bluuebunny/crossref_metadata_2025 huggingface dataset:
Approaching Higher Dimension Imaging Data Using Cluster-Based Hierarchical Modeling in Patients with Heart Failure Preserved Ejection Fraction
Authors: Kobayashi Yukari , Tremblay-Gravel Maxime , Boralkar Kalyani A. , Li Xiao , Nishi Tomoko , Amsallem Myriam , Moneghetti Kegan J. , Bouajila Sara , Selej Mona , Ozen Mehmet O. , Demirci Utkan , Ashley Euan , Wheeler Matthew , Knowlton Kirk U. , Kouznetsova Tatiana , Haddad Francois
Published: July 2019

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality, accounting for the majority of heart failure (HF) hospitalization. To identify the most complementary predictors of mortality among clinical, laboratory and echocardiographic data, we used cluster based hierarchical modeling. Using Stanford Translational Research Database, we identified patients hospitalized with HFpEF between 2005 and 2016 in whom echocardiogram and NT-proBNP were both available at the time of admission. Comprehensive echocardiographic assessment including left ventricular longitudinal strain (LVLS), right ventricular function and right ventricular systolic pressure (RVSP) was performed. The outcome was defined as all-cause mortality. Among patients identified, 186 patients with complete echocardiographic assessment were included in the analysis. The cohort included 58% female, with a mean age of 78.7 ± 13.5 years, LVLS of −13.3 ± 2.5%, an estimated RVSP of 38 ± 13 mmHg. Unsupervised cluster analyses identified six clusters including ventricular systolic-function cluster, diastolic-hemodynamic cluster, end-organ function cluster, vital-sign cluster, complete blood count and sodium clusters. Using a stepwise hierarchical selection from each cluster, we identified NT-proBNP (standard hazard ratio [95%CI] = 1.56 [1.17–2.08]) and RVSP (1.37 [1.09–1.78]) as independent correlates of outcome. When adding these parameters to the well validated Get with the Guideline Heart Failure risk score, the Chi-square was significantly improved (p = 0.01). In conclusion, NT-proBNP and RVSP were independently predictive in HFpEF among clinical, imaging, and biomarker parameters. Cluster-based hierarchical modeling may help identify the complementally predictive parameters in small cohorts with higher dimensional clinical data.
Proteo-metabolomic investigation of transgenic rice unravels metabolic alterations and accumulation of novel proteins potentially involved in defence against Rhizoctonia solani
Authors: Karmakar Subhasis , Datta Karabi , Molla Kutubuddin Ali , Gayen Dipak , Das Kaushik , Sarkar Sailendra Nath , Datta Swapan K.
Published: July 2019

The generation of sheath blight (ShB)-resistant transgenic rice plants through the expression of Arabidopsis NPR1 gene is a significant development for research in the field of biotic stress. However, to our knowledge, regulation of the proteomic and metabolic networks in the ShB-resistant transgenic rice plants has not been studied. In the present investigation, the relative proteome and metabolome profiles of the non–transformed wild-type and the AtNPR1-transgenic rice lines prior to and subsequent to the R. solani infection were investigated. Total proteins from wild type and transgenic plants were investigated using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS). The metabolomics study indicated an increased abundance of various metabolites, which draws parallels with the proteomic analysis. Furthermore, the proteome data was cross-examined using network analysis which identified modules that were rich in known as well as novel immunity-related prognostic proteins, particularly the mitogen-activated protein kinase 6, probable protein phosphatase 2C1, probable trehalose-phosphate phosphatase 2 and heat shock protein. A novel protein, 14–3–3GF14f was observed to be upregulated in the leaves of the transgenic rice plants after ShB infection, and the possible mechanistic role of this protein in ShB resistance may be investigated further.
Inverse dose-rate effect of ionising radiation on residual 53BP1 foci in the eye lens
Authors: Barnard Stephen G. R. , McCarron Roisin , Moquet Jayne , Quinlan Roy , Ainsbury Elizabeth
Published: July 2019

The influence of dose rate on radiation cataractogenesis has yet to be extensively studied. One recent epidemiological investigation suggested that protracted radiation exposure increases radiation-induced cataract risk: cumulative doses of radiation mostly <100 mGy received by US radiologic technologists over 5 years were associated with an increased excess hazard ratio for cataract development. However, there are few mechanistic studies to support and explain such observations. Low-dose radiation-induced DNA damage in the epithelial cells of the eye lens (LECs) has been proposed as a possible contributor to cataract formation and thus visual impairment. Here, 53BP1 foci was used as a marker of DNA damage. Unexpectedly, the number of 53BP1 foci that persisted in the mouse lens samples after γ-radiation exposure increased with decreasing dose-rate at 4 and 24 h. The C57BL/6 mice were exposed to 0.5, 1 and 2 Gy ƴ-radiation at 0.063 and 0.3 Gy/min and also 0.5 Gy at 0.014 Gy/min. This contrasts the data we obtained for peripheral blood lymphocytes collected from the same animal groups, which showed the expected reduction of residual 53BP1 foci with reducing dose-rate. These findings highlight the likely importance of dose-rate in low-dose cataract formation and, furthermore, represent the first evidence that LECs process radiation damage differently to blood lymphocytes.
The possible involvement of oxidative stress in the oocyte ageing process in goldfish Carassius auratus (Linnaeus, 1758)
Authors: Samarin Azadeh Mohagheghi , Samarin Azin Mohagheghi , Østbye Tone-Kari Knutsdatter , Ruyter Bente , Sampels Sabine , Burkina Viktoriia , Blecha Miroslav , Policar Tomas
Published: July 2019

