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Life
Volume 11
Issue 5
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Life, Volume 11, Issue 5 (May 2021) – 93 articles

Cover Story (view full-size image): The submarine alkaline vent theory addresses how life emerged from the water world that was our Earth 4 billion years ago. At that time, the mantle of the Earth was so hot and soft as to preclude the protrusion of any land, volcanic or otherwise, from the ~5 km deep Hadean Ocean floor. The main mineral precipitated at the vent was the 2-layered fougerite (supported by subsidiary mackinawite), which acted as a nanoengine, pump, and non-return valve producing a small but continuous supply of charged protobiological molecules derived from the interaction of an alkaline solution of hydrogen, methane and hydrogen sulfide with acidic ocean water bearing metals, nitrate and carbon dioxide. At the same time, non-cooperative molecules were excreted as waste. View this paper
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18 pages, 2782 KiB  
Article
Use of NanoSIMS to Identify the Lower Limits of Metabolic Activity and Growth by Serratia liquefaciens Exposed to Sub-Zero Temperatures
by Petra Schwendner, Ann N. Nguyen and Andrew C. Schuerger
Life 2021, 11(5), 459; https://doi.org/10.3390/life11050459 - 20 May 2021
Viewed by 3202
Abstract
Serratia liquefaciens is a cold-adapted facultative anaerobic astrobiology model organism with the ability to grow at a Martian atmospheric pressure of 7 hPa. Currently there is a lack of data on its limits of growth and metabolic activity at sub-zero temperatures found in [...] Read more.
Serratia liquefaciens is a cold-adapted facultative anaerobic astrobiology model organism with the ability to grow at a Martian atmospheric pressure of 7 hPa. Currently there is a lack of data on its limits of growth and metabolic activity at sub-zero temperatures found in potential habitable regions on Mars. Growth curves and nano-scale secondary ion mass spectrometry (NanoSIMS) were used to characterize the growth and metabolic threshold for S. liquefaciens ATCC 27,592 grown at and below 0 °C. Cells were incubated in Spizizen medium containing three stable isotopes substituting their unlabeled counterparts; i.e., 13C-glucose, (15NH4)2SO4, and H218O; at 0, −1.5, −3, −5, −10, or −15 °C. The isotopic ratios of 13C/12C, 15N/14N, and 18O/16O and their corresponding fractions were determined for 240 cells. NanoSIMS results revealed that with decreasing temperature the cellular amounts of labeled ions decreased indicating slower metabolic rates for isotope uptake and incorporation. Metabolism was significantly reduced at −1.5 and −3 °C, almost halted at −5 °C, and shut-down completely at or below −10 °C. While growth was observed at 0 °C after 5 days, samples incubated at −1.5 and −3 °C exhibited significantly slower growth rates until growth was detected at 70 days. In contrast, cell densities decreased by at least half an order of magnitude over 70 days in cultures incubated at ≤ −5 °C. Results suggest that S. liquefaciens, if transported to Mars, might be able to metabolize and grow in shallow sub-surface niches at temperatures above −5 °C and might survive—but not grow—at temperatures below −5 °C. Full article
(This article belongs to the Special Issue Microbial Life in the Solar System)
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10 pages, 237 KiB  
Article
Comparing Endovascular Treatment Methods in Acute Ischemic Stroke Due to Tandem Occlusion Focusing on Clinical Aspects
by Peter Janos Kalmar, Gabor Tarkanyi, Csaba Balazs Nagy, Peter Csecsei, Gabor Lenzser, Edit Bosnyak, Zsofia Nozomi Karadi, Adam Annus, Istvan Szegedi, Andras Buki and Laszlo Szapary
Life 2021, 11(5), 458; https://doi.org/10.3390/life11050458 - 20 May 2021
Cited by 4 | Viewed by 2923
Abstract
Introduction: Acute ischemic strokes (AIS) due to tandem occlusion (TO) of intracranial anterior large vessel and concomitant extracranial internal carotid artery (EICA) are represent in 15–20% of all ischemic strokes. The endovascular treatment (EVT) strategy for those patients is still unclear. Although the [...] Read more.
Introduction: Acute ischemic strokes (AIS) due to tandem occlusion (TO) of intracranial anterior large vessel and concomitant extracranial internal carotid artery (EICA) are represent in 15–20% of all ischemic strokes. The endovascular treatment (EVT) strategy for those patients is still unclear. Although the intracranial mechanical thrombectomy (MT) is considered as a standard treatment approach, the EICA lesion stent necessity remains a matter of debate. We sought to assess the efficacy and safety of EVT in tandem lesions, particularly the EICA stenting management. Methods: We retrospectively analyzed all patients with anterior circulation stroke associated with EICA lesion and receiving EVT in the three participated stroke centers between November 2017 and December 2020. Patients’ data were collected from our prospective stroke registry (STAY ALIVE). Patients enrolled in our study were divided into two groups depending on whether acute carotid stenting (ACS) or balloon angioplasty only (BAO) technique was used. Our primary outcome was the 90-day functional outcome assessed by modified Rankin scale (mRS). Mortality at 90 days and symptomatic intracranial hemorrhage (sICH) were considered as secondary outcomes. Results: A total of 101 patients (age: 67 ± 10 years, 38.6% female) were enrolled in our study, including 29 (28.3%) BAO cases, and 72 (71.3%) patients treated with ACS. Patients in the BAO group were slightly older (70 ± 9 years vs. 66 ± 10 years, p = 0.054), and had higher prevalence of comorbidities such as hypertension (100.0% vs. 59.4%, p < 0.001). There was no significant difference in favorable outcomes (51.7% vs. 54.4%, p = 0.808) between the groups. However, we observed a trend towards higher rates of sICH (8.3% vs. 3.4%, p = 0.382) and 90-day mortality (23.5% vs. 13.8%, p = 0.278) with significantly higher frequency of distal embolization (39.1% vs. 17.9%, p = 0.043) in patients with ACS. In the overall population age (p = 0.013), atrial fibrillation (AF) (p = 0.008), National Institutes of Health Stroke Scale (NIHSS) baseline (p = 0.029), and successful recanalization (p = 0.023) were associated with favorable outcome. Conclusion: Endovascular approach of EICA in addition to MT was safe and effective in tandem occlusion of anterior circulation. Furthermore, our results suggest that balloon angioplasty technique without acute stenting shows a comparable favorable outcome rate to ACS with moderately less hemorrhagic events and mortality rates. Full article
(This article belongs to the Special Issue Challenges in Stroke Care)
9 pages, 590 KiB  
Review
Iguratimod: Novel Molecular Insights and a New csDMARD for Rheumatoid Arthritis, from Japan to the World
by Yuji Nozaki
Life 2021, 11(5), 457; https://doi.org/10.3390/life11050457 - 20 May 2021
Cited by 15 | Viewed by 4627
Abstract
Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), [...] Read more.
