bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational design and characterization of new thieno‐expanded tricyclic purine analogs
Authors: Zhang Laibin , Wang Mei , Zheng Mengmeng , Kong Xiangmu
Published: December 2018

Unnatural nucleobases are under intense research due to their widespread applications in nucleic acids research. In this work, four new thieno‐expanded purine analogs comprising ttzA, tthA, ttzG, and tthG were computationally designed based on the isomorphic tz‐ and th‐bases. These base analogs can also be seen as modified derivatives of the previously reported tricyclic purine analogs (ttA and ttG). The structural, electronic, and photophysical properties are studied by means of DFT and TDDFT calculations. We find out that these new bases can form stable Watson‐Crick base pairs with natural counterparts, thus potentially mimicking natural nucleobases in DNA/RNA duplexes. Calculations reveal that these bases have smaller AIPs and HOMO‐LUMO gaps than natural ones, suggesting that they are candidates for applications in nanowire technology. Particularly, the photophysical properties were explored, and the results are compared with those for tz‐, th‐, and tt‐bases. The nature of the low‐lying excited states is discussed, and analyses reveal that the thiophene‐homologation would not change excitation maxima of thA and tzA, while it will result in large red‐shifts of those of thG and tzG. Meanwhile, thiophene insertion has relatively larger influences on the emissions thA and tzG, for which the fluorescence was 37 nm blue‐shifted and 19 nm red‐shifted, respectively. Taking these new bases as derivatives of ttA and ttG, it was found that the modifications would result in large red‐shifts of both the excitation maxima and the fluorescence. The effects of water solution and base paring on the phtotophysical properties were also considered.
The SO2 Resistance Improvement of Mn‐Fe/ZSM‐5 for NH3‐SCR at Low Temperature by Optimizing Synthetic Method
Authors: Zou Chunlei , Wu Xu , Meng Hao , Du Yali , Li Zhe
Published: December 2018

Mn‐Fe/ZSM‐5 was prepared via co‐precipitation (CP) and precipitation–chemical vapor deposition (P‐CVD) methods. Catalytic performance investigation showed that Mn‐Fe/ZSM‐5 by P‐CVD method had higher catalytic activity and SO2 resistance than the ones by CP method for NH3‐SCR at low temperature. Characterization results proved that the amount of ammonium sulfate deposited on the surface of Mn‐Fe/ZSM‐5(P‐CVD) was less than that of Mn‐Fe/ZSM‐5(CP) catalyst. Further investigations revealed that the deposition and decomposition of ammonium sulfate proceeded in a dynamic balance on Mn‐Fe/ZSM‐5(P‐CVD) catalyst, which was crucial for the excellent catalytic performances in the presence of SO2 and H2O.
Study of K‐Feldspar and Lime Hydrothermal Reaction at 190 °C: Phase, Kinetics and Mechanism with Reaction Time
Authors: Liu Shanke , Han Cheng , Liu Jianming
Published: December 2018

An artificial silicate composite material prepared by the hydrothermal reaction of K‐feldspar and lime, showed excellent performance in remediating the soil. To elucidate the physicochemical properties of the artificial silicate composite material, K‐feldspar and lime were reacted in mild hydrothermal conditions (T=190 °C; P∼12.4 atm; t=0∼36 h). The hydrothermal product was systematically investigated using various techniques such as X‐ray powder diffraction (XRPD), scanning electron microscopy, and inductively coupled plasma‐optical emission spectrometry (ICP–OES). Quantitative evaluation of the extent of reaction by ICP–OES and XRPD methods enabled the analysis of hydrothermal evolution with prolonged time. The hydrothermal treatment of K‐feldspar with lime exhibits complex product phases, including leftover K‐feldspar, calcium hydroxide, calcite, grossular, tobermorite, alpha‐dicalcium silicate hydrate, potassium carbonate, bütschliite, and amorphous calcium silicate hydrate. The analysis of the reaction reveals that the K‐feldspar dissolution showed a clear transition, with the hydrothermal reaction beginning to slow down after 20 h. The slowdown of the K‐feldspar dissolution was essentially caused by different reaction kinetics and mechanisms before and after 20 h. The study yields vital and valuable insights into comprehending the chemistry and mineralogy of the artificial silicate composite material and producing a multielement reservoir from potassium‐rich rocks.
Detection of NO2 Down to One ppb Using Ion‐in‐Conjugation‐Inspired Polymer
Authors: Zhou Jin , Cheng Xue‐Feng , Gao Bi‐Jun , Yu Chuang , He Jing‐Hui , Xu Qing‐Feng , Li Hua , Li Na‐Jun , Chen Dong‐Yun , Lu Jian‐Mei
Published: December 2018

