bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudobactins bounded iron nanoparticles for control of an antibiotic‐resistant Pseudomonas aeruginosa ryn32
Authors: Kotb Essam , Ahmed Asmaa A. , Saleh Tawfik A. , Ajeebi Afnan M. , Al‐Gharsan Mona S. , Aldahmash Noura F.
Published: September 2019

Among 50 strains of Pseudomonas aeruginosa tested for the resistance to antibiotics, strain ryn32 was selected for this study based on its resistance level. It showed complete resistance toward aztreonam and almost complete resistance (96%) against kanamycin. Iron nanoparticles (FeNPs) were then prepared and found with diameters 30–50 nm. The threshold level of FeNPs for pyoverdines (PVDs) production by P. aeruginosa ryn32 was found at 25 μM concentration. PVDs production was optimal with pH 7.5, 35°C, succinate as carbon source, ammonium sulfate as nitrogen source at 60 hr fermentation time. Interestingly, when used the PVDs as conjugates with FeNPs they showed antibacterial action against the producing strain and some other gram‐negative bacteria. This suggests that the conjugates enter the bacterial cell via the ferriPVDs uptake pathway, which triggers the accumulation of FeNPs inside the cell, which is crucial on bacterial viability. Growth stimulation with the same concentrations of FeNPs and PVDs in separate treatments supported this view.
Process characterization strategy for a precipitation step for host cell protein reduction
Authors: Prentice Jessica , Vu Diemchi , Robbins David , Ferreira Gisela
Published: September 2019

Process characterization using QbD approaches has rarely been described for precipitation steps used for impurity removal in biopharmaceutical processes. We propose a two‐step approach for process characterization in which the first step focuses on product quality and the second focuses on process performance. This approach provides an efficient, streamlined strategy for the characterization of precipitation steps under the Quality by Design paradigm. This strategy is demonstrated by a case study for the characterization of a precipitation using sodium caprylate to reduce host cell proteins (HCP) during a monoclonal antibody purification process. Process parameters were methodically selected through a risk assessment based on prior development data and scientific knowledge described in the literature. The characterization studies used two multivariate blocks to decouple and distinguish the impact of product quality (e.g., measured HCP of the recovered product from the precipitation) and process performance (e.g., step yield). Robustness of the precipitation step was further demonstrated through linkage studies across the overall purification process. HCP levels could be robustly reduced to ≤100 ppm in the drug substance when the precipitation step operated within an operation space of ≤1% (m/v) sodium caprylate, pH 5.0–6.0, and filter flux ≤300 L/m2‐hr for a load HCP concentration up to 19,000 ppm. This two‐step approach for characterization of precipitation steps has several advantages, including tailoring of the experimental design and scale‐down model to the intended purpose for each step, use of a manageable number of experiments without compromising scientific understanding, and limited time and material consumption.
Bioprocess strategies for enhancing biomolecules productivity in Chlorella fusca LEB 111 using CO2 a carbon source
Authors: Moraes Luiza , Santos Lucielen O. , Costa Jorge A. V.
Published: September 2019

The aim of this study was to evaluate the influence of different carbon dioxide (CO2) concentrations on the distribution of carbon forms in the culture medium and the biomass production and biomolecules productivity of the strain Chlorella fusca LEB 111. In this study, experiments were carried out in which C. fusca cultures were exposed to different CO2 concentrations, 0.03% (0.08 mlCO2 mlmedium−1 days−1), 5% (0.18 mlCO2 mlmedium−1 days−1), and 15% vol/vol CO2 (0.54 mlCO2 mlmedium−1 days−1). Among the carbon chemical species distributions in the culture medium, bicarbonate was predominant (94.2–98.9%), with the highest quantitative percentage in the experiment receiving a 15% CO2 injection. C. fusca LEB 111 cultivated with 15% CO2 showed the highest biomass productivity (194.3 mg L−1 days−1) and CO2 fixation rate (390.9 mg L−1 days−1). The carbohydrate productivity in the culture that received 15% CO2 was 46.2% higher than the value verified for the culture with the addition of CO2 from the air (0.03% CO2). In addition, CO2 concentration providing increases of 0.03–15% to C. fusca cultures resulted in a 31.6% increase in the lipid productivity. These results showed that C. fusca can be used for CO2 bioconversion and for producing biomass with potential applications for biofuels and bioproducts.
Combining pretreatment plasma Epstein‐Barr virus DNA level and cervical node necrosis improves prognostic stratification in patients with nasopharyngeal carcinoma: A cohort study
Authors: Du Yu‐Yun , Luo Dong‐Hua , Sun Xue‐Song , Tang Lin‐Quan , Mai Hai‐Qiang , Chen Qiu‐Yan , Zhong Jing‐Hua , Mai Dong‐Mei , Zhang Wan‐Ru , Chen Wen‐Hui , Mo Hao‐Yuan
Published: September 2019

