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Life, Volume 10, Issue 12 (December 2020) – 61 articles

Cover Story (view full-size image): Light-emitting and light-sensing proteins from nature have been repurposed to monitor or control biological processes. Recently, the fields of bioluminescence and optogenetics have started to converge to deploy biological light to drive cell behaviour. In this review, the initial achievements in bioluminescence-driven optogenetics are summarised, with the emphasis on its potential for engineering programmable light-based molecular interactions and communication. View this paper
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Review
Virus-Like Particle Mediated CRISPR/Cas9 Delivery for Efficient and Safe Genome Editing
Life 2020, 10(12), 366; https://doi.org/10.3390/life10120366 - 21 Dec 2020
Cited by 4 | Viewed by 1476
Abstract
The discovery of designer nucleases has made genome editing much more efficient than before. The designer nucleases have been widely used for mechanistic studies, animal model generation and gene therapy development. However, potential off-targets and host immune responses are issues still need to [...] Read more.
The discovery of designer nucleases has made genome editing much more efficient than before. The designer nucleases have been widely used for mechanistic studies, animal model generation and gene therapy development. However, potential off-targets and host immune responses are issues still need to be addressed for in vivo uses, especially clinical applications. Short term expression of the designer nucleases is necessary to reduce both risks. Currently, various delivery methods are being developed for transient expression of designer nucleases including Zinc Finger Nuclease (ZNF), Transcription Activator-Like Effector Nuclease (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated (CRISPR/Cas). Recently, virus-like particles are being used for gene editing. In this review, we will talk through commonly used genome editing nucleases, discuss gene editing delivery tools and review the latest literature using virus-like particles to deliver gene editing effectors. Full article
(This article belongs to the Special Issue Capsid Protein)
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Review
The Circadian Clock—A Molecular Tool for Survival in Cyanobacteria
Life 2020, 10(12), 365; https://doi.org/10.3390/life10120365 - 20 Dec 2020
Viewed by 953
Abstract
Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. [...] Read more.
Cyanobacteria are photosynthetic organisms that are known to be responsible for oxygenating Earth’s early atmosphere. Having evolved to ensure optimal survival in the periodic light/dark cycle on this planet, their genetic codes are packed with various tools, including a sophisticated biological timekeeping system. Among the cyanobacteria is Synechococcus elongatus PCC 7942, the simplest clock-harboring organism with a powerful genetic tool that enabled the identification of its intricate timekeeping mechanism. The three central oscillator proteins—KaiA, KaiB, and KaiC—drive the 24 h cyclic gene expression rhythm of cyanobacteria, and the “ticking” of the oscillator can be reconstituted inside a test tube just by mixing the three recombinant proteins with ATP and Mg2+. Along with its biochemical resilience, the post-translational rhythm of the oscillation can be reset through sensing oxidized quinone, a metabolite that becomes abundant at the onset of darkness. In addition, the output components pick up the information from the central oscillator, tuning the physiological and behavioral patterns and enabling the organism to better cope with the cyclic environmental conditions. In this review, we highlight our understanding of the cyanobacterial circadian clock and discuss how it functions as a molecular chronometer that readies the host for predictable changes in its surroundings. Full article
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Article
Association between Systemic Antioxidant Capacity and Retinal Vessel Diameters in Patients with Primary-Open Angle Glaucoma
Life 2020, 10(12), 364; https://doi.org/10.3390/life10120364 - 20 Dec 2020
Viewed by 639
Abstract
The retinal vessel narrowing may be implicated in the pathogenesis of glaucoma; however, the association between systemic oxidative stress and retinal vessel diameter remains largely unknown. We examined the relationship between serum oxidative stress markers and retinal vessel diameters in eyes with primary [...] Read more.
The retinal vessel narrowing may be implicated in the pathogenesis of glaucoma; however, the association between systemic oxidative stress and retinal vessel diameter remains largely unknown. We examined the relationship between serum oxidative stress markers and retinal vessel diameters in eyes with primary open-angle glaucoma (POAG) and cataract, using central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). We included 66 eyes of 66 patients with POAG (37 men, 29 women; 65.4 ± 11.7 years) and 20 eyes of 20 patients with cataract (7 men, 13 women; 69.4 ± 9.0 years) as the controls. The CRAE (p < 0.0001), CRVE (p < 0.0001), and serum biological antioxidant potential (BAP) (p = 0.0419) were significantly lower in the POAG group compared to the controls. The BAP showed significant correlation both with CRAE (ρ = 0.2148, p = 0.0471) and systolic blood pressure (ρ = −0.2431, p = 0.0241), while neither Diacron reactive oxygen metabolites nor sulfhydryl test correlated with them. The multivariate analyses indicated that age, best corrected visual acuity, and BAP were independent factors for CRAE or CRVE. The present study suggested that lower systemic antioxidant capacity was significantly associated with the intraocular pressure-independent vascular narrowing in POAG patients. This study provided a novel insight into the pathophysiology of glaucoma and highlighted the clinical impact on systemic antioxidant treatment for patients with glaucoma. Full article
(This article belongs to the Special Issue Retinal Disease and Metabolism)
Review
The Role of Connexin 43 in Lung Disease
Life 2020, 10(12), 363; https://doi.org/10.3390/life10120363 - 19 Dec 2020
Viewed by 556
Abstract
The term lung disease describes a broad category of disorders that impair lung function. More than 35 million Americans have a preventable chronic lung disease with high mortality rates due to limited treatment efficacy. The recent increase in patients with lung disease highlights [...] Read more.
