Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

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, Volume 13 Issue 4

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REVIEW
Signal integration in the (m)TORC1 growth pathway
Kailash Ramlaul, Christopher H. S. Aylett
Front. Biol.. 2018, 13 (4): 237-262.  
https://doi.org/10.1007/s11515-018-1501-7

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BACKGROUND: The protein kinase Target Of Rapamycin (TOR) is a nexus for the regulation of eukaryotic cell growth. TOR assembles into one of two distinct signalling complexes, TOR complex 1 (TORC1) and TORC2 (mTORC1/2 in mammals), with a set of largely non-overlapping protein partners. (m)TORC1 activation occurs in response to a series of stimuli relevant to cell growth, including nutrient availability, growth factor signals and stress, and regulates much of the cell’s biosynthetic activity, from proteins to lipids, and recycling through autophagy. mTORC1 regulation is of great therapeutic significance, since in humans many of these signalling complexes, alongside subunits of mTORC1 itself, are implicated in a wide variety of pathophysiologies, including multiple types of cancer, neurological disorders, neurodegenerative diseases and metabolic disorders including diabetes.

METHODOLOGY: Recent years have seen numerous structures determined of (m)TOR, which have provided mechanistic insight into (m)TORC1 activation in particular, however the integration of cellular signals occurs upstream of the kinase and remains incompletely understood. Here we have collected and analysed in detail as many as possible of the molecular and structural studies which have shed light on (m)TORC1 repression, activation and signal integration.

CONCLUSIONS: A molecular understanding of this signal integration pathway is required to understand how (m)TORC1 activation is reconciled with the many diverse and contradictory stimuli affecting cell growth. We discuss the current level of molecular understanding of the upstream components of the (m)TORC1 signalling pathway, recent progress on this key biochemical frontier, and the future studies necessary to establish a mechanistic understanding of this master-switch for eukaryotic cell growth.

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Origin of tendon stem cells in situ
Tyler Harvey, Chen-Ming Fan
Front. Biol.. 2018, 13 (4): 263-276.  
https://doi.org/10.1007/s11515-018-1504-4

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BACKGROUND: Adult stem cells are surveillance repositories capable of supplying a renewable source of progenitors for tissue repair and regeneration to maintain tissue homeostasis throughout life. Many tissue-resident stem cells have been identified in situ, which lays the foundation for studying them in their native microenvironment, i.e. the niche. Within the musculoskeletal system, muscle stem cells have been unequivocally identified in the mouse, which have led to considerable advances in understanding their role in muscle homeostasis and regeneration. On the other hand, for bone and tendon progenitor cells, mesenchymal stem cells have been used as the main in vitro cell model as they can differentiate into osteogenic, chondrogenic and tenogenic fates. Despite considerable efforts and employment of modern tools, the in vivo origins of bone and tendon stem cells remain debated. Tendon regeneration via stem cells is understudied and deserves attention as tendon damage is noted for a bleak, time-consuming recovery and the repaired tendon seldom regains the structural integrity and strength of the native, uninjured state.

OBJECTIVE: Here we review the past efforts and recent studies toward defining adult tendon stem cells and understanding tendon regeneration instead of tendon development. The focus is on adult tendon resident cells in situ and the uncertainty of their roles in regeneration.

METHODS: A systematic literature search using the Pubmed search engine was conducted encompassing the seminal papers in the tendon field.

CONCLUSIONS: Investigation of tendon stem cells in situ is in its infancy mainly due to lack of necessary tools and standardized injury model. We propose a concerted effort toward establishing a comprehensive cell atlas of the tendon, making genetic tools and choosing a reliable injury model for coordinated studies among different laboratories. Increasing our basic understanding should aid future therapeutic innovations to shorten and enhance the tendon repair/regeneration process.

