Identifying new molecular players in extracellular proteostasis

2021 ◽  
Author(s):  
Sandeep Satapathy ◽  
Mark R. Wilson
Keyword(s):  
Protein Synthesis ◽  
Tissue Damage ◽  
Future Research ◽  
New Members ◽  
Infection And Inflammation ◽  
Experimental Strategies

Proteostasis refers to a delicately tuned balance between the processes of protein synthesis, folding, localization, and the degradation of proteins found inside and outside cells. Our understanding of extracellular proteostasis is rather limited and largely restricted to knowledge of 11 currently established extracellular chaperones (ECs). This review will briefly outline what is known of the established ECs, before moving on to discuss experimental strategies used to identify new members of this growing family, and an examination of a group of putative new ECs identified using one of these approaches. An observation that emerges from an analysis of the expanding number of ECs is that all of these proteins are multifunctional. Strikingly, the armory of activities each possess uniquely suit them as a group to act together at sites of tissue damage, infection, and inflammation to restore homeostasis. Lastly, we highlight outstanding questions to guide future research in this field.

scholarly journals Knowledge Gaps in Understanding the Etiology of Anemia in Indonesian Adolescents

2021 ◽  
Vol 42 (1_suppl) ◽  
pp. S39-S58
Author(s):  
Kesso Gabrielle van Zutphen ◽  
Klaus Kraemer ◽  
Alida Melse-Boonstra
Keyword(s):  
Current Knowledge ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
Population Group ◽  
Future Research ◽  
Folic Acid Deficiency ◽  
Knowledge Gaps ◽  
Local Conditions ◽  
Etiological Factors ◽  
Infection And Inflammation

Background: Anemia is a public health problem among adolescents in Indonesia. Strategies to prevent or treat anemia should be tailored to local conditions, taking into account its specific etiology and prevalence in a given setting and population group. Objective: This review aims to (1) identify and synthesize the current knowledge on the etiology of anemia among adolescents in Indonesia, (2) reveal knowledge gaps in this area, and (3) suggest directions for future research and programmatic work. Methods: We systematically searched PubMed, Web of Science, Scopus, Medline, and WorldCat databases for peer-reviewed journal articles to identify which etiological factors were related to anemia among Indonesian adolescents. Research papers were reviewed and included in the review according to inclusion criteria. Results: Of 13 studies, 8 showed that anemia was associated with iron deficiency; 4 are suggestive of vitamin A deficiency; and 2 of folic acid deficiency. Five studies underscore different etiological determinants for anemia, such as malaria, protein and energy malnutrition, vitamin B2 deficiency, calcium, and vitamin C deficiency. Based on these findings, we developed a framework on knowledge gaps on the etiology of anemia among adolescents in Indonesia, divided in 3 levels of knowledge: (1) significant knowledge gaps, (2) knowledge gaps, and (3) established knowledge. Conclusions: The knowledge gaps around the etiology of anemia among Indonesian adolescents are significant. Our framework emphasizes the need for further research across all etiological factors, namely inadequate nutritional intake and absorption, genetic hemoglobin disorders, infection and inflammation, and menstrual disorders.

204 Awardee Talk: Recent Advances in Protein Nutrition in Horses

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 109-109
Author(s):  
Kristine Urschel
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Protein Digestibility ◽  
Future Research ◽  
Amino Acid Supplementation ◽  
Protein Nutrition ◽  
Active Research

Abstract Protein has been recognized as an essential nutrient for animals for well over 100 years. Protein plays many important structural and metabolic roles, and some of its component amino acids have additional functions, including as regulatory molecules, as energy substrates and in the synthesis of other non-protein molecules. Skeletal muscle makes up approximately 50% of body weight in horses, with protein being the major non-water component. As an athletic species, the development and maintenance of muscle mass is of the utmost importance in horses. Because muscle mass is largely determined by the balance of rates of muscle protein synthesis and breakdown, understanding how these pathways are regulated and influenced by dietary protein and amino acid provision is essential. Historically, much research regarding protein nutrition in horses has focused on the protein digestibility of different feed ingredients, and the adequacy of different protein sources in supporting the growth and maintenance of horses. This presentation will focus on some of the current areas of active research relating to protein nutrition in horses: the activation of the signaling pathways that regulate muscle protein synthesis, amino acid supplementation in athletic horses, protein metabolism in aged and horses and those with insulin dysregulation, and amino acid and protein nutrition in predominantly forage-fed horses. There are many exciting opportunities for future research in the area of protein and amino acid nutrition in horses across the lifespan.

scholarly journals 3D quantum Hall effects and nonlinear Hall effect

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Li ◽  
C. M. Wang ◽  
Z. Z. Du ◽  
Fang Qin ◽  
Hai-Zhou Lu ◽  
...  
Keyword(s):  
Hall Effect ◽  
Condensed Matter ◽  
Quantum Hall ◽  
Future Research ◽  
Research Directions ◽  
New Members ◽  
Quantum Hall Effects ◽  
Open Questions ◽  
Hall Effects ◽  
Future Research Directions

