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The theory of ecological cognition poses that the brains and behaviour of animals are shaped by the environmental challenges they face in their everyday lives. Site fidelity and homing ability was tested for five species of intertidal rock pool fish by tagging and displacing them to new rock pools at various distances from their ‘home’ rock pools. Three of the species were rock pool specialists whilst the remaining two spend a small proportion of their life in rock pools during early ontogeny. The three specialists showed strong site fidelity with >50 % of individuals found in the same pool 42 days after tagging. In contrast, the non-specialist species showed low fidelity and poor homing abilities. Homing success in the rock pool specialists remained relatively stable as displacement distance increased. The effect of body size on homing ability was species dependent, with only one species showing a significantly greater tendency to home with increasing size.

For the majority of animals, the ability to orient in familiar locations is a fundamental part of life, and spatial memory allows individuals to remember key locations such as food patches, shelter, mating sites or areas regularly occupied by predators. This study determined if gobies collected from rocky platforms and sandy beaches differ in their ability to learn and memorise the locations of tide pools in a simulated rocky intertidal zone. Intertidal rock pool gobies show acute homing abilities and, therefore, should be expected to display superior learning and memory capabilities. In contrast, it is unlikely that natural selection would favour similar learning skills in sandy shore fishes because they simply shift back and forth with the tides. The learning abilities of gobies were tested using small replica rock platforms, containing four tide pools that retained varying depths of water at simulated low tide. Gobies were categorised as having learnt the task if they were able to consistently locate the tide pool that retained the most water at simulated low tide as the pool with the most favourable conditions. Rock pool species were able to locate the deepest pool to wait out low tide for ~95 % of the trials, while species from sandy shores were found in the deepest pool ~10 % of trials. Despite repeated stranding, sandy shore fish continued to follow the tide out. We propose that rock pool species memorised the location of rock pools during simulated high tide enabling them to relocate the best refuge for low tide.

The ecological cognition hypothesis poses that the brains and behaviours of individuals are largely shaped by the environments in which they live and the associated challenges they must overcome during their lives. Here we examine the effect of environmental complexity on relative brain size in 4 species of intertidal gobies from differing habitats. Two species were rock pool specialists that lived on spatially complex rocky shores, while the remainder lived on dynamic, but structurally simple, sandy shores. We found that rock pool-dwelling species had relatively larger brains and telencephalons in particular, while sand-dwelling species had a larger optic tectum and hypothalamus. In general, it appears that various fish species trade off neural investment in specific brain lobes depending on the environment in which they live. Our previous research suggests that rock pool species have greater spatial learning abilities, enabling them to navigate their spatially complex environment, which may account for their enlarged telencephalon, while sand-dwelling species likely have a reduced need for spatial learning, due to their spatially simple habitat, and a greater need for visual acuity. The dorsal medulla and cerebellum size was unaffected by the habitat in which the fish lived, but there were differences between species indicative of species-specific trade-offs in neural investment.

When correlating brain size and structure with behavioural and environmental characteristics, a range of techniques can be utilised. This study used gobiid fishes to quantitatively compare brain volumes obtained via three different methods; these included the commonly used techniques of histology and approximating brain volume to an idealised ellipsoid, and the recently established technique of X-ray micro-computed tomography (micro-CT). It was found that all three methods differed significantly from one another in their volume estimates for most brain lobes. The ellipsoid method was prone to over- or under-estimation of lobe size, histology caused shrinkage in the telencephalon, and although micro-CT methods generated the most reliable results, they were also the most expensive. Despite these differences, all methods depicted quantitatively similar relationships among the four different species for each brain lobe. Thus, all methods support the same conclusions that fishes inhabiting rock pool and sandy habitats have different patterns of brain organisation. In particular, fishes from spatially complex rock pool habitats were found to have larger telencephalons, while those from simple homogenous sandy shores had a larger optic tectum. Where possible we recommend that micro-CT be used in brain volume analyses, as it allows for measurements without destruction of the brain and fast identification and quantification of individual brain lobes, and minimises many of the biases resulting from the histology and ellipsoid methods.

