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Life, Volume 10, Issue 6 (June 2020) – 22 articles

Cover Story (view full-size image): Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds specific consensus sequences on Gab2 through its two SH2 domains. A complete mutational analysis of the kinetics of binding between the N-SH2 domain of SHP2 and a peptide mimicking a specific region of Gab2 allowed us to unveil structural features of the transition state of the N-SH2 domain binding to Gab2, revealing remarkable cooperativity of the binding reaction. Comparison with kinetic data from another SH2 domain suggests the presence of underlying general features characterizing the binding process of SH2 domains. View this paper
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12 pages, 1603 KiB  
Article
In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes
by Carlos Navarro-Paya, Maximo Sanz-Hernandez and Alfonso De Simone
Life 2020, 10(6), 98; https://doi.org/10.3390/life10060098 - 26 Jun 2020
Cited by 8 | Viewed by 2624
Abstract
The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the [...] Read more.
The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the protein. In the present study, we used enhanced coarse-grained MD simulations to characterize the sequence and conformational determinants of the binding to synaptic-like vesicles by the N-terminal region of αS. This region is the membrane anchor and is of crucial importance for the properties of the physiological monomeric state of αS as well as for its aberrant aggregates. These results identify the key factors that play a role in the binding of αS with synaptic lipid bilayers in both membrane-tethered and membrane-locked conformational states. Full article
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16 pages, 1303 KiB  
Article
Development of a Simple Kinetic Mathematical Model of Aggregation of Particles or Clustering of Receptors
by Andrei K. Garzon Dasgupta, Alexey A. Martyanov, Aleksandra A. Filkova, Mikhail A. Panteleev and Anastasia N. Sveshnikova
Life 2020, 10(6), 97; https://doi.org/10.3390/life10060097 - 26 Jun 2020
Cited by 5 | Viewed by 3068
Abstract
The process of clustering of plasma membrane receptors in response to their agonist is the first step in signal transduction. The rate of the clustering process and the size of the clusters determine further cell responses. Here we aim to demonstrate that a [...] Read more.
The process of clustering of plasma membrane receptors in response to their agonist is the first step in signal transduction. The rate of the clustering process and the size of the clusters determine further cell responses. Here we aim to demonstrate that a simple 2-differential equation mathematical model is capable of quantitative description of the kinetics of 2D or 3D cluster formation in various processes. Three mathematical models based on mass action kinetics were considered and compared with each other by their ability to describe experimental data on GPVI or CR3 receptor clustering (2D) and albumin or platelet aggregation (3D) in response to activation. The models were able to successfully describe experimental data without losing accuracy after switching between complex and simple models. However, additional restrictions on parameter values are required to match a single set of parameters for the given experimental data. The extended clustering model captured several properties of the kinetics of cluster formation, such as the existence of only three typical steady states for this system: unclustered receptors, receptor dimers, and clusters. Therefore, a simple kinetic mass-action-law-based model could be utilized to adequately describe clustering in response to activation both in 2D and in 3D. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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9 pages, 1090 KiB  
Article
Rat Animal Model of Pectus Excavatum
by Vlad-Laurentiu David, Bogdan Ciornei, Florin-George Horhat, Elena Amaricai, Ioana-Delia Horhat, Teodora Hoinoiu and Eugen-Sorin Boia
Life 2020, 10(6), 96; https://doi.org/10.3390/life10060096 - 26 Jun 2020
Cited by 3 | Viewed by 2788
Abstract
Background: pectus excavatum (PE) is the most common congenital deformity of the thoracic wall. Lately, significant achievements have been made in finding new, less invasive treatment methods for PE. However, most of the experimental work was carried out without the help of an [...] Read more.
Background: pectus excavatum (PE) is the most common congenital deformity of the thoracic wall. Lately, significant achievements have been made in finding new, less invasive treatment methods for PE. However, most of the experimental work was carried out without the help of an animal model. In this report we describe a method to create an animal model for PE in Sprague-Dawley rats. Methods: We selected 15 Sprague-Dawley rat pups and divided them into two groups: 10 for the experimental group (EG) and 5 for the control group (CG). We surgically resected the last four pairs of costal cartilages in rats from the EG. The animals were assessed by CT-scan prior to surgery and weekly for four consecutive weeks. After four weeks, the animals were euthanized and the thoracic cage was dissected from the surrounding tissue. Results: On the first postoperative CT, seven days after surgery, we observed a marked depression of the lower sternum in all animals from the EG. This deformity was present at every CT-scan after surgery and at the post-euthanasia assessment. Conclusions: By decreasing the structural strength of the lower costal cartilages, we produced a PE animal model in Sprague-Dawley rats. Full article
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15 pages, 3622 KiB  
Review
Bioinformatics Analysis of Evolution and Human Disease Related Transposable Element-Derived microRNAs
by Hee-Eun Lee, Jae-Won Huh and Heui-Soo Kim
Life 2020, 10(6), 95; https://doi.org/10.3390/life10060095 - 25 Jun 2020
Cited by 17 | Viewed by 3389
Abstract
Transposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of [...] Read more.
