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"Giles, Sarah"
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Black enough : stories of being young & black in America
A collection of short stories explore what it is like to be young and black, centering on the experiences of black teenagers and emphasizing that one person's experiences, reality, and personal identity are different than someone else.
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Antimicrobial proteins from oyster hemolymph improve the efficacy of conventional antibiotics
Discovering new antibiotics and increasing the efficacy of existing antibiotics are priorities to address antimicrobial resistance. Antimicrobial proteins and peptides (AMPPs) are considered among the most promising antibiotic alternatives and complementary therapies. Here, we build upon previous work investigating the antibacterial activity of a semi-purified hemolymph protein extract (HPE) of the Australian oyster Saccostrea glomerata . HPE showed antimicrobial-biofilm inhibitory activity toward laboratory and clinical strains of Streptococcus pneumoniae and Streptococcus pyogenes at 4.4 and 24.1 μg/mL total protein, respectively. In combination assays, the effectiveness of conventional antibiotics (ampicillin, gentamicin, trimethoprim and ciprofloxacin) was improved between 2 to 32-fold in the presence of HPE (1–12 μg/mL) against a range of clinically important bacteria including Streptococcus spp., Pseudomonas aeruginosa , Moraxella catarrhalis , Klebsiella pneumoniae and Staphylococcus aureus . Effective HPE concentrations are comparable to AMPPs currently approved for use or in clinical trials pipelines. Proteomics analysis of HPE identified a number of proteins including abundant known AMPPs. It was non-toxic to A549 human lung cells up to 205 μg/mL, demonstrating safety well above effective concentrations. Activity was retained with storage at -80°C and ambient laboratory temperature (~24°C), but declined after treatment at either 37°C or 60°C (1 h). This study is in agreement with growing evidence that AMPPs show specificity and a high capacity for synergism with antibiotics. The discovery of HPE provides great opportunities for both pharmaceutical and aquaculture industry development.
Journal Article
Imbalanced unfolded protein response signaling contributes to 1-deoxysphingolipid retinal toxicity
The accumulation of atypical, cytotoxic 1-deoxysphingolipids (1-dSLs) has been linked to retinal diseases such as diabetic retinopathy and Macular Telangiectasia Type 2. However, the molecular mechanisms by which 1-dSLs induce toxicity in retinal cells remain poorly understood. Here, we integrate bulk and single-nucleus RNA-sequencing to define biological pathways that modulate 1-dSL toxicity in human retinal organoids. Our results demonstrate that 1-dSLs differentially activate signaling arms of the unfolded protein response (UPR) in photoreceptor cells and Müller glia. Using a combination of pharmacologic activators and inhibitors, we show that sustained PERK signaling through the integrated stress response (ISR) and deficiencies in signaling through the protective ATF6 arm of the UPR are implicated in 1-dSL-induced photoreceptor toxicity. Further, we demonstrate that pharmacologic activation of ATF6 mitigates 1-dSL toxicity without impacting PERK/ISR signaling. Collectively, our results identify new opportunities to intervene in 1-dSL linked diseases through targeting different arms of the UPR.
The accumulation of cytotoxic deoxysphingolipids causes retinopathies through unknown mechanisms. Here the authors use retinal organoids to show that photoreceptor toxicity is mediated by unfolded protein response signaling.
Journal Article
Binge eating in patients with polycystic ovary syndrome: prevalence, causes, and management strategies
Emerging evidence suggests that disordered eating, particularly binge-eating symptomatology, is overrepresented within Polycystic Ovary Syndrome (PCOS) populations. This comorbidity presents a clinical dilemma as current treatment approaches for PCOS emphasize the importance of weight management, diet, exercise, and the potential for harm of such treatment approaches in PCOS patients with comorbid disordered eating. However, limited research has assessed the occurrence of binge eating and disordered eating in PCOS patients. Consequently, little is known about the prevalence of binge eating in PCOS, and the possible etiological processes to explain this comorbidity remain poorly understood. Given the paucity of research on this topic, the aims of this narrative review are fourfold: 1) to outline the main symptoms of PCOS and binge eating; 2) to provide an overview of the prevalence of binge eating in PCOS; 3) to outline possible etiological factors for the comorbidity between PCOS and binge eating; and 4) to provide an overview of management strategies of binge eating in PCOS.
Journal Article
Obesity prevalence and associated risk factors in outdoor living domestic horses and ponies
Reasons for performing study. The prevalence of obesity in companion animals, including horses and ponies has risen drastically in recent years and risk factors have been little investigated. Horses are unique amongst companion animals in that many are outdoor-living and forage independently on pasture; they also have a dual utility and companionship role. The body condition of wild and free-living equines is known to vary seasonally, yet previous estimates of the prevalence of obesity and associated risk factors in domestic animals do not consider this. Most previous studies were conducted during the summer months when pasture quality is greater and obesity prevalence is likely to be highest. In addition, many previous estimates do not use validated body condition scoring methods and rely on owner reporting. Objectives. To examine the prevalence and risk factors predictive of equine obesity at both the end of winter and the end of summer, in a domestic population of leisure horses with daily access to pasture. Using validated body condition scoring methods and a single, trained observer. Methods. Body condition and belly girth measurements were taken at the end of winter and during the summer in a population of leisure horses (n = 96) with outdoor pasture access for ≥6 h per day. Risk factor information was obtained by two owner questionnaires and analysed statistically using a mixed effects logistic regression model. The dependent variable was obese (BCS ≥ 7/9) or non-obese (BCS < 7/9). Risk factors associated with seasonal change in belly girth were also explored using a mixed effects linear regression model. Results. Obesity prevalence rose significantly from 27.08% at the end of winter to 35.41% during summer (p < 0.001). Breed was the risk factor most strongly associated with obesity (p < 0.001). Supplementary feed was not a strong predictor and there was no association with low intensity structured exercise. As winter BCS increased, the percentage seasonal change in belly girth decreased. Conclusions. Obesity prevalence differed between winter and summer in domestic equines. Supplementary feed and low intensity structured exercise in equines living outdoors for ≥6 h per day had limited or no effect on obesity levels. Seasonal variation in body condition was lower in obese equines. Potential relevance. It is important to consider season when studying equine obesity and obesity-associated disorders. Risk factor analysis suggests preventative measures may need to be breed specific. The metabolic implications of a lessened seasonal change in body condition in obese animals, warrants investigation.
