bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Domain‐Confined Growth Strategy for In Situ Controllable Fabrication of Individual Hollow Nanostructures
Authors: Tang Luping , He Longbing , Zhang Lei , Yu Kaihao , Xu Tao , Zhang Qiubo , Dong Hui , Zhu Chao , Sun Litao
Published: February 2018

The manipulation and tailoring of the structure and properties of semiconductor nanocrystals (NCs) is significant particularly for the design and fabrication of future nanodevices. Here, a novel domain‐confined growth strategy is reported for controllable fabrication of individual monocrystal hollow NCs (h‐NCs) in situ inside a transmission electron microscope, which enables the atomic scale monitoring of the entire reaction. During the process, the preformed carbon shells serve as nanoreaction cells for the formation of CdSeS h‐NCs. Electron beam (e‐beam) irradiation is demonstrated to be the key activation factor for the solid‐to‐hollow shape transformation. The formation of CdSeS hollow NCs is also found to be sensitive to the volume ratio of the CdSe/CdS NCs to the carbon shell and only those CdSe/CdS NCs with a volume ratio in the range 0.2–0.8 are successfully converted into hollow NCs. The method paves the way to potentially use an e‐beam for the in situ tailoring of individual semiconductor NCs targeted toward future nanodevice applications.
Hydrophilicity Regulates the Stealth Properties of Polyphosphoester‐Coated Nanocarriers
Authors: Simon Johanna , Wolf Thomas , Klein Katja , Landfester Katharina , Wurm Frederik R. , Mailänder Volker
Published: February 2018

Increasing the plasma half‐life is an important goal in the development of drug carriers, and can be effectively achieved through the attachment of polymers, in particular poly(ethylene glycol) (PEG). While the increased plasma half‐life has been suggested to be a result of decreased overall protein adsorption on the hydrophilic surface in combination with the adsorption of specific proteins, the molecular reasons for the success of PEG and other hydrophilic polymers are still widely unknown. We prepared polyphosphoester‐coated nanocarriers with defined hydrophilicity to control the stealth properties of the polymer shell. We found that the log P value of the copolymer controls the composition of the protein corona and the cell interaction. Upon a significant change in hydrophilicity, the overall amount of blood proteins adsorbed on the nanocarrier remained unchanged, while the protein composition varied. This result underlines the importance of the protein type for the protein corona and cellular uptake.
Similarly sized protein separation of charge‐selective ethylene‐vinyl alcohol copolymer membrane by grafting dimethylaminoethyl methacrylate
Authors: Huang Lilan , Ye Hui , Yu Tengfei , Zhang Xiangyu , Zhang Yuzhong , Zhao Lizhi , Xin Qingping , Wang Shaofei , Ding Xiaoli , Li Hong
Published: February 2018

Similarly sized protein separation was investigated using a charge‐selective membrane, which prepared by grafting dimethylaminoethyl methacrylate (DMAEMA) onto ethylene vinyl alcohol copolymer (EVAL) membrane. Bovine serum albumin (BSA) and bovine hemoglobin (BHb) was used as model proteins. P(DMAEMA), the weak cationic polyelectrolyte with ionizable tertiary amine groups, contributed to the charge‐selective separation for BSA and BHb. At pH 6.0, the grafted EVAL membrane surface was positively charged and BSA was negatively charged, while BHb was positively charged. The BSA was adsorbed onto the membrane surface due to electrostatic interaction and the BHb passed through the membrane into the permeate. The charge‐selective behavior resulted in the separation of the similarly sized protein. The maximum separation factors of static adsorption separation for model protein and binary mixture were 32.4 and 37.2, respectively. In the dynamic separation process, the maximum separation factor value was 6.2. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46374.
Inflammation Intensity–Dependent Expression of Osteoinductive Wnt Proteins Is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis
Authors: Li Xiang , Wang Jianru , Zhan Zhongping , Li Sibei , Zheng Zhaomin , Wang Taiping , Zhang Kuibo , Pan Hehai , Li Zemin , Zhang Nu , Liu Hui
Published: February 2018

Objective

To investigate the molecular mechanism underlying inflammation‐related ectopic new bone formation in ankylosing spondylitis (AS).

Methods

Spinal tissues and sera were collected from patients with AS and healthy volunteers and examined for the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone‐forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation‐induced Wnt expression, and the role of Wnt signaling in new bone formation. Modified collagen‐induced arthritis (CIA) and proteoglycan‐induced spondylitis (PGIS) animal models were used to confirm the key findings in vivo.

Results

The levels of osteoinductive Wnt proteins were increased in sera and spinal ligament tissues from patients with AS. Constitutive low‐intensity tumor necrosis factor (TNF) stimulation, but not short‐term or high‐intensity TNF stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF‐κB (p65) and JNK/activator protein 1 (c‐Jun) signaling pathways. Furthermore, inhibition of either the Wnt/β‐catenin or Wnt/protein kinase Cδ (PKCδ) pathway significantly suppressed new bone formation. The increased expression of Wnt proteins was confirmed in both the modified CIA and PGIS models. A kyphotic and ankylosing phenotype of the spine was seen during long‐term observation in the modified CIA model. Inhibition of either the Wnt/β‐catenin or Wnt/PKCδ signaling pathway significantly reduced the incidence and severity of this phenotype.

