Biology

25 pages, 2436 KiB

Open AccessArticle

β2-Adrenergic Signalling Promotes Cell Migration by Upregulating Expression of the Metastasis-Associated Molecule LYPD3

by Michael Gruet, Daniel Cotton, Clare Coveney, David J. Boocock, Sarah Wagner, Lucie Komorowski, Robert C. Rees, A. Graham Pockley, A. Christopher Garner, John D. Wallis, Amanda K. Miles and Desmond G. Powe

Biology 2020, 9(2), 39; https://doi.org/10.3390/biology9020039 - 22 Feb 2020

Cited by 28 | Viewed by 5441

Abstract

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line [...] Read more.

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers. Full article

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23 pages, 1157 KiB

Open AccessReview

A Review of Diatom Lipid Droplets

by Ben Leyland, Sammy Boussiba and Inna Khozin-Goldberg

Biology 2020, 9(2), 38; https://doi.org/10.3390/biology9020038 - 21 Feb 2020

Cited by 33 | Viewed by 6710

Abstract

The dynamic nutrient availability and photon flux density of diatom habitats necessitate buffering capabilities in order to maintain metabolic homeostasis. This is accomplished by the biosynthesis and turnover of storage lipids, which are sequestered in lipid droplets (LDs). LDs are an organelle conserved [...] Read more.

The dynamic nutrient availability and photon flux density of diatom habitats necessitate buffering capabilities in order to maintain metabolic homeostasis. This is accomplished by the biosynthesis and turnover of storage lipids, which are sequestered in lipid droplets (LDs). LDs are an organelle conserved among eukaryotes, composed of a neutral lipid core surrounded by a polar lipid monolayer. LDs shield the intracellular environment from the accumulation of hydrophobic compounds and function as a carbon and electron sink. These functions are implemented by interconnections with other intracellular systems, including photosynthesis and autophagy. Since diatom lipid production may be a promising objective for biotechnological exploitation, a deeper understanding of LDs may offer targets for metabolic engineering. In this review, we provide an overview of diatom LD biology and biotechnological potential. Full article

(This article belongs to the Special Issue The Molecular Life of Diatoms: From Genes to Ecosystems)

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18 pages, 2677 KiB

Open AccessArticle

Effects of Ascorbic Acid and β-1,3-Glucan on Survival, Physiological Response and Flesh Quality of Cultured Tiger Grouper (Epinephelus fuscoguttatus) during Simulated Transport in Water

by Bo Wu, Qi Wang, Jie Cao, Jun Mei and Jing Xie

Biology 2020, 9(2), 37; https://doi.org/10.3390/biology9020037 - 21 Feb 2020

Cited by 33 | Viewed by 3390

Abstract

Transport in water is the most common method for achieving high survival rates when transporting cultured fish in China; yet, transport success relies on proper water quality and conditions. This research was designed to explore the effects of ascorbic acid and β-1,3-glucan on [...] Read more.

Transport in water is the most common method for achieving high survival rates when transporting cultured fish in China; yet, transport success relies on proper water quality and conditions. This research was designed to explore the effects of ascorbic acid and β-1,3-glucan on survival, physiological responses, and flesh quality of farmed tiger grouper (Epinephelus fuscoguttatus) during simulated transport. The transport water temperature for live tiger grouper was 15 °C, which had the highest survival rate, the lowest stress response, and metabolic rate, and this will reduce the susceptibility to diseases. It is stated that β-1,3-glucan influences the changes of cortisol content, heat shock protein 70, IL-1β, and IgM transcription levels during simulated transport. Rather than using ascorbic acid alone (the A-group), β-1,3-glucan (3.2 mg/L) in the presence of ascorbic acid (25 mg/L) can effectively reduce the increase of transport-induced serum cortisol content, heat shock protein 70, and IL-1β, but stimulated IgM. 25 mg/L ascorbic acid and 3.2 mg/L β-1,3-glucan had no obvious effect on the nutritional indexes and flavor of live tiger grouper; however, these can effectively reduce the stress response, improve the innate immune activity, and ensure a higher survival rate. Full article

