Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

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, Volume 13 Issue 1

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REVIEW
RNA-dependent pseudouridylation catalyzed by box H/ACA RNPs
Meemanage D. De Zoysa, Yi-Tao Yu
Front. Biol.. 2018, 13 (1): 1-10.  
https://doi.org/10.1007/s11515-018-1480-8

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BACKGROUND: Pseudouridine (Y) is the most abundant post-transcriptionally modified nucleotide found in RNA. Y is clustered in functionally important and evolutionary conserved regions of RNAs in all three domains of life. Pseudouridylation is catalyzed by two distinct mechanisms: an RNA-independent and an RNA-dependent mechanism. The former involves a group of stand-alone protein enzymes, and the latter involves a family of complex enzymes called box H/ACA RNPs, each of which consists of one RNA (box H/ACA RNA) and a set of four core proteins. Over the years, the mechanism of RNA-dependent pseudouridylation has been extensively studied. The crystal structures of partial and complete box H/ACA RNP have been solved. However, the detailed picture of RNA-dependent pseudouridylation is still not entirely clear.

OBJECTIVE: In this work, we review what is known about box H/ACA RNP and the mechanism by which box H/ACA RNP catalyzes RNA-dependent pseudouridylation. We also discuss some examples of the dual nature and redundancy of box H/ACA RNPs that deviate from the usual mechanism.

METHODS: A methodical literature search was performed using the Pubmed central search engine and International Digital Publishing Forum (EPUB) using the following keywords: “pseudouridylation,” “pseudouridine,” and “box H/ACA RNP.” The necessary information was extracted and cited.

RESULTS: A detailed introduction is made including the discovery, mechanism and crystal structure of box H/ACA RNP. Three sequence/structural requirements for box H/ACA RNA-guided pseudouridylation are discussed and the exceptions to those rules are explored.

CONCLUSION: Over the years, box H/ACA RNP-catalyzed pseudouridylation has been extensively studied, generating fruitful results. However, a detailed picture regarding the mechanism of this reaction is still to be deciphered. More work is needed to fully understand box H/ACA RNP-catalyzed pseudouridylation.

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Preclinical and clinical studies on cancer-associated cachexia
D. Brooke Widner, D. Clark Files, Kathryn E. Weaver, Yusuke Shiozawa
Front. Biol.. 2018, 13 (1): 11-18.  
https://doi.org/10.1007/s11515-018-1484-4

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BACKGROUND: Cancer cachexia is the wasting condition that is often seen in advanced stage cancer patients. This wasting is largely attributable to a systemic and progressive loss of skeletal muscle mass that greatly hinders performance of normal daily activities, resulting in reduced quality of life. Moreover, it negatively influences the prognosis of cancer patients. A general consensus in the field is that the loss of muscle mass is due both to an increase in protein degradation and a decrease in protein synthesis. Recent studies using preclinical models for studying cachexia have been useful in identifying the contribution of inflammatory cytokines (e.g. tumor necrosis factor-α and Interleukin-6), and myostatin receptors (e.g. the type IIB activin receptor) to cachexia development, and have led to several clinical trials. However, many questions remain about the molecular mechanisms thought to play a role in the development of cachexia.

METHODS: We conducted a literature search using search engines, such as PubMed and Google Scholar to identify publications within the cancer cachexia field.

RESULTS: We summarized our current knowledge of: 1) the driving mechanisms of cancer cachexia, 2) the preclinical models available for studying the condition, and 3) the findings of recent clinical trials.

CONCLUSION: Cancer cachexia is a complex and variable condition that currently has no standard effective therapeutic treatment. Further studies are desperately needed to better understand this condition and develop effective combination treatments for patients.