Conclusion

Inflammation intensity–dependent expression of osteoinductive Wnt proteins is a key link between inflammation and ectopic new bone formation in AS. Activation of both the canonical Wnt/β‐catenin and noncanonical Wnt/PKCδ pathways is required for inflammation‐induced new bone formation.
Comparison of the Reactivities and Selectivities of Group 9 [Cp*MIII] Catalysts in C−H Functionalization Reactions
Authors: Park Juhyeon , Chang Sukbok
Published: February 2018

Pentamethylcyclopentadienyl (Cp*)‐based Group 9 metal (Co, Rh, or Ir) catalysts have emerged as powerful tools for C−H functionalization reactions. Whilst a diverse range of organic transformations have been developed by using [Cp*MIII] catalysts, they have often exhibited orthogonal reactivities and varied selectivities that depended on the choice of the central metal atom. An understanding of the physicochemical properties of the metals, as well as of their reaction mechanisms, has led to significant expansion of the synthetic scope of C−H functionalization reactions. This Focus Review summarizes and discusses the comparative catalytic reactivities and selectivities of the [Cp*MIII] catalysts, with an emphasis on metal‐dependent pathway‐switching by considering the mechanistic rationale.
Validating the pivotal role of the immune system in low‐dose radiation‐induced tumor inhibition in Lewis lung cancer‐bearing mice
Authors: Zhou Lei , Zhang Xiaoying , Li Hui , Niu Chao , Yu Dehai , Yang Guozi , Liang Xinyue , Wen Xue , Li Min , Cui Jiuwei
Published: February 2018

Although low‐dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR‐induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high‐dose radiation (HDR) of 1 Gy. Additionally, the LDR‐induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR‐activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR‐induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice.
Determinants of malignant pleural mesothelioma survival and burden of disease in France: a national cohort analysis
Authors: Chouaid Christos , Assié Jean Baptiste , Andujar Pascal , Blein Cecile , Tournier Charlène , Vainchtock Alexandre , Scherpereel Arnaud , Monnet Isabelle , Pairon Jean Claude
Published: February 2018

This study was undertaken to determine the healthcare burden of malignant pleural mesothelioma (MPM) in France and to analyze its associations with socioeconomic deprivation, population density, and management outcomes. A national hospital database was used to extract incident MPM patients in years 2011 and 2012. Cox models were used to analyze 1‐ and 2‐year survival according to sex, age, co‐morbidities, management, population‐density index, and social deprivation index. The analysis included 1,890 patients (76% men; age: 73.6 ± 10.0 years; 84% with significant co‐morbidities; 57% living in urban zones; 53% in highly underprivileged areas). Only 1% underwent curative surgical procedure; 65% received at least one chemotherapy cycle, 72% of them with at least one pemetrexed and/or bevacizumab administration. One‐ and 2‐year survival rates were 64% and 48%, respectively. Median survival was 14.9 (95% CI: 13.7–15.7) months. The mean cost per patient was 27,624 ± 17,263 euros (31% representing pemetrexed and bevacizumab costs). Multivariate analyses retained men, age >70 years, chronic renal failure, chronic respiratory failure, and never receiving pemetrexed as factors of poor prognosis. After adjusting the analysis to age, sex, and co‐morbidities, living in rural/semi‐rural area was associated with better 2‐year survival (HR: 0.83 [95% CI: 0.73–0.94]; P < 0.01); social deprivation index was not significantly associated with survival. With approximately 1,000 new cases per year in France, MPMs represents a significant national health care burden. Co‐morbidities, sex, age, and living place appear to be significant factors of prognosis.
Long noncoding RNA MALAT1 knockdown reverses chemoresistance to temozolomide via promoting microRNA‐101 in glioblastoma
Authors: Cai Tao , Liu Yu , Xiao Jie
Published: February 2018

Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system with highly infiltrative and resistant to chemotherapy. Temozolomide (TMZ) is widely used as the first‐line treatment for the therapy of GBM. However, a considerable percentage inherent or acquired resistance in GBM accounts for many treatment failures of the TMZ chemotherapy. Therefore, a deeper understanding of the molecular characteristics underlying TMZ resistance and the identification of novel therapeutic target is urgent. Here, we show that MALAT1 was significantly upregulated in TMZ‐resistant GBM cells. On the other hand, MALAT1 knockdown reduces TMZ resistance of GBM cells both in vitro and in vivo by inhibiting cell proliferation and promoting apoptosis. We also show that miR‐101 overexpression reduced TMZ resistance of GBM cells and played an antagonistic role compared with MALAT1. Importantly, we demonstrate that MALAT1 promoted the chemoresistance through suppressing miR‐101 signaling pathway via directly binding it in GBM cells. In conclusion, our study indicates that knockdown of MALAT1 reverses chemoresistance to TMZ via promoting miR‐101 regulatory network in GBM and thus offers a novel prognostic marker and potential target for GBM TMZ‐based chemotherapy.
Efficient Synthesis of Light‐Triggered Circular Antisense Oligonucleotides Targeting Cellular Protein Expression
Authors: Yang Linlin , Kim Hyun Bum , Sul Jai‐Yoon , Yeldell Sean B. , Eberwine James H. , Dmochowski Ivan J.
Published: February 2018