(This article belongs to the Special Issue Fish Metabolic Physiology in Response to Stress)

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5 pages, 166 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Biology in 2019

by Biology Editorial Office

Biology 2020, 9(2), 36; https://doi.org/10.3390/biology9020036 - 21 Feb 2020

Viewed by 1912

Abstract

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article

17 pages, 4171 KiB

Open AccessArticle

Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity

by Wei Liu, Nathan A. Krump, Meenhard Herlyn and Jianxin You

Biology 2020, 9(2), 35; https://doi.org/10.3390/biology9020035 - 19 Feb 2020

Cited by 10 | Viewed by 4082

Abstract

Merkel cell carcinoma (MCC) is a highly lethal skin cancer. MCC tumors rapidly develop resistance to the chemotherapies tested to date. While PD-1/PD-L1 immune checkpoint blockade has demonstrated success in MCC treatment, a significant portion of MCC patients are nonresponsive. Therefore, the pressing [...] Read more.

Merkel cell carcinoma (MCC) is a highly lethal skin cancer. MCC tumors rapidly develop resistance to the chemotherapies tested to date. While PD-1/PD-L1 immune checkpoint blockade has demonstrated success in MCC treatment, a significant portion of MCC patients are nonresponsive. Therefore, the pressing need for effective MCC chemotherapies remains. We screened a library of natural products and discovered that one compound, glaucarubin, potently reduced the viability of Merkel cell polyomavirus (MCPyV)-positive MCCs, while remaining nontoxic to primary human fibroblasts and MCPyV-negative MCC cell lines tested. Protein array and Western blot analyses revealed that glaucarubin induces DNA damage and PARP-1 cleavage that correlates with the loss of viability in MCC cells. However, high basal expression of the antiapoptotic factor BCL-2 allowed a subpopulation of cells to survive glaucarubin treatment. Previous studies have shown that, while targeting BCL-2 family proteins significantly decreases MCC cell viability, BCL-2 antisense therapy alone was insufficient to inhibit tumor growth in patients with advanced MCC. We discovered that treatment with an FDA-approved BCL-2 inhibitor in the context of glaucarubin-induced DNA damage led to near complete killing in multiple MCPyV-positive MCC cell lines that express high levels of BCL-2. The combination of DNA damage-induced apoptosis and BCL-2 inhibition thus represents a novel therapeutic strategy for MCPyV-positive MCCs. Full article

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23 pages, 944 KiB

Open AccessReview

Extracellular Traps: An Ancient Weapon of Multiple Kingdoms

by Ariane Neumann, Graham Brogden and Maren von Köckritz-Blickwede

Biology 2020, 9(2), 34; https://doi.org/10.3390/biology9020034 - 18 Feb 2020

Cited by 36 | Viewed by 5452

Abstract

The discovery, in 2004, of extracellular traps released by neutrophils has extended our understanding of the mode of action of various innate immune cells. This fascinating discovery demonstrated the extracellular trapping and killing of various pathogens by neutrophils. During the last decade, evidence [...] Read more.

The discovery, in 2004, of extracellular traps released by neutrophils has extended our understanding of the mode of action of various innate immune cells. This fascinating discovery demonstrated the extracellular trapping and killing of various pathogens by neutrophils. During the last decade, evidence has accumulated showing that extracellular traps play a crucial role in the defence mechanisms of various cell types present in vertebrates, invertebrates, and plants. The aim of this review is to summarise the relevant literature on the evolutionary history of extracellular traps used as a weapon in various kingdoms of life. Full article

(This article belongs to the Special Issue Neutrophil Extracellular Traps)

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9 pages, 1363 KiB

Open AccessArticle

From One Ejaculate to Another: Transference of Sperm Traits via Seminal Plasma Supplementation in the Ram

by Christine Green, Jessica P. Rickard, Simon P. de Graaf and Angela J. Crean

Biology 2020, 9(2), 33; https://doi.org/10.3390/biology9020033 - 18 Feb 2020

Cited by 7 | Viewed by 3409

Abstract

Males can adjust sperm motility instantaneously in response to the perceived risk of sperm competition. The speed of this response suggests that sperm motility is regulated by changes in seminal plasma rather than changes in the sperm cells themselves. Hence, here we test [...] Read more.

