where European brown hares (Lepus europaeus) and Iberian hares (Lepus granatensis) were found dead with lesions consistent with those observed in myxomatosis. To investigate the possibility of a new cross-species transmission event by MYXV, tissue samples collected from a wild Iberian hare found dead in Spain (Toledo region) were analyzed and deep sequenced. Our results report a new MYXV strain (MYXV Toledo) in the tissues of this species. The genome of this new strain encodes three disrupted genes (M009L, M036L and M152R) and a novel 2.8 KB recombinant region that resulted from an insertion of four novel poxviral genes towards the 5 end of its genome. From the open reading frames inserted into the MYXV Toledo strain, a new orthologue of a poxvirus host range gene family member was identified which is related to the MYXV gene M064R. Overall, we confirmed the identity of a new MYXV strain in Iberian hares that we hypothesize was able to more effectively counteract the host defenses in hares and start an infectious process in this new host.

microbiology↗