Determination of the nutritional value, protein quality and safety of krill protein concentrate isolated using an isolelectric solubilization/precipitation technique

Despite its abundance and nutritional value, krill has not been widely utilized for human consumption due to the lack of proper technology for protein recovery. The study objectives were to isolate krill protein concentrate (KPC) and to determine the nutritional value, health benefits, and safety of KPC for human consumption. Proximate analysis indicated KPC on a dry basis is composed of ∼78% protein and ∼8% fat of which ∼27% are omega-3 polyunsaturated fatty acids (o-3 PUFAs). The amino acid composition of KPC indicated that all nine essential amino acids were present in amounts that met the requirements for adult humans assuming sufficient protein was consumed. Protein quality measurements were determined by feeding KPC or casein diets to growing female rats. In regards to bioavailability, KPC was equal to that of casein in digestibility, protein digestibility corrected for amino acid score (PDCAAS), and protein efficiency ratio (PER). In terms of safety, there were no differences in the absolute weights of the major organs except for the kidneys. Kidney weights and total mineral content were higher ( P\u3c0.001) in rats fed the casein compared to the KPC diet. Based on the nutritional and safety analysis, KPC appears to be a promising high quality protein source for human consumption with the advantage of being a rich source of o-3 PUFAs

Influencing Kidney Health and Function in Young Female Rats Through Dietary Alterations

The occurrence of kidney failure in the US has drastically increased over the past decade. The decline in health associated with chronic kidney disease can be prevented if detected early in disease progression. However, substantial damage has often occurred before detection of renal disease is possible. Therefore, disease prevention (as in all diseases) is the optimal treatment.;In regards to the kidneys, dietary habits can have a profound influence on the function and overall kidney health. This is particularly evident in female rats due to their susceptibility to diet induced renal disease. In female rats, the initiation of chronic kidney disease typically involves nephrocalcinosis (NC). NC is characterized by increased renal calcium (Ca) content, and involves the pathological deposition of mineral deposits in renal tissue. Fluctuations in dietary Ca and phosphorus (P) content are the major consideration in managing NC. However, other dietary components can mediate the development and severity of this disease in rats.;Based on our study results, the source of dietary protein and lipid can influence the development of NC in female rats. Our initial study compared the nutritional quality of a novel protein source derived from krill to the milk protein, casein. Rats fed krill protein concentrate (KPC) had lower kidney weights (P\u3c0.001), lower kidney Ca content (P =0.002), and lower incidence of renal damage than rats fed casein based diets. These changes occurred in the absence of fluctuating urinary mineral content, which is a major cause of NC. Further analysis showed that KPC contained residual krill oil, which is rich in omega-3 polyunsaturated fatty acids (o-3 PUFAs). The next study involved isolation and characterization of krill oil. Krill oil is a unique lipid with high (\u3e65%) polar lipid content including phospholipids, whereas other dietary sources of o-3 PUFAs were found to be predominately triacyglyceride. In the final study, the characterized oils were added to casein-based diets and fed to female rats to determine if lipid content influences the development of NC. While rats fed KPC appeared to be protected from NC, rats fed the high fat diet as krill oil were the only rats who developed NC. The high inclusion of krill oil resulted in elevated dietary P content due to its high phospholipid content. Aside from NC, the renal fatty acid content was influenced by the diet and lead to an apparent decrease in urinary prostaglandin production in all rats consuming the long-chain o-3 polyunsaturated fatty acids (o-3 LCPUFAs) eicosapentaenoic (EPA) and docosahexaenoic acid (DHA). The consumption of the different o-3 PUFA sources also resulted in reduced activity of the proinflammatory transcription factor NFkappaB, and expression of the proinflammatory cyclooxygenase -2 (COX-II) and transforming growth factor-beta (TGF-beta). Despite these observed results, no differences were noted in serum measures of kidney function. We concluded that changing the source of dietary protein and lipid can mediate renal health in female rats. It appears that o-3 PUFAs do not influence the nephrocalcigenic nature of casein. However, providing dietary o-3 PUFAs resulted in decreased renal inflammatory activity as compared to rats fed corn oil. This supports the benefit of o-3 PUFA supplementation in reducing the onset of diseases caused by inflammatory processes, and suggests that different dietary sources of o- PUFAs vary in regards to biological activity

Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA) consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d) were randomly assigned (n = 10/group) to be fed a high fat 12% (wt) diet consisting of either corn oil (CO) or n-3 PUFA rich flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs) and thromoboxanes (TXBs) using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR). Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should provide high digestibility and efficient tissue incorporation with the least tissue lipid peroxidation, TO and SO appeared to be the most beneficial of the n-3 PUFAs sources evaluated in this study

Mouse Models of Acute Kidney Injury

Acute Kidney Injury (AKI) is a poor prognosis in hospitalized patients that is associated with high degree of mortality. AKI is also a major risk factor for development of chronic kidney disease. Despite these serious complications associated with AKI there has not been a great amount of progress made over the last half-century. Here we have outlined and provided details on variety of mouse models of AKI. Some of the mouse models of AKI are renal pedicle clamping (ischemia reperfusion injury), Cisplatin induced nephrotoxicity, sepsis (LPS, cecal slurry, and cecal ligation and puncture), folic acid, and rhabdomyolysis. In this chapter we describe in detail the protocols that are used in our laboratories