Iguratimod (IGU) is a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) routinely prescribed in Japan since 2012 to patients with rheumatoid arthritis (RA). Iguratimod acts directly on B cells by inhibiting the production of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, IL-17), thereby suppressing the production of immunoglobulin and inhibiting the activity of nuclear factor kappa-light chain enhancer of activated B cells. In Japan, it is one of the most used csDMARDs in daily practice, but it is not recommended as a treatment for RA due to the lack of large-scale evidence established overseas. However, recent reports on the novel pharmacological effects of IGU on lymphocytes and synovial fibroblasts, as well as its efficacy in daily practice, have increased its importance as a drug for the treatment of RA. In this review, we highlighted the basic and clinical studies in IGU and discuss its potential as a new therapeutic agent for the treatment of RA. Full article
(This article belongs to the Special Issue New Insights in Autoimmune Arthritis and Nephritis)
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25 pages, 3621 KiB  
Article
The Use of Response Surface Methodology as a Statistical Tool for the Optimisation of Waste and Pure Canola Oil Biodegradation by Antarctic Soil Bacteria
by Khadijah Nabilah Mohd Zahri, Azham Zulkharnain, Claudio Gomez-Fuentes, Suriana Sabri, Khalilah Abdul Khalil, Peter Convey and Siti Aqlima Ahmad
Life 2021, 11(5), 456; https://doi.org/10.3390/life11050456 - 20 May 2021
Cited by 13 | Viewed by 3654
Abstract
Hydrocarbons can cause pollution to Antarctic terrestrial and aquatic ecosystems, both through accidental release and the discharge of waste cooking oil in grey water. Such pollutants can persist for long periods in cold environments. The native microbial community may play a role in [...] Read more.
Hydrocarbons can cause pollution to Antarctic terrestrial and aquatic ecosystems, both through accidental release and the discharge of waste cooking oil in grey water. Such pollutants can persist for long periods in cold environments. The native microbial community may play a role in their biodegradation. In this study, using mixed native Antarctic bacterial communities, several environmental factors influencing biodegradation of waste canola oil (WCO) and pure canola oil (PCO) were optimised using established one-factor-at-a-time (OFAT) and response surface methodology (RSM) approaches. The factors include salinity, pH, type of nitrogen and concentration, temperature, yeast extract and initial substrate concentration in OFAT and only the significant factors proceeded for the statistical optimisation through RSM. High concentration of substrate targeted for degradation activity through RSM compared to OFAT method. As for the result, all factors were significant in PBD, while only 4 factors were significant in biodegradation of PCO (pH, nitrogen concentration, yeast extract and initial substrate concentration). Using OFAT, the most effective microbial community examined was able to degrade 94.42% and 86.83% (from an initial concentration of 0.5% (v/v)) of WCO and PCO, respectively, within 7 days. Using RSM, 94.99% and 79.77% degradation of WCO and PCO was achieved in 6 days. The significant interaction for the RSM in biodegradation activity between temperature and WCO concentration in WCO media were exhibited. Meanwhile, in biodegradation of PCO the significant factors were between (1) pH and PCO concentration, (2) nitrogen concentration and yeast extract, (3) nitrogen concentration and PCO concentration. The models for the RSM were validated for both WCO and PCO media and it showed no significant difference between experimental and predicted values. The efficiency of canola oil biodegradation achieved in this study provides support for the development of practical strategies for efficient bioremediation in the Antarctic environment. Full article
(This article belongs to the Special Issue Microbial Degradation and Biosorbents)
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13 pages, 844 KiB  
Review
Accessory Subunits of the Matrix Arm of Mitochondrial Complex I with a Focus on Subunit NDUFS4 and Its Role in Complex I Function and Assembly
by Flora Kahlhöfer, Max Gansen and Volker Zickermann
Life 2021, 11(5), 455; https://doi.org/10.3390/life11050455 - 19 May 2021
Cited by 17 | Viewed by 3758
Abstract
NADH:ubiquinone-oxidoreductase (complex I) is the largest membrane protein complex of the respiratory chain. Complex I couples electron transfer to vectorial proton translocation across the inner mitochondrial membrane. The L shaped structure of complex I is divided into a membrane arm and a matrix [...] Read more.
NADH:ubiquinone-oxidoreductase (complex I) is the largest membrane protein complex of the respiratory chain. Complex I couples electron transfer to vectorial proton translocation across the inner mitochondrial membrane. The L shaped structure of complex I is divided into a membrane arm and a matrix arm. Fourteen central subunits are conserved throughout species, while some 30 accessory subunits are typically found in eukaryotes. Complex I dysfunction is associated with mutations in the nuclear and mitochondrial genome, resulting in a broad spectrum of neuromuscular and neurodegenerative diseases. Accessory subunit NDUFS4 in the matrix arm is a hot spot for mutations causing Leigh or Leigh-like syndrome. In this review, we focus on accessory subunits of the matrix arm and discuss recent reports on the function of accessory subunit NDUFS4 and its interplay with NDUFS6, NDUFA12, and assembly factor NDUFAF2 in complex I assembly. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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53 pages, 3761 KiB  
Article
Multi-Gene Phylogeny and Morphology Reveal Haplohelminthosporium gen. nov. and Helminthosporiella gen. nov. Associated with Palms in Thailand and A Checklist for Helminthosporium Reported Worldwide
by Sirinapa Konta, Kevin D. Hyde, Samantha C. Karunarathna, Ausana Mapook, Chanokned Senwanna, Lucas A. P. Dauner, Chandrika M. Nanayakkara, Jianchu Xu, Saowaluck Tibpromma and Saisamorn Lumyong
Life 2021, 11(5), 454; https://doi.org/10.3390/life11050454 - 19 May 2021
Cited by 12 | Viewed by 4349
Abstract
Palms (Arecaceae) are substrates for a highly diverse range of fungi. Many species are known as saprobes and many are important plant pathogens. Over the course of our studies of micro-fungi from palms in Thailand, two new taxa were discovered. Morphological characteristics and [...] Read more.