Decreasing egg quality following oocyte ageing is a major restricting factor for the breeding programs. The mechanisms behind this process has not yet been clarified. To examine the possible involvement of oxidative stress in the oocyte ageing process, the relative mRNA abundance of specific transcripts were determined in oocytes collected from 6 females and incubated in vitro for 18 hours post stripping at 20 °C in goldfish Carassius auratus. During the 18 hour-post-stripping ageing of the oocytes, relative mRNA levels of candidate transcripts involved in oxidative injury, mitochondrial function and stress response, cell cycles, apoptosis, reproduction and germ line speciation and developmental competence were measured by real-time PCR. None of the relative mRNA abundance of the examined genes were significantly altered through oocyte ageing. In addition, the amount of thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation, did not change over time following stripping. The activity of the antioxidant enzymes also remained constant during oocyte ageing. The results of the current study indicated that oxidative stress unlikely plays a role as an initiator or promotor in the progress of oocyte ageing in goldfish.
Shortening time scale to reduce thermal effects in quantum transistors
Authors: de Ponte M. A. , Santos Alan C.
Published: July 2019

In this article, we present a quantum transistor model based on a network of coupled quantum oscillators destined to quantum information processing tasks in linear optics. To this end, we show in an analytical way how a set of N quantum oscillators (data-bus) can be used as an optical quantum switch, in which the energy gap of the data bus oscillators plays the role of an adjustable “potential barrier”. This enables us to “block or allow” the quantum information to flow from the source to the drain. In addition, we discuss how this device can be useful for implementing single qubit phase-shift quantum gates with high fidelity, so that it can be used as a useful tool. To conclude, during the study of the performance of our device when considering the interaction of this with a thermal reservoir, we highlight the important role played by the set of oscillators which constitute the data-bus in reducing the unwanted effects of the thermal reservoir. This is achieved by reducing the information exchange time (shortening time scale) between the desired oscillators. In particular, we have identified a non-trivial criterion in which the ideal size of the data-bus can be obtained so that it presents the best possible performance. We believe that our study can be perfectly adapted to a large number of thermal reservoir models.
Co-cultivation of the marine sponge Halichondria panicea and its associated microorganisms
Authors: Knobloch Stephen , Jóhannsson Ragnar , Marteinsson Viggó
Published: July 2019

Marine sponges host bacterial symbionts with biotechnological potential, yet isolation of true sponge symbionts remains difficult due to their host dependency. Moreover, attempts to grow sponges for their pharmacologically-active compounds outside of their habitat often results in a shift of their microbial community. In this study we evaluate suitable sponge cultivation methods that allow maintenance of both the marine sponge Halichondria panicea and its associated bacteria in an ex situ environment. In addition, we present a method for co-cultivation of sponge explants and microbes separated by a membrane in a multi-chamber device. Tests on ex situ cultivation of H. panicea under different controlled conditions showed that only high water exchange rates in the aquarium enabled maintenance of its dominant symbiont “Candidatus Halichondribacter symbioticus” at a high relative abundance in the sponge body, a prerequisite for co-cultivation. The bacterial enrichment retrieved from co-cultivation contained bacteria from nine different classes in addition to sequences corresponding to “Ca. H. symbioticus”. This represents an increase of the cultivable bacterial classes from H. panicea compared to standard isolation techniques on solid media plates. The current study provides insights into sponge-microbe maintenance under ex situ conditions and proposes a new method for the isolation of sponge-associated bacteria.
Evolution and diversity of alpha-carbonic anhydrases in the mantle of the Mediterranean mussel (Mytilus galloprovincialis)
Authors: Cardoso João C. R. , Ferreira Vinicius , Zhang Xushuai , Anjos Liliana , Félix Rute C. , Batista Frederico M. , Power Deborah M.
Published: July 2019

The α-carbonic anhydrases (α-CAs) are a large and ancient group of metazoan-specific enzymes. They generate bicarbonate from metabolic carbon dioxide and through calcium carbonate crystal formation play a key role in the regulation of mineralized structures. To better understand how α-CAs contribute to shell mineralization in the marine Mediterranean mussel (Mytilus galloprovincialis) we characterized them in the mantle. Phylogenetic analysis revealed that mollusc α-CA evolution was affected by lineage and species-specific events. Ten α-CAs were found in the Mediterranean mussel mantle and the most abundant form was named, MgNACR, as it grouped with oyster nacreins (NACR). Exposure of the Mediterranean mussel to reduced water salinity (18 vs 37 ppt), caused a significant reduction (p < 0.05) in mantle esterase activity and MgNACR transcript abundance (p < 0.05). Protonograms revealed multiple proteins in the mantle with α–CA hydratase activity and mapped to a protein with a similar size to that deduced for monomeric MgNACR. Our data indicate that MgNACR is a major α–CA enzyme in mantle and that by homology with oyster nacreins likely regulates mussel shell production. We propose that species-dependent α-CA evolution may contribute to explain the diversity of bivalve shell structures and their vulnerability to environmental changes.
Overweight/obesity affects histological features and inflammatory gene signature of synovial membrane of Rheumatoid Arthritis
Authors: Alivernini Stefano , Tolusso Barbara , Gigante Maria Rita , Petricca Luca , Bui Laura , Fedele Anna Laura , Di Mario Clara , Benvenuto Roberta , Federico Francesco , Ferraccioli Gianfranco , Gremese Elisa
Published: July 2019