Transposable element (TE) has the ability to insert into certain parts of the genome, and due to this event, it is possible for TEs to generate new factors and one of these factors are microRNAs (miRNA). miRNAs are non-coding RNAs made up of 19 to 24 nucleotides and numerous miRNAs are derived from TE. In this study, to support general knowledge on TE and miRNAs derived from TE, several bioinformatics tools and databases were used to analyze miRNAs derived from TE in two aspects: evolution and human disease. The distribution of TEs in diverse species presents that almost half of the genome is covered with TE in mammalians and less than a half in other vertebrates and invertebrates. Based on selected evolution-related miRNAs studies, a total of 51 miRNAs derived from TE were found and analyzed. For the human disease-related miRNAs, total of 34 miRNAs derived from TE were organized from the previous studies. In summary, abundant miRNAs derived from TE are found, however, the function of miRNAs derived from TE is not informed either. Therefore, this study provides theoretical understanding of miRNAs derived from TE by using various bioinformatics tools. Full article
(This article belongs to the Special Issue Genomic Impact of Transposable Elements)
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42 pages, 9081 KiB  
Review
The Clinical Use of Platelet-Rich Plasma in Knee Disorders and Surgery—A Systematic Review and Meta-Analysis
by Ewa Trams, Krzysztof Kulinski, Katarzyna Kozar-Kaminska, Stanislaw Pomianowski and Rafal Kaminski
Life 2020, 10(6), 94; https://doi.org/10.3390/life10060094 - 25 Jun 2020
Cited by 22 | Viewed by 4879
Abstract
In recent years, the interest in biological treatment of knee lesions has increased, especially the application of platelet-rich plasma is of particular note. The number of articles evaluating platelet-rich plasma (PRP) efficacy in the recovery of knee disorders and during knee surgery has [...] Read more.
In recent years, the interest in biological treatment of knee lesions has increased, especially the application of platelet-rich plasma is of particular note. The number of articles evaluating platelet-rich plasma (PRP) efficacy in the recovery of knee disorders and during knee surgery has exponentially increased over the last decade. A systematic review with meta-analyses was performed by assessing selected studies of local PRP injections to the knee joint. The study was completed in accordance with 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A multistep search of PubMed, Embase, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov was performed to identify studies on knee surgery and knee lesion treatment with PRP. Of the 4004 articles initially identified, 357 articles focusing on knee lesions were selected and, consequently, only 83 clinical trials were analyzed using the revised Cochrane risk-of-bias tool to evaluate risk. In total, seven areas of meta-analysis reported a positive effect of PRP. Among them, 10 sub-analyses demonstrated significant differences in favor of PRP when compared to the control groups (p < 0.05). This study showed the positive effects of PRP, both on the recovery of knee disorders and during knee surgery; however further prospective and randomized studies with a higher number of subjects and with lower biases are needed. Full article
(This article belongs to the Section Medical Research)
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21 pages, 3002 KiB  
Article
Arsenolipids in Cultured Picocystis Strain ML and Their Occurrence in Biota and Sediment from Mono Lake, California
by Ronald A. Glabonjat, Jodi S. Blum, Laurence G. Miller, Samuel M. Webb, John F. Stolz, Kevin A. Francesconi and Ronald S. Oremland
Life 2020, 10(6), 93; https://doi.org/10.3390/life10060093 - 24 Jun 2020
Cited by 12 | Viewed by 2713
Abstract
Primary production in Mono Lake, a hypersaline soda lake rich in dissolved inorganic arsenic, is dominated by Picocystis strain ML. We set out to determine if this photoautotrophic picoplankter could metabolize inorganic arsenic and in doing so form unusual arsenolipids (e.g., arsenic bound [...] Read more.