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Physiological significance of oxidative stress and its role in adaptation of the human body to deleterious factors
Vadim V. Davydov, Alexander V. Shestopalov, Evgenya R. Grabovetskaya
Front. Biol.. 2018, 13 (1): 19-27.  
https://doi.org/10.1007/s11515-018-1482-6

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BACKGROUND: Oxidative stress is an extremely widespread condition manifested in an increased rate of free-radical processes and accumulation of reactive oxygen species (ROS) in the tissues. It appears in different physiologic states and pathological processes accompanied by stimulation of the sympathetic adrenal system or tissue hypoxia or under stress. However, until now, there is still no clarity on the issue of the significance of oxidative stress in the development of adaptation processes in the organism.

OBJECTIVE: In the present work we will review the most recent finding about physiologic role of oxidative stress and its participation in adaptation of an organism to effect of different adverse factors.

METHODS: A systematic literature search was performed using the Pubmed search engine. Studies published over past 18 years, i.e. between 1998 and 2015 were considered for review. Followed keywords were used: “oxidative stress,” “free radical oxidation,” “ROS,” “endogenous aldehydes,” “adaptation.”

RESULTS: The article cites arguments supporting the notion that oxidative stress serves as a nonspecific link in the adaptation of the human body to the effects of injurious factors. Oxidative stress exerts regulatory effects by changing the redox state of the cell. Oxidative stress affects on various intracellular proteins containing cysteine ??residues, e.g., enzymes, chaperones, and transcription factors, etc. For this reason, the use of antioxidants for the treatment and prophylaxis of a wide range of diseases is not recommended.

CONCLUSION: Further investigation is needed in this field. The most attention should be paid to careful experimental verification aimed at quantitative assessment of the ROS level in tissues under oxidative stress, as well as at the study of possibility of enhancing the catabolism of free radical oxidation carbonyl products in order to prevent tissue damage under oxidative stress.

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Threatening biomarkers in lupus pregnancy: Biochemistry and genetic challenges
Karim Mowla, Elham Rajaei, Mohammad Taha Jalali, Zeinab Deris Zayeri
Front. Biol.. 2018, 13 (1): 28-35.  
https://doi.org/10.1007/s11515-017-1477-8

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OBJECTIVES: Using genetic markers and miRs work strongly beside other sensitive biomarkers in lupus management during sensitive period of pregnancy.

METHOD: PubMed and Google Scholar databases were searched from 2000 to 2017 using the terms “lupus,” “lupus pregnancy,” “biomarkers,” “micro-RNA,” “polymorphisms,” “anti-phospholipid antibodies,” and “cluster differentiation markers.”

DISCUSSION: Complement is a valuable biomarker in lupus pregnancy. However, the complement profile has ambiguous meaning because decreased levels of C3 and C4 reflect inflammation and because they are also prognostic biomarkers for abortion. Furthermore, increased C3 and C4 levels indicate hepatic protein synthesis in hepatocytes. Anti-phospholipid (APL) antibodies are present in 25% to 50% of lupus patients, and can lead to thrombotic and obstetric complications in some pregnancies and increase the risk of abortion, especially in a pregnant woman in the active phase of lupus. Several studies have associated APL with HELLP syndrome. However, other pregnancy complications have not been associated with APL. Autoantibodies against the major vault protein and anti-double strand DNA antibodies are valuable biomarkers in evaluating lupus activity. The expression pattern of micro-RNAs (miRs) differs in various diseases. Current studies have demonstrated the potential of miRs as diagnostic and prognostic biomarkers in various diseases; for example, the level of miR-126 is higher in lupus.

CONCLUSION: miR-223-3p and miR-451 are informative biomarkers in estimating disease activity. TWEAK, BAFF, and APOL1 genes, and their polymorphisms are informative in estimating disease activity, especially renal effects, and in monitoring higher-risk pregnant women. Further studies of these genes and their relevant polymorphisms are needed.