This study aimed to evaluate the prognostic value of combining pretreatment Epstein‐Barr virus (EBV) DNA level and cervical node necrosis (CNN) for patients with nasopharyngeal carcinoma (NPC) receiving intensity‐modulated radiotherapy (IMRT). A total of 607 incident nonmetastatic NPC patients treated with IMRT ± chemotherapy were reviewed. Patients were divided into four groups based on EBV DNA level and CNN status. The primary endpoint was progression‐free survival (PFS). Kaplan‐Meier curves with log‐rank test were applied to compare survival outcomes and the Cox proportional model was used to identify independent prognostic factors. Pretreatment EBV DNA level and CNN status were independent prognostic factors. Patients in the low‐level EBV DNA group or non‐CNN group had significantly better 5‐year PFS. Multivariate analyses demonstrated that CNN was an independent prognostic factor for overall survival (OS) (HR = 1.927, 95% CI: 1.129‐3.290, P = .016), PFS (HR = 1.492, 95% CI: 1.005‐2.214, P = .047), distant metastasis‐free survival (DMFS) (HR = 1.661, 95% CI: 1.044‐2.644, P = .032), but not locoregional relapse‐free survival. EBV DNA levels correlated significantly with CNN with a correlation coefficient of .324 (P < .001). Compared with low‐level EBV DNA and non‐CNN grouping, high‐level EBV DNA and CNN grouping had poor PFS. The combined classification was an independent prognostic factor for OS (P < .001), PFS (P = .001), and DMFS (P = .018). Pretreatment plasma EBV DNA level and CNN status both closely correlated with prognosis of NPC patients in the IMRT era. Combined EBV DNA level and CNN status improves risk stratification and prognostic value.
Synthesis, Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives
Authors: Khan Rehan , Ulusan Sinem , Banerjee Sreeparna , Dogan Özdemir
Published: September 2019

New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel−Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent.
Silencing long noncoding RNA OGFRP1 inhibits the proliferation and migration of cervical carcinoma cells
Authors: Zou Kun , Yu Haifeng , Chen Xuehua , Ma Qian , Hou Lifang
Published: September 2019

Cervical cancer is still a serious threat to women's health and life safety worldwide, and new treatment strategies are urgently needed. Accumulating evidences also imply that long non‐coding RNAs (lncRNAs) are involved in a wide range of cellular processes, such as cell proliferation, apoptosis, and cell cycle. We found that the expression of lncOGFRP1 in cervical cancer tissues was significantly higher than that in normal cervical tissues (P < .05). Further, CCK8 detection found when lncOGFRP1 was silenced, the proliferation of cells was inhibited. After depleting lncOGFRP1, the proportion of apoptosis cells in C33A (3.71 ± 0.38% VS 11.98 ± 1.26%, P < .05) and SiHa (0.69 ± 0.06% VS 11.06 ± 1.03%, P < .05) cells increased significantly, and cell cycle was arrested in S phase. On the other hand, migration detection found the migration of cells also was hindered when lncOGFRP1 level was reduced. And the depletion of lncOGFRP1 inhibited the expression of β‐catenin, Vimentin, N‐cadherin, and SNAIL and promoted the expression of E‐cadherin. In summary, we first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells.

Significance of the study

We first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells. These results help to better understand the pathogenesis and development of cervical cancer and provide insight to develop better diagnosis and treatment strategies.
Insight into the Mechanism of Phenylacetate Decarboxylase (PhdB), a Toluene‐Producing Glycyl Radical Enzyme
Authors: Rodrigues Andria V. , Tantillo Dean J. , Mukhopadhyay Aindrila , Keasling Jay D. , Beller Harry R.
Published: September 2019

We recently reported the discovery of phenylacetate decarboxylase (PhdB), representing one of only ten glycyl‐radical‐enzyme reaction types known, and a promising biotechnological tool for first‐time biochemical synthesis of toluene from renewable resources. Here, we used experimental and computational data to evaluate the plausibility of three candidate PhdB mechanisms, involving either attack at the phenylacetate methylene carbon or carboxyl group [via H‐atom abstraction from COOH or single‐electron oxidation of COO− (Kolbe‐type decarboxylation)]. In vitro experimental data included assays with F‐labeled phenylacetate, kinetic studies, and tests with site‐directed PhdB mutants; computational data involved estimation of reaction energetics using density functional theory (DFT). The DFT results indicated that all three mechanisms are thermodynamically challenging (beyond the range of many known enzymes in terms of endergonicity or activation energy barrier), reflecting the formidable demands on PhdB for catalysis of this reaction. Evidence that PhdB was able to bind α,α‐difluorophenylacetate but was unable to catalyze its decarboxylation supported the enzyme's abstraction of a methylene H atom. Diminished activity of H327A and Y691F mutants was consistent with proposed proton donor roles for His327 and Tyr691. Collectively, these and other data most strongly support PhdB attack at the methylene carbon.
Procedural, clinical, and health status outcomes in chronic total coronary occlusion revascularization: Results from the PERSPECTIVE study
Authors: Kandzari David E. , Lembo Nicholas J. , Carlson Harold D. , Kalynych Anna , Spertus John A. , Gibson C. Michael , Chi Gerald , Morgan Jayne , Rinehart Sarah , Yehya Amin , Qian Zhen , Ajose Bola , Karmpaliotis Dimitri
Published: September 2019

Background

Limited research has detailed the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) with independent core laboratory and event adjudication. This study examined procedural, clinical, and patient‐reported health status outcomes among patients undergoing CTO PCI with specific focus on outcomes for those treated with zotarolimus‐eluting stents (ZES).

