bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of 4-aminoquinoline core for the design of new cholinesterase inhibitors
Authors: Chen Yao , Bian Yaoyao , Sun Yuan , Kang Chen , Yu Sheng , Fu Tingming , Li Wei , Pei Yuqiong , Sun Haopeng
Published: July 2016

Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer’s disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects. Considering the simple structure and high inhibitory potency against AChE, 4-aminoquinoline provides a good starting core for further designing novel multifunctional AChEIs.
The wings before the bird: an evaluation of flapping-based locomotory hypotheses in bird antecedents
Authors: Dececchi T. Alexander , Larsson Hans C.E. , Habib Michael B.
Published: July 2016

Background:Powered flight is implicated as a major driver for the success of birds. Here we examine the effectiveness of three hypothesized pathways for the evolution of the flight stroke, the forelimb motion that powers aerial locomotion, in a terrestrial setting across a range of stem and basal avians: flap running, Wing Assisted Incline Running (WAIR), and wing-assisted leaping.

Methods:Using biomechanical mathematical models based on known aerodynamic principals and in vivo experiments and ground truthed using extant avians we seek to test if an incipient flight stroke may have contributed sufficient force to permit flap running, WAIR, or leaping takeoff along the phylogenetic lineage from Coelurosauria to birds.

Results:None of these behaviours were found to meet the biomechanical threshold requirements before Paraves. Neither was there a continuous trend of refinement for any of these biomechanical performances across phylogeny nor a signal of universal applicability near the origin of birds. None of these flap-based locomotory models appear to have been a major influence on pre-flight character acquisition such as pennaceous feathers, suggesting non-locomotory behaviours, and less stringent locomotory behaviours such as balancing and braking, played a role in the evolution of the maniraptoran wing and nascent flight stroke. We find no support for widespread prevalence of WAIR in non-avian theropods, but can’t reject its presence in large winged, small-bodied taxa likeMicroraptorandArchaeopteryx.

Discussion:Using our first principles approach we find that “near flight” locomotor behaviors are most sensitive to wing area, and that non-locomotory related selection regimes likely expanded wing area well before WAIR and other such behaviors were possible in derived avians. These results suggest that investigations of the drivers for wing expansion and feather elongation in theropods need not be intrinsically linked to locomotory adaptations, and this separation is critical for our understanding of the origin of powered flight and avian evolution.
Dugong dugonfeeding in tropical Australian seagrass meadows: implications for conservation planning
Authors: Tol Samantha J. , Coles Rob G. , Congdon Bradley C.
Published: July 2016

Dugongs (Dugong dugon) are listed as vulnerable to extinction due to rapid population reductions caused in part by loss of seagrass feeding meadows. Understanding dugong feeding behaviour in tropical Australia, where the majority of dugongs live, will assist conservation strategies. We examined whether feeding patterns in intertidal seagrass meadows in tropical north-eastern Australia were related to seagrass biomass, species composition and/or nitrogen content. The total biomass of each seagrass species removed by feeding dugongs was measured and compared to its relative availability. Nitrogen concentrations were also determined for each seagrass species present at the sites. Dugongs consumed seagrass species in proportion to their availability, with biomass being the primary determining factor. Species composition and/or nitrogen content influenced consumption to a lesser degree. Conservation plans focused on protecting high biomass intertidal seagrass meadows are likely to be most effective at ensuring the survival of dugong in tropical north-eastern Australia.
Solar cycle variations in ion composition in the dayside ionosphere of Titan
Authors: Madanian H. , Cravens T. E. , Richard M. S. , Waite J. H. , Edberg N. J. T. , Westlake J. H. , Wahlund J.‐E.
Published: July 2016

One Titanian year spans over two complete solar cycles, and the solar irradiance has a significant effect on ionospheric densities. Solar cycle 24 has been one of the quietest cycles on record. In this paper we show data from the Cassini ion and neutral mass spectrometer (INMS) and the radio and plasma wave science Langmuir probe spanning the time period from early 2005, at the declining phase of solar cycle 23, to late 2015 at the declining phase of solar cycle 24. Densities of different ion species measured by the INMS show a consistent enhancement for high solar activity, particularly near the ionospheric peak. The density enhancement is best seen in primary ion species such as CH3+ rather than heavier ion species such as HCNH+. Unlike at Earth, where the ionosphere and atmosphere thermally expand at high solar activity, at Titan the altitude of the ionospheric peak decreases, indicating that the underlying neutral atmosphere was less extensive. Among the major ion species, CH5+ shows the largest decrease in peak altitude, whereas heavy ions such as C3H5+ show very little decrease. We also calculate the ion production rates using a theoretical model and a simple empirical model using INMS data and show that these effectively predict the increased ion production rates at high solar activity.
Impacts of sea spray geoengineering on ocean biogeochemistry
Authors: Partanen Antti‐Ilari , Keller David P. , Korhonen Hannele , Matthews H. Damon
Published: July 2016

