bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Gene Expression is Associated with Incomplete Penetrance in Inherited Eye Disorders
Authors: Green David J. , Sallah Shalaw R. , Ellingford Jamie M. , Lovell Simon C. , Sergouniotis Panagiotis I.
Published: February 2020

Inherited eye disorders (IED) are a heterogeneous group of Mendelian conditions that are associated with visual impairment. Although these disorders often exhibit incomplete penetrance and variable expressivity, the scale and mechanisms of these phenomena remain largely unknown. Here, we utilize publicly-available genomic and transcriptomic datasets to gain insights into variable penetrance in IED. Variants in a curated set of 340 IED-implicated genes were extracted from the Human Gene Mutation Database (HGMD) 2019.1 and cross-checked with the Genome Aggregation Database (gnomAD) 2.1 control-only dataset. Genes for which >1 variants were encountered in both HGMD and gnomAD were considered to be associated with variable penetrance (n = 56). Variability in gene expression levels was then estimated for the subset of these genes that was found to be adequately expressed in two relevant resources: the Genotype-Tissue Expression (GTEx) and Eye Genotype Expression (EyeGEx) datasets. We found that genes suspected to be associated with variable penetrance tended to have significantly more variability in gene expression levels in the general population (p = 0.0000015); this finding was consistent across tissue types. The results of this study point to the possible influence of cis and/or trans-acting elements on the expressivity of variants causing Mendelian disorders. They also highlight the potential utility of quantifying gene expression as part of the investigation of families showing evidence of variable penetrance.
The Mitochondrial Genome of Amara aulica (Coleoptera, Carabidae, Harpalinae) and Insights into the Phylogeny of Ground Beetles
Authors: Li Zhenya , Li Xinxin , Song Nan , Tang Huiji , Yin Xinming
Published: February 2020

Carabidae are one of the most species-rich families of beetles, comprising more than 40,000 described species worldwide. Forty-three complete or partial mitochondrial genomes (mitogenomes) from this family have been published in GenBank to date. In this study, we sequenced a nearly complete mitogenome of Amara aulica (Carabidae), using a next-generation sequencing method. This mitogenome was 16,646 bp in length, which encoded the typical 13 mitochondrial protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a putative control region. Combining with the published mitogenomes of Carabidae and five outgroup species from Trachypachidae, Gyrinidae and Dytiscidae, we performed phylogenetic estimates under maximum likelihood and Bayesian inference criteria to investigate the phylogenetic relationships of carabid beetles. The results showed that the family Carabidae was a non-monophyletic assemblage. The subfamilies Cicindelinae, Elaphrinae, Carabinae, Trechinae and Harpalinae were recovered as monophyletic groups. Moreover, the clade (Trechinae + (Brachininae + Harpalinae)) was consistently recovered in all analyses.
Sledgehammer to Scalpel: Broad Challenges to the Heart and Other Tissues Yield Specific Cellular Responses via Transcriptional Regulation of the ER-Stress Master Regulator ATF6α
Authors: Stauffer Winston T. , Arrieta Adrian , Blackwood Erik A. , Glembotski Christopher C.
Published: February 2020

There are more than 2000 transcription factors in eukaryotes, many of which are subject to complex mechanisms fine-tuning their activity and their transcriptional programs to meet the vast array of conditions under which cells must adapt to thrive and survive. For example, conditions that impair protein folding in the endoplasmic reticulum (ER), sometimes called ER stress, elicit the relocation of the ER-transmembrane protein, activating transcription factor 6α (ATF6α), to the Golgi, where it is proteolytically cleaved. This generates a fragment of ATF6α that translocates to the nucleus, where it regulates numerous genes that restore ER protein-folding capacity but is degraded soon after. Thus, upon ER stress, ATF6α is converted from a stable, transmembrane protein, to a rapidly degraded, nuclear protein that is a potent transcription factor. This review focuses on the molecular mechanisms governing ATF6α location, activity, and stability, as well as the transcriptional programs ATF6α regulates, whether canonical genes that restore ER protein-folding or unexpected, non-canonical genes affecting cellular functions beyond the ER. Moreover, we will review fascinating roles for an ATF6α isoform, ATF6β, which has a similar mode of activation but, unlike ATF6α, is a long-lived, weak transcription factor that may moderate the genetic effects of ATF6α.
Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging
Authors: Tamura Hiroshi , Jozaki Mai , Tanabe Manabu , Shirafuta Yuichiro , Mihara Yumiko , Shinagawa Masahiro , Tamura Isao , Maekawa Ryo , Sato Shun , Taketani Toshiaki , Takasaki Akihisa , Reiter Russel J. , Sugino Norihiro
Published: February 2020

Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light–dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer’s and Parkinson’s disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.
The Role of Connexin Channels in the Response of Mechanical Loading and Unloading of Bone
Authors: Riquelme Manuel A. , Cardenas Eduardo R. , Xu Huiyun , Jiang Jean X.
Published: February 2020