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Metastatic tumor cells – genotypes and phenotypes
Dingcheng Gao, Vivek Mittal, Yi Ban, Ana Rita Lourenco, Shira Yomtoubian, Sharrell Lee
Front. Biol.. 2018, 13 (4): 277-286.  
https://doi.org/10.1007/s11515-018-1513-3

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BACKGROUND: Metastasis is the primary cause of mortality in cancer patients. Therefore, elucidating the genetics and epigenetics of metastatic tumor cells and the mechanisms by which tumor cells acquire metastatic properties constitute significant challenges in cancer research.

OBJECTIVE: To summarize the current understandings of the specific genotype and phenotype of the metastatic tumor cells.

METHOD and RESULT: In-depth genetic analysis of tumor cells, especially with advances in the next-generation sequencing, have revealed insights of the genotypes of metastatic tumor cells. Also, studies have shown that the cancer stem cell (CSC) and epithelial to mesenchymal transition (EMT) phenotypes are associated with the metastatic cascade.

CONCLUSION: In this review, we will discuss recent advances in the field by focusing on the genomic instability and phenotypic dynamics of metastatic tumor cells.

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Biobanking and omics
David T. Harris
Front. Biol.. 2018, 13 (4): 287-292.  
https://doi.org/10.1007/s11515-018-1505-3

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BACKGROUND: The “Era of Big Data” and “Precision Medicine” is now upon us. That is, interrogation of large data sets obtained from groups of similar patients or from the patient themselves over time will now hypothetically permit therapies to be designed to provide maximal efficacy with minimal side effects. However, such discoveries depend upon recruitment of very large numbers of subjects (tens of thousands) along with their associated biospecimens and medical records. When considering the establishment of a biobank or the refocusing of an existing repository for the purpose of “omics” research (i.e., genomics, metabolomics, proteomics, microbiomics, etc.) and/or precision medicine, there are a number of considerations to ponder. Each of these facets is discussed.

OBJECTIVE: The objective of this review is to describe best practices for the establishment and operations of a biobank that will be used for omics (genomics, proteomics, metabolomics, microbiomics) analyses based on published literature and our own practical experiences.

METHODS: We describe the most commonly described approaches to a variety of biobanking issues, including our own practical experiences over the past 5 years.

RESULTS: Based on the particular biobanking situation and downstream application, we have described best practices based on the literature and own experience, taking into consideration ease of application and costs.

CONCLUSIONS: The banking of various types of clinical biospecimens has many valuable uses but often depends on overall costs versus sample utility. In addition, specimen flexibility is important but is influenced by the ease or difficulty of the application. It is always preferable to collect and stored a biospecimen in a format that allows for multiple types of downstream analyses, but that often requires additional expertise, equipment and reagents that can increase overall costs. We have described the methodologies most successfully applied to many situations.

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HspX protein as a candidate vaccine against Mycobacterium tuberculosis: an overview
Arshid Yousefi-Avarvand, Mohsen Tafaghodi, Saman Soleimanpour, Farzad Khademi
Front. Biol.. 2018, 13 (4): 293-296.  
https://doi.org/10.1007/s11515-018-1494-2

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BACKGROUND: Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Mtb). This disease with two million deaths per year has the highest mortality rate among bacterial infections. The only available vaccine against TB is BCG vaccine. BCG is an effective vaccine against TB in childhood, however, due to some limitations, has not proper efficiency in adults. Also, BCG cannot produce an adequately protective response against reactivation of latent infections.

OBJECTIVE: In the present study we will review the most recent findings about contribution of HspX protein in the vaccines against tuberculosis.

METHODS: Therefore, many attempts have been made to improve BCG or to find its replacement. Most of the subunit vaccines for TB in various phases of clinical trials were constructed as prophylactic vaccines using Mtb proteins expressed in the replicating stage. These vaccines might prevent active TB but not reactivation of latent tuberculosis infection (LTBI). A literature search was performed on various online databases (PubMed, Scopus, and Google Scholar) regarding the roles of HspX protein in tuberculosis vaccines.

RESULTS: Ideal subunit post-exposure vaccines should target all forms of TB infection, including active symptomatic and dormant (latent) asymptomatic forms. Among these subunit vaccines, HspX is the most important latent phase antigen of M. tuberculosis with a strong immunological response. There are many studies that have evaluated the immunogenicity of this protein to improve TB vaccine.