We used an Earth system model of intermediate complexity to study the effects of Solar Radiation Management (SRM) by sea spray geoengineering on ocean biogeochemistry. SRM slightly decreased global ocean net primary productivity (NPP) relative to the control run. The lower temperatures in the SRM run decreased NPP directly but also indirectly increased NPP in some regions due to changes in nutrient availability resulting from changes in ocean stratification and circulation. Reduced light availability had a minor effect on global total NPP but a major regional effect near the nutrient‐rich upwelling region off the coast of Peru, where light availability is the main limiting factor for phytoplankton growth in our model. Unused nutrients from regions with decreased NPP also fueled NPP elsewhere. In the context of RCP4.5 simulation used here, SRM decreased ocean carbon uptake due to changes in atmospheric CO2 concentrations, seawater chemistry, NPP, temperature, and ocean circulation.
The Fonualei Rift and Spreading Center: Effects of ultraslow spreading and arc proximity on back‐arc crustal accretion
Authors: Sleeper Jonathan D. , Martinez Fernando , Arculus Richard
Published: July 2016

Back‐arc spreading center characteristics reflect interactions between plate‐driven mantle advection and melting and slab‐driven hydrous melting and buoyant upwelling in the mantle wedge. At the Fonualei Rift and Spreading Center (FRSC) in the Lau Basin, spreading rates decrease from slow to ultraslow, providing an opportunity to examine crustal accretion as the plate‐driven component is minimized. A new Lau Basin kinematic analysis predicts FRSC spreading rates of ~32–8 mm/yr southward, much slower than previous estimates of ~95–47 mm/yr. Here we examine FRSC morphology and geophysical characteristics as it approaches the Tofua arc volcanic front southward and spreading rates decrease, minimizing the plate‐driven component of mantle advection and maximizing buoyant hydrous flux melting. Axial morphology changes abruptly from a deep, flat, faulted axis ~100 km away from the arc to a volcanic ridge that shoals and increases in relief southward. Within ~50 km of the arc at the south end, the volcanic ridge is abruptly replaced by isolated volcanic cones bisected by volcanic rift zones and surrounded by anomalously deep seafloor. These morphologic changes likely reflect along‐axis focusing of mantle upwelling and melting similar to that seen at ultraslow mid‐ocean ridges, causing the change in morphology from a segmented ridge to spaced axial cones. We propose that as opening rates slow and the ridge approaches the arc, more of the inherently three‐dimensional pattern of hydrous flux melting and buoyant upwelling in the mantle wedge is expressed volcanically. With faster opening, two‐dimensional plate‐driven mantle advection dominates melt production, favoring ridges over point‐source features.
Outcome Expectations and Osteoarthritis: Association of Perceived Benefits of Exercise With Self‐Efficacy and Depression
Authors: Marszalek Jolanta , Price Lori Lyn , Harvey William F. , Driban Jeffrey B. , Wang Chenchen
Published: July 2016

Objective

Outcome expectancy is recognized as a determinant of exercise engagement and adherence. However, little is known about which factors influence outcome expectations for exercise among people with knee osteoarthritis (OA). This is the first study to examine the association of outcome expectations for exercise with demographic, physical, and psychosocial outcomes in individuals with knee OA.

Methods

We performed a cross‐sectional analysis of the baseline data from a randomized trial of tai chi versus physical therapy in participants with symptomatic knee OA. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Outcome expectations for exercise, self‐efficacy, depression, anxiety, stress, and social support were measured using standard instruments. Logistic regression models were utilized to determine associations with outcome expectations.

Results

There were 262 participants, with a mean age of 59.8 years and a mean body mass index of 32.1 kg/m2; 69.1% of the participants were female, 51.5% were white, the mean disease duration was 8.6 years, and the mean WOMAC knee pain and function scores were 260.8 and 906.8, respectively. Higher outcome expectations for exercise were associated with greater self‐efficacy (odds ratio [OR] 1.25 [95% confidence interval (95% CI) 1.11–1.41]; P = 0.0004), as well as with fewer depressive symptoms (OR 0.84 for each 5‐point increase [95% CI 0.73–0.97]; P = 0.01). Outcome expectancy was not significantly associated with sex, race, education, pain, function, radiographic severity, social support, anxiety, or stress.