The skeleton adapts to mechanical loading to promote bone formation and remodeling. While most bone cells are involved in mechanosensing, it is well accepted that osteocytes are the principal mechanosensory cells. The osteocyte cell body and processes are surrounded by a fluid-filled space, forming an extensive lacuno-canalicular network. The flow of interstitial fluid is a major stress-related factor that transmits mechanical stimulation to bone cells. The long dendritic processes of osteocytes form a gap junction channel network connecting not only neighboring osteocytes, but also cells on the bone surface, such as osteoblasts and osteoclasts. Mechanosensitive osteocytes also form hemichannels that mediate the communication between the cytoplasmic and extracellular microenvironment. This paper will discuss recent research progress regarding connexin (Cx)-forming gap junctions and hemichannels in osteocytes, osteoblasts, and other bone cells, including those richly expressing Cx43. We will then cover the recent progress regarding the regulation of these channels by mechanical loading and the role of integrins and signals in mediating Cx43 channels, and bone cell function and viability. Finally, we will summarize the recent studies regarding bone responses to mechanical unloading in Cx43 transgenic mouse models. The osteocyte has been perceived as the center of bone remodeling, and connexin channels enriched in osteocytes are a likely major player in meditating the function of bone. Based on numerous studies, connexin channels may present as a potential new therapeutic target in the treatment of bone loss and osteoporosis. This review will primarily focus on Cx43, with some discussion in other connexins expressed in bone cells.
Dynamic Analysis of Sphere-Like Iron Particles Based Magnetorheological Damper for Waveform-Generating Test System
Authors: Oh Jong-Seok , Shul Chang Won , Kim Tae Hyeong , Lee Tae-Hoon , Son Sung-Wan , Choi Seung-Bok
Published: February 2020

In this study, a new double pulse waveform-generating test system with an integrated magnetorheological (MR) damper is proposed. Since the total shear stress of MR fluid can be varied according to the shape of particles, sphere-like iron particles-based MR fluid is filled into the MR damper. The test system consists of a velocity generator, three masses (impact, test, and dummy), a spring, and an MR damper. To tune the double pulse waveform profile, a damping force model is constructed to determine the fundamental parameters of the simulator. Then, the first and second shock waveform profiles are analyzed to solve the governing equation of motions representing the damping force and velocity. The mathematical model of the MR damper is formulated and applied to a simulator with a graphical user interface programmed using MATLAB. The effectiveness of the proposed simulator-featuring controllable MR damper is demonstrated by comparing the simulation and experimental results.
Dynamic Transcriptome Analysis of Anther Response to Heat Stress during Anthesis in Thermotolerant Rice (Oryza sativa L.)
Authors: Liu Gang , Zha Zhongping , Cai Haiya , Qin Dandan , Jia Haitao , Liu Changyan , Qiu Dongfeng , Zhang Zaijun , Wan Zhenghuang , Yang Yuanyuan , Wan Bingliang , You Aiqing , Jiao Chunhai
Published: February 2020

High temperature at anthesis is one of the most serious stress factors for rice (Oryza sativa L.) production, causing irreversible yield losses and reduces grain quality. Illustration of thermotolerance mechanism is of great importance to accelerate rice breeding aimed at thermotolerance improvement. Here, we identified a new thermotolerant germplasm, SDWG005. Microscopical analysis found that stable anther structure of SDWG005 under stress may contribute to its thermotolerance. Dynamic transcriptomic analysis totally identified 3559 differentially expressed genes (DEGs) in SDWG005 anthers at anthesis under heat treatments, including 477, 869, 2335, and 2210 for 1, 2, 6, and 12 h, respectively; however, only 131 were regulated across all four-time-points. The DEGs were divided into nine clusters according to their expressions in these heat treatments. Further analysis indicated that some main gene categories involved in heat-response of SDWG005 anthers, such as transcription factors, nucleic acid and protein metabolisms related genes, etc. Comparison with previous studies indicates that a core gene-set may exist for thermotolerance mechanism. Expression and polymorphic analysis of agmatine-coumarin-acyltransferase gene OsACT in different accessions suggested that it may involve in SDWG005 thermotolerance. This study improves our understanding of thermotolerance mechanisms in rice anthers during anthesis, and also lays foundation for breeding thermotolerant varieties via molecular breeding.
The Role of (E)-2-octenyl Acetate as a Pheromone of Bagrada hilaris (Burmeister): Laboratory and Field Evaluation
Authors: Arif Mokhtar Abdulsattar , Guarino Salvatore , Colazza Stefano , Peri Ezio
Published: February 2020