Light‐activated (“caged”) antisense oligonucleotides are powerful molecules for regulating gene expression at submicron spatial resolution through the focal modulation of endogenous cellular processes. Cyclized caged oligos are particularly promising structures because of their inherent stability and similarity to naturally occurring circular DNA and RNA molecules. Here, we introduce an efficient route for cyclizing an antisense oligodeoxynucleotide incorporating a photocleavable linker. Oligo cyclization was achieved for several sequences in nearly quantitative yields through intramolecular copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC). Caging stability and light activation were characterized by FRET efficiency, denaturing gel assay, and melting temperature measurements. Finally, a cyclized caged oligo was designed to target gfap, and it gave a tenfold reduction in glial fibrillary acidic protein upon photoactivation in astrocytes.
Substituents Have a Large Effect on Photochemical Generation of Benzyl Cations and DNA Cross‐Linking
Authors: Fan Heli , Sun Huabing , Peng Xiaohua
Published: February 2018

Photoactivated DNA interstrand cross‐linking agents have a wide range of biological applications. Recently, several aryl boronates have been reported to induce DNA interstrand cross‐link (ICL) formation via carbocations upon photoirradiation. Herein, we synthesized a series of new bifunctional phenyl compounds to test the generality of such a mechanism, and to understand how the chemical structure influences carbocation formation and the DNA cross‐linking process. These compounds efficiently form DNA ICLs via generated benzyl cations upon 350 nm irradiation. The DNA cross‐linking efficiency and the pathway for carbocation generation depend on both the aromatic substituents and the leaving groups. Bromine as a leaving group facilitates the DNA cross‐linking process in comparison with trimethyl ammonium salt. Both electron‐donating and ‐withdrawing substituents induce bathochromic shifts, which favor photoinduced DNA ICL formation. For the bromides, the benzyl cation intermediates were generated through oxidation of the corresponding benzyl radicals. However, for the ammonia salts, the benzyl cations were formed through two pathways: either through oxidation of the benzyl radicals or by direct heterolysis of the C−N bond. Photoinduced C−N homolysis to form benzyl radicals occurred with compounds having donating substituents, whereas direct heterolysis of the C−N bond occurred with those bearing withdrawing substituents. The adducts formed between 1 a and four natural nucleosides were characterized, indicating that the alkylation sites for the photogenerated benzyl cations are dG, dA, and dC.
Dinuclear Lanthanide(III)‐m‐ODO2A‐dimer Macrocyclic Complexes: Solution Speciation, DFT Calculations, Luminescence Properties, and Promoted Nitrophenyl‐Phosphate Hydrolysis Rates
Authors: Chang C. Allen , Lee Hwa‐Yu , Lin Syue‐Liang , Meng Ching‐Ning , Wu Tsung‐Ta
Published: February 2018

Potentiometric speciation studies, mass spectrometry, and DFT calculations helped to predict the various structural possibilities of the dinuclear trivalent lanthanide ion (LnIII, Ln=La, Eu, Tb, Yb, Y) complexes of a novel macrocyclic ligand, m‐ODO2A‐dimer (H4L), to correlate with their luminescence properties and the promoted BNPP and HPNP phosphodiester bond hydrolysis reaction rates. The stability constants of the dinuclear Ln2(m‐ODO2A‐dimer) complexes and various hydrolytic species confirmed by mass spectrometry were determined. DFT calculations revealed that the Y2LH−1 and the Y2LH−2 species tended to form structures with the respective closed‐ and open‐form conformations. Luminescence lifetime data for the heterodimetallic TbEuL system confirmed the fluorescence resonance energy transfer from the TbIII to EuIII ion. The internuclear distance RTbEu values were estimated to be in the range of 9.4–11.3 Å (pH 6.7–10.6), which were comparable to those of the DFT calculated open‐form conformations. Multiple linear regression analysis of the kobs data was performed using the equation: kobs,corr.=kobs−kobs,OH=k
[Ln2LH−1]+k
[Ln2LH−2] for the observed Ln2L‐promoted BNPP/HPNP hydrolysis reactions in solution pH from 7 to 10.5 (Ln=Eu, Yb). The results showed that the second‐order rate constants for the Eu2LH−2 and Yb2LH−2 species were about 50–400 times more reactive than the structural analogous Zn2(m‐12 N3O‐dimer) system.
Elevated lipoprotein(a) and familial hypercholesterolemia in the coronary care unit: Between Scylla and Charybdis
Authors: Ellis Katrina L. , Pang Jing , Chieng David , Bell Damon A. , Burnett John R. , Schultz Carl J. , Hillis Graham S. , Watts Gerald F.
Published: February 2018

Background

Elevated lipoprotein(a) (Lp[a]) and familial hypercholesterolemia (FH) are inherited lipid disorders. Their frequencies, coexistence, and associations with premature coronary artery disease (CAD) in patients admitted to the coronary care unit (CCU) remain to be defined.

Hypothesis

Elevated Lp(a) and FH are commonly encountered among CCU patients and independently associated with increased premature CAD risk.

Methods

Plasma Lp(a) concentrations were measured in consecutive patients admitted to the CCU with an acute coronary syndrome (ACS) or prior history of CAD for 6.5 months. Elevated Lp(a) was defined as concentrations ≥0.5 g/L. Patients with LDL‐C ≥ 5 mmol/L exhibited phenotypic FH. Premature CAD was diagnosed in those age < 60 years, and the relationship between this and elevated Lp(a) and FH was determined by logistic regression.