The term lung disease describes a broad category of disorders that impair lung function. More than 35 million Americans have a preventable chronic lung disease with high mortality rates due to limited treatment efficacy. The recent increase in patients with lung disease highlights the need to increase our understanding of mechanisms driving lung inflammation. Connexins, gap junction proteins, and more specifically connexin 43 (Cx43), are abundantly expressed in the lung and are known to play a role in lung diseases. This review focuses on the role of Cx43 in pathology associated with acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and asthma. Additionally, we discuss the role of Cx43 in preventing disease through the transfer of mitochondria between cells. We aim to highlight the need to better understand what cell types are expressing Cx43 and how this expression influences lung disease. Full article
(This article belongs to the Section Physiology and Pathology)
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Communication
Shed Light in the DaRk LineagES of the Fungal Tree of Life—STRES
Life 2020, 10(12), 362; https://doi.org/10.3390/life10120362 - 19 Dec 2020
Viewed by 1164
Abstract
The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to stresses including UV- and ionizing-radiation, heat and desiccation, toxic metals, and [...] Read more.
The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to stresses including UV- and ionizing-radiation, heat and desiccation, toxic metals, and organic pollutants. Consequently, they are amongst the most stunning extremophiles and poly-extreme-tolerant organisms on Earth. Even though ca. 60 black fungal genomes have been sequenced to date, [mostly in the family Herpotrichiellaceae (Eurotiomycetes)], the class Dothideomycetes that hosts the largest majority of extremophiles has only been sparsely sampled. By sequencing up to 92 species that will become reference genomes, the “Shed light in The daRk lineagES of the fungal tree of life” (STRES) project will cover a broad collection of black fungal diversity spread throughout the Fungal Tree of Life. Interestingly, the STRES project will focus on mostly unsampled genera that display different ecologies and life-styles (e.g., ant- and lichen-associated fungi, rock-inhabiting fungi, etc.). With a resequencing strategy of 10- to 15-fold depth coverage of up to ~550 strains, numerous new reference genomes will be established. To identify metabolites and functional processes, these new genomic resources will be enriched with metabolomics analyses coupled with transcriptomics experiments on selected species under various stress conditions (salinity, dryness, UV radiation, oligotrophy). The data acquired will serve as a reference and foundation for establishing an encyclopedic database for fungal metagenomics as well as the biology, evolution, and ecology of the fungi in extreme environments. Full article
(This article belongs to the Special Issue Advances in Fungal -Omics)
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Article
A Biomarker Panel of Radiation-Upregulated miRNA as Signature for Ionizing Radiation Exposure
Life 2020, 10(12), 361; https://doi.org/10.3390/life10120361 - 18 Dec 2020
Viewed by 698
Abstract
Ionizing radiation causes serious injury to the human body and has long-time impacts on health. It is important to find optimal biomarkers for the early quick screening of exposed individuals. A series of miRNAs signatures have been developed as the new biomarkers for [...] Read more.
Ionizing radiation causes serious injury to the human body and has long-time impacts on health. It is important to find optimal biomarkers for the early quick screening of exposed individuals. A series of miRNAs signatures have been developed as the new biomarkers for diagnosis, survival, and prognostic prediction of cancers. Here, we have identified the ionizing radiation-inducible miRNAs profile through microarray analysis. The biological functions were predicted for the top six upregulated miRNAs by 4 Gy γ-rays: miR-1246, miR-1307-3p, miR-3197, miR-4267, miR-5096 and miR-7641. The miRNA-gene network and target gene-pathway network analyses revealed that DNAH3 is the target gene associated with all the six miRNAs. GOLGB1 is related to 4 miRNAs and other 26 genes targeted by 3 miRNAs. The upregulation of fifteen miRNAs were further verified at 4 h and 24 h after 0 to 10 Gy irradiation in the human lymphoblastoid AHH-1 cells, and some demonstrated a dose-dependent increased. Six miRNAs, including miR-145, miR-663, miR-1273g-3p, miR-6090, miR-6727-5p and miR-7641, were validated to be dose-dependently upregulated at 4 h or 24 h post-irradiation in both AHH-1 and human peripheral blood lymphocytes irradiated ex vivo. This six-miRNA signature displays the superiority as a radiation biomarker for the translational application of screening and assessment of radiation exposed individuals. Full article
(This article belongs to the Section Radiobiology, Nuclear Medicine and Medical Imaging)
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Article
Characterization of Sensorineural Hearing Loss in Children with Alport Syndrome
Life 2020, 10(12), 360; https://doi.org/10.3390/life10120360 - 18 Dec 2020
Viewed by 705
Abstract
Most adults with Alport syndrome (AS) suffer from progressive sensorineural hearing loss. However, little is known about the early characteristics of hearing loss in children with AS. As a part of the EARLY PRO-TECT Alport trial, this study was the first clinical trial [...] Read more.