The pentatomid bug Bagrada hilaris is a key pest of brassicaceous crops in several areas of the world. Previous studies suggest that mate location of this species is mediated by volatile chemicals produced by males, among which the main compound is (E)-2-octenyl acetate. However, the possible attraction of males, females, and nymphs to this compound has not yet been specifically tested. In this study, we tested the response of B. hilaris females, males, and nymphs to (E)-2-octenyl acetate using an electroantennogram (EAG) and olfactometer in the presence or absence of a host plant. Moreover, (E)-2-octenyl acetate as an attractant lure in field trap bioassays was evaluated. EAG recordings showed that this compound evokes antennal responses in B. hilaris females. Olfactometer behavioral responses showed that females and nymphs were attracted to (E)-2-octenyl acetate, while males showed no attraction. In the field trap bioassays, captures were obtained in traps baited with 5 and 10 mg of (E)-2-octenyl acetate, while in traps loaded with 2 mg and control traps, there were no recorded catches. These results suggest the involvement of (E)-2-octenyl acetate in intraspecific interactions of this species.
Species Composition, Temporal Abundance and Distribution of Insect Captures Inside and Outside Commercial Peanut Shelling Facilities
Authors: Perez Lauren M. , Moore Patricia J. , Abney Mark R. , Toews Michael D.
Published: February 2020

Insect populations were studied within two commercial peanut shelling facilities located in the southeastern United States. Commercially available pheromone/kairomone-baited dome traps and pheromone-baited flight traps were deployed throughout processing and shipping portions of the shelling plants and serviced weekly over one year. Lasioderma serricorne, Tribolium castaneum, Typhaea stercorea, Carpophilus spp., Plodia interpunctella and Cadra cautella were the most common captures across locations. Lasioderma serricorne made up 87% and 88% of all captures in dome traps in plants one and two, respectively. While L. serricorne was not captured during the winter months in flight traps, it was captured with near 100% frequency in dome traps, suggesting that populations persisted throughout the year inside the facilities. Tribolium castaneum populations were active year round. Across insect species and trap type, temperature was a significant covariate for explaining variation in insect counts. After accounting for the effect of temperature, there were always more insects captured in the processing portions of the facilities compared to the shipping areas. A negative linear relationship was observed between captures of L. serricorne and T. castaneum and trap distance from in-shell peanuts entering the shelling facilities. Conversely, fungivores were more evenly distributed throughout all parts of the shelling plants. These data suggest that management efforts should be focused where in-shell peanuts enter to reduce breeding and harborage sites for grain feeding insects.
Invasion History of Sirex noctilio Based on COI Sequence: The First Six Years in China
Authors: Sun Xueting , Tao Jing , Roques Alain , Luo Youqing
Published: February 2020

Sirex noctilio F. (Hymenoptera: Siricidae: Siricinae), a new invasive species in China, is a significant international forestry pest which, transported via logs and related wood packing materials, has led to environmental damage and substantial economic loss in many countries around the world. It was first detected in China in 2013, and since then infestations have been found in 18 additional sites. Using a 322 bp fragment of the mitochondrial barcode gene COI, we studied the genetic diversity and structure of S. noctilio populations in both native and invaded ranges, with a specific focus in China. Twelve haplotypes were found across the native and invaded distribution of the pest, of which three were dominant; among these there were only one or two mutational steps between each pair of haplotypes. No obvious genetic structure was found other than in Chinese populations. China has a unique and dominant haplotype not found elsewhere, and compared with the rest of the world, the genetic structure of Chinese populations suggested a multiple invasion scenario.
Evaluation of the Factors that Promote Improved Experience and Better Outcomes of Older Adults in Intermediate Care Setting
Authors: Blendell Rona , Ojo Omorogieva
Published: February 2020

The aim of this article was to identify the main contributing factors to optimising improved experience and better outcomes for older adults participating in intermediate care setting. Background: Intermediate care is an integrated team intervention for patients experiencing an acute change in their function and well-being. Crisis intervention is one of several intermediate care pathways and provides a timely, person-centred, goal setting assessment to determine appropriate care and support for patients in the community. Method: This systematic review was conducted using key search terms and Boolean operators. A Critical Appraisal Skills Programme (CASP) tool was used to evaluate the studies and the data was extracted and synthesised systematically to develop themes relating to the research question. Results: Seven qualitative primary research studies and one mixed methods study were identified. The main themes were ‘communicating with patients’ and ‘patient participation’. Results showed neither themes are parallel entities but co-dependent. Patient-centred approaches to communication by professionals encouraged active patient participation, in turn optimising patient outcomes. Conclusion: This review showed that patient participation in intermediate care requires professionals using advanced communication skills and taking time to actively listen to what is important to the patients. In addition, poor professional communication resulted in passive patient participation. Implications for future practice are discussed.
Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development
Authors: Catale Clarissa , Gironda Stephen , Lo Iacono Luisa , Carola Valeria
Published: February 2020