Palms (Arecaceae) are substrates for a highly diverse range of fungi. Many species are known as saprobes and many are important plant pathogens. Over the course of our studies of micro-fungi from palms in Thailand, two new taxa were discovered. Morphological characteristics and phylogenetic analyses of combined ITS, LSU, SSU, and tef1-α sequence data revealed their taxonomic positions within Massarinaceae. There are currently ten genera identified and accepted in Massarinaceae, with the addition of the two new genera of Haplohelminthosporium and Helminthosporiella, that are introduced in this paper. Each new genus is provided with a full description and notes, and each new taxon is provided with an illustration for the holotype. A list of identified and accepted species of Helminthosporium with morphology, host information, locality, sequence data, and related references of Helminthosporium reported worldwide is provided based on records in Species Fungorum 2021. This work provides a micro-fungi database of Haplohelminthosporium, Helminthosporiella, and Helminthosporium which can be modified and validated as new data come to light. Full article
(This article belongs to the Special Issue Biodiversity and Ecology of Fungi in Terrestrial and Marine Ecosystems)
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11 pages, 398 KiB  
Article
Antioxidant Status in the Vitreous of Eyes with Rhegmatogenous Retinal Detachment with and without Proliferative Vitreoretinopathy, Macular Hole and Epiretinal Membrane
by Agata Pietras-Baczewska, Katarzyna Nowomiejska, Agnieszka Brzozowska, Mario Damiano Toro, Wojciech Załuska, Małgorzata Sztanke, Krzysztof Sztanke and Robert Rejdak
Life 2021, 11(5), 453; https://doi.org/10.3390/life11050453 - 19 May 2021
Cited by 12 | Viewed by 2310
Abstract
(1) Background: The aim of the study was to test the hypothesis that the antioxidant status in the vitreous body of eyes, which had been vitrectomized due to rhegmatogenous retinal detachment (RRD) with or without proliferative vitreoretinopathy (PVR), is higher than in eyes [...] Read more.
(1) Background: The aim of the study was to test the hypothesis that the antioxidant status in the vitreous body of eyes, which had been vitrectomized due to rhegmatogenous retinal detachment (RRD) with or without proliferative vitreoretinopathy (PVR), is higher than in eyes vitrectomized due to other retinal diseases. (2) Methods: four patient groups were analyzed: 22 eyes of patients with RRD without PVR, 27 eyes with RRD and PVR, 22 eyes with macular hole (MH) and 10 eyes with epiretinal membrane (ERM). Spectrophotometric methods were used to determine the total antioxidant status (TAS) values as well as superoxide dismutase (SOD) and glutathione reductase (GR) activities in the vitreous fluid samples. (3) Results: no significant differences in TAS values and antioxidant enzyme activities were observed among patient with RRD with and without PVR and with MH and ERM. The longer the duration of RRD leading to PVR and better postoperative visual acuity, the higher the TAS level. No significant differences were found between “macula on” and “macula off” subgroups within the RRD group and the RRD combined with PVR group. (4) Conclusions: The preliminary results do not support the thesis that the antioxidant status of vitrectomized eyes is different in patients with RRD with or without PVR in comparison to patients with MH and ERM. In patients with RRD, PVR presence and detached macula do not affect the values of TAS, SOD and GR in the vitreous fluid. The duration of the disease influences TAS in the vitreous in eyes with RRD complicated with PVR. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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21 pages, 715 KiB  
Review
Vitamin D: Not Just Bone Metabolism but a Key Player in Cardiovascular Diseases
by Marcello Izzo, Albino Carrizzo, Carmine Izzo, Enrico Cappello, Domenico Cecere, Michele Ciccarelli, Patrizia Iannece, Antonio Damato, Carmine Vecchione and Francesco Pompeo
Life 2021, 11(5), 452; https://doi.org/10.3390/life11050452 - 18 May 2021
Cited by 25 | Viewed by 6444
Abstract
Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin [...] Read more.
Vitamin D is the first item of drug expenditure for the treatment of osteoporosis. Its deficiency is a condition that affects not only older individuals but also young people. Recently, the scientific community has focused its attention on the possible role of vitamin D in the development of several chronic diseases such as cardiovascular and metabolic diseases. This review aims to highlight the possible role of vitamin D in cardiovascular and metabolic diseases. In particular, here we examine (1) the role of vitamin D in diabetes mellitus, metabolic syndrome, and obesity, and its influence on insulin secretion; (2) its role in atherosclerosis, in which chronic vitamin D deficiency, lower than 20 ng/mL (50 nmol/L), has emerged among the new risk factors; (3) the role of vitamin D in essential hypertension, in which low plasma levels of vitamin D have been associated with both an increase in the prevalence of hypertension and diastolic hypertension; (4) the role of vitamin D in peripheral arteriopathies and aneurysmal pathology, reporting that patients with peripheral artery diseases had lower vitamin D values than non-suffering PAD controls; (5) the genetic and epigenetic role of vitamin D, highlighting its transcriptional regulation capacity; and (6) the role of vitamin D in cardiac remodeling and disease. Despite the many observational studies and meta-analyses supporting the critical role of vitamin D in cardiovascular physiopathology, clinical trials designed to evaluate the specific role of vitamin D in cardiovascular disease are scarce. The characterization of the importance of vitamin D as a marker of pathology should represent a future research challenge. Full article
(This article belongs to the Special Issue New Molecules and Mechanisms to Fight the Onset and Progression Cardiovascular Diseases—the Role of Oxidative Stress)
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18 pages, 4119 KiB  
Article
Ionizing Radiation Induces Resistant Glioblastoma Stem-Like Cells by Promoting Autophagy via the Wnt/β-Catenin Pathway
by Cheng-Yu Tsai, Huey-Jiun Ko, Chi-Ying F. Huang, Ching-Yi Lin, Shean-Jaw Chiou, Yu-Feng Su, Ann-Shung Lieu, Joon-Khim Loh, Aij-Lie Kwan, Tsung-Hsien Chuang and Yi-Ren Hong
Life 2021, 11(5), 451; https://doi.org/10.3390/life11050451 - 18 May 2021
Cited by 12 | Viewed by 3288
Abstract
Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence [...] Read more.
Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence showed cancer stem cells (CSCs) play a vital role in therapy resistance in many cancer types, including GBM. However, the molecular mechanism is poorly understood. Here, we proposed that autophagy could be involved in GSC induction for radioresistance. In a clinical setting, patients who received radiation/chemotherapy had higher LC3II expression and showed poor overall survival compared with those with low LC3 II. In a cell model, U87MG and GBM8401 expressed high level of stemness markers CD133, CD44, Nestin, and autophagy marker P62/LC3II after receiving standard fractionated IR. Furthermore, Wnt/β-catenin proved to be a potential pathway and related to P62 by using proteasome inhibitor (MG132). Moreover, pharmacological inhibition of autophagy with BAF and CQ inhibit GSC cell growth by impairing autophagy flux as demonstrated by decrease Nestin, CD133, and SOX-2 levels. In conclusion, we demonstrated that fractionated IR could induce GSCs with the stemness phenotype by P62-mediated autophagy through the Wnt/β-catenin for radioresistance. This study offers a new therapeutic strategy for targeting GBM in the future. Full article
(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)
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7 pages, 210 KiB  
Article
Sensitivity Patterns of Bacterial Pathogens Isolated from Blood Cultures of Under-Five Children with Pneumonia and Clinical Sepsis
by Sufia Islam, Ashiqur Rahman Akand, Tasnova Tasnim Nova, Christian Lehmann and Mohammod Jobayer Chisti
Life 2021, 11(5), 450; https://doi.org/10.3390/life11050450 - 18 May 2021
Cited by 2 | Viewed by 2739
Abstract
Treatment options for pneumonia and sepsis by antibiotics are limited due to the development of multidrug-resistant bacterial strains. This unmatched case-control study determined the antibiotic sensitivity against bacterial isolates obtained from septic and nonseptic children with pneumonia. Children of either sex aged 0–59 [...] Read more.