Most adults with Alport syndrome (AS) suffer from progressive sensorineural hearing loss. However, little is known about the early characteristics of hearing loss in children with AS. As a part of the EARLY PRO-TECT Alport trial, this study was the first clinical trial ever to investigate hearing loss in children with AS over a timespan of up to six years Nine of 51 children (18%) had hearing impairment. Audiograms were divided into three age groups: in the 5–9-year-olds, the 4-pure tone average (4PTA) was 8.9 decibel (dB) (n = 15) in those with normal hearing and 43.8 dB (n = 2, 12%) in those with hearing impairment. Among the 10–13-year-olds, 4PTA was 4.8 dB (healthy, n = 12) and 41.4 dB (hearing impaired, n = 6.33%). For the 14–20-year-olds, the 4PTA was 7.0 dB (healthy; n = 9) and 48.2 dB (hearing impaired, n = 3.25%). On average, hearing thresholds of the hearing impaired group increased, especially at frequencies between 1–3 kHz. In conclusion, 18% of children developed hearing loss, with a maximum hearing loss in the audiograms at 1–3 kHz. The percentage of children with hearing impairment increased from 10% at baseline to 18% at end of trial as did the severity of hearing loss. Full article
(This article belongs to the Section Medical Research)
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Article
Screening, Linkage to Care and Treatment of Hepatitis C Infection in Primary Care Setting in the South of Italy
Life 2020, 10(12), 359; https://doi.org/10.3390/life10120359 - 18 Dec 2020
Cited by 1 | Viewed by 616
Abstract
Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was [...] Read more.
Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment. Full article
(This article belongs to the Special Issue The New Challenges in Infectious Diseases)
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Article
Quality Outcomes in Appendicitis Care: Identifying Opportunities to Improve Care
Life 2020, 10(12), 358; https://doi.org/10.3390/life10120358 - 18 Dec 2020
Cited by 1 | Viewed by 613
Abstract
Introduction: Appendicitis is one of the most common causes of acute abdominal pain requiring surgical intervention, but the variability of diagnosis and management continue to challenge the surgeons. Aim: This study assessed patients undergoing appendectomy to identify opportunities to improve diagnostic accuracy [...] Read more.
Introduction: Appendicitis is one of the most common causes of acute abdominal pain requiring surgical intervention, but the variability of diagnosis and management continue to challenge the surgeons. Aim: This study assessed patients undergoing appendectomy to identify opportunities to improve diagnostic accuracy and outcomes. Methods: An ethically approved retrospective cohort study was undertaken between March 2016 and March 2017 at a single university hospital of all consecutive adult and paediatric patients undergoing appendectomy. Demographic data including age, gender, co-morbidities, presentation and triage timings along with investigation, imaging and operative data were analysed. Appendicitis was defined as acute based on histology coupled with intraoperative grading with the American Association for the Surgery of Trauma (AAST) grades. Complications using the Clavien–Dindo classification along with 30-day re-admission rates and the negative appendectomy rates (NAR) were recorded and categorised greater and less than 25%. The use of scoring systems was assessed, and retrospective scoring performed to compare the Alvarado, Adult Appendicitis Score (AAS) and the Appendicitis Inflammatory Response (AIR) score. Results: A total of 201 patients were studied, 115 male and 86 females, of which 136/201 (67.6%) were adults and 65/201 (32.3%) paediatric. Of the adult group, 83 were male and 53 were female, and of the paediatric group, 32 were male and 33 were female. Median age was 20 years (range: 5 years to 81 years) and no patient below the age of 5 years had an appendectomy during our study period. All patients were admitted via the emergency department and median time from triage to surgical review was 2 h and 38 min, (range: 10 min to 26 h and 10 min). Median time from emergency department review to surgical review, 55 min (range: 5 min to 6 h and 43 min). Median time to operating theatre was 21 h from admission (range: 45 min to 140 h and 30 min). Out of the total patients, 173 (86.1%) underwent laparoscopic approach, 28 (13.9%) had an open approach and 12 (6.9%) of the 173 were converted to open. Acute appendicitis occurred in 166/201 (82.6%). There was no significant association between grade of appendicitis and surgeons’ categorical NAR rate (p = 0.07). Imaging was performed in 118/201 (58.7%); abdominal ultrasound (US) in 53 (26.4%), abdominal computed tomography (CT) in 59 (29.2%) and both US and CT in 6 (3%). The best cut-off point was 4 (sensitivity 84.3% and specificity of 65.7%) for AIR score, 9 (sensitivity of 74.7% and specificity of 68.6%) for AAS, and 7 (sensitivity of 77.7% and specificity of 71.4%) for the Alvarado score. Twenty-four (11.9%) were re-admitted, due to pain in 16 (58.3%), collections in 3 (25%), 1 (4.2%) wound abscess, 1 (4.2%) stump appendicitis, 1 (4.2%) small bowel obstruction and 1 (4.2%) fresh rectal bleeding. CT guided drainage was performed in 2 (8.3%). One patient had release of wound collection under general anaesthetic whereas another patient had laparoscopic drain placement. A laparotomy was undertaken in 3 (12.5%) patients with division of adhesions in 1, the appendicular stump removed in 1 and 1 had multiple collections drained. Conclusion: The negative appendectomy and re-admission rates were unacceptably high and need to be reduced. Minimising surgical variance with use of scoring systems and introduction of pathways may be a strategy to reduce NAR. New systems of feedback need to be introduced to improve outcomes. Full article
(This article belongs to the Special Issue Trauma and Emergency: Beyond Damage Control Surgery)
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Article
β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice
Life 2020, 10(12), 357; https://doi.org/10.3390/life10120357 - 17 Dec 2020
Cited by 3 | Viewed by 799
Abstract
The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific β-catenin knockout [...] Read more.