The putative effects of early-life stress (ELS) on later behavior and neurobiology have been widely investigated. Recently, microglia have been implicated in mediating some of the effects of ELS on behavior. In this review, findings from preclinical and clinical literature with a specific focus on microglial alterations induced by the exposure to ELS (i.e., exposure to behavioral stressors or environmental agents and infection) are summarized. These studies were utilized to interpret changes in developmental trajectories based on the time at which the stress occurred, as well as the paradigm used. ELS and microglial alterations were found to be associated with a wide array of deficits including cognitive performance, memory, reward processing, and processing of social stimuli. Four general conclusions emerged: (1) ELS interferes with microglial developmental programs, including their proliferation and death and their phagocytic activity; (2) this can affect neuronal and non-neuronal developmental processes, which are dynamic during development and for which microglial activity is instrumental; (3) the effects are extremely dependent on the time point at which the investigation is carried out; and (4) both pre- and postnatal ELS can prime microglial reactivity, indicating a long-lasting alteration, which has been implicated in behavioral abnormalities later in life.
Association of rs699947 (−2578 C/A) and rs2010963 (−634 G/C) Single Nucleotide Polymorphisms of the VEGF Gene, VEGF-A and Leptin Serum Level, and Cardiovascular Risk in Patients with Excess Body Mass: A Case–Control Study
Authors: Skrypnik Damian , Mostowska Adrianna , Jagodziński Paweł , Bogdański Paweł
Published: February 2020

Background: Two single nucleotide polymorphisms (SNPs) of the VEGF gene, rs699947 and rs2010963, are responsible for differentiated gene expression. A mutual dependence between VEGF and leptin serum level has been observed. This study investigated the associations between the rs699947 and rs2010963 SNPs of VEGF gene, VEGF-A, and leptin serum concentrations, and cardiometabolic risk of body mass excess. Methods: In this case–control study, 212 subjects with excess body mass and 145 normal-weight controls gave blood samples and underwent anthropometric and pulse wave analysis. Genotyping of VEGF gene was carried out to analyze the rs699947 (−2578 C/A) and rs2010963 (−634 G/C) SNPs. (ClinicalTrials.gov ID: NCT04077554). Results: This study showed a significant positive correlation between serum levels of VEGF-A and leptin in individuals with excess body mass possessing the CC genotype of the rs699947 variant of the VEGF gene. It has been registered that an increase in VEGF-A serum level correlates with an increase in arterial stiffness in excess body mass patients harboring AA genotype of the rs699947 (−2578 C/A) variant of the VEGF gene. No differences in VEGF-A and leptin serum concentrations were noted between particular genotypes. Conclusions: The CC genotype of the rs699947 variant of the VEGF gene promotes a positive interdependency between leptin and VEGF-A serum levels in subjects with excess body mass.
Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation
Authors: Clahsen Thomas , Büttner Christian , Hatami Niloofar , Reis André , Cursiefen Claus
Published: February 2020

Under normal conditions, the cornea, being the transparent “windscreen” of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem- and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem- and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.
Acute Alcohol Effects on Response Inhibition Depend on Response Automatization, but not on GABA or Glutamate Levels in the ACC and Striatum
Authors: Bensmann Wiebke , Zink Nicolas , Werner Annett , Beste Christian , Stock Ann-Kathrin
Published: February 2020

Alcohol increases GABAergic signaling and decreases glutamatergic signaling in the brain. Variations in these neurotransmitter levels may modulate/predict executive functioning. Matching this, strong impairments of response inhibition are one of the most consistently reported cognitive/behavioral effects of acute alcohol intoxication. However, it has never been investigated whether baseline differences in these neurotransmitters allow to predict how much alcohol intoxication impairs response inhibition, and whether this is reflected in neurophysiological measures of cognitive control. We used MR spectroscopy to assess baseline (i.e., sober) GABA and glutamate levels in the anterior cingulate cortex (ACC) and striatum in n = 30 healthy young males, who were subsequently tested once sober and once intoxicated (1.01 permille). Inhibition was assessed with the sustained attention to response task (SART). This paradigm also allows to examine the effect of different degrees of response automatization, which is a known modulator for response inhibition, but does not seem to be substantially impaired during acute intoxication. As a neurophysiological correlate of response inhibition and control, we quantified EEG-derived theta band power and located its source using beamforming analyses. We found that alcohol-induced response inhibition deficits only occurred in the case of response automatization. This was reflected by decreased theta band activity in the left supplementary motor area (SMA), which may reflect modulations in the encoding of a surprise signal in response to inhibition cues. However, we did not find that differences in baseline (i.e., sober) GABA or glutamate levels significantly modulated differences in the size of alcohol-induced inhibition deficits.
Canopy Height Estimation at Landsat Resolution Using Convolutional Neural Networks
Authors: Shah Syed Aamir Ali , Manzoor Muhammad Asif , Bais Abdul
Published: February 2020