Treatment options for pneumonia and sepsis by antibiotics are limited due to the development of multidrug-resistant bacterial strains. This unmatched case-control study determined the antibiotic sensitivity against bacterial isolates obtained from septic and nonseptic children with pneumonia. Children of either sex aged 0–59 months with a history of cough or shortness of breath and radiologically confirmed pneumonia were enrolled in this study. Cases with clinical signs of sepsis at admission (n = 151) were compared to cases without sepsis as controls (n = 107). A total of 205 children had a performance of blood culture, with 123 children suffering from clinical sepsis. Blood cultures showed bacterial growth in 19% of the septic samples, with 8% coagulase-negative staphylococci and 2.4% Acinetobacter species. Only 1.6% of the cases were infected by Streptococcus pneumonia, Haemophilus influenzae, Salmonella typhi and Klebsiella. In contrast, children without sepsis presented positive blood cultures with growth of Salmonella typhi in 2.4% of the cases and growth of Klebsiella in 1.2%. Bacteria were sensitive to imipenem in 100% of the cases (86% for meropenem, 83% for ceftazidime and 76% for ciprofloxacin). The mortality rate was significantly higher in children with pneumonia complicated by sepsis (odds ratio (OR) = 3.02, 95% confidence interval (CI), 1.11–8.64, p < 0.027). Knowledge about specific laboratory characteristics in children with pneumonia will facilitate an early diagnosis and treatment of sepsis and reduce mortality. Full article
8 pages, 772 KiB  
Article
Plantar Stimulations during 3-Day Hindlimb Unloading Prevent Loss of Neural Progenitors and Maintain ERK1/2 Activity in the Rat Hippocampus
by Anna S. Berezovskaya, Sergey A. Tyganov, Svetlana D. Nikolaeva, Alexandra A. Naumova, Boris S. Shenkman and Margarita V. Glazova
Life 2021, 11(5), 449; https://doi.org/10.3390/life11050449 - 17 May 2021
Cited by 6 | Viewed by 2268
Abstract
Adult neurogenesis is a flexible process that depends on the environment and correlates with cognitive functions. Cognitive functions are impaired by various factors including space flight conditions and reduced physical activity. Physically active life significantly improves both cognition and the hippocampal neurogenesis. Here, [...] Read more.
Adult neurogenesis is a flexible process that depends on the environment and correlates with cognitive functions. Cognitive functions are impaired by various factors including space flight conditions and reduced physical activity. Physically active life significantly improves both cognition and the hippocampal neurogenesis. Here, we analyzed how 3-day simulated microgravity caused by hindlimb unloading (HU) or dynamic foot stimulation (DFS) during HU can affect the hippocampal neurogenesis. Adult Wistar rats were recruited in the experiments. The results demonstrated a decrease in the number of doublecortine (DCX) positive neural progenitors, but proliferation in the subgranular zone of the dentate gyrus was not changed after 3-day HU. Analysis of the effects of DFS showed restoration of neural progenitor population in the subgranular zone of the dentate gyrus. Additionally, we analyzed activity of the cRaf/ERK1/2 pathway, which is one of the major players in the regulation of neuronal differentiation. The results demonstrated inhibition of cRaf/ERK1/2 signaling in the hippocampus of HU rats. In DFS rats, no changes in the activity of cRaf/ERK1/2 were observed. Thus, we demonstrated that the process of neurogenesis fading during HU begins with inhibition of the formation of immature neurons and associated ERK1/2 signaling activity, while DFS prevents the development of mentioned alterations. Full article
(This article belongs to the Collection Space Life Sciences)
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13 pages, 252 KiB  
Review
Update on Biomarkers Associated to Cardioembolic Stroke: A Narrative Review
by Ana Catarina Fonseca and Pedro Coelho
Life 2021, 11(5), 448; https://doi.org/10.3390/life11050448 - 17 May 2021
Cited by 12 | Viewed by 3723
Abstract
Background: In the last years, several studies were conducted that evaluated biomarkers that could be helpful for cardioembolic stroke diagnosis, prognosis, and the determination of risk of stroke recurrence. Methods: We performed a narrative review of the main studies that evaluated biomarkers related [...] Read more.
Background: In the last years, several studies were conducted that evaluated biomarkers that could be helpful for cardioembolic stroke diagnosis, prognosis, and the determination of risk of stroke recurrence. Methods: We performed a narrative review of the main studies that evaluated biomarkers related to specific cardioembolic causes: atrial fibrillation, patent foramen ovale, atrial cardiomyopathy, and left ventricular wall motion abnormalities. Results: BNP and NT-proBNP are, among all biomarkers of cardioembolic stroke, the ones that have the highest amount of evidence for their use. NT-proBNP is currently used for the selection of patients that will be included in clinical trials that aim to evaluate the use of anticoagulation in patients suspected of having a cardioembolic stroke and for the selection of patients to undergo cardiac monitoring. NT-proBNP has also been incorporated in tools used to predict the risk of stroke recurrence (ABC-stroke score). Conclusions: NT-proBNP and BNP continue to be the biomarkers most widely studied in the context of cardioembolic stroke. The possibility of using other biomarkers in clinical practice is still distant, mainly because of the low methodological quality of the studies in which they were evaluated. Both internal and external validation studies are rarely performed for most biomarkers. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
15 pages, 1174 KiB  
Review
Antithrombotic Therapy for Secondary Prevention in Patients with Non-Cardioembolic Stroke or Transient Ischemic Attack: A Systematic Review
by Dániel Tornyos, Alexandra Bálint, Péter Kupó, Oumaima El Alaoui El Abdallaoui and András Komócsi
Life 2021, 11(5), 447; https://doi.org/10.3390/life11050447 - 15 May 2021
Cited by 9 | Viewed by 3512
Abstract
Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search [...] Read more.
Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification. Full article
(This article belongs to the Special Issue Challenges in Stroke Care)
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15 pages, 2608 KiB  
Article
The Eastern Nebraska Salt Marsh Microbiome Is Well Adapted to an Alkaline and Extreme Saline Environment
by Sierra R. Athen, Shivangi Dubey and John A. Kyndt
Life 2021, 11(5), 446; https://doi.org/10.3390/life11050446 - 15 May 2021
Cited by 5 | Viewed by 3609
Abstract
The Eastern Nebraska Salt Marshes contain a unique, alkaline, and saline wetland area that is a remnant of prehistoric oceans that once covered this area. The microbial composition of these salt marshes, identified by metagenomic sequencing, appears to be different from well-studied coastal [...] Read more.