The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific β-catenin knockout that were subjected to a swimming training model. β-Catenin haploinsufficient mice subjected to endurance training displayed a decreased β-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase–Akt (Pi3K–Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice. We further observed an increased level of proteins involved in glucose aerobic metabolism and β-oxidation along with perturbed activity of mitochondrial oxidative phosphorylation complexes (OXPHOS) in trained β-catenin haploinsufficient mice. Taken together, Wnt/β-catenin signaling appears to govern metabolic regulatory programs, sustaining metabolic plasticity in adult hearts during the adaptation to endurance training. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Review
An Overview of Genomics, Phylogenomics and Proteomics Approaches in Ascomycota
Life 2020, 10(12), 356; https://doi.org/10.3390/life10120356 - 17 Dec 2020
Cited by 3 | Viewed by 1237
Abstract
Fungi are among the most successful eukaryotes on Earth: they have evolved strategies to survive in the most diverse environments and stressful conditions and have been selected and exploited for multiple aims by humans. The characteristic features intrinsic of Fungi have required evolutionary [...] Read more.
Fungi are among the most successful eukaryotes on Earth: they have evolved strategies to survive in the most diverse environments and stressful conditions and have been selected and exploited for multiple aims by humans. The characteristic features intrinsic of Fungi have required evolutionary changes and adaptations at deep molecular levels. Omics approaches, nowadays including genomics, metagenomics, phylogenomics, transcriptomics, metabolomics, and proteomics have enormously advanced the way to understand fungal diversity at diverse taxonomic levels, under changeable conditions and in still under-investigated environments. These approaches can be applied both on environmental communities and on individual organisms, either in nature or in axenic culture and have led the traditional morphology-based fungal systematic to increasingly implement molecular-based approaches. The advent of next-generation sequencing technologies was key to boost advances in fungal genomics and proteomics research. Much effort has also been directed towards the development of methodologies for optimal genomic DNA and protein extraction and separation. To date, the amount of proteomics investigations in Ascomycetes exceeds those carried out in any other fungal group. This is primarily due to the preponderance of their involvement in plant and animal diseases and multiple industrial applications, and therefore the need to understand the biological basis of the infectious process to develop mechanisms for biologic control, as well as to detect key proteins with roles in stress survival. Here we chose to present an overview as much comprehensive as possible of the major advances, mainly of the past decade, in the fields of genomics (including phylogenomics) and proteomics of Ascomycota, focusing particularly on those reporting on opportunistic pathogenic, extremophilic, polyextremotolerant and lichenized fungi. We also present a review of the mostly used genome sequencing technologies and methods for DNA sequence and protein analyses applied so far for fungi. Full article
(This article belongs to the Special Issue Advances in Fungal -Omics)
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Review
Structural Determinants and Their Role in Cyanobacterial Morphogenesis
Life 2020, 10(12), 355; https://doi.org/10.3390/life10120355 - 17 Dec 2020
Cited by 5 | Viewed by 1373
Abstract
Cells have to erect and sustain an organized and dynamically adaptable structure for an efficient mode of operation that allows drastic morphological changes during cell growth and cell division. These manifold tasks are complied by the so-called cytoskeleton and its associated proteins. In [...] Read more.
Cells have to erect and sustain an organized and dynamically adaptable structure for an efficient mode of operation that allows drastic morphological changes during cell growth and cell division. These manifold tasks are complied by the so-called cytoskeleton and its associated proteins. In bacteria, FtsZ and MreB, the bacterial homologs to tubulin and actin, respectively, as well as coiled-coil-rich proteins of intermediate filament (IF)-like function to fulfil these tasks. Despite generally being characterized as Gram-negative, cyanobacteria have a remarkably thick peptidoglycan layer and possess Gram-positive-specific cell division proteins such as SepF and DivIVA-like proteins, besides Gram-negative and cyanobacterial-specific cell division proteins like MinE, SepI, ZipN (Ftn2) and ZipS (Ftn6). The diversity of cellular morphologies and cell growth strategies in cyanobacteria could therefore be the result of additional unidentified structural determinants such as cytoskeletal proteins. In this article, we review the current advances in the understanding of the cyanobacterial cell shape, cell division and cell growth. Full article
(This article belongs to the Special Issue Cellular and Molecular Strategies in Cyanobacterial Survival)
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Article
VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions
Life 2020, 10(12), 354; https://doi.org/10.3390/life10120354 - 17 Dec 2020
Cited by 2 | Viewed by 606
Abstract
High glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal transition (EMT) has been reported in several diseases, little [...] Read more.
High glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal transition (EMT) has been reported in several diseases, little is known about its relationship with VSIG4 under diabetic conditions. This study aimed to investigate the role of VSIG4 in human tubule cells stimulated by high glucose (HG, 55 mM). HG upregulated both mRNA and protein levels of VSIG4 in proximal tubule cells (HK-2 cells) and Madin Darby Canine Kidney cells. These upregulations were accompanied by increased expression of mesenchymal markers such as fibronectin, N-cadherin, matrix metalloproteinase 9, and vimentin, and by decreased expression of the epithelial marker, E-cadherin. The siRNA-mediated inhibition of VSIG4 in HK-2 cells restored the dysregulation of EMT in cells. Interestingly, VSIG4 inhibition did not affect the expression of transforming growth factor (TGF)-β, whereas inhibition of TGF-β reduced VSIG4 expression, subsequently suppressing fibrosis markers. These findings suggest that VSIG4 plays an important role in mediating renal tubular EMT through the downstream action of HG-induced TGF-β activation. Full article
(This article belongs to the Section Medical Research)
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Article
High Variability of Postsurgical Anatomy Supports the Need for Individualized Drug-Eluting Implants to Treat Chronic Rhinosinusitis
Life 2020, 10(12), 353; https://doi.org/10.3390/life10120353 - 17 Dec 2020
Cited by 2 | Viewed by 600
Abstract
Chronic rhinosinusitis (CRS) is a common disease in the general population that is increasing in incidence and prevalence, severely affecting patients’ quality of life. Medical treatment for CRS includes self-management techniques, topical and oral medical treatments, and functional endoscopic sinus surgery (FESS). FESS [...] Read more.
