Mouse Organ-Specific Proteins and Functions

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them—such as alanine transaminase, aspartate transaminase, and troponins—in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Download Full-text

Mouse Organ Specific Proteins and Functions

10.1101/2021.11.01.466788 ◽

2021 ◽

Author(s):

Bingyun Sun ◽

Cynthia Lorang ◽

Yijuan Zhang ◽

Ken Liu ◽

Zhi Sun ◽

...

Keyword(s):

Human Population ◽

Molecular Diversity ◽

Alanine Transaminase ◽

Organ Specificity ◽

Mouse Strains ◽

Biological Functions ◽

Organ Specific ◽

Specific Proteins ◽

Mouse Organ

Organ specific proteins (OSPs) possess great medical potentials both in clinics and in biomedical research. Applications of them - such as alanine transaminase, aspartate transaminase, and troponins - in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human population are well known, yet their effects on OSPs are less addressed. Here we use mouse as a model and implemented a scheme of breadth study to examine the pan-organ proteome for potential variations of organ specificity in different genetic backgrounds. Using reasonable resources, we generated pan-organ proteomes of four in-bred mouse strains. The results revealed a large diversity that is more profound among OSPs than the overall proteomes. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ specific that are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Download Full-text

Methods for the Determination of the Purity of Exosomes

Current Pharmaceutical Design ◽

10.2174/1381612825666191206162712 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4464-4485 ◽

Cited By ~ 4

Author(s):

Katarzyna Kluszczyńska ◽

Liliana Czernek ◽

Wojciech Cypryk ◽

Łukasz Pęczek ◽

Markus Düchler

Keyword(s):

Drug Transport ◽

Biological Fluids ◽

Drug Carriers ◽

Biological Functions ◽

Isolation And Purification ◽

Pubmed Database ◽

High Concentrations ◽

Targeted Release

Background: Exosomes open exciting new opportunities for advanced drug transport and targeted release. Furthermore, exosomes may be used for vaccination, immunosuppression or wound healing. To fully utilize their potential as drug carriers or immune-modulatory agents, the optimal purity of exosome preparations is of crucial importance. Methods: Articles describing the isolation and purification of exosomes were retrieved from the PubMed database. Results: Exosomes are often separated from biological fluids containing high concentrations of proteins, lipids and other molecules that keep vesicle purification challenging. A great number of purification protocols have been published, however, their outcome is difficult to compare because the assessment of purity has not been standardized. In this review, we first give an overview of the generation and composition of exosomes, as well as their multifaceted biological functions that stimulated various medical applications. Finally, we describe various methods that have been used to purify small vesicles and to assess the purity of exosome preparations and critically compare the quality of these evaluation protocols. Conclusion: Combinations of various techniques have to be applied to reach the required purity and quality control of exosome preparations.

Download Full-text

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

Current Cancer Drug Targets ◽

10.2174/1568009619666190326120457 ◽

2019 ◽

Vol 19 (10) ◽

pp. 765-781

Author(s):

Seema Rohilla ◽

Harish Dureja ◽

Vinay Chawla

Keyword(s):

Adverse Effects ◽

Anticancer Agents ◽

Therapeutic Index ◽

Chemotherapeutic Agents ◽

Vital Role ◽

Normal Cells ◽

Normal Tissues ◽

Organ Specific ◽

Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

Download Full-text

Circadian rhythms, sleep, and anti-cancer treatments

10.1093/oso/9780198778240.003.0016 ◽

2018 ◽

Author(s):

Pasquale F. Innominato ◽

David Spiegel

Keyword(s):

Quality Of Life ◽

Circadian Rhythms ◽

Biological Functions ◽

Cancer Treatments ◽

Anti Cancer ◽

Timing System ◽

Physical Wellbeing ◽

Circadian Timing System ◽

Chemotherapy Agents

The circadian timing system temporally regulates biological functions relevant for psycho-physical wellbeing, spanning all the systems related to health. Hence, disruption of circadian rhythms, along with sleep cycles, is associated with the development of several diseases, including cancer. Moreover, altered circadian and sleep functions negatively impact on cancer patients’ quality of life and survival, above and beyond known determinants of outcome. This alteration can occur as a consequence of cancer, but also of anti-cancer treatments. Indeed, circadian rhythms govern also the ability of detoxifying chemotherapy agents across the 24 hours. Hence, adapting chemotherapy delivery to the molecular oscillations in relevant drug pathways can decrease toxicity to healthy cells, while increasing the number of cancer cells killing. This chronomodulated chemotherapy approach, together with the maintenance of proper circadian function throughtout the whole disease challenge, would finally result in safer and more active anticancer treatments, and in patients experiencing better quality and quantity of life.

Download Full-text

Breathing Well Across the Lifespan: Pulmonary Aging and Geroscience-Targeted Therapies

Innovation in Aging ◽

10.1093/geroni/igaa057.2697 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 749-749

Author(s):

Jason Sanders

Keyword(s):