Males can adjust sperm motility instantaneously in response to the perceived risk of sperm competition. The speed of this response suggests that sperm motility is regulated by changes in seminal plasma rather than changes in the sperm cells themselves. Hence, here we test whether inter-ejaculate variation in seminal plasma can be used to alter sperm quality prior to use in assisted reproductive technologies. We supplemented fresh ejaculates of Merino rams with seminal plasma collected from previous ‘donor’ ejaculates to test whether changes in sperm kinetics were related to the relative quality of donor to focal ejaculates. We found a positive relationship between the change in sperm traits before and after supplementation, and the difference in sperm traits between the donor and focal ejaculate. Hence, sperm motility can be either increased or decreased through the addition of seminal plasma from a superior or inferior ejaculate, respectively. This positive relationship held true even when seminal plasma was added from a previous ejaculate of the same ram, although the slope of the relationship depended on the identity of both the donor and receiver ram. These findings indicate that seminal plasma plays a key role in the control and regulation of sperm kinetics, and that sperm kinetic traits can be transferred from one ejaculate to another through seminal plasma supplementation. Full article

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17 pages, 9570 KiB

Open AccessArticle

Morphological Features of the Anther Development in Tomato Plants with Non-Specific Male Sterility

by Inna A. Chaban, Neonila V. Kononenko, Alexander A. Gulevich, Liliya R. Bogoutdinova, Marat R. Khaliluev and Ekaterina N. Baranova

Biology 2020, 9(2), 32; https://doi.org/10.3390/biology9020032 - 17 Feb 2020

Cited by 7 | Viewed by 6661

Abstract

The study was devoted to morphological and cytoembryological analysis of disorders in the anther and pollen development of transgenic tomato plants with a normal and abnormal phenotype, which is characterized by the impaired development of generative organs. Various abnormalities in the structural organization [...] Read more.

The study was devoted to morphological and cytoembryological analysis of disorders in the anther and pollen development of transgenic tomato plants with a normal and abnormal phenotype, which is characterized by the impaired development of generative organs. Various abnormalities in the structural organization of anthers and microspores were revealed. Such abnormalities in microspores lead to the blocking of asymmetric cell division and, accordingly, the male gametophyte formation. Some of the non-degenerated microspores accumulate a large number of storage inclusions, forming sterile mononuclear pseudo-pollen, which is similar in size and appearance to fertile pollen grain (looks like pollen grain). It was discussed that the growth of tapetal cells in abnormal anthers by increasing the size and ploidy level of nuclei contributes to this process. It has been shown that in transgenic plants with a normal phenotype, individual disturbances are also observed in the development of both male and female gametophytes. The reason for the developmental arrest of some ovules was the death of endosperm at different stages of the globular embryo. At the same time, noticeable hypertrophy of endothelial cells performing a secretory function was observed. In the ovules of transgenic plants with abnormalities, the endothelium forms a pseudo-embryo instead of the embryo sac, stimulating the development of parthenocarpic fruits. The data obtained in this study can be useful for a better understanding of the genetic and molecular mechanisms of cytoplasmic male sterility and parthenocarpic fruit development in tomatoes. Full article

(This article belongs to the Section Developmental and Reproductive Biology)

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10 pages, 1488 KiB

Open AccessCommunication

CXCR4 Antagonists as Stem Cell Mobilizers and Therapy Sensitizers for Acute Myeloid Leukemia and Glioblastoma?

by Vashendriya V.V. Hira, Cornelis J.F. Van Noorden and Remco J. Molenaar

Biology 2020, 9(2), 31; https://doi.org/10.3390/biology9020031 - 17 Feb 2020

Cited by 19 | Viewed by 3837

Abstract

Glioblastoma is the most aggressive and malignant primary brain tumor in adults and has a poor patient survival of only 20 months after diagnosis. This poor patient survival is at least partly caused by glioblastoma stem cells (GSCs), which are slowly-dividing and therefore [...] Read more.