Chronic rhinosinusitis (CRS) is a common disease in the general population that is increasing in incidence and prevalence, severely affecting patients’ quality of life. Medical treatment for CRS includes self-management techniques, topical and oral medical treatments, and functional endoscopic sinus surgery (FESS). FESS is a standard procedure to restore sinus ventilation and drainage by physically enlarging the inflamed sinus passageways. Nasal drug-releasing stents are implanted to keep the surgically expanded aperture to the sinus frontalis open. The outcome of such an intervention is highly variable. We defined the anatomical structures which should be removed, along with ‘no-go areas’ which need to be preserved during FESS. Based on these definitions, we used cone beam computed tomography (CBCT) images to measure the dimensions of the frontal neo-ostium in 22 patients. We demonstrate anatomical variability in the volume and diameter of the frontal sinus recess after surgery. This variability could be the cause of therapy failure of drug-eluting implants after FESS in some patients. Implants individually made to fit a given patient’s postsurgical anatomy may improve the therapeutic outcome. Full article
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Review
Prebiotic Reaction Networks in Water
Life 2020, 10(12), 352; https://doi.org/10.3390/life10120352 - 16 Dec 2020
Cited by 2 | Viewed by 1396
Abstract
A prevailing strategy in origins of life studies is to explore how chemistry constrained by hypothetical prebiotic conditions could have led to molecules and system level processes proposed to be important for life’s beginnings. This strategy has yielded model prebiotic reaction networks that [...] Read more.
A prevailing strategy in origins of life studies is to explore how chemistry constrained by hypothetical prebiotic conditions could have led to molecules and system level processes proposed to be important for life’s beginnings. This strategy has yielded model prebiotic reaction networks that elucidate pathways by which relevant compounds can be generated, in some cases, autocatalytically. These prebiotic reaction networks provide a rich platform for further understanding and development of emergent “life-like” behaviours. In this review, recent advances in experimental and analytical procedures associated with classical prebiotic reaction networks, like formose and Miller-Urey, as well as more recent ones are highlighted. Instead of polymeric networks, i.e., those based on nucleic acids or peptides, the focus is on small molecules. The future of prebiotic chemistry lies in better understanding the genuine complexity that can result from reaction networks and the construction of a centralised database of reactions useful for predicting potential network evolution is emphasised. Full article
(This article belongs to the Special Issue Frontiers of Astrobiology)
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Communication
Investigation of Genetic Variations of IL6 and IL6R as Potential Prognostic and Pharmacogenetics Biomarkers: Implications for COVID-19 and Neuroinflammatory Disorders
Life 2020, 10(12), 351; https://doi.org/10.3390/life10120351 - 16 Dec 2020
Cited by 7 | Viewed by 949
Abstract
In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population [...] Read more.
In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID-19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID-19 may be helpful to counteract harmful complications and prevent multiorgan failure. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize personalized medicine protocols for chronic, age-related and modern public health emergencies. Full article
(This article belongs to the Section Genetics and Genomics)
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Article
Outcomes Evaluated in Controlled Clinical Trials on the Management of COVID-19: A Methodological Systematic Review
Life 2020, 10(12), 350; https://doi.org/10.3390/life10120350 - 15 Dec 2020
Cited by 1 | Viewed by 1652
Abstract
It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs [...] Read more.
It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5 May 2020, and the instruments used to measure these outcomes. Significant heterogeneity was observed in the selection of outcomes and instruments. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality (72.5%) and adverse events (55.6%), while hospital admission (50.8%) and viral detection/load (55.6%) are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for greater consistency, to enable decision makers to compare and contrast studies. Full article
(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)
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Article
Loganic Acid, an Iridoid Glycoside Extracted from Cornus mas L. Fruits, Reduces of Carbonyl/Oxidative Stress Biomarkers in Plasma and Restores Antioxidant Balance in Leukocytes of Rats with Streptozotocin-Induced Diabetes Mellitus
Life 2020, 10(12), 349; https://doi.org/10.3390/life10120349 - 15 Dec 2020
Cited by 2 | Viewed by 759
Abstract
The various complications related to diabetes are due to the alteration in plasma components and functional activity of blood cells, hence the search for preventive remedies that would ameliorate the clinical condition of patients is a relevant problem today. The main aim of [...] Read more.
The various complications related to diabetes are due to the alteration in plasma components and functional activity of blood cells, hence the search for preventive remedies that would ameliorate the clinical condition of patients is a relevant problem today. The main aim of the present study was to examine the antidiabetic potency and antioxidant effects of loganic acid (LA) in blood of diabetic rats. LA showed a restoration of balance between functioning of antioxidant defense system and oxidative stress in leukocytes without notable effects on blood glucose levels when administered orally to rats (20 mg/kg b.w./day) for 14 days. LA ameliorated antioxidant status in leukocytes, as indicated by increasing the content of reduced glutathione and activities of catalase, glutathione peroxidase and glutathione reductase along with decreasing levels of intracellular reactive oxygen species. In addition, we observed the ability of LA to protect against formation and accumulation of glycation and oxidation protein products and malondialdehyde derivates in plasma. Therefore, LA showed antioxidant properties that may have beneficial effects under diabetes. Such results may represent LA as one of the plant components in the development of new drugs that will correct metabolic and functional disorders in leukocytes under diabetes. Full article
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Article
Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus
Life 2020, 10(12), 348; https://doi.org/10.3390/life10120348 - 14 Dec 2020
Cited by 4 | Viewed by 1308
Abstract
Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different [...] Read more.
Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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Review
Bird Eye View of Protein Subcellular Localization Prediction
Life 2020, 10(12), 347; https://doi.org/10.3390/life10120347 - 14 Dec 2020
Cited by 2 | Viewed by 1537
Abstract
Proteins are made up of long chain of amino acids that perform a variety of functions in different organisms. The activity of the proteins is determined by the nucleotide sequence of their genes and by its 3D structure. In addition, it is essential [...] Read more.
Proteins are made up of long chain of amino acids that perform a variety of functions in different organisms. The activity of the proteins is determined by the nucleotide sequence of their genes and by its 3D structure. In addition, it is essential for proteins to be destined to their specific locations or compartments to perform their structure and functions. The challenge of computational prediction of subcellular localization of proteins is addressed in various in silico methods. In this review, we reviewed the progress in this field and offered a bird eye view consisting of a comprehensive listing of tools, types of input features explored, machine learning approaches employed, and evaluation matrices applied. We hope the review will be useful for the researchers working in the field of protein localization predictions. Full article
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Review
De Novo Nucleic Acids: A Review of Synthetic Alternatives to DNA and RNA That Could Act as Bio-Information Storage Molecules
Life 2020, 10(12), 346; https://doi.org/10.3390/life10120346 - 11 Dec 2020
Cited by 3 | Viewed by 1126
Abstract
Modern terran life uses several essential biopolymers like nucleic acids, proteins and polysaccharides. The nucleic acids, DNA and RNA are arguably life’s most important, acting as the stores and translators of genetic information contained in their base sequences, which ultimately manifest themselves in [...] Read more.
Modern terran life uses several essential biopolymers like nucleic acids, proteins and polysaccharides. The nucleic acids, DNA and RNA are arguably life’s most important, acting as the stores and translators of genetic information contained in their base sequences, which ultimately manifest themselves in the amino acid sequences of proteins. But just what is it about their structures; an aromatic heterocyclic base appended to a (five-atom ring) sugar-phosphate backbone that enables them to carry out these functions with such high fidelity? In the past three decades, leading chemists have created in their laboratories synthetic analogues of nucleic acids which differ from their natural counterparts in three key areas as follows: (a) replacement of the phosphate moiety with an uncharged analogue, (b) replacement of the pentose sugars ribose and deoxyribose with alternative acyclic, pentose and hexose derivatives and, finally, (c) replacement of the two heterocyclic base pairs adenine/thymine and guanine/cytosine with non-standard analogues that obey the Watson–Crick pairing rules. This manuscript will examine in detail the physical and chemical properties of these synthetic nucleic acid analogues, in particular on their abilities to serve as conveyors of genetic information. If life exists elsewhere in the universe, will it also use DNA and RNA? Full article
(This article belongs to the Special Issue Selected Papers from the 2021 NoR CEL Conference)
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Review
The Microbiota/Host Immune System Interaction in the Nose to Protect from COVID-19
Life 2020, 10(12), 345; https://doi.org/10.3390/life10120345 - 11 Dec 2020
Cited by 2 | Viewed by 1262
Abstract
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection [...] Read more.
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection affect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology. Full article
(This article belongs to the Section Medical Research)
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Review
Cardiotoxicity of Novel Targeted Hematological Therapies
Life 2020, 10(12), 344; https://doi.org/10.3390/life10120344 - 11 Dec 2020
Cited by 1 | Viewed by 958
Abstract
Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or [...] Read more.
Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or hypertension, which dramatically reduce quality of life of cancer survivors. Standard chemotherapy exerts its toxic effect mainly by inducing oxidative stress and genomic instability, while new targeted therapies work by interfering with signaling pathways important not only in cancer cells but also in myocytes. For example, Bruton’s tyrosine kinase (BTK) inhibitors interfere with class I phosphoinositide 3-kinase isoforms involved in cardiac hypertrophy, contractility, and regulation of various channel forming proteins; thus, off-target effects of BTK inhibitors are associated with increased frequency of arrhythmias, such as atrial fibrillation, compared to standard chemotherapy. In this review, we summarize current knowledge of cardiotoxic effects of targeted therapies used in hematology. Full article
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Article
Time Course and Magnitude of Tolerance to the Ergogenic Effect of Caffeine on the Second Ventilatory Threshold
Life 2020, 10(12), 343; https://doi.org/10.3390/life10120343 - 10 Dec 2020
Cited by 1 | Viewed by 828
Abstract
Pre-exercise caffeine ingestion has been shown to increase the workload at ventilatory threshold, suggesting an ergogenic effect of this stimulant on submaximal aerobic exercise. However, the time course of tolerance to the effect of caffeine on ventilatory threshold is unknown. This study aimed [...] Read more.
