The Effect of Ageing on Ocular Blood Flow,Oxygen Tension and Retinal Function during and after Intraocular Pressure Elevation

Purpose

To investigate the effect of ageing on the recovery of ocular blood flow, intravitreal oxygen tension and retinal function during and after intraocular pressure (IOP) elevation.

Methods

Long Evans rats (3- and 14-month-old) underwent acute stepwise IOP elevation from 10 to 120 mmHg (5 mmHg steps each 3 minutes). IOP was then returned to baseline and recovery was monitored for 2 hours. Photopic electroretinograms (ERG) were recorded at each IOP step during stress and at each minute during recovery. Ocular blood flow and vitreal oxygen tension (pO₂) were assayed continuously and simultaneously using a combined laser Doppler flow meter (LDF) and an oxygen sensitive fibre-optic probe, respectively. The combined sensor was placed in the vitreous chamber, proximal to the retina. Data were binned into 3 minute intervals during stress and 1 min intervals during recovery. Recovery data was described using a bi-logistic function.

Results

Rats of both ages showed similar susceptibility to IOP elevation, with pO₂ showing a closer relationship to ERG than LDF. During recovery, both ages showed a distinctive two-phased recovery for all three measures with the exception of the LDF in 3-month-old rats, which showed only 1 phase. In all animals, LDF recovered fastest (<1 minute), followed by pO₂ (<10 minute) and ERG (>1 hour). 14-month-old rats showed surprisingly faster and greater LDF recovery compared to the younger group, with similar levels of pO₂ recovery. However, the ERG in these middle-aged animals did not fully recover after two hours, despite showing no difference in susceptibility to IOP during stress compared to the young group.

Conclusions

Young and middle-aged eyes showed similar susceptibility to IOP elevation in terms of pO₂, LDF and ERG. Despite this lack of difference during stress, older eyes did not completely recover function, suggesting a more subtle age-related susceptibility to IOP.     

Peptidoglycan ld-Carboxypeptidase Pgp2 Influences Campylobacter jejuni Helical Cell Shape and Pathogenic Properties and Provides the Substrate for the dl-Carboxypeptidase Pgp1

Despite the importance of Campylobacter jejuni as a pathogen, little is known about the fundamental aspects of its peptidoglycan (PG) structure and factors modulating its helical morphology. A PG dl-carboxypeptidase Pgp1 essential for maintenance of C. jejuni helical shape was recently identified. Bioinformatic analysis revealed the CJJ81176_0915 gene product as co-occurring with Pgp1 in several organisms. Deletion of cjj81176_0915 (renamed pgp2) resulted in straight morphology, representing the second C. jejuni gene affecting cell shape. The PG structure of a Δpgp2 mutant showed an increase in tetrapeptide-containing muropeptides and a complete absence of tripeptides, consistent with ld-carboxypeptidase activity, which was confirmed biochemically. PG analysis of a Δpgp1Δpgp2 double mutant demonstrated that Pgp2 activity is required to generate the tripeptide substrate for Pgp1. Loss of pgp2 affected several pathogenic properties; the deletion strain was defective for motility in semisolid agar, biofilm formation, and fluorescence on calcofluor white. Δpgp2 PG also caused decreased stimulation of the human nucleotide-binding oligomerization domain 1 (Nod1) proinflammatory mediator in comparison with wild type, as expected from the reduction in muropeptide tripeptides (the primary Nod1 agonist) in the mutant; however, these changes did not alter the ability of the Δpgp2 mutant strain to survive within human epithelial cells or to elicit secretion of IL-8 from epithelial cells after infection. The pgp2 mutant also showed significantly reduced fitness in a chick colonization model. Collectively, these analyses enhance our understanding of C. jejuni PG maturation and help to clarify how PG structure and cell shape impact pathogenic attributes.     

Blood Levels of S-100 Calcium-Binding Protein B,High-Sensitivity C-Reactive Protein,and Interleukin-6 for Changes in Depressive Symptom Severity after Coronary Artery Bypass Grafting: Prospective Cohort Nested within a Randomized,Controlled Trial

Background

Cross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.

