bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcineurin and Systemic Lupus Erythematosus: The Rationale for Using Calcineurin Inhibitors in the Treatment of Lupus Nephritis
Authors: Rafael-Vidal Carlos , Altabás Irene , Pérez Nair , Mourino Rodríguez Coral , Pego-Reigosa Jose M. , Garcia Samuel
Published: January 2021

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN.
Feasibility of Human Platelet Lysate as an Alternative to Foetal Bovine Serum for In Vitro Expansion of Chondrocytes
Authors: Liau Ling Ling , Hassan Muhammad Najib Fathi bin , Tang Yee Loong , Ng Min Hwei , Law Jia Xian
Published: January 2021

Osteoarthritis (OA) is a degenerative joint disease that affects a lot of people worldwide. Current treatment for OA mainly focuses on halting or slowing down the disease progress and to improve the patient’s quality of life and functionality. Autologous chondrocyte implantation (ACI) is a new treatment modality with the potential to promote regeneration of worn cartilage. Traditionally, foetal bovine serum (FBS) is used to expand the chondrocytes. However, the use of FBS is not ideal for the expansion of cells mean for clinical applications as it possesses the risk of animal pathogen transmission and animal protein transfer to host. Human platelet lysate (HPL) appears to be a suitable alternative to FBS as it is rich in biological factors that enhance cell proliferation. Thus far, HPL has been found to be superior in promoting chondrocyte proliferation compared to FBS. However, both HPL and FBS cannot prevent chondrocyte dedifferentiation. Discrepant results have been reported for the maintenance of chondrocyte redifferentiation potential by HPL. These differences are likely due to the diversity in the HPL preparation methods. In the future, more studies on HPL need to be performed to develop a standardized technique which is capable of producing HPL that can maintain the chondrocyte redifferentiation potential reproducibly. This review discusses the in vitro expansion of chondrocytes with FBS and HPL, focusing on its capability to promote the proliferation and maintain the chondrogenic characteristics of chondrocytes.
The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia
Authors: Urwanisch Laura , Luciano Michela , Horejs-Hoeck Jutta
Published: January 2021

Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.
Fatty Acids and a High-Fat Diet Induce Epithelial–Mesenchymal Transition by Activating TGFβ and β-Catenin in Liver Cells
Authors: Kwapisz Oliwia , Górka Judyta , Korlatowicz Agata , Kotlinowski Jerzy , Waligórska Agnieszka , Marona Paulina , Pydyn Natalia , Dobrucki Jurek W. , Jura Jolanta , Miekus Katarzyna
Published: January 2021

Nonalcoholic fatty liver disease is defined as the accumulation of excessive fat in the liver in the absence of excessive alcohol consumption or any secondary cause. Although the disease generally remains asymptomatic, chronic liver inflammation leads to fibrosis, liver cirrhosis, and even to the development of hepatocellular carcinoma (HCC). Fibrosis results from epithelial–mesenchymal transition (EMT), which leads to dedifferentiation of epithelial cells into cells with a mesenchymal-like phenotype. During EMT, epithelial cells with high expression of E-cadherin, influenced by growth factors, cytokines, and inflammatory processes, undergo morphological changes via enhanced expression of, e.g., vimentin, fibronectin, and N-cadherin. An inducer of EMT and, consequently, of fibrosis development is transforming growth factor beta (TGFβ), a pleiotropic cytokine associated with the progression of hepatocarcinogenesis. However, the understanding of the molecular events that direct the development of steatosis into steatohepatitis and liver fibrosis remains incomplete. Our study revealed that both prolonged exposure of hepatocarcinoma cells to fatty acids in vitro and high-fat diet in mice (20 weeks) result in inflammation. Prolonged treatment with fatty acids increased the levels of TGFβ, MMP9, and β-catenin, important EMT inducers. Moreover, the livers of mice fed a high-fat diet exhibited features of liver fibrosis with increased TGFβ and IL-1 levels. Increased expression of IL-1 correlated with a decrease in monocyte chemoattractant protein-induced protein 1 (MCPIP1), a negative regulator of the inflammatory response that regulates the stability of proinflammatory transcripts encoding IL-1. Our study showed that a high-fat diet induced EMT by increasing the levels of EMT-activating transcription factors, including Zeb1, Zeb2, and Snail and changed the protein profile to a profile characteristic of the mesenchymal phenotype.
PLEKHA7, an Apical Adherens Junction Protein, Suppresses Inflammatory Breast Cancer in the Context of High E-Cadherin and p120-Catenin Expression
Authors: Pence Lindy J. , Kourtidis Antonis , Feathers Ryan W. , Haddad Mary T. , Sotiriou Sotiris , Decker Paul A. , Nassar Aziza , Ocal Idris T. , Shah Sejal S. , Anastasiadis Panos Z.
Published: January 2021

