Structural Basis for the Calmodulin-Mediated Activation of eEF-2K

Translation is a highly energy consumptive process tightly regulated for optimal protein quality and adaptation to energy and nutrient availability. A key facilitator of this process is the α-kinase eEF-2K that specifically phosphorylates the GTP-dependent translocase eEF-2, thereby reducing its affinity for the ribosome and suppressing the elongation phase of protein synthesis. eEF-2K activation requires calmodulin binding and auto-phosphorylation at the primary stimulatory site, T348. Biochemical studies have predicted that calmodulin activates eEF-2K through a unique allosteric process mechanistically distinct from other calmodulin-dependent kinases. Here we resolve the atomic details of this mechanism through a 2.3 Å crystal structure of the heterodimeric complex of calmodulin with the functional core of eEF-2K (eEF-2KTR). This structure, which represents the activated T348-phosphorylated state of eEF-2KTR, highlights how through an intimate association with the calmodulin C-lobe, the kinase creates a spine that extends from its N-terminal calmodulin-targeting motif through a conserved regulatory element to its active site. Modification of key spine residues has deleterious functional consequences.

Amino acid profile and scores of some selected traditional diets commonly consumed in northwest zone, Nigeria

Background and aims: Amino acids composition of local and regional dietary proteins determines the protein quality. The study was aimed at evaluating amino acid profiles of some selected traditional diets commonly consumed in Jigawa (JG), Kano (KN) and Katsina (KT) States, Northwest Zone-Nigeria. Methods: The selected prepared diets (four per state) include; JG Tuwon masara using white maize served with Kuka soup (JG TMW SWKS), JG Tuwon masara using yellow maize served with Kuka soup (JG TMY SWKS), JG Danwake served with groundnut oil and pepper (JG Danwake SWGOP), JG Moimoi, KN Tuwon masara using white maize served with Kuka soup (KN TMW SWKS), KN Tuwon masara using yellow maize served with Kuka soup (KN TMY SWKS), KN rice and beans served with groundnut oil and pepper (KN Rice and Beans SWGOP), KN Danwake served with groundnut oil and pepper (KN Danwake SWGOP), KT Tuwon masara using white maize served with Kuka soup (KT TMW SWKS), KT Tuwon masara using yellow maize served with Kuka soup (KT TMY SWKS), KT Danwake served with groundnut oil and pepper (KT Danwake SWGOP) and KT Dambu. The preparations were dried and grounded into powdered form and analyzed using standard methods. Results: The amino acid profile of the diets consumed in the three states show higher content of total non-essential amino acids (NEAA) compared with essential amino acids (EAA). The amino acid score of the prepared diets though higher than the standard amino acid score by WHO/FAO/UNU (2007), may support the normal growth of all age groups except lysine. The limiting amino acid score was found to be either lysine or SAA (cysteine + methionine) in all the 3 states’ diets. Histidine was found to have the highest score in all the diets except in JG Moimoi and KN Danwake served with groundnut oil and pepper (SWGOP) respectively. The low levels of lysine and SAA in some of the diets may be due to low contents of these amino acids in the ingredients used. Conclusion: This study showed that, the amino acid score of the prepared diets though higher than the standard amino acid score established by WHO/FAO/UNU may support the normal growth of infants, children as well as adults except lysine. Keywords: traditional diets, amino acids, amino acid profile, amino acid score.

Altered Expression of TRIM Proteins-Inimical Outcome and Inimitable Oncogenic Function in Breast Cancer with Diverse Carcinogenic Hallmarks

