Astrogliosis mapping in individual brains using multidimensional MRI

There are currently no noninvasive imaging methods available for astrogliosis mapping in the central nervous system despite its essential role in the response to injury, disease, and infection. We have developed a machine learning-based multidimensional MRI framework that provides a signature of astrogliosis, distinguishing it from normative brain at the individual level. We investigated ex vivo cortical tissue specimen derived from subjects who sustained blast induced injuries, which resulted in scar-border forming astrogliosis without being accompanied by other types of neuropathology. By performing a combined postmortem radiology and histopathology correlation study we found that astrogliosis induces microstructural changes that are robustly detected using our framework, resulting in MRI neuropathology maps that are significantly and strongly correlated with co-registered histological images of increased glial fibrillary acidic protein deposition. The demonstrated high spatial sensitivity in detecting reactive astrocytes at the individual level has great potential to significantly impact neuroimaging studies in diseases, injury, repair, and aging.

Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

Human prion diseases are fatal neurodegenerative disorders that may have prolonged asymptomatic incubation periods. However, the underlying mechanism by which prions cause brain damage remains unclear. In turn, characterization of early pathological aspects would be of benefit for the diagnosis and potential treatment of these progressive neurodegenerative disorders. We investigated chemical exchange saturation transfer (CEST) MRI based on its exquisite sensitivity to cytosol protein content as a surrogate for prion disease pathology. Three groups of prion-infected mice at different stages of the disease underwent conventional magnetic resonance imaging and CEST MRI at 9.4T. For each mouse, chemical exchange contrasts were measured by applying five RF powers at various frequency offsets using magnetization transfer asymmetries. Relayed Nuclear Overhauser effects (NOE*) and amide proton transfer (APT*) were also assessed. For comparison, CEST MRI measurements were also made in healthy control mice brains. Here we show that alterations in CEST signal were detected before structural modifications or any clinical signs of prion disease. The detected CEST signal displayed different patterns at different stages of the disease indicating its potential for use as a longitudinal marker of disease progression. Highly significant correlations were found between CEST metrics and histopathological findings. A decline in NOE signal was positively correlated with abnormal prion protein deposition (R2 = 0.91) in the thalami of prion infected mice. Moreover, the NOE signal was negatively correlated with astrogliosis (R2 = 0.71) in the thalamus. No significant correlations were detected between NOE signals and spongiosis. MTR asymmetry at 3.5 ppm was also correlated with astrogliosis (R2 = 0.59), and prion protein deposition (R2 = 0.63) in thalamus. No significant changes were detected in APT* between prion-infected and control mice at all stages of the disease. Finally, MTR asymmetry between 2.8 and 3.2 ppm was correlated with prion protein deposition (R2 = 0.47) in the thalamus of prion -infected mice. To conclude, CEST MRI has potential utility as a biomarker of neurodegenerative processes in prion disease

The Effect of Different Cleaning Methods on Protein Deposition and Optical Characteristics of Orthokeratology Lenses

Orthokeratology lenses are commonly used for myopia control, especially in children. Tear lipids and proteins are immediately adsorbed when the lens is put on the cornea, and protein deposition may cause discomfort or infection. Therefore, we established an in vitro protein deposition analysis by mimicking the current cleaning methods for orthokeratology lens wearers for both short-term and long-term period. The results showed that the amounts of tear proteins accumulated daily and achieved a balance after 14 days when the lens was rubbed to clean or not. Protein deposition also affected the optical characteristics of the lens regardless of cleaning methods. Our results provided an in vitro analysis for protein deposition on the lens, and they may provide a potential effective method for developing care solutions or methods that can more effectively remove tear components from orthokeratology lenses.