Primary production in Mono Lake, a hypersaline soda lake rich in dissolved inorganic arsenic, is dominated by Picocystis strain ML. We set out to determine if this photoautotrophic picoplankter could metabolize inorganic arsenic and in doing so form unusual arsenolipids (e.g., arsenic bound to 2-O-methyl ribosides) as reported in other saline ecosystems and by halophilic algae. We cultivated Picocystis strain ML on a seawater-based medium with either low (37 µM) or high (1000 µM) phosphate in the presence of arsenite (400 µM), arsenate (800 µM), or without arsenic additions (ca 0.025 µM). Cultivars formed a variety of organoarsenic compounds, including a phytyl 2-O-methyl arsenosugar, depending upon the cultivation conditions and arsenic exposure. When the cells were grown at low P, the organoarsenicals they produced when exposed to both arsenite and arsenate were primarily arsenolipids (~88%) with only a modest content of water-soluble organoarsenic compounds (e.g., arsenosugars). When grown at high P, sequestration shifted to primarily water-soluble, simple methylated arsenicals such as dimethylarsinate; arsenolipids still constituted ~32% of organoarsenic incorporated into cells exposed to arsenate but < 1% when exposed to arsenite. Curiously, Picocystis strain ML grown at low P and exposed to arsenate sequestered huge amounts of arsenic into the cells accounting for 13.3% of the dry biomass; cells grown at low P and arsenite exposure sequestered much lower amounts, equivalent to 0.35% of dry biomass. Extraction of a resistant phase with trifluoroacetate recovered most of the sequestered arsenic in the form of arsenate. Uptake of arsenate into low P-cultivated cells was confirmed by X-ray fluorescence, while XANES/EXAFS spectra indicated the sequestered arsenic was retained as an inorganic iron precipitate, similar to scorodite, rather than as an As-containing macromolecule. Samples from Mono Lake demonstrated the presence of a wide variety of organoarsenic compounds, including arsenosugar phospholipids, most prevalent in zooplankton (Artemia) and phytoplankton samples, with much lower amounts detected in the bottom sediments. These observations suggest a trophic transfer of organoarsenicals from the phytoplankton (Picocystis) to the zooplankton (Artemia) community, with efficient bacterial mineralization of any lysis-released organoarsenicals back to inorganic oxyanions before they sink to the sediments. Full article
(This article belongs to the Special Issue Metabolism of Photosynthetic Organisms)
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7 pages, 499 KiB  
Communication
Clopidogrel, an ADP-P2Y12 Receptor Antagonist, Can Prevent Severe Postoperative Pain: A Retrospective Chart Review
by Rikuhei Tsuchida, Masahiko Sumitani, Hiroaki Abe, Masae Ando, Kosuke Saita, Kohshi Hattori, Kazuhito Mietani, Reo Inoue and Kanji Uchida
Life 2020, 10(6), 92; https://doi.org/10.3390/life10060092 - 22 Jun 2020
Cited by 4 | Viewed by 2147
Abstract
The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain [...] Read more.
The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP, n = 17) or clopidogrel (CLP, n = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann–Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia. Full article
(This article belongs to the Section Medical Research)
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16 pages, 3249 KiB  
Article
Antimicrobial Activity of Microorganisms Isolated from Ant Nests of Lasius niger
by Tatiana A. Efimenko, Alla A. Glukhova, Mariia V. Demiankova, Yuliya V. Boykova, Natalia D. Malkina, Irina G. Sumarukova, Byazilya F. Vasilieva, Eugene A. Rogozhin, Igor A. Ivanov, Vladislav A. Krassilnikov and Olga V. Efremenkova
Life 2020, 10(6), 91; https://doi.org/10.3390/life10060091 - 22 Jun 2020
Cited by 9 | Viewed by 2976
Abstract
In this study, the microbial communities of two nests of black garden ants (Lasius niger) in the hollows of stem branches of old apple trees were found to have similar species compositions: each community contained representatives of three species from the Bacillaceae [...] Read more.
In this study, the microbial communities of two nests of black garden ants (Lasius niger) in the hollows of stem branches of old apple trees were found to have similar species compositions: each community contained representatives of three species from the Bacillaceae family and one species of actinomycetes from the genus Streptomyces. In total, four types of bacilli and two actinomycetes were isolated. Actinomycetes were identified as Streptomyces antibioticus-like and Streptomyces sp. None of the bacilli had antibiotic activity, whereas both streptomycetes produced antibiotics that inhibited the growth of Gram-positive bacteria in vitro, including isolates from their community. Antibiotic compounds of S. antibioticus-like strain INA 01148 (Institute of New Antibiotics) were identified as actinomycin D and its closest homologue, actinomycin A. Actinomycins presumably change the microbial community of the ant nest substrate as they act against Gram-positive bacteria and against fungi and Gram-negative bacteria. The antibiotic activity of the isolated Streptomyces sp. INA 01156 is of interest, since the substances produced by this strain inhibit the growth of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and vancomycin-resistant strain Leuconostoc mesenteroides VKPM B-4177 (VR) (VKPM–National Collection of Industrial Microorganisms (Russian acronym)). Full article
(This article belongs to the Section Microbiology)
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14 pages, 1194 KiB  
Article
Validating the Use of Corifollitropin Alfa in Progestin-Primed Ovarian Stimulation Protocol on Normal and High Responders by Comparing with Conventional Antagonist Protocol: A Retrospective Study
by Chen-Yu Huang, Guan-Yeu Chen, Miawh-Lirng Shieh and Hsin-Yang Li
Life 2020, 10(6), 90; https://doi.org/10.3390/life10060090 - 21 Jun 2020
Cited by 8 | Viewed by 3302
Abstract
Our previous study showed a satisfactory reproductive outcome resulting from the patient-friendly ovarian stimulation protocol using long-acting follicle stimulation hormone (FSH) plus oral medroxyprogesterone acetate (MPA). The present retrospective study aims to compare the efficacy of the patient-friendly ovarian stimulation protocol with that [...] Read more.