Deregulation of ubiquitin-mediated degradation of oncogene products or tumor suppressors appears to be implicated in the genesis of carcinomas, according to new clinical findings. Conferring to recent research, some members of the tripartite motif (TRIM) proteins (a subfamily of the RING type E3 ubiquitin ligases) act as significant carcinogenesis regulators. Intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy, and carcinogenesis are all regulated by TRIM family proteins, the majority of which have E3 ubiquitin ligase activity. The expression of TRIMs in tumors is likely to be related to the formation and/or progression of the disease, and TRIM expression could be used to predict cancer prognosis. Breast cancer is the most common malignancy in women and also the leading cause of death. TRIM family proteins have unique, vital activities, and their dysregulation, such as TRIM 21, promotes breast cancer, according to growing evidence. Many TRIM proteins have been identified as important cancer biomarkers, with decreased or elevated levels of expression. TRIM29 functions as a hypoxia-induced tumor suppressor gene, revealing a new molecular mechanism for ATM-dependent breast cancer suppression. In breast cancer cells, the TRIM28-TWIST1-EMT axis exists, and TRIM28 enhances breast cancer metastasis by stabilizing TWIST1 and thereby increasing epithelial-to-mesenchymal transition. Interestingly, many TRIM proteins are involved in the control of p53, and many TRIM proteins are likewise regulated by p53, according to current research. Furthermore, TRIMs linked to specific tumors may aid in the creation of innovative TRIM-targeted cancer treatments. This review focuses on TRIM proteins that are involved in tumor development, progression, and clinical significance in breast cancer.

METHOD OF INCREASING MEAT PRODUCTIVITY AND ENVIRONMENTAL SAFETY OF BROILER MEAT BY FEEDING ADSORBENT AND ANTIOXIDANT

In recent years, the use of adsorbent and antioxidant preparations in the formulation of feed with a high content of heavy metals is a promising direction in the industrial production of broiler meat. The study aims to study the consumer and hygienic properties of broiler meat when including adsorbent Ferrotsin and antioxidant Selenopyran in diets with high heavy metals and aflatoxin B 1 content. The authors experimentally established the necessity of containing the adsorbent Ferrotsin in the dose of 300 g/t feed and the antioxidant Selenopyran in the quantity of 300 g/t feed into the composition of mixed fodder with excessive concentration of heavy metals. This inclusion of adsorbents and antioxidants in the compound feed composition is necessary to increase the nutritional properties and protective properties of poultry meat. Group 3 broiler chickens significantly exceeded (P < 0.05) the control counterparts by 18.88 % by weight of half-gutted carcass and 18.26 % by weight of the gutted carcass. Also, broiler chickens of the 3rd experimental group exceeded the content of solids in the thoracic and thigh muscles by 1,40 and 0,60, and protein by 0,67 % and 0,67 %. Group 3 broilers significantly (P < 0.05) exceeded the control in protein quality index (PQI) of meat by 18.86 %. In broilers of experimental group 3, there was a reliable (P < 0.05) decrease in the level of zinc by 3.07, cadmium by 2.25 and lead by 3.24 times in the samples of breast muscle relative to the control counterparts. The highest final score was obtained by boiled white poultry meat of the 3rd experimental group. This sample of meat reliably (P < 0.05) exceeded the total sum of organoleptic parameters of the control sample by 0.81 points. In broilers of experimental group 3 in examples of breast, thigh muscles and meat homogenate, the level of selenium was significantly higher than in control due to the presence of this substance in Selenopyran.