Results

316 patients were screened; 163 (51.6%) had premature CAD. Overall, elevated Lp(a) and FH were identified in 27.0% and 11.6% of patients, respectively. Both disorders were detected in 4.4% of individuals. Elevated Lp(a) (32.0% vs 22.2%; P = 0.019) and FH phenotype (15.5% vs 8.0%; P = 0.052) were more common with premature vs nonpremature CAD. Elevated Lp(a) alone conferred a 1.9‐fold, FH alone a 3.2‐fold, and the combination a 5.3‐fold increased risk of premature CAD (P = 0.005).

Conclusions

Elevated Lp(a) and phenotypic FH were commonly encountered and more frequent with premature CAD. The combination of both disorders is especially associated with increased CAD risk. Patients admitted to the CCU with ACS or previously documented CAD should be routinely screened for elevated Lp(a) and FH.
NT‐proBNP is associated with mortality and adverse cardiac events in patients with atrial fibrillation presenting to the emergency department
Authors: Holl Marijn J. , van den Bos Ewout J. , van Domburg Ron T. , Fouraux Michael A. , Kofflard Marcel J.
Published: February 2018

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the emergency department. The CHA2DS2‐VASc score helps to predict thromboembolic risk; however, the rate of other adverse cardiac events is more difficult to predict.

Hypothesis

The biomarker N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has prognostic value in patients presenting to the emergency department with AF.

Methods

During a 1.5‐year period, a prospective study was performed in consecutive patients presenting to the emergency department with AF on the presenting electrocardiogram. At baseline, NT‐proBNP was measured. The primary endpoints were all‐cause death and major adverse cardiac events (MACE: all‐cause mortality, myocardial infarction, or revascularization).

Results

A total of 355 patients were included (mean age, 71 years; 55% male). The median duration of follow‐up was 2 years. After adjustment for baseline variables, the logNT‐proBNP was independently correlated with death (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.18‐1.99) and MACE (HR: 1.27, 95% CI: 1.03‐1.58). After adjustment for baseline variables, a high NT‐proBNP value (>500 pmol/L) was independently correlated with death (HR: 2.26, 95% CI: 1.19‐4.28), and for MACE a trend was seen (HR: 1.67, 95% CI: 0.96‐2.91) compared with a low value (<250 pmol/L).

Conclusions

In patients presenting to the emergency department with AF, higher NT‐proBNP values are independently associated with an increased mortality and MACE. Therefore, this biomarker may be a useful prognostic marker in the management and treatment of these patients.
How do we attract and retain women in cardiology?
Authors: Lau Emily S. , Wood Malissa J.
Published: February 2018

The recruitment and advancement of women in cardiology is an important priority for the cardiology community. Despite improvements in sex disparities over the last 2 decades, women remain a small minority in cardiology. Recent studies have revealed key obstacles facing female cardiologists including radiation exposure, family responsibilities, unequal financial compensations, and lack of career advancement. To attract and retain more women into the field of cardiology, the cardiology community, including professional society leaders, division chiefs, and program directors, must all work to overcome these barriers.
Ultrasound‐Assisted Anti‐Solvent Crystallization of Telmisartan Using Dimethyl Sulfoxide as Organic Solvent
Authors: Sharma Chetan , Desai Meghal A. , Patel Sanjaykumar R.
Published: February 2018

In recent years, ultrasound assisted anti‐solvent crystallization has emerged as an excellent approach to reduce the particle size of poorly water‐soluble drugs, thereby achieving improvement in the solubility and bioavailability. In the present study, this concept is employed for telmisartan by studying various critical parameters like the effect of sonication time, sonication amplitude, drug solution concentration, solvent to anti‐solvent ratio, injection rate and crystallization temperature. The particle size of the commercial telmisartan is reduced from 10 µm to 200 nm by anti‐solvent crystallization method by applying 60% ultrasound amplitude for 15 min with 10 mg mL−1 drug concentration, 1:3 of solvent to anti‐solvent ratio, and 10 mL min−1 of injection rate at 30 °C. Physicochemical characteristics; morphology, crystalline structure, the presence of other chemical compounds, enthalpy change, and the melting point of a recovered drug are analyzed using various analytical tools. It is possible to achieve nanoparticles of telmisartan by symbiotic effect of sonication with anti‐solvent crystallization.
Cellular endogenous NAD(P)H fluorescence as a label‐free method for the identification of erythrocytes and reticulocytes
Authors: Tauzin L. , Campos V. , Tichet M.
Published: February 2018

Reticulocytes and erythrocytes are the ultimate differentiated stages of erythropoiesis. In addition to being anucleate cells, they are characterized by the clearance of their mitochondrial pool or lack thereof. Given that for most research‐oriented flow cytometry experiments erythrocytes and reticulocytes are often undesirable cell types, their identification and exclusion from analyses can be essential. Here, we describe a flow cytometric method based on cellular NAD(P)H‐related autofluorescence, whose localization is mainly associated with mitochondria. By increasing the sensitivity of the specific NAD(P)H‐fluorescence detector, we discovered a population with weak levels of NAD(P)H fluorescence signals whose immunophenotypical and physiological characterization in mouse bone marrow led to its identification as both erythrocytes and reticulocytes. Our method showed comparable sensitivity and specificity to the detection of red blood cells based on the absorption of light by oxyhemoglobin. This NAD(P)H‐based approach consistently identified over 95% of the total pool of erythrocytes and reticulocytes in bone marrow samples and revealed robust as over 93% of these two erythropoietic subsets were identified in melanoma tumor samples with the same method. The measurement of cellular endogenous NAD(P)H fluorescence, therefore, offers a reliable and straightforward alternative to identify erythrocytes and reticulocytes without additional immunostaining or the need to modify the cytometer's optical configuration. © 2018 International Society for Advancement of Cytometry
Development of Nonthermal Sterilization Treatment System without Impacting to Enzyme in Vegetable Drink by Pulsed Electric Field
Authors: SAITO KOKI , NOZAWA YASUHITO , MINAMITANI YASUSHI , FUKATA HIDEKI
Published: February 2018