Overweight/obesity influence disease burden and clinical outcome of Rheumatoid Arthritis (RA). The impact of overweight/obesity on synovial tissue (ST) inflammation is largely unknown. Here, we investigated the histological and transcriptional signature of ST obtained from RA in different disease phases (disease onset, failure to first-line conventional DMARDs and in sustained clinical and ultrasound remission) finding that overweight/obese DMARDs naive RA showed higher likelihood of follicular synovitis, higher IHC scores for sublining inflammatory cells (CD68+, CD21+ and CD20+) and higher IL-1RA plasma levels than normal weight RA. Regardless to the synovitis pattern, overweight/obese DMARDs naive RA showed a worse clinical response to “Treat-to-target” (T2T) than normal weight RA at 6 and 12 months follow-up. Conversely, MTX-IR RA did not show significant differences in synovial inflammation based on BMI category. Overweight/obese RA in stable clinical and US remission showed higher degree of residual synovitis in terms of sublining CD68+, CD20+ cells and lining and sublining CD3+ compared to normal weight RA. Finally, gene expression profile analysis revealed that ST of overweight/obese DMARDs naive RA is enriched by CCL3 and MyD88 compared to normal weight RA in sustained disease remission, the latter correlating with BMI and IHC scores for synovial CD68+ cells. These findings suggest that indeed overweight/obese RA show higher degree of synovitis at disease onset and after remission achievement that influences the response rate to T2T and should be considered within the management of patients with RA.
Metabolomic Analysis of Skeletal Muscle in Aged Mice
Authors: Uchitomi Ran , Hatazawa Yukino , Senoo Nanami , Yoshioka Kiyoshi , Fujita Mariko , Shimizu Takahiko , Miura Shinji , Ono Yusuke , Kamei Yasutomi
Published: July 2019

Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function. To better understand changes in skeletal muscle during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice by using capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry. Principal component analysis showed clear changes in metabolites between young and aged mice. Glucose metabolism products were decreased in aged mice, specifically fructose 1,6-diphosphate (0.4-fold) and dihydroxyacetone phosphate (0.6-fold), possibly from decreased glycolytic muscle fibers. Multiple metabolic products associated with phospholipid metabolism were significantly changed in aged mice, which may reflect changes in cell membrane phospholipids of skeletal muscle. Products of polyamine metabolism, which are known to increase nucleic acid and protein synthesis, decreased in spermine (0.5-fold) and spermidine (0.6-fold) levels. By contrast, neurotransmitter levels were increased in skeletal muscle of aged mice, including acetylcholine (1.8-fold), histamine (2.6-fold), and serotonin (1.7-fold). The increase in acetylcholine might compensate for age-associated dropout of neuromuscular junctions, whereas the increases in histamine and serotonin might be due to muscle injury associated with aging. Further analysis focusing on the altered metabolites observed in this study will provide essential data for understanding aging muscles.
Transcriptome analysis identifies a robust gene expression program in the mouse intestinal epithelium on aging
Authors: Kazakevych Juri , Stoyanova Elena , Liebert Anke , Varga-Weisz Patrick
Published: July 2019

The intestinal epithelium undergoes constant regeneration driven by intestinal stem cells. How old age affects the transcriptome in this highly dynamic tissue is an important, but poorly explored question. Using transcriptomics on sorted intestinal stem cells and adult enterocytes, we identified candidate genes, which change expression on aging. Further validation of these on intestinal epithelium of multiple middle-aged versus old-aged mice highlighted the consistent up-regulation of the expression of the gene encoding chemokine receptor Ccr2, a mediator of inflammation and several disease processes. We observed also increased expression of Strc, coding for stereocilin, and dramatically decreased expression of Rps4l, coding for a ribosome subunit. Ccr2 and Rps4l are located close to the telomeric regions of chromosome 9 and 6, respectively. As only few genes were differentially expressed and we did not observe significant protein level changes of identified ageing markers, our analysis highlights the overall robustness of murine intestinal epithelium gene expression to old age.
Factors triggering queen executions in the Argentine ant
Authors: Abril Sílvia , Gómez Crisanto
Published: July 2019

Competition among queens in polygynous societies may result in queen executions or conflicts over personal reproduction. Understanding the factors that mediate the executions of ant queens should provide insight into how queen numbers are regulated in polygynous insect societies. The Argentine ant is a widespread invasive species that displays secondary polygyny, and workers execute 90% of their nestmate queens each spring. In this study, we investigated: (1) whether ambient temperature, queen number, and protein deprivation have an effect on queen executions and (2) whether workers select the queens slated for execution based on their cuticular hydrocarbon (CHC) profiles. We found that the percentage of queens executed was positively correlated with temperature and queen number but that protein deprivation did not play a role. As for queen fate, the levels of some CHCs were higher in surviving queens. One of these CHCs is associated with queen productivity (i.e egg-laying rate and ovarian index) suggesting that workers execute the least productive queens. Our findings suggest that chemical cues related to fertility signaling may mediate queen executions in Argentine ants.
Morphological features of the inferior fascicle of the anterior inferior tibiofibular ligament
Authors: Edama M. , Takeishi M. , Kurata S. , Kikumoto T. , Takabayashi T. , Hirabayashi R. , Inai T. , Ikezu M. , Kaneko F. , Kageyama I.
Published: July 2019