Nitrogen dioxide (NO2) emission has severe impact on human health and the ecological environment and effective monitoring of NO2 requires the detection limit (limit of detection) of several parts‐per‐billion (ppb). All organic semiconductor‐based NO2 sensors fail to reach such a level. In this work, using an ion‐in‐conjugation inspired‐polymer (poly(3,3′‐diaminobenzidine‐squarine, noted as PDBS) as the sensory material, NO2 can be detected as low as 1 ppb, which is the lowest among all reported organic NO2 sensors. In addition, the sensor has high sensitivity, good reversibility, and long‐time stability with a period longer than 120 d. Theoretical calculations reveal that PDBS offers unreacted amine and zwitterionic groups, which can offer both the H‐bonding and ion‐dipole interaction to NO2. The moderate binding energies (≈0.6 eV) offer high sensitivity, selectivity as well as good reversibility. The results demonstrate that the ion‐in‐conjugation can be employed to greatly improve sensitivity and selectivity in organic gas sensors by inducing both H‐bonding and ion‐dipole attraction.
YHp as a highly stable, hyper‐copy, hyper‐expression plasmid constructed using a full 2‐μm circle sequence in cir0 strains of Saccharomyces cerevisiae
Authors: Misumi Yukie , Nishioka Satoko , Fukuda Akira , Uemura Takeshi , Nakamura Mikiko , Hoshida Hisashi , Akada Rinji
Published: December 2018

In the yeast Saccharomyces cerevisiae, the yeast episomal plasmid (YEp), containing a partial sequence from a natural 2‐μm plasmid, has been frequently used to induce high levels of gene expression. In this study, we used Japanese sake yeast natural cir0 strain as a host for constructing an entire 2‐μm plasmid with an expression construct using the three‐fragment gap‐repair method without Escherichia coli manipulation. The 2‐μm plasmid contains two long inverted repeats, which is problematic for the amplification by polymerase chain reaction. Therefore, we amplified it by dividing into two fragments, each containing a single repeat together with an overlapping sequence for homologous recombination. TDH3 promoter‐driven yEmRFP (TDH3p‐yEmRFP) and the URA3 were used as a reporter gene and a selection marker, respectively, and inserted at the 3′ end of the RAF1 gene on the 2‐μm plasmid. The three fragments were combined and used for the transformation of sake yeast cir0 ura3‐ strain. The resulting transformant colonies showed a red or purple coloration, which was significantly stronger than that of the cells transformed with YEp‐TDH3p‐yEmRFP. The 2‐μm transformants were cultured in YPD medium and observed by fluorescence microscopy. Almost all cells showed strong fluorescence, suggesting that the plasmid was preserved during nonselective culture conditions. The constructed plasmid maintained a high copy state similar to that of the natural 2‐μm plasmid, and the red fluorescent protein expression was 54 fold compared with the chromosomal integrant. This vector is named YHp, the Yeast Hyper expression plasmid.
Systemic Complications and Radiographic Findings of Opioid Use and Misuse: An Overview for Orthopedic Surgeons
Authors: Greditzer Harry G. , Massel Dustin H. , Barrera Carlos M. , Ezuddin Nisreen S. , Emerson Christopher P. , Jose Jean
Published: December 2018

Amid growing concern about the misuse of prescribed opioids, the rising rates of opioid use disorder, and the use of illicit opioids, clinicians in ambulatory, inpatient, and operative environments are encountering opioid-related complications in their patients. These complications can affect multiple organ systems including cardiovascular, pulmonary, gastrointestinal, and neurologic and are related to excess opioid levels in the body or contamination from non-sterile injection. It is important for the orthopedic surgeon to have a general understanding of the pathologies associated with opioid use disorder and their appearance on diagnostic imaging. This article reviews image findings of several complications, organized in a systems-based approach, for the orthopedic surgeon.
Efficacy of Borides in Grain Refining Al-Si Alloys
Authors: Bolzoni Leandro , Hari Babu Nadendla
Published: December 2018

The grain refining efficacy of titanium, aluminum, and niobium borides, as well as niobium aluminides, introduced via commercial and lab made master alloys on Al-Si alloys was investigated. Significant grain refinement is achieved via the introduction of these heterogeneous nuclei regardless of their chemistry, stoichiometry of the master alloy, and addition rate. However, the grain refinement is affected by variable such as contact time, as the inoculating particle may sediment or be poisoned, and cooling rate. Specifically, a faster cooling rate generally leads to finer grains due to the lower time for grain growth. In the case of borides, the chemical inoculation efficiency is greatly affected by their thermodynamic stability in molten Al-Si alloys. Conversely, the grain refining potency of properitectic Al3Nb remains unaffected. The underlying grain refining mechanism was finally investigated using current models based on the growth restriction factor Q to simultaneously consider the effect of nucleant potency and alloy chemistry. Among Ti-, Al-, and Nb-based borides with similar particle size and distribution, the latter are the most efficient to grain refine Al-Si alloys.
Putative Microbial Population Shifts Attributable to Nasal Administration of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a
Authors: De Grandi Roberta , Drago Lorenzo , Bidossi Alessandro , Bottagisio Marta , Gelardi Matteo , De Vecchi Elena
Published: December 2018