Our previous study showed a satisfactory reproductive outcome resulting from the patient-friendly ovarian stimulation protocol using long-acting follicle stimulation hormone (FSH) plus oral medroxyprogesterone acetate (MPA). The present retrospective study aims to compare the efficacy of the patient-friendly ovarian stimulation protocol with that of the antagonist protocol on normal and high responders aged between 24 and 39 years in a tertiary fertility center in Taiwan. To prevent premature luteinizing hormone (LH) surge, oral MPA was given to patients in group 1 (n = 57), whereas antagonist protocol was applied to group 2 (n = 53). Duration and dosage of stimulation, number of injections and visits before trigger, incidence of premature LH surge, number of oocytes retrieved, fertilization rate, cleavage rate, rate of good embryos available, incidence of ovarian hyperstimulation syndrome, cumulative clinical pregnancy rate and live birth rate per retrieval were compared between groups. We conclude that our patient-friendly ovarian stimulation protocol with MPA demonstrates satisfactory stimulation and reproductive outcomes that are comparable to those of an antagonist protocol. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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22 pages, 1250 KiB  
Review
Mass Spectrometry: A Rosetta Stone to Learn How Fungi Interact and Talk
by Erika Calla-Quispe, Hammerly Lino Fuentes-Rivera, Pablo Ramírez, Carlos Martel and Alfredo J. Ibañez
Life 2020, 10(6), 89; https://doi.org/10.3390/life10060089 - 20 Jun 2020
Cited by 9 | Viewed by 4233
Abstract
Fungi are a highly diverse group of heterotrophic organisms that play an important role in diverse ecological interactions, many of which are chemically mediated. Fungi have a very versatile metabolism, which allows them to synthesize a large number of still little-known chemical compounds, [...] Read more.
Fungi are a highly diverse group of heterotrophic organisms that play an important role in diverse ecological interactions, many of which are chemically mediated. Fungi have a very versatile metabolism, which allows them to synthesize a large number of still little-known chemical compounds, such as soluble compounds that are secreted into the medium and volatile compounds that are chemical mediators over short and long distances. Mass spectrometry (MS) is currently playing a dominant role in mycological studies, mainly due to its inherent sensitivity and rapid identification capabilities of different metabolites. Furthermore, MS has also been used as a reliable and accurate tool for fungi identification (i.e., biotyping). Here, we introduce the readers about fungal specialized metabolites, their role in ecological interactions and provide an overview on the MS-based techniques used in fungal studies. We particularly present the importance of sampling techniques, strategies to reduce false-positive identification and new MS-based analytical strategies that can be used in mycological studies, further expanding the use of MS in broader applications. Therefore, we foresee a bright future for mass spectrometry-based research in the field of mycology. Full article
(This article belongs to the Special Issue Advances in Fungal -Omics)
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20 pages, 2374 KiB  
Article
Representational Difference Analysis of Transcripts Involved in Jervine Biosynthesis
by Magdalena Szeliga, Joanna Ciura and Mirosław Tyrka
Life 2020, 10(6), 88; https://doi.org/10.3390/life10060088 - 19 Jun 2020
Cited by 9 | Viewed by 2194
Abstract
Veratrum-type steroidal alkaloids (VSA) are the major bioactive ingredients that strongly determine the pharmacological activities of Veratrum nigrum. Biosynthesis of VSA at the molecular and genetic levels is not well understood. Next-generation sequencing of representational difference analysis (RDA) products after elicitation and [...] Read more.