Inflammatory breast cancer is a highly aggressive form of breast cancer that forms clusters of tumor emboli in dermal lymphatics and readily metastasizes. These cancers express high levels of E-cadherin, the major mediator of adherens junctions, which enhances formation of tumor emboli. Previous studies suggest that E-cadherin promotes cancer when the balance between apical and basolateral cadherin complexes is disrupted. Here, we used immunohistochemistry of inflammatory breast cancer patient samples and analysis of cell lines to determine the expression of PLEKHA7, an apical adherens junction protein. We used viral transduction to re-express PLEKHA7 in inflammatory breast cancer cells and examined their aggressiveness in 2D and 3D cultures and in vivo. We determined that PLEKHA7 was deregulated in inflammatory breast cancer, demonstrating improper localization or lost expression in most patient samples and very low expression in cell lines. Re-expressing PLEKHA7 suppressed proliferation, anchorage independent growth, spheroid viability, and tumor growth in vivo. The data indicate that PLEKHA7 is frequently deregulated and acts to suppress inflammatory breast cancer. The data also promote the need for future inquiry into the imbalance between apical and basolateral cadherin complexes as driving forces in inflammatory breast cancer.
Effects of CREG1 on Age-Associated Metabolic Phenotypes and Renal Senescence in Mice
Authors: Hashimoto Michihiro , Goto Ayumi , Endo Yuki , Sugimoto Masataka , Ueda Jun , Yamashita Hitoshi
Published: January 2021

Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein that accelerates p16-dependent cellular senescence in vitro. We recently reported the ability of CREG1 to stimulate brown adipogenesis using adipocyte P2-CREG1-transgenic (Tg) mice; however, little is known about the effect of CREG1 on aging-associated phenotypes. In this study, we investigated the effects of CREG1 on age-related obesity and renal dysfunction in Tg mice. Increased brown fat formation was detected in aged Tg mice, in which age-associated metabolic phenotypes such as body weight gain and increases in blood glucose were improved compared with those in wild-type (WT) mice. Blood CREG1 levels increased significantly in WT mice with age, whereas the age-related increase was suppressed, and its levels were reduced, in the livers and kidneys of Tg mice relative to those in WT mice at 25 months. Intriguingly, the mRNA levels of Ink4a, Arf, and senescence-associated secretory phenotype (SASP)-related genes and p38MAPK activity were significantly lowered in the aged kidneys of Tg mice, in which the morphological abnormalities of glomeruli as well as filtering function seen in WT kidneys were alleviated. These results suggest the involvement of CREG1 in kidney aging and its potential as a target for improving age-related renal dysfunction.
Mechanical Brain Injury Increases Cells’ Production of Cystathionine β-Synthase and Glutamine Synthetase, but Reduces Pax2 Expression in the Telencephalon of Juvenile Chum Salmon, Oncorhynchus keta
Authors: Pushchina Evgeniya V. , Zharikova Eva I. , Varaksin Anatoly A.
Published: January 2021

The considerable post-traumatic brain recovery in fishes makes them a useful model for studying the mechanisms that provide reparative neurogenesis, which is poorly represented in mammals. After a mechanical injury to the telencephalon in adult fish, lost neurons are actively replaced due to the proliferative activity of neuroepithelial cells and radial glia in the neurogenic periventricular zone. However, it is not enough clear which signaling mechanisms are involved in the activation of adult neural stem cells (aNSC) after the injury (reactive proliferation) and in the production of new neurons (regenerative neurogenesis) from progenitor cells (NPC). In juvenile Pacific salmon, the predominant type of NSCs in the telencephalon are neuroepithelial cells corresponding to embryonic NSCs. Expression of glutamine synthetase (GS), a NSC molecular marker, was detected in the neuroepithelial cells of the pallium and subpallium of juvenile chum salmon, Oncorhynchus keta. At 3 days after a traumatic brain injury (TBI) in juvenile chum salmon, the GS expression was detected in the radial glia corresponding to aNSC in the pallium and subpallium. The maximum density of distribution of GS+ radial glia was found in the dorsal pallial region. Hydrogen sulfide (H2S) is a proneurogenic factor that reduces oxidative stress and excitotoxicity effects, along with the increased GS production in the brain cells of juvenile chum salmon. In the fish brain, H2S producing by cystathionine β-synthase in neurogenic zones may be involved in maintaining the microenvironment that provides optimal conditions for the functioning of neurogenic niches during constitutive neurogenesis. After injury, H2S can determine cell survivability, providing a neuroprotective effect in the area of injury and reducing the process of glutamate excitotoxicity, acting as a signaling molecule involved in changing the neurogenic environment, which leads to the reactivation of neurogenic niches and cell regeneration programs. The results of studies on the control of the expression of regulatory Sonic Hedgehog genes (Shh) and the transcription factors Paired Box2 (Pax2) regulated by them are still insufficient. A comparative analysis of Pax2 expression in the telencephalon of intact chum salmon showed the presence of constitutive patterns of Pax2 expression in neurogenic areas and non-neurogenic parenchymal zones of the pallium and subpallium. After mechanical injury, the patterns of Pax2 expression changed, and the amount of Pax2+ decreased (p < 0.05) in lateral (Dl), medial (Dm) zones of the pallium, and the lateral zone (Vl) of the subpallium compared to the control. We believe that the decrease in the expression of Pax2 may be caused by the inhibitory effect of the Pax6 transcription factor, whose expression in the juvenile salmon brain increases upon injury.
Alteration of Cx37, Cx40, Cx43, Cx45, Panx1, and Renin Expression Patterns in Postnatal Kidneys of Dab1-/- (yotari) Mice
Authors: Lozić Mirela , Filipović Natalija , Jurić Marija , Kosović Ivona , Benzon Benjamin , Šolić Ivana , Kelam Nela , Racetin Anita , Watanabe Koichiro , Katsuyama Yu , Ogata Masaki , Saraga-Babić Mirna , Vukojević Katarina
Published: January 2021