Glioblastoma is the most aggressive and malignant primary brain tumor in adults and has a poor patient survival of only 20 months after diagnosis. This poor patient survival is at least partly caused by glioblastoma stem cells (GSCs), which are slowly-dividing and therefore therapy-resistant. GSCs are localized in protective hypoxic peri-arteriolar niches where these aforementioned stemness properties are maintained. We previously showed that hypoxic peri-arteriolar GSC niches in human glioblastoma are functionally similar to hypoxic peri-arteriolar hematopoietic stem cell (HSC) niches in human bone marrow. GSCs and HSCs express the receptor C-X-C receptor type 4 (CXCR4), which binds to the chemoattractant stromal-derived factor-1α (SDF-1α), which is highly expressed in GSC niches in glioblastoma and HSC niches in bone marrow. This receptor–ligand interaction retains the GSCs/HSCs in their niches and thereby maintains their slowly-dividing state. In acute myeloid leukemia (AML), leukemic cells use the SDF-1α–CXCR4 interaction to migrate to HSC niches and become slowly-dividing and therapy-resistant leukemic stem cells (LSCs). In this communication, we aim to elucidate how disruption of the SDF-1α–CXCR4 interaction using the FDA-approved CXCR4 inhibitor plerixafor (AMD3100) may be used to force slowly-dividing cancer stem cells out of their niches in glioblastoma and AML. Ultimately, this strategy aims to induce GSC and LSC differentiation and their sensitization to therapy. Full article

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20 pages, 1654 KiB

Open AccessArticle

Genome-Scale Metabolic Reconstruction and in Silico Perturbation Analysis of the Polar Diatom Fragilariopsis cylindrus Predicts High Metabolic Robustness

by Michel Lavoie, Blanche Saint-Béat, Jan Strauss, Sébastien Guérin, Antoine Allard, Simon V. Hardy, Angela Falciatore and Johann Lavaud

Biology 2020, 9(2), 30; https://doi.org/10.3390/biology9020030 - 17 Feb 2020

Cited by 9 | Viewed by 5666

Abstract

Diatoms are major primary producers in polar environments where they can actively grow under extremely variable conditions. Integrative modeling using a genome-scale model (GSM) is a powerful approach to decipher the complex interactions between components of diatom metabolism and can provide insights into [...] Read more.

Diatoms are major primary producers in polar environments where they can actively grow under extremely variable conditions. Integrative modeling using a genome-scale model (GSM) is a powerful approach to decipher the complex interactions between components of diatom metabolism and can provide insights into metabolic mechanisms underlying their evolutionary success in polar ecosystems. We developed the first GSM for a polar diatom, Fragilariopsis cylindrus, which enabled us to study its metabolic robustness using sensitivity analysis. We find that the predicted growth rate was robust to changes in all model parameters (i.e., cell biochemical composition) except the carbon uptake rate. Constraints on total cellular carbon buffer the effect of changes in the input parameters on reaction fluxes and growth rate. We also show that single reaction deletion of 20% to 32% of active (nonzero flux) reactions and single gene deletion of 44% to 55% of genes associated with active reactions affected the growth rate, as well as the production fluxes of total protein, lipid, carbohydrate, DNA, RNA, and pigments by less than 1%, which was due to the activation of compensatory reactions (e.g., analogous enzymes and alternative pathways) with more highly connected metabolites involved in the reactions that were robust to deletion. Interestingly, including highly divergent alleles unique for F. cylindrus increased its metabolic robustness to cellular perturbations even more. Overall, our results underscore the high robustness of metabolism in F. cylindrus, a feature that likely helps to maintain cell homeostasis under polar conditions. Full article