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RESEARCH ARTICLE
miRACA: A database for miRNAs associated with cancers and age related disorders (ARD)
Razia Rahman, Lokesh Kumar Gahlot, Yasha Hasija
Front. Biol.. 2018, 13 (1): 36-50.  
https://doi.org/10.1007/s11515-018-1481-7

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BACKGROUND: With the given diversity and abundance of several targets of miRNAs, they functionally appear to interact with several elements of the multiple cellular networks to maintain physiologic homeostasis. They can function as tumor suppressors or oncogenes, whose under or overexpression has both diagnostic and prognostic significance in various cancers while being implicated as prospective regulators of age-related disorders (ARD) as well. Establishing a concatenate between ARD and cancers by looking into the insights of the shared miRNAs may have a practical relevance.

METHODS: In the present work, we performed network analysis of miRNA-disease association and miRNA-target gene interaction to prioritize miRNAs that play significant roles in the manifestation of cancer as well as ARD. Also, we developed a repository that stores miRNAs common to both ARD and cancers along with their target genes.

RESULTS: We have comprehensively curated all miRNAs that we found to be shared in both the diseases in the human genome and established a database, miRACA (Database for microRNAs Associated with Cancers and ARD) that currently houses information of 1648 miRNAs that are significantly associated with 38 variants supported with pertinent data. It has been made available online at http://genomeinformatics.dtu.ac.in/miraca/ for easy retrieval and utilization of data by the scientific community.

CONCLUSION: To the best of our knowledge, our database is the first attempt at compilation of such data. We believe this work may serve as a significant resource and facilitate the analysis of miRNA regulatory mechanisms shared between cancers and ARD to apprehend disease etiology.

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The relationship between serum zinc levels and rheumatoid arthritis activity
Elham Rajaee, Karim Mowla, Ali Ghorbani, Mehrdad Dargahi-Malamir, Marzieh Zarei, Faraj Allah Rahimikhah
Front. Biol.. 2018, 13 (1): 51-55.  
https://doi.org/10.1007/s11515-017-1474-y

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OBJECTIVES: Rheumatoid arthritis (RA) is one of the most prevalent chronic autoimmune diseases; it typically involves the hands, wrists, ankles, and eventually all joints. Some studies have reported that zinc serum levels are lower in patients with RA than in healthy individuals.

MATERIALS and METHODS: Seventy-nine patients with RA were selected. The patients were all less than 75 years old and were diagnosed by a rheumatologist. Serum zinc levels were measured using the flame photometry method with a blood sample of 5 mL. The relationship between the average serum zinc level and disease activity was analyzed based on the DAS28 scoring scale for different RA groups. The significance threshold was set at p<0.05. Data analyses were implemented in SPSS 22.0.

RESULTS: There was a significant inverse relationship between the serum zinc levels and disease activity. Chi-square tests were used to compare zinc serum levels with respect to disease activity. There were significant differences in zinc levels among three groups of patients with different levels of disease severity, such that disease activity increased as the serum zinc level decreased (p<0.001).

CONCLUSION: There was a significant inverse relationship between the serum zinc level and RA activity based on the DAS28 score. Therefore, it is recommended that mineral deficiencies should be addressed by optimizing the zinc supply along with other standard medications in order to reduce RA activity.

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Invulnerability of bromelain against oxidative degeneration and cholinergic deficits imposed by dichlorvos in mice brains
Bharti Chaudhary, Sonam Agarwal, Renu Bist
Front. Biol.. 2018, 13 (1): 56-62.  
https://doi.org/10.1007/s11515-018-1479-1

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BACKGROUND: The present study elucidates the protective potential of bromelain against dichlorvos intoxication in mice brains. Dichlorvos induces the oxidative stress by disproportionating the balance between free radicals generation and their scavenging in neurons which leads to neuronal degeneration.

METHODS: In this study, mice were divided into four groups- group I (control), group II (dichlorvos treated), group III (bromelain treated) and group IV (exposed to both bromelain and dichlorvos both).

RESULTS: Dichlorvos treatment increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) which indicate the increased oxidative stress. Meanwhile, brain endogenous antioxidants and cholinesterases level was decreased after dichlorvos exposure. Levels of TBARS and PCC decreased whereas cholinesterases level was recorded to be elevated after bromelain exposure.