Numerous evidence corroborates roles of gap junctions/hemichannels in proper kidney development. We analyzed how Dab1 gene functional silencing influences expression and localization of Cx37, Cx40, Cx43, Cx45, Panx1 and renin in postnatal kidneys of yotari mice, by using immunohistochemistry and electron microscopy. Dab1 Δ102/221 might lead to the activation of c-Src tyrosine kinase, causing the upregulation of Cx43 in the medulla of yotari mice. The expression of renin was more prominent in yotari mice (p < 0.001). Renin granules were unusually present inside the vascular walls of glomeruli capillaries, in proximal and distal convoluted tubules and in the medulla. Disfunction of Cx40 is likely responsible for increased atypically positioned renin cells which release renin in an uncontrolled fashion, but this doesn’t rule out simultaneous involvement of other Cxs, such as Cx45 which was significantly increased in the yotari cortex. The decreased Cx37 expression in yotari medulla might contribute to hypertension reduction provoked by high renin expression. These findings imply the relevance of Cxs/Panx1 as markers of impaired kidney function (high renin) in yotari mice and that they have a role in the preservation of intercellular signaling and implicate connexopathies as the cause of premature death of yotari mice.
Understanding the Effects of Anesthesia on Cortical Electrophysiological Recordings: A Scoping Review
Authors: Sorrenti Vincenzo , Cecchetto Claudia , Maschietto Marta , Fortinguerra Stefano , Buriani Alessandro , Vassanelli Stefano
Published: January 2021

General anesthesia in animal experiments is an ethical must and is required for all the procedures that are likely to cause more than slight or momentary pain. As anesthetics are known to deeply affect experimental findings, including electrophysiological recordings of brain activity, understanding their mechanism of action is of paramount importance. It is widely recognized that the depth and type of anesthesia introduce significant bias in electrophysiological measurements by affecting the shape of both spontaneous and evoked signals, e.g., modifying their latency and relative amplitude. Therefore, for a given experimental protocol, it is relevant to identify the appropriate anesthetic, to minimize the impact on neuronal circuits and related signals under investigation. This review focuses on the effect of different anesthetics on cortical electrical recordings, examining their molecular mechanisms of action, their influence on neuronal microcircuits and, consequently, their impact on cortical measurements.
Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa
Authors: Gnodi Elisa , Mancuso Clara , Elli Luca , Ballarini Elisa , Meneveri Raffaella , Beaulieu Jean François , Barisani Donatella
Published: January 2021

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.
MicroRNA Profiles in Monocyte-Derived Macrophages Generated by Interleukin-27 and Human Serum: Identification of a Novel HIV-Inhibiting and Autophagy-Inducing MicroRNA
Authors: Imamichi Tomozumi , Goswami Suranjana , Hu Xiaojun , Laverdure Sylvain , Yang Jun , Qiu Ju , Chen Qian , Sherman Brad T. , Chang Weizhong
Published: January 2021

Interleukin-27 (IL-27) is a pleiotropic cytokine that influences the innate and adaptive immune systems. It inhibits viral infection and regulates the expression of microRNAs (miRNAs). We recently reported that macrophages differentiated from human primary monocytes in the presence of IL-27 and human AB serum resisted human immunodeficiency virus (HIV) infection and showed significant autophagy induction. In the current study, the miRNA profiles in these cells were investigated, especially focusing on the identification of novel miRNAs regulated by IL-27-treatment. The miRNA sequencing analysis detected 38 novel miRNAs. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed that IL-27 differentially regulated the expression of 16 of the 38 miRNAs. Overexpression of the synthesized miRNA mimics by transfection revealed that miRAB40 had potent HIV-inhibiting and autophagy-inducing properties. B18R, an interferon (IFN)-neutralization protein, partially suppressed both activities, indicating that the two functions were induced via IFN-dependent and -independent pathways. Although the target mRNA(s) of miRAB40 involving in the induction of both functions was unable to identify in this study, the discovery of miRAB40, a potential HIV-inhibiting and autophagy inducing miRNA, may provide novel insights into the miRNA (small none-coding RNA)-mediated regulation of HIV inhibition and autophagy induction as an innate immune response.
Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels
Authors: Ruan Yue , Jiang Subao , Gericke Adrian
Published: January 2021