Methods

Among 500 consecutive patients undergoing attempted CTO PCI, procedural and in‐hospital clinical outcomes were examined in addition to the 1‐year composite endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events, MACE). In a pre‐specified cohort of 250 patients, health status measures were ascertained at baseline and 1 year. A powered secondary endpoint was 1‐year MACE among patients treated with ZES compared with a performance goal.

Results

Demographic, lesion, and procedural characteristics for the overall population included prior bypass surgery, 29.8%; diabetes, 35.2%; occlusion length >20 mm, 71.3%; J‐CTO score, 2.5 ± 1.1; and primary retrograde strategy, 30.8%. Overall guidewire crossing was 90.9%; clinical success following guidewire crossing, 94.3%; and 1‐year MACE rate, 12.1%. One‐year health status significantly improved from baseline with successful CTO‐PCI (angina frequency, 72.7 ± 26.5 at baseline to 96.0 ± 10.8, p < .0001). Compared with a performance goal derived from prior CTO DES trials (1‐year hierarchal MACE, 25.2%), treatment with ZES was associated with significantly lower MACE (18.2%, one‐sided upper CI, 23.6%, p = .017).

Conclusions

Favorable procedural success, health status improvements and late‐term clinical outcomes inform the relative risks and benefits of CTO PCI when performed in a clinically indicated, complex patient population representative of those treated in clinical practice.
Predictors of survival in patients with acute coronary syndrome undergoing percutaneous coronary intervention of unprotected left main coronary artery stenosis
Authors: Staudacher Dawid L. , Schmitt Charlotte , Zirlik Andreas , Zehender Manfred , Stachon Peter , Bothe Wolfgang , Zotzmann Viviane , Bode Christoph , von zur Muehlen Constantin
Published: September 2019

Objective

Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX‐1‐score.

Background

In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX‐1‐score > 32, PCI may be preferable in unstable or high operative risk patients.

Methods

Retrospective single‐center all‐comers registry study.

Results

A total of 142 patients underwent ULMCA‐PCI (~72.9 years, 23.2% females, 54.2% survival in 2‐year follow‐up), 84 of whom had a SYNTAX‐1 > 32 (37.4 ± 12.8). Patients in the high‐SYNTAX‐1‐group (score > 32) were more often in an acute condition compared to low‐SYNTAX‐2‐group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX‐1‐score was limited in our patient collective in both groups (c‐index 0.65 vs. 0.63) while SYNTAX‐2‐PCI‐score performed better (c‐index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c‐index 0.87 vs. 0.78).

Conclusions

The majority of patients undergoing ULMCA‐PCI presented in acute conditions with high SYNTAX‐1‐score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX‐1‐score.
Engineering resilience with precast monolithic refractory articles
Authors: Goski Dana , Lambert Matthew
Published: September 2019

Precast refractory ceramic shapes have had well‐known benefits over other refractory lining methods: consistent and controlled manufacturing processes with faster turnaround than traditional cast‐in‐place monolithic refractories, reduced labor cost over classic brick installations, and, if well designed, simple repair assemblies. By analyzing the common failure modes of precast monolithic shapes, a distinct method to enhance these advantages was theorized. Through modeling and in‐field testing, the use of multicomponent and heterogeneous composite refractory systems incorporating high‐temperature reinforcement structures increased reliability and provided more predictable modes of failure.
One‐Step Photochemical Green Synthesis of Water‐Dispersible Ag, Au, and Au@Ag Core–Shell Nanoparticles
Authors: Perez‐Lloret Marta , Fraix Aurore , Petralia Salvatore , Conoci Sabrina , Tafani Virginie , Cutrone Giovanna , Vargas‐Berenguel Antonio , Gref Ruxandra , Sortino Salvatore
Published: September 2019

A simple and green synthetic protocol for the rapid and effective preparation of Ag, Au and Au@Ag core–shell nanoparticles (NPs) is reported based on the light irradiation of a biocompatible, water‐soluble dextran functionalized with benzophenone (BP) in the presence of AgNO3, HAuCl4, or both. Photoactivation of the BP moiety produces the highly reducing ketyl radicals through fast (<50 ns) intramolecular H‐abstraction from the dextran scaffold, which, in turn, ensures excellent dispersibility of the obtained metal NPs in water. The antibacterial activity of the AgNPs and the photothermal action of the Au@Ag core–shell are also shown.
Fluorescence Properties and Exciplex Formation of Emissive Naphthyridine Derivatives: Application as Sensors for Amines
Authors: Hirota Junko , Usui Kazuteru , Fuchi Yasufumi , Sakuma Masaomi , Matsumoto Shota , Hagihara Ryusuke , Karasawa Satoru
Published: September 2019