(This article belongs to the Special Issue The Molecular Life of Diatoms: From Genes to Ecosystems)

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16 pages, 2209 KiB

Open AccessArticle

Contributions of Chondroitin Sulfate, Keratan Sulfate and N-linked Oligosaccharides to Inhibition of Neurite Outgrowth by Aggrecan

by Thomas M. Hering, Justin A. Beller, Christopher M. Calulot and Diane M. Snow

Biology 2020, 9(2), 29; https://doi.org/10.3390/biology9020029 - 12 Feb 2020

Cited by 9 | Viewed by 4128

Abstract

The role of proteoglycans in the central nervous system (CNS) is a rapidly evolving field and has major implications in the field of CNS injury. Chondroitin sulfate proteoglycans (CSPGs) increase in abundance following damage to the spinal cord and inhibit neurite outgrowth. Major [...] Read more.

The role of proteoglycans in the central nervous system (CNS) is a rapidly evolving field and has major implications in the field of CNS injury. Chondroitin sulfate proteoglycans (CSPGs) increase in abundance following damage to the spinal cord and inhibit neurite outgrowth. Major advances in understanding the interaction between outgrowing neurites and CSPGs has created a need for more robust and quantitative analyses to further our understanding of this interaction. We report the use of a high-throughput assay to determine the effect of various post-translational modifications of aggrecan upon neurite outgrowth from NS-1 cells (a PC12 cell line derivative). Aggrecan contains chondroitin sulfate, keratan sulfate, and N-linked oligosaccharides (N-glycans), each susceptible to removal through different enzymatic digestions. Using a sequential digestion approach, we found that chondroitin sulfate and N-glycans, but not keratan sulfate, contribute to inhibition of neurite outgrowth by substrate-bound aggrecan. For the first time, we have shown that N-linked oligosaccharides on aggrecan contribute to its inhibition of neuritogenesis. Full article

(This article belongs to the Special Issue Models of CNS Regeneration: Mind the Gap!)

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8 pages, 3091 KiB

Open AccessCase Report

Rapid Efficacy of Gemtuzumab Ozogamicin in Refractory AML Patients with Pulmonary and Kidney Failure

by Daniil Zaytsev, Larisa Girshova, Vladimir Ivanov, Irina Budaeva, Dmitri Motorin, Renat Badaev, Julia Mirolubova, Evgeni Grobovenko, Tamara Chitanava, Ekaterina Zaykova, Julia Alexeeva and Andrey Zaritskey

Biology 2020, 9(2), 28; https://doi.org/10.3390/biology9020028 - 10 Feb 2020

Cited by 3 | Viewed by 2960

Abstract

Objectives: To the best of our knowledge, data from Gemtuzumab ozogamicin in Acute Myeloid Leukemia (AML) patients with failure of organ functions and poor performance status are extremely lacking. Moreover, the fast recovery from organ failure, after Gemtuzumab ozogamicin administration, has never been [...] Read more.

Objectives: To the best of our knowledge, data from Gemtuzumab ozogamicin in Acute Myeloid Leukemia (AML) patients with failure of organ functions and poor performance status are extremely lacking. Moreover, the fast recovery from organ failure, after Gemtuzumab ozogamicin administration, has never been reported. This study aimed to demonstrate the efficacy and rapid response of Gemtuzumab ozogamicin in refractory acute myeloid leukemia (AML) patients with pulmonary and kidney failure and poor performance status. Three refractory AML patients, with organ dysfunction, are described. One patient was pre-treated with intensive chemotherapy, and two other patients progressed during Azacitidine treatment. Two patients had respiratory failure grade 2 and one patient suffered from acute kidney insufficiency. Two patients were highly febrile with an elevated С-Reactive Protein (CRP) level. The WHO performance status of three was measured in all patients. Gemtuzumab ozogamicin administration was performed in three patients, followed by a further switch to Gemtuzumab ozogamicin + Azacitidine or “7+3” treatment. Results: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with a rapid decrease in CRP level and fast resolution of respiratory failure. Recovery of kidney function was noticed rapidly in patients with renal insufficiency. The WHO performance status was elevated in all three patients. No adverse grade II–III effects were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient underwent allogeneic stem cell transplantation, and the patient with kidney failure obtained complete remission. Conclusions: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunction, like pulmonary or renal failure and poor performance status, and may contribute to rapid recovery from organ failures. Full article

