Biology subjects

Gray, R. J.

Publications and source records attributed to Gray, R. J..

5 recordsLinked to original sources

bioRxiv2024

Developmental and adult striatal patterning of nociceptin ligand marks striosomal population with direct dopamine projections

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting early developmental expression of Pnoc. In the ventral striatum, Pnoc expression was was clustered across the nucleus accumbens core and medial shell, including in adult striatum. We found that PnoctdTomato reporter cells largely comprise a population of dopamine receptor D1 (Drd1) expressing medium spiny projection neurons localized in dorsal striosomes, known to be unique among striatal projections neurons for their direct innervation of midbrain dopamine neurons. These findings provide new understanding of the intersection of the N/OFQ system among basal ganglia circuits with particular implications for developmental regulation or wiring of striatal-nigral circuits.

neuroscience↗

bioRxiv2022

Integration of multi-omics data shows downregulation of mismatch repair, purin, and tublin pathways in AR-negative triple-negative chemotherapy-resistant breast tumors

Triple negative breast cancer (TNBC) patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy (NAC) will likely experience recurrence of the disease within 3-4 years. Prognostic assessment of early recurrence could facilitate clinical decisions and impact disease survival. This study investigated pre- and post-NAC multi-omics data from both an in-house and a public clinical study to identify biomarkers of NAC response. We observed significant transcriptional differences associated with response in the residual disease (post-NAC biopsies), which did not exist in the pre-NAC biopsies. We further refined the post-NAC transcriptional changes to a 17-gene signature and machine learning models were applied to evaluate the signatures diagnostic potential (area under the curve [≥] 0.8). Interestingly, the signature was enriched with down-regulated immune genes and several of these genes demonstrated prognostic potential in basal TNBC tumors. Our 17-gene signature provides additional insight into TNBC recurrence, which warrants further investigation.

cancer biology↗

bioRxiv2020

Exotic Hobos: Release, escape, and potential secondary dispersal of African red-headed agamas (Agama picticauda PETERS, 1877) through the Florida railway systems.

ContextInvasive reptile species are introduced and established through a variety of distribution channels (e.g. accidental/intentional release by pet owners, hitchhiking on imported goods), and can be detrimental to native ecosystems. Understanding the origins and spread of non-native species can help land managers to make informed decisions when attempting to prevent future introductions and remove established populations. AimsThe objectives of this study were to employ modelling techniques with open-source observational data to confirm putative local origins of African red-headed agamas in Florida and to locate potential distribution channels in which they are spreading throughout the state. MethodsGeographic profiling, a technique commonly used for criminal investigations, was used along with suspected origin locations of introduced African red-headed agamas (Agama picticauda) from the literature and observations from the Early Detection and Distribution Mapping System (EDDMapS). Anchor points and their immediate surroundings were investigated for potential patterns of origination and dispersal. Key resultsThe results of this study provide evidence that African red-headed agamas likely established themselves through both intentional releases and unintentional escapes from the pet owners and breeders, while also potentially hitchhiking on plant exports, and dispersing throughout Florida via the railway systems. ConclusionsGiven the potential for railways as a method of assisted dispersal, and given the potential exports they may be hitchhiking on, the results of this study suggest that railcars and railway export facilities should be included in future management of non-native African red-headed agamas in Florida. ImplicationsThe implications of this study builds on prior evidence that geographic profiling is an effective modelling tool in regards to biological invasions, which can accurately confirm suspected origins while also effectively mapping previously unknown epicenters of population clusters to be investigated by managers.

ecology↗

bioRxiv2020

Sorry, we're open: Golden Open Access and inequality in the natural sciences

Global Open Access (GOA) journals make research more accessible and therefore more citable; however, the publication fees associated with GOA journals can be costly and therefore not a viable option for many researchers seeking high-impact publication outlets. In this study, I collect metadata from 237 open-access natural science journals and analyze them in terms of Article Processing Charges (APC), Impact Factor (IF), Eigen Factor (EF), citability, and country of publisher. The results of this study provide evidence that with IF, EF, and citability all increase as APC increases, and each of these metrics are higher in publishers from developed countries in comparison to developing countries. Implications of these trends are discussed in regards to natural sciences and inequality within the global scientific community.

scientific communication and education↗

bioRxiv2017

Meta-analysis and Commentary: Preemptive Correction of Arteriovenous Access Stenosis

BackgroundA recent meta-analysis by Ravani and colleagues (Ravani, P., et al., Am J Kidney Dis, 2016. 67(3): p. 446-60.) studied the effect of pre-emptive correction of arterio-venous dialysis vascular access versus deferred care, based on data from 11 trials. The authors reported a non-significant protective treatment effect of pre-emptive correction on access loss, while showing a significant protective effect on thrombosis rates conferred by pre-emptive correction. We revisit this analysis, including data extraction and effects of a heterogenous study population.\n\nMethodsWe repeated data extraction from all referenced publications in the meta-analysis by Ravani et al. and corrected event counts where applicable. We repeated the meta-analyses with access loss as the outcome for studies that recruited patients with arterio-venous fistulae (AVF) and grafts (AVG), respectively, using a random effects model with relative risk (RR) and risk difference (RD) of access loss as the outcomes of interest. We repeated data extraction from all referenced publications, and corrected event counts where applicable.\n\nResultsOur conclusions differ from the original findings in two ways. First, after some amendment of the event counts extracted from Mayer et al. (Vascular and Endovascular Surgery 1993), we find a significant overall positive effect of pre-emptive correction on arterio-venous access loss in the overall study population [RR 0.80 (95% CI 0.64 to 0.99), RD -0.07 (95% CI -0.12 to -0.02); Figure 1]. Secondly, we highlight the impact of heterogeneous study populations on the meta-analysis. Whereas the data do not conclusively show a benefit of pre-emptive correction for arteriovenous grafts (AVG; RR = 0.87, 95% CI: 0.69 - 1.11), they show a strong protective effect for arteriovenous fistulae (AVF; RR = 0.5, 95% CI: 0.29 to 0.86).\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC=\"FIGDIR/small/179580_fig1.gif\" ALT=\"Figure 1\">\nView larger version (41K):\norg.highwire.dtl.DTLVardef@af3c13org.highwire.dtl.DTLVardef@911a50org.highwire.dtl.DTLVardef@568cf1org.highwire.dtl.DTLVardef@3f3c08_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Meta-analysis of access loss, overall and by access type using risk ratio (RR) as the measure of association.\n\nC_FIG\n\nDiscussion and ConclusionThese findings corroborate clinical arguments such as superior long-term patency of AVF and the nature of AVG failure that often involve infectious causes. The available data indicate mild or no benefit of pre-emptive correction for AVG, but strongly support tight monitoring of dialysis accesses and preemptive intervention and correction upon the slightest suspicion of access stenosis for AVF.

epidemiology↗