bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Neglected Tropical Diseases (NTDs) on Women’s Health and Wellbeing in Sub-Saharan Africa (SSA): A Case Study of Kenya
Authors: Ochola Elizabeth A. , Elliott Susan J. , Karanja Diana M. S.
Published: February 2021

Neglected Tropical Diseases (NTDs) trap individuals in a cycle of poverty through their devastating effects on health, wellbeing and social–economic capabilities that extend to other axes of inequity such as gender and/or ethnicity. Despite NTDs being regarded as equity tracers, little attention has been paid toward gender dynamics and relationships for gender-equitable access to NTD programs in sub-Saharan Africa (SSA). This paper examines the impact of NTDs on women’s health and wellbeing in SSA using Kenya as a case study. This research is part of a larger research program designed to examine the impact of NTDs on the health and wellbeing of populations in Kenya. Thematic analysis of key informants’ interviews (n = 21) and focus groups (n = 5) reveals first that NTDs disproportionately affect women and girls due to their assigned gender roles and responsibilities. Second, women face financial and time constraints when accessing health care due to diminished economic power and autonomy. Third, women suffer more from the related social consequences of NTDs (that is, stigma, discrimination and/or abandonment), which affects their health-seeking behavior. As such, we strongly suggest a gender lens when addressing NTD specific exposure, socio-economic inequities, and other gender dynamics that may hinder the successful delivery of NTD programs at the local and national levels.
Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race
Authors: Sterrett Mary E. , Bloom Michael S. , Jamro Erica L. , Wenzel Abby G. , Wineland Rebecca J. , Unal Elizabeth R. , Brock John , Kucklick John , Garcia Kelly , Newman Roger B.
Published: February 2021

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women’s reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; p < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; p < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; p < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.
The Impact of Individual Mobility on Long-Term Exposure to Ambient PM2.5: Assessing Effect Modification by Travel Patterns and Spatial Variability of PM2.5
Authors: Yoo Eun-hye , Pu Qiang , Eum Youngseob , Jiang Xiangyu
Published: February 2021

The impact of individuals’ mobility on the degree of error in estimates of exposure to ambient PM2.5 concentrations is increasingly reported in the literature. However, the degree to which accounting for mobility reduces error likely varies as a function of two related factors—individuals’ routine travel patterns and the local variations of air pollution fields. We investigated whether individuals’ routine travel patterns moderate the impact of mobility on individual long-term exposure assessment. Here, we have used real-world time–activity data collected from 2013 participants in Erie/Niagara counties, New York, USA, matched with daily PM2.5 predictions obtained from two spatial exposure models. We further examined the role of the spatiotemporal representation of ambient PM2.5 as a second moderator in the relationship between an individual’s mobility and the exposure measurement error using a random effect model. We found that the effect of mobility on the long-term exposure estimates was significant, but that this effect was modified by individuals’ routine travel patterns. Further, this effect modification was pronounced when the local variations of ambient PM2.5 concentrations were captured from multiple sources of air pollution data (‘a multi-sourced exposure model’). In contrast, the mobility effect and its modification were not detected when ambient PM2.5 concentration was estimated solely from sparse monitoring data (‘a single-sourced exposure model’). This study showed that there was a significant association between individuals’ mobility and the long-term exposure measurement error. However, the effect could be modified by individuals’ routine travel patterns and the error-prone representation of spatiotemporal variability of PM2.5.
Comparison of the Effect on Fetal Growth of a Mixture of Atrazine and Nitrates in Drinking Water and of Active Tobacco Exposure during Pregnancy
Authors: Carles Camille , Albouy-Llaty Marion , Dupuis Antoine , Rabouan Sylvie , Migeot Virginie
Published: February 2021

Active tobacco exposure during pregnancy is a known determinant of fetal growth. Nitrates and atrazine metabolites in drinking water may affect fetal growth as a mixture of endocrine disruptors (ED). We aimed to determine whether EDC have an additional effect on fetal growth compared to active tobacco exposure. A historic cohort study was carried out with a sample stratified with regard to the maternity unit, drinking water exposure, and year of birth. The women included were living in Deux-Sèvres, had given birth between 2005 and 2010 in three selected maternity units, and ultrasound data were available in their obstetrical records. Mixed linear models were used to analyze fetal weight evolution from the second trimester to the time of birth according to drinking water exposure to EDC mixture and active tobacco exposure. We included 558 mother-neonate couples, of whom 9% were exposed to high doses of the mixture and 21% to active tobacco smoking. There was no difference in fetal weight evolution according to drinking water mixture exposure (0.97 g; 95% CI [−3.01; 4.94]). We could not show a supplementary effect of mixture exposure in drinking-water on fetal growth as compared to active tobacco exposure. Further research is needed, using more precise methods to estimate EDC exposure.
Mental Health Status of Healthcare Professionals and Students of Health Sciences Faculties in Kuwait during the COVID-19 Pandemic
Authors: Alsairafi Zahra , Naser Abdallah Y. , Alsaleh Fatemah M. , Awad Abdelmoneim , Jalal Zahraa
Published: February 2021

Objectives: This study aimed to assess the impact of the COVID-19 pandemic on the mental health status of healthcare professionals (HCPs) and undergraduate students in the health sciences center (HSCUs). In addition, it explored the factors associated with the increased levels of mental health burden among the study population. Methods: A cross-sectional study was performed using two online-administered questionnaires: the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 7-item (GAD-7), which were distributed in parallel to HCPs and HSCUs in Kuwait. These instruments are validated assessment scales to assess mental health status: depression (PHQ-9) and anxiety (GAD-7). Statistical analyses were carried out using SPSS- version 25. Results: A total of 857 individuals (559 HCPs and 298 HSCUs) participated in this study. The prevalence of moderately severe depression or severe depression (PHQ-9 total score of ≥15) among respondents was 66.6%. The median (interquartile range, IQR) PHQ-9 score was significantly higher among HSCUs (20 {11.5}) compared to HCPs (17 {8}). The prevalence of severe anxiety (GAD-7 total score of ≥15) among respondents was 36.7%. There were no significant differences between the median (IQR) GAD-7 scores among the HCPs (14 {7}) and HSCUs (13 {8}). Binary logistic regression analysis revealed that three variables were significantly and independently associated with severe depression among HCPs. The prevalence of severe depression was found to be greater among females compared to males. In addition, it was significantly lower among those who were aged ≥50 years, and those who reported that they were not in direct contact with COVID-19 patients. Among HSCUs, females showed greater depression than males. In contrast, those aged >29 years and who had no history of chronic disease showed lower depression compared to their counterparts in the 18–29 years age group and who had a chronic disease history. Conclusions: The COVID-19 pandemic had a significant negative impact on the mental health of HCPs and HSCUs in Kuwait. This highlights the need for proactive efforts to support their mental health and well-being through educational campaigns and psychological support programs.
Do Different Models Induce Changes in Mortality Indicators? That Is a Key Question for Extending the Lee-Carter Model
Authors: Debón Ana , Haberman Steven , Montes Francisco , Otranto Edoardo
Published: February 2021

The parametric model introduced by Lee and Carter in 1992 for modeling mortality rates in the USA was a seminal development in forecasting life expectancies and has been widely used since then. Different extensions of this model, using different hypotheses about the data, constraints on the parameters, and appropriate methods have led to improvements in the model’s fit to historical data and the model’s forecasting of the future. This paper’s main objective is to evaluate if differences between models are reflected in different mortality indicators’ forecasts. To this end, nine sets of indicator predictions were generated by crossing three models and three block-bootstrap samples with each of size fifty. Later the predicted mortality indicators were compared using functional ANOVA. Models and block bootstrap procedures are applied to Spanish mortality data. Results show model, block-bootstrap, and interaction effects for all mortality indicators. Although it was not our main objective, it is essential to point out that the sample effect should not be present since they must be realizations of the same population, and therefore the procedure should lead to samples that do not influence the results. Regarding significant model effect, it follows that, although the addition of terms improves the adjustment of probabilities and translates into an effect on mortality indicators, the model’s predictions must be checked in terms of their probabilities and the mortality indicators of interest.
Vibrational Spectroscopic Investigation of Blood Plasma and Serum by Drop Coating Deposition for Clinical Application
Authors: Huang Jing , Ali Nairveen , Quansah Elsie , Guo Shuxia , Noutsias Michel , Meyer-Zedler Tobias , Bocklitz Thomas , Popp Jürgen , Neugebauer Ute , Ramoji Anuradha
Published: February 2021

In recent decades, vibrational spectroscopic methods such as Raman and FT-IR spectroscopy are widely applied to investigate plasma and serum samples. These methods are combined with drop coating deposition techniques to pre-concentrate the biomolecules in the dried droplet to improve the detected vibrational signal. However, most often encountered challenge is the inhomogeneous redistribution of biomolecules due to the coffee-ring effect. In this study, the variation in biomolecule distribution within the dried-sample droplet has been investigated using Raman and FT-IR spectroscopy and fluorescence lifetime imaging method. The plasma-sample from healthy donors were investigated to show the spectral differences between the inner and outer-ring region of the dried-sample droplet. Further, the preferred location of deposition of the most abundant protein albumin in the blood during the drying process of the plasma has been illustrated by using deuterated albumin. Subsequently, two patients with different cardiac-related diseases were investigated exemplarily to illustrate the variation in the pattern of plasma and serum biomolecule distribution during the drying process and its impact on patient-stratification. The study shows that a uniform sampling position of the droplet, both at the inner and the outer ring, is necessary for thorough clinical characterization of the patient’s plasma and serum sample using vibrational spectroscopy.
New Insights into the Transcriptional Regulation of Genes Involved in the Nitrogen Use Efficiency under Potassium Chlorate in Rice (Oryza sativa L.)
Authors: Kabange Nkulu Rolly , Park So-Yeon , Lee Ji-Yun , Shin Dongjin , Lee So-Myeong , Kwon Youngho , Cha Jin-Kyung , Cho Jun-Hyeon , Duyen Dang Van , Ko Jong-Min , Lee Jong-Hee
Published: February 2021

Potassium chlorate (KClO3) has been widely used to evaluate the divergence in nitrogen use efficiency (NUE) between indica and japonica rice subspecies. This study investigated the transcriptional regulation of major genes involved in the NUE in rice treated with KClO3, which acts as an inhibitor of the reducing activity of nitrate reductase (NR) in higher plants. A set of two KClO3 sensitive nitrate reductase (NR) and two nitrate transporter (NRT) introgression rice lines (BC2F7), carrying the indica alleles of NR or NRT, derived from a cross between Saeilmi (japonica, P1) and Milyang23 (indica, P2), were exposed to KClO3 at the seedling stage. The phenotypic responses were recorded 7 days after treatment, and samples for gene expression, physiological, and biochemical analyses were collected at 0 h (control) and 3 h after KClO3 application. The results revealed that Saeilmi (P1, japonica) and Milyang23 (P2, indica) showed distinctive phenotypic responses. In addition, the expression of OsNR2 was differentially regulated between the roots, stem, and leaf tissues, and between introgression lines. When expressed in the roots, OsNR2 was downregulated in all introgression lines. However, in the stem and leaves, OsNR2 was upregulated in the NR introgression lines, but downregulation in the NRT introgression lines. In the same way, the expression patterns of OsNIA1 and OsNIA2 in the roots, stem, and leaves indicated a differential transcriptional regulation by KClO3, with OsNIA2 prevailing over OsNIA1 in the roots. Under the same conditions, the activity of NR was inhibited in the roots and differentially regulated in the stem and leaf tissues. Furthermore, the transcriptional divergence of OsAMT1.3 and OsAMT2.3, OsGLU1 and OsGLU2, between NR and NRT, coupled with the NR activity pattern in the roots, would indicate the prevalence of nitrate (NO3¯) transport over ammonium (NH4+) transport. Moreover, the induction of catalase (CAT) and polyphenol oxidase (PPO) enzyme activities in Saeilmi (P1, KClO3 resistant), and the decrease in Milyang23 (P2, KClO3 sensitive), coupled with the malondialdehyde (MDA) content, indicated the extent of the oxidative stress, and the induction of the adaptive response mechanism, tending to maintain a balanced reduction–oxidation state in response to KClO3. The changes in the chloroplast pigments and proline content propose these compounds as emerging biomarkers for assessing the overall plant health status. These results suggest that the inhibitory potential of KClO3 on the reduction activity of the nitrate reductase (NR), as well as that of the genes encoding the nitrate and ammonium transporters, and glutamate synthase are tissue-specific, which may differentially affect the transport and assimilation of nitrate or ammonium in rice.
Integrin Regulation in Immunological and Cancerous Cells and Exosomes
Authors: Soe Zay Yar , Park Eun Jeong , Shimaoka Motomu
Published: February 2021

Integrins represent the biologically and medically significant family of cell adhesion molecules that govern a wide range of normal physiology. The activities of integrins in cells are dynamically controlled via activation-dependent conformational changes regulated by the balance of intracellular activators, such as talin and kindlin, and inactivators, such as Shank-associated RH domain interactor (SHARPIN) and integrin cytoplasmic domain-associated protein 1 (ICAP-1). The activities of integrins are alternatively controlled by homotypic lateral association with themselves to induce integrin clustering and/or by heterotypic lateral engagement with tetraspanin and syndecan in the same cells to modulate integrin adhesiveness. It has recently emerged that integrins are expressed not only in cells but also in exosomes, important entities of extracellular vesicles secreted from cells. Exosomal integrins have received considerable attention in recent years, and they are clearly involved in determining the tissue distribution of exosomes, forming premetastatic niches, supporting internalization of exosomes by target cells and mediating exosome-mediated transfer of the membrane proteins and associated kinases to target cells. A growing body of evidence shows that tumor and immune cell exosomes have the ability to alter endothelial characteristics (proliferation, migration) and gene expression, some of these effects being facilitated by vesicle-bound integrins. As endothelial metabolism is now thought to play a key role in tumor angiogenesis, we also discuss how tumor cells and their exosomes pleiotropically modulate endothelial functions in the tumor microenvironment.
Neuroinflammation in Prion Disease
Authors: Li Bei , Chen Meiling , Zhu Caihong
Published: February 2021

Neuroinflammation, typically manifest as microglial activation and astrogliosis accompanied by transcriptomic alterations, represents a common hallmark of various neurodegenerative conditions including prion diseases. Microglia play an overall neuroprotective role in prion disease, whereas reactive astrocytes with aberrant phenotypes propagate prions and contribute to prion-induced neurodegeneration. The existence of heterogeneous subpopulations and dual functions of microglia and astrocytes in prion disease make them potential targets for therapeutic intervention. A variety of neuroinflammation-related molecules are involved in prion pathogenesis. Therapeutics targeting neuroinflammation represents a novel approach to combat prion disease. Deciphering neuroinflammation in prion disease will deepen our understanding of pathogenesis of other neurodegenerative disorders.
Advances in Targeting HPV Infection as Potential Alternative Prophylactic Means
Authors: Carse Sinead , Bergant Martina , Schäfer Georgia
Published: February 2021

Infection by oncogenic human papillomavirus (HPV) is the primary cause of cervical cancer and other anogenital cancers. The majority of cervical cancer cases occur in low- and middle- income countries (LMIC). Concurrent infection with Human Immunodeficiency Virus (HIV) further increases the risk of HPV infection and exacerbates disease onset and progression. Highly effective prophylactic vaccines do exist to combat HPV infection with the most common oncogenic types, but the accessibility to these in LMIC is severely limited due to cost, difficulties in accessing the target population, cultural issues, and maintenance of a cold chain. Alternative preventive measures against HPV infection that are more accessible and affordable are therefore also needed to control cervical cancer risk. There are several efforts in identifying such alternative prophylactics which target key molecules involved in early HPV infection events. This review summarizes the current knowledge of the initial steps in HPV infection, from host cell-surface engagement to cellular trafficking of the viral genome before arrival in the nucleus. The key molecules that can be potentially targeted are highlighted, and a discussion on their applicability as alternative preventive means against HPV infection, with a focus on LMIC, is presented.
Rainbow Trout (Oncorhynchus mykiss) Na+/H+ Exchangers tNhe3a and tNhe3b Display Unique Inhibitory Profiles Dissimilar from Mammalian NHE Isoforms
Authors: Blair Salvatore , Li Xiuju , Dutta Debajyoti , Chamot Danuta , Fliegel Larry , Goss Greg
Published: February 2021

Freshwater fishes maintain an internal osmolality of ~300 mOsm, while living in dilute environments ranging from 0 to 50 mOsm. This osmotic challenge is met at least partially, by Na+/H+ exchangers (NHE) of fish gill and kidney. In this study, we cloned, expressed, and pharmacologically characterized fish-specific Nhes of the commercially important species Oncorhynchus mykiss. Trout (t) Nhe3a and Nhe3b isoforms from gill and kidney were expressed and characterized in an NHE-deficient cell line. Western blotting and immunocytochemistry confirmed stable expression of the tagged trout tNhe proteins. To measure NHE activity, a transient acid load was induced in trout tNhe expressing cells and intracellular pH was measured. Both isoforms demonstrated significant activity and recovered from an acute acid load. The effect of the NHE transport inhibitors amiloride, EIPA (5-(N-ethyl-N-isopropyl)-amiloride), phenamil, and DAPI was examined. tNhe3a was inhibited in a dose-dependent manner by amiloride and EIPA and tNhe3a was more sensitive to amiloride than EIPA, unlike mammalian NHE1. tNhe3b was inhibited by high concentrations of amiloride, while even in the presence of high concentrations of EIPA (500 µM), some activity of tNhe3b remained. Phenamil and DAPI were ineffective at inhibiting tNhe activity of either isoform. The current study aids in understanding the pharmacology of fish ion transporters. Both isoforms display inhibitory profiles uniquely different from mammalian NHEs and show resistance to inhibition. Our study allows for more direct interpretation of past, present, and future fish-specific sodium transport studies, with less reliance on mammalian NHE data for interpretation.
KRAB-ZFP Transcriptional Regulators Acting as Oncogenes and Tumor Suppressors: An Overview
Authors: Sobocińska Joanna , Molenda Sara , Machnik Marta , Oleksiewicz Urszula
Published: February 2021

Krüppel-associated box zinc finger proteins (KRAB-ZFPs) constitute the largest family of transcriptional factors exerting co-repressor functions in mammalian cells. In general, KRAB-ZFPs have a dual structure. They may bind to specific DNA sequences via zinc finger motifs and recruit a repressive complex through the KRAB domain. Such a complex mediates histone deacetylation, trimethylation of histone 3 at lysine 9 (H3K9me3), and subsequent heterochromatization. Nevertheless, apart from their repressive role, KRAB-ZFPs may also co-activate gene transcription, likely through interaction with other factors implicated in transcriptional control. KRAB-ZFPs play essential roles in various biological processes, including development, imprinting, retroelement silencing, and carcinogenesis. Cancer cells possess multiple genomic, epigenomic, and transcriptomic aberrations. A growing number of data indicates that the expression of many KRAB-ZFPs is altered in several tumor types, in which they may act as oncogenes or tumor suppressors. Hereby, we review the available literature describing the oncogenic and suppressive roles of various KRAB-ZFPs in cancer. We focused on their association with the clinicopathological features and treatment response, as well as their influence on the cancer cell phenotype. Moreover, we summarized the identified upstream and downstream molecular mechanisms that may govern the functioning of KRAB-ZFPs in a cancer setting.
GBA Mutations Influence the Release and Pathological Effects of Small Extracellular Vesicles from Fibroblasts of Patients with Parkinson’s Disease
Authors: Cerri Silvia , Ghezzi Cristina , Ongari Gerardo , Croce Stefania , Avenali Micol , Zangaglia Roberta , Di Monte Donato A. , Valente Enza Maria , Blandini Fabio
Published: February 2021

Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are the strongest known genetic risk factor for Parkinson’s disease (PD). The molecular mechanisms underlying the increased PD risk and the variable phenotypes observed in carriers of different GBA mutations are not yet fully elucidated. Extracellular vesicles (EVs) have gained increasing importance in neurodegenerative diseases since they can vehiculate pathological molecules potentially promoting disease propagation. Accumulating evidence showed that perturbations of the endosomal–lysosomal pathway can affect EV release and composition. Here, we investigate the impact of GCase deficiency on EV release and their effect in recipient cells. EVs were purified by ultracentrifugation from the supernatant of fibroblast cell lines derived from PD patients with or without GBA mutations and quantified by nanoparticle tracking analysis. SH-SY5Y cells over-expressing alpha-synuclein (α-syn) were used to assess the ability of patient-derived small EVs to affect α-syn expression. We observed that defective GCase activity promotes the release of EVs, independently of mutation severity. Moreover, small EVs released from PD fibroblasts carrying severe mutations increased the intra-cellular levels of phosphorylated α-syn. In summary, our work shows that the dysregulation of small EV trafficking and alpha-synuclein mishandling may play a role in GBA-associated PD.
Structural Determinants of Substrate Specificity of SplF Protease from Staphylococcus aureus
Authors: Stach Natalia , Karim Abdulkarim , Golik Przemyslaw , Kitel Radoslaw , Pustelny Katarzyna , Gruba Natalia , Groborz Katarzyna , Jankowska Urszula , Kedracka-Krok Sylwia , Wladyka Benedykt , Drag Marcin , Lesner Adam , Dubin Grzegorz
Published: February 2021

Accumulating evidence suggests that six proteases encoded in the spl operon of a dangerous human pathogen, Staphylococcus aureus, may play a role in virulence. Interestingly, SplA, B, D, and E have complementary substrate specificities while SplF remains to be characterized in this regard. Here, we describe the prerequisites of a heterologous expression system for active SplF protease and characterize the enzyme in terms of substrate specificity and its structural determinants. Substrate specificity of SplF is comprehensively profiled using combinatorial libraries of peptide substrates demonstrating strict preference for long aliphatic sidechains at the P1 subsite and significant selectivity for aromatic residues at P3. The crystal structure of SplF was provided at 1.7 Å resolution to define the structural basis of substrate specificity of SplF. The obtained results were compared and contrasted with the characteristics of other Spl proteases determined to date to conclude that the spl operon encodes a unique extracellular proteolytic system.
KRASG12C Can Either Promote or Impair Cap-Dependent Translation in Two Different Lung Adenocarcinoma Cell Lines
Authors: Kyriakopoulos George , Katopodi Vicky , Skeparnias Ilias , Kaliatsi Eleni G. , Grafanaki Katerina , Stathopoulos Constantinos
Published: February 2021

KRASG12C is among the most common oncogenic mutations in lung adenocarcinoma and a promising target for treatment by small-molecule inhibitors. KRAS oncogenic signaling is responsible for modulation of tumor microenvironment, with translation factors being among the most prominent deregulated targets. In the present study, we used TALENs to edit EGFRWT CL1-5 and A549 cells for integration of a Tet-inducible KRASG12C expression system. Subsequent analysis of both cell lines showed that cap-dependent translation was impaired in CL1-5 cells via involvement of mTORC2 and NF-κB. In contrast, in A549 cells, which additionally harbor the KRASG12S mutation, cap-dependent translation was favored via recruitment of mTORC1, c-MYC and the positive regulation of eIF4F complex. Downregulation of eIF1, eIF5 and eIF5B in the same cell line suggested a stringency loss of start codon selection during scanning of mRNAs. Puromycin staining and polysome profile analysis validated the enhanced translation rates in A549 cells and the impaired cap-dependent translation in CL1-5 cells. Interestingly, elevated translation rates were restored in CL1-5 cells after prolonged induction of KRASG12C through an mTORC1/p70S6K-independent way. Collectively, our results suggest that KRASG12C signaling differentially affects the regulation of the translational machinery. These differences could provide additional insights and facilitate current efforts to effectively target KRAS.
The Self-Assembly and Design of Polyfunctional Nanosystems
Authors: Kashapov Ruslan , Zakharova Lucia
Published: February 2021

The current task of the molecular sciences is to create unique nanostructured materials with a given structure and with specific physicochemical properties on the basis of the existing wide range of molecules of natural and synthetic origin. A promising and inexpensive way to obtain nanostructured materials is the spontaneous self-assembly of molecular building blocks during random collisions in real dispersive systems in solution and at interfaces. This editorial aims to summarize the major points from the 11 scientific papers that contributed to the special issue “The Self-Assembly and Design of Polyfunctional Nanosystems”, assessing the modern self-assembly potential and strategies for maintaining sustainable development of the nanoindustry.
Development of Antimicrobial Phototreatment Tolerance: Why the Methodology Matters
Authors: Rapacka-Zdonczyk Aleksandra , Wozniak Agata , Nakonieczna Joanna , Grinholc Mariusz
Published: February 2021

Due to rapidly growing antimicrobial resistance, there is an urgent need to develop alternative, non-antibiotic strategies. Recently, numerous light-based approaches, demonstrating killing efficacy regardless of microbial drug resistance, have gained wide attention and are considered some of the most promising antimicrobial modalities. These light-based therapies include five treatments for which high bactericidal activity was demonstrated using numerous in vitro and in vivo studies: antimicrobial blue light (aBL), antimicrobial photodynamic inactivation (aPDI), pulsed light (PL), cold atmospheric plasma (CAP), and ultraviolet (UV) light. Based on their multitarget activity leading to deleterious effects to numerous cell structures—i.e., cell envelopes, proteins, lipids, and genetic material—light-based treatments are considered to have a low risk for the development of tolerance and/or resistance. Nevertheless, the most recent studies indicate that repetitive sublethal phototreatment may provoke tolerance development, but there is no standard methodology for the proper evaluation of this phenomenon. The statement concerning the lack of development of resistance to these modalities seem to be justified; however, the most significant motivation for this review paper was to critically discuss existing dogma concerning the lack of tolerance development, indicating that its assessment is more complex and requires better terminology and methodology.
Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1
Authors: Labeit Siegfried , Hirner Stephanie , Bogomolovas Julijus , Cruz André , Myrzabekova Moldir , Moriscot Anselmo , Bowen Thomas Scott , Adams Volker
Published: February 2021

The muscle-specific ubiquitin ligase MuRF1 regulates muscle catabolism during chronic wasting states, although its roles in general metabolism are less-studied. Here, we metabolically profiled MuRF1-deficient knockout mice. We also included knockout mice for MuRF2 as its closely related gene homolog. MuRF1 and MuRF2-KO (knockout) mice have elevated serum glucose, elevated triglycerides, and reduced glucose tolerance. In addition, MuRF2-KO mice have a reduced tolerance to a fat-rich diet. Western blot and enzymatic studies on MuRF1-KO skeletal muscle showed perturbed FoxO-Akt signaling, elevated Akt-Ser-473 activation, and downregulated oxidative mitochondrial metabolism, indicating potential mechanisms for MuRF1,2-dependent glucose and fat metabolism regulation. Consistent with this, the adenoviral re-expression of MuRF1 in KO mice normalized Akt-Ser-473, serum glucose, and triglycerides. Finally, we tested the MuRF1/2 inhibitors MyoMed-205 and MyoMed-946 in a mouse model for type 2 diabetes mellitus (T2DM). After 28 days of treatment, T2DM mice developed progressive muscle weakness detected by wire hang tests, but this was attenuated by the MyoMed-205 treatment. While MyoMed-205 and MyoMed-946 had no significant effects on serum glucose, they did normalize the lymphocyte–granulocyte counts in diabetic sera as indicators of the immune response. Thus, small molecules directed to MuRF1 may be useful in attenuating skeletal muscle strength loss in T2DM conditions.
Mutation of GGMP Repeat Segments of Plasmodium falciparum Hsp70-1 Compromises Chaperone Function and Hop Co-Chaperone Binding
Authors: Makumire Stanley , Dongola Tendamudzimu Harmfree , Chakafana Graham , Tshikonwane Lufuno , Chauke Cecilia Tshikani , Maharaj Tarushai , Zininga Tawanda , Shonhai Addmore
Published: February 2021

Parasitic organisms especially those of the Apicomplexan phylum, harbour a cytosol localised canonical Hsp70 chaperone. One of the defining features of this protein is the presence of GGMP repeat residues sandwiched between α-helical lid and C-terminal EEVD motif. The role of the GGMP repeats of Hsp70s remains unknown. In the current study, we introduced GGMP mutations in the cytosol localised Hsp70-1 of Plasmodium falciparum (PfHsp70-1) and a chimeric protein (KPf), constituted by the ATPase domain of E. coli DnaK fused to the C-terminal substrate binding domain of PfHsp70-1. A complementation assay conducted using E. coli dnaK756 cells demonstrated that the GGMP motif was essential for chaperone function of the chimeric protein, KPf. Interestingly, insertion of GGMP motif of PfHsp70-1 into DnaK led to a lethal phenotype in E. coli dnaK756 cells exposed to elevated growth temperature. Using biochemical and biophysical assays, we established that the GGMP motif accounts for the elevated basal ATPase activity of PfHsp70-1. Furthermore, we demonstrated that this motif is important for interaction of the chaperone with peptide substrate and a co-chaperone, PfHop. Our findings suggest that the GGMP may account for both the specialised chaperone function and reportedly high catalytic efficiency of PfHsp70-1.
Development of Nano-Antifungal Therapy for Systemic and Endemic Mycoses
Authors: Martínez-Montelongo Jorge H. , Medina-Ramírez Iliana E. , Romo-Lozano Yolanda , González-Gutiérrez Antonio , Macías-Díaz Jorge E.
Published: February 2021

Fungal mycoses have become an important health and environmental concern due to the numerous deleterious side effects on the well-being of plants and humans. Antifungal therapy is limited, expensive, and unspecific (causes toxic effects), thus, more efficient alternatives need to be developed. In this work, Copper (I) Iodide (CuI) nanomaterials (NMs) were synthesized and fully characterized, aiming to develop efficient antifungal agents. The bioactivity of CuI NMs was evaluated using Sporothrix schenckii and Candida albicans as model organisms. CuI NMs were prepared as powders and as colloidal suspensions by a two-step reaction: first, the CuI2 controlled precipitation, followed by hydrazine reduction. Biopolymers (Arabic gum and chitosan) were used as surfactants to control the size of the CuI materials and to enhance its antifungal activity. The materials (powders and colloids) were characterized by SEM-EDX and AFM. The materials exhibit a hierarchical 3D shell morphology composed of ordered nanostructures. Excellent antifungal activity is shown by the NMs against pathogenic fungal strains, due to the simultaneous and multiple mechanisms of the composites to combat fungi. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of CuI-AG and CuI-Chitosan are below 50 μg/mL (with 5 h of exposition). Optical and Atomic Force Microscopy (AFM) analyses demonstrate the capability of the materials to disrupt biofilm formation. AFM also demonstrates the ability of the materials to adhere and penetrate fungal cells, followed by their lysis and death. Following the concept of safe by design, the biocompatibility of the materials was tested. The hemolytic activity of the materials was evaluated using red blood cells. Our results indicate that the materials show an excellent antifungal activity at lower doses of hemolytic disruption.
Special Issue: Advanced Materials in Drug Release and Drug Delivery Systems
Authors: Winnicka Katarzyna
Published: February 2021

Development of new drug molecules is costly and requires longitudinal, wide-ranging studies; therefore, designing advanced pharmaceutical formulations for existing and well-known drugs seems to be an attractive device for the pharmaceutical industry [...]
Green Nanocoatings Based on the Deposition of Zirconium Oxide: The Role of the Substrate
Authors: Bonamigo Moreira Vitor , Puiggalí-Jou Anna , Jiménez-Piqué Emilio , Alemán Carlos , Meneguzzi Alvaro , Armelin Elaine
Published: February 2021

Herein, the influence of the substrate in the formation of zirconium oxide monolayer, from an aqueous hexafluorozirconic acid solution, by chemical conversion and by electro-assisted deposition, has been approached. The nanoscale dimensions of the ZrO2 film is affected by the substrate nature and roughness. This study evidenced that the mechanism of Zr-EAD is dependent on the potential applied and on the substrate composition, whereas conversion coating is uniquely dependent on the adsorption reaction time. The zirconium oxide based nanofilms were more homogenous in AA2024 substrates if compared to pure Al grade (AA1100). It was justified by the high content of Cu alloying element present in the grain boundaries of the latter. Such intermetallic active sites favor the obtaining of ZrO2 films, as demonstrated by XPS and AFM results. From a mechanistic point of view, the electrochemical reactions take place simultaneously with the conventional chemical conversion process driven by ions diffusion. Such findings will bring new perspectives for the generation of controlled oxide coatings in modified electrodes used, as for example, in the construction of battery cells; in automotive and in aerospace industries, to replace micrometric layers of zinc phosphate by light-weight zirconium oxide nanometric ones. This study is particularly addressed for the reduction of industrial waste by applying green bath solutions without the need of auxiliary compounds and using lightweight ceramic materials.
Poly(Ethylene Furanoate) along Its Life-Cycle from a Polycondensation Approach to High-Performance Yarn and Its Recyclate
Authors: Höhnemann Tim , Steinmann Mark , Schindler Stefan , Hoss Martin , König Simon , Ota Antje , Dauner Martin , Buchmeiser Michael R.
Published: February 2021

We report on the pilot scale synthesis and melt spinning of poly(ethylene furanoate) (PEF), a promising bio-based fiber polymer that can heave mechanical properties in the range of commercial poly(ethylene terephthalate) (PET) fibers. Catalyst optimization and solid state polycondensation (SSP) allowed for intrinsic viscosities of PEF of up to 0.85 dL·g−1. Melt-spun multifilament yarns reached a tensile strength of up to 65 cN·tex−1 with an elongation of 6% and a modulus of 1370 cN·tex−1. The crystallization behavior of PEF was investigated by differential scanning calorimetry (DSC) and XRD after each process step, i.e., after polymerization, SSP, melt spinning, drawing, and recycling. After SSP, the previously amorphous polymer showed a crystallinity of 47%, which was in accordance with literature. The corresponding XRD diffractograms showed signals attributable to α-PEF. Additional, clearly assignable signals at 2θ > 30° are discussed. A completely amorphous structure was observed by XRD for as-spun yarns, while a crystalline phase was detected on drawn yarns; however, it was less pronounced than for the granules and independent of the winding speed.
Buckling Resistance of Two-Segment Stepped Steel Columns
Authors: Fliegner Bartłomiej , Marcinowski Jakub , Sakharov Volodymyr
Published: February 2021

Columns of stepwise variable bending stiffness are encountered in the engineering practice quite often. Two different load cases can be distinguished: firstly, the axial force acting only at the end of the column; secondly, besides the force acting at the end, the additional force acting at the place where the section changes suddenly. Expressions for critical forces for these two cases of loading are required to correctly design such columns. Analytical formulae defining critical forces for pin-ended columns are derived and presented in the paper. Derivations were based on the Euler-Bernoulli theory of beams. The energetic criterion of Timoshenko was adopted as the buckling criterion. Both formulae were derived in the form of Rayleigh quotients using the Mathematica® system. The correctness of formulae was verified based on one the of transcendental equations derived from differential equations of stability and presented by Volmir. Comparisons to results obtained by other authors were presented, as well. The derived formulae on the critical forces can be directly used by designers in procedures leading to the column’s buckling resistance assessment. The relatively simple procedure leading to buckling resistance assessment of steel stepped columns and based on general Ayrton-Perry approach was proposed in this work. The series of experimental tests made on steel, stepped columns and numerical simulations have confirmed the correctness of the presented approach.
Development of Multifunctional Materials Based on Poly(ether ether ketone) with Improved Biological Performances for Dental Applications
Authors: Montaño-Machado Vanessa , Chevallier Pascale , Bonilla-Gameros Linda , Copes Francesco , Quarta Chiara , Kú-Herrera José de Jesús , Soriano Florentino , Padilla-Gainza Victoria , Morales Graciela , Mantovani Diego
Published: February 2021

The main target for the future of materials in dentistry aims to develop dental implants that will have optimal integration with the surrounding tissues, while preventing or avoiding bacterial infections. In this project, poly(ether ether ketone) (PEEK), known for its suitable biocompa-tibility and mechanical properties for dental applications, was loaded with 1, 3, and 5 wt.% ZnO nanoparticles to provide antibacterial properties and improve interaction with cells. Sample cha-racterization by X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) as well as mechanical properties showed the presence of the nanoparticles and their effect in PEEK matrices, preserving their relevant properties for dental applications. Al-though, the incorporation of ZnO nanoparticles did not improve the mechanical properties and a slight decrease in the thermal stability of the materials was observed. Hemocompatibility and osteoblasts-like cell viability tests showed improved biological performances when ZnO was present, demonstrating high potential for dental implant applications.
Characterization of Phosphate Coatings: Influence of the Acid Pickling Conditions
Authors: Díaz Belén , Nóvoa X. Ramón , Pérez Carmen , Silva-Fernández Sheila
Published: February 2021

This research emphasizes the importance of the acid cleaning prior to the phosphate development on high-strength steel rods. It compares the phosphate properties achieved after different acid-pickling conditions. The most common inorganic acids were considered in this study. Additionally, taking into account the environmental and safety concerns of these acids, the assessment of a less harmful organic acid is presented. This study revealed significant differences in the coating morphology and chemical composition whereas no great changes were found in terms of the coating weight or porosity. Thus, hydrochloric and sulfuric acid promote the growth of a Fe-enriched phosphate layer with a less conductive character that is not developed after the pickling with phosphoric acid. The phosphate developed after the citric acid pickling is comparable to that developed after the inorganic acids although with a porosity slightly higher. The temperature of the citric acid bath is an important parameter that affects to the phosphate appearance, composition, and porosity.
Comparison of Osmotic Resistance, Shape and Transmembrane Potential of Erythrocytes Collected from Healthy and Fed with High Fat-Carbohydrates Diet (HF-CD) Pigs—Protective Effect of Cistus incanus L. Extracts
Authors: Cyboran-Mikołajczyk Sylwia , Pasławski Robert , Pasławska Urszula , Nowak Kacper , Płóciennik Michał , Męczarska Katarzyna , Oszmiański Jan , Bonarska-Kujawa Dorota , Kowalczyk Paweł , Wawrzyńska Magdalena
Published: February 2021

Long-term high fat-carbohydrates diet (HF-CD) contributes to the formation of irreversible changes in the organism that lead to the emergence of civilization diseases. In this study, the impact of three-month high-fat diet on the physical properties of erythrocytes (RBCs) was studied. Furthermore, the biological activity of Cistus incanus L. extracts, plant known with high pro-health potential, in relation to normal and HF-CD RBCs, was determined. Obtained results have shown that, applied HF-CD modified shape, membrane potential and osmotic resistance of erythrocytes causing changes in membrane lipid composition and the distribution of lipids. The impact of HF-CD on physical properties of RBCs along with atherosclerotic lesions of the artery was visible, despite the lack of statistically significant changes in blood morphology and plasma lipid profile. This suggests that erythrocytes may be good markers of obesity-related diseases. The studies of biological activity of Cistus incanus L. extracts have demonstrated that they may ameliorate the effect of HF-CD on erythrocytes through the membrane-modifying and antioxidant activity.
Ball versus Locator® Attachments: A Retrospective Study on Prosthetic Maintenance and Effect on Oral-Health-Related Quality of Life
Authors: Brandt Silvia , Lauer Hans-Christoph , Fehrenz Michael , Güth Jan-Frederik , Romanos Georgios , Winter Anna
Published: February 2021

Locator® and ball attachments are well-established systems to attach overdentures to two inter-foraminal implants. This study aimed to evaluate differences between the two systems regarding prosthetic maintenance and patients’ oral-health-related quality of life (OHRQoL). Dental records of patients with a mandibular implant-retained overdenture were retrospectively analyzed. Prosthetic maintenance measures involving the denture suprastructure and attachment matrix and patrix were analyzed. Furthermore, the Oral Health Impact Profile-G14 (OHIP-G14) was used to evaluate OHRQoL. Results were analyzed by means of Kaplan–Meier analysis and Student’s t- and log-rank tests. The records of 122 patients were evaluated. Kaplan–Meier survival analysis revealed a significant difference between ball attachments (Group B; n patients = 47) and Locator® attachments (Group L; n patients = 75) regarding the occurrence of denture fractures (p < 0.001) and events affecting the matrix (p = 0.028) and patrix (p = 0.030). Group L had a significantly lower total OHIP-G14 score than Group B (p = 0.002). The most common maintenance events were matrix-related and denture relining for both attachment systems. Group B required more maintenance measures than Group L. Moreover, patients in Group L had better OHRQoL than patients in Group B.