In this study, the inferior fascicle of the anterior inferior tibiofibular ligament (AITFL) was classified to provide basic information to help elucidate the mechanism of ankle joint anterolateral impingement, and the morphological features of each type were compared for the purpose of clarification. This investigation examined 100 feet from 52 cadavers. The AITFL was classified into four types according to the presence or absence of the inferior fascicle and the positional relationship between the AITFL and the inferior fascicle of the AITFL. The morphological features of the AITFL that were measured included the fibre bundle length, fibre bundle width, fibre bundle angle, and the distance between the joint levels. A distinct, independent inferior fascicle of the AITFL was identified in 15 feet (15%). There were no significant differences in the morphological features based on differences in the AITFL classification. Therefore, these findings suggest that the presence or absence of the inferior fascicle and the difference in the positional relationship between the AITFL and the inferior fascicle of the AITFL are less likely to be involved in impingement during ankle dorsiflexion.
An asymmetry of treatment between lotteries involving gains and losses in rhesus monkeys
Authors: Nioche Aurélien , Bourgeois-Gironde Sacha , Boraud Thomas
Published: July 2019

Decision-making in humans is known to be subject to several biases. For instance, when facing bets, humans demonstrate some asymmetry concerning their preference for the riskiest option depending on whether stakes involve potential gains or potential losses. They are indeed risk-averse for bets involving gains but risk seeking for bets involving losses. They also exhibit a distorted perception of probabilities. It is not clear whether non-human primates exhibit the same biases. Setting up a protocol that allowed two rhesus monkeys to make choices between lotteries involving either gains or losses, we demonstrated that rhesus monkeys facing bets exhibited an asymmetry in the treatment of gains and losses comparable with that of humans.
MRI-based radiomics signature is a quantitative prognostic biomarker for nasopharyngeal carcinoma
Authors: Ming Xue , Oei Ronald Wihal , Zhai Ruiping , Kong Fangfang , Du Chengrun , Hu Chaosu , Hu Weigang , Zhang Zhen , Ying Hongmei , Wang Jiazhou
Published: July 2019

This study aimed to develop prognosis signatures through a radiomics analysis for patients with nasopharyngeal carcinoma (NPC) by their pretreatment diagnosis magnetic resonance imaging (MRI). A total of 208 radiomics features were extracted for each patient from a database of 303 patients. The patients were split into the training and validation cohorts according to their pretreatment diagnosis date. The radiomics feature analysis consisted of cluster analysis and prognosis model analysis for disease free-survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Additionally, two prognosis models using clinical features only and combined radiomics and clinical features were generated to estimate the incremental prognostic value of radiomics features. Patients were clustered by non-negative matrix factorization (NMF) into two groups. It showed high correspondence with patients’ T stage (p < 0.00001) and overall stage information (p < 0.00001) by chi-squared tests. There were significant differences in DFS (p = 0.0052), OS (p = 0.033), and LRFS (p = 0.037) between the two clustered groups but not in DMFS (p = 0.11) by log-rank tests. Radiomics nomograms that incorporated radiomics and clinical features could estimate DFS with the C-index of 0.751 [0.639, 0.863] and OS with the C-index of 0.845 [0.752, 0.939] in the validation cohort. The nomograms improved the prediction accuracy with the C-index value of 0.029 for DFS and 0.107 for OS compared with clinical features only. The DFS and OS radiomics nomograms developed in our study demonstrated the excellent prognostic estimation for NPC patients with a noninvasive way of MRI. The combination of clinical and radiomics features can provide more information for precise treatment decision.
Contactless, nondestructive determination of dopant profiles of localized boron-diffused regions in silicon wafers at room temperature
Authors: Nguyen Hieu T. , Li Zhuofeng , Han Young-Joon , Basnet Rabin , Tebyetekerwa Mike , Truong Thien N. , Wu Huiting , Yan Di , Macdonald Daniel
Published: July 2019

We develop a photoluminescence-based technique to determine dopant profiles of localized boron-diffused regions in silicon wafers and solar cell precursors employing two excitation wavelengths. The technique utilizes a strong dependence of room-temperature photoluminescence spectra on dopant profiles of diffused layers, courtesy of bandgap narrowing effects in heavily-doped silicon, and different penetration depths of the two excitation wavelengths in silicon. It is fast, contactless, and nondestructive. The measurements are performed at room temperature with micron-scale spatial resolution. We apply the technique to reconstruct dopant profiles of a large-area (1 cm × 1 cm) boron-diffused sample and heavily-doped regions (30 μm in diameter) of passivated-emitter rear localized-diffused solar cell precursors. The reconstructed profiles are confirmed with the well-established electrochemical capacitance voltage technique. The developed technique could be useful for determining boron dopant profiles in small doped features employed in both photovoltaic and microelectronic applications.
Nucleophilic reactivity of a copper(II)-hydroperoxo complex
Authors: Kim Bohee , Jeong Donghyun , Ohta Takehiro , Cho Jaeheung
Published: July 2019

Copper(II)-hydroperoxo species are often detected as key intermediates in metalloenzymes and biomimetic compounds containing copper. However, the only reactivity has previously been observed for the copper(II)-hydroperoxo complexes is electrophilic, occurring through O-O bond cleavage. Here we report that a mononuclear end-on copper(II)-hydroperoxo complex, which has been successfully characterized by various physicochemical methods including UV-vis, rRaman, CSI-MS and EPR, is a reactive oxidant that utilizes a nucleophilic mechanism. In addition, DFT calculations fully support the electronic structure of this complex as a copper(II)-hydroperoxo complex with trigonal bipyramidal coordination geometry. A positive Hammett ρ value (2.0(3)) is observed in the reaction of copper(II)-hydroperoxo complex with para-substituted acyl chlorides, which clearly indicates nucleophilic character for the copper(II)-hydroperoxo complex. The copper(II)-hydroperoxo complex is an especially reactive oxidant in aldehyde deformylation with 2-PPA and CCA relative to the other metal-bound reactive oxygen species reported so far. The observation of nucleophilic reactivity for a copper(II)-hydroperoxo species expands the known chemistry of metal-reactive oxygen species.
The Fate of Micronuclei and Micronucleated Cells
Authors: Stopper H. , Hintzsche H.
Published: July 2019

