Biology subjects

Green, S.

Publications and source records attributed to Green, S..

24 records · Page 2Linked to original sources

bioRxiv2020

Uncovering microbial populations in the lumen of neonatal enteral feeding tubes utilising 16s rRNA sequencing.

Gastrointestinal microbiome is increasingly implicated in the morbidity associated with being born preterm. Enteral tubes (ET) are essential for the nutritional care of preterm infants. Limited culture-based studies have suggested they are colonised by high densities of microorganisms. Microbial DNA was extracted from 60 ETs retrieved from infants in a tertiary neonatal unit and analysed by16s rRNA sequencing of the V4 variable region. Relative abundance analysis on dominant microorganisms demonstrated that compared to breast milk, formula significantly increased abundance of Streptococcus spp and significantly decreased Enterococcus spp and Enterobacteriaceae Vaginal birth was also associated with significantly increased relative abundance of Streptococcus. This study more accurately demonstrates the extent of microbial diversity in neonatal ETs, with feeding regime significantly influencing colonisation patterns. Colonisation with unwanted organisms, as a result of specific care regimes, could result in disruption of the fragile infant gut microbiome, with implications for long-term morbidity.

microbiology↗

bioRxiv2020

Promoter keyholes enable specific and persistent multi-gene expression programs in primary T cells without genome modification

Human genes are regulated quantitatively, yet the ability to specify the expression level of a native gene accurately and specifically using a defined reagent has remained elusive. Here we show that precise targeting of KRAB repressive domain within regulatory DNA unlocks an endogenous quantitative dial that can be engaged at nucleotide resolution to program expression levels across a wide physiologic range, with single-gene specificity and high reproducibly in primary cells.

synthetic biology↗

bioRxiv2020

Sexually dimorphic responses to MPTP found in microglia, inflammation and gut microbiota in a progressive monkey model of Parkinson's disease

Inflammation has been linked to the development of nonmotor symptoms in Parkinsons disease (PD), which greatly impact patients quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a "gold standard" model that closely mimics the clinical motor symptoms and the nigrostriatal dopaminergic loss of PD, however MPTP toxicity extends to other nondopaminergic regions. Yet, there are limited reports monitoring the MPTP-induced progressive central and peripheral inflammation as well as other nonmotor symptoms such as gastrointestinal function and microbiota. The main objective of this study is to gain a broader understanding of central and peripheral inflammatory dysfunction triggered by exposure to a neurotoxicant known to degenerate nigral dopaminergic neurons in order to understand the potential role of inflammation in prodromal/pre-motor features of PD-like degeneration in a progressive non-human primate model of the disease. We measured inflammatory proteins in plasma and CSF and performed [18F]FEPPA PET scans to evaluate translocator proteins (TSPO) or microglial activation in a small cohort of rhesus monkeys (n=5) given weekly low doses of MPTP (0.2-0.8 mg/kg, im). Additionally, monkeys were evaluated for working memory and executive function using various behavior tasks and for gastrointestinal hyperpermeability and microbiota composition. Monkeys were also treated with novel TNF inhibitor XPro1595 (10mg/kg, n=3) or vehicle (n=2) every three days starting 11 weeks after the initiation of MPTP to determine whether nonmotor symptoms are tied to TNF signaling and whether XPro1595 would alter inflammation and microglial behavior in a progressive model of PD. Our analyses revealed sex-dependent sensitivity to MPTP that resulted in early microglial activation by PET, acute plasma IL-6 and CSF TNF, and earlier parkinsonism as measured by motor deficits in males compared to female monkeys. Sex differences were also identified in microbiota and their metabolites and targeted short chain fatty acids at both basal levels and in response to MPTP. Both sexes displayed cognitive impairment prior to a significant motor phenotype. Importantly, XPro1595 shifted peripheral and central inflammation, and significantly reduced CD68-immunoreactivity in the colon. As such, our findings revealed a sexually dimorphic inflammatory response to chronic MPTP treatment and suggest that males may have higher vulnerability than females to inflammation-induced degeneration. If these findings reflect potential differences in humans, these sex differences have significant implications for therapeutic development of inflammatory targets in the clinic.

neuroscience↗

bioRxiv2018

Investigating speech and language impairments in delirium: a preliminary case-control study

Introduction\n\nLanguage impairment is recognized as a diagnostic feature of delirium, yet there is little neuropsychological research on the nature of this dysfunction. Here we hypothesized that patients with delirium show impairments in language formation, coherence and comprehension.\n\nMethods\n\nThis was a case-control study in 45 hospitalized patients (aged 65-97 years) with delirium, dementia without delirium, or no cognitive impairment (N=15 per group). DSM-5 criteria were used for delirium. Speech was elicited during (1) structured conversational questioning, and (2) the \"Cookie Theft\" picture description task. Language comprehension was assessed through standardized verbal and written commands. Interviews were audio-recorded and transcribed.\n\nResults\n\nDelirium and dementia groups scored lower on the conversational assessment than the control group (p<0.01, moderate effect sizes (r) of 0.48 and 0.51, resp.). In the Cookie Theft task, the average length of utterances (i.e. unit of speech), indicating language productivity and fluency, distinguished patients with delirium from those with dementia (p<0.01, r=0.50) and no cognitive impairment (p<0.01, r=0.55). Patients with delirium performed worse on written comprehension tests compared to cognitively unimpaired patients (p<0.01, r=0.63), but not compared to the dementia group.\n\nConclusions\n\nProduction of spontaneous speech, word quantity, speech content and verbal and written language comprehension are impaired in delirious patients compared to cognitively unimpaired patients. Additionally, patients with delirium produced significantly less fluent speech than those with dementia. These findings have implications for how speech and language are evaluated in delirium assessments, and also for communication with patients with delirium.

neuroscience↗

bioRxiv2018

A genome-wide assessment of the ancestral neural crest gene regulatory network

The neural crest is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional profiles and chromatin accessibility of neural crest cells in the basal sea lamprey, in order to gain insight into the ancestral state of the neural crest gene regulatory network (GRN) at the dawn of vertebrates. Transcriptome analyses reveal clusters of co-regulated genes during neural crest specification and migration that show high conservation across vertebrates for dynamic programmes like Wnt modulation during the epithelial to mesenchymal transition, but also reveal novel transcription factors and cell-adhesion molecules not previously implicated in neural crest migration. ATAC-seq analysis refines the location of known cis-regulatory elements at the Hox-2 locus and uncovers novel cis-regulatory elements for Tfap2B and SoxE1. Moreover, cross-species deployment of lamprey elements in zebrafish reveals that the lamprey SoxE1 enhancer activity is deeply conserved, mediating homologous expression in jawed vertebrates. Together, our data provide new insight into the core elements of the GRN that are conserved to the base of the vertebrates, as well as expose elements that are unique to lampreys.

developmental biology↗

bioRxiv2017

Umbilical Cord Blood Diagnostics for Early Onset Sepsis in Premature Infants: Detection of Bacterial DNA and Systemic Inflammatory Response

Statement of financial supportThis work has been supported by a Thrasher Research Fund Early Career Award (#12573), National Institutes of Health (K23 HL093302 [KKM], R01GM108494 [PCS])), the Gerber Foundation, the Hartwall Foundation, and the Northwestern Memorial Foundation (Friends of Prentice Grants Initiative).\n\nDisclosure statementThe authors of this manuscript have no conflicts of interest to disclose.\n\nCategory of StudyTranslational

microbiology↗