For the sterilization of food, heat sterilization, chemical sterilization, and similar methods are available. However, they cause the change of the quality and flavor of the food. As the solution, the intense pulsed high electric field (IPEF) sterilization method has been studied. IPEF sterilization is used for the nonthermal sterilization of the foods because it destroys the cell membrane of bacteria physically. In this study, we have attempted to apply the IPEF sterilization for green juice. The development of a circulation sterilization system for a practical test was carried out. It was confirmed that enzyme included in the green juice was not deactivated when IPEF was applied. As a result, at applying 20‐min pulse electric field in 30 kV/cm and 40 kV/cm, survival ratios of viable bacteria in the green juice were reduced to about 40% and 12%, respectively. Also, deactivation of superoxide dismutase did not occur when the bacteria were sterilized.
Understanding social–ecological interdependence using ecosystem services perspective in Bhutan, Eastern Himalayas
Authors: Kandel Pratikshya , Tshering Dago , Uddin Kabir , Lhamtshok Tshering , Aryal Kamal , Karki Seema , Sharma Bikash , Chettri Nakul
Published: February 2018

Biophysical and economic values are often used to aid understanding of the complex interplay between ecosystems, their services, and human well‐being, but community values are rarely considered. In a case study of Barshong gewog in Bhutan, we used mapping methods that involved (1) local knowledge and perceptions collected using participatory rural appraisal tools, (2) a household survey, and (3) geospatial inputs, to understand the linkages between human well‐being and ecosystem services at the local level, as perceived by the community. The study identified three major ecosystems—forest, agriculture, and freshwater—that contribute highly to local livelihoods. Collectively, these ecosystems provide a wide range of goods and services, including 22 provisioning, 13 regulating, 4 supporting, and 6 cultural services. About 85% of the households depend directly upon provisioning ecosystem services for their livelihoods and income. The study also identified the importance of the ecosystems in terms of three value domains—ecological, socioeconomic, and cultural.
Aminocatalytic Privileged Diversity‐Oriented Synthesis (ApDOS): An Efficient Strategy to Populate Relevant Chemical Spaces
Authors: Pawar Tushar J. , Jiang Hao , Vázquez Miguel A. , Villegas Gómez Clarisa , Cruz Cruz David
Published: February 2018

Diversity‐oriented synthesis and aminocatalysis constitute two important tools for access to important compounds. The extraordinary development in these two areas has allowed chemists to populate new regions in chemical space. As a consequence, new libraries of complex and diverse frameworks are becoming available for drug discovery. ApDOS is presented as a new concept that shows the scope of aminocatalysis for the synthesis and diversification of privileged structures.
2‐Hydroxypyridine‐N‐oxide (HOPO): Equivocal in the ames assay
Authors: Dobo Krista L. , Cheung Jennifer R. , Gunther William C. , Kenyon Michelle O.
Published: February 2018

2‐Hydroxypyridine‐N‐oxide (HOPO) is a useful coupling reagent for synthesis of active pharmaceutical ingredients. It has been reported to be weakly mutagenic in the Ames assay (Ding W et al. []: J Chromatogr A 1386:47–52). According to the ICH M7 guidance (2014) regarding control of mutagenic impurities to limit potential carcinogenic risk, mutagens require control in drug substances such that exposure not exceeds the threshold of toxicological concern. Given the weak response observed in the Ames assay and the lack of any obvious structural features that could confer DNA reactivity we were interested to determine if the results were reproducible and investigate the role of potentially confounding experimental parameters. Specifically, Ames tests were conducted to assess the influence of compound purity, solvent choice, dose spacing, toxicity, type of S9 (aroclor vs phenobarbital/β‐napthoflavone), and lot variability on the frequency of HOPO induced revertant colonies. Initial extensive testing using one lot of HOPO produced no evidence of mutagenic potential in the Ames assays. Subsequent studies with four additional lots produced conflicting results, with an ∼2.0‐fold increase in revertant colonies observed. Given the rigor of the current investigation, lack of reproducibility between lots, and the weak increase in revertants, it is concluded that HOPO is equivocal in the bacterial reverse mutation assay. It is highly unlikely that HOPO poses a mutagenic risk in vivo; therefore, when it is used as a reagent in pharmaceutical synthesis, it should not be regarded as a mutagenic impurity, but rather a normal process related impurity. Environ. Mol. Mutagen. 59:312–321, 2018. © 2018 Wiley Periodicals, Inc.
Higher education predictions for 2018
Authors: Dennis Marguerite J.
Published: February 2018