METHOD TO IMPROVE THE CONSUMER QUALITY AND ENVIRONMENTAL SAFETY OF QUAIL MEAT DURING DENITRIFICATION

Phospholipids are a kind of “solvents” of cholesterol and show a hepatoprotective effect. Also, phospholipids regulate fat and carbohydrate metabolism, improve the functional activity of the liver and its detoxification function. The study aims to study the impact of different doses of phos-pholipid lecithin preparation on economically useful indicators, meat productivity, nutritional value and environmental safety of quail meat at a subtoxic dose of nitrates in their compound feed. This article presents materials that indicate the feasibility of introducing phospholipid preparation of lecithin in the amount of 1.0 % by weight of feed under the presence of a sub-toxic dose of nitrates in the compound feed quail grown for meat. This introduction of phospholipid preparation of lecithin increases the preservation of livestock, body weight gain and reduces the cost of feed per unit gain. Poultry of the 2nd experimental group had an advantage over their control counterparts in preservation rate by 4.0 % and average daily growth by 9.50 % (P<0.05). The authors observed the benefit over the control samples in the concentration of dry substances by 0.98 and 0.99 %, protein by 0.98 and 0.97 % (P<0.05) in the examples of thigh and breast muscles of the poultry of the 2nd experimental group. The value of the protein-quality index (PQI) was higher by 13,55 % (P<0,05) in the samples of white meat from poultry carcasses of the 2nd experimental group as compared with the control counterparts. Also, the examples of poultry meat of the 2nd experimental group had better sanitary and hygienic characteristics. For instance, they had 36.83 % lower nitrate content (P<0.05) and 40.91 % lower nitrites content (P<0.05). This content indicates high denitrifying properties of phospholipid lecithin.

Hexosamine pathway activation improves memory but does not extend lifespan in mice.

Glucosamine feeding and genetic activation of the hexosamine biosynthetic pathway (HBP) have been linked to improved protein quality control and lifespan extension in various species. Thus, there is considerable interest in the potential health benefits of dietary supplementation with glucosamine or other HBP metabolites in people. The HBP is a sensor for energy availability and its activation has been implicated in tumor progression and diabetes in higher organisms. As the activation of the HBP has been linked to longevity in lower animals, it is imperative to explore the long-term effects of chronic HBP activation in mammals, which has not been examined so far. To address this issue, we activated the HBP in mice both genetically and through metabolite supplementation, and evaluated metabolism, memory, and survival. GlcNAc supplementation in the drinking water had no adverse effect on weight gain in males but increased weight in young female mice. Glucose or insulin tolerance were not affected up to 20 months of age. Of note, we observed improved memory in the Morris water maze in young male mice supplemented with GlcNAc. Survival was not changed by GlcNAc supplementation. To assess the effects of genetic HBP activation we overexpressed the key enzyme GFAT1 as well as a constitutively activated mutant form in all mouse tissues. We detected elevated UDP-GlcNAc levels in mouse brains, but did not find any effects on behavior, memory, or survival. Together, while dietary GlcNAc supplementation did not extend survival in mice, it positively affected memory and is generally well tolerated.

Effects of Microwaves, Ultrasonication, and Thermosonication on the Secondary Structure and Digestibility of Bovine Milk Protein

Cow’s milk is considered an excellent protein source. However, the digestibility of milk proteins needs to be improved. This study aimed to evaluate the relationship between the functional properties of milk proteins and their structure upon microwave, ultrasound, and thermosonication treatments. The protein content, digestibility, and secondary-structure changes of milk proteins were determined. The results demonstrated that almost 35% of the proteins in the untreated samples had a α-helix structure and approximately 29% a β-sheet and turns structure. Regarding the untreated samples, the three treatments increased the α-helices and correspondingly decreased the β-sheets and turns. Moreover, the highest milk protein digestibility was observed for the ultrasound-treated samples (90.20–94.41%), followed by the microwave-treated samples (72.56–93.4%), whereas thermosonication resulted in a lower digestibility (68.76–78.81%). The milk protein content was reduced as the microwave processing time and the temperature increased. The final milk protein available in the sample was lower when microwave processing was conducted at 75 °C and 90 °C compared to 60 °C, whereas the ultrasound treatment significantly improved the protein content, and no particular trend was observed for the thermosonicated samples. Thus, ultrasound processing shows a potential application in improving the protein quality of cow’s milk.

A Retrotranslocation Assay That Predicts Defective VCP/p97-Mediated Trafficking of a Retroviral Signal Peptide

Endoplasmic reticulum-associated degradation (ERAD) is a form of cellular protein quality control that is manipulated by viruses, including the betaretrovirus, mouse mammary tumor virus (MMTV). MMTV-encoded signal peptide (SP) has been shown to interact with an essential ERAD factor, VCP/p97 ATPase, to mediate its extraction from the ER membrane, also known as retrotranslocation, for RNA binding and nuclear function.