AbstractThe classical and quantum Hall effects are important subjects in condensed matter physics. The emergent 3D quantum Hall effects and nonlinear Hall effect have attracted considerable interest recently, with the former elevating the quantum Hall effect to a higher dimension and the latter extending the Hall effect to higher-order responses. In this perspective, we briefly introduce these two new members of the Hall family and discuss the open questions and future research directions.

scholarly journals “What the Hell Is This, and Who the Hell Are You?” Role and Identity Negotiation in Research-Practice Partnerships

AERA Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 233285841984959 ◽  
Author(s):  
Caitlin C. Farrell ◽  
Christopher Harrison ◽  
Cynthia E. Coburn
Keyword(s):  
School District ◽  
Identity Negotiation ◽  
Future Research ◽  
Research Practice ◽  
District Leaders ◽  
New Members ◽  
Role Negotiation ◽  
School District Leaders ◽  
Collaborative Efforts

In research-practice partnerships (RPPs), the line between researcher and practitioner can be blurred, and the roles for everyone involved may be unclear. Yet little is known about how these roles are negotiated and with what consequences for collaborative efforts. Guided by organizational theory, we share findings from a multiyear case study of one RPP, drawing on observations of partnership leadership meetings and interviews with school district leaders and partners. Role negotiation occurred in more than one third of leadership meetings, as evidenced by identity-referencing discourse. When roles were unclear, collaborative efforts stalled; once partners renegotiated their roles, it changed how they engaged in the work together. Several forces contributed to these dynamics, including the partner’s ambitious yet ambiguous identity and the introduction of new members to the group. This study offers implications for those engaged in partnership work and provides a foundation for future research regarding role negotiation in RPPs.

scholarly journals Determining Ideal Balance Among Branched-Chain Amino Acids (BCAA) as a Proof of Concept Study in Healthy Children

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1068-1068
Author(s):  
Haneen Saleemani ◽  
Rajavel Elango ◽  
Gabriella Horvath ◽  
Sylvia Stockler
Keyword(s):  
Protein Synthesis ◽  
Future Research ◽  
Acid Oxidation ◽  
P Value ◽  
Healthy Children ◽  
Proof Of Concept ◽  
Body Protein ◽  
Wide Range ◽  
Medical Foods ◽  
Total Body

Abstract Objectives Medical foods for children with in-born errors of metabolism (propionic academia, PROP) are formulated with imbalanced mixture of the BCAA (high leucine, to minimal or no valine and isoleucine), and therefore their use is controversial. The objective of the current study was to determine an ideal BCAA ratio at which total body protein synthesis is optimized in healthy children using the indicator amino acid oxidation (IAAO) method. Methods The study design was based on the oxidation of the stable isotope L-[1–,13C] phenylalanine to ,13CO2 to compare protein synthesis among seven different BCAA ratios. Leucine intake was gradually reduced from current high doses in medical foods; isoleucine and valine were kept constant. This study was done as a proof of concept in healthy children, to allow characterization of the metabolic responses to wide range of leucine test intakes, to help design narrow BCAA ratio range to test in children with PROP. Results A total of 8 healthy children were studied, completing 42 study days. ANOVA showed significant differences in F13CO2 with different BCAA ratios; P value <0.001. A BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0) was associated with the highest F13CO2 compared to other ratios (p value <0.001), indicating low total body protein synthesis. By reducing leucine intake, with BCAA ratio between (1: 0.26: 0.28 to 1:0.35:0.4) protein synthesis was optimized. Conclusions Using the IAAO method in healthy children, we tested for the first time the effect of different BCAA ratios on protein synthesis. Results from this study confirmed that the BCAA ratio of (leucine: Isoleucine: Valine = 1:0:0), which is similar to the ratio in medical foods, limited total body protein synthesis. Furthermore, a balanced BCAA ratio that optimized protein synthesis was found to be between (1: 0.26: 0.28) and (1: 0.35:0.4). Thus, we propose reformulating the BCAA mixture in medical foods, by reducing leucine content by 50%. Future research in children with PROP with our proposed BCAA ratio is necessary to confirm improved patient growth outcomes. Funding Sources Faculty of Applied Medical Sciences, Department of Clinical Nutrition, King Abdulaziz University and BC Children's Hospital Research Institute.

scholarly journals Medicinal Plants for the Treatment of Local Tissue Damage Induced by Snake Venoms: An Overview from Traditional Use to Pharmacological Evidence