Despite the wise advice from Mr. Goldwyn, I thought I would share with you some of my predictions about higher education for the coming year. In six months, I will update you on the accuracy of my predictions, and at the end of the year I will do the same.
Honestly evaluate staff goals to build professional development pathways
Authors: Sutton Halley
Published: February 2018

PHOENIX — How engaged are the workers in your office? That was the question Joellen Shendy, associate vice provost and university registrar at the University of Maryland University College; and Insiya Bream, assistant vice provost for registrar strategic operations at UMUC, sought to answer when they took a survey to determine professional engagement and goals.
Expanding spectrum of RARS2 gene disorders: Myoclonic epilepsy, mental retardation, spasticity, and extrapyramidal features
Authors: Mathew Thomas , Avati Amrutha , D'Souza Delon , Therambil Manjusha
Published: February 2018

Pontocerebellar hypoplasia type 6 (PCH6) is an autosomal recessive mitochondrial disease, typically characterized by pontine atrophy, vermian hypoplasia, infantile encephalopathy, generalized hypotonia, and intractable seizures. The purpose of this study is to describe the seizures and other neurological manifestations of RARS2 gene mutations and to compare the clinical features with other causes of progressive myoclonic epilepsy. Detailed history, physical examination, and clinical and genetic work‐up were performed in 2 siblings who presented with progressive myoclonic epilepsy. One sibling, a 20‐year‐old woman, and the other a 24‐year‐old man, had a homozygous missense variant (c.848T>A; p.Leu283Gln) in exon 10 of the RARS2 gene. The female patient had action and audiogenic myoclonic jerks, postural tremors, spastic dysarthria, and bradykinesia, and her male sibling had similar features with oculomotor apraxia. The RARS2 gene mutation can present with myoclonic epilepsy, mental retardation, and pyramidal and extrapyramidal features, and is an important differential for causes of progressive myoclonic epilepsy.
Combined effects of interspecies interaction, temperature, and zinc on Daphnia longispina population dynamics
Authors: Van de Perre Dimitri , Janssen Colin R. , De Schamphelaere Karel A.C.
Published: February 2018

Under natural conditions, organisms can experience a variety of abiotic (e.g., temperature, pH) and biotic (e.g., species interactions) factors, which can interact with toxicant effects. By ignoring species interactions conventional ecotoxicological studies (i.e., single-species tests) oversimplify the actual field situation. We investigated whether temperature and interspecific competition affected the effects of zinc (Zn) on a Daphnia longispina population. The D. longispina populations were exposed in a full factorial design to 3 different Zn treatments (background, 29, and 110 μg Zn/L), 2 different temperature regimes (cold, 17–18 °C; warm, 21–22 °C), and 2 interspecific competition levels (no interspecific Brachionus competition = no Brachionus calyciflorus added; interspecific Brachionus competition = B. calyciflorus added). Interspecific Brachionus competition and temperature by itself had a limited effect on the Daphnia abundance but significantly interacted with the highest Zn concentration. Without Brachionus competition the D. longispina juvenile and adult abundances under warm conditions were up to 5.5 and 21 times lower, respectively, in the high Zn treatment in comparison with the Zn control, whereas under cold conditions no significant Zn effect was observed. However, with Brachionus competition the highest Zn treatment was on average 2.2 times less toxic to the D. longispina juvenile abundance at higher temperatures. Under cold conditions the highest Zn treatment affected the juvenile abundance sooner and up to 9 times more negatively when simultaneously faced with Brachionus competition. It is possible that the competition for food reduced the amount of energy that could be used by D. longispina for reproduction, and the metabolic costs increased as a result of Zn stress. The present study clearly illustrated the influence of temperature and competition on the effects of a chemical stressor. Thus, not considering such factors in ecological risk assessment may underestimate or overestimate risks in aquatic ecosystems when extrapolating data from standard single-species tests to the field. Environ Toxicol Chem 2018;37:1668–1678. © 2018 SETAC
Hydrological and biogeochemical controls governing the speciation and accumulation of selenium in a wetland influenced by mine drainage
Authors: Martin Alan J. , Fraser Colin , Simpson Stephanie , Belzile Nelson , Chen Y.-W. , London Jacqueline , Wallschläger Dirk
Published: February 2018

Controls governing the speciation and accumulation of Se in a 3.7-ha marsh influenced by mine drainage were assessed through examination of water balance, water quality, sediment, and plant tissue components. Over the 8-mo study period (April through November, 2009), mean monthly flows ranged from 1600 to 2300 m3 d−1 (hydraulic retention time of 1–3 d). Total Se concentrations in the marsh outflow were lower than the inflow by 0.4 to 6.2 μg L−1 (mean difference = 3.3 μg L−1), illustrating Se removal. The Se accumulation pathways are illustrated by elevated concentrations of Se in sediments (3–35 mg kg−1 dry wt) as well as in below-ground (2–41 mg kg−1 dry wt; mean = 10 mg kg−1 dry wt) and above-ground (0.8–6.3 mg kg−1 dry wt; mean = 2 mg kg−1 dry wt) emergent plant tissues. Redox stratification in the shallow water column had a marked effect on Se speciation and behavior, illustrating bottom water removal of dissolved selenate in suboxic horizons and increased mobility of dissolved organo-Se. Mass balance data yielded inflow and outflow loading rates for Se of 27 and 23 g d−1, respectively (net accumulation rate of 4 g d−1 or 0.11 mg m2 d−1). The rate of accumulation as calculated from the mass balance agrees with independently measured rates of Se accumulation in sediments for the site (3.6–8.1 g d−1 or 0.10–0.22 mg m−2 d−1). Environ Toxicol Chem 2018;37:1824–1838. © 2018 SETAC
Localization of the cannabinoid type‐1 receptor in subcellular astrocyte compartments of mutant mouse hippocampus
Authors: Gutiérrez‐Rodríguez Ana , Bonilla‐Del Río Itziar , Puente Nagore , Gómez‐Urquijo Sonia M. , Fontaine Christine J. , Egaña‐Huguet Jon , Elezgarai Izaskun , Ruehle Sabine , Lutz Beat , Robin Laurie M. , Soria‐Gómez Edgar , Bellocchio Luigi , Padwal Jalindar D. , van der Stelt Mario , Mendizabal‐Zubiaga Juan , Reguero Leire , Ramos Almudena , Gerrikagoitia Inmaculada , Marsicano Giovanni , Grandes Pedro
Published: February 2018

