Biology subjects

Yates, N.

Publications and source records attributed to Yates, N..

4 recordsLinked to original sources

bioRxiv2025

DNA Divers: volunteer-based eDNA capture for local and global marine biodiversity monitoring

Volunteer-based biodiversity recording is a powerful source of scalable data yet to be used to its full potential by the scientific community. Coastal ecosystems are varied and diverse, making it difficult for managers to identify flexible methods for monitoring biological components. Emerging technologies such as environmental DNA (eDNA) analysis are promising for measuring aquatic biodiversity, yet most management organizations lack personnel and capacity to collect molecular data. Here we investigate, together as professional and non-professional scientists, the efficacy of a quasi-passive eDNA capture technique. Volunteer SCUBA divers and snorkelers used low-cost materials, namely cotton medical gauze, to capture eDNA via swimming. We compared this method to conventional eDNA capture techniques in an aquarium and nature, collectively iterating the field and laboratory procedures to improve feasibility. With a small (< 30) network of volunteers, we detected 275 unique teleost and elasmobranch species from varied marine habitats spanning 90 degrees of latitude. The swimming motion of divers was more effective than stationary soaking and the fish communities sampled by divers were comparable to that of conventional eDNA samples. The ease of this technique matched by the eagerness and generosity of volunteers presents an untapped, viable approach for scaling multi-species marine eDNA monitoring as well as an avenue for improving science literacy. Data availabilityhttps://zenodo.org/records/14853820?token=eyJhbGciOiJIUzUxMiJ9.eyJpZCI6ImYxMTlhODFiLTI3NGYtNDQ2Ni05MDYyLTIyOTlkNWVhY2FkNiIsImRhdGEiOnt9LCJyYW5kb20iOiIwYmZlMzJhMWU0YWZkM2ZhMWEwYTE0NmY0ZWM5YWZkNSJ9.0R7GJjVJLEuq-UJVKA1CcMT8LCTamv3GEvPl-5ItzP10pFRd-cAzAr_Q5ggjEewZUtByHjBu-eSegWWlLAx_Rw

ecology↗

bioRxiv2025

Reciprocal Regulation Between the SCFFBXO24 Ubiquitin E3 Ligase and FoxP1 Protein

Forkhead Box Protein P1 (FoxP1) is a crucial transcriptional repressor essential for the development of the brain and heart. In adults, FoxP1 protein levels are dysregulated in a variety of disorders, including chronic obstructive pulmonary disease (COPD), atherosclerosis, and heart failure, where they causally contribute to disease pathogenesis. Although independent investigators have reported that FoxP1 protein is ubiquitinated, and E3 ligases have been identified for other FoxP family proteins, the identity of the E3 ligase that controls FoxP1 protein stability has remained unknown. Here, we identify FBXO24, a subunit of the Skp-Cullin-F-box (SCF) ubiquitin E3 ligase complex, as the regulator of FoxP1 ubiquitination and stability. Specifically, FBXO24 regulates K48 and K63 ubiquitination, complexes with, and co-localizes to the nucleus with FoxP1 protein in lung epithelial cells. Depleting FBXO24 reverses the unfolded protein response and cell death triggered by loss of FoxP1 protein in lung epithelium, suggesting a protective role. Additionally, FBXO24 knockout mice exhibit elevated FoxP1 levels in the lung and heart and reduced unfolded protein response activity after short-term cigarette smoke exposure. Intriguingly, we also uncovered bidirectional regulation, whereby FoxP1 protein binds to the FBXO24 promoter to suppress FBXO24 transcription. To our knowledge, this is the first evidence that a substrate for an E3 ligase can also regulate the E3 ligase and, therefore, control levels of other substrates, revealing new regulatory networks. Targeting FBXO24 may offer a therapeutic strategy for COPD, atherosclerosis, and heart failure by stabilizing FoxP1 levels in the heart and lungs and mitigating harmful downstream effects.

molecular biology↗

bioRxiv2023

Anti-manic effect of deep brain stimulation of the ventral tegmental area in an animal model of mania induced by methamphetamine

BackgroundTreatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD. AimThe present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph). MethodsWistar rats were given 14 days of mamph injections, in the last day animals were submitted to 20 minutes of VTA DBS in two different patterns: intermittent low frequency stimulation (LFS) or continuous high frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field test and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry. ResultsM-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. Mamph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc. ConclusionThese results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.

neuroscience↗

bioRxiv2019

Synaptic Proteome Alterations in the Primary Auditory Cortex of Schizophrenia

ImportanceFindings from unbiased genetic studies have consistently implicated synaptic protein networks in Schizophrenia (Sz), but the molecular pathology at these networks and their potential contribution to the synaptic and circuit deficits thought to underlie disease symptoms remain unknown.\n\nObjectiveTo determine if protein levels are altered within synapses from primary auditory cortex (A1) of subjects with Sz; and if so, are these differences restricted to the synapse or present throughout the grey matter?\n\nDesignA paired case-control design was utilized for this study. Biochemical fractional - targeted Mass Spectrometry (MS) was used to measure the levels of >350 proteins in A1 grey matter homogenate and synaptosome preparations, respectively. All experimenters were blinded to diagnosis at every stage of sample preparation, MS analysis, and raw data processing. The effects of postmortem interval (PMI) and antipsychotic drug treatment on protein levels were assessed in mouse and monkey models, respectively.\n\nSettingAll cases were recruited from a single site, The Allegheny County Office of the Medical Examiner, and all tissues were processed at the University of Pittsburgh.\n\nParticipantsBrain specimens from all subjects were obtained during autopsies conducted at the Allegheny County Office of the Medical Examiner after receiving consent from the next-of-kin. An independent panel of experienced clinicians made consensus Diagnostic and Statistical Manual of Mental Disorders Fourth Edition diagnoses. Unaffected comparison subjects underwent identical assessments and were determined to be free of lifetime psychiatric illness. Each Sz subject was matched by sex, and as closely as possible for age and PMI, with one unaffected comparison subject.\n\nMain Outcomes and MeasuresPrimary measures were homogenate and synaptosome protein levels and their co-regulation network features. Prior to data collection we hypothesized: 1. That levels of canonical postsynaptic proteins in A1 synaptosome preparations would differ between Sz and control subjects; and 2. That these differences would not be explained by changes in total A1 homogenate protein levels.\n\nResultsMean subject age was 48 years for both groups with a range of 17-83; each group included 35 males and 13 females; mean PMI was 17.7 hours in controls and 17.9 in Sz. We observed robust alterations (q < 0.05) in synaptosome levels of canonical mitochondrial and postsynaptic proteins that were highly co-regulated and not readily explained by postmortem interval, antipsychotic drug treatment, synaptosome yield, or underlying alterations in homogenate protein levels.\n\nConclusions and RelevanceOur findings indicate a robust and highly coordinated rearrangement of the synaptic proteome likely driven by aberrant synaptic, not cell-wide, proteostasis. In line with unbiased genetic findings, our results identified alterations in synaptic levels of postsynaptic proteins, providing a road map to identify the specific cells and circuits that are impaired in Sz A1.

neuroscience↗