Veratrum-type steroidal alkaloids (VSA) are the major bioactive ingredients that strongly determine the pharmacological activities of Veratrum nigrum. Biosynthesis of VSA at the molecular and genetic levels is not well understood. Next-generation sequencing of representational difference analysis (RDA) products after elicitation and precursor feeding was applied to identify candidate genes involved in VSA biosynthesis. A total of 12,048 contigs with a median length of 280 bases were received in three RDA libraries obtained after application of methyl jasmonate, squalene and cholesterol. The comparative analysis of annotated sequences was effective in identifying candidate genes. GABAT2 transaminase and hydroxylases active at C-22, C-26, C-11, and C-16 positions in late stages of jervine biosynthesis were selected. Moreover, genes coding pyrroline-5-carboxylate reductase and enzymes from the short-chain dehydrogenases/reductases family (SDR) associated with the reduction reactions of the VSA biosynthesis process were proposed. The data collected contribute to better understanding of jervine biosynthesis and may accelerate implementation of biotechnological methods of VSA biosynthesis. Full article
(This article belongs to the Section Plant Science)
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27 pages, 1834 KiB  
Review
Serum and Plasma Tumor Necrosis Factor Alpha Levels in Individuals with Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Meta-Regression
by Mohammad Moslem Imani, Masoud Sadeghi, Habibolah Khazaie, Mehrdad Emami, Dena Sadeghi Bahmani and Serge Brand
Life 2020, 10(6), 87; https://doi.org/10.3390/life10060087 - 12 Jun 2020
Cited by 20 | Viewed by 3664
Abstract
Background: Obstructive sleep apnea syndrome (OSAS) is associated with a variety of inflammatory factors. Specifically, proinflammatory cytokines appear to be associated with the pathogenesis of OSAS. Methods: For the present meta-analysis and meta-regression on serum and plasma tumor necrosis factor alpha (TNF-α) levels [...] Read more.
Background: Obstructive sleep apnea syndrome (OSAS) is associated with a variety of inflammatory factors. Specifically, proinflammatory cytokines appear to be associated with the pathogenesis of OSAS. Methods: For the present meta-analysis and meta-regression on serum and plasma tumor necrosis factor alpha (TNF-α) levels in individuals with and without OSAS, we performed a systematic search without any restrictions of the PubMed/Medline, Scopus, Cochrane Library, and Web of Science databases to find relevant articles published up to 1 February 2020. Results: Fifty-five (adults: 29 studies on serum and 17 studies on plasma; children: 4 studies on serum and 5 studies on plasma) were included and analyzed. Always compared to age-matched healthy controls, the pooled MDs were as follows: adults, serum: 10.22 pg/mL (95% CI = 8.86, 11.58; p < 0.00001); adults, plasma: 5.90 pg/mL (95% CI = 4.00, 7.80; p < 0.00001); children, serum: 0.21 pg/mL (95% CI = 0.05, 0.37; p = 0.01); children, plasma: 5.90 pg/mL (95% CI = 4.00, 7.80; p < 0.00001). Conclusions: Compared to healthy and age-matched controls, adult individuals with OSAS had significantly higher serum/plasma TNF-α levels. For children with OSAS, significantly higher levels were observed for TNF-α in serum but not in plasma. Full article
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35 pages, 2166 KiB  
Review
Neuroprotection or Neurotoxicity of Illicit Drugs on Parkinson’s Disease
by Carla Ferreira, Catarina Almeida, Sandra Tenreiro and Alexandre Quintas
Life 2020, 10(6), 86; https://doi.org/10.3390/life10060086 - 11 Jun 2020
Cited by 5 | Viewed by 7694
Abstract
Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown [...] Read more.
Parkinson’s Disease (PD) is currently the most rapid growing neurodegenerative disease and over the past generation, its global burden has more than doubled. The onset of PD can arise due to environmental, sporadic or genetic factors. Nevertheless, most PD cases have an unknown etiology. Chemicals, such as the anthropogenic pollutant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amphetamine-type stimulants, have been associated with the onset of PD. Conversely, cannabinoids have been associated with the treatment of the symptoms’. PD and medical cannabis is currently under the spotlight, and research to find its benefits on PD is on-going worldwide. However, the described clinical applications and safety of pharmacotherapy with cannabis products are yet to be fully supported by scientific evidence. Furthermore, the novel psychoactive substances are currently a popular alternative to classical drugs of abuse, representing an unknown health hazard for young adults who may develop PD later in their lifetime. This review addresses the neurotoxic and neuroprotective impact of illicit substance consumption in PD, presenting clinical evidence and molecular and cellular mechanisms of this association. This research area is utterly important for contemporary society since illicit drugs’ legalization is under discussion which may have consequences both for the onset of PD and for the treatment of its symptoms. Full article
(This article belongs to the Section Pharmaceutical Science)
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9 pages, 1296 KiB  
Article
Understanding the Mechanism of Recognition of Gab2 by the N-SH2 Domain of SHP2
by Lorenzo Visconti, Francesca Malagrinò, Livia Pagano and Angelo Toto
Life 2020, 10(6), 85; https://doi.org/10.3390/life10060085 - 11 Jun 2020
Cited by 7 | Viewed by 2494
Abstract
Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and it is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds, through its two SH2 domains, specific consensus sequences presenting a phosphorylated [...] Read more.