Changes in bacterial composition of nasal microbiota may alter the host’s susceptibility to several infectious and allergic diseases such as chronic rhinosinusitis and allergic rhinitis. The aim of this study was to evaluate the effects of 1-week administration of a probiotic product, composed by a combination of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a, on the nostril microbiota. Differences in the nasal microbiota composition were investigated by using a next-generation sequencing approach. A strong and significant decrease in Staphylococcus aureus abundance was detected immediately after the bacterial administration. Moreover, comparing the microbial networks of nostril microbiota before and 1 month after the end of treatment, we detected an increase in the total number of both bacterial nodes and microbial correlations, with particular regard to the beneficial ones. Furthermore, a less abundance of microbial genera commonly associated to potential harmful bacteria has been observed. These results suggest a potential ability of S. salivarius 24SMBc and S. oralis 89a to regulate and reorganize the nasal microbiota composition, possibly favoring those microorganisms that may be able to limit the overgrowth of potential pathogens.
Fecal calprotectin role in diagnosis of ulcerative colitis and treatment follow-up
Authors: Mahdipour Mahsa , Shafaghi Afshin , Mansour-Ghanaei Fariborz , Hojati Amineh , Joukar Farahnaz , Mavaddati Sara
Published: December 2018

Objective Ulcerative colitis usually affects the rectum and potentially can involve the whole colon. Noninvasive methods such as fecal calprotectin measurement may be considered as a reliable and inexpensive approach in assessing disease severity or treatment change strategy.

Methods In this retrospective cross-sectional study, records of 56 ulcerative colitis patients who hospitalized with exacerbation between May 2016 and April 2017 were assessed based on IBD Data Bank Software in Gastrointestinal and Liver Diseases and Research Center (GLDRC), Guilan province, Iran between. A questionnaire of demographic characteristics, clinical findings and fecal calprotectin level was completed. Montreal classification severity of ulcerative colitis and Mayo disease activity index were scored. Data were analyzed for descriptive and analytical analysis.

Results Fecal calprotectin was significantly different in terms of disease severity based on both Mayo score (p = 0.007) and Montreal classification (p = 0.001). In patients with mild symptoms, no increase in fecal calprotectin was observed, but in patients with moderate and severe elevations in fecal calprotectin levels was significant. Also, C-Reactive Protein surge was related to disease severity (p = 0.02). Furthermore, regression comparison among high-chance patients based on fecal calprotectin was significantly related to higher Erythrocyte Sedimentation Rate levels and smoking, p = 0.01 and p = 0.05, respectively.

Conclusion It seems fecal calprotectin levels are related to the disease severity. Non-invasive methods, such as fecal calprotectin assay, may seem to be an alternative to aggressive, costly and time-consuming methods, such as colonoscopy and biopsy, to reduce the suffering of patients and ultimately help improve the patients’ life quality.
Sharing is not always a good thing: Use of a DNA marker to investigate the potential for ward-to-ward dissemination of healthcare-associated pathogens
Authors: Alhmidi Heba , Cadnum Jennifer L. , Jencson Annette L. , Gweder Ali Abdulfatah , Donskey Curtis J.
Published: December 2018

A DNA marker inoculated onto portable equipment on a medical ward was disseminated to other wards when equipment was shared and to a physician work room and the hospital cafeteria by personnel. These results demonstrate the plausibility of pathogen transmission in healthcare facilities in the absence of shared ward exposure.
Use of diagnostic stewardship practices to improve urine culturing among SHEA Research Network hospitals
Authors: Sullivan Kaede V. , Morgan Daniel J. , Leekha Surbhi
Published: December 2018

This survey investigated interventions used by acute-care hospitals to reduce the detection of asymptomatic bacteriuria. Half of the respondents reported using reflex urine cultures but with varied urinalysis criteria and perceived outcomes. Other diagnostic stewardship interventions for urine culture ordering and specimen quality were less common.
The enhancement of viscous fingering with bidisperse particle suspension
Authors: Xu Feng , Lee Sungyon
Published: December 2018

Viscous fingering is observed experimentally when a bidisperse suspension displaces air inside a Hele-Shaw cell, despite the stabilising viscosity ratio between the invading (suspension) and defending (air) phases. Careful experiments are carried out to characterise this instability by either systematically varying the large-particle concentrations $\unicode[STIX]{x1D719}_{l0}$ at constant total concentrations $\unicode[STIX]{x1D719}_{0}$, or changing $\unicode[STIX]{x1D719}_{0}$ with fixed $\unicode[STIX]{x1D719}_{l0}$. Leading to the instability, we observe that larger particles consistently enrich the fluid–fluid interface at a faster rate than small particles. This size-dependent enrichment of the interface leads to an earlier onset of the fingering instability for bidisperse suspensions, compared to their monodisperse counterpart of all small particles. In particular, even the small presence of large particles is shown to effectively lower the total particle concentration needed for fingering, compared to the all-small-particle case. We hypothesise that the key mechanism behind this enhanced viscous fingering is the size-dependent nature of shear-induced migration of particles far upstream from the interface. A reduced equilibrium model is derived based on the modified suspension balance model to verify this hypothesis, in reasonable agreement with experiments.
The ‘cash value’ of the rules of treaty interpretation
Authors: Zarbiyev Fuad
Published: December 2018