(This article belongs to the Section Immunology)

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11 pages, 2040 KiB

Open AccessArticle

Acute Exposure to Key Aquaculture Environmental Stressors Impaired the Aerobic Metabolism of Carassius auratus gibelio

by Zongli Yao, Xiaoying Zhang, Qifang Lai, Kai Zhou and Pengcheng Gao

Biology 2020, 9(2), 27; https://doi.org/10.3390/biology9020027 - 10 Feb 2020

Cited by 8 | Viewed by 2924

Abstract

Carassius auratus gibelio is an omnivore favored for its flavor and is commonly used as a benthic species in traditional pond polyculture. This study investigated the effects of common aquaculture stressors, such as high ammonia, high nitrite, high pH, and hypoxia on the [...] Read more.

Carassius auratus gibelio is an omnivore favored for its flavor and is commonly used as a benthic species in traditional pond polyculture. This study investigated the effects of common aquaculture stressors, such as high ammonia, high nitrite, high pH, and hypoxia on the aerobic metabolism of C. auratus gibelio. The results showed that the standard metabolic rate (SMR) was positively correlated with ammonia, nitrite, and pH, while the maximum metabolic rate (MMR) was negatively correlated with all four stressors. Thus, aerobic scope (AS) was reduced when C. auratus gibelio was exposed to high ammonia, high nitrite, high pH, and hypoxia. The peak of post-prandial O₂ consumption was positively correlated with nitrite, pH, and the occurrence of the peak metabolic rate post-prandial was delayed in high ammonia, high nitrite, hypoxia, and high pH conditions. These findings indicated that, in experimental conditions, exposure to these environmental stressors can influence aerobic metabolism in C. auratus gibelio. With more energy required to maintain standard metabolic rates, less will be available for growth. While the C. auratus gibelio is one of the most hypoxia tolerance species, the reduction we observed in AS caused by stressors that commonly occur in ponds and in nature will likely affect growth in ponds and fitness in nature. These data have provided insight into the optimal, fitness-maximizing thresholds for these common stressors in this species of interest. Full article

(This article belongs to the Special Issue Fish Metabolic Physiology in Response to Stress)

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9 pages, 1645 KiB

Open AccessArticle

Determining Ancestry between Rodent- and Human-Derived Virus Sequences in Endemic Foci: Towards a More Integral Molecular Epidemiology of Lassa Fever within West Africa

by Ayodeji Olayemi, Adetunji Samuel Adesina, Thomas Strecker, N’Faly Magassouba and Elisabeth Fichet-Calvet

Biology 2020, 9(2), 26; https://doi.org/10.3390/biology9020026 - 7 Feb 2020

Cited by 11 | Viewed by 3848

Abstract

Lassa fever is a viral hemorrhagic illness responsible for thousands of human deaths in West Africa yearly. Rodents are known as natural reservoirs of the causative Lassa mammarenavirus (LASV) while humans are regarded as incidental, spill-over hosts. Analysis of genetic sequences continues to [...] Read more.