Gab2 is a scaffold protein with a crucial role in colocalizing signaling proteins and it is involved in the regulation of several important molecular pathways. SHP2 is a protein phosphatase that binds, through its two SH2 domains, specific consensus sequences presenting a phosphorylated tyrosine located on the disordered tail of Gab2. To shed light on the details of such a fundamental interaction for the physiology of the cell, we present a complete mutational analysis of the kinetics of binding between the N-SH2 domain of SHP2 and a peptide mimicking a specific region of Gab2. By analyzing kinetic data, we determined structural features of the transition state of the N-SH2 domain binding to Gab2, highlighting a remarkable cooperativity of the binding reaction. Furthermore, comparison of these data with ones previously obtained for another SH2 domain suggests the presence of underlying general features characterizing the binding process of SH2 domains. Data are discussed under the light of previous works on SH2 domains. Full article
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47 pages, 6096 KiB  
Article
On the Potential of Silicon as a Building Block for Life
by Janusz Jurand Petkowski, William Bains and Sara Seager
Life 2020, 10(6), 84; https://doi.org/10.3390/life10060084 - 10 Jun 2020
Cited by 41 | Viewed by 28652
Abstract
Despite more than one hundred years of work on organosilicon chemistry, the basis for the plausibility of silicon-based life has never been systematically addressed nor objectively reviewed. We provide a comprehensive assessment of the possibility of silicon-based biochemistry, based on a review of [...] Read more.
Despite more than one hundred years of work on organosilicon chemistry, the basis for the plausibility of silicon-based life has never been systematically addressed nor objectively reviewed. We provide a comprehensive assessment of the possibility of silicon-based biochemistry, based on a review of what is known and what has been modeled, even including speculative work. We assess whether or not silicon chemistry meets the requirements for chemical diversity and reactivity as compared to carbon. To expand the possibility of plausible silicon biochemistry, we explore silicon’s chemical complexity in diverse solvents found in planetary environments, including water, cryosolvents, and sulfuric acid. In no environment is a life based primarily around silicon chemistry a plausible option. We find that in a water-rich environment silicon’s chemical capacity is highly limited due to ubiquitous silica formation; silicon can likely only be used as a rare and specialized heteroatom. Cryosolvents (e.g., liquid N2) provide extremely low solubility of all molecules, including organosilicons. Sulfuric acid, surprisingly, appears to be able to support a much larger diversity of organosilicon chemistry than water. Full article
(This article belongs to the Special Issue Frontiers of Astrobiology)
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13 pages, 1598 KiB  
Article
Carotenoid Raman Signatures Are Better Preserved in Dried Cells of the Desert Cyanobacterium Chroococcidiopsis than in Hydrated Counterparts after High-Dose Gamma Irradiation
by Mickael Baqué, Alessandro Napoli, Claudia Fagliarone, Ralf Moeller, Jean-Pierre de Vera and Daniela Billi
Life 2020, 10(6), 83; https://doi.org/10.3390/life10060083 - 08 Jun 2020
Cited by 7 | Viewed by 2720
Abstract
Carotenoids are promising targets in our quest to search for life on Mars due to their biogenic origin and easy detection by Raman spectroscopy, especially with a 532 nm excitation thanks to resonance effects. Ionizing radiations reaching the surface and subsurface of Mars [...] Read more.
Carotenoids are promising targets in our quest to search for life on Mars due to their biogenic origin and easy detection by Raman spectroscopy, especially with a 532 nm excitation thanks to resonance effects. Ionizing radiations reaching the surface and subsurface of Mars are however detrimental for the long-term preservation of biomolecules. We show here that desiccation can protect carotenoid Raman signatures in the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 even after high-dose gamma irradiation. Indeed, while the height of the carotenoids Raman peaks was considerably reduced in hydrated cells exposed to gamma irradiation, it remained stable in dried cells irradiated with the highest tested dose of 113 kGy of gamma rays, losing only 15-20% of its non-irradiated intensity. Interestingly, even though the carotenoid Raman signal of hydrated cells lost 90% of its non-irradiated intensity, it was still detectable after exposure to 113 kGy of gamma rays. These results add insights into the preservation potential and detectability limit of carotenoid-like molecules on Mars over a prolonged period of time and are crucial in supporting future missions carrying Raman spectrometers to Mars’ surface. Full article
(This article belongs to the Special Issue Life on Mars)
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23 pages, 1821 KiB  
Review
State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders
by Federico Mucci, Donatella Marazziti, Alessandra Della Vecchia, Stefano Baroni, Paolo Morana, Barbara Carpita, Paola Mangiapane, Florinda Morana, Benedetto Morana and Liliana Dell’Osso
Life 2020, 10(6), 82; https://doi.org/10.3390/life10060082 - 06 Jun 2020
Cited by 15 | Viewed by 3464
Abstract
Mounting evidence highlights the involvement of inflammatory/immune systems and their relationships with neurotransmitters and different metabolic processes in mood disorders. Nevertheless, there is a general agreement that available findings are still inconclusive. Therefore, further investigations are required, aimed at deepening the role of [...] Read more.