The Eastern Nebraska Salt Marshes contain a unique, alkaline, and saline wetland area that is a remnant of prehistoric oceans that once covered this area. The microbial composition of these salt marshes, identified by metagenomic sequencing, appears to be different from well-studied coastal salt marshes as it contains bacterial genera that have only been found in cold-adapted, alkaline, saline environments. For example, Rubribacterium was only isolated before from an Eastern Siberian soda lake, but appears to be one of the most abundant bacteria present at the time of sampling of the Eastern Nebraska Salt Marshes. Further enrichment, followed by genome sequencing and metagenomic binning, revealed the presence of several halophilic, alkalophilic bacteria that play important roles in sulfur and carbon cycling, as well as in nitrogen fixation within this ecosystem. Photosynthetic sulfur bacteria, belonging to Prosthecochloris and Marichromatium, and chemotrophic sulfur bacteria of the genera Sulfurimonas, Arcobacter, and Thiomicrospira produce valuable oxidized sulfur compounds for algal and plant growth, while alkaliphilic, sulfur-reducing bacteria belonging to Sulfurospirillum help balance the sulfur cycle. This metagenome-based study provides a baseline to understand the complex, but balanced, syntrophic microbial interactions that occur in this unique inland salt marsh environment. Full article
(This article belongs to the Section Microbiology)
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12 pages, 2073 KiB  
Article
Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress
by Yang Deng, Ji Ma, Xin Weng, Yuqin Wang, Maoru Li, Tingting Yang, Zhiyang Dou, Zhiqi Yin and Jing Shang
Life 2021, 11(5), 445; https://doi.org/10.3390/life11050445 - 14 May 2021
Cited by 14 | Viewed by 3521
Abstract
NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form [...] Read more.
NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2 was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 μM) and in vitro (K3O, 20 μM). Additionally, K3O (40 μM) reduced neutrophil aggregation in vivo. K3O (20 μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-α, and il-6 mRNA were all significantly reversed by K3O (20 μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20 μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model. Full article
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12 pages, 246 KiB  
Article
Sugar Intake: Are All Children Made of Sugar?
by Lucia Diani and Maria Luisa Forchielli
Life 2021, 11(5), 444; https://doi.org/10.3390/life11050444 - 14 May 2021
Cited by 9 | Viewed by 3353
Abstract
Introduction: A healthy diet is characterized by a variety of food and a balanced energy intake, which should accompany every human being since early childhood. Unfortunately, excessive consumption of protein, fat, and lately sugar are very common in developed countries. Sugar intakes are [...] Read more.
Introduction: A healthy diet is characterized by a variety of food and a balanced energy intake, which should accompany every human being since early childhood. Unfortunately, excessive consumption of protein, fat, and lately sugar are very common in developed countries. Sugar intakes are not easily quantifiable and comparable among subjects. Therefore, we decide to analyze dietary patterns in children of different ages and diets (with and without gluten) using a food and nutrient database and a new application called the “Zuccherometro”. Patients and methods: This is a descriptive observational study conducted among children that are recruited consecutively either during a pediatric evaluation or through a school survey. Sociodemographic, nutritional and anthropometric data, degree of physical activity, and presence of medical conditions are collected. Dietary intake data are obtained by a 24 h recall diet. Results: The study analyzes 400 children: 213 girls and 187 boys. The majority of children (70.7%) are in normal weight range with similar extreme values (6.5% obese and 6.7% underweight). Celiac disease is diagnosed in 186 children. Caloric intakes are in line with the recommendations in all age-distributed groups with the exception of adolescents (11–17 years old), whose caloric intake is lower than recommendations. Protein intakes, on the contrary, are always exceeding recommendations and are significantly elevated in preschool children, (more than three times the population reference intakes). As for sugar intakes, all the children except the 11–17 years adolescents exceed the recommended cut off of 15% of daily calories. The same trend is obtained using the “Zuccherometro” that shows different percentages of age-stratified children exceeding the reference values: 1–3 years, 59% of children; 4–6 years, 68%; 7–10 years, 39.8%; 11–14 years, 25.5%; 15–17 years, 24.5%. The sugar load consists of both natural or added sugars (fructose and lactose) in food or beverages. Sugar intakes are more generously consumed by all age-stratified controls than by celiac children with the exception of the youngest ones (1–3 years old) and male adolescents. Conclusion: Since high sugar intakes are constantly accompanying children during their growth, important dietary education and coordination between families and institutions are mandatory. Full article
(This article belongs to the Special Issue Pediatric Nutrition for a Healthy Life)
20 pages, 552 KiB  
Hypothesis
Does Compression Sensory Axonopathy in the Proximal Tibia Contribute to Noncontact Anterior Cruciate Ligament Injury in a Causative Way?—A New Theory for the Injury Mechanism
by Balázs Sonkodi, Rita Bardoni, László Hangody, Zsolt Radák and István Berkes
Life 2021, 11(5), 443; https://doi.org/10.3390/life11050443 - 14 May 2021
Cited by 18 | Viewed by 5603
Abstract
Anterior cruciate ligament injury occurs when the ligament fibers are stretched, partially torn, or completely torn. The authors propose a new injury mechanism for non-contact anterior cruciate ligament injury of the knee. Accordingly, non-contact anterior cruciate ligament injury could not happen without the [...] Read more.
Anterior cruciate ligament injury occurs when the ligament fibers are stretched, partially torn, or completely torn. The authors propose a new injury mechanism for non-contact anterior cruciate ligament injury of the knee. Accordingly, non-contact anterior cruciate ligament injury could not happen without the acute compression microinjury of the entrapped peripheral proprioceptive sensory axons of the proximal tibia. This would occur under an acute stress response when concomitant microcracks-fractures in the proximal tibia evolve due to the same excessive and repetitive compression forces. The primary damage may occur during eccentric contractions of the acceleration and deceleration moments of strenuous or unaccustomed fatiguing exercise bouts. This primary damage is suggested to be an acute compression/crush axonopathy of the proprioceptive sensory neurons in the proximal tibia. As a result, impaired proprioception could lead to injury of the anterior cruciate ligament as a secondary damage, which is suggested to occur during the deceleration phase. Elevated prostaglandin E2, nitric oxide and glutamate may have a critical neuro-modulatory role in the damage signaling in this dichotomous neuronal injury hypothesis that could lead to mechano-energetic failure, lesion and a cascade of inflammatory events. The presynaptic modulation of the primary sensory axons by the fatigued and microdamaged proprioceptive sensory fibers in the proximal tibia induces the activation of N-methyl-D-aspartate receptors in the dorsal horn of the spinal cord, through a process that could have long term relevance due to its contribution to synaptic plasticity. Luteinizing hormone, through interleukin-1β, stimulates the nerve growth factor-tropomyosin receptor kinase A axis in the ovarian cells and promotes tropomyosin receptor kinase A and nerve growth factor gene expression and prostaglandin E2 release. This luteinizing hormone induced mechanism could further elevate prostaglandin E2 in excess of the levels generated by osteocytes, due to mechanical stress during strenuous athletic moments in the pre-ovulatory phase. This may explain why non-contact anterior cruciate ligament injury is at least three-times more prevalent among female athletes. Full article
(This article belongs to the Special Issue Impact of Physical Exercises on Bone Activities)
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9 pages, 982 KiB  
Communication
An Unsupervised Algorithm for Host Identification in Flaviviruses
by Phuoc Truong Nguyen, Santiago Garcia-Vallvé and Pere Puigbò
Life 2021, 11(5), 442; https://doi.org/10.3390/life11050442 - 14 May 2021
Cited by 2 | Viewed by 2468
Abstract
Early characterization of emerging viruses is essential to control their spread, such as the Zika Virus outbreak in 2014. Among other non-viral factors, host information is essential for the surveillance and control of virus spread. Flaviviruses (genus Flavivirus), akin to other viruses, [...] Read more.