Apolipoprotein A1 (apoA1) is the major protein component of high-density lipoprotein (HDL) and has well documented anti-inflammatory properties. To better understand the cellular and molecular basis of the anti-inflammatory actions of apoA1, we explored the effect of acute human apoA1 exposure on the migratory capacity of monocyte-derived cells in vitro and in vivo. Acute (20–60 min) apoA1 treatment induced a substantial (50–90%) reduction in macrophage chemotaxis to a range of chemoattractants. This acute treatment was anti-inflammatory in vivo as shown by pre-treatment of monocytes prior to adoptive transfer into an on-going murine peritonitis model. We find that apoA1 rapidly disrupts membrane lipid rafts, and as a consequence, dampens the PI3K/Akt signalling pathway that coordinates reorganization of the actin cytoskeleton and cell migration. Our data strengthen the evidence base for therapeutic apoA1 infusions in situations where reduced monocyte recruitment to sites of inflammation could have beneficial outcomes. A molecule called cholesterol is an important component of the membranes found in cells and is also used to make some hormones and other useful molecules. However, cholesterol can also contribute to the formation of plaques in arteries, which can lead to a disease called atherosclerosis, the cause of heart attacks. Particles called high density lipoproteins (HDL) carry cholesterol around the body in the bloodstream and are thought to have anti-inflammatory properties. A protein called apoA1 is a major component of HDL particles and, acting as part of a HDL particle or alone, it removes cholesterol from cells. Atherosclerotic plaques form when white blood cells collect in places where the arteries are inflamed. The membranes that surround the white blood cells contain receptors that are able to detect inflammatory signals called chemokines. These receptors eventually communicate with the machinery needed for cell movement. This machinery is concentrated in parts of the membrane known as lipid rafts. Iqbal, Barrett et al. investigated whether apoA1 can block the movement of mouse and human white blood cells towards the chemokines produced during inflammation. The experiments show that apoA1 treatment strongly inhibited the movement of white blood cells towards a range of chemokines in a culture dish. The apoA1 protein removes cholesterol from lipid rafts in the membrane of the white blood cell, which changes the properties of the membrane and decreases the activity of the machinery needed for cell movement. Further experiments in mice with inflammation of the peritoneum, the thin layer of tissue that lines the inside of the abdomen, produced similar findings. The next step following on from this work would be to investigate whether apoA1 treatment can reduce the accumulation of white blood cells in mice that act as models of other inflammatory diseases, such as arthritis and atherosclerosis.

Chemotaxis assays are an invaluable tool for studying the biological activity of inflammatory mediators such as CC chemokines, which have been implicated in a wide range of chronic inflammatory diseases. Conventional chemotaxis systems such as the modified Boyden chamber are limited in terms of the data captured given that the assays are analysed at a single time-point. We report the optimisation and validation of a label-free, real-time cell migration assay based on electrical cell impedance to measure chemotaxis of different primary murine macrophage populations in response to a range of CC chemokines and other chemoattractant signalling molecules. We clearly demonstrate key differences in the migratory behavior of different murine macrophage populations and show that this dynamic system measures true macrophage chemotaxis rather than chemokinesis or fugetaxis. We highlight an absolute requirement for Gαi signaling and actin cytoskeletal rearrangement as demonstrated by Pertussis toxin and cytochalasin D inhibition. We also studied the chemotaxis of CD14(+) human monocytes and demonstrate distinct chemotactic profiles amongst different monocyte donors to CCL2. This real-time chemotaxis assay will allow a detailed analysis of factors that regulate macrophage responses to chemoattractant cytokines and inflammatory mediators.

Starkly unaware of herself and struggling to make the passage from child to adult, the narrator in this collection points the finger, repeatedly exposes her heart and wonders why things just never seem to work out. Join her flirtations with strangers, intoxicating relationships and explorations to the edge of the void. This is poetry of the imagination where madness grows, memory holds sway and the night is an octopus \"awkwardly getting caught. Tentacles fastening onto telegraph poles...\".