The rules of treaty interpretation are ordinarily met with scepticism not only by critically-minded international law theorists, but also by mainstream international legal scholars who otherwise believe in international law’s normative power. The objective of this article is to inquire whether, despite their much-discussed shortcomings, the rules of treaty interpretation have any ‘cash value’ in the sense given to this expression by one of the founding fathers of the philosophy of pragmatism William James, in other words, whether they make any practical difference. To do so, this article revisits the traditional understanding of the rules of treaty interpretation and argues that they cannot directly bridge the gap between the signifier and signified, but rather are designed to impose a ‘common discipline’ with respect to the admissible means that can be used in treaty interpretation.
Response of ‘Russet Burbank’ Seed Tubers Containing Dicamba and Glyphosate
Authors: Geary Nelson D. , Hatterman-Valenti Harlene , Secor Gary A. , Zollinger Richard K. , Robinson Andrew P.
Published: December 2018

Increased use of dicamba and/or glyphosate in dicamba/glyphosate-tolerant soybean might affect many sensitive crops, including potato. The objective of this study was to determine the growth and yield of ‘Russet Burbank’ potato grown from seed tubers (generation 2) from mother plants (generation 1) treated with dicamba (4, 20, and 99 g ae ha−1), glyphosate (8, 40, and 197 g ae ha−1), or a combination of dicamba and glyphosate during tuber initiation. Generation 2 tubers were planted near Oakes and Inkster, ND, in 2016 and 2017, at the same research farm where the generation 1 tubers were grown the previous year. Treatment with 99 g ha−1dicamba, 197 g ha−1glyphosate, or 99 g ha−1dicamba + 197 g ha−1glyphosate caused emergence of generation 2 plants to be reduced by up to 84%, 86%, and 87%, respectively, at 5 wk after planting. Total tuber yield of generation 2 was reduced up to 67%, 55%, and 68% when 99 g ha−1dicamba, 197 g ha−1glyphosate, or 99 g ha−1dicamba + 197 g ha−1glyphosate was applied to generation 1 plants, respectively. At each site year, 197 g ha−1glyphosate reduced total yield and marketable yield, while 99 g ha−1dicamba reduced total yield and marketable yield in some site-years. This study confirms that exposure to glyphosate and dicamba of potato grown for potato seed tubers can negatively affect the growth and yield potential of the subsequently grown daughter generation.
Enhancing Employee Self-Care
Authors: Horstmann David
Published: December 2018

Abstract. The present study investigates the relationship between health-specific leadership and employee burnout. Health-specific leadership is a domain-specific leadership style that is characterized by the focus of leaders on employee well-being and their intentional support of employee health. Following the theory, I argue that managers influence employee burnout not only directly but also indirectly by encouraging employees to take care of their own health. Further, I extend the scope of previous research and argue that managers’ personal initiative acts as a moderator for health-specific leadership; as indicated by previous research, proactivity is crucial for effective leadership behavior. A cross-sectional questionnaire study (n = 525) was conducted. Health-specific leadership, managers’ personal initiative, employee self-care, and employee burnout symptoms have been measured. A moderated mediation was tested using structural equation modeling. The findings confirm a positive relationship between health-specific leadership and employee burnout. As expected, this relationship is partially mediated by employee self-care. Managers’ personal initiative shows an interaction effect on employee self-care but not on burnout symptoms. The study results verify the concept of health-specific leadership and highlight the importance of proactive leadership behavior as a facilitator for health-specific leadership. Finally, implications for leadership research and practice are provided.
Simulation of Longwave Enhancement in Boreal and Montane Forests
Authors: Todt M. , Rutter N. , Fletcher C. G. , Wake L. M. , Bartlett P. A. , Jonas T. , Kropp H. , Loranty M. M. , Webster C.
Published: December 2018

Boreal forests cover about a fifth of seasonally snow‐covered land over the Northern Hemisphere. Enhancement of longwave radiation beneath coniferous forests has been found to impact the surface energy balance and rates of snowmelt. Although the skill of model‐simulated snowmelt has been shown to be lower for forests than for open areas, model intercomparisons and evaluations of model parameterizations have not yet focused on longwave enhancement. This study uses stand‐scale forcing for the simulation of subcanopy longwave radiation by Community Land Model version 4.5 (CLM4.5) and to drive SNOWPACK, a snow model featuring more complex canopy structure, as a benchmark model for CLM4.5. Simulated subcanopy longwave radiation and longwave enhancement are assessed using measurements from forest stands located within perennially snow‐covered regions. These forest stands, of varying canopy density, cover the range of boreal plant functional types in CLM4.5. CLM4.5 is found to overestimate the diurnal range of subcanopy longwave radiation and longwave enhancement, and simulation errors increase with decreasing cloudiness and increasing vegetation density. Implementation of a parameterization of heat storage by biomass reduces simulation errors but only marginally affects the amplitude of diurnal ranges. These results reaffirm previous findings that simulation of subcanopy longwave radiation can be improved by partitioning the vegetation canopy into two layers. Moreover, this study reveals the variations of simulation errors across meteorological conditions and vegetation density, the latter of which is the most important parameter for longwave enhancement independent of vegetation type.
Modeling Geoelectric Fields in Ireland and the UK for Space Weather Applications
Authors: Campanyà J. , Gallagher P. T. , Blake S. P. , Gibbs M. , Jackson D. , Beggan C. D. , Richardson G. S. , Hogg C.
Published: December 2018