Early characterization of emerging viruses is essential to control their spread, such as the Zika Virus outbreak in 2014. Among other non-viral factors, host information is essential for the surveillance and control of virus spread. Flaviviruses (genus Flavivirus), akin to other viruses, are modulated by high mutation rates and selective forces to adapt their codon usage to that of their hosts. However, a major challenge is the identification of potential hosts for novel viruses. Usually, potential hosts of emerging zoonotic viruses are identified after several confirmed cases. This is inefficient for deterring future outbreaks. In this paper, we introduce an algorithm to identify the host range of a virus from its raw genome sequences. The proposed strategy relies on comparing codon usage frequencies across viruses and hosts, by means of a normalized Codon Adaptation Index (CAI). We have tested our algorithm on 94 flaviviruses and 16 potential hosts. This novel method is able to distinguish between arthropod and vertebrate hosts for several flaviviruses with high values of accuracy (virus group 91.9% and host type 86.1%) and specificity (virus group 94.9% and host type 79.6%), in comparison to empirical observations. Overall, this algorithm may be useful as a complementary tool to current phylogenetic methods in monitoring current and future viral outbreaks by understanding host–virus relationships. Full article
(This article belongs to the Special Issue Viral-Host Metabolic Interactions)
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15 pages, 3685 KiB  
Article
Evaluation of Blood Coagulation Parameters and ADMA, NO, IL-6, and IL-18 Serum Levels in Patients with Neovascular AMD before, during, and after the Initial Loading Phase of Intravitreal Aflibercept
by Michał Wiciński, Małgorzata Seredyka-Burduk, Sławomir Liberski, Daria Marczak, Magdalena Pol, Bartosz Malinowski, Katarzyna Pawlak-Osińska and Bartlomiej J. Kaluzny
Life 2021, 11(5), 441; https://doi.org/10.3390/life11050441 - 14 May 2021
Cited by 5 | Viewed by 2540
Abstract
We evaluated the effect of intravitreal injections of aflibercept (IVA) on blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), as well as asymmetric dimethylarginine (ADMA), nitric oxide (NO), interleukin 6 (IL-6), and interleukin 18 (IL-18) [...] Read more.
We evaluated the effect of intravitreal injections of aflibercept (IVA) on blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT), as well as asymmetric dimethylarginine (ADMA), nitric oxide (NO), interleukin 6 (IL-6), and interleukin 18 (IL-18) serum levels in patients with neovascular AMD (nAMD). Twenty-two eyes of 22 patients with nAMD were included. Parameters were evaluated before and 2–3 days after the first IVA injection, and then immediately before and 2–3 days after the third IVA injection. We revealed prolongation of the TT after the initial loading phase of IVA (p = 0.041) and a significant increase in IL-18 serum concentration immediately before the third IVA administration compared to baseline (p = 0.037). There were no statistically significant differences of other parameters and PT, APTT, ADMA, NO, and IL-6 values remained within the normal range at each of the time points of the study. Our results suggest that repeated IVA administration may affect the common blood coagulation pathway, which manifests as a prolongation of the TT value. Furthermore, we showed a significant increase in serum concentration of the pro-inflammatory cytokineIL-18during the initial loading phase of IVA. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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17 pages, 888 KiB  
Review
Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications
by Arianna Giorgetti, Jennifer P. Pascali, Paolo Fais, Guido Pelletti, Andrea Gabbin, Giorgia Franchetti, Giovanni Cecchetto and Guido Viel
Life 2021, 11(5), 440; https://doi.org/10.3390/life11050440 - 14 May 2021
Cited by 16 | Viewed by 4807
Abstract
Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the [...] Read more.
Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions. Full article
(This article belongs to the Collection Feature Review Papers for Life)
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17 pages, 450 KiB  
Article
Nutritional Characteristics, Sites of Origin, and Cost of Foods Consumed during School Hours and Their Relationship to Nutritional Status of Schoolchildren in Mexico City
by Gloria Martínez-Andrade, Marco González-Unzaga, Guillermina Romero-Quechol, Eugenia Mendoza, Jenny Vilchis-Gil and Ximena Duque
Life 2021, 11(5), 439; https://doi.org/10.3390/life11050439 - 14 May 2021
Cited by 2 | Viewed by 2812
Abstract
Access, nutritional characteristics, preferences, and cost can affect food intake at school. A cross-sectional study was performed to determine the nutritional characteristics, sites of origin, and cost of foods consumed during school hours. Three hundred and sixty-nine children from five public elementary schools [...] Read more.
Access, nutritional characteristics, preferences, and cost can affect food intake at school. A cross-sectional study was performed to determine the nutritional characteristics, sites of origin, and cost of foods consumed during school hours. Three hundred and sixty-nine children from five public elementary schools in Mexico City participated. The children gave information about the foods that they consumed five days out of the week during school hours, including the place of acquisition, cost of the food, and portion size. Anthropometric measurements of height and weight of the children were taken. Caloric consumption and percentage of recommended daily energy intake from food during school hours was determined. Children were 10.9 ± 0.9 years old; 55.6% were girls, 26% were overweight, 23% were obese, and 3.3% were of low height for age. The average calorie intake was 515 kilocalories (kcal) (boys, 535 kcal; girls, 476 kcal, p = 0.051); calorie intake was higher when school meal intakes included foods from home, school, and outside of school. No significant differences were found in calorie intake by children’s nutritional status. The cost in Mexican pesos per 100 kcal consumed showed differences according to the nutritional status of the children; it was 4.0 Mexican pesos for children with normal weight and 4.2 and 3.8 pesos in children who were overweight or obese, respectively. The information obtained in this study should be used to provide nutritional guidance. The food portion size intake during school hours should be reduced, and the food should come from one or at most two sites, because each extra food represents an increase in the total kilocalorie intake. Full article
(This article belongs to the Special Issue Pediatric Nutrition for a Healthy Life)
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10 pages, 2612 KiB  
Article
A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase
by Angela Tramonti, Roberto Contestabile, Rita Florio, Caterina Nardella, Anna Barile and Martino L. Di Salvo
Life 2021, 11(5), 438; https://doi.org/10.3390/life11050438 - 14 May 2021
Cited by 3 | Viewed by 3337
Abstract
Cysteine sulfinic acid decarboxylase catalyzes the last step of taurine biosynthesis in mammals, and belongs to the fold type I superfamily of pyridoxal-5′-phosphate (PLP)-dependent enzymes. Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in animal tissues; it is highly present in [...] Read more.