Pulmonary Fibrosis ◽

Pulmonary Function ◽

Pulmonary Diseases ◽

Human Populations ◽

Aging Research ◽

Novel Treatments ◽

Organ Specific ◽

Nutrient Signaling ◽

Telomere Biology ◽

Increased Susceptibility

Abstract Excellent pulmonary function is one of the strongest predictors of longevity across animal models and human populations. Unfortunately, none of the major age-associated pulmonary diseases – obstructive lung disease, pulmonary fibrosis, and increased susceptibility to pneumonia – have strongly effective disease modifying therapies. There is growing evidence that normal age-associated decline in pulmonary function and major age-associated pulmonary diseases are linked to the hallmarks of aging including senescence, nutrient signaling dysregulation, mitochondrial dysfunction, and telomere disorders. This presents opportunities for collaboration between gerontologists and pulmonologists to unravel age-associated developmental mechanisms and design novel treatments. In this symposium, leaders in pulmonary aging research will present novel data on links between aging and pulmonary health and geroscience-based interventions under study. Dr. Sanders will provide an overview of the scientific and clinical space and present epidemiologic associations between aging biomarkers, early pulmonary fibrosis, and mortality. Dr. Le Saux will discuss senescence and specifically how eicosanoid biology may explain organ-specific patterns of senescence-associated fibrosis. Dr. Thannickal will discuss age-associated perturbations in metabolism and mitochondrial function and targeting these pathways to improve lung function and treat pulmonary diseases. Dr. Newton will discuss mechanisms and clinical applications of telomere biology to pulmonary aging. Symposium attendees will (1) be poised to generate collaborations between gerontologists and pulmonologists to address existing knowledge gaps in mechanisms of pulmonary aging, and (2) develop a better understanding of translational opportunities to design geroscience-based diagnostics and therapeutics to improve pulmonary health with aging.

Download Full-text

Urbanization, housing and environmental quality indicators

Journal of Agriculture Forestry and the Social Sciences ◽

10.4314/joafss.v11i2.5 ◽

2015 ◽

Vol 11 (2) ◽

pp. 51-56

Author(s):

A Oladele

Keyword(s):

Quality Indicators ◽

Environmental Quality ◽

Power Supply ◽

Housing Stock ◽

Housing Quality ◽

Human Populations ◽

Urbanization Process ◽

Reconnaissance Survey ◽

Urban Settlements

The migration of human populations from rural to urban settlements known as urbanization in its most basic sense suggests an improvement in various facets of life. Urbanization ideally should also imply an enhancement of housing quality and other components of human settlements such as power supply, portable water, good roads, proper refuse and sewage disposal facilities, maintenance of ecological balance and a reduction in environmental pollution. Globally, the urbanization process has occurred in a disorganized and nearly uncontrollable manner. The spontaneity in growth of urban settlements has affected negatively several components of the urban fabric such that these components (previously mentioned) are either severely inadequate or non-existent in majority of instances where urbanization has taken place. Arguably, the success of any urbanization process can be measured by the quality of the environments produced and the housing stock found within such environments. This paper seeks to identify and evaluate the components of urban settlements that can be used as indices for establishing quality of our housing, environments and urban clusters particularly for the Nigerian context. The research methodology is a reconnaissance survey, field observation and comparison of four main areas within Ido Local Government Area of Ibadan, Oyo State, namely Apete, Elebu, Elenusonso and Ologuneru.Key words: Urbanization, Environmental quality indicators.

Download Full-text

Exercising D. melanogaster Modulates the Mitochondrial Proteome and Physiology. The Effect on Lifespan Depends upon Age and Sex

International Journal of Molecular Sciences ◽

10.3390/ijms222111606 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11606

Author(s):

Brad Ebanks ◽

Ying Wang ◽

Gunjan Katyal ◽

Chloe Sargent ◽

Thomas L. Ingram ◽

...

Keyword(s):

Healthy Ageing ◽

Exercise Interventions ◽

Complex Ii ◽

Mitochondrial Proteome ◽

Transport Chain ◽

Specific Proteins ◽

Aged Society ◽

Exercise Induced ◽

Response To Exercise

Ageing is a major risk factor for many of the most prevalent diseases, including neurodegenerative diseases, cancer, and heart disease. As the global population continues to age, behavioural interventions that can promote healthy ageing will improve quality of life and relieve the socioeconomic burden that comes with an aged society. Exercise is recognised as an effective intervention against many diseases of ageing, but we do not know the stage in an individual’s lifetime at which exercise is most effective at promoting healthy ageing, and whether or not it has a direct effect on lifespan. We exercised w1118 Drosophila melanogaster, investigating the effects of sex and group size at different stages of their lifetime, and recorded their lifespan. Climbing scores at 30 days were measured to record differences in fitness in response to exercise. We also assessed the mitochondrial proteome of w1118 Drosophila that had been exercised for one week, alongside mitochondrial respiration measured using high-resolution respirometry, to determine changes in mitochondrial physiology in response to exercise. We found that age-targeted exercise interventions improved the lifespan of both male and female Drosophila, and grouped males exercised in late life had improved climbing scores when compared with those exercised throughout their entire lifespan. The proteins of the electron transport chain were significantly upregulated in expression after one week of exercise, and complex-II-linked respiration was significantly increased in exercised Drosophila. Taken together, our findings provide a basis to test specific proteins, and complex II of the respiratory chain, as important effectors of exercise-induced healthy ageing.

Download Full-text

Terc Gene Cluster Variants Predict Liver Telomere Length in Mice

Cells ◽

10.3390/cells10102623 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2623

Author(s):

Dana Zeid ◽

Sean Mooney-Leber ◽

Laurel R. Seemiller ◽

Lisa R. Goldberg ◽

Thomas J. Gould

Keyword(s):

Linkage Disequilibrium ◽

Telomere Length ◽

Gene Cluster ◽

Inbred Mice ◽

Inbred Mouse ◽

Mouse Strains ◽

Chromosome 3 ◽

Human Populations ◽

Nucleotide Polymorphisms ◽

Initial Finding

Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster’s regulation of telomere length.

Download Full-text