Biology subjects

Blair, R.

Publications and source records attributed to Blair, R..

10 recordsLinked to original sources

bioRxiv2026

Building an open ecosystem for molecular neuroimaging: standards and tools from the OpenNeuroPET initiative

Molecular neuroimaging with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) enables quantification of specific molecular targets in the living brain. Despite its scientific impact, molecular neuroimaging research has historically faced challenges due to high costs, small sample sizes, laboratory-specific analysis pipelines, and limited large-scale data sharing. These factors have hindered reproducibility and the broader reuse of valuable PET datasets. The OpenNeuroPET initiative was established to address these barriers by developing standards, infrastructure, and open-source tools currently focused on PET. Through collaborations across Europe and North America, OpenNeuroPET has supported the PET extension of the Brain Imaging Data Structure (PET-BIDS), providing a standardized framework for PET datasets and metadata. Building on PET-BIDS, tools such as PET2BIDS, ezBIDS, and BIDSCoin facilitate data conversion and curation. In parallel, OpenNeuro now hosts PET-BIDS datasets for open sharing, while complementary platforms such as PublicnEUro provide controlled-access pathways designed to support compliance with the European Union General Data Protection Regulation (GDPR). Emerging open-source workflows further support automated, reproducible PET analysis, promoting harmonization across centers. Together, these developments mark an important step toward an open molecular neuroimaging community in which datasets, software, and workflows can be transparently shared, reused, and scaled for collaborative research.

bioinformatics↗

bioRxiv2025

Persistent Activation of Monocytes/Macrophages and Cell Senescence in SIV-Infected Macaques on ART

Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-{kappa}B signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-{kappa}B, and inflammasome (NLRP3/or NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-{kappa}B activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART- treated macaque revealed macrophage-rich plaques with p21 senescent cells with intraluminal thrombus formation, recapitulating key features of HIV-associated atherogenesis. Together, these findings demonstrate that while ART normalizes acute infection-induced immune dysregulation, chronic SIV infection sustains a chronic, macrophage- and TLR-driven inflammatory state linked to vascular injury and aging process regardless of long-term suppression of viremia. Targeting inflammasome, NF-{kappa}B, and senescence pathways may mitigate non-AIDS comorbidities in PLWH.

immunology↗

bioRxiv2025

Resolving Inflammation: The Impact of Antiretroviral Therapy on Macrophage Traffic In and Out of the CNS.

The effect of antiretroviral therapy (ART) and therapy interruption on myeloid cell traffic out of the central nervous system (CNS) with human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are understudied. Using intracisternal (i.c.) injection of dual-colored fluorescent superparamagnetic iron oxide nanoparticles (SPION) in SIV-infected macaques early (12-14 dpi) and late (30 days before sacrifice) we studied CNS macrophage viral infection, turnover, and traffic out. SPION are preferentially taken up by perivascular, meningeal, and choroid plexus macrophages. In non-infected macaques, SPION+ macrophages can traffic out of the CNS to the periphery (deep cervical lymph node (dcLN), spleen, and dorsal root ganglia (DRG)), but accumulate in the CNS with SIV infection. ART reduces the accumulation of CNS SPION+ perivascular macrophages but not meningeal or choroid plexus macrophages. ART interruption does not affect the number of SPION+ perivascular and choroid plexus but the number of SPION+ meningeal macrophages increase. ART eliminates SIV-RNA perivascular macrophages, but few scattered RNA+ macrophages in the meninges and choroid plexus remain. With ART interruption, perivascular macrophages remain SIV-but scattered SIV+ meningeal and choroid plexus macrophages exist. In non-infected animals SPION+ macrophages traffic to dcLN, spleen, and DRG at a rate that is decreased with SIV infection and AIDS. SIV- RNA+ SPION+ macrophages that traffic out of the CNS are eliminated by ART and do not rebound with ART interruption. Using two different colored SPION to study the establishment of CNS SIV viral reservoirs, we find greater numbers of early SPION+ macrophages within and outside of the CNS with SIVE, ART, and ART interruption. These data are consistent with SIV-infected perivascular macrophages establishing an early viral reservoir, and continual viral seeding of the meninges and choroid plexus during infection. These findings are consistent with ART reducing traffic of infected macrophages out of the CNS, clearing the CNS perivascular macrophage viral reservoir but not SIV-RNA+ macrophages in meninges and choroid plexus that can rebound with ART interruption.

immunology↗

bioRxiv2023

Comparison of spontaneous recurrent seizures in rats following status epilepticus induced by organophosphate paraoxon, DFP, and sarin

Organophosphate (OP) compounds are highly toxic and include household, industrial, agricultural, and chemical warfare nerve agents (CWNA). OP exposure inhibits acetylcholinesterase enzyme, causing cholinergic overstimulation that can evolve into status epilepticus (SE) and produce lethality. Furthermore, OP-SE survival is associated with mood and memory dysfunction and spontaneous recurrent seizures (SRS). Here we assessed hippocampal pathology and chronic SRS following SE induced by OP agents in rats. Male Sprague-Dawley rats were injected with 1.5x LD50 of various OP agents, followed by atropine and 2-PAM. At 1-h post-OP-SE onset, midazolam was administered to control SE. Approximately 6 months following OP-SE, SRS were evaluated using continuous video-EEG monitoring. Histopathology was conducted using Hematoxylin and Eosin (H&E), while silver sulfide (Timm) staining was utilized to assess Mossy Fiber Sprouting (MFS). Over 60% of OP-SE surviving rats developed SRS with varying seizure frequencies, durations, and Racine severity scores. H&E staining revealed a significant hippocampal neuronal loss, while Timm staining revealed extensive MFS within the inner molecular region of the dentate gyrus of SRS-expressing OP-SE rats. This study demonstrates that OP-SE is associated with hippocampal neuronal loss, extensive MFS, and SRS, all hallmarks of chronic epilepsy.