Methods

Fifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative.

Results

Changes in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman ρ, 0.62; P = 0.0004) and accounted for about one-fourth of their observed variance (R², 0.23; P = 0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or β-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C-reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative.

Conclusions

Acute changes in depressive symptom severity were specifically associated with incremental changes in S-100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals.     

Enzyme Promiscuity: Engine of Evolutionary Innovation

Catalytic promiscuity and substrate ambiguity are keys to evolvability, which in turn is pivotal to the successful acquisition of novel biological functions. Action on multiple substrates (substrate ambiguity) can be harnessed for performance of functions in the cell that supersede catalysis of a single metabolite. These functions include proofreading, scavenging of nutrients, removal of antimetabolites, balancing of metabolite pools, and establishing system redundancy. In this review, we present examples of enzymes that perform these cellular roles by leveraging substrate ambiguity and then present the structural features that support both specificity and ambiguity. We focus on the phosphatases of the haloalkanoate dehalogenase superfamily and the thioesterases of the hotdog fold superfamily.     

Ixodid ticks of African buffalo (<Emphasis Type="Italic">Syncerus caffer</Emphasis>), impala (<Emphasis Type="Italic">Aepyceros melampus</Emphasis>) and elephant (<Emphasis Type="Italic">Loxodonta africana</Emphasis>) in five protected park estates in the Zambezi valley,Zimbabwe

Wildlife hosts many pathogens of economic importance and is considered as a reservoir of important tick-borne diseases of livestock in southern Africa. The species composition of ticks parasitizing buffalo (Syncerus caffer), impala (Aepyceros melampus) and elephant (Loxodonta africana) was investigated in five protected parks in the Zambezi valley, Zimbabwe. A total of 1104 adult ticks was collected from 75 adult animals comprising five buffaloes, five elephants and five impalas drawn from five protected wildlife parks. Five tick species belonging to two genera were recovered, with Rhipicephalus decoloratus being the most prevalent species in all the three animal groups. Amblyomma hebraeum was only recovered from buffaloes whereas Rhipicephalus zambeziensis was recovered from buffalos and elephants. Significant differences in mean tick species distribution and concentration were observed amongst the wildlife parks and these appeared to be influenced by the number of hosts in each park. The study revealed that buffaloes are the major host of R. decoloratus in the Zambezi valley. The presence of these ixodid ticks within the Zambezi valley may have significant ecological and economic impacts on wildlife conservation, domestic animals and human health.     

Quantifying site-level usage and certainty of absence for an invasive species through occupancy analysis of camera-trap data

Efficient implementation of management programs for invasive species depends on accurate surveillance for guiding prioritization of surveillance and control resources in space and time. Occupancy probabilities can be used to determine where surveillance should occur. Conversely, knowledge of the certainty of site-level absence is of special interest in situations where the objective is to completely remove populations despite substantial risk of re-invasion. Indeed, the decision to shift from emphasizing control activities over the full range to emphasizing reinvasion prevention, surveillance, and response near the borders, depends on accurate knowledge of absence across space. We used a dynamic occupancy model to monitor changes in the distribution of an invasive species, feral swine (Sus scrofa), based on camera-trap data collected as part of a management program from June 2014 to January 2016 in San Diego County, California. Site usage of feral swine declined overall. The most informative predictors of site usage were spatial (latitude and longitude). Site-level non-usage rates increased over time and in response to management removal efforts; and site-level usage rates were heavily impacted by having neighboring sites that were used. Combining the detection probability estimated from the occupancy model and Bayes Theorem, we demonstrated how certainty of local (site-level) absence can be estimated iteratively in time in areas with negative surveillance (no detections) data. Our framework provides a means for using management-based surveillance data to quantify certainty of site-level absence of an invasive species, allowing for adaptive prioritization of surveillance and control resources. Our approach is flexible for application to other species and types of surveillance (e.g., track-plates, eDNA).