Water‐soluble donor–acceptor‐type fluorophore 15Nap‐Cl having two trifluoromethyl groups and a Cl group on a 1,5‐aminonaphthyridine framework was prepared. Fluorophore 15Nap‐Cl showed strong solvatochromic fluorescence, and, as the solvent polarity increased, a bathochromic shift was observed accompanied by an increase in the fluorescence quantum yield. In addition, in the presence of amines such as ethylamine, diethylamine, and aniline, further considerable bathochromic shifts in the fluorescence were observed. Density functional calculations identified the source of the fluorescence behavior as exciplex formation between 15‐Nap‐Cl and the corresponding amine. The fluorescence behavior was exploited to fabricate a sensor that can identify various primary, secondary, and tertiary amines.
Development of a Measuring Method for the Determination of Bisulfite and Sulfite in Seawater
Authors: Birkmann Jan , Pasel Christoph , Luckas Michael , Bathen Dieter
Published: September 2019

In conventional reverse osmosis processes for seawater desalination, a disinfection of the process stream with chlorine compounds is carried out for antifouling. After disinfection the reduction agent Na2S2O5 is used for the removal of residual chlorine in a strongly overstoichiometric way in order to protect the membranes from oxidational damages. To save chemicals a controlled dosing of Na2S2O5 based on a reliable concentration measurement is desirable. Therefore, a measuring method for the determination of the sulfur(IV) components bisulfite and sulfite in seawater is developed based on the combination of UV spectroscopy and a PLS regression method. Experimental results as well as the development of the regression model for sulfur species in ultrapure and seawater is described.
Acid Extraction from Liquid Phase Pyrolysis Oil Using Cyanex®923 and Subsequent Solvent Regeneration
Authors: Painer Daniela , Treusch Klara , Schwaiger Nikolaus , Weiß Tanja , Pucher Peter , Siebenhofer Matthäus
Published: September 2019

Liquid phase pyrolysis (LPP) oil, an intermediate from biofuel production using second‐generation biomass, is a promising source of biobased platform chemicals like acetic acid, however, displaying a complex, multicomponent mixture. Reactive extraction with Cyanex®923 was investigated for selective recovery of acids and subsequent solvent regeneration in distillation at 200 mbar. In a three‐stage extraction 81 % of acids were removed from the LPP oil without loss of Cyanex®923 to the raffinate. Solvent regeneration efficiency of acids was up to 99.7 % with mainly acids and water in the distillate.
Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans, rats, and mice
Authors: Tapia‐González Silvia , Insausti Ricardo , DeFelipe Javier
Published: September 2019

Secretagogin (SCGN) is a recently discovered calcium‐binding protein belonging to the group of EF‐hand calcium‐binding proteins. SCGN immunostaining has been described in various regions of the human, rat and mouse brain. In these studies, it has been reported that, in general, the patterns of SCGN staining differ between rodents and human brains. These differences have been interpreted as uncovering phylogenetic differences in SCGN expression. Nevertheless, an important aspect that is not usually taken into account is that different methods are used for obtaining and processing brain tissue coming from humans and experimental animals. This is a critical issue since it has been shown that post‐mortem time delay and the method of fixation (i.e., perfused vs. nonperfused brains) may influence the results of the immunostaining. Thus, it is not clear whether differences found in comparative studies with the human brain are simply due to technical factors or species‐specific differences. In the present study, we analyzed the pattern of SCGN immunostaining in the adult human hippocampal formation (DG, CA1, CA2, CA3, subiculum, presubiculum, and parasubiculum) as well as in the entorhinal and perirhinal cortices. This pattern of immunostaining was compared with rat and mouse that were fixed either by perfusion or immersion and with different post‐mortem time delays (up to 5 hr) to mimic the way the human brain tissue is usually processed. We found a number of clear similarities and differences in the pattern of labeling among the human, rat, and mouse in these brain regions as well as between the different brain regions examined within each species. These differences were not due to the fixation.
Quantum‐behaved RS‐PSO‐LSSVM method for quality prediction in parts production processes
Authors: Yingying Su , Lianjuan Han , Jianan Wang , Huimin Wang
Published: September 2019