Geoelectric fields at the Earth's surface caused by geomagnetic storms have the potential to disrupt and damage ground‐based infrastructure such as electrical power distribution networks, pipelines, and railways. Here we model geoelectric fields in Ireland and the UK during both quiet and active time intervals of geomagnetic conditions using measurements from magnetic observatories and electromagnetic tensor relationships. The analysis focused on (1) defining periods of the magnetic field variations that are largely affected by the geomagnetic storms, between 30 and 30,000 s; (2) constraining the electromagnetic tensor relationships that defines the Earth's response to magnetic field variations; (3) implementing and validating two approaches for modeling geoelectric fields based on measurements from magnetic observatories and local and interstation electromagnetic transfer functions; and (4) estimating uncertainties when modeling geoelectric fields. The use of interstation tensor relationships allowed us to differentiate between regional and local geomagnetic sources. We found coherence values of 0.5–0.95, signal‐to‐noise ratio of 1–15 dB, normalized root‐mean‐square values of 0.8–3.4, and root‐mean‐square values of 0.7–84 mV/km. Within these ranges of values, sites in close proximity (<100 km) to a magnetic observatory and not affected by local storms will provide the most accurate results, while sites located at further distances and affected by spatially localized features of the storm will be less accurate. These methods enable us to more accurately model geomagnetically induced currents, and their associated uncertainties, in the British and Irish power networks.
Inverse photonic design of functional elements that focus Bloch surface waves
Authors: Augenstein Yannick , Vetter Andreas , Lahijani Babak Vosoughi , Herzig Hans Peter , Rockstuhl Carsten , Kim Myun-Sik
Published: December 2018

Bloch surface waves (BSWs) are sustained at the interface of a suitably designed one-dimensional (1D) dielectric photonic crystal and an ambient material. The elements that control the propagation of BSWs are defined by a spatially structured device layer on top of the 1D photonic crystal that locally changes the effective index of the BSW. An example of such an element is a focusing device that squeezes an incident BSW into a tiny space. However, the ability to focus BSWs is limited since the index contrast achievable with the device layer is usually only on the order of Δn≈0.1 for practical reasons. Conventional elements, e.g., discs or triangles, which rely on a photonic nanojet to focus BSWs, operate insufficiently at such a low index contrast. To solve this problem, we utilize an inverse photonic design strategy to attain functional elements that focus BSWs efficiently into spatial domains slightly smaller than half the wavelength. Selected examples of such functional elements are fabricated. Their ability to focus BSWs is experimentally verified by measuring the field distributions with a scanning near-field optical microscope. Our focusing elements are promising ingredients for a future generation of integrated photonic devices that rely on BSWs, e.g., to carry information, or lab-on-chip devices for specific sensing applications.
Glassy carbon microneedles—new transdermal drug delivery device derived from a scalable C-MEMS process
Authors: Mishra Richa , Pramanick Bidhan , Maiti Tapas Kumar , Bhattacharyya Tarun Kanti
Published: December 2018

Because carbon is the basic element of all life forms and has been successfully applied as a material for medical applications, it is desirable to investigate carbon for drug delivery applications, as well. In this work, we report the fabrication of a hollow carbon microneedle array with flow channels using a conventional carbon-microelectromechanical system (C-MEMS) process. This process utilizes the scalable and irreversible step of pyrolysis, where prepatterned SU-8 microneedles (precursor) are converted to glassy carbon structures in an inert atmosphere at high temperature (900 °C) while retaining their original shape upon shrinkage. Once converted to glassy carbon, the microneedles inherit the unique properties of hardness, biocompatibility, and thermal and chemical resistance associated with this material. A comparative study of hardness and Young’s modulus for carbon microneedles and SU-8 microneedles was performed to evaluate the increased strength of the microneedles induced by the C-MEMS process steps. Structural shrinkage of the carbon microneedles upon pyrolysis was observed and estimated. Material characterizations including energy-dispersive X-ray spectroscopy (EDX) and Raman spectroscopy were carried out to estimate the atomic percentage of carbon in the microneedle structure and its crystalline nature, respectively. Our investigations confirm that the microneedles are glassy in nature. Compression and bending tests were also performed to determine the maximum forces that the carbon microneedles can withstand, and it was found that these forces were approximately two orders of magnitude higher than the resistive forces presented by skin. A microneedle array was inserted into mouse skin multiple times and was successfully removed without the breakage of any microneedles.
S100A3 a partner protein regulating the stability/activity of RARα and PML-RARα in cellular models of breast/lung cancer and acute myeloid leukemia
Authors: Gianni Maurizio , Terao Mineko , Kurosaki Mami , Paroni Gabriela , Brunelli Laura , Pastorelli Roberta , Zanetti Adriana , Lupi Monica , Acquavita Andrea , Bolis Marco , Fratelli Maddalena , Rochette-Egly Cecile , Garattini Enrico
Published: December 2018