CONCLUSION: According to the studies, HspX protein is a good candidate for development of subunit vaccines against TB infection.

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RESEARCH ARTICLE
Comparative evaluation of physico-chemical characteristics of biopolyesters P(3HB) and P(3HB-co-3HV) produced by endophytic Bacillus cereus RCL 02
Rituparna Das, Nayan Ranjan Saha, Arundhati Pal, Dipankar Chattopadhyay, Amal Kanti Paul
Front. Biol.. 2018, 13 (4): 297-308.  
https://doi.org/10.1007/s11515-018-1509-z

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BACKGROUND: Bacteria endogenously residing within the plant tissues have attracted significant attention for production of biopolyester, polyhydroxyalkanoates (PHAs). Bacillus cereus RCL 02 (MCC 3436), a leaf endophyte of oleaginous plant Ricinus communis L. accumulates 81% poly(3-hydroxybutyrate) [P(3HB)] of its cell dry biomass when grown in mineral salts (MS) medium.

METHODS: The copolymer production efficiency of B. cereus RCL 02 was evaluated in valeric acid supplemented MS medium under biphasic cultivation condition. The copolymer so produced has been compared with the P(3HB) isolated from RCL 02 in terms of thermal, mechanical and chemical properties.

RESULTS: Valeric acid supplementation as co-substrate in the medium has led to the production of copolymer of 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV) [P(3HB-co-3HV)] with 14.6 mol% 3HV. The identity of the polymers has been confirmed by X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopic studies. Thermogravimetric analysis (TGA) revealed that P(3HB) and P(3HB-co-3HV) films degraded at 278.66°C and 273.49°C, respectively. The P(3HB-co-3HV) showed lower melting temperature (165.03°C) compared to P(3HB) (170.74°C) according to differential scanning calorimetry (DSC). Incorporation of 3HV monomers decreased the tensile strength (21.52 MPa), tensile modulus (0.93 GPa), storage modulus (E′) (0.99 GPa) and increased % elongation at break (12.2%) of the copolyester. However, P(3HB) showed better barrier properties with lower water vapor transmission rate (WVTR) of 0.55 g-mil/100 in2/24 h.

CONCLUSION: These findings emphasized exploration of endophytic bacterial strain (RCL 02) to produce biodegradable polyesters which might have significant potential for industrial application.

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Relationship between breast arterial calcification on mammography with coronary CT angiography findings
Mohammad Ghasem Hanafi, Mojgan Samet Zadeh, Mohammad Momeni, Sorour Rajabkordi
Front. Biol.. 2018, 13 (4): 309-313.  
https://doi.org/10.1007/s11515-018-1510-6

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BACKGROUND: Breast arterial calcification is a frequently benign finding on mammography that usually is not reported. An increasing attention has been formed to determine the association between breast arterial calcification (BAC) and Coronary artery disease. In the current study we have aimed to evaluate the relationship between BAC on mammography with coronary CT angiography findings.

METHODS: The case control study was carried out on 60 women; 30 CAD and 30 healthy subjects as control, admitted to Golestan hospital radiology department. The mammography was performed in two views; Craniocaudal (CC) view and mediolateral oblique (MLO) and BAC was graded based on the severity and extent of calcifications. Coronary Arterial Calcification (CAC) were scored by Agatston criteria.

RESULTS: Overly, 36 patients (60%) were positive for BAC. Twenty six out of them (72%) were CAD. There was a positive significant correlation between BAC and CAD. The sensitivity and specificity of BAC for CAD were 69% and 47%, respectively. Moreover, the severe BAC scores were significantly higher in CAD patients than non-CAD.

CONCLUSION: Our findings in line with several previous studies indicated the positive significant association between BAC and CAD occurrence. While the sensitivity and specificity of BAC in diagnosis of CAD is low, suggested the using of BAC just as a CAD risk factor. The relatively low sample size is the major limitation of the study.

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7 articles