Astroglial type‐1 cannabinoid (CB1) receptors are involved in synaptic transmission, plasticity and behavior by interfering with the so‐called tripartite synapse formed by pre‐ and post‐synaptic neuronal elements and surrounding astrocyte processes. However, little is known concerning the subcellular distribution of astroglial CB1 receptors. In particular, brain CB1 receptors are mostly localized at cells' plasmalemma, but recent evidence indicates their functional presence in mitochondrial membranes. Whether CB1 receptors are present in astroglial mitochondria has remained unknown. To investigate this issue, we included conditional knock‐out mice lacking astroglial CB1 receptor expression specifically in glial fibrillary acidic protein (GFAP)‐containing astrocytes (GFAP‐CB1‐KO mice) and also generated genetic rescue mice to re‐express CB1 receptors exclusively in astrocytes (GFAP‐CB1‐RS). To better identify astroglial structures by immunoelectron microscopy, global CB1 knock‐out (CB1‐KO) mice and wild‐type (CB1‐WT) littermates were intra‐hippocampally injected with an adeno‐associated virus expressing humanized renilla green fluorescent protein (hrGFP) under the control of human GFAP promoter to generate GFAPhrGFP‐CB1‐KO and ‐WT mice, respectively. Furthermore, double immunogold (for CB1) and immunoperoxidase (for GFAP or hrGFP) revealed that CB1 receptors are present in astroglial mitochondria from different hippocampal regions of CB1‐WT, GFAP‐CB1‐RS and GFAPhrGFP‐CB1‐WT mice. Only non‐specific gold particles were detected in mouse hippocampi lacking CB1 receptors. Altogether, we demonstrated the existence of a precise molecular architecture of the CB1 receptor in astrocytes that will have to be taken into account in evaluating the functional activity of cannabinergic signaling at the tripartite synapse.
Nonalcoholic fatty liver disease contributes to subclinical atherosclerosis: A systematic review and meta‐analysis
Authors: Zhou Yao‐Yao , Zhou Xiao‐Dong , Wu Sheng‐Jie , Fan Dan‐Hong , Van Poucke Sven , Chen Yong‐Ping , Fu Shen‐Wen , Zheng Ming‐Hua
Published: February 2018

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease. In our meta‐analysis, we aimed to assess the correlation of NAFLD and four surrogate markers of subclinical atherosclerosis. PubMed, Embase, and the Cochrane Library were searched up until April 2017. Original studies investigating the association between NAFLD and subclinical atherosclerosis were included. The outcome data were extracted and pooled for the effect estimate by using a random‐effects model. We used the Newcastle‐Ottawa Quality Assessment Scale to assess the quality of the included studies. Of the 434 initially retrieved studies, 26 studies involving a total of 85,395 participants (including 29,493 patients with NAFLD) were included in this meta‐analysis. The Newcastle‐Ottawa Quality Assessment Scale scores suggested the included studies were of high quality. The pooled effects estimate showed that subjects with NAFLD exhibited a significant independent association with subclinical atherosclerosis compared to the non‐NAFLD group (odds ratio, 1.60; 95% confidence interval, 1.45‐1.78). Subgroup analysis suggested that the presence of NAFLD yielded a remarkable higher risk of increased carotid artery intima‐media thickness/plaques, arterial stiffness, coronary artery calcification, and endothelial dysfunction with odds ratios (95% confidence interval) of 1.74 (1.47‐2.06), 1.56 (1.24‐1.96), 1.40 (1.22‐1.60), and 3.73 (0.99‐14.09), respectively. Conclusion: Our meta‐analysis revealed a close link between NAFLD and subclinical atherosclerosis in light of four different indices. Patients with NAFLD might benefit from screening and surveillance of early atherosclerosis, which would facilitate the prediction of potential cardiovascular disease burden, risk stratification, and appropriate intervention in the long term. (Hepatology Communications 2018;2:376‐392)
Sibling presence, executive function, and the role of parenting
Authors: Rolan Emily P. , Schmitt Sara A. , Purpura David J. , Nichols Deborah L.
Published: February 2018

Siblings offer a unique context for practising skills such as executive function (EF). Further, siblings are influential agents in parenting practices, which may, in turn, be related to EF. The current study investigated the extent to which the presence of a sibling is related to parent‐reported EF in preschoolers and whether the presence of a sibling is indirectly related to EF through global parenting practices. Participants included children 30 to 60 months old and their caregivers (n = 505). Caregivers indicated that target children were predominately White (n = 354, 72%) and African American (n = 51, 10%), with the remaining participants representing multiple other racial categories (23%). Caregivers reported on parenting characteristics, their child's EF, and demographic information. Analyses revealed a negative association between sibling presence and parent‐reported EF. Initial analyses suggested that sibling presence was indirectly related to EF through a broad measure of global parenting practices; however, Follow‐up analyses indicated that when the global parenting practices scale was broken down into distinct parenting practices (e.g., warmth), indirect effects were not significant. These findings begin to clarify the influence of parenting behaviours and sibling presence in the home on young children's EF, suggesting that continued research is necessary to further elucidate these relations.