Quality control in the production process is the core of the enterprise to ensure product quality, and quality prediction is the key link of quality control and quality management. Aiming at the quality prediction of parts in the production process, a product quality prediction model is established. In this model, Rough Set (RS), Particle Swarm Optimization (PSO), and Least Square Support Vector Machine (LSSVM) are applied to solve the problem of product quality prediction and a RS‐PSO‐LSSVM synthesis algorithm is established. First, the 5M1E analysis of production process for parts is carried out, and the index system of influencing factors is established. Based on this index system, the condition attributes and decision attributes of RS are determined, in which RS is used to the reduction to extract rules and the optimal condition attribute value is obtained, which is used as the pre‐processing of LSSVM input data. Second, in order to improve the learning and generalization ability of LSSVM, PSO is used to optimize the relevant parameters and find the optimal solution. Finally, an example is given to verify the feasibility and effectiveness of the product quality prediction model and the RS‐PSO‐LSSVM comprehensive algorithm established above, and the prediction accuracy is higher than that of the RS‐LSSVM algorithm.
Early exposure to a methyl donor supplemented diet and the development of repetitive motor behavior in a mouse model
Authors: Muehlmann Amber M. , Bliznyuk Nikolay , Duerr Isaac , Yang Thomas P. , Lewis Mark H.
Published: September 2019

Motor behaviors that are repetitive and exhibit little variability in form are common in neurodevelopmental disorders (e.g., autism spectrum disorder). C58 mice exhibit persistent, high levels of repetitive motor behavior when reared in restricted, but not enriched, environments implicating epigenetic mechanisms (e.g., DNA methylation). We sought to determine if alteration of DNA methylation played a role in the development of repetitive behavior in C58 mice. Thus, we tested the hypothesis that early exposure (in utero and preweaning) to a methyl donor supplemented diet would alter the developmental trajectory of repetitive behavior. Such dietary exposure resulted in significant attenuation of repetitive motor behavior development, persisting through early adulthood. This was despite mice being housed in standard cages and maintained on a standard diet, postweaning. Early exposure to methyl donor supplementation not only affected the frequency of repetitive behavior but also its temporal structure, resulting in more variable patterns of repetitive behavior. Early exposure to the diet was also shown to induce long‐lasting increases in DNA methylation in brain tissue of female mice. The role for alterations in DNA methylation in this model may be one mechanism accounting for the robust effects of the environment on the development of repetitive behavior.
Kv2.1 voltage‐gated potassium channels in developmental perspective
Authors: Jędrychowska Justyna , Korzh Vladimir
Published: September 2019

Kv2.1 voltage‐gated potassium channels consist of two types of α‐subunits: (a) electrically‐active Kcnb1 α‐subunits and (b) silent or modulatory α‐subunits plus β‐subunits that, similar to silent α‐subunits, also regulate electrically‐active subunits. Voltage‐gated potassium channels were traditionally viewed, mainly by electrophysiologists, as regulators of the electrical activity of the plasma membrane in excitable cells, a role that is performed by transmembrane protein domains of α‐subunits that form the electric pore. Genetic studies revealed a role for this region of α‐subunits of voltage‐gated potassium channels in human neurodevelopmental disorders, such as epileptic encephalopathy. The N‐ and C‐terminal domains of α‐subunits interact to form the cytoplasmic subunit of heterotetrameric potassium channels that regulate electric pores. Subsequent animal studies revealed the developmental functions of Kcnb1‐containing voltage‐gated potassium channels and illustrated their role during brain development and reproduction. These functions of potassium channels are discussed in this review in the context of regulatory interactions between electrically‐active and regulatory subunits.
Generation of Nanog reporter mice that distinguish pluripotent stem cells from unipotent primordial germ cells
Authors: Terada Maiko , Kawamata Masaki , Kimura Ryota , Sekiya Sayaka , Nagamatsu Go , Hayashi Katsuhiko , Horisawa Kenichi , Suzuki Atsushi
Published: September 2019

Nanog is a core transcription factor specifically expressed not only in the pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs), embryonic germ cells (EGCs), and induced PSCs (iPSCs), but also in the unipotent primordial germ cells (PGCs). Although Nanog promoter/enhancer regions are well characterized by in vitro analyses, direct correlations between the regulatory elements for Nanog expression and in vivo expression patterns of Nanog have not been fully clarified. In this study, we generated Nanog‐RFP transgenic (Tg) mice in which expression of red fluorescent protein (RFP) is driven by a 5.2 kb Nanog promoter/enhancer region. As expected, RFP was expressed in the inner cell mass of blastocysts, ESCs, and iPSCs. However, RFP fluorescence was not observed in PGCs, although Nanog was expressed in PGCs. Because RFP fluorescence was visible in the PGC‐derived pluripotent EGCs in culture, it was suggested that the reporter gene expression was specifically activated in PSCs. In conclusion, we have generated a novel Nanog‐RFP Tg mouse line that can selectively tag PSCs over unipotent PGCs.
Population genetic structure, migration, and polyploidy origin of a medicinal species Gynostemma pentaphyllum (Cucurbitaceae)
Authors: Zhang Xiao , Su Hailun , Yang Jia , Feng Li , Li Zhonghu , Zhao Guifang
Published: September 2019