Forest structure estimation is very important in geological, ecological and environmental studies. It provides the basis for the carbon stock estimation and effective means of sequestration of carbon sources and sinks. Multiple parameters are used to estimate the forest structure like above ground biomass, leaf area index and diameter at breast height. Among all these parameters, vegetation height has unique standing. In addition to forest structure estimation it provides the insight into long term historical changes and the estimates of stand age of the forests as well. There are multiple techniques available to estimate the canopy height. Light detection and ranging (LiDAR) based methods, being the accurate and useful ones, are very expensive to obtain and have no global coverage. There is a need to establish a mechanism to estimate the canopy height using freely available satellite imagery like Landsat images. Multiple studies are available which contribute in this area. The majority use Landsat images with random forest models. Although random forest based models are widely used in remote sensing applications, they lack the ability to utilize the spatial association of neighboring pixels in modeling process. In this research work, we define Convolutional Neural Network based model and analyze that model for three test configurations. We replicate the random forest based setup of Grant et al., which is a similar state-of-the-art study, and compare our results and show that the convolutional neural networks (CNN) based models not only capture the spatial association of neighboring pixels but also outperform the state-of-the-art.
Qualitative Analysis of Multi-Terms Fractional Order Delay Differential Equations via the Topological Degree Theory
Authors: Sher Muhammad , Shah Kamal , Fečkan Michal , Khan Rahmat Ali
Published: February 2020

With the help of the topological degree theory in this manuscript, we develop qualitative theory for a class of multi-terms fractional order differential equations (FODEs) with proportional delay using the Caputo derivative. In the same line, we will also study various forms of Ulam stability results. To clarify our theocratical analysis, we provide three different pertinent examples.
Permeation Properties of Ions through Inorganic Silica-Based Membranes
Authors: Yoshiura Junko , Ishii Katsunori , Saito Yuta , Nagataki Takaya , Nagataki Yuhei , Ikeda Ayumi , Nomura Mikihiro
Published: February 2020

The development of inorganic membranes has mainly found applicability in liquid separation technologies. However, only a few reports cite the permeation and separation of liquids through inorganic nanofiltration membranes compared with the more popular microfiltration membranes. Herein, we prepared silica membranes using 3,3,3-trifluoropropyltrimethoxysilane (TFPrTMOS) to investigate its liquid permeance performance using four different ion solutions (i.e., NaCl, Na2SO4, MgCl2, and MgSO4). The TFPrTMOS-derived membranes were deposited above a temperature of 175 °C, where the deposition behavior of TFPrTMOS was dependent on the organic functional groups decomposition temperature. The highest membrane rejection was from NaCl at 91.0% when deposited at 200 °C. For anions, the SO42− rejections were the greatest. It was also possible to separate monovalent and divalent anions, as the negatively charged groups on the membrane surfaces retained pore sizes >1.48 nm. Ions were also easily separated by molecular sieving below a pore size of 0.50 nm. For the TFPrTMOS-derived membrane deposited at 175 °C, glucose showed 67% rejection, which was higher than that achieved through the propyltrimethoxysilane membrane. We infer that charge exclusion might be due to the dissociation of hydroxyl groups resulting from decomposition of organic groups. Pore size and organic functional group decomposition were found to be important for ion permeation.
Electrodischarge Drilling of Microholes in c-BN
Authors: Wyszynski Dominik , Bizon Wojciech , Miernik Krzysztof
Published: February 2020

Cubic boron nitride (c-BN) is a “difficult-to-cut” material. High precision machining of this material is problematic because it is difficult to control the material removal rate and maintain acceptable accuracy. This paper describes an application of electrodischarge machining (EDM) for drilling micro holes in c-BN. The goal of this research was to determine a set of parameters and technical specifications for such a process. We used an isoenergetic transistor power supply with a microsecond voltage pulse generator and a tungsten tool electrode of diameter d = 381 μm. Each hole was drilled for 10 min. The holes did not exceed 410 μm in diameter and were at least 1000 μm deep. The process was carried out in a hydrocarbon dielectric liquid. We assess the quality of the holes from a qualitative and quantitative point of view. The results show that electrodischarge is a precise, accurate, and efficient method for machining c-BN.
Peptide Nucleic Acids and Gene Editing: Perspectives on Structure and Repair
Authors: Economos Nicholas G. , Oyaghire Stanley , Quijano Elias , Ricciardi Adele S. , Saltzman W. Mark , Glazer Peter M.
Published: February 2020