Journal Article
Identification of genes essential for pellicle formation in Acinetobacter baumannii
Background
Acinetobacter baumannii
is an opportunistic pathogen, which has the ability to persist in the clinical environment, causing acute and chronic infections. A possible mechanism contributing to survival of
A. baumannii
is its ability to form a biofilm-like structure at the air/liquid interface, known as a pellicle. This study aimed to identify and characterise the molecular mechanisms required for pellicle formation in
A. baumannii
and to assess a broad range of clinical
A. baumannii
strains for their ability to form these multicellular structures.
Results
Random transposon mutagenesis was undertaken on a previously identified hyper-motile variant of
A. baumannii
ATCC 17978 designated 17978hm. In total three genes critical for pellicle formation were identified;
cpdA
, a phosphodiesterase required for degradation of cyclic adenosine monophosphate (cAMP), and A1S_0112 and A1S_0115 which are involved in the production of a secondary metabolite. While motility of the A1S_0112::Tn and A1S_0115::Tn mutant strains was abolished, the
cpdA
::Tn mutant strain displayed a minor alteration in its motility pattern. Determination of cAMP levels in the
cpdA
::Tn strain revealed a ~24-fold increase in cellular cAMP, confirming the role CpdA plays in catabolising this secondary messenger molecule. Interestingly, transcriptional analysis of the
cpdA
::Tn strain showed significant down-regulation of the operon harboring the A1S_0112 and A1S_0115 genes, revealing a link between these three genes and pellicle formation. Examination of our collection of 54 clinical
A. baumannii
strains revealed that eight formed a measurable pellicle; all of these strains were motile.
Conclusions
This study shows that pellicle formation is a rare trait in
A. baumannii
and that a limited number of genes are essential for the expression of this phenotype. Additionally, an association between pellicle formation and motility was identified. The level of the signalling molecule cAMP was found to be controlled, in part, by the
cpdA
gene product, in addition to playing a critical role in pellicle formation, cellular hydrophobicity and motility. Furthermore, cAMP was identified as a novel regulator of the operon A1S_0112-0118.
Journal Article
iPSC–derived retinal pigmented epithelial cells from patients with macular telangiectasia show decreased mitochondrial function
Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful tool for identifying cellular and molecular mechanisms of disease. Macular telangiectasia type 2 (MacTel) is a rare, late-onset degenerative retinal disease with an extremely heterogeneous genetic architecture, lending itself to the use of iPSCs. Whole-exome sequencing screens and pedigree analyses have identified rare causative mutations that account for less than 5% of cases. Metabolomic surveys of patient populations and GWAS have linked MacTel to decreased circulating levels of serine and elevated levels of neurotoxic 1-deoxysphingolipids (1-dSLs). However, retina-specific, disease-contributing factors have yet to be identified. Here, we used iPSC-differentiated retinal pigmented epithelial (iRPE) cells derived from donors with or without MacTel to screen for novel cell-intrinsic pathological mechanisms. We show that MacTel iRPE cells mimicked the low serine levels observed in serum from patients with MacTel. Through RNA-Seq and gene set enrichment pathway analysis, we determined that MacTel iRPE cells are enriched in cellular stress pathways and dysregulation of central carbon metabolism. Using respirometry and mitochondrial stress testing, we functionally validated that MacTel iRPE cells had a reduction in mitochondrial function that was independent of defects in serine biosynthesis and 1-dSL accumulation. Thus, we identified phenotypes that may constitute alternative disease mechanisms beyond the known serine/sphingolipid pathway.
Journal Article
Foraging efficiency, social status and body condition in group-living horses and ponies
Individual animals experience different costs and benefits associated with group living, which may impact on their foraging efficiency in ways not yet well specified. This study investigated associations between social dominance, body condition and interruptions to foraging behaviour in a cross-sectional study of 116 domestic horses and ponies, kept in 20 discrete herds. Social dominance was measured for each individual alongside observations of winter foraging behaviour. During bouts of foraging, the duration, frequency and category (vigilance, movement, social displacements given and received, scratching and startle responses) of interruptions were recorded, with total interruption time taken as a proxy measure of foraging efficiency. Total foraging time was not influenced by body condition or social dominance. Body condition was associated with social dominance, but more strongly associated with foraging efficiency. Specifically, lower body condition was associated with greater vigilance. This demonstrates that factors other than social dominance can result in stable differences in winter body condition.
Journal Article