Lassa fever is a viral hemorrhagic illness responsible for thousands of human deaths in West Africa yearly. Rodents are known as natural reservoirs of the causative Lassa mammarenavirus (LASV) while humans are regarded as incidental, spill-over hosts. Analysis of genetic sequences continues to add to our understanding of the evolutionary history, emergence patterns, and the epidemiology of LASV. Hitherto, the source of data in such investigations has mainly comprised human clinical samples. Presently, a rise in the quantity of virus strains accessed through ecological studies over the last 15 years now allows us to explore how LASV sequences obtained from rodents might affect phylogenetic patterns. In this study, we phylogenetically compared LASV sequences obtained from both rodents and humans across West Africa, including those from two localities highly endemic for the disease: Ekpoma in Nigeria and Kenema in Sierra Leone. We performed a time-calibrated phylogeny, using a Bayesian analysis on 198 taxa, including 102 sequences from rodents and 96 from humans. Contrary to expectation, our results show that LASV strains detected in humans within these localities, even those sampled recently, are consistently ancient to those circulating in rodents in the same area. We discuss the possibilities connected to this preliminary outcome. We also propose modalities to guide more comprehensive comparisons of human and rodent data in LASV molecular epidemiological studies. Full article

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16 pages, 1248 KiB

Open AccessReview

“What You Need, Baby, I Got It”: Transposable Elements as Suppliers of Cis-Operating Sequences in Drosophila

by Roberta Moschetti, Antonio Palazzo, Patrizio Lorusso, Luigi Viggiano and René Massimiliano Marsano

Biology 2020, 9(2), 25; https://doi.org/10.3390/biology9020025 - 3 Feb 2020

Cited by 38 | Viewed by 5052

Abstract

Transposable elements (TEs) are constitutive components of both eukaryotic and prokaryotic genomes. The role of TEs in the evolution of genes and genomes has been widely assessed over the past years in a variety of model and non-model organisms. Drosophila is undoubtedly among [...] Read more.

Transposable elements (TEs) are constitutive components of both eukaryotic and prokaryotic genomes. The role of TEs in the evolution of genes and genomes has been widely assessed over the past years in a variety of model and non-model organisms. Drosophila is undoubtedly among the most powerful model organisms used for the purpose of studying the role of transposons and their effects on the stability and evolution of genes and genomes. Besides their most intuitive role as insertional mutagens, TEs can modify the transcriptional pattern of host genes by juxtaposing new cis-regulatory sequences. A key element of TE biology is that they carry transcriptional control elements that fine-tune the transcription of their own genes, but that can also perturb the transcriptional activity of neighboring host genes. From this perspective, the transposition-mediated modulation of gene expression is an important issue for the short-term adaptation of physiological functions to the environmental changes, and for long-term evolutionary changes. Here, we review the current literature concerning the regulatory and structural elements operating in cis provided by TEs in Drosophila. Furthermore, we highlight that, besides their influence on both TEs and host genes expression, they can affect the chromatin structure and epigenetic status as well as both the chromosome’s structure and stability. It emerges that Drosophila is a good model organism to study the effect of TE-linked regulatory sequences, and it could help future studies on TE–host interactions in any complex eukaryotic genome. Full article

(This article belongs to the Section Genetics and Genomics)

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14 pages, 3255 KiB

Open AccessArticle

High-Fat Diet Propelled AOM/DSS-Induced Colitis-Associated Colon Cancer Alleviated by Administration of Aster glehni via STAT3 Signaling Pathway

by Bo-Ram Jin, Kyung-Sook Chung, Minho Lee and Hyo-Jin An

Biology 2020, 9(2), 24; https://doi.org/10.3390/biology9020024 - 2 Feb 2020

Cited by 26 | Viewed by 8185

Abstract

Many epidemiological observational studies suggest that a high-fat diet (HFD) accelerates the risk of colorectal cancer (CRC). Inflammation can play a key role in the relationship between colon cancer and HFD. Although reported by several studies, controlled experimental studies have not explored this [...] Read more.