Gynostemma pentaphyllum, a member of family Cucurbitaceae, is a perennial creeping herb used as a traditional medicinal plant in China. In this study, six polymorphic nSSR and four EST‐SSR primers were used to genotype 1,020 individuals in 72 wild populations of G. pentaphyllum. The genetic diversity and population structure were investigated, and ecological niche modeling was performed to reveal the evolution and demographic history of its natural populations. The results show that G. pentaphyllum has a low level of genetic diversity and high level of variation among populations because of pervasive asexual propagation, genetic drift, and long‐term habitat isolation. Results of the Mantel test demonstrate that the genetic distance and geographic distance are significantly correlated among G. pentaphyllum natural populations. The populations can be divided into two clusters on the basis of genetic structure. Asymmetrical patterns of historical gene flow were observed among the clusters. For the contemporary, almost all the bidirectional gene flow of the related pairs was symmetrical with slight differences. Recent bottlenecks were experienced by 34.72% of the studied populations. The geographic range of G. pentaphyllum continues to expand northward and eastward from Hengduan Mountains. The present distribution of G. pentaphyllum is a consequence of its complex evolution. Polyploidy in G. pentaphyllum is inferred to be polygenetic. Finally, G. pentaphyllum is a species in need of protection, so in situ and ex situ measures should be considered in the future.
Population structure and spatial ecology of Kordofan giraffe in Garamba National Park, Democratic Republic of Congo
Authors: D'haen Mathias , Fennessy Julian , Stabach Jared A. , Brandlová Karolína
Published: September 2019

Population numbers of Kordofan giraffe (Giraffa camelopardalis antiquorum) have declined throughout its range by more than 85% in the last three decades, including in the isolated easternmost population found in the Garamba National Park (NP) in the Democratic Republic of Congo.

We provide new data on the conservation status and ecology of Kordofan giraffe in Garamba NP, specifically on the current population dynamics, distribution patterns, and spatial ecology for informed conservation management decisions.

Data were gathered between September 26, 2016, and August 17, 2017, through direct observation and from eight GPS satellite collars deployed in early 2016. Movements, distribution patterns, and autocorrelated kernel density home ranges were estimated using the Continuous‐Time Movement Modeling (CTMM) framework. We then compared results with home ranges calculated using the kernel density estimation (95% KDE) method.

The Garamba NP population was estimated to be 45 giraffe with a female‐dominated sex ratio (35% males; 65% females), and adult‐dominated age class ratio (11.2% juveniles; 17.7% subadults; 71.1% adults). The giraffe's distribution was limited to the south‐central sector of the Park, and giraffe were divided over different areas with some degree of connectivity. The average giraffe home range size was 934.3 km2 using AKDE and 268.8 km2 using KDE. Both methods have shown surprisingly large home ranges despite of the relatively high humidity of Garamba NP.

Based on the outcomes of this research, urgent conservation action is needed to protect Garamba's remaining giraffe population.
Photothermally Active Inorganic Nanoparticles: from Colloidal Solutions to Photothermally Active Printed Surfaces and Polymeric Nanocomposite Materials
Authors: Borzenkov Mykola , Pallavicini Piersandro , Chirico Giuseppe
Published: September 2019

Nanoparticles with absorption in Near‐Infrared (NIR) region and subsequent efficient release of heat, are receiving great attention due to wide opportunities of applications in different fields including biotechnology and nanomedicine. However, the colloidal solutions of such nanoparticles may have limitations in effective application connected with long‐term stability of nanoparticle solutions and possible re‐usability. Therefore, this minireview focuses on the state‐of‐the art of research and application of photothermally active nanoparticles to engineer remotely activated materials with controllable photothermal properties: printed surfaces and polymeric nanocomposite materials. We highlight in this minireview different types of photothermally active nanoparticles (e.g. non‐spherical gold nanoparticles, copper sulfide nanoparticles) that already have been applied for fabrication of printed patterns and polymeric nanocomposites, the properties of the resulting materials and further application opportunities.
Redox‐Active Guanidines with One or Two Guanidino Groups and Their Integration in Low‐Dimensional Perovskite Structures
Authors: Walter Petra , Kaifer Elisabeth , Herrmann Hendrik , Wadepohl Hubert , Hübner Olaf , Himmel Hans‐Jörg
Published: September 2019

Redox‐active guanidines are versatile reagents in redox and proton‐coupled electron‐transfer (PCET) reactions. Recently, they were integrated as sacrificial electron donors for the prohibition of metal oxidation in perovskite materials. Herein we report the synthesis and characterization of several new redox‐active guanidines with aromatic (benzene, naphthalene or anthraquinone) cores. Two of these compounds are then integrated in lead iodide materials. The structure, thermal stability and optical band‐gap of the resulting materials are evaluated.
Zn‐Catalyzed [3+2]‐Annulation Strategy: Straightforward Access to Aminoalkyl Indolizines
Authors: Li Junxuan , Yang Daji , Wang Hua , Zhu Baofu , Cao Hua
Published: September 2019