While the mechanisms of micronucleus induction have been the objectives of many investigations, the fate of micronuclei or micronucleus-containing cells is still very uncertain. They may be the origin of malignant transformation resulting in tumor development or they may be prone to cell death, not harming the organism. Available information regarding the survival of micronucleated cells, the elimination or reintegration of micronuclei, the role of apoptosis and chromothripsis in this context, and possible influences of test substances and cell types is summarized here.
Micronuclei and Their Association with Infertility, Pregnancy Complications, Developmental Defects, Anaemias, Inflammation, Diabetes, Chronic Kidney Disease, Obesity, Cardiovascular Disease, Neurodegenerative Diseases and Cancer
Authors: Bonassi Stefano , Fenech Michael
Published: July 2019

Micronuclei (MN) are a strong cytogenetic indicator of a catastrophic change in the genetic structure and stability of a cell because they originate from either chromosome breaks or whole chromosomes that have been lost from the main nucleus during cell division. The resulting genetic abnormalities can to lead to cellular malfunction, altered gene expression and impaired regenerative capacity. Furthermore, MN are increased as a consequence of genetic defects in DNA repair, deficiency in micronutrients required for DNA replication and repair and exposure to genotoxic chemicals and ultraviolet or ionising radiation. For all of these reasons, the measurement of MN has become one of the best-established methods to measure DNA damage in humans at the cytogenetic level. This chapter is a narrative review of the current evidence for the association of increased MN frequency with developmental and degenerative diseases. In addition, important knowledge gaps are identified, and recommendations for future studies required to consolidate the evidence are provided. The great majority of published studies show a significant association of increased MN in lymphocytes and/or buccal cells with infertility, pregnancy complications, developmental defects, anaemias, inflammation, diabetes, cardiovascular disease, kidney disease, neurodegenerative diseases and cancer. However, the strongest evidence is from prospective studies showing that MN frequency in lymphocytes predicts cancer risk and cardiovascular disease mortality.
Micronucleus Cytome Assay with Buccal Cells
Authors: Bolognesi Claudia
Published: July 2019

The buccal micronucleus cytome (BMNCyt) assay is a minimally invasive cytogenetic technique to evaluate genomic damage, cell differentiation and cell death in human studies. This assay has been successfully applied in the biomonitoring of occupational or environmental exposure to genotoxic agents by inhalation or by direct contact. Possible clinical applications in prescreening and in the follow-up of oral diseases and cancer have been also envisaged. The micronucleus (MN) assay in buccal cells, as a surrogate tissue, to evaluate risk/susceptibility for cancer and other degenerative diseases deserves further investigation. A standardized protocol for buccal cell collection, slide preparation and scoring of cell types and nuclear anomalies has been established. Detailed scoring criteria and a comprehensive gallery of photomicrographs for cellular and nuclear scoring have also been developed to complement the protocol. Validation studies through interlaboratory scoring exercises have shown that current criteria are sufficiently robust to obtain consistent results concerning the identification of differentiated cells and MN and nuclear buds within them, which represent the main biomarkers for the evaluation of chromosomal damage. Improvements in scoring and analysis methods and further investigation about the biological significance of other BMNCyt biomarkers associated with cell differentiation and cell death are also needed in order to define their role and justify their application in human biomonitoring studies.
Micronucleus Assays with Human Lymphocytes for in Vitro Genetic Toxicology Testing
Authors: Kirsch-Volders Micheline , Fenech Michael
Published: July 2019

The toxicological relevance of the micronucleus (MN) assay is well defined: it is a multi-target genotoxicity endpoint, assessing both clastogenic and aneugenic events, it is simple to score, accurate, applicable in different cell types, predictive for cancer and amenable for automation. Using human lymphocytes for the in vitro MN (IVMN) assay has the advantage to provide a primary cell system with a normal mitotic machinery. In this chapter, we discuss the prerequisites for an acceptable MN assay, including the cell as a unit of observation, the importance of cell membranes, necessary assessment of cell division in the presence of the test substance and selection of an adequate top concentration. The advantages and disadvantages of using lymphocytes as a primary cell model system are discussed. The importance of adequate design of protocols is highlighted and references to the relevant OECD (Organisation for Economic Co-operation and Development) and HUMN (HUman MicroNucleus project) guidelines are provided. The main achievements over the last decades with regards to the lymphocyte IVMN assay and its application using the cytokinesis-block technique are summarized. Adaptation of the IVMN assays to assess the genotoxic potential of new materials, in particular nanomaterials, including the scoring of nucleoplasmic bridges and understanding their modes of action will strength the predictivity of the assay for hazard and risk assessment.
Micronucleus Experiments with Reptiles
Authors: Poletta G. L. , Siroski P. A.
Published: July 2019

Reptiles remain the least studied group of vertebrates in genetic toxicology, even though they have very interesting characteristics. Our studies conducted on native crocodiles, lizards, and turtles have demonstrated the sensitivity of the micronucleus (MN) test as a good indicator for genotoxicity biomonitoring. Reptiles are relevant components of the ecosystems and represent important resources that contribute to the regional economy. This leads to the awareness and commitment of local people in the protection of the ecosystem that contains them. In contrast, environmental pressure brought about by an increase in pollution would significantly disrupt the diversity and variability of these resources. Our studies confirmed that the MN test is also a highly suitable tool for the detection of DNA damage caused by chemical and physical agents found in reptiles, under different conditions of exposure and in different life stages, as has been widely reported for other vertebrates.
Micronucleus Assays in Amphibians
Authors: Giri Anirudha , Giri Sarbani
Published: July 2019