Unusual nucleic acid structures are salient triggers of endogenous repair and can occur in sequence-specific contexts. Peptide nucleic acids (PNAs) rely on these principles to achieve non-enzymatic gene editing. By forming high-affinity heterotriplex structures within the genome, PNAs have been used to correct multiple human disease-relevant mutations with low off-target effects. Advances in molecular design, chemical modification, and delivery have enabled systemic in vivo application of PNAs resulting in detectable editing in preclinical mouse models. In a model of β-thalassemia, treated animals demonstrated clinically relevant protein restoration and disease phenotype amelioration, suggesting a potential for curative therapeutic application of PNAs to monogenic disorders. This review discusses the rationale and advances of PNA technologies and their application to gene editing with an emphasis on structural biochemistry and repair.
Smart, Tunable CQDs with Antioxidant Properties for Biomedical Applications—Ecofriendly Synthesis and Characterization
Authors: Janus Łukasz , Radwan-Pragłowska Julia , Piątkowski Marek , Bogdał Dariusz
Published: February 2020

Carbon quantum dots (CQDs) are nanoobjects of a size below 10 nm. Due to their favorable features, such as tunable luminescence, unique optical properties, water solubility, and lack of cytotoxicity, they are willingly applied in biomedicine. They can be obtained via bottom-up and top-down methods. However, to increase their quantum yield they must undergo post-processing. The aim of the following research was to obtain a new type of CQDs modified with a rhodamine b derivative to enhance their fluorescence performance without biocompability deterioration. For their preparation glucose was used as a precursor and four different carbonizing agents which affected semi- and final products luminescence properties. The ready nanomaterials were investigated over their chemical structure by FTIR and NMR, whereas morphology was investigated by the TEM method. Their optical properties were determined by UV–VIS spectroscopy. Fluorescence behavior, photo- and pH-stability, as well as solvatochromism showed their applicability in various biomedical applications due to the controlled properties. The samples exhibited excellent antioxidant activity and lack of cytotoxicity on L929 mouse fibroblasts. The results showed that proposed strategy enables preparation of the superior nanomaterials with outstanding luminescence properties such as quantum yield up to 17% which can be successfully applied in cell labelling, bioimaging, and theranostics.
Current Approaches to and Future Perspectives on Methomyl Degradation in Contaminated Soil/Water Environments
Authors: Lin Ziqiu , Zhang Wenping , Pang Shimei , Huang Yaohua , Mishra Sandhya , Bhatt Pankaj , Chen Shaohua
Published: February 2020

Methomyl is a broad-spectrum oxime carbamate commonly used to control arthropods, nematodes, flies, and crop pests. However, extensive use of this pesticide in agricultural practices has led to environmental toxicity and human health issues. Oxidation, incineration, adsorption, and microbial degradation methods have been developed to remove insecticidal residues from soil/water environments. Compared with physicochemical methods, biodegradation is considered to be a cost-effective and ecofriendly approach to the removal of pesticide residues. Therefore, micro-organisms have become a key component of the degradation and detoxification of methomyl through catabolic pathways and genetic determinants. Several species of methomyl-degrading bacteria have been isolated and characterized, including Paracoccus, Pseudomonas, Aminobacter, Flavobacterium, Alcaligenes, Bacillus, Serratia, Novosphingobium, and Trametes. The degradation pathways of methomyl and the fate of several metabolites have been investigated. Further in-depth studies based on molecular biology and genetics are needed to elaborate their role in the evolution of novel catabolic pathways and the microbial degradation of methomyl. In this review, we highlight the mechanism of microbial degradation of methomyl along with metabolic pathways and genes/enzymes of different genera.
Temperature Effect on the Adsorption and Volumetric Properties of Aqueous Solutions of Kolliphor®ELP
Authors: Szymczyk Katarzyna , Szaniawska Magdalena , Krawczyk Joanna
Published: February 2020

Density, viscosity and surface tension of Kolliphor® ELP, the nonionic surfactant aqueous solutions were measured at temperature T = 293–318 K and at 5K interval. Steady-state fluorescence measurements have been also made using pyrene as a probe. On the basis of the obtained results, a number of thermodynamic, thermo-acoustic and anharmonic parameters of the studied surfactant have been evaluated and interpreted in terms of structural effects and solute–solvent interactions. The results suggest that the molecules of studied surfactant at concentrations higher than the critical micelle concentration act as structure makers of the water structure.
Identification and Characterization of Nematicidal Volatile Organic Compounds from Deep-Sea Virgibacillus dokdonensis MCCC 1A00493
Authors: Huang Dian , Yu Chen , Shao Zongze , Cai Minmin , Li Guangyu , Zheng Longyu , Yu Ziniu , Zhang Jibin
Published: February 2020