All trans-retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia (APL) and it is a promising agent also in solid tumors. The pharmacological activity of ATRA is mediated by the ligand-activated RAR and RXR transcription factors. In the present study, we define the basal and ATRA dependent RARα interactome in a RARα-overexpressing breast cancer cellular model, identifying 28 nuclear proteins. We focus our attention on the S100A3 calcium-binding protein, which interacts with RARα constitutively. In ATRA-sensitive breast cancer cells, S100A3 binds to RARα in basal conditions and binding is reduced by the retinoid. The interaction of S100A3 with RARα is direct and in lung cancer, APL and acute-myeloid-leukemia (AML) cells. In APL, S100A3 interacts not only with RARα, but also with PML-RARα. The interaction surface maps to the RARα ligand-binding domain, where the I396 residue plays a crucial role. Binding of S100A3 to RARα/PML-RARα controls the constitutive and ATRA-dependent degradation of these receptors. S100A3 knockdown decreases the amounts of RARα in breast- and lung cancer cells, inducing resistance to ATRA-dependent anti-proliferative/differentiating effects. Conversely, S100A3 knockdown in PML-RARα+ APL and PML-RARα− AML cells reduces the amounts of RARα/PML-RARα and increases basal and ATRA-induced differentiation. In this cellular context, opposite effects on RARα/PML-RARα levels and ATRA-induced differentiation are observed upon S100A3 overexpression. Our results provide new insights into the molecular mechanisms controlling RARα activity and have practical implications, as S100A3 represents a novel target for rational drug combinations aimed at potentiating the activity of ATRA.
Selfish, sharing and scavenging bacteria in the Atlantic Ocean: a biogeographical study of bacterial substrate utilisation
Authors: Reintjes Greta , Arnosti Carol , Fuchs B , Amann Rudolf
Published: December 2018

Identifying the roles played by individual heterotrophic bacteria in the degradation of high molecular weight (HMW) substrates is critical to understanding the constraints on carbon cycling in the ocean. At five sites in the Atlantic Ocean, we investigated the processing of organic matter by tracking changes in microbial community composition as HMW polysaccharides were enzymatically hydrolysed over time. During this investigation, we discovered that a considerable fraction of heterotrophic bacteria uses a newly-identified ‘selfish’ mode of substrate processing. We therefore additionally examined the balance of individual substrate utilisation mechanisms at different locations by linking individual microorganisms to distinct substrate utilisation mechanisms. Through FISH and uptake of fluorescently-labelled polysaccharides, ‘selfish’ organisms were identified as belonging to the Bacteroidetes, Planctomycetes and Gammaproteobacteria. ‘Sharing’ (extracellular enzyme producing) and ‘scavenging’ (non-enzyme producing) organisms predominantly belonged to the Alteromonadaceae and SAR11 clades, respectively. The extent to which individual mechanisms prevail depended on the initial population structure of the bacterial community at a given location and time, as well as the growth rate of specific bacteria. Furthermore, the same substrate was processed in different ways by different members of a pelagic microbial community, pointing to significant follow-on effects for carbon cycling.
Replicated associations of FADS1, MAD1L1, and a rare variant at 10q26.13 with bipolar disorder in Chinese population
Authors: Zhao Lijuan , Chang Hong , Zhou Dong-Sheng , Cai Jun , Fan Weixing , Tang Wei , Tang Wenxin , Li Xingxing , Liu Weiqing , Liu Fang , He Yuanfang , Bai Yan , Sun Yan , Dai Jiapei , Li Lingyi , Xiao Xiao , Zhang Chen , Li Ming
Published: December 2018

Genetic analyses of psychiatric illnesses, such as bipolar disorder (BPD), have revealed essential information regarding the underlying pathological mechanisms. While such studies in populations of European ancestry have achieved prominent success, understanding the genetic risk factors of these illnesses (especially BPD) in Chinese population remains an urgent task. Given the lack of genome-wide association study (GWAS) of BPD in Chinese population from Mainland China, replicating the previously reported GWAS hits in distinct populations will provide valuable information for future GWAS analysis in Han Chinese. In the present study, we have recruited 1146 BPD cases and 1956 controls from Mainland China for genetic analyses, as well as 65 Han Chinese brain amygdala tissues for mRNA expression analyses. Using this clinical sample, one of the largest Han Chinese BPD samples till now, we have conducted replication analyses of 21 single nucleotide polymorphisms (SNPs) extracted from previous GWAS of distinct populations. Among the 21 tested SNPs, 16 showed the same direction of allelic effects in our samples compared with previous studies; 6 SNPs achieved nominal significance (p < 0.05) at one-tailed test, and 2 additional SNPs showed marginal significance (p < 0.10). Aside from replicating previously reported BPD risk SNPs, we herein also report several intriguing findings: (1) the SNP rs174576 was associated with BPD in our Chinese sample and in the overall global meta-analysis, and was significantly correlated with FADS1 mRNA in diverse public RNA-seq datasets as well as our in house collected Chinese amygdala samples; (2) two (partially) independent SNPs in MAD1L1 were both significantly associated with BPD in our Chinese sample, which was also supported by haplotype analysis; (3) a rare SNP rs78089757 in 10q26.13 region was a genome-wide significant variant for BPD in East Asians, and this SNP was near monomorphic in Europeans. In sum, these results confirmed several significant BPD risk genes. We hope this Chinese BPD case–control sample and the current brain amygdala tissues (with continuous increasing sample size in the near future) will provide helpful resources in elucidating the genetic and molecular basis of BPD in this major world population.
Exosomes—the enigmatic regulators of bone homeostasis
Authors: Gao Minhao , Gao Weiyang , Papadimitriou J. M. , Zhang Changqing , Gao Junjie , Zheng Minghao
Published: December 2018

Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells. Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.
Assessing the nature of the charge-transfer electronic states in organic solar cells
Authors: Chen Xian-Kai , Coropceanu Veaceslav , Brédas Jean-Luc
Published: December 2018

The charge-transfer electronic states appearing at the donor-acceptor interfaces in organic solar cells mediate exciton dissociation, charge generation, and charge recombination. To date, the characterization of their nature has been carried out on the basis of models that only involve the charge-transfer state and the ground state. Here, we demonstrate that it is essential to go beyond such a two-state model and to consider explicitly as well the electronic and vibrational couplings with the local absorbing state on the donor and/or acceptor. We have thus developed a three-state vibronic model that allows us: to provide a reliable description of the optical absorption features related to the charge-transfer states; to underline the erroneous interpretations stemming from the application of the semi-classical two-state model; and to rationalize how the hybridization between the local-excitation state and charge-transfer state can lead to lower non-radiative voltage losses and higher power conversion efficiencies.
Spatial fine-mapping for gene-by-environment effects identifies risk hot spots for schizophrenia
Authors: Fan Chun Chieh , McGrath John J. , Appadurai Vivek , Buil Alfonso , Gandal Michael J. , Schork Andrew J. , Mortensen Preben Bo , Agerbo Esben , Geschwind Sandy A. , Geschwind Daniel , Werge Thomas , Thompson Wesley K. , Pedersen Carsten Bøcker
Published: December 2018

Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale. Effects of specific locales vary substantially within the most densely populated city of Denmark, with hazard ratios ranging from 0.26 to 9.26 for environment and from 0.20 to 5.95 for gene-by-environment. These findings indicate the critical synergism of gene and environment on the etiology of schizophrenia and demonstrate the potential of incorporating geolocation in genetic studies.
Machine learning plastic deformation of crystals
Authors: Salmenjoki Henri , Alava Mikko J. , Laurson Lasse
Published: December 2018

Plastic deformation of micron-scale crystalline solids exhibits stress-strain curves with significant sample-to-sample variations. It is a pertinent question if this variability is purely random or to some extent predictable. Here we show, by employing machine learning techniques such as regression neural networks and support vector machines that deformation predictability evolves with strain and crystal size. Using data from discrete dislocations dynamics simulations, the machine learning models are trained to infer the mapping from features of the pre-existing dislocation configuration to the stress-strain curves. The predictability vs strain relation is non-monotonic and exhibits a system size effect: larger systems are more predictable. Stochastic deformation avalanches give rise to fundamental limits of deformation predictability for intermediate strains. However, the large-strain deformation dynamics of the samples can be predicted surprisingly well.
Virus-mediated export of chromosomal DNA in plants
Authors: Catoni Marco , Noris Emanuela , Vaira Anna Maria , Jonesman Thomas , Matić Slavica , Soleimani Reihaneh , Behjatnia Seyed Ali Akbar , Vinals Nestor , Paszkowski Jerzy , Accotto Gian Paolo
Published: December 2018

The propensity of viruses to acquire genetic material from relatives and possibly from infected hosts makes them excellent candidates as vectors for horizontal gene transfer. However, virus-mediated acquisition of host genetic material, as deduced from historical events, appears to be rare. Here, we report spontaneous and surprisingly efficient generation of hybrid virus/host DNA molecules in the form of minicircles during infection of Beta vulgaris by Beet curly top Iran virus (BCTIV), a single-stranded DNA virus. The hybrid minicircles replicate, become encapsidated into viral particles, and spread systemically throughout infected plants in parallel with the viral infection. Importantly, when co-infected with BCTIV, B. vulgaris DNA captured in minicircles replicates and is transcribed in other plant species that are sensitive to BCTIV infection. Thus, we have likely documented in real time the initial steps of a possible path of virus-mediated horizontal transfer of chromosomal DNA between plant species.
A Novel Soft Contact Piezo-Controlled Liquid Cell for Probing Polymer Films under Confinement using Synchrotron FTIR Microspectroscopy
Authors: Benbow Natalie L. , Webber Jessie L. , Pawliszak Piotr , Sebben Damien A. , Ho Tracey T. M. , Vongsvivut Jitraporn , Tobin Mark J. , Krasowska Marta , Beattie David A.
Published: December 2018

Soft polymer films, such as polyelectrolyte multilayers (PEMs), are useful coatings in materials science. The properties of PEMs often rely on the degree of hydration, and therefore the study of these films in a hydrated state is critical to allow links to be drawn between their characteristics and performance in a particular application. In this work, we detail the development of a novel soft contact cell for studying hydrated PEMs (poly(sodium 4-styrenesulfonate)/poly(allylamine hydrochloride)) using FTIR microspectroscopy. FTIR spectroscopy can interrogate the nature of the polymer film and the hydration water contained therein. In addition to reporting spectra obtained for hydrated films confined at the solid-solid interface, we also report traditional ATR FTIR spectra of the multilayer. The spectra (microspectroscopy and ATR FTIR) reveal that the PEM film build-up proceeds as expected based on the layer-by-layer assembly methodology, with increasing signals from the polymer FTIR peaks with increasing bilayer number. In addition, the spectra obtained using the soft contact cell indicate that the PEM film hydration water has an environment/degree of hydrogen bonding that is affected by the chemistry of the multilayer polymers, based on differences in the spectra obtained for the hydration water within the film compared to that of bulk electrolyte.
The formation of chromatin domains involves a primary step based on the 3-D structure of DNA
Authors: Bernardi Giorgio
Published: December 2018