Induction of micronucleus (MN) expression is a well-validated biomarker of genotoxic exposure in eukaryotic cells and is widely used in biomonitoring programs. The presence of permeable skin, which facilitates toxicant exposure and local abundance, is among the characteristics that make amphibians good indicators of ecosystem health. The presence of large nucleated erythrocytes, which divide in the circulation, makes amphibian erythrocytes an ideal target tissue to detect genotoxin exposure using the MN assay. Published literature have highlighted the promising prospects of using the amphibian MN assay as a sensitive biomonitoring tool for water quality assessment to detect potential genotoxins. The present chapter provides the basic outline of the amphibian MN assay and highlights its use in genotoxicity testing in experimental and biomonitoring studies.
Micronucleus Experiments with Bivalve Molluscs
Authors: Bolognesi Claudia
Published: July 2019

The micronucleus (MN) test, as an index of accumulated DNA damage during the lifespan of cells, is the most applied assay in aquatic animals to assess the exposure to a complex mixture of genotoxic pollutants. An increase in MN frequency was reported on mussels exposed to the most common environmental pollutants under laboratory conditions, such as heavy metals, polycyclic aromatic hydrocarbons, and ionizing radiation. The test was applied in a large number of biomonitoring studies in different geographic areas to identify the exposure to different classes of pollutants with good discrimination power and to evaluate the recovery effects after accidental pollution events. A standardized MN assay protocol in hemocytes and gill cells for use in bivalve species, including scoring of different cell types, necrotic and apoptotic cells and nuclear anomalies, was established following the “cytome approach”. The mussel MNcytome (MUMNcyt) assay, using the proposed detailed criteria for the identification of cell types, is suitable for application in experimental studies under controlled conditions and in biomonitoring programs in aquatic environments.
Automated Identification and Scoring of Micronuclei
Authors: Wilkins R. C. , Rodrigues M. A. , Beaton-Green L. A.
Published: July 2019

Micronucleus (MN) assays are used as a measure of cellular damage, and are often preferred over other chromosomal aberration assays since they possess similar statistical robustness for detection of genotoxins and require less technical expertise, making them easier to perform. However, the traditional visual scoring methods are tedious and prone to scorer subjectivity. A number of techniques to automate the MN assays have been developed using a variety of technologies. This chapter will provide an overview of several current methods used to automate MN assays, including automated slide-scoring and laser scanning cytometry, as well as conventional and imaging flow cytometry techniques.
The Micronucleus Assay as a Cytogenetic Biomarker of Ethylene Oxide Exposure
Authors: Ghosh Manosij , Hoet Peter H. M. , Godderis Lode
Published: July 2019

Ethylene oxide (EtO), a chemical widely used in the sterilisation of medical equipment, is categorized as a Group 1 carcinogen by the International Agency for Research on Cancer. In this chapter, we discuss the results from epidemiological studies that have used the micronucleus (MN) assay to determine MN formation as a result of EtO exposure and provide a mechanistic understanding from the limited number of in vitro and in vivo studies available. Most of the epidemiological studies published in the period of 1985–2000, differ significantly in terms of the exposure conditions, cell type and MN assay outcome. The in vitro and in vivo studies provide comparable results, however they do not provide any definite mechanistic explanation. The studies also reveal that MN is comparatively less sensitive than sister chromatid exchanges, as a cytogenetic marker for EtO exposure.
Micronucleus Induction by Exposure to Vinyl Chloride
Authors: Feng Nannan , Xia Zhao-lin
Published: July 2019

Monomeric vinyl chloride is a colorless, with a slightly fragrant smell, gas at ordinary temperatures and pressures, which is widely used in the production of polyvinyl chloride, and is classified as a Group I human carcinogen by the International Agency for Research on Cancer (IARC) on the basis of increased risk for angiosarcoma of liver and hepatocellular carcinoma. The carcinogenicity of vinyl chloride could be mediated by a mutagenic mechanism. Following inhalation, vinyl chloride is rapidly absorbed and metabolized in the liver to the electrophilic metabolites chloroethylene oxide and chloroacetaldehyde, which could form DNA adducts that can be processed into point mutations in genes involved in pathways related to cancer in humans and rats exposed to vinyl chloride. The present chapter analyzes the published studies in which the cytokinesis-block micronucleus assay in peripheral lymphocytes was applied in vinyl chloride-exposed workers. Eight similar studies performed in China among three regions showed increased micronucleus frequencies (Frequency Ratio 1.92–3.79) associated with increased cumulative vinyl chloride exposure. The benchmark dose lower limit for 10% excess risk calculated from three studies resulted in an estimated exposure limit of 0.03–0.50 mg m−3. Furthermore, the results suggested it is very important to re-evaluate the recommended exposure limits using new bio-monitoring methods in addition to the micronucleus assay.
Vacuum pouch microfluidic system and its application for thin-film micromixers
Authors: Lee Cheng-Je , Hsu Yu-Hsiang
Published: July 2019

Vacuum pouch microfluidic system: a new type of lab-on-a-chip device that uses an on-chip vacuum pouch to drive a thin-film micromixer with a wide operation range.
In situ monitoring of electrochemical reactions through CNT-assisted paper cell mass spectrometry
Authors: Narayanan Rahul , Basuri Pallab , Jana Sourav Kanti , Mahendranath Ananthu , Bose Sandeep , Pradeep Thalappil
Published: July 2019