Root-knot nematode diseases cause severe yield and economic losses each year in global agricultural production. Virgibacillus dokdonensis MCCC 1A00493, a deep-sea bacterium, shows a significant nematicidal activity against Meloidogyne incognita in vitro. However, information about the active substances of V. dokdonensis MCCC 1A00493 is limited. In this study, volatile organic compounds (VOCs) from V. dokdonensis MCCC 1A00493 were isolated and analyzed through solid-phase microextraction and gas chromatography–mass spectrometry. Four VOCs, namely, acetaldehyde, dimethyl disulfide, ethylbenzene, and 2-butanone, were identified, and their nematicidal activities were evaluated. The four VOCs had a variety of active modes on M. incognita juveniles. Acetaldehyde had direct contact killing, fumigation, and attraction activities; dimethyl disulfide had direct contact killing and attraction activities; ethylbenzene had an attraction activity; and 2-butanone had a repellent activity. Only acetaldehyde had a fumigant activity to inhibit egg hatching. Combining this fumigant activity against eggs and juveniles could be an effective strategy to control the different developmental stages of M. incognita. The combination of direct contact and attraction activities could also establish trapping and killing strategies against root-knot nematodes. Considering all nematicidal modes or strategies, we could use V. dokdonensis MCCC 1A00493 to set up an integrated strategy to control root-knot nematodes.
A Novel Dimeric Exoglucanase (GH5_38): Biochemical and Structural Characterisation towards its Application in Alkyl Cellobioside Synthesis
Authors: Mafa Mpho S. , Dirr Heinrich W. , Malgas Samkelo , Krause Rui W. M. , Rashamuse Konanani , Pletschke Brett I.
Published: February 2020

An exoglucanase (Exg-D) from the glycoside hydrolase family 5 subfamily 38 (GH5_38) was heterologously expressed and structurally and biochemically characterised at a molecular level for its application in alkyl glycoside synthesis. The purified Exg-D existed in both dimeric and monomeric forms in solution, which showed highest activity on mixed-linked β-glucan (88.0 and 86.7 U/mg protein, respectively) and lichenin (24.5 and 23.7 U/mg protein, respectively). They displayed a broad optimum pH range from 5.5 to 7 and a temperature optimum from 40 to 60 °C. Kinetic studies demonstrated that Exg-D had a higher affinity towards β-glucan, with a Km of 7.9 mg/mL and a kcat of 117.2 s−1, compared to lichenin which had a Km of 21.5 mg/mL and a kcat of 70.0 s−1. The circular dichroism profile of Exg-D showed that its secondary structure consisted of 11% α-helices, 36% β-strands and 53% coils. Exg-D performed transglycosylation using p-nitrophenyl cellobioside as a glycosyl donor and several primary alcohols as acceptors to produce methyl-, ethyl- and propyl-cellobiosides. These products were identified and quantified via thin-layer chromatography (TLC) and liquid chromatography–mass spectrometry (LC-MS). We concluded that Exg-D is a novel and promising oligomeric glycoside hydrolase for the one-step synthesis of alkyl glycosides with more than one monosaccharide unit.
Selection of Aptamers Specific for DEHP Based on ssDNA Library Immobilized SELEX and Development of Electrochemical Impedance Spectroscopy Aptasensor
Authors: Lu Qi , Liu Xixia , Hou Jianjun , Yuan Qiuxue , Li Yani , Chen Sirui
Published: February 2020

A selection of aptamers specific for di(2-ethylhexyl) phthalate (DEHP) and development of electrochemical impedance spectroscopy (EIS) aptasensor are described in this paper. The aptamers were selected from an immobilized ssDNA library using the systematic evolution of ligands by exponential enrichment (SELEX). The enrichment was monitored using real-time quantitative PCR (Q-PCR), and the aptamers were identified by high-throughput sequencing (HTS), gold nanoparticles (AuNPs) colorimetric assay, and localized surface plasmon resonance (LSPR). The EIS aptasensor was developed to detect DEHP in water samples. After eight rounds of enrichment, HTS, AuNPs colorimetric assay, and LSPR analysis indicated that four aptamers had higher binding activity, and aptamer 31 had the highest affinity (Kd = 2.26 ± 0.06 nM). The EIS aptasensor had a limit of detection (LOD) of 0.103 pg/mL with no cross-reactivity to DEHP analogs and a mean recovery of 76.07% to 141.32% for detection of DEHP in water samples. This aptamer is novel with the highest affinity and sensitivity.
Recent Advances in Copper Catalyzed Alcohol Oxidation in Homogeneous Medium
Authors: Silva Telma F. S. , Martins Luísa M. D. R. S.
Published: February 2020

The development of sustainable processes and products through innovative catalytic materials and procedures that allow a better use of resources is undoubtedly one of the most significant issues facing researchers nowadays. Environmental and economically advanced catalytic processes for selective oxidation of alcohols are currently focused on designing new catalysts able to activate green oxidants (dioxygen or peroxides) and applying unconventional conditions of sustainable significance, like the use of microwave irradiation as an alternative energy source. This short review aims to provide an overview of the recently (2015–2020) discovered homogeneous aerobic and peroxidative oxidations of primary and secondary alcohols catalyzed by copper complexes, highlighting new catalysts with potential application in sustainable organic synthesis, with significance in academia and industry.
Effect of Polyvinyl Alcohol on the Rheological Properties of Cement Mortar
Authors: Liu Fang , Wang Baomin , Xing Yunqing , Zhang Kunkun , Jiang Wei
Published: February 2020