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.
Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice
Authors: Ryu Youngjae , Kim Yong , Kim Yoon , Kim Jungwoo , Kim Sung , Kim Hoon , Ku Seung
Published: January 2021

Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow the exploration of the specific mechanism underlying PCOS. We focused on streptozotocin (STZ) to develop a non-steroidal and non-diabetic PCOS model. We administered multiple STZ injections to female C57BL/6 mice (3–4 weeks old) at different concentrations: STZ-15 (15 mg/kg), STZ-30 (30 mg/kg), and STZ-60 (60 mg/kg) treatments. During the experimental period, we analyzed body weight, blood glucose levels, and estrous cycle pattern. Furthermore, five weeks after STZ administration, we examined hormone levels and the morphology of ovarian tissues. Mice in the STZ-15 group did not show differences in body weights, blood glucose level, insulin level, and insulin tolerance compared to wild-type and control groups whereas those in the STZ-60 group presented a typical diabetes phenotype. In the case of the STZ-30 group, only increased blood glucose level was observed. Total testosterone levels were significantly elevated in STZ-15 and STZ-30 groups. Luteinizing hormone (LH) and estradiol levels were not significantly changed in the STZ-treated groups. The number of ovarian antral follicles and atretic follicles significantly increased in the ovary of mice in the STZ-15 and STZ-30 groups. All STZ-treated groups manifested irregular estrus cycles. However, the patterns of estrous cycles were different between mice treated with different STZ concentrations. We found that PI3K-AKT and IRS-1 signaling in the ovary was enhanced by low doses of STZ treatment. Taken together, our finding indicates that multiple injections of STZ at low doses induce PCOS features in mice without induction of diabetes features.
Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K+ Current
Authors: Lo Yi-Ching , Lin Chih-Lung , Fang Wei-Yu , Lőrinczi Bálint , Szatmári István , Chang Wan-Hsuan , Fülöp Ferenc , Wu Sheng-Nan
Published: January 2021

Kynurenic acid (KYNA, 4-oxoquinoline-2-carboxylic acid), an intermediate of the tryptophan metabolism, has been recognized to exert different neuroactive actions; however, the need of how it or its aminoalkylated amide derivative N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) exerts any effects on ion currents in excitable cells remains largely unmet. In this study, the investigations of how KYNA and other structurally similar KYNA derivatives have any adjustments on different ionic currents in pituitary GH3 cells and hippocampal mHippoE-14 neurons were performed by patch-clamp technique. KYNA or KYNA-A4 increased the amplitude of M-type K+ current (IK(M)) and concomitantly enhanced the activation time course of the current. The EC50 value required for KYNA- or KYNA-A4 -stimulated IK(M) was yielded to be 18.1 or 6.4 μM, respectively. The presence of KYNA or KYNA-A4 shifted the relationship of normalized IK(M)-conductance versus membrane potential to more depolarized potential with no change in the gating charge of the current. The voltage-dependent hysteretic area of IK(M) elicited by long-lasting triangular ramp pulse was observed in GH3 cells and that was increased during exposure to KYNA or KYNA-A4. In cell-attached current recordings, addition of KYNA raised the open probability of M-type K+ channels, along with increased mean open time of the channel. Cell exposure to KYNA or KYNA-A4 mildly inhibited delayed-rectifying K+ current; however, neither erg-mediated K+ current, hyperpolarization-activated cation current, nor voltage-gated Na+ current in GH3 cells was changed by KYNA or KYNA-A4. Under whole-cell, current-clamp recordings, exposure to KYNA or KYNA-A4 diminished the frequency of spontaneous action potentials; moreover, their reduction in firing frequency was attenuated by linopirdine, yet not by iberiotoxin or apamin. In hippocampal mHippoE-14 neurons, the addition of KYNA also increased the IK(M) amplitude effectively. Taken together, the actions presented herein would be one of the noticeable mechanisms through which they modulate functional activities of excitable cells occurring in vivo.
Strain-Specific Effects of Bifidobacterium longum on Hypercholesterolemic Rats and Potential Mechanisms
Authors: Jiang Jinchi , Wu Caie , Zhang Chengcheng , Zhang Qingsong , Yu Leilei , Zhao Jianxin , Zhang Hao , Narbad Arjan , Chen Wei , Zhai Qixiao
Published: January 2021