Cysteine sulfinic acid decarboxylase catalyzes the last step of taurine biosynthesis in mammals, and belongs to the fold type I superfamily of pyridoxal-5′-phosphate (PLP)-dependent enzymes. Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in animal tissues; it is highly present in liver, kidney, muscle, and brain, and plays numerous biological and physiological roles. Despite the importance of taurine in human health, human cysteine sulfinic acid decarboxylase has been poorly characterized at the biochemical level, although its three-dimensional structure has been solved. In the present work, we have recombinantly expressed and purified human cysteine sulfinic acid decarboxylase, and applied a simple spectroscopic direct method based on circular dichroism to measure its enzymatic activity. This method gives a significant advantage in terms of simplicity and reduction of execution time with respect to previously used assays, and will facilitate future studies on the catalytic mechanism of the enzyme. We determined the kinetic constants using L-cysteine sulfinic acid as substrate, and also showed that human cysteine sulfinic acid decarboxylase is capable to catalyze the decarboxylation—besides its natural substrates L-cysteine sulfinic acid and L-cysteic acid—of L-aspartate and L-glutamate, although with much lower efficiency. Full article
(This article belongs to the Special Issue Novel and Innovative Methods for Measuring Enzyme Activity)
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10 pages, 1547 KiB  
Article
Exploratory Study of the Association between the Severity of Idiopathic Intracranial Hypertension and Electroretinogram Photopic Negative Response Amplitude Obtained Using a Handheld Device
by Antony Raharja, Shaun M. Leo, Isabelle Chow, Mathura Indusegaran, Christopher J. Hammond, Omar A. Mahroo and Sui H. Wong
Life 2021, 11(5), 437; https://doi.org/10.3390/life11050437 - 13 May 2021
Cited by 6 | Viewed by 3008
Abstract
The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal [...] Read more.
The photopic negative response (PhNR) is a negative component of the photopic flash electroretinogram that follows the b-wave and is thought to arise from the retinal ganglion cells. Reduction in its amplitude in idiopathic intracranial hypertension (IIH) has been previously documented using formal electroretinography. This study explored the use of a handheld device (RETeval, LKC technologies, Gaithersburg, MD, USA) in 72 IIH patients of varying stages and severity (and seven controls) and investigated associations between PhNR parameters and disease severity. PhNR amplitudes at 72 ms (P72) and p-ratio (ratio to b-wave peak value) differed significantly across groups, with a trend towards smaller amplitudes in those with severe IIH, defined as papilloedema with Modified Frisén Scale (MFS) ≥ 3, retinal nerve fibre layer (RNFL) ≥ 150 μm or atrophic papilloedema (p = 0.0048 and p = 0.018 for P72 and p-ratio, respectively). PhNR parameters did not correlate with MFS, RNFL thickness, standard automated perimetry mean deviation or macular ganglion cell layer volume. This study suggests that PhNR measurement using a handheld device is feasible and could potentially augment the assessment of disease severity in IIH. The clinical utility of PhNR monitoring in IIH patients requires further investigation. Full article
(This article belongs to the Special Issue Idiopathic Intracranial Hypertension)
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22 pages, 1631 KiB  
Review
Mitochondrial Bioenergetics and Dynamism in the Failing Heart
by Giampaolo Morciano, Veronica Angela Maria Vitto, Esmaa Bouhamida, Carlotta Giorgi and Paolo Pinton
Life 2021, 11(5), 436; https://doi.org/10.3390/life11050436 - 12 May 2021
Cited by 18 | Viewed by 4693
Abstract
The heart is responsible for pumping blood, nutrients, and oxygen from its cavities to the whole body through rhythmic and vigorous contractions. Heart function relies on a delicate balance between continuous energy consumption and generation that changes from birth to adulthood and depends [...] Read more.
The heart is responsible for pumping blood, nutrients, and oxygen from its cavities to the whole body through rhythmic and vigorous contractions. Heart function relies on a delicate balance between continuous energy consumption and generation that changes from birth to adulthood and depends on a very efficient oxidative metabolism and the ability to adapt to different conditions. In recent years, mitochondrial dysfunctions were recognized as the hallmark of the onset and development of manifold heart diseases (HDs), including heart failure (HF). HF is a severe condition for which there is currently no cure. In this condition, the failing heart is characterized by a disequilibrium in mitochondrial bioenergetics, which compromises the basal functions and includes the loss of oxygen and substrate availability, an altered metabolism, and inefficient energy production and utilization. This review concisely summarizes the bioenergetics and some other mitochondrial features in the heart with a focus on the features that become impaired in the failing heart. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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28 pages, 908 KiB  
Hypothesis
Ticks, Hair Loss, and Non-Clinging Babies: A Novel Tick-Based Hypothesis for the Evolutionary Divergence of Humans and Chimpanzees
by Jeffrey G. Brown
Life 2021, 11(5), 435; https://doi.org/10.3390/life11050435 - 12 May 2021
Cited by 6 | Viewed by 18910
Abstract
Human straight-legged bipedalism represents one of the earliest events in the evolutionary split between humans (Homo spp.) and chimpanzees (Pan spp.), although its selective basis is a mystery. A carrying-related hypothesis has recently been proposed in which hair loss within the [...] Read more.