Mounting evidence highlights the involvement of inflammatory/immune systems and their relationships with neurotransmitters and different metabolic processes in mood disorders. Nevertheless, there is a general agreement that available findings are still inconclusive. Therefore, further investigations are required, aimed at deepening the role of possible alterations of biomarkers in the pathophysiology of mood disorders that might lead to more focused and tailored treatments. The present study is a comprehensive review on these topics that seem to represent intriguing avenues for the development of real innovative therapeutic strategies of mood disorders. Full article
(This article belongs to the Section Medical Research)
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22 pages, 1498 KiB  
Concept Paper
Universal Codons with Enrichment from GC to AU Nucleotide Composition Reveal a Chronological Assignment from Early to Late Along with LUCA Formation
by Anastas Gospodinov and Dimiter Kunnev
Life 2020, 10(6), 81; https://doi.org/10.3390/life10060081 - 05 Jun 2020
Cited by 9 | Viewed by 3246
Abstract
The emergence of a primitive genetic code should be considered the most essential event during the origin of life. Almost a complete set of codons (as we know them) should have been established relatively early during the evolution of the last universal common [...] Read more.
The emergence of a primitive genetic code should be considered the most essential event during the origin of life. Almost a complete set of codons (as we know them) should have been established relatively early during the evolution of the last universal common ancestor (LUCA) from which all known organisms descended. Many hypotheses have been proposed to explain the driving forces and chronology of the evolution of the genetic code; however, none is commonly accepted. In the current paper, we explore the features of the genetic code that, in our view, reflect the mechanism and the chronological order of the origin of the genetic code. Our hypothesis postulates that the primordial RNA was mostly GC-rich, and this bias was reflected in the order of amino acid codon assignment. If we arrange the codons and their corresponding amino acids from GC-rich to AU-rich, we find that: 1. The amino acids encoded by GC-rich codons (Ala, Gly, Arg, and Pro) are those that contribute the most to the interactions with RNA (if incorporated into short peptides). 2. This order correlates with the addition of novel functions necessary for the evolution from simple to longer folded peptides. 3. The overlay of aminoacyl-tRNA synthetases (aaRS) to the amino acid order produces a distinctive zonal distribution for class I and class II suggesting an interdependent origin. These correlations could be explained by the active role of the bridge peptide (BP), which we proposed earlier in the evolution of the genetic code. Full article
(This article belongs to the Section Origin of Life)
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16 pages, 1611 KiB  
Article
Almond Skin Extracts and Chlorogenic Acid Delay Chronological Aging and Enhanced Oxidative Stress Response in Yeast
by Duangjai Tungmunnithum, Malika Abid, Ahmed Elamrani, Samantha Drouet, Mohamed Addi and Christophe Hano
Life 2020, 10(6), 80; https://doi.org/10.3390/life10060080 - 28 May 2020
Cited by 16 | Viewed by 3808
Abstract
Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained [...] Read more.
Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the chronological life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS/RNS, resulting in a significant reduction in cellular oxidative damage, as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the chronological life-span and control of the oxidative stress response of yeast. Full article
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16 pages, 2777 KiB  
Review
Distinctive Features of PipX, a Unique Signaling Protein of Cyanobacteria
by Jose I. Labella, Raquel Cantos, Paloma Salinas, Javier Espinosa and Asunción Contreras
Life 2020, 10(6), 79; https://doi.org/10.3390/life10060079 - 28 May 2020
Cited by 11 | Viewed by 3574
Abstract
PipX is a unique cyanobacterial protein identified by its ability to bind to PII and NtcA, two key regulators involved in the integration of signals of the nitrogen/carbon and energy status, with a tremendous impact on nitrogen assimilation and gene expression in cyanobacteria. [...] Read more.