Hypercholesterolemia is an independent risk factor of cardiovascular disease, which is among the major causes of death worldwide. The aim of this study was to explore whether Bifidobacterium longum strains exerted intra-species differences in cholesterol-lowering effects in hypercholesterolemic rats and to investigate the potential mechanisms. SD rats underwent gavage with each B. longum strain (CCFM 1077, I3, J3 and B3) daily for 28 days. B. longum CCFM 1077 exerted the most potent cholesterol-lowering effect, followed by B. longum I3 and B3, whereas B. longum B3 had no effect in alleviating hypercholesterolemia. Divergent alleviation of different B. longum strains on hypercholesterolemia can be attributed to the differences in bile salt deconjugation ability and cholesterol assimilation ability in vitro. By 16S rRNA metagenomics analysis, the relative abundance of beneficial genus increased in the B. longum CCFM 1077 treatment group. The expression of key genes involved in cholesterol metabolism were also altered after the B. longum CCFM 1077 treatment. In conclusion, B. longum exhibits strain-specific effects in the alleviation of hypercholesterolemia, mainly due to differences in bacterial characteristics, bile salt deconjugation ability, cholesterol assimilation ability, expressions of key genes involved in cholesterol metabolism and alterations of gut microbiota.
Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
Authors: Sakamoto Akihiko , Terui Yusuke , Uemura Takeshi , Igarashi Kazuei , Kashiwagi Keiko
Published: January 2021

Polyamines stimulate the synthesis of specific proteins at the level of translation, and the genes encoding these proteins are termed as the “polyamine modulon”. The circadian clock generates daily rhythms in mammalian physiology and behavior. We investigated the role of polyamines in the circadian rhythm using control and polyamine-reduced NIH3T3 cells. The intracellular polyamines exhibited a rhythm with a period of about 24 h. In the polyamine-reduced NIH3T3 cells, the circadian period of circadian clock genes was lengthened and the synthesis of BMAL1 and REV-ERBα was significantly reduced at the translation level. Thus, the mechanism of polyamine stimulation of these protein syntheses was analyzed using NIH3T3 cells transiently transfected with genes encoding enhanced green fluorescent protein (EGFP) fusion mRNA with normal or mutated 5′-untranslated region (5′-UTR) of Bmal1 or Rev-erbα mRNA. It was found that polyamines stimulated BMAL1 and REV-ERBα synthesis through the enhancement of ribosomal shunting during the ribosome shunting within the 5′-UTR of mRNAs. Accordingly, the genes encoding Bmal1 and Rev-erbα were identified as the members of “polyamine modulon”, and these two proteins are significantly involved in the circadian rhythm control.
ELOVL5 Participates in Embryonic Lipid Determination of Cellular Membranes and Cytoplasmic Droplets
Authors: Lanzarini Franciele , Pereira Fernanda Alves , Camargo Janine de , Oliveira Andressa Minozzo , Belaz Katia Roberta Anacleto , Melendez-Perez Jose Javier , Eberlin Marcos Nogueira , Brum Mário Celso Sperotto , Mesquita Fernando Silveira , Sudano Mateus José
Published: January 2021

Embryonic lipids are crucial for the formation of cellular membranes and dynamically participate in metabolic pathways. Cells can synthesize simple fatty acids, and the elongation of fatty acids facilitates the formation of complex lipids. The aim of this work was to investigate the involvement of the elongation of very long chain fatty acid enzyme 5 (ELOVL5) in embryonic development and lipid determination. Bovine embryos were produced in vitro using a standard protocol and randomly divided to receive one of three treatments at Day 4: morpholino (Mo) gene expression knockdown assay for ELOVL5 (ELOVL5-Mo), Mo antisense oligonucleotides for the thalassemic β-globulin human mRNA (technical control Mo), and placebo (biological control). The phenotypes of embryonic development, cell number, ELOVL5 protein abundance, lipid droplet deposits, and lipid fingerprint were investigated. No detrimental effects (p > 0.05) were observed on embryo development in terms of cleavage (59.4 ± 3.5%, 63.6 ± 4.1%, and 65.4 ± 2.2%), blastocyst production (31.3 ± 4.2%, 28.1 ± 4.9%, and 36.1 ± 2.1%), and blastocyst cell number (99.6 ± 7.7, 100.2 ± 6.2, 86.8 ± 5.6), respectively, for biological control, technical control Mo, and ELOVL5-Mo. ELOVL5 protein abundance and cytoplasmic lipid droplet deposition were increased (p < 0.05) in ELOVL5-Mo–derived blastocysts compared with the controls. However, seven lipid species, including phosphatidylcholines, phosphatidylethanolamines, and triacylglycerol, were downregulated in the ELOVL5-Mo–derived blastocysts compared with the biological control. Therefore, ELOVL5 is involved in the determination of embryonic lipid content and composition. Transient translational blockage of ELOVL5 reduced the expression of specific lipid species and promoted increased cytoplasmic lipid droplet deposition, but with no apparent deleterious effect on embryonic development and blastocyst cell number.
Focusing on the Cell Type Specific Regulatory Actions of NLRX1
Authors: Fekete Tünde , Bencze Dóra , Bíró Eduárd , Benkő Szilvia , Pázmándi Kitti
Published: January 2021