Pre-exercise caffeine ingestion has been shown to increase the workload at ventilatory threshold, suggesting an ergogenic effect of this stimulant on submaximal aerobic exercise. However, the time course of tolerance to the effect of caffeine on ventilatory threshold is unknown. This study aimed to determine the evolution of tolerance to the ergogenic effect of caffeine on the ventilatory threshold. Methods: Eleven participants (age 32.3 ± 4.9 yrs, height 171 ± 8 cm, body mass 66.6 ± 13.6 kg, VO2max = 48.0 ± 3.8 mL/kg/min) took part in a longitudinal, double-blind, placebo-controlled, randomized, crossover experimental design. Each participant took part in two identical treatments: in one treatment, participants ingested a capsule containing 3 mg of caffeine per kg of body mass per day (mg/kg/day) for twenty consecutive days; in the other treatment, participants ingested a capsule filled with a placebo for the same duration and frequency. During these treatments, participants performed a maximal ramp test on a cycle ergometer three times per week and the second ventilatory threshold (VT2) was assessed by using the ventilatory equivalents for oxygen and carbon dioxide. Results: A two-way ANOVA with repeated measures (substance × time) revealed statistically significant main effects of caffeine (p < 0.01) and time (p = 0.04) on the wattage obtained at VT2, although there was no interaction (p = 0.09). In comparison to the placebo, caffeine increased the workload at VT2 on days 1, 4, 6 and 15 of ingestion (p < 0.05). The size of the ergogenic effect of caffeine over the placebo on the workload at VT2 was progressively reduced with the duration of the treatment. In addition, there were main effects of caffeine (p = 0.03) and time (p = 0.16) on VO2 obtained at VT2, with no interaction (p = 0.49). Specifically, caffeine increased oxygen uptake at VT2 on days 1 and 4 (p < 0.05), with no other caffeine–placebo differences afterwards. For heart rate obtained at VT2, there was a main effect of substance (p < 0.01), while the overall effect of time (p = 0.13) and the interaction (p = 0.22) did not reach statistical significance. Heart rate at VT2 was higher with caffeine than with the placebo on days 1 and 4 (p < 0.05). The size of the effect of caffeine on VO2 and heart at VT2 tended to decline over time. Conclusion: Pre-exercise intake of 3 mg/kg/day of caffeine for twenty days enhanced the wattage obtained at VT2 during cycling ramp tests for ~15 days of ingestion, while there was a progressive attenuation of the size of the ergogenic effect of caffeine on this performance variable. Therefore, habituation to caffeine through daily ingestion may reduce the ergogenic effect of this stimulant on aerobic exercise of submaximal intensity. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Article
Independent Evolution of Sex Chromosomes in Eublepharid Geckos, A Lineage with Environmental and Genotypic Sex Determination
Life 2020, 10(12), 342; https://doi.org/10.3390/life10120342 - 10 Dec 2020
Cited by 3 | Viewed by 1116
Abstract
Geckos demonstrate a remarkable variability in sex determination systems, but our limited knowledge prohibits accurate conclusions on the evolution of sex determination in this group. Eyelid geckos (Eublepharidae) are of particular interest, as they encompass species with both environmental and genotypic sex determination. [...] Read more.
Geckos demonstrate a remarkable variability in sex determination systems, but our limited knowledge prohibits accurate conclusions on the evolution of sex determination in this group. Eyelid geckos (Eublepharidae) are of particular interest, as they encompass species with both environmental and genotypic sex determination. We identified for the first time the X-specific gene content in the Yucatán banded gecko, Coleonyx elegans, possessing X1X1X2X2/X1X2Y multiple sex chromosomes by comparative genome coverage analysis between sexes. The X-specific gene content of Coleonyx elegans was revealed to be partially homologous to genomic regions linked to the chicken autosomes 1, 6 and 11. A qPCR-based test was applied to validate a subset of X-specific genes by comparing the difference in gene copy numbers between sexes, and to explore the homology of sex chromosomes across eleven eublepharid, two phyllodactylid and one sphaerodactylid species. Homologous sex chromosomes are shared between Coleonyx elegans and Coleonyx mitratus, two species diverged approximately 34 million years ago, but not with other tested species. As far as we know, the X-specific gene content of Coleonyx elegans / Coleonyx mitratus was never involved in the sex chromosomes of other gecko lineages, indicating that the sex chromosomes in this clade of eublepharid geckos evolved independently. Full article
(This article belongs to the Section Evolutionary Biology)
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Article
Repair Kinetics of DNA Double Strand Breaks Induced by Simulated Space Radiation
Life 2020, 10(12), 341; https://doi.org/10.3390/life10120341 - 10 Dec 2020
Cited by 1 | Viewed by 1078
Abstract
Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. [...] Read more.
Radiation is unavoidable in space. Energetic particles in space radiation are reported to induce cluster DNA damage that is difficult to repair. In this study, normal human fibroblasts were irradiated with components of space radiation such as proton, helium, or carbon ion beams. Immunostaining for γ-H2AX and 53BP1 was performed over time to evaluate the kinetics of DNA damage repair. Our data clearly show that the repair kinetics of DNA double strand breaks (DSBs) induced by carbon ion irradiation, which has a high linear energy transfer (LET), are significantly slower than those of proton and helium ion irradiation. Mixed irradiation with carbon ions, followed by helium ions, did not have an additive effect on the DSB repair kinetics. Interestingly, the mean γ-H2AX focus size was shown to increase with LET, suggesting that the delay in repair kinetics was due to damage that is more complex. Further, the 53BP1 focus size also increased in an LET-dependent manner. Repair of DSBs, characterized by large 53BP1 foci, was a slow process within the biphasic kinetics of DSB repair, suggesting non-homologous end joining with error-prone end resection. Our data suggest that the biological effects of space radiation may be significantly influenced by the dose as well as the type of radiation exposure. Full article
(This article belongs to the Special Issue Radiobiology in Space)
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Article
Influence of Artificial Turf Surface Stiffness on Athlete Performance
Life 2020, 10(12), 340; https://doi.org/10.3390/life10120340 - 10 Dec 2020
Cited by 1 | Viewed by 1104
Abstract
Properties of conventional playing surfaces have been investigated for many years and the stiffness of the surface has potential to influence athletic performance. However, despite the proliferation of different infilled artificial turfs with varying properties, the effect of surface stiffness of these types [...] Read more.