Human straight-legged bipedalism represents one of the earliest events in the evolutionary split between humans (Homo spp.) and chimpanzees (Pan spp.), although its selective basis is a mystery. A carrying-related hypothesis has recently been proposed in which hair loss within the hominin lineage resulted in the inability of babies to cling to their mothers, requiring mothers to walk upright to carry their babies. However, a question remains for this model: what drove the hair loss that resulted in upright walking? Observers since Darwin have suggested that hair loss in humans may represent an evolutionary strategy for defence against ticks. The aim of this review is to propose and evaluate a novel tick-based evolutionary hypothesis wherein forest fragmentation in hominin paleoenvironments created conditions that were favourable for tick proliferation, selecting for hair loss in hominins and grooming behaviour in chimpanzees as divergent anti-tick strategies. It is argued that these divergent anti-tick strategies resulted in different methods for carrying babies, driving the locomotor divergence of humans and chimpanzees. Full article
(This article belongs to the Section Evolutionary Biology)
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11 pages, 877 KiB  
Article
Are Juglans neotropica Plantations Useful as a Refuge of Bryophytes Diversity in Tropical Areas?
by Jefferson Medina, Wilson Quizhpe, Jorge Déleg, Karina Gonzalez, Zhofre Aguirre, Nikolay Aguirre, Luis Montaño and Ángel Benítez
Life 2021, 11(5), 434; https://doi.org/10.3390/life11050434 - 12 May 2021
Cited by 1 | Viewed by 2592
Abstract
Neotropical montane forests are considered biodiversity hotspots, where epiphytic bryophytes are an important component of the diversity, biomass and functioning of these ecosystems. We evaluated the richness and composition of bryophytes in secondary successional forests and mixed plantations of Juglans neotropica. In [...] Read more.
Neotropical montane forests are considered biodiversity hotspots, where epiphytic bryophytes are an important component of the diversity, biomass and functioning of these ecosystems. We evaluated the richness and composition of bryophytes in secondary successional forests and mixed plantations of Juglans neotropica. In each forest type, the presence and cover of epiphytic bryophytes was registered in 400 quadrats of 20 cm × 30 cm. We analyzed the effects of canopy openness, diameter at breast height (DBH) and forest type on bryophyte richness, using a generalized linear model (GLM), as well as the changes in species composition using multivariate analysis. Fifty-five bryophyte species were recorded, of which 42 species were in secondary forests and 40 were in mixed plantations. Bryophyte richness did not change at forest level; however, at tree level, richness was higher in the mixed plantation of J. neotropica compared to the secondary forests, due to the presence of species adapted to high light conditions. On the other hand, bryophyte communities were negatively affected by the more open canopy in the mixed plantation of J. neotropica, species adapted to more humid conditions being less abundant. We conclude that species with narrow microclimatic niches are threatened by deforestation, and J. neotropica plantations do not act as refuge for drought-sensitive forest species present in secondary forests. Full article
(This article belongs to the Special Issue Bryophyte Responses to Climate Changes)
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18 pages, 1388 KiB  
Systematic Review
Perfusion Parameters in Near-Infrared Fluorescence Imaging with Indocyanine Green: A Systematic Review of the Literature
by Lauren N. Goncalves, Pim van den Hoven, Jan van Schaik, Laura Leeuwenburgh, Cas H. F. Hendricks, Pieter S. Verduijn, Koen E. A. van der Bogt, Carla S. P. van Rijswijk, Abbey Schepers, Alexander L. Vahrmeijer, Jaap F. Hamming and Joost R. van der Vorst
Life 2021, 11(5), 433; https://doi.org/10.3390/life11050433 - 11 May 2021
Cited by 32 | Viewed by 4218
Abstract
(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is [...] Read more.
(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging. Full article
(This article belongs to the Section Medical Research)
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44 pages, 1901 KiB  
Review
Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration
by Hope I. Needs, Margherita Protasoni, Jeremy M. Henley, Julien Prudent, Ian Collinson and Gonçalo C. Pereira
Life 2021, 11(5), 432; https://doi.org/10.3390/life11050432 - 11 May 2021
Cited by 19 | Viewed by 8816
Abstract
The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required [...] Read more.
The fact that >99% of mitochondrial proteins are encoded by the nuclear genome and synthesised in the cytosol renders the process of mitochondrial protein import fundamental for normal organelle physiology. In addition to this, the nuclear genome comprises most of the proteins required for respiratory complex assembly and function. This means that without fully functional protein import, mitochondrial respiration will be defective, and the major cellular ATP source depleted. When mitochondrial protein import is impaired, a number of stress response pathways are activated in order to overcome the dysfunction and restore mitochondrial and cellular proteostasis. However, prolonged impaired mitochondrial protein import and subsequent defective respiratory chain function contributes to a number of diseases including primary mitochondrial diseases and neurodegeneration. This review focuses on how the processes of mitochondrial protein translocation and respiratory complex assembly and function are interlinked, how they are regulated, and their importance in health and disease. Full article
(This article belongs to the Special Issue Impaired Mitochondrial Bioenergetics under Pathological Conditions)
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16 pages, 3925 KiB  
Article
Exploring the Release of Toxic Oligomers from α-Synuclein Fibrils with Antibodies and STED Microscopy
by Alessandra Bigi, Emilio Ermini, Serene W. Chen, Roberta Cascella and Cristina Cecchi
Life 2021, 11(5), 431; https://doi.org/10.3390/life11050431 - 11 May 2021
Cited by 22 | Viewed by 3334
Abstract
α-Synuclein (αS) is an intrinsically disordered and highly dynamic protein involved in dopamine release at presynaptic terminals. The abnormal aggregation of αS as mature fibrils into intraneuronal inclusion bodies is directly linked to Parkinson’s disease. Increasing experimental evidence suggests that soluble oligomers formed [...] Read more.
α-Synuclein (αS) is an intrinsically disordered and highly dynamic protein involved in dopamine release at presynaptic terminals. The abnormal aggregation of αS as mature fibrils into intraneuronal inclusion bodies is directly linked to Parkinson’s disease. Increasing experimental evidence suggests that soluble oligomers formed early during the aggregation process are the most cytotoxic forms of αS. This study investigated the uptake by neuronal cells of pathologically relevant αS oligomers and fibrils exploiting a range of conformation-sensitive antibodies, and the super-resolution stimulated emission depletion (STED) microscopy. We found that prefibrillar oligomers promptly penetrate neuronal membranes, thus resulting in cell dysfunction. By contrast, fibril docking to the phospholipid bilayer is accompanied by αS conformational changes with a progressive release of A11-reactive oligomers, which can enter into the neurons and trigger cell impairment. Our data provide important evidence on the role of αS fibrils as a source of harmful oligomers, which resemble the intermediate conformers formed de novo during aggregation, underling the dynamic and reversible nature of protein aggregates responsible for α-synucleinopathies. Full article
(This article belongs to the Special Issue Function, Regulation, and Dysfunction of Intrinsically Disordered Proteins, Volume II)
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10 pages, 692 KiB  
Review
Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance
by Catharina van Heusden, Barbara R. Grubb, Brian Button and Eduardo R. Lazarowski
Life 2021, 11(5), 430; https://doi.org/10.3390/life11050430 - 11 May 2021
Cited by 9 | Viewed by 2938
Abstract
Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated [...] Read more.
Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates. Full article
(This article belongs to the Topic ATP Release in Health and Disease)
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