pharmacology and toxicology↗

bioRxiv2021

OpenNeuro: An open resource for sharing of neuroimaging data

The sharing of research data is essential to ensure reproducibility and maximize the impact of public investments in scientific research. Here we describe OpenNeuro, a BRAIN Initiative data archive that provides the ability to openly share data from a broad range of brain imaging data types following the FAIR principles for data sharing. We highlight the importance of the Brain Imaging Data Structure (BIDS) standard for enabling effective curation, sharing, and reuse of data. The archive presently shares more than 600 datasets including data from more than 20,000 participants, comprising multiple species and measurement modalities and a broad range of phenotypes. The impact of the shared data is evident in a growing number of published reuses, currently totalling more than 150 publications. We conclude by describing plans for future development and integration with other ongoing open science efforts.

neuroscience↗

bioRxiv2019

Diversity and complexity of the large surface protein family in the compacted genomes of various Pneumocystis species

Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multi-copy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins, and provide detailed description of the classification, unique characteristics and phylogenetic relatedness of five Msg families. We further describe the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests a wide variety of functions for this superfamily, not only conferring antigenic variation to allow immune evasion but also mediating life-stage development, optimizing cell mobility and adhesion, and adapting to specific host niches or environmental conditions. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.

molecular biology↗

bioRxiv2019

Multi-objective optimisation of material properties and strut geometry for poly(L-lactic acid) coronary stents using response surface methodology

Coronary stents for treating atherosclerosis are traditionally manufactured from metallic alloys. However, metal stents permanently reside in the body and may trigger undesirable immunological responses. Bioresorbable polymer stents can provide a temporary scaffold that resorbs once the artery heals but are mechanically inferior, requiring thicker struts for equivalent radial support, which may increase thrombosis risk. This study addresses the challenge of designing mechanically effective but sufficiently thin poly(L-lactic acid) stents through a computational approach that optimises material properties and stent geometry. Forty parametric stent designs were generated: cross-sectional area (post-dilation), foreshortening, stent-to-artery ratio and radial collapse pressure were evaluated computationally using finite element analysis. Response surface methodology was used to identify performance trade-offs by formulating relationships between design parameters and response variables. Multi-objective optimisation was used to identify suitable stent designs from approximated Pareto fronts and an optimal design is proposed that offers comparable performance to designs in clinical practice. In summary, a computational framework has been developed that has potential application in the design of high stiffness, thin strut polymeric stents that contend with the performance of their metallic counterparts.

bioengineering↗

bioRxiv2019

Maternal antibodies provide partial protection from postnatal Zika viremia in nonhuman primates

Zika virus (ZIKV) will remain a public health threat until effective vaccines and therapeutics are made available in the hardest hit areas of the world. Recent data in a nonhuman primate model showed that infants postnatally infected with ZIKV were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. We addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding, possibly non-neutralizing antibodies remained detectable until viral infection at 5 months of age. Post-infection acute serum viremia was substantially reduced relative to adults infected with the same dose of the same stock of a Brazilian isolate of ZIKV (n=11 pregnant females) and another stock of the same isolate (n=4 males and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection, suggesting reduced viral burden relative to adults and published data from infants. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

microbiology↗

bioRxiv2017

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission. Pregnant, CD4+ T cell-depleted, rhesus CMV (RhCMV)-seronegative rhesus monkeys were treated with either standardly-produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV swarm. HIG passive infusion provided complete protection against fetal loss in both groups, and the potently-neutralizing HIG additionally inhibited placental transmission of RhCMV. Our findings suggest that antibody alone at the time of primary infection can prevent congenital CMV and therefore could be a primary target of vaccines to eliminate this neonatal infection.

immunology↗

bioRxiv2017

Neurodesign: Optimal experimental designs for task fMRI

1A recent stream of alarmist publications has questioned the validity of published neuroimaging findings. As a consequence, fMRI teams worldwide have been encouraged to increase their sample sizes to reach higher power and thus increase the positive predictive value of their findings. However, an often-overlooked factor influencing power is the experimental design: by choosing the appropriate experimental design, the statistical power of a study can be increased within subjects. By optimizing the order and timing of the stimuli, power can be gained at no extra cost. To facilitate design optimization, we created a python package and web-based tool called Neurodesign to maximize the detection power or estimation efficiency within subjects, while controlling for psychological factors such as the predictability of the design. We implemented both a simulation-based optimisation, as well as an optimisation using the genetic algorithm, introduced by Wager and Nichols (2003) and further improved by Kao et al. (2009), to optimize the experimental design. The toolbox Neurodesign allows more complex experimental setups than existing toolboxes, while the GUI provides a more user-friendly experience. The toolbox is accessible online at www.neuropowertools.org.

neuroscience↗