The general model presented here for the formation of chromatin domains, LADs and TADs, is primarily based on the 3-D structures of the corresponding DNA sequences, the GC-poor and GC-rich isochores. Indeed, the low-heterogeneity GC-poor isochores locally are intrinsically stiff and curved because of the presence of interspersed oligo-Adenines. In contrast, the high-heterogeneity GC-rich isochores are in the shape of peaks characterized by increasing levels of GC and of interspersed oligo-Guanines. In LADs, oligo-Adenines induce local nucleosome depletions leading to structures that are well suited for the attachment to (and embedding in) the lamina. In TADs, the gradients of GC and of oligo-Guanines are responsible for a decreasing nucleosome density, decreasing supercoiling and increasing accessibility. This “moulding step” shapes the “primary TADs” into loops that lack self-interactions, being CTCF/cohesin-free structures. The cohesin complex then binds to the tips of “primary TADs” and slides down the loops, thanks to Nipbl, an essential factor for loading cohesin and for stimulating its ATPase activity and its translocation. This “extruding step” leads to closer contacts and to self-interactions in the loops and stops at the CTCF binding sites located at the base of the loops that are thus closed and insulated.
Fresh-blood-free diet for rearing malaria mosquito vectors
Authors: Marques Joana , Cardoso João C. R. , Felix Rute C. , Santana Rosa A. G. , Guerra Maria das Graças Barbosa , Power Deborah , Silveira Henrique
Published: December 2018

Mosquito breeding depends on the supply of fresh vertebrate blood, a major bottleneck for large-scale production of Anopheles spp. Feeding alternatives to fresh blood are thus a priority for research, outdoor large-cage trials and control interventions. Several artificial meal compositions were tested and Anopheles oogenesis, egg laying and development into the next generation of adult mosquitoes were followed. We identified blood-substitute-diets that supported ovarian development, egg maturation and fertility as well as, low progeny larval mortality, and normal development of offspring into adult mosquitoes. The formulated diet is an effective artificial meal, free of fresh blood that mimics a vertebrate blood meal and represents an important advance for the sustainability of Anopheles mosquito rearing in captivity.
An automated bacterial concentration and recovery system for pre-enrichment required in rapid Escherichia coli detection
Authors: Zhang Yushan , Xu Chang-qing , Guo Tianyi , Hong Lingcheng
Published: December 2018

One of the biggest challenges in rapid low concentration bacterial detection is the pre-concentration or pre-enrichment, which aims to increase bacteria concentration and reduce sample volume for easy bacterial detection. In practical bacterial detection, large-volume water samples with a pathogenic bacterial concentration of less than 1 CFU/mL have to be tested rapidly. The reported biosensors either have insufficient detection limit or have limited capability of handling a sufficiently large water sample. Therefore, a high-performance automated pre-enrichment process is strongly demanded in rapid practical bacterial detection. In this paper, a practical high performance automated bacterial concentration and recovery system (ABCRS) based on the combination of a ceramic membrane and tangential flow filtration technique was presented with short processing time (less than one hour), low pre-enrichment limit (≤0.005 CFU/mL), high concentration ratio (≥ 500), high recovery efficiency (~ 90%), and small final retentate volume (≤ 5 mL).
Quantitative Model for Ion Transport and Cytoplasm Conductivity of Chinese Hamster Ovary Cells
Authors: Fazelkhah Azita , Braasch Katrin , Afshar Samaneh , Salimi Elham , Butler Michael , Bridges Greg , Thomson Douglas
Published: December 2018

In mammalian cells cytoplasm ion concentrations and hence cytoplasm conductivity is an important indicator of their physiological state. Changes in the cytoplasm conductivity has been associated with physiological changes such as progression of cancer and apoptosis. In this work, a model that predicts the effects of physiological changes in ion transport on the cytoplasm conductivity of Chinese hamster ovary (CHO) cells is demonstrated. We determined CHO-specific model parameters, Na+/K+ATPase pumps and ion channels densities, using a flux assay approach. The obtained sodium (PNa), potassium (PK) and chloride (PCl) permeability and Na+/K+ATPase pump density were estimated to be 5.6 × 10−8 cm/s, 5.6 × 10−8 cm/s, 3.2 × 10−7 cm/s and 2.56 × 10−11 mol/cm2, respectively. The model was tested by comparing the model predictions with the experimentally determined temporal changes in the cytoplasm conductivity of Na+/K+ATPase pump inhibited CHO cells. Cells’ Na+/K+ATPase pumps were inhibited using 5 mM Ouabain and the temporal behavior of their cytoplasm conductivity was measured using dielectrophoresis cytometry. The measured results are in close agreement with the model-calculated values. This model will provide insight on the effects of processes such as apoptosis or external media ion concentration on the cytoplasm conductivity of mammalian cells.