Many epidemiological observational studies suggest that a high-fat diet (HFD) accelerates the risk of colorectal cancer (CRC). Inflammation can play a key role in the relationship between colon cancer and HFD. Although reported by several studies, controlled experimental studies have not explored this relationship. We established an HFD-fed colitis-associated colon cancer (CAC) mice model and evaluated the anti-tumorigenic effects of AG on HFD-propelled CAC along with its mechanism of action. Previously, we found that Aster glehni (AG) exerts chemopreventive effects on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC in a mice model, and has anti-adipogenic effects in a HFD-induced obesity mice model. In the HFD-propelled CAC mice model, AG significantly reduced cancer-related death, prevented body weight loss, and alleviated splenic enlargement. Additionally, AG prevented colon shortening and reduced the number of colorectal polyps. Histological studies demonstrated the up-regulation of inflammation, hyperplasia, and neoplasia in HFD-propelled CAC mice, whereas AG suppressed colonic disease progression and tumorigenesis. Furthermore, AG significantly inhibited the signal transducer and activator of transcription 3 (STAT3) signaling pathway and attenuated the protein expression of the STAT3 target gene, which mediates transcription factor-dependent tumor cell proliferation. These results indicate that AG abrogates inflammation-induced tumor progression in HFD-propelled CAC mice by inhibiting STAT3 activation. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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11 pages, 1353 KiB

Open AccessArticle

Value of SUV_max for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma

by Stephanie A. Stalder, Paul Schumann, Martin Lanzer, Martin W. Hüllner, Niels J. Rupp, Martina A. Broglie and Grégoire B. Morand

Biology 2020, 9(2), 23; https://doi.org/10.3390/biology9020023 - 2 Feb 2020

Cited by 15 | Viewed by 4740 | Correction

Abstract

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine [...] Read more.

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUV_max) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUV_max in an almost linear manner. A pretherapeutic SUV_max of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUV_max between 9.5–14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning. Full article

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16 pages, 2350 KiB

Open AccessArticle

Centrifugation Force and Time Alter CASA Parameters and Oxidative Status of Cryopreserved Stallion Sperm

by Giuseppina Marzano, Natalina Moscatelli, Mariangela Di Giacomo, Nicola Antonio Martino, Giovanni Michele Lacalandra, Maria Elena Dell’Aquila, Giuseppe Maruccio, Elisabetta Primiceri, Maria Serena Chiriacò, Vincenzo Zara and Alessandra Ferramosca

Biology 2020, 9(2), 22; https://doi.org/10.3390/biology9020022 - 27 Jan 2020

Cited by 11 | Viewed by 4969

Abstract

Conventional sperm selection techniques used in ARTs rely on centrifugation steps. To date, the different studies reported on the effects of centrifugation on stallion sperm motility provided contrasting results and do not include effects on mitochondrial functionality and different oxidative parameters. The effects [...] Read more.

Conventional sperm selection techniques used in ARTs rely on centrifugation steps. To date, the different studies reported on the effects of centrifugation on stallion sperm motility provided contrasting results and do not include effects on mitochondrial functionality and different oxidative parameters. The effects of different centrifugation protocols (300× g for 5′, 300× g for 10′, 1500× g for 5′ and 1500× g for 10′ vs. no centrifugation) on motility and oxidative status in cryopreserved stallion sperm, were analyzed. After centrifugation, almost all motility parameters were significantly altered, as observed by computer-assisted sperm analysis. A polarographic assay of oxygen consumption showed a progressive decrease in mitochondria respiration from the gentlest to the strongest protocol. By laser scanning confocal microscopy, significant reduction of mitochondrial membrane potential, at any tested protocol, and time-dependent effects, at the same centrifugal force, were found. Increased DNA fragmentation index at any tested protocol and time-dependent effects at the same centrifugal force were found, whereas increased protein carbonylation was observed only at the strongest centrifugal force. These results provide more comprehensive understandings on centrifugation-induced effects on cryopreserved stallion sperm and suggest that, even at a weak force for a short time, centrifugation impairs different aspects of equine sperm metabolism and functionality. Full article

(This article belongs to the Section Cell Biology)

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Biology, Volume 9, Issue 2 (February 2020) – 18 articles

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