2017 ◽  
Vol 2017 ◽  
pp. 1-52 ◽  
Author(s):  
Juliana Félix-Silva ◽  
Arnóbio Antônio Silva-Junior ◽  
Silvana Maria Zucolotto ◽  
Matheus de Freitas Fernandes-Pedrosa
Keyword(s):  
Medicinal Plants ◽  
Tissue Damage ◽  
Herbal Medicines ◽  
Specific Treatment ◽  
Future Research ◽  
Snake Venoms ◽  
Local Effects ◽  
Traditional Use ◽  
Permanent Disability ◽  
Local Tissue

Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage.

scholarly journals Dysregulation of skeletal muscle protein metabolism by alcohol

2015 ◽  
Vol 308 (9) ◽  
pp. E699-E712 ◽  
Author(s):  
Jennifer L. Steiner ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Interactions ◽  
Contractile Function ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Developed Countries ◽  
Acute Intoxication ◽  
Future Research ◽  
Skeletal Muscle Protein

Alcohol abuse, either by acute intoxication or prolonged excessive consumption, leads to pathological changes in many organs and tissues including skeletal muscle. As muscle protein serves not only a contractile function but also as a metabolic reserve for amino acids, which are used to support the energy needs of other tissues, its content is tightly regulated and dynamic. This review focuses on the etiology by which alcohol perturbs skeletal muscle protein balance and thereby over time produces muscle wasting and weakness. The preponderance of data suggest that alcohol primarily impairs global protein synthesis, under basal conditions as well as in response to several anabolic stimuli including growth factors, nutrients, and muscle contraction. This inhibitory effect of alcohol is mediated, at least in part, by a reduction in mTOR kinase activity via a mechanism that remains poorly defined but likely involves altered protein-protein interactions within mTOR complex 1. Furthermore, alcohol can exacerbate the decrement in mTOR and/or muscle protein synthesis present in other catabolic states. In contrast, alcohol-induced changes in muscle protein degradation, either global or via specific modulation of the ubiquitin-proteasome or autophagy pathways, are relatively inconsistent and may be model dependent. Herein, changes produced by acute intoxication versus chronic ingestion are contrasted in relation to skeletal muscle metabolism, and limitations as well as opportunities for future research are discussed. As the proportion of more economically developed countries ages and chronic illness becomes more prevalent, a better understanding of the etiology of biomedical consequences of alcohol use disorders is warranted.

Induced metabolic sequelae of tularemia in the rat: correlation with tissue damage

1975 ◽  
Vol 229 (2) ◽  
pp. 479-483 ◽  
Author(s):  
MC Powanda ◽  
GL Cockerell ◽  
JB Moe ◽  
FB Abeles ◽  
RS Pekarek ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Serum Protein ◽  
Liver Damage ◽  
Tissue Damage ◽  
Zinc Concentration ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Schu S4

Serum and liver zinc concentration, amino acid uptake by liver, seromucoid content, and alpha2-macrofetoprotein production were measured in vaccinated as well as nonimmune rats exposed to either virulent (SCHU S4) or attenuated (LVS) strains of Francisella tularensi. It appears that liver damage (pyogranulomatous lesions) must occur before there is any alteration in the above variables. The presence of bacteria in the liver is not of itself sufficient to lead to the onset of systemic, induced metabolic sequelae (IMS). The occurrence of zinc redistribution in all instances of increased serum protein synthesis may imply a necessary relationship between these two sequelae. Amino acid redistribution does not appear to be linked to serum protein synthesis. An endogenous mediator of systemic IMS can be detected in tularemic rats by injection of the serum of these animals into healthy recipients. The occurrence of zinc redistribution and increased serum protein synthesis in some groups of rats in the absence of amino acids uptake by liver, as well as the apparent differential dose responsiveness of these responses, are suggestive of a multiplicity of endogenous mediators.

scholarly journals Serpin functions in host-pathogen interactions

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4557 ◽  
Author(s):  
Jialing Bao ◽  
Guoqing Pan ◽  
Mortimer Poncz ◽  
Junhong Wei ◽  
Maoshuang Ran ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Cysteine Proteases ◽  
Future Research ◽  
Host Pathogen Interactions ◽  
Defense Proteins ◽  
Pathogenic Factors ◽  
Therapeutic Value ◽  
Host Pathogen ◽  
Infection And Inflammation ◽  
Novel Target

Serpins are a broadly distributed superfamily of protease inhibitors that are present in all kingdoms of life. The acronym, serpin, is derived from their function as potentserineproteasesinhibitors. Early studies of serpins focused on their functions in haemostasis since modulating serine proteases activities are essential for coagulation. Additional research has revealed that serpins function in infection and inflammation, by modulating serine and cysteine proteases activities. The aim of this review is to summarize the accumulating findings and current understanding of the functions of serpins in host-pathogen interactions, serving as host defense proteins as well as pathogenic factors. We also discuss the potential crosstalk between host and pathogen serpins. We anticipate that future research will elucidate the therapeutic value of this novel target.

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