Inhibiting Host Protein Deposition on Urinary Catheters Reduces Urinary Tract Infections

SummaryMicrobial adhesion to medical devices is common for hospital-acquired infections, particularly for urinary catheters. If not properly treated these infections cause complications and exacerbate antimicrobial resistance. Catheter use elicits bladder inflammation, releasing host serum-proteins, including fibrinogen, into the bladder, which deposit on the urinary catheter. Enterococcus faecalis uses fibrinogen as a scaffold to bind and persist in the bladder despite antibiotic treatments. Inhibition of fibrinogen-pathogen interaction significantly reduces infection. Here, we show deposited fibrinogen is advantageous for uropathogens, suggesting that targeting catheter protein deposition may reduce colonization creating an effective intervention. Hostprotein deposition was reduced, using liquid-infused catheters, resulting in decreased colonization on catheters, in bladders, and dissemination in vivo. Furthermore, proteomics revealed a significant decrease in deposition of host-secreted proteins on liquid-infused catheter surfaces. Our findings suggest targeting microbial binding scaffolds may be an effective antibiotic-sparing intervention for use against catheter-associated urinary tract infections and other medical device infections.

Estimating Amino Acid Requirements in Real-Time for Precision-Fed Pigs: The Challenge of Variability among Individuals

This study aimed to measure protein deposition (PD) in pigs fed with daily tailored diets where either dietary lysine (Lys) or threonine (Thr) were provided at independent levels (ignoring an ideal ratio). A total of 95 growing pigs (35 kg body weight (BW)) with electronic ear tags granting them access to automatic feeders were randomly assigned to treatments. The setup was an unbalanced 2 × 5 factorial arrangement with Lys and Thr provided at five levels (i.e., 60%, 80%, 100%, 120%, and 140% of the estimated individual requirements of Lys and Thr), resulting in 25 treatments for 21 days. The observed PD variation to Lys and Thr provisions was large, with Lys and Thr intake explaining only 11% of the variation. Cluster analysis discriminated pigs with low (167 g/d, n = 16), medium (191 g/d, n = 38), and high (213 g/d, n = 37) PD, but with a similar amino acid intake. Differences in PD were associated with differences in nutrient efficiency of utilization. Providing Lys and Thr in a factorial mode, ignoring an ideal ratio, did not decrease the variability in PD. Future research efforts should focus on identifying and investigating the sources of interindividual variability—a necessary step before final recommendations can be made for AA in precision-fed pigs.

Relationship between energy intake and growth performance and body composition in pigs selected for low backfat thickness

Genetic selection of pigs over recent decades has sought to reduce carcass fat content to meet consumer demands for lean meat in many countries (e.g.: Australia). Due to the impacts of genetic changes, it is unknown whether the carcass fat measures are still responsive to energy intake. Thus, the present experiment aimed to quantify the relationship between tissue composition and dietary energy intake in finisher pigs selected for low carcass backfat. Intact male and female pigs (n=56 for each sex; PrimegroGenetics, Corowa, NSW, Australia) were fed seven different amounts of an amino acid adequate wheat-based diet containing 14.3 MJ digestible energy (DE)/kg to provide the following daily DE intakes- 25.8, 29.0, 32.6, 35.3, 38.5, 41.5 and 44.2 (ad libitum) MJ DE/d for males, and 25.8, 28.9, 32.0, 35.6, 38.3, 40.9 and 44.5 (ad libitum) MJ DE/d for females between 60 kg and 108 kg live weight. Body composition of anaesthetised pigs was measured using the Dual Energy X-ray Absorptiometry (DXA) method when individual pigs reached 108 kg, and protein, fat and ash deposition rates were calculated. Pigs were slaughtered on the 2nd day post-DXA scan for carcass backfat measurement. The results showed that the carcass backfat thickness (standardized at 83.7 kg carcass) increased by 0.125 mm for every MJ increase in daily DE intake in male pigs (P = 0.004; R2 = 0.130), but carcass backfat of female pigs (standardized at 85.1 kg carcass) was not responsive to daily DE intake. Whole-body fat composition and fat deposition rate increased linearly (both P < 0.01) in male pigs but quadratically (both P < 0.01) in female pigs in response to DE intake. Every MJ increase of daily DE intake increased the rate of daily protein deposition by 3.8 g in intact male pigs (P < 0.001; R2 = 0.781) and by 2.5 g in female pigs (P < 0.001; R2 = 0.643). In conclusion, the selection for low backfat thickness over the last two decades has altered the response of fat deposition and backfat thickness to energy intake, particularly in female pigs. Despite this change, the linear relationship between DE intake and protein deposition rate was maintained in these modern genetics.