Highlights

Researchers investigated the relation between sibling presence and executive function and if global parenting practices were important in the association.

Caregivers reported on their child, revealing that having a sibling was associated with lower executive function.

Executive function is an important predictor of numerous developmental outcomes; research must replicate our findings and continue to explore the mechanisms through which siblings may be impacting children's executive function development.
Comparison of in vitro biocompatibility of silicone and polymethyl methacrylate during the curing phase of polymerization
Authors: Song Wei , Seta Joseph , Eichler Michael K. , Arts Jacobus J. , Boszczyk Bronek M. , Markel David C. , Gasbarrini Alessandro , Ren Weiping
Published: February 2018

Adverse events have been reported with acrylic bone cements. However, current test standards for acrylic materials fail to characterize the potentially harmful monomers released during the curing stage. In clinical applications, materials are implanted into the human body during this phase. Silicone may be a safer alternative to acrylic cements. Silicone is used in medical applications for its biocompatibility and stability characteristics. Previously, no study has been completed which compares silicone to acrylic cements. In this study, both materials were injected into the cell medium during the curing process which more accurately reflects clinical use of material. Initially, cell cultures followed ASTM standard F813‐07 which fails to capture the effects of monomer released during curing. Subsequently, a modified cell culture method was employed which evaluated cytotoxicity while the materials cured. The objective of this study was to capture toxicity data during curing phase. Thus, the test method employed measured and excluded the impact of the exothermic reaction temperature of polymethyl methacrylate (PMMA) on cell growth. The concentration of PMMA monomer was measured at 1 and 24 h after injecting PMMA into culture plates in a manner consistent with established cell growth methodologies. Our results indicate current in vitro cytotoxicity assays recommended by ASTM standards are unable to reveal the real cytotoxic effect caused by methyl methacrylate monomers during polymerization. Our modified experiment can more accurately illustrate the true nature of the toxicity of materials and improve assay results. In these tests, silicone based elastomeric polymers showed excellent cytocompatibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2693–2699, 2018.
Tumor mechanosensing and its therapeutic potential
Authors: Gargalionis Antonios N. , Basdra Efthimia K. , Papavassiliou Athanasios G.
Published: February 2018

Cancer mechanics have lately emerged as a distinct tumor feature that promotes tumor development, invasion, and metastasis. Tumor mechanosensing involves a mechanical interplay between cancer cells, extracellular matrix, and cells of the surrounding stroma. Mechanoreceptors sense alterations of the extracellular mechanical cues and activate signaling molecules, which mediate oncogenic transcription in favor of cancer initiation, survival, growth, and metastasis. Furthermore, alterations of the matrix rigidity and activation of mechano‐induced transcriptional regulators has been strongly associated with resistance to anti‐cancer agents. In this context, new mechanosensitive molecules arise as potential therapeutic targets. Therefore, tumor mechanosignaling represents a promising field that can potentially offer new combination regimens to overcome drug resistance, but also suggest novel targeting strategies.
Rare LPL gene missense mutation in an infant with hypertriglyceridemia
Authors: Qin Yuan‐yuan , Wei Ai‐qiu , Shan Qing‐wen , Xian Xiao‐ying , Wu Yang‐yang , Liao Lin , Yan Jie , Lai Zhan‐feng , Lin Fa‐quan
Published: February 2018

Background

Severe hypertriglyceridemia usually results from a combination of genetic and environmental factors and is most often attributable to mutations in the lipoprotein lipase (LPL) gene.

Objectives

The aim of this study was to identify rare mutations in the LPL gene causing severe hypertriglyceridemia.

Methods

A Chinese infant who presented classical features of severe hypertriglyceridemia recruited for DNA sequencing of the LPL gene. The pathogenicity grade of the variants was defined based on the prediction of pathogenicity using in silico prediction tools. Review some studies to understand the molecular mechanisms underlying the severe hypertriglyceridemia.

Results

We identified a rare mutation in the LPL gene causing severe hypertriglyceridemia: a nucleotide substitution (c.836T>G) resulting in a leucine to arginine substitution at position 279 of the protein (p.Leu279Arg).The pathogenicity of the variant was predicted by in silico analysis using PolyPhen2 and SIFT prediction programs, which indicated that mutation p.Leu279Arg is probably harmful. We have also reviewed published studies concerning the molecular mechanisms underlying severe hypertriglyceridemia. A missense mutation in the 6 exon of the LPL gene is reportedly associated with LPL deficiency.

Conclusions

We have here identified a rare pathogenic mutation in the LPL gene in a Chinese infant with severe hypertriglyceridemia.