Diet Significantly Influences the Immunopathology and Severity of Kidney Injury in Male C57Bl/6J Mice in a Model Dependent Manner

Diet is a leading causative risk factor for morbidity and mortality worldwide, yet it is rarely considered in the design of preclinical animal studies. Several of the nutritional inadequacies reported in Americans have been shown to be detrimental to kidney health; however, the mechanisms responsible are unclear and have been largely attributed to the development of diabetes or hypertension. Here, we set out to determine whether diet influences the susceptibility to kidney injury in male C57Bl/6 mice. Mice were fed a standard chow diet, a commercially available “Western” diet (WD), or a novel Americanized diet (AD) for 12 weeks prior to the induction of kidney injury using the folic acid nephropathy (FAN) or unilateral renal ischemia reperfusion injury (uIRI) models. In FAN, the mice that were fed the WD and AD had worse histological evidence of tissue injury and greater renal expression of genes associated with nephrotoxicity and monocyte infiltration as compared to mice fed chow. Mice fed the AD developed more severe renal hypertrophy following FAN, and gene expression data suggest the mechanism for FAN differed among the diets. Meanwhile, mice fed the WD had the greatest circulating interleukin-6 concentrations. In uIRI, no difference was observed in renal tissue injury between the diets; however, mice fed the WD and AD displayed evidence of suppressed inflammatory response. Taken together, our data support the hypothesis that diet directly impacts the severity and pathophysiology of kidney disease and is a critical experimental variable that needs to be considered in mechanistic preclinical animal studies

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Cracks, microcracks and fracture in polymer structures: Formation, detection, autonomic repair

The first author would like to acknowledge the financial support from the European Union under the FP7 COFUND Marie Curie Action. N.M.P. is supported by the European Research Council (ERC StG Ideas 2011 n. 279985 BIHSNAM, ERC PoC 2015 n. 693670 SILKENE), and by the EU under the FET Graphene Flagship (WP 14 “Polymer nano-composites” n. 696656)

\u3ci\u3eEts\u3c/i\u3e in the Kidney—Unraveling the Molecular Mechanism Underlying Renal Damage in Salt-Sensitive Hypertension

Originally identified as a homolog of a viral oncogene (v-ets), the ETS family of transcription factors consists of over 25 proteins involved in regulating several biologic processes at the transcriptional level. The ETS DNA binding domain consists of a winged helix conformation and binds the DNA sequences 5′-GGA(A/T)-3′ with varying affinity depending on ETS phosphorylation status, epigenetic modifications, and various protein-protein interactions

Recharacterizing the Murine Chronic Angiotensin II Infusion Model of Cardiovascular and Renal Injury

The chronic angiotensin II (AngII) infusion model is one of the most commonly used to study cardiovascular and kidney injury. However, the dosages of AngII used to induce cardiovascular or renal injury vary significantly in the literature. Therefore, we set out to determine the dosages of angiotensin II needed to produce renal injury and hypertension in mice. All experiments were performed in accordance with protocols approved by the Liberty University IACUC and conform to the FASEB standards for the use of animals in research and education. Male C57Bl/6J mice (~20 grams body weight) were purchased from The Jackson Laboratory and acclimated to our environment for one week. Mice were then assigned to receive 0, 400, 800, or 1200 ng AngII/kg BW*min for four weeks via osmotic minipumps (subcutaneous). Blood pressure (tail-cuff) was recorded each week of the study. At baseline, 2 and 4 weeks, renal blood flow and renal hemodynamics were estimated using contrast-enhanced ultrasonography. After 4 weeks, mice were placed in metabolic cages for the quantification of water intake and urinary output. Urine was stored for determination of albumin concentration using a commercially available ELISA. Mice were then euthanized and kidney tissues collected to measure the mRNA expression of several genes involved in the intrarenal renin-angiotensin system (RAS) (renin, angiotensinogen, angiotensin converting enzyme (ACE), ACE2, angiotensin II-receptor 1a (AT1a), and AT1b receptor) and tissue inflammation and remodeling [CCL5, α-smooth muscle actin (αSMA), collagen 1, collagen 3, and tumor growth factor β (TGFβ)]. All data were analyzed using general linear models in SPSS. Mice administered the 800 dose had the greatest and most consistent increase in systolic blood pressure (147 ± 8mmHg) as compared to mice administered the saline (114 ± 9, P=0.004) and the 400 dose (121 ± 11mmHg, P=0.01). Mice administered the 1200 dose tended (P=0.08) to have a greater total renal blood flow throughout the study, with a significant increase (P=0.047) in cortical blood flow as compared to mice administered saline. Despite the modest changes in estimated renal blood flow, mice administered the 800 and 1200 doses of AngII had similar, yet significantly greater (P≤0.001) water intake and urinary output as compared to mice treated with saline or the 400 dose. Similarly, mice with the 800 and 1200 doses had significantly greater evidence of tissue damage evident by increased albuminuria (P≤0.05) and increased renal gene expression of CCL5, TGFβ, collagen 1, and collagen 3. There was also an effect on the intrarenal RAS, with mice administered the 800 and 1200 doses having significant (