Blockade of CC chemokines is an attractive yet under utilized therapeutic strategy. We report the in vivo pharmacokinetics of a broad-spectrum vaccinia virus CC chemokine binding protein (35 K) fused to human IgG1 Fc. We demonstrate that the in vivo efficacy of the protein can be interrogated using hydrodynamic gene delivery of a standard mammalian expression plasmid. High plasma levels of the 35 K-Fc protein are maintained for at least 14 days post gene transfer, with the protein still detectable at 5 weeks. We confirm that the protein has biological activity in acute inflammation, causing a significant reduction in monocyte recruitment during zymosan induced peritonitis. The ability of 35 K-Fc to block more complex pathologies is demonstrated using aortic digests to assess angiotensin II mediated leukocyte recruitment to the aorta. Angiotensin II causes upregulation of mCCL2 in the aorta causing the accumulation of CCR2+ cells. Peak monocyte recruitment to the aorta occurs within 3 days and this process is CC chemokine dependent, being significantly reduced by hydrodynamic delivery of 35 K-Fc.

ObjectiveThe aim of this observational study was to evaluate the UK and Dutch referral criteria for short stature to determine their sensitivity and specificity in predicting pathological short stature. Adherence to the recommended panel of investigations was also assessed.Study designRetrospective review of medical records to examine the auxological parameters, investigations and diagnosis of subjects referred to two paediatric endocrine clinics at the Royal London Children’s Hospital between 2016 and 2021. We analysed: height SD score (HtSDS), height SDS minus target height SDS (Ht-THSDS) and height deflection SDS (HtDefSDS). The UK referral criteria were HtSDS <−2.7, Ht-THSDS >2.0 and HtDefSDS >1.3. The Dutch referral criteria were HtSDS <−2.0, Ht-THSDS >1.6 and HtDefSDS >1.0.ResultsData were available for 143 subjects (72% males) with mean (range) age 8.7 years (0.5–19.9). HtSDS and Ht-THSDS were significantly lower in the pathological stature (n=66) versus the non-pathological stature (n=77) subjects (−2.67±0.82 vs −1.97±0.70; p<0.001 and −2.07±1.02 vs −1.06±0.99; p<0.001, respectively). The sensitivity and specificity to detect pathology was 41% and 83% for the UK criteria (HtSDS <−2.7) compared with 59% and 79% for the Dutch criteria (HtSDS <−2.0), 48% and 83% for UK criteria (Ht-THSDS <−2.0) compared with 74% and 72% for Dutch criteria (Ht-THSDS <−1.6) and 33% and 68% for UK criteria (HtDefSDS >1.3) compared with 44% and 63% for the Dutch criteria (HtDefSDS >1.0). On average, each patient had 88% of the recommended investigations, and 53% had all the recommended testing. New pathology was identified in 36% of subjects.ConclusionsIn isolation, the UK auxological referral thresholds have limited sensitivity and specificity for pathological short stature. The combination of HtSDS and Ht-THSDS improved the sensitivity of UK criteria to detect pathology from 41% to 68%. Attention to the child’s genetic height potential prior to referral can prevent unnecessary assessments.

Treatment of cells with cytokines and growth factors leads to the synthesis of Suppressor of Cytokine Signalling (SOCS) proteins that act as potent negative regulators of signalling via the Jak/STAT pathway. We used immunohistochemistry to identify cells and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues. Epitope and GFP tagged SOCS3 fusion proteins were localised predominantly in the nucleus of transfected cells and a validated anti SOCS3 antiserum revealed the expression of SOCS3 in the nucleus and cytoplasm of macrophages, endothelial and epithelial cells in a wide range of normal tissues in tissue microarrays ( n  = 31 different tissues). Nuclear SOCS3 was only seen in cells expressing a high level of the protein. Comparative immunostaining of acute, chronically and granulomatously inflamed human tissues revealed higher levels of nuclear and cytoplasmic SOCS3 expression in inflamed than in corresponding normal tissues, particularly in recruited leukocyte populations, but also in epithelia. The staining appeared more intense, suggesting higher expression levels, in areas where inflammation was more acute, consistent with the time course of SOCS3 induction described in vitro. Expression of SOCS3 protein by leucocytes and other cell types in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo.