bluuebunny/crossref_metadata_2025 huggingface dataset:
The Genome Stability Maintenance DNA Helicase DDX11 and Its Role in Cancer
Authors: Mahtab Mohammad , Boavida Ana , Santos Diana , Pisani Francesca M.
Published: March 2021

DDX11/ChlR1 is a super-family two iron–sulfur cluster containing DNA helicase with roles in DNA replication and sister chromatid cohesion establishment, and general chromosome architecture. Bi-allelic mutations of the DDX11 gene cause a rare hereditary disease, named Warsaw breakage syndrome, characterized by a complex spectrum of clinical manifestations (pre- and post-natal growth defects, microcephaly, intellectual disability, heart anomalies and sister chromatid cohesion loss at cellular level) in accordance with the multifaceted, not yet fully understood, physiological functions of this DNA helicase. In the last few years, a possible role of DDX11 in the onset and progression of many cancers is emerging. Herein we summarize the results of recent studies, carried out either in tumoral cell lines or in xenograft cancer mouse models, suggesting that DDX11 may have an oncogenic role. The potential of DDX11 DNA helicase as a pharmacological target for novel anti-cancer therapeutic interventions, as inferred from these latest developments, is also discussed.
A Meta-Analysis on Prophylactic Donor Heart Tricuspid Annuloplasty in Orthotopic Heart Transplantation: High Hopes from a Small Intervention
Authors: Bacusca Alberto Emanuel , Tarus Andrei , Burlacu Alexandru , Enache Mihail , Tinica Grigore
Published: March 2021

(1) Background: Tricuspid regurgitation (TR) is the most frequent valvulopathy in heart transplant recipients (HTX). We aimed to assess the influence of prophylactic donor heart tricuspid annuloplasty (TA) in orthotopic HTX (HTX-A), comparing the outcomes with those of HTX patients. (2) Methods: Electronic databases of PubMed, EMBASE, and SCOPUS were searched. The endpoints were as follows: the overall rate of postprocedural TR (immediate, one week, six months, and one year after the procedure), postoperative complications (permanent pacemaker implantation rate, bleeding), redo surgery for TR, and mortality. (3) Results: This meta-analysis included seven studies. Immediate postprocedural, one-week, six-month and one-year tricuspid insufficiency rates were significantly lower in the HTX-A group. There was no difference in permanent pacemaker implantation rate between the groups. The incidence of postoperative bleeding was similar in both arms. The rate of redo surgery for severe TR was reported only by two authors. In both publications, the total number of events was higher in the HTX cohort, meanwhile pooled effect analysis showed no difference among the intervention and control groups. Mortality at one year was similar in both arms. (4) Conclusion: Our study showed that donor heart TA reduces TR incidence in the first year after orthotopic heart transplantation without increasing the surgical complexity. This is a potentially important issue, given the demand for heart transplants and the need to optimize outcomes when this resource is scarce.
Differences in Function and Healthcare Cost of Older Adults with Dementia by Long-Term Care Service Type: A National Dataset Analysis
Authors: Park Ilsu , Lee Kyounga , Yim Eunshil , Noh Kyunghee
Published: March 2021

This study aims to analyze the function and cost changes among long-term care insurance (LTCI) beneficiaries with low-severity dementia according to their LTCI service type. Data were collected from the Korean LTCI and national health insurance (NHI) datasets. Participants were 4414 beneficiaries with dementia aged 65 or older who received LTC services continuously for 4 years (2008–2011). LTCI service types were classified into home care (HC), institutional care (IC), and combined care (CC). Activities of daily living (ADL), cognitive function, medical cost, and benefit-cost were assessed. Linear mixed models and multiple regression models were used to analyze the changes in function and costs of the beneficiaries. ADL, cognitive function, medical cost, and benefit-cost differed significantly depending on the service type and time (p < 0.001). LTCI service types affected the degree of changes in ADL, cognitive function, medical cost, and benefit-cost over four years and showed negative changes in IC and CC beneficiaries than HC beneficiaries. HC is a cost-effective way to maintain the function of beneficiaries with low-severity dementia. Thus, efforts are needed to actively promote HC services.
Artisanal and Small Gold Mining and Petroleum Production as Potential Sources of Heavy Metal Contamination in Ecuador: A Call to Action
Authors: Rivera-Parra José Luis , Beate Bernardo , Diaz Ximena , Ochoa María Belén
Published: March 2021

Mining and petroleum production are the source of many elements and base materials fundamental for our modern way of life. The flip side of these keystone industries is the environmental degradation they can cause if not properly managed. Metallic mining and petroleum production can contaminate the local ecosystem with sediments, chemicals used in the industrial processes and heavy metals, part of the metallic ore or oil reservoir. The objective of this project was to analyze the spatial distribution of the presence of different potentially hazardous elements that make up the metallic deposits and oil reservoirs in Ecuador, focused mainly on artisanal and small-scale gold mining (ASGM) districts. Additionally, we were interested in analyzing this information under the local political and administrative contexts which are key to determining how likely it is that mismanagement of the local mineral deposits and petroleum exploitation projects will end up causing environmental degradation. An extensive and intensive literature search was conducted for information on the presence and concentration of 19 potentially harmful elements. We analyzed data on 11 metallic deposits throughout Ecuador and a major oilfield in the Ecuadorian Amazon basin. We used geographic information systems to analyze the spatial distribution of these reservoirs and their mineral compositions. The results indicated a widespread distribution and high concentration of elements potentially harmful for human health, such as mercury, cadmium and arsenic, throughout the metallic deposits in Ecuador. This is particularly true for long-exploited ASGM districts, such as Ponce-Enríquez, Portovelo-Zaruma and Nambija. This study highlights the importance of understanding geological diversity and its potential risks to better protect the biological diversity and public health of its inhabitants. Furthermore, we consider our work not as a call to stop ASGM mining nor petroleum production, but on the contrary as a strong call to plan every mining and petroleum production project considering these risks. Moreover, our work is a call to action by the local government and authorities to stop corruption and fulfill their duties overseeing the activities of mining and petroleum companies, stopping illegal mining, helping ASGM communities to improve their environmental standards, finding alternative income sources and protecting the local environment.
Association between Participation Activities, Pain Severity, and Psychological Distress in Old Age: A Population-Based Study of Swedish Older Adults
Authors: Dragioti Elena , Gerdle Björn , Levin Lars-Åke , Bernfort Lars , Dong Huan-Ji
Published: March 2021

Although chronic pain is common in old age, previous studies on participation activities in old age seldom consider pain aspects and its related consequences. This study analyses associations between participation activities, pain severity, and psychological distress in an aging population of Swedish older adults (N = 6611). We examined older adults’ participation in five common leisure activities using the Multidimensional Pain Inventory (MPI), sociodemographic factors, pain severity, weight status, comorbidities, and pain-related psychological distress (anxiety, depression, insomnia severity, and pain catastrophising). We found that gender, body mass index (BMI) levels, and psychological distress factors significantly affected older adults’ participation in leisure activities. Pain severity and multimorbidity were not significantly associated with older adults’ participation in leisure activities nor with gender stratification in generalised linear regression models. The potentially modifiable factors, such as high levels of BMI and psychological distress, affected activity participation in men and women differently. Health professionals and social workers should consider gender and target potentially modifiable factors such as weight status and psychological distress to increase older adults’ participation in leisure activities.
The Geography of the Covid-19 Pandemic: A Data-Driven Approach to Exploring Geographical Driving Forces
Authors: Hass Frederik Seeup , Jokar Arsanjani Jamal
Published: March 2021

The Covid-19 pandemic emerged and evolved so quickly that societies were not able to respond quickly enough, mainly due to the nature of the Covid-19 virus’ rate of spread and also the largely open societies that we live in. While we have been willingly moving towards open societies and reducing movement barriers, there is a need to be prepared for minimizing the openness of society on occasions such as large pandemics, which are low probability events with massive impacts. Certainly, similar to many phenomena, the Covid-19 pandemic has shown us its own geography presenting its emergence and evolving patterns as well as taking advantage of our geographical settings for escalating its spread. Hence, this study aims at presenting a data-driven approach for exploring the spatio-temporal patterns of the pandemic over a regional scale, i.e., Europe and a country scale, i.e., Denmark, and also what geographical variables potentially contribute to expediting its spread. We used official regional infection rates, points of interest, temperature and air pollution data for monitoring the pandemic’s spread across Europe and also applied geospatial methods such as spatial autocorrelation and space-time autocorrelation to extract relevant indicators that could explain the dynamics of the pandemic. Furthermore, we applied statistical methods, e.g., ordinary least squares, geographically weighted regression, as well as machine learning methods, e.g., random forest for exploring the potential correlation between the chosen underlying factors and the pandemic spread. Our findings indicate that population density, amenities such as cafes and bars, and pollution levels are the most influential explanatory variables while pollution levels can be explicitly used to monitor lockdown measures and infection rates at country level. The choice of data and methods used in this study along with the achieved results and presented discussions can empower health authorities and decision makers with an interactive decision support tool, which can be useful for imposing geographically varying lockdowns and protectives measures using historical data.
Sleep and Mental Health Disturbances Due to Social Isolation during the COVID-19 Pandemic in Mexico
Authors: Terán-Pérez Guadalupe , Portillo-Vásquez Angelica , Arana-Lechuga Yoaly , Sánchez-Escandón Oscar , Mercadillo-Caballero Roberto , González-Robles Rosa Obdulia , Velázquez-Moctezuma Javier
Published: March 2021

The coronavirus disease (COVID-19) that broke out in China in December 2019 rapidly became a worldwide pandemic. In Mexico, the conditions requiring the declaration of a sanitary emergency were reached by the last week of March 2020, and health authorities’ limited mobility and imposed social isolation were the main strategies to keep the virus from spreading. Thus, daily living conditions changed drastically in a few days, generating a stressful situation characterized by an almost complete lack of mobility, social isolation, and forced full-time interactions with family members. Soon, complaints of sleep disturbances, anxiety, and symptoms of depression were reported. The present study reports the results of an online survey performed during the first two months of isolation. Questionnaires exploring sleep disturbances, anxiety, and depression were sent to people who responded to an open invitation. A total of 1230 participants filled out the sleep questionnaire, 812 responded to the anxiety questionnaire, and 814 responded to the depression questionnaire. Both men and women reported poor sleep quality, but women showed a higher proportion (79%) than men (60%); young women were more likely to be affected by social isolation. Concerning anxiety and depression, both sexes reported high similar symptoms. These data suggest that stressful conditions related to social isolation and the economic uncertainty caused by the pandemic may induce mental health disturbances, which may become worse with sleep restriction.
Longitudinal Changes in Gambling, Buying and Materialism in Adolescents: A Population-Based Study
Authors: Estévez Ana , Jauregui Paula , Momeñe Janire , Macia Laura , López-González Hibai , Iruarrizaga Iciar , Riquelme-Ortiz Conchi , Granero Roser , Fernández-Aranda Fernando , Vintró-Alcaraz Cristina , Mestre-Bach Gemma , Munguía Lucero , Solé-Morata Neus , Jiménez-Murcia Susana
Published: March 2021

Gambling disorder, gambling-related cognitive biases, compulsive buying, and materialistic values lead to impaired functioning in important areas of life. The aims of the present longitudinal study are (1) to evaluate the change produced after one year in those mentioned variables and (2) to examine the gender role in these changes and to analyze the mediational mechanisms among the variables of the study. The sample was composed of 182 adolescents (103 females and 79 males) from secondary education Spanish institutions who completed self-administered questionnaires. Structural equation modeling has been used to explore associations between the different variables. Our results show significant decreases in compulsive buying, materialism, and cognitive biases related to gambling after one year. Gambling disorder severity was directly related to cognitive distortions of gambling and being a man. Compulsive buying was associated with older age and the female gender. Materialism was associated with compulsive buying and the male gender. In conclusion, gambling disorder, gambling-related cognitive biases, compulsive buying, and materialistic values change over time in different ways, according to gender. The understanding of gambling disorder and compulsive buying in adolescents could potentially lead to early prevention and treatment programs for the specific needs of gender and age.
Disengaging Leadership Scale (DLS): Evidence of Initial Validity
Authors: Nikolova Irina , Caniëls Marjolein C. J. , Schaufeli Wilmar , Semeijn Judith H.
Published: March 2021

The main goal of this study was to develop a scale for measuring Disengaging Leader-ship (DEL) behaviors and to provide preliminary evidence for the validity of this new instrument. Developing such new measures is needed given current concepts that tap into negative leadership behaviors are rarely based on a sound theoretical framework. Drawing on the core premises of Self-Determination Theory (SDT) regarding employees’ basic needs and, more specifically, building on its more recent extended framework, including employees’ needs frustration, we derived four dimensions that constitute Disengaging Leadership behaviors (coercive disengaging leadership, isolating disengaging leadership, eroding disengaging leadership, and demotivating disengaging leadership). To examine the factor structure and psychometric properties of the new Disengaging Leadership Scale (DLS), Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and reliability analyses were conducted. Results supported the hypothesized four-factor structure of the DLS and showed that this factorial structure remained invariant across employees occupying blue-collar, white-collar, or managerial positions. Finally, we successfully tested convergent, divergent, and construct validity of DLS. We established that DEL is associated with employees’ needs frustration and with their experiences of emotional exhaustion. It is concluded that the DLS has sound psychometric properties and can be used in future research on the dark side of leadership.
Association of Acculturation Status with Longitudinal Changes in Health-Related Quality of Life—Results from a Cohort Study of Adults with Turkish Origin in Germany
Authors: Krist Lilian , Dornquast Christina , Reinhold Thomas , Becher Heiko , Jöckel Karl-Heinz , Schmidt Börge , Schramm Sara , Icke Katja , Danquah Ina , Willich Stefan N. , Keil Thomas , Brand Tilman
Published: March 2021

Health-related quality of life (HRQL) among migrant populations can be associated with acculturation (i.e., the process of adopting, acquiring and adjusting to a new cultural environment). Since there is a lack of longitudinal studies, we aimed to describe HRQL changes among adults of Turkish descent living in Berlin and Essen, Germany, and their association with acculturation. Participants of a population-based study were recruited in 2012–2013 and reinvited six years later to complete a questionnaire. Acculturation was assessed at baseline using the Frankfurt acculturation scale (integration, assimilation, separation and marginalization). HRQL was assessed at baseline (SF-8) and at follow-up (SF-12) resulting in a physical (PCS) and mental (MCS) sum score. Associations with acculturation and HRQL were analyzed with linear regression models using a time-by-acculturation status interaction term. In the study 330 persons were included (65% women, mean age ± standard deviation 43.3 ± 11.8 years). Over the 6 years, MCS decreased, while PCS remained stable. While cross-sectional analyses showed associations of acculturation status with both MCS and PCS, temporal changes including the time interaction term did not reveal associations of baseline acculturation status with HRQL. When investigating HRQL in acculturation, more longitudinal studies are needed to take changes in both HRQL and acculturation status into account.
A Century of French Railways: The Value of Remote Sensing and VGI in the Fusion of Historical Data
Authors: Jeansoulin Robert
Published: March 2021

Providing long-term data about the evolution of railway networks in Europe may help us understand how European Union (EU) member states behave in the long-term, and how they can comply with present EU recommendations. This paper proposes a methodology for collecting data about railway stations, at the maximal extent of the French railway network, a century ago.The expected outcome is a geocoded dataset of French railway stations (gares), which: (a) links gares to each other, (b) links gares with French communes, the basic administrative level for statistical information. Present stations are well documented in public data, but thousands of past stations are sparsely recorded, not geocoded, and often ignored, except in volunteer geographic information (VGI), either collaboratively through Wikipedia or individually. VGI is very valuable in keeping track of that heritage, and remote sensing, including aerial photography is often the last chance to obtain precise locations. The approach is a series of steps: (1) meta-analysis of the public datasets, (2) three-steps fusion: measure-decision-combination, between public datasets, (3) computer-assisted geocoding for ‘gares’ where fusion fails, (4) integration of additional gares gathered from VGI, (5) automated quality control, indicating where quality is questionable. These five families of methods, form a comprehensive computer-assisted reconstruction process (CARP), which constitutes the core of this paper. The outcome is a reliable dataset—in geojson format under open license—encompassing (by January 2021) more than 10,700 items linked to about 7500 of the 35,500 communes of France: that is 60% more than recorded before. This work demonstrates: (a) it is possible to reconstruct transport data from the past, at a national scale; (b) the value of remote sensing and of VGI is considerable in completing public sources from an historical perspective; (c) data quality can be monitored all along the process and (d) the geocoded outcome is ready for a large variety of further studies with statistical data (demography, density, space coverage, CO2 simulation, environmental policies, etc.).
TRP Channels as Cellular Targets of Particulate Matter
Authors: Milici Alina , Talavera Karel
Published: March 2021

Particulate matter (PM) is constituted by particles with sizes in the nanometer to micrometer scales. PM can be generated from natural sources such as sandstorms and wildfires, and from human activities, including combustion of fuels, manufacturing and construction or specially engineered for applications in biotechnology, food industry, cosmetics, electronics, etc. Due to their small size PM can penetrate biological tissues, interact with cellular components and induce noxious effects such as disruptions of the cytoskeleton and membranes and the generation of reactive oxygen species. Here, we provide an overview on the actions of PM on transient receptor potential (TRP) proteins, a superfamily of cation-permeable channels with crucial roles in cell signaling. Their expression in epithelial cells and sensory innervation and their high sensitivity to chemical, thermal and mechanical stimuli makes TRP channels prime targets in the major entry routes of noxious PM, which may result in respiratory, metabolic and cardiovascular disorders. On the other hand, the interactions between TRP channel and engineered nanoparticles may be used for targeted drug delivery. We emphasize in that much further research is required to fully characterize the mechanisms underlying PM-TRP channel interactions and their relevance for PM toxicology and biomedical applications.
Toward the Pathogenicity of the SLC26A4 p.C565Y Variant Using a Genetically Driven Mouse Model
Authors: Hu Chin-Ju , Lu Ying-Chang , Yang Ting-Hua , Chan Yen-Hui , Tsai Cheng-Yu , Yu I-Shing , Lin Shu-Wha , Liu Tien-Chen , Cheng Yen-Fu , Wu Chen-Chi , Hsu Chuan-Jen
Published: March 2021

Recessive variants of the SLC26A4 gene are globally a common cause of hearing impairment. In the past, cell lines and transgenic mice were widely used to investigate the pathogenicity associated with SLC26A4 variants. However, discrepancies in pathogenicity between humans and cell lines or transgenic mice were documented for some SLC26A4 variants. For instance, the p.C565Y variant, which was reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice that were heterozygous (Slc26a4+/C565Y), homozygous (Slc26a4C565Y/C565Y), and compound heterozygous (Slc26a4919-2A>G/C565Y) for this variant. Subsequent phenotypic characterization revealed that mice with these genotypes demonstrated normal auditory and vestibular functions, and normal inner-ear morphology and pendrin expression. These findings indicate that the p.C565Y variant is nonpathogenic for mice, and that a single p.C565Y allele is sufficient to maintain normal inner-ear physiology in mice. Our results highlight the differences in pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be considered when interpreting the results of animal studies for SLC26A4-related deafness.
Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug
Authors: Ryu Suji , Park Seungyeop , Lee Ha Yeon , Lee Hyungjun , Cho Cheong-Weon , Baek Jong-Suep
Published: March 2021

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.
Kidney-Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Inflammation, Oxidative Stress, and Cisplatin-Induced Nephrotoxicity
Authors: Imig John D. , Hye Khan Md Abdul , Burkhan Anna , Chen Guan , Adebesin Adeniyi Michael , Falck John R.
Published: March 2021

Although epoxyeicosatrienoic acid (EET) analogs have performed well in several acute and chronic kidney disease models, targeted delivery of EET analogs to the kidney can be reasonably expected to reduce the level of drug needed to achieve a therapeutic effect and obviate possible side effects. For EET analog kidney-targeted delivery, we conjugated a stable EET analog to folic acid via a PEG-diamine linker. Next, we compared the kidney targeted EET analog, EET-F01, to a well-studied EET analog, EET-A. EET-A or EET-F01 was infused i.v. and plasma and kidney tissue collected. EET-A was detected in the plasma but was undetectable in the kidney. On the other hand, EET-F01 was detected in the plasma and kidney. Experiments were conducted to compare the efficacy of EET-F01 and EET-A for decreasing cisplatin nephrotoxicity. Cisplatin was administered to WKY rats treated with vehicle, EET-A (10 mg/kg i.p.) or EET-F01 (20 mg/kg or 2 mg/kg i.p.). Cisplatin increased kidney injury markers, viz., blood urea nitrogen (BUN), N-acetyl-β-(D)-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1), and thiobarbituric acid reactive substances (TBARS). EET-F01 was as effective as EET-A in decreasing BUN, NAG, KIM-1, TBARS, and renal histological injury caused by cisplatin. Despite its almost 2×-greater molecular weight compared with EET-A, EET-F01 was comparably effective in decreasing renal injury at a 10-fold w/w lower dose. EET-F01 decreased cisplatin nephrotoxicity by reducing oxidative stress and inflammation. These data demonstrate that EET-F01 targets the kidney, allows for a lower effective dose, and combats cisplatin nephrotoxicity. In conclusion, we have developed a kidney targeted EET analog, EET-F01, that demonstrates excellent potential as a therapeutic for kidney diseases.
Inhibition of NUPR1–Karyopherin β1 Binding Increases Anticancer Drug Sensitivity
Authors: Park Chanhee , Oh Jiwon , Lee Won Mo , Koh Hye Ran , Sohn Uy Dong , Ham Seung Wook , Oh Kyungsoo
Published: March 2021

Background: Nuclear protein-1 (NUPR1, also known as p8/Com-1) is a transcription factor involved in the regulation of cellular stress responses, including serum starvation and drug stimulation. Methods: We investigated the mechanism of NUPR1 nuclear translocation involving karyopherin β1 (KPNB1), using a single-molecule binding assay and confocal microscopy. The cellular effects associated with NUPR1–KPNB1 inhibition were investigated by gene expression profiling and cell cycle analysis. Results: The single-molecule binding assay revealed that KPNB1 bound to NUPR1 with a binding affinity of 0.75 nM and that this binding was blocked by the aminothiazole ATZ-502. Following doxorubicin-only treatment, NUPR1 was translocated to the nucleus in more than 90% and NUPR1 translocation was blocked by the ATZ-502 combination treatment in MDA-MB-231 with no change in NUPR1 expression, providing strong evidence that NUPR1 nuclear translocation was directly inhibited by the ATZ-502 treatment. Inhibition of KPNB1 and NUPR1 binding was associated with a synergistic anticancer effect (up to 19.6-fold) in various cancer cell lines. NUPR1-related genes were also downregulated following the doxorubicin–ATZ-502 combination treatment. Conclusion: Our current findings clearly demonstrate that NUPR1 translocation into the nucleus requires karyopherin β1 binding. Inhibition of the KPNB1 and NUPR1 interaction may constitute a new cancer therapeutic approach that can increase the drug efficacy while reducing the side effects.
An Inside Look into Biological Miniatures: Molecular Mechanisms of Viroids
Authors: Venkataraman Srividhya , Badar Uzma , Shoeb Erum , Hashim Ghyda , AbouHaidar Mounir , Hefferon Kathleen
Published: March 2021

Viroids are tiny single-stranded circular RNA pathogens that infect plants. Viroids do not encode any proteins, yet cause an assortment of symptoms. The following review describes viroid classification, molecular biology and spread. The review also discusses viroid pathogenesis, host interactions and detection. The review concludes with a description of future prospects in viroid research.
Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action
Authors: Łukasik Paweł , Baranowska-Bosiacka Irena , Kulczycka Katarzyna , Gutowska Izabela
Published: March 2021

Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.
A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment
Authors: Abd-El-Aziz Alaa S. , Alsaggaf Azhaar , Assirey Eman , Naqvi Arshi , Okasha Rawda M. , Afifi Tarek H. , Hagar Mohamed
Published: March 2021

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV–visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Molecules 4a, 4g, and 4h were discovered to be more efficacious against Syncephalastrum racemosum (RCMB 05922) in comparison to the reference drugs, while compounds 4b and 4h demonstrated the highest inhibitory activity against Escherichia coli (E. coli) in evaluation against the reference drugs. Moreover, their cytotoxicity was assessed against three different human cell lines, including human colon carcinoma (HCT-116), human hepatocellular carcinoma (HepG-2), and human breast adenocarcinoma (MCF-7) with a selection of molecules illustrating potency against the HCT-116 and MCF-7 cell lines. Furthermore, the molecular modeling results depicted the binding interactions of the synthesized compounds 3b and 3h in the active site of the E. coli DNA gyrase B enzyme with a clear SAR (structure–activity relationship) analysis. Lastly, the density functional theory’s (DFTs) theoretical calculations were performed to quantify the energy levels of the Frontier Molecular Orbitals (FMOs) and their energy gaps, dipole moments, and molecular electrostatic potentials. These data were utilized in the chemical descriptor estimations to confirm the biological activity.
Exopolysaccharide Carbohydrate Structure and Biofilm Formation by Rhizobium leguminosarum bv. trifolii Strains Inhabiting Nodules of Trifoliumrepens Growing on an Old Zn–Pb–Cd-Polluted Waste Heap Area
Authors: Oleńska Ewa , Małek Wanda , Kotowska Urszula , Wydrych Jerzy , Polińska Weronika , Swiecicka Izabela , Thijs Sofie , Vangronsveld Jaco
Published: March 2021

Heavy metals polluting the 100-year-old waste heap in Bolesław (Poland) are acting as a natural selection factor and may contribute to adaptations of organisms living in this area, including Trifolium repens and its root nodule microsymbionts—rhizobia. Exopolysaccharides (EPS), exuded extracellularly and associated with bacterial cell walls, possess variable structures depending on environmental conditions; they can bind metals and are involved in biofilm formation. In order to examine the effects of long-term exposure to metal pollution on EPS structure and biofilm formation of rhizobia, Rhizobium leguminosarum bv. trifolii strains originating from the waste heap area and a non-polluted reference site were investigated for the characteristics of the sugar fraction of their EPS using gas chromatography mass-spectrometry and also for biofilm formation and structural characteristics using confocal laser scanning microscopy under control conditions as well as when exposed to toxic concentrations of zinc, lead, and cadmium. Significant differences in EPS structure, biofilm thickness, and ratio of living/dead bacteria in the biofilm were found between strains originating from the waste heap and from the reference site, both without exposure to metals and under metal exposure. Received results indicate that studied rhizobia can be assumed as potentially useful in remediation processes.
Functional Coupling between DNA Replication and Sister Chromatid Cohesion Establishment
Authors: Boavida Ana , Santos Diana , Mahtab Mohammad , Pisani Francesca M.
Published: March 2021

Several lines of evidence suggest the existence in the eukaryotic cells of a tight, yet largely unexplored, connection between DNA replication and sister chromatid cohesion. Tethering of newly duplicated chromatids is mediated by cohesin, an evolutionarily conserved hetero-tetrameric protein complex that has a ring-like structure and is believed to encircle DNA. Cohesin is loaded onto chromatin in telophase/G1 and converted into a cohesive state during the subsequent S phase, a process known as cohesion establishment. Many studies have revealed that down-regulation of a number of DNA replication factors gives rise to chromosomal cohesion defects, suggesting that they play critical roles in cohesion establishment. Conversely, loss of cohesin subunits (and/or regulators) has been found to alter DNA replication fork dynamics. A critical step of the cohesion establishment process consists in cohesin acetylation, a modification accomplished by dedicated acetyltransferases that operate at the replication forks. Defects in cohesion establishment give rise to chromosome mis-segregation and aneuploidy, phenotypes frequently observed in pre-cancerous and cancerous cells. Herein, we will review our present knowledge of the molecular mechanisms underlying the functional link between DNA replication and cohesion establishment, a phenomenon that is unique to the eukaryotic organisms.
Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder
Authors: Joo Yuyoung , Benavides David R.
Published: March 2021

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.
Digestive Inflammation: Role of Proteolytic Dysregulation
Authors: Mariaule Vincent , Kriaa Aicha , Soussou Souha , Rhimi Soufien , Boudaya Houda , Hernandez Juan , Maguin Emmanuelle , Lesner Adam , Rhimi Moez
Published: March 2021

Dysregulation of the proteolytic balance is often associated with diseases. Serine proteases and matrix metalloproteases are involved in a multitude of biological processes and notably in the inflammatory response. Within the framework of digestive inflammation, several studies have stressed the role of serine proteases and matrix metalloproteases (MMPs) as key actors in its pathogenesis and pointed to the unbalance between these proteases and their respective inhibitors. Substantial efforts have been made in developing new inhibitors, some of which have reached clinical trial phases, notwithstanding that unwanted side effects remain a major issue. However, studies on the proteolytic imbalance and inhibitors conception are directed toward host serine/MMPs proteases revealing a hitherto overlooked factor, the potential contribution of their bacterial counterpart. In this review, we highlight the role of proteolytic imbalance in human digestive inflammation focusing on serine proteases and MMPs and their respective inhibitors considering both host and bacterial origin.
Genome-Wide Identification and Characterization of AP2/ERF Transcription Factor Family Genes in Oil Palm under Abiotic Stress Conditions
Authors: Zhou Lixia , Yarra Rajesh
Published: March 2021

The AP2/ERF transcription factor family members play crucial roles in controlling plant growth and development, as well as responses to various abiotic stresses. Genome-wide identification and characterization of AP2/ERF genes has not yet been carried out in the oil palm genome. In the present work, we reported the occurrence of 172 EgAP2/ERFs (AP2, ERF, RAV & Soloist members) through genome-wide identification. Phylogenetic analysis was used to divide them into four groups, including: 34 AP2, 131 ERF, 5 RAV, and 2 Soloist gene family members. All 172 AP2/ERF members were unevenly distributed across 16 chromosomes of oil palm. Gene duplication analysis elucidated the tandem duplication of AP2/ERFs on chromosome blocks of the oil palm genome during evolution. Gene structure as well as conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the AP2/ERF genes. Several cis-regulatory elements—related to hormone, stress, and defense responses—were identified in the promoter regions of AP2/ERFs. Tissue-specific expression of 172 AP2/ERFs in five different tissues of oil palm was also revealed by heatmap analysis using the available transcriptome data. Finally, abiotic stress (salinity, cold & drought)-responsive AP2/ERFs in the oil palm genome were validated through qPCR analysis. Our study provided valuable information on oil palm AP2/ERF superfamily members and dissected their role in abiotic stress conditions.
The Anti-Melanogenesis Effect of 3,4-Dihydroxybenzalacetone through Downregulation of Melanosome Maturation and Transportation in B16F10 and Human Epidermal Melanocytes
Authors: Liu Yi-Jung , Lyu Jia-Ling , Kuo Yueh-Hsiung , Chiu Chen-Yuan , Wen Kuo-Chiang , Chiang Hsiu-Mei
Published: March 2021