An efficient Zn‐catalyzed [3+2]‐annulation strategy for the synthesis of aminoalkyl indolizines has been developed. The three‐component domino reaction of 2‐(pyridin‐2‐yl)acetates, ynals and amines proceeds smoothly with high efficiency to afford the indolizines in good yields. This transformation may facilitate the development of new synthetic methods for the efficient and sustainable construction of aminoalkyl indolizines in an atom‐economic way from simple, abundant starting materials.
Photocatalytic Isomerization of Styrenyl Halides: Stereodivergent Synthesis of Functionalized Alkenes
Authors: Zhang Hao , Xu Qing , Yu Lei , Yu Shouyun
Published: September 2019

An efficient and general method for the isomerization of styrenyl halides under different photocatalytic conditions (fac‐Ir(ppy)3 in methanol for E to Z isomerization and fluorescein in 1,4‐dioxane for Z to E isomerization, respectively) is disclosed. A series of stereospecific transformations constitute preliminary validation of this strategy in the synthesis of functionalized alkenes, including two diaryl alkenes, a styrenyl boronic ester and an enyne. The photocatalytic isomerization and subsequent cross coupling reaction can be run in a one‐pot manner. The stereodivergent synthesis of all four isomers of a conjugated diene, as well as the antitumor agent DMU‐212 and its (Z)‐isomer highlights the synthetic applicability of this method.
Tightly linked antagonistic-effect loci underlie polygenic phenotypic variation inC. elegans
Authors: Bernstein Max R. , Zdraljevic Stefan , Andersen Erik C. , Rockman Matthew V.
Published: September 2019

Recent work has provided strong empirical support for the classic polygenic model for trait variation. Population-based findings suggest that most regions of genome harbor variation affecting most traits. Here, we use the approach of experimental genetics to show that, indeed, most genomic regions carry variants with detectable effects on growth and reproduction in Caenorhabditis elegans populations sensitized by nickel stress. Nine of 15 adjacent intervals on the X chromosome, each encompassing ∼0.001 of the genome, have significant effects when tested individually in near-isogenic lines (NILs). These intervals have effects that are similar in magnitude to those of genome-wide significant loci that we mapped in a panel of recombinant inbred advanced intercross lines (RIAILs). If NIL-like effects were randomly distributed across the genome, the RIAILs would exhibit phenotypic variance that far exceeds the observed variance. However, the NIL intervals are arranged in a pattern that significantly reduces phenotypic variance relative to a random arrangement; adjacent intervals antagonize one another, cancelling each other's effects. Contrary to the expectation of small additive effects, our findings point to large-effect variants whose effects are masked by epistasis or linkage disequilibrium between alleles of opposing effect.
Elevated incidence of head and neck cancer in solid organ transplant recipients
Authors: Mowery Alia J. , Conlin Michael J. , Clayburgh Daniel R.
Published: September 2019

Background

Solid organ transplant recipients are known to be at an increased risk of cancer development, but research on head and neck cancer in transplant recipients has been limited and prior risk assessments may not be accurate.

Methods

A retrospective review using a national Veterans Administration database to query outpatient problem lists for ICD codes indicating solid organ transplant and subsequent diagnosis of head and neck cancer.

Results

In a study of 30 939 656 patients (37 969 solid organ transplants and 113 995 head and neck cancers), history of transplant significantly predicted head and neck cancer, with relative risks ranging from 1.85 (thyroid) to 2.91 (salivary gland). Worse overall survival (OS) was seen for head and neck cancer patients with prior transplants.

Conclusions

In a large case‐control study, prior transplant was a risk factor for head and neck cancer development and worse OS for head and neck cancer patients.
Free flap salvage from venous thrombosis by creation of a venocutaneous fistula: Case report and review of the literature
Authors: Sethia Rishabh , Allarakhia Zahir , Puram Sidharth , Kang Stephen , Ozer Enver , Agrawal Amit , Carrau Ricardo , Rocco James , Old Matthew
Published: September 2019

Background

Venous congestion is the most frequently reported complication of free flap tissue transfer in head and neck patient with cancer. Numerous methods are utilized and prompt correction is necessary to prevent flap failure.

Methods

A 77‐year‐old woman underwent oral cavity resection and neck dissection for squamous cell carcinoma followed by radial forearm free flap for reconstruction. Three days later, the flap became congested and surgical exploration revealed extensive venous thrombosis throughout the free flap venous system and internal jugular vein. The flap vein was evacuated and flowing, and a venocutaneous fistula was created thereafter.

Results

Venocutaneous fistula resulted in flap decongestion and successful salvage. The patient was discharged from the hospital with no further flap or surgical complications.