A novel method of coupling electrochemistry (EC) with mass spectrometry (MS) is illustrated with a paper-based electrochemical cell supported by carbon nanotubes (CNTs).
Non-enzymatic determination of purine nucleotides using a carbon dot modified glassy carbon electrode
Authors: Karthikeyan R. , Nelson D. James , John S. Abraham
Published: July 2019

Selective and sensitive determination of one of the purine nucleotides, inosine (INO) using a low cost carbon dot (CD) modified glassy carbon (GC) electrode in 0.2 M phosphate buffer solution (pH 7.2) was demonstrated in this paper.
Recent development in biodegradable nanovehicle delivery system-assisted immunotherapy
Authors: Wen Zhenfu , Liu Fengyu , Chen Qing , Xu Yongqian , Li Hongjuan , Sun Shiguo
Published: July 2019

A schematic illustration of BNDS biodegradation and release antigen delivery for assisting immunotherapy.
Asymmetric behaviour of Li/Li symmetric cells for Li metal batteries
Authors: Koo Dongho , Kwon Bomee , Lee Jeonghyeop , Lee Kyu Tae
Published: July 2019

The asymmetric behaviour of Li metal electrodes in Li/Li symmetric cells is demonstrated in terms of electrochemical performance and changes in the morphology of Li metal.
Accelerated acquisition in pure-shift spectra based on prior knowledge from 1H NMR
Authors: Shchukina Alexandra , Kaźmierczak Magdalena , Kasprzak Paweł , Davy Matthew , Akien Geoffrey R. , Butts Craig P. , Kazimierczuk Krzysztof
Published: July 2019

Pure shift NMR with maximum performance by non-uniform sampling with prior knowledge.
Rational synthesis, crystal structure, and sensing and adsorption properties of luminescent metal–organic frameworks
Authors: Fan Chuanbin , Zong Ziao , Meng Xiangmin , Zhang Xia , Zhang Xiaoyin , Zhang Dongmei , Xu Cungang , Wang Hu , Fan Yuhua
Published: July 2019

Five novel Cd(ii) metal–organic frameworks (Cd-MOFs) were synthesized employing a rational design approach under solvothermal conditions. The luminescence sensing and the targeted dye adsorption properties of the MOFs 1–5 are investigated.
Manifestation of strong magnetic and giant Raman anisotropy in single crystals of Cu for H substituted strontium hydroxyapatite
Authors: Kazin Pavel E. , Zykin Mikhail A. , Jesche Anton , Seidler Maximilian L. , Tafeenko Victor A. , Eliseev Andrey A. , Trusov Lev A. , Jansen Martin
Published: July 2019

The linear [O–Cu–O]− reveals a strong easy axis magnetic anisotropy with a high energy of 4 × 102 cm−1 probed by magnetization measurements and polarized Raman spectroscopy of a single crystal.
The effects of extreme conditions on molecular solids
Authors: Oswald Iain D. H. , Beavers Christine M.
Published: July 2019

Welcome to this themed issue of CrystEngComm entitled: ‘The effects of extreme conditions on molecular solids’.
Influence of polar co-solutes and salt on the hydration of lipid membranes
Authors: Wolde-Kidan Amanuel , Pham Quoc Dat , Schlaich Alexander , Loche Philip , Sparr Emma , Netz Roland R. , Schneck Emanuel
Published: July 2019

The influence of the co-solutes TMAO, urea, and NaCl on the hydration repulsion between lipid membranes is investigated in a combined experimental/simulation approach.
Intermolecular interactions and solvation effects of dimethylsulfoxide on type III deep eutectic solvents
Authors: Shah Dhawal , Mansurov Ulan , Mjalli Farouq S.
Published: July 2019

Intermolecular interactions within the mixtures of DMSO and reline, a typical type III Deep Eutectic Solvent (DES), composed of urea and choline chloride, is examined along with the mixtures' physical properties.
Analysis of the EPR spectra of transferrin: the importance of a zero-field-splitting distribution and 4th-order terms
Authors: Azarkh Mykhailo , Gast Peter , Mason Anne B. , Groenen Edgar J. J. , Mathies Guinevere
Published: July 2019

A new method is implemented to extract the distribution of zero-field-splitting parameters from the EPR spectra of transferrin. This promotes the effective use of multi-frequency EPR to characterize high-spin iron sites in biological systems.
Ultrafast dynamics in polycyclic aromatic hydrocarbons: the key case of conical intersections at higher excited states and their role in the photophysics of phenanthrene monomer
Authors: Nazari M. , Bösch C. D. , Rondi A. , Francés-Monerris A. , Marazzi M. , Lognon E. , Gazzetto M. , Langenegger S. M. , Häner R. , Feurer T. , Monari A. , Cannizzo A.
Published: July 2019

Proper interpretation of phenanthrene's and similar PAHs’ photocycle relies on two higher excited state relaxations due to the simultaneous presence of non-adiabatic and adiabatic transitions.
Two-dimensional transition-metal halide CoBr3 with spin-polarized Dirac cone
Authors: Zhang Wei-xi , Li Yong , Jin Hui , She Yan-chao
Published: July 2019

Recently, the discovery of two-dimensional transition-metal materials with non-trivial magnetic and electronic properties has spurred huge interest in investigating their applications in nanotechnology.
Ethanol-quenching modified the surface environment of titanium dioxide for visible light-assisted hydrogen production
Authors: Chen Shihao , Xiao Yang , Wang Yinhai , Zhang Wei , Hu Zhengfa , Zhao Hui , Xie Wei
Published: July 2019