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3β), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics.
Body Size and Behavioural Plasticity Interact to Influence the Performance of Free-Foraging Bumble Bee Colonies
Authors: Holland Jacob , Nakayama Shinnosuke , Porfiri Maurizio , Nov Oded , Bloch Guy
Published: March 2021

Specialisation and plasticity are important for many forms of collective behaviour, but the interplay between these factors is little understood. In insect societies, workers are often developmentally primed to specialise in different tasks, sometimes with morphological or physiological adaptations, facilitating a division of labour. Workers may also plastically switch between tasks or vary their effort. The degree to which developmentally primed specialisation limits plasticity is not clear and has not been systematically tested in ecologically relevant contexts. We addressed this question in 20 free-foraging bumble bee (Bombus terrestris) colonies by continually manipulating colonies to contain either a typically diverse, or a reduced (“homogeneous”), worker body size distribution while keeping the same mean body size, over two trials. Pooling both trials, diverse colonies produced a larger comb mass, an index of colony performance. The link between body size and task was further corroborated by the finding that foragers were larger than nurses even in homogeneous colonies with a very narrow body size range. However, the overall effect of size diversity stemmed mostly from one trial. In the other trial, homogeneous and diverse colonies showed comparable performance. By comparing behavioural profiles based on several thousand observations of individuals, we found evidence that workers in homogeneous colonies in this trial rescued colony performance by plastically increasing behavioural specialisation and/or individual effort, compared to same-sized individuals in diverse colonies. Our results are consistent with a benefit to colonies of large and small specialists under certain conditions, but also suggest that plasticity or effort can compensate for reduced (size-related) specialisation. Thus, we suggest that an intricate interplay between specialisation and plasticity is functionally adaptive in bumble bee colonies.
Impact of the COVID-19 Pandemic on the Loading and Quality of an Emergency Department in Taiwan: Enlightenment from a Low-Risk Country in a Public Health Crisis
Authors: Chen Jamie Yu-Hsuan , Chang Feng-Yee , Lin Chin-Sheng , Wang Chih-Hung , Tsai Shih-Hung , Lee Chia-Cheng , Chen Sy-Jou
Published: March 2021

The impact of the coronavirus disease 2019 (COVID-19) pandemic on health-care quality in the emergency department (ED) in countries with a low risk is unclear. This study aimed to explore the effects of the COVID-19 pandemic on ED loading, quality of care, and patient prognosis. Data were retrospectively collected from 1 January 2018 to 30 September 2020 at the ED of Tri-service general hospital. Analyses included day-based ED loading, quality of care, and patient prognosis. Data on triage assessment, physiological states, disease history, and results of laboratory tests were collected and analyzed. The number of daily visits significantly decreased after the pandemic, leading to a reduction in the time to examination. Admitted patients benefitted from the pandemic with a reduction of 0.80 h in the length of stay in the ED, faster discharge without death, and reduced re-admission. However, non-admitted visits with chest pain increased the risk of mortality after the pandemic. In conclusion, the COVID-19 pandemic led to a significant reduction in low-acuity ED visits and improved prognoses for hospitalized patients. However, clinicians should be alert about patients with chest pain due to their increased risk of mortality in subsequent admission.
Assessment of Multiple Sclerosis Disability Progression Using a Wearable Biosensor: A Pilot Study
Authors: Abbadessa Gianmarco , Lavorgna Luigi , Miele Giuseppina , Mignone Alfredo , Signoriello Elisabetta , Lus Giacomo , Clerico Marinella , Sparaco Maddalena , Bonavita Simona
Published: March 2021

Background: The evaluation of walking activity of people with multiple sclerosis (pwMS) is desirable. We evaluate the power of the correlation of motor parameters detected by the accelerometer in the Samsung Gear S2 smartwatch with multiple sclerosis (MS) disability measures and patient reported outcomes (PROs). Methods: We enrolled 25 relapsing remitting MS patients. We assessed disability with the expanded disability status scale, two-minute walking test (2MWT), timed 25-foot walk test (T25FWT), and nine-hole peg test. We collected PROs measuring fatigue, ambulatory ability, depression, quality of life, and bladder/bowel function. Participants were asked to wear the accelerometer for a period of 30 days. Results: The Spearman’s rank correlation coefficient showed a moderate negative correlation between the patient-determined disease steps (PDDS) score with the mean steps/day, a strong negative correlation between the PDDS score with the maximum number of daily steps (MNDS) and a moderate negative correlation between the fatigue severity scale score and MNDS. A moderate negative correlation between MNDS and the 2MWT and a moderate negative correlation between MNDS and the T25FW was found. Conclusion: Our results suggest that motor parameters derived from the accelerometer could be a reliable measure of motor disability in pwMS.