Metabolizable energy levels in diets with a fixed nutrient: calorie ratio for free-range broilers

The present study proposes to examine the effect of dietary levels of metabolizable energy, under a fixed nutrient:calorie ratio, on the production performance; body fat and protein deposition; and carcass characteristics of free-range broilers from 1 to 84 days of age. Nine hundred unsexed chicks were allocated to six treatments in a completely randomized design with six replicates of 25 birds each. Treatments consisted of diets with varying levels of metabolizable energy (2700, 2800, 2900, 3000, 3100 and 3200 Kcal ME/kg of diet) and a fixed proportion of nutrients relative to the energy level according to the nutritional requirements for each rearing phase. Body weight, weight gain, feed intake, feed conversion, production viability, metabolizable energy intake, protein intake, lysine intake, body fat deposition, body protein deposition and carcass characteristics were evaluated. Data were subjected to analysis of variance and, later, to regression analysis. Increasing levels of metabolizable energy, coupled with a fixed nutrient:calorie ratio, reduced feed intake, increased body weight and weight gain, improved feed conversion and did not affect carcass characteristics. In conclusion, adjusting the nutrient supply according to the dietary energy level improves production performance by improving feed conversion, ensuring adequate nutrient intake and preserving fat and protein deposition in the carcass when the metabolizable energy level is raised up to 3200 Kcal/kg in all rearing stages.

Interpreting Immunoregulation in Lung Fibrosis: A New Branch of the Immune Model

Immunostimulation is recognized as an important contribution in lung fibrosis in some animal models and patient subsets. With this review, we illustrate an additional scenario covering the possible implication of immunoregulation during fibrogenesis. Available animal and human data indicate that pulmonary fibrosis also includes diverse and discrete immunoregulating populations comprising regulatory lymphocytes (T and B regs) and myeloid cells (immunosuppressive macrophages and myeloid-derived suppressive cells; MDSC). They are initially recruited to limit the establishment of deleterious inflammation but participate in the development of lung fibrosis by producing immunoregulatory mediators (mainly TGF-β1 and IL-10) that directly or indirectly stimulate fibroblasts and matrix protein deposition. The existence of this silent immunoregulatory environment sustains an alternative mechanism of fibrosis that explains why in some conditions neither pro-inflammatory cytokine deficiency nor steroid and immunosuppressive therapies limit lung fibrosis. Therefore, the persistent presence of immunoregulation is an important parameter to consider for refining therapeutical strategies in lung fibrotic disorders under non-immunostimulatory conditions.

The Dynamic Conversion of Dietary Protein and Amino Acids into Chicken-Meat Protein

This review considers the conversion of dietary protein and amino acids into chicken-meat protein and seeks to identify strategies whereby this transition may be enhanced. Viable alternatives to soybean meal would be advantageous but the increasing availability of non-bound amino acids is providing the opportunity to develop reduced-crude protein (CP) diets, to promote the sustainability of the chicken-meat industry and is the focus of this review. Digestion of protein and intestinal uptakes of amino acids is critical to broiler growth performance. However, the transition of amino acids across enterocytes of the gut mucosa is complicated by their entry into either anabolic or catabolic pathways, which reduces their post-enteral availability. Both amino acids and glucose are catabolised in enterocytes to meet the energy needs of the gut. Therefore, starch and protein digestive dynamics and the possible manipulation of this ‘catabolic ratio’ assume importance. Finally, net deposition of protein in skeletal muscle is governed by the synchronised availability of amino acids and glucose at sites of protein deposition. There is a real need for more fundamental and applied research targeting areas where our knowledge is lacking relative to other animal species to enhance the conversion of dietary protein and amino acids into chicken-meat protein.