Polyvinyl alcohol (PVA) is a kind of water-soluble polymer, which has been widely used in different industries due to its excellent mechanical and chemical properties. In this paper, the effects of polyvinyl alcohol with different hydrolysis and polymerization degrees on the rheological properties of cement mortar are studied. The results show that the rheological properties of PVA-modified cement mortar can be described by the modified Bingham model. The yield stress of modified cement mortar is less than that of unmodified mortar when the degree of polymerization and the content of PVA are small. With the increase of polyvinyl alcohol content and polymerization degree, the yield stress and plastic viscosity of modified cement mortar increase sharply, which are larger than those of the unmodified cement mortar. However, the effect of hydrolysis degree of PVA on yield stress and plastic viscosity of modified cement mortar is not obvious.
Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile
Authors: Puglia Carmelo , Santonocito Debora , Ostacolo Carmine , Maria Sommella Eduardo , Campiglia Pietro , Carbone Claudia , Drago Filippo , Pignatello Rosario , Bucolo Claudio
Published: February 2020

The present work was aimed for the preparation of a stable nanostructured lipid carrier (NLC) system for the delivery of N-palmitoylethanolamide (PEA) to the back of the eye. PEA is an interesting natural compound showing anti-inflammatory and neuroprotective activities. The limits of PEA (poor solubility and high instability) justify its nanoencapsulation into drug delivery systems. Two different well-known techniques were compared to formulate NLC: the high shear homogenization technique (HSH) and the method based on a combination of HSH technique and ultrasonication (HSH/US). Nanoparticles were evaluated in relation to mean size, homogeneity, surface charge, and physical stability by Turbiscan technology. Retinal distribution of PEA was carried out in a rat eye after single instillation of PEA-NLC ophthalmic formulation. The novel formulation delivered remarkable levels of PEA to the retina. Lastly, topical administration of PEA-NLC ophthalmic formulation was able to significantly inhibits retinal tumor necrosis factor-α (TNF-α) levels in streptozotocin-induced diabetic rats. The present findings suggest that the novel ophthalmic formulation may be useful for the treatment of retinal diseases such as diabetic retinopathy. Clinical studies are in progress to evaluate this possibility.
Lanthanide-Doped SPIONs Bioconjugation with Trastuzumab for Potential Multimodal Anticancer Activity and Magnetic Hyperthermia
Authors: Gawęda Weronika , Osial Magdalena , Żuk Michał , Pękała Marek , Bilewicz Aleksander , Krysinski Pawel
Published: February 2020

Iron oxide-based nanoparticles have been modified in their core with holmium(III) in an amount affecting only slightly their magnetic properties. Nanoparticles were conjugated covalently with biomolecule of trastuzumab (Herceptin®), the monoclonal antibody that recognizes cancer cells overexpressing HER2 receptors targeting such nanoparticles to the specified tumor tissues. Systematic studies of Ho3+-doped bioconjugates were carried out as a preliminary step for future replacement of ‘cold’ Ho with 166Ho radionuclide, emitting ‘soft’ beta(-) radiation for possible targeted radionuclide therapy. Physicochemical properties of the obtained bioconjugates were subsequently tested for use in magnetic hyperthermia, considered as an effective, low-invasiveness anticancer therapy. With such a system we expect to achieve both: active targeting and multimodal action by simultaneous internal and localized irradiation and magnetic hyperthermia of specific cancers.
The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance
Authors: Winiarska-Mieczan Anna , Baranowska-Wójcik Ewa , Kwiecień Małgorzata , Grela Eugeniusz R. , Szwajgier Dominik , Kwiatkowska Katarzyna , Kiczorowska Bożena
Published: February 2020

Neurodegenerative diseases are progressive diseases of the nervous system that lead to neuron loss or functional disorders. Neurodegenerative diseases require long-term, sometimes life-long pharmacological treatment, which increases the risk of adverse effects and a negative impact of pharmaceuticals on the patients’ general condition. One of the main problems related to the treatment of this type of condition is the limited ability to deliver drugs to the brain due to their poor solubility, low bioavailability, and the effects of the blood-brain barrier. Given the above, one of the main objectives of contemporary scientific research focuses on the prevention of neurodegenerative diseases. As disorders related to the competence of the antioxidative system are a marker in all diseases of this type, the primary prophylactics should entail the use of exogenous antioxidants, particularly ones that can be used over extended periods, regardless of the patient’s age, and that are easily available, e.g., as part of a diet or as diet supplements. The paper analyzes the significance of the oxidoreductive balance in the pathogenesis of neurodegenerative diseases. Based on information published globally in the last 10 years, an analysis is also provided with regard to the impact of exogenous antioxidants on brain functions with respect to the prevention of this type of diseases.