Conclusion

When anatomical revision of the venous anastomosis is not feasible in a venous‐congested free flap, the creation of a venocutaneous fistula should be considered as a viable option for salvage.
EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks
Authors: Gouya Laurent , Ventura Paolo , Balwani Manisha , Bissell D. Montgomery , Rees David C. , Stölzel Ulrich , Phillips John D. , Kauppinen Raili , Langendonk Janneke G. , Desnick Robert J. , Deybach Jean‐Charles , Bonkovsky Herbert L. , Parker Charles , Naik Hetanshi , Badminton Michael , Stein Penelope E. , Minder Elisabeth , Windyga Jerzy , Bruha Radan , Cappellini Maria Domenica , Sardh Eliane , Harper Pauline , Sandberg Sverre , Aarsand Aasne K. , Andersen Janice , Alegre Félix , Ivanova Aneta , Talbi Neila , Chan Amy , Querbes William , Ko John , Penz Craig , Liu Shangbin , Lin Tim , Simon Amy , Anderson Karl E.
Published: September 2019

Background and Aims

Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long‐term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients.

Approach and Results

EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0‐52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0‐37.0]). Elevated levels of hepatic δ‐aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ‐aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization.

Conclusions

Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day‐to‐day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
Protective Effect of SMAD‐Specific E3 Ubiquitin Protein Ligase 1 in Alcoholic Steatohepatitis in Mice
Authors: Petrasek Jan , Erhartova Denisa , Levine Beth
Published: September 2019

Excessive accumulation of lipids in the liver is crucial in the pathogenesis of alcoholic steatohepatitis and may be partly mediated by impaired degradation of lipid droplets by autophagy. The E3 ubiquitin ligase SMAD‐specific E3 ubiquitin protein ligase 1 (SMURF1) regulates selective autophagy by ubiquitinating proteins on cargo destined for autophagic delivery to the lysosome for degradation. Here, we evaluated the role of SMURF1 in the regulation of hepatic lipid degradation in alcoholic steatohepatitis. In patients with severe alcoholic hepatitis, SMURF1 colocalized with lipid droplet membranes in liver explants. In a mouse model of alcoholic steatohepatitis, Smurf1
−/− mice fed an alcohol diet displayed increased hepatocyte accumulation of lipid droplets and triglycerides as well as more severe liver injury compared to wild‐type mice. The increased severity of liver steatosis in alcohol‐fed Smurf1
−/− mice was rescued by adeno‐associated virus (AAV) serotype 8‐mediated hepatic expression of wild‐type Smurf1 protein but not by mutant Smurf1 proteins either lacking the catalytically active cysteine 699 required for ubiquitin transfer or the N‐terminal C2 phospholipid membrane‐binding domain. Conclusion: Smurf1 plays a protective role in the pathogenesis of alcoholic steatohepatitis through a mechanism that requires both its ubiquitin‐ligase activity and C2 phospholipid‐binding domains. These findings have implications for understanding the roles of ubiquitin ligases in fatty liver disease.
The development of emotional intelligence, self‐efficacy, and locus of control in Master of Business Administration students
Authors: Thompson Claire L. , Kuah Adrian T. H. , Foong Regina , Ng Eddy S.
Published: September 2019

Successful managers must develop strong interpersonal skills alongside their ability to achieve personal and organizational goals. For educational institutions to stay relevant, courses must equip students with necessary psychological competencies in addition to technical knowledge, skills and abilities for the constantly evolving business climate. We explored whether Master of Business Administration (MBA) programs aid in the development of psychological competencies, given that MBAs are a popular management development tool. Specifically, we investigated changes in MBA candidates' emotional intelligence (EI) ability, self‐efficacy (SE), and locus of control (LoC) in a pre‐post survey design over the course of a 1‐year MBA educational program and explored the relationship of candidate's baseline psychological status to their academic success in the MBA educational program. Participants were recruited from newly enrolled students at an international university in Asia. The study participants (53 MBA students, plus 26 psychology students, and 34 nonstudents as comparison groups) completed self‐report measures of EI, SE, and LoC at the beginning and end of a 1‐year MBA period. The MBA candidates showed significant improvement in EI, SE, and LoC‐internality, as well as an increase in LoC‐powerful others during the program. LoC‐powerful others at the beginning of the program also predicted MBA students' academic performance. The findings provide evidence that psychological competencies that may positively affect work performance are key benefits of MBA education.
The potential role of regulatory microRNAs of RAS/MAPK signaling pathway in the pathogenesis of colorectal cancer
Authors: Soleimani Atena , Rahmani Farzad , Saeedi Nikoo , Ghaffarian Rana , Khazaei Majid , Ferns Gordon A. , Avan Amir , Hassanian Seyed Mahdi
Published: September 2019

Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Dysregulation of RAS/MAPK signaling axis is frequently found in CRC patients. The RAS/MAPK axis regulates cancer cell proliferation, apoptosis, inflammation, migration, and metastasis. Oncogenic or tumor‐suppressor microRNAs (miRNAs) for RAS/MAPK signaling play a key role in the pathogenesis of CRC and are considered as novel potential biomarkers for diagnosis and prognosis of human malignancies. This review summarizes the current knowledge of mechanisms of action of RAS/MAPK miRNAs in the development and progression of CRC for a better understanding and hence a better management of this disease.