Cells utilize a diverse repertoire of cell surface and intracellular receptors to detect exogenous or endogenous danger signals and even the changes of their microenvironment. However, some cytosolic NOD-like receptors (NLR), including NLRX1, serve more functions than just being general pattern recognition receptors. The dynamic translocation between the cytosol and the mitochondria allows NLRX1 to interact with many molecules and thereby to control multiple cellular functions. As a regulatory NLR, NLRX1 fine-tunes inflammatory signaling cascades, regulates mitochondria-associated functions, and controls metabolism, autophagy and cell death. Nevertheless, literature data are inconsistent and often contradictory regarding its effects on individual cellular functions. One plausible explanation might be that the regulatory effects of NLRX1 are highly cell type specific and the features of NLRX1 mediated regulation might be determined by the unique functional activity or metabolic profile of the given cell type. Here we review the cell type specific actions of NLRX1 with a special focus on cells of the immune system. NLRX1 has already emerged as a potential therapeutic target in numerous immune-related diseases, thus we aim to highlight which regulatory properties of NLRX1 are manifested in disease-associated dominant immune cells that presumably offer promising therapeutic solutions to treat these disorders.
Introduction of Universal Newborn Screening for Sickle Cell Disease in Germany—A Brief Narrative Review
Authors: Lobitz Stephan , Kunz Joachim B. , Cario Holger , Hakimeh Dani , Jarisch Andrea , Kulozik Andreas E. , Oevermann Lena , Grosse Regine
Published: January 2021

Sickle cell disease (SCD) is a severe non-malignant disorder of hemoglobin and is inherited in an autosomal-recessive manner [...]
Diversity, Co-Occurrence, and Nestedness Patterns of Sand Fly Species (Diptera: Psychodidae) in Two Rural Areas of Western Panamá
Authors: Rigg Chystrie A. , Perea Milixa , González Kadir , Saldaña Azael , Calzada José E. , Gao Yan , Gottdenker Nicole L. , Chaves Luis Fernando
Published: January 2021

Cutaneous Leishmaniasis transmission in the New World is observed in areas with rich sand fly species’ faunas. The diversity and composition of sand fly species can change in response to seasonal weather and land use changes. Here, we present results from a two-year-long study where we collected, using Centers for Disease Control (CDC) light traps, sand flies from two rural areas, Las Pavas (LP) and Trinidad de las Minas (T) in western Panamá. Over 710 trap-nights, we collected 16,156 sand flies from 15 genera and 35 species. We identified 34 species in T, and the most abundant species collected was Nyssomyia trapidoi (Fairchild and Hertig, 1952) (n = 2278, 37%), followed by Psychodopygus panamensis (Shannon, 1926) (n = 1112, 18%), and Trichopygomyia triramula (Fairchild and Hertig, 1952) (n = 1063, 17%). In LP, we identified 26 species, and the most abundant species collected were Ty. triramula (n = 4729, 48%), and Ps. panamensis (n = 3444, 35%). We estimated a higher species’ richness in T (Chao2 ± S.E.: 36.58 ± 3.84) than in LP (27.49 ± 2.28). In T, species’ richness was significantly higher in the rainy season, but no seasonal differences were observed in LP. Species’ assemblages were nested in the two areas. Phlebotomine sand fly species’ abundance increased at the two sites during the rainy season. Our data suggest that seasonality is more important than land use as a factor driving sand fly species’ diversity at the studied sites.
Oral Health Status in Older People with Dementia: A Case-Control Study
Authors: Lopez-Jornet Pia , Zamora Lavella Carmen , Pons-Fuster Lopez Eduardo , Tvarijonaviciute Asta
Published: January 2021

Dementia is characterized by a range of cognitive defects with impaired activities of daily living that have implications for patient oral health. Objectives. A case-control study was made of the impact of dementia upon oral health. A total of 152 patients were included: 69 with dementia and 83 controls from the region of Murcia (Spain). The Global Deterioration Scale (GDS) was used to classify the patients and an oral exploration was carried out. Odds ratios (ORs) and confidence intervals (CIs) were estimated using regression models. The patients with more severe disease were significantly more likely to have fewer natural teeth (OR 11.00, 95%CI 1.28–23.22; p = 0.001), a higher plaque index (p = 0.001), and a greater bleeding index (p = 0.001) than the control group. These findings suggest that older adults with dementia have deficient oral health. A higher bleeding index increases the risk of deterioration of cognitive function. The oral hygiene and health of older people with dementia need to be improved.
The Prevalence of Urinary Incontinence among Adolescent Female Athletes: A Systematic Review
Authors: Rebullido Tamara Rial , Gómez-Tomás Cinta , Faigenbaum Avery D. , Chulvi-Medrano Iván
Published: January 2021

This review aimed to synthesize the most up-to-date evidence regarding the prevalence of urinary incontinence (UI) among adolescent female athletes. We conducted a systematic review of studies regarding UI in female athletes less than 19 years of age. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRIMSA). The electronic databases of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science (WOS) were searched between October and November 2020. After blinded peer evaluation, a total of 215 studies were identified and nine were included. Risk of bias was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. This review identified a prevalence of UI in adolescent female athletes between 18% to 80% with an average of 48.58%. The most prevalent sports were trampolining followed by rope skipping. The prevalence of UI among adolescent female athletes practicing impact sports was significantly prevalent. There is a need for further research, education, and targeted interventions for adolescent female athletes with UI.
Assessment of the Performance of an Artificial Reef Made of Modular Elements through Small Scale Experiments
Authors: Cardenas-Rojas Dea , Mendoza Edgar , Escudero Mireille , Verduzco-Zapata Manuel
Published: January 2021

Artificial reefs have proven to be an optimal and effective solution in stabilizing coastlines around the world. They are submerged structures that imitate the protection service provided by natural reefs accomplishing the functions of dissipating wave energy and protecting beach morphology, but also being an ecological solution. In this paper, 2D small-scale experiments were performed to analyze the hydrodynamic, morphological, and ecological behavior of an artificial reef constructed of modular elements. Two typical beach-dune profiles were constructed in a wave flume over which two locations of an artificial reef were tested. From these tests, transmission coefficients were obtained as well as the beach profile response to the presence of the artificial reef. These results are used to discuss about the hydrodynamic, morphological, and ecological performance of the artificial reef. The proposed artificial reef showed good morphological performance while its hydrodynamic function had limited success. In turn, the ecologic performance was theoretically addressed.
Gravel Barrier Beach Morphodynamic Response to Extreme Conditions
Authors: Ions Kristian , Karunarathna Harshinie , Reeve Dominic E. , Pender Douglas
Published: January 2021

Gravel beaches and barriers form a valuable natural protection for many shorelines. The paper presents a numerical modelling study of gravel barrier beach response to storm wave conditions. The XBeach non-hydrostatic model was set up in 1D mode to investigate barrier volume change and overwash under a wide range of unimodal and bimodal storm conditions and barrier cross sections. The numerical model was validated against conditions at Hurst Castle Spit, UK. The validated model is used to simulate the response of a range of gravel barrier cross sections under a wide selection of statistically significant storm wave and water level scenarios thus simulating an ensemble of barrier volume change and overwash. This ensemble of results was used to develop a simple parametric model for estimating barrier volume change during a given storm and water level condition under unimodal storm conditions. Numerical simulations of barrier response to bimodal storm conditions, which are a common occurrence in many parts of the UK were also investigated. It was found that barrier volume change and overwash from bimodal storms will be higher than that from unimodal storms if the swell percentage in the bimodal spectrum is greater than 40%. The model is demonstrated as providing a useful tool for estimating barrier volume change, a commonly used measure used in gravel barrier beach management.
Current and Future Treatments for Classic Galactosemia
Authors: Delnoy Britt , Coelho Ana I. , Rubio-Gozalbo Maria Estela
Published: January 2021

Type I (classic) galactosemia, galactose 1-phosphate uridylyltransferase (GALT)-deficiency is a hereditary disorder of galactose metabolism. The current therapeutic standard of care, a galactose-restricted diet, is effective in treating neonatal complications but is inadequate in preventing burdensome complications. The development of several animal models of classic galactosemia that (partly) mimic the biochemical and clinical phenotypes and the resolution of the crystal structure of GALT have provided important insights; however, precise pathophysiology remains to be elucidated. Novel therapeutic approaches currently being explored focus on several of the pathogenic factors that have been described, aiming to (i) restore GALT activity, (ii) influence the cascade of events and (iii) address the clinical picture. This review attempts to provide an overview on the latest advancements in therapy approaches.
Evaluation of Land Suitability Methods with Reference to Neglected and Underutilised Crop Species: A Scoping Review
Authors: Mugiyo Hillary , Chimonyo Vimbayi G. P. , Sibanda Mbulisi , Kunz Richard , Masemola Cecilia R. , Modi Albert T. , Mabhaudhi Tafadzwanashe
Published: January 2021

In agriculture, land use and land classification address questions such as “where”, “why” and “when” a particular crop is grown within a particular agroecology. To date, there are several land suitability analysis (LSA) methods, but there is no consensus on the best method for crop suitability analysis. We conducted a scoping review to evaluate methodological strategies for LSA. Secondary to this, we assessed which of these would be suitable for neglected and underutilised crop species (NUS). The review classified LSA methods reported in articles as traditional (26.6%) and modern (63.4%). Modern approaches, including multi-criteria decision-making (MCDM) methods such as analytical hierarchy process (AHP) (14.9%) and fuzzy methods (12.9%); crop simulation models (9.9%) and machine learning related methods (25.7%) are gaining popularity over traditional methods. The MCDM methods, namely AHP and fuzzy, are commonly applied to LSA while crop models and machine learning related methods are gaining popularity. A total of 67 parameters from climatic, hydrology, soil, socio-economic and landscape properties are essential in LSA. Unavailability and the inclusion of categorical datasets from social sources is a challenge. Using big data and Internet of Things (IoT) improves the accuracy and reliability of LSA methods. The review expects to provide researchers and decision-makers with the most robust methods and standard parameters required in developing LSA for NUS. Qualitative and quantitative approaches must be integrated into unique hybrid land evaluation systems to improve LSA.
The Interplay between Whey Protein Fibrils with Carbon Nanotubes or Carbon Nano-Onions
Authors: Kang Ning , Hua Jin , Gao Lizhen , Zhang Bin , Pang Jiewen
Published: January 2021