PipX is a unique cyanobacterial protein identified by its ability to bind to PII and NtcA, two key regulators involved in the integration of signals of the nitrogen/carbon and energy status, with a tremendous impact on nitrogen assimilation and gene expression in cyanobacteria. PipX provides a mechanistic link between PII, the most widely distributed signaling protein, and NtcA, a global transcriptional regulator of cyanobacteria. PII, required for cell survival unless PipX is inactivated or down-regulated, functions by protein–protein interactions with transcriptional regulators, transporters, and enzymes. In addition, PipX appears to be involved in a wider signaling network, supported by the following observations: (i) PII–PipX complexes interact with PlmA, an as yet poorly characterized transcriptional regulator also restricted to cyanobacteria; (ii) the pipX gene is functionally connected with pipY, a gene encoding a universally conserved pyridoxal phosphate binding protein (PLPBP) involved in vitamin B6 and amino acid homeostasis, whose loss-of-function mutations cause B6-dependent epilepsy in humans, and (iii) pipX is part of a relatively robust, six-node synteny network that includes pipY and four additional genes that might also be functionally connected with pipX. In this overview, we propose that the study of the protein–protein interaction and synteny networks involving PipX would contribute to understanding the peculiarities and idiosyncrasy of signaling pathways that are conserved in cyanobacteria. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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19 pages, 3156 KiB  
Article
Comparative Study of SPA Mud from “Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)–Italy” and Industrially Optimized Mud for Skin Applications
by Beatrice Bergamaschi, Laura Marzola, Matteo Radice, Stefano Manfredini, Erika Baldini, Chiara Beatrice Vicentini, Elena Marrocchino, Sonia Molesini, Paola Ziosi, Carmela Vaccaro and Silvia Vertuani
Life 2020, 10(6), 78; https://doi.org/10.3390/life10060078 - 26 May 2020
Cited by 9 | Viewed by 2514
Abstract
The term “Salus per aquam (SPA) therapies” refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes [...] Read more.
The term “Salus per aquam (SPA) therapies” refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved. Full article
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17 pages, 2183 KiB  
Article
The Hypopiezotolerant Bacterium, Serratia liquefaciens, Failed to Grow in Mars Analog Soils under Simulated Martian Conditions at 7 hPa
by Andrew C. Schuerger, Rebecca L. Mickol and Petra Schwendner
Life 2020, 10(6), 77; https://doi.org/10.3390/life10060077 - 26 May 2020
Cited by 2 | Viewed by 3841
Abstract
The search for life on Mars is predicated on the idea that Earth and Mars life (if present) should be both carbon- and water-based with similar forms of evolution. However, the astrobiology community can currently only investigate plausible Martian microbial ecosystems by using [...] Read more.
The search for life on Mars is predicated on the idea that Earth and Mars life (if present) should be both carbon- and water-based with similar forms of evolution. However, the astrobiology community can currently only investigate plausible Martian microbial ecosystems by using Terran life-forms as proxies. In order to examine how life might persist on Mars, we used a hypopiezotolerant bacterium (def., able to grow at 7–10 hPa)—Serratia liquefaciens—in growth assays with four Mars analog soils conducted under a subset of simulated Martian conditions including 7 hPa, 0 °C, and a CO2-enriched anoxic atmosphere (called low-PTA conditions). The four Mars analog soils included an Aeolian dust analog, the Mars JSC-1 analog, a Phoenix lander-site simulant, and a high-Salts analog. Serratia liquefaciens cells were able to grow at 30 °C in a liquid minimal basal medium (MBM) supplemented with 10- or 20-mM sucrose, Spizizen salts, and micronutrients. When the four analog soils were doped with both MBM and cells of S. liquefaciens, and subsequently incubated at 30 °C for 72 h, cell densities increased between 2-logs (Phoenix analog) and 4-logs (Aeolian and JSC-1 analogs); the Salts analog led to complete inactivation of S. liquefaciens within 24 h. In contrast, when the experiment was repeated, but incubated under low-PTA conditions, S. liquefaciens cells were either killed immediately by the Salts analog, or decreased by >5 logs over 28 d by the Aeolian, JSC-1, and Phoenix analogs. The failure of S. liquefaciens to grow in the analog soils under low-PTA conditions was attributed to the synergistic interactions among six factors (i.e., low pressure, low temperature, anoxic atmosphere (i.e., the low-PTA conditions), low-pH in the Salts soil, dissolved salts in all analogs, and oligotrophic conditions) that increased the biocidal or inhibitory conditions within the analog soils. Results suggest that even if a hypopiezotolerant Terran microbe is displaced from a spacecraft surface on Mars, and lands in a hydrated and nutrient-rich niche, growth in the Martian regolith is not automatically assured. Full article
(This article belongs to the Special Issue Life on Mars)
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