There are numerous approaches for modifying the surface structure of titanium dioxide (TiO2) crystals.
Rare-earth complexes supported by an ansa-bis(amidinate) ligand with a rigid o-phenylene linker: synthesis, structure, and catalytic activity for polymerization of cyclic esters
Authors: Wang Fenhua , Zhao Xu , Meng Xianfu , Wang Shaowu
Published: July 2019

Two types of rare-earth complexes supported by a linked-bis(amidinate) ligand were constructed; their coordination chemistry and catalytic activity were studied.
Copper(ii) complexes with 2,2′:6′,2′′-terpyridine, 2,6-di(thiazol-2-yl)pyridine and 2,6-di(pyrazin-2-yl)pyridine substituted with quinolines. Synthesis, structure, antiproliferative activity, and catalytic activity in the oxidation of alkanes and alcohols with peroxides
Authors: Choroba Katarzyna , Machura Barbara , Kula Slawomir , Raposo Luis R. , Fernandes Alexandra R. , Kruszynski Rafal , Erfurt Karol , Shul'pina Lidia S. , Kozlov Yuriy N. , Shul'pin Georgiy B.
Published: July 2019

The toxicity of six new Cu(ii) complexes was evaluated in cancer derived cell lines. A model of competitive interaction of hydroxyl radicals with CH3CN and RH in the catalyst cavity has been proposed.
Structural and spectroscopic analysis of a new family of monomeric diphosphinoboranes
Authors: Ordyszewska Anna , Szynkiewicz Natalia , Perzanowski Emil , Chojnacki Jarosław , Wiśniewska Aleksandra , Grubba Rafał
Published: July 2019

A series of monomeric amino- and aryl(diphosphino)boranes has been synthesized and structurally characterized.
Pre- and post-synthetic modulation of the ordering temperatures in a family of anilato-based magnets
Authors: Martínez-Hernández Cristian , Gómez-Claramunt Patricia , Benmansour Samia , Gómez-García Carlos J.
Published: July 2019

Pre- and post-synthetic inclusion of solvent molecules in the anilato-based 2D honeycomb ferrimagnets (NBu4)[MnCr(C6O4Br2)]·G, G = PhCl, PhBr, PhI, PhCH3, PhCN and PhNO2, increases their ordering temperatures (from 5.5–6.3 K to 9.5–11.4 K).
Biocatalytic retrosynthesis approaches tod-(2,4,5-trifluorophenyl)alanine, key precursor of the antidiabetic sitagliptin
Authors: Parmeggiani Fabio , Rué Casamajo Arnau , Colombo Danilo , Ghezzi Maria Chiara , Galman James L. , Chica Roberto A. , Brenna Elisabetta , Turner Nicholas J.
Published: July 2019

Six chemo-enzymatic routes for the synthesis of a trifluorinatedd-phenylalanine have been described and compared, including the first example of a fully biocatalyticd-hydroamination.
Direct determination of cadmium in rice by solid sampling electrothermal vaporization atmospheric pressure glow discharge atomic emission spectrometry using a tungsten coil trap
Authors: Deng Qisi , Yang Chun , Zheng Hongtao , Liu Jixin , Mao Xuefei , Hu Shenghong , Zhu Zhenli
Published: July 2019

A fast, cost-effective and sensitive method for the direct determination of Cd in rice was developed based on a miniaturized APGD-AES system coupled with solid sampling electrothermal vaporization with a tungsten coil trap (ETV-TC).
Selective in vitro anti-cancer activity of non-alkylating minor groove binders
Authors: Nichol Ryan J. O. , Khalaf Abedawn I. , Sooda Kartheek , Hussain Omar , Griffiths Hollie B. S. , Phillips Roger , Javid Farideh A. , Suckling Colin J. , Allison Simon J. , Scott Fraser J.
Published: July 2019

We describe the synthesis and evaluation of Strathclyde Minor Groove Binders (S-MGBs) as selective anti-cancer agents which act through a non-alkylating mechanism.
Vibration assisted electron tunneling through nano-gaps in graphene nano-ribbons for amino-acid and peptide bond recognition
Authors: Zollo Giuseppe , Rossini Aldo Eugenio
Published: July 2019

Vibrational modes assisted tunneling in nano-gaps of graphene nanoribbons reveal specific features allowing the recognition of amino-acids and peptide bonds with atomistic resolution.
In situliquid cell TEM observation of solution-mediated interaction behaviour of Au/CdS nanoclusters
Authors: Wu Yulian , Chen Xin , Li Chang , Fang Jiali , Liu Haiyang
Published: July 2019

Near a thicker liquid region, droplets grow and become overlap-like, liquid fronts push forward to facilitate NC coalescence. In a thin liquid region, e-beam induces bubble formation, dissolution of CdS, and deformation of the Au/CdS composite.
Carbon-templated conductive oxide supports for oxygen evolution catalysis
Authors: Hufnagel Alexander G. , Häringer Sebastian , Beetz Michael , Böller Bernhard , Fattakhova-Rohlfing Dina , Bein Thomas
Published: July 2019

We present a novel route for the preparation of niobium-doped titanium oxide supported IrO2 for the oxygen evolution reaction.
Near-infrared optical transitions in PdSe2 phototransistors
Authors: Walmsley Thayer S. , Andrews Kraig , Wang Tianjiao , Haglund Amanda , Rijal Upendra , Bowman Arthur , Mandrus David , Zhou Zhixian , Xu Ya-Qiong
Published: July 2019

We explore near-infrared optical transitions and photocurrent dynamics in few-layer PdSe2 phototransistors through spatially-resolved photocurrent measurements.