Properties of conventional playing surfaces have been investigated for many years and the stiffness of the surface has potential to influence athletic performance. However, despite the proliferation of different infilled artificial turfs with varying properties, the effect of surface stiffness of these types of surfaces on athlete performance remains unknown. Therefore, the purpose of this project was to determine the influence of surface stiffness of artificial turf systems on athlete performance. Seventeen male athletes performed four movements (running, 5-10-5 agility, vertical jumping and sprinting) on five surfaces of varying stiffness: Softest (−50%), Softer (−34%), Soft (−16%), Control, Stiff (+17%). Performance metrics (running economy, jump height, sprint/agility time) and kinematic data were recorded during each movement and participants performed a subjective evaluation of the surface. When compared to the Control surface, performance was significantly improved during running (Softer, Soft), the agility drill (Softest) and vertical jumping (Soft). Subjectively, participants could not discern between any of the softer surfaces in terms of surface cushioning, however, the stiffer surface was rated as harder and less comfortable. Overall, changes in surface stiffness altered athletic performance and, to a lesser extent, subjective assessments of performance, with changes in performance being surface and movement specific. Full article
(This article belongs to the Special Issue Exercise Biomechanics and Physiology)
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Article
The Medium Is the Message: How Do Canadian University Students Want Digital Medication Information?
Life 2020, 10(12), 339; https://doi.org/10.3390/life10120339 - 10 Dec 2020
Cited by 1 | Viewed by 610
Abstract
(1) Background: To facilitate optimal prescription medication benefits and safety, it is important that people are informed about their prescription medications. As we shift towards using the digital medium to communicate medication information, it is important to address the needs and preferences of [...] Read more.
(1) Background: To facilitate optimal prescription medication benefits and safety, it is important that people are informed about their prescription medications. As we shift towards using the digital medium to communicate medication information, it is important to address the needs and preferences of different user groups so that they are more likely to read and use this information. In this study, we examined what digital medication information (DMI) format Canadian University students want and why. (2) Methods: This study was a qualitative investigation of young (aged 18–35) Canadian University students’ (N = 36) preferences and rationale supporting these preferences with respect to three potential formats for providing DMI: email, a mobile application (app), and online. Reported advantages and disadvantages of each of the three DMI formats were identified and categorized into unique themes. (3) Results: Findings from this study suggest that Canadian University Students most want to receive DMI by email, followed by a mobile app, and finally they were least receptive to online DMI. Participants provided diverse themes of reasons supporting their preferences. (4) Conclusions: Different user groups may have different needs with respect to receiving DMI. The themes from this study suggest that using a formative evaluation framework for assessing different DMI formats may be useful in future research. Email may be the best way to share DMI with younger, generally healthy, Canadian University students who are on few medications. Further research is required to explore whether other mediums for DMI are more appropriate for users with other characteristics (e.g., older and less educated) and contexts (e.g., polypharmacy and complex conditions). Given the flexibility of digital information, DMI could plausibly be provided in multiple formats and could allow users to choose the option they like best and would be most likely to use. Full article
(This article belongs to the Special Issue Advances in eHealth)
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Article
Quantifying Mineral-Ligand Structural Similarities: Bridging the Geological World of Minerals with the Biological World of Enzymes
Life 2020, 10(12), 338; https://doi.org/10.3390/life10120338 - 10 Dec 2020
Cited by 1 | Viewed by 762
Abstract
Metal compounds abundant on Early Earth are thought to play an important role in the origins of life. Certain iron-sulfur minerals for example, are proposed to have served as primitive metalloenzyme cofactors due to their ability to catalyze organic synthesis processes and facilitate [...] Read more.
Metal compounds abundant on Early Earth are thought to play an important role in the origins of life. Certain iron-sulfur minerals for example, are proposed to have served as primitive metalloenzyme cofactors due to their ability to catalyze organic synthesis processes and facilitate electron transfer reactions. An inherent difficulty with studying the catalytic potential of many metal compounds is the wide range of data and parameters to consider when searching for individual minerals and ligands of interest. Detecting mineral-ligand pairs that are structurally analogous enables more relevant selections of data to study, since structural affinity is a key indicator of comparable catalytic function. However, current structure-oriented approaches tend to be subjective and localized, and do not quantify observations or compare them with other potential targets. Here, we present a mathematical approach that compares structural similarities between various minerals and ligands using molecular similarity metrics. We use an iterative substructure search in the crystal lattice, paired with benchmark structural similarity methods. This structural comparison may be considered as a first stage in a more advanced analysis tool that will include a range of chemical and physical factors when computing mineral-ligand similarity. This approach will seek relationships between the mineral and enzyme worlds, with applications to the origins of life, ecology, catalysis, and astrobiology. Full article
(This article belongs to the Special Issue From Messy Chemistry to the Origin of Life)
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Brief Report
Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis
Life 2020, 10(12), 337; https://doi.org/10.3390/life10120337 - 10 Dec 2020
Cited by 1 | Viewed by 1011
Abstract
Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of [...] Read more.
Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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