CONCLUSION: Bromelain offered neuroprotection by decreasing oxidative stress and augmenting cholinesterases in mice brains. This study highlights the invulnerability of bromelain against oxidative and cholinergic deficits in mice brains.

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Synthesis of scl-poly (3-hydroxyalkanoates) by Bacillus cereus found in freshwater, from monosaccharides and disaccharides
Tayyaba Naeem, Naima Khan, Nazia Jamil
Front. Biol.. 2018, 13 (1): 63-69.  
https://doi.org/10.1007/s11515-018-1478-2

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BACKGROUND: Polyhydroxyalkanoates are a good substitute for synthetic plastic because they are highly biocompatible, ecofriendly, and biodegradable. Bacteria in freshwater bodies such as rivers, tube wells, and canals are exposed to alternating high and low concentrations of substrates that induce PHA production.

METHODS: Fresh water samples were collected for isolation of bacterial strains. Screening of PHA in bacterial cells was performed with Sudan and Nile Red staining. Extracted PHA was characterized by FTIR.

RESULTS: In this study, nine bacterial isolates were selected for PHA production on the basis of phenotypic screening. Their ability to accumulate PHAs was determined using different monosaccharides and disaccharides. Two bacterial isolates Bacillus cereus T1 (KY746353) and Bacillus cereus R3 (KY746354) produced PHAs. Optimal growth of the bacterial strain (T1) was observed in the presence of glucose, followed by maximum production of PHAs (63% PHAs) during the logarithmic phase of growth. B. cereus R3 (KY746354) accumulated 60% PHAs by dry cell weight.

CONCLUSION: PHA accumulation was relatively less with fructose, but both strains showed increased production (up to 50%) with sucrose. The polymer produced was characterized by Fourier-transform infrared spectroscopy (FTIR), which showed that the compound contains short-chain PHAs.

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Optimization and modeling studies on the production of a new fibrinolytic protease using Streptomyces radiopugnans_VITSD8
Dhamodharan Duraikannu, Subathra Devi Chandrasekaran
Front. Biol.. 2018, 13 (1): 70-77.  
https://doi.org/10.1007/s11515-017-1476-9

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BACKGROUND: The current study demonstrated the possibility of statistical design tools combination with computational tools for optimization of fermentation conditions for enhanced fibrinolytic protease production.

METHODS: The effects of using different carbon and nitrogen sources for protease production by Streptomyces radiopugnans_VITSD8 were examined by a full factorial design method. The incubation time, temperature, pH of the medium, and RPM were assessed by the predictable one factor at a time (OFAT) method. Optimization was carried out using starch and oat meal as carbon source, nitrogen source as peptic and malt extract using Fractional Factorial Design (FFD). The analysis was further continued for medium volume, temperature, initial medium pH, inoculum concentration, high determination co-efficient as (R’-0.965), and lower determination co-efficient of variation (CV-8.19%), which defines a reliable and accurate experimental value.

RESULTS: Analysis of variance by the fixed slope effect by temperature and starch; temperature and L-aspargine, temperature and oat meal, temperature and peptic extracts, temperature and pH, temperature and duration of incubation were more vital for protease production at an interactive level. Response surface plots revealed that temperature, starch, and peptic extracts affix critical concerning in temperature. Programming estimated a 28% increase in protease production. Incubation temperature and medium volume portrayed extreme impact among all factor. Starch, peptic and temperature play an important regulatory role in protease production. Optimium temperature for protease production was 33°C. The ratio of carbon and nitrogen sources and pH were the major regulatory factors in protease production by Streptomyces radiopugnans_VITSD8. It demonstrated a 4% noteworthy change in condition.

CONCLUSION: Among all the selected parameters, temperature was the most intuitive factor, demonstrating a notable connection with the type of media and pH, while inoculum fixation had a direct impact on protein production.

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9 articles