Whey protein isolate (WPI) fibrils were prepared using an acid hydrolysis induction process. Carbon nanotubes (CNTs) and carbon nano-onions (CNOs) were made via the catalytic chemical vapor deposition (CVD) of methane. WPI fibril–CNTs and WPI fibril–CNOs were prepared via hydrothermal synthesis at 80 °C. The composites were characterized by SEM, TEM, FTIR, XRD, Raman, and TG analyses. The interplay between WPI fibrils and CNTs and CNOs were studied. The WPI fibrils with CNTs and CNOs formed uniform gels and films. CNTs and CNOs were highly dispersed in the gels. Hydrogels of WPI fibrils with CNTs (or CNOs) could be new materials with applications in medicine or other fields. The CNTs and CNOs shortened the WPI fibrils, which might have important research value for curing fibrosis diseases such as Parkinson’s and Alzheimer’s diseases. The FTIR revealed that CNTs and CNOs both had interactions with WPI fibrils. The XRD analysis suggested that most of the CNTs were wrapped in WPI fibrils, while CNOs were partially wrapped. This helped to increase the biocompatibility and reduce the cytotoxicity of CNTs and CNOs. HR-TEM and Raman spectroscopy studies showed that the graphitization level of CNTs was higher than for CNOs. After hybridization with WPI fibrils, more defects were created in CNTs, but some original defects were dismissed in CNOs. The TG results indicated that a new phase of WPI fibril–CNTs or CNOs was formed.
A Lochs-Type Approach via Entropy in Comparing the Efficiency of Different Continued Fraction Algorithms
Authors: Lascu Dan , Sebe Gabriela Ileana
Published: January 2021

We investigate the efficiency of several types of continued fraction expansions of a number in the unit interval using a generalization of Lochs theorem from 1964. Thus, we aim to compare the efficiency by describing the rate at which the digits of one number-theoretic expansion determine those of another. We study Chan’s continued fractions, θ-expansions, N-continued fractions, and Rényi-type continued fractions. A central role in fulfilling our goal is played by the entropy of the absolutely continuous invariant probability measures of the associated dynamical systems.
Optimal Design of a High-Speed Flux Reversal Motor with Bonded Rare-Earth Permanent Magnets
Authors: Prakht Vladimir , Dmitrievskii Vladimir , Kazakbaev Vadim
Published: January 2021

Single-phase flux reversal motors (FRMs) with sintered rare-earth permanent magnets on the stator for low-cost high-speed applications have a reliable rotor and a good specific power. However, to reduce eddy current loss, the sintered rare-earth magnets on the stator have to be segmented into several pieces and their cost increases with the number of magnet segments. An alternative to the sintered magnets can be bonded magnets, in which eddy current loss is almost absent. The remanence of bonded magnets is lower than that of sintered magnets, and they are prone to demagnetization. However, the cost of low-power motors with bonded magnets can be lower because of the simpler manufacturing technology and the lower material cost. This paper discusses various aspects of the optimal design of FRM with bonded magnets, applying the Nelder–Mead method. An objective function for optimizing an FRM with bonded magnets is designed to ensure the required efficiency, reduce torque oscillations, and prevent the bonded magnets from demagnetizing. As a result, it is shown that the FRM with bonded magnets has approximately the same efficiency as the FRM with sintered magnets. In addition, the peak-to-peak torque ripple is minimized and the minimal instantaneous torque is maximized.
Small Intestinal Intussusception Due to Complicated Giant Jejunal Diverticulosis
Authors: Grudzińska Ewa , Mrowiec Sławomir , Pilch-Kowalczyk Joanna , Ciupińska Monika , Kusnierz Katarzyna
Published: January 2021

Background: Jejunal diverticulosis and jejunal lipomatosis are uncommon conditions. Usually asymptomatic, they may cause severe complications in some cases. Intussusception is unusual in adults, but when diagnosed swiftly it can be treated surgically, usually with good outcome. Case presentation: We present a 60-year-old female patient with a history of chronic malnutrition and anemia, complaining of acute abdominal pain, vomiting and diarrhea. Contrast-enhanced abdominal computed tomography (CT) showed intussusception, multiple giant jejunal diverticula and multiple lipomas. The patient underwent urgent surgery, but radical treatment was not possible due to the extent of the diseases. One month later, another surgery was needed due to ileostomy obstruction caused by lipomas. The patient’s condition deteriorated due to malnutrition and concomitant metabolic disorders, which eventually led to her demise. Conclusions: Radical treatment is not always possible in an extensive jejunal disease. Prolonged malnutrition impairs postoperative healing, and therefore surgical or nutritional treatment should be considered in jejunal diverticulosis before the onset of severe complications requiring urgent surgical intervention.