Conclusion

Our results suggest significant associations between outcome expectations for exercise and self‐efficacy and depression. Future studies should examine how these relationships longitudinally affect long‐term clinical outcomes of exercise‐based treatment for knee OA.
Nationwide Trends in Hospitalizations and In‐Hospital Mortality in Granulomatosis With Polyangiitis (Wegener's)
Authors: Wallace Zachary S. , Lu Na , Miloslavsky Eli , Unizony Sebastian , Stone John H. , Choi Hyon K.
Published: July 2016

Objective

Granulomatosis with polyangiitis (Wegener's) (GPA) is a type of antineutrophil cytoplasmic antibody–associated vasculitis that often entails severe end‐organ damage and treatment‐related complications that frequently lead to hospitalization and death. Nationwide trends in hospitalizations and in‐hospital mortality over the past 2 decades are unknown and were evaluated in this study.

Methods

Using the National Inpatient Sample, the largest all‐payer inpatient database in the US, trends in hospitalizations with a discharge diagnosis of GPA (formerly Wegener's granulomatosis; International Classification of Disease, Ninth Revision, Clinical Modification code 446.4) between 1993 and 2011 were studied. Analyses were performed using hospital‐level sampling weights to obtain US national estimates.

Results

From 1993 to 2011, the annual hospitalization rate for patients with a principal diagnosis of GPA increased by 24%, from 5.1 to 6.3 per 1 million US persons (P < 0.0001 for trend); however, in‐hospital deaths in this group declined by 73%, from 9.1% to 2.5% (P < 0.0001 for trend), resulting in a 66% net reduction in the annual in‐hospital mortality rate. The median length of stay declined by 20%, from 6.9 days in 1993 to 5.5 days in 2011 (P = 0.0002 for trend). Infection was the most common principal discharge diagnosis when GPA was a secondary diagnosis, including among those who died during hospitalization.

Conclusion

The findings from these nationally representative, contemporary inpatient data indicate that the in‐hospital mortality of GPA has declined substantially over the past 2 decades, while the overall hospitalization rate for GPA increased slightly. Infection remains a common principal hospitalization diagnosis among GPA patients, including hospitalizations resulting in mortality.
Symptom Recognition and Perceived Urgency of Help‐Seeking for Rheumatoid Arthritis and Other Diseases in the General Public: A Mixed Method Approach
Authors: Simons Gwenda , Belcher John , Morton Chris , Kumar Kanta , Falahee Marie , Mallen Christian D. , Stack Rebecca J. , Raza Karim
Published: July 2016

Objective

Clinical outcomes in rheumatoid arthritis (RA) are improved if the disease is treated early. However, treatment is often significantly delayed as a result of delayed help‐seeking by patients who fail to recognize its symptoms or the need for rapid medical attention. Two studies were conducted to investigate the role of symptom recognition in help‐seeking for the symptoms of RA, and compared this to symptom recognition and help‐seeking in angina and bowel cancer.

Methods

A qualitative interview study with 31 individuals and a survey of 1,088 members of the general public (all without RA) were conducted. Both studies used vignettes describing the symptoms of RA, bowel cancer, and angina. Participants made causal attributions and rated the perceived seriousness of the symptoms and the urgency with which they would seek medical help if confronted with these symptoms.

Results

Only a small proportion of participants in both studies recognized the symptoms of RA, whereas the symptoms of bowel cancer and angina were readily recognized by many participants and considered to be more serious and to require more rapid medical attention (Z = 14.7–34.2, P < 0.001).

Conclusion

Accurate symptom attribution and the perception that symptoms are indicative of a serious underlying condition are both important drivers for rapid help‐seeking. In the case of angina and bowel cancer, recent campaigns have promoted not only recognition of symptoms and their seriousness, but also emphasized the consequences of not seeking timely help. Our results suggest that these consequences should also be addressed in any public health campaign for RA.
Clinical Risk Factors for the Presence and Development of Vertebral Fractures in Patients With Ankylosing Spondylitis
Authors: Maas Fiona , Spoorenberg Anneke , van der Slik Boukje P. G. , van der Veer Eveline , Brouwer Elisabeth , Bootsma Hendrika , Bos Reinhard , Wink Freke R. , Arends Suzanne
Published: July 2016

Introduction

To investigate the prevalence and incidence of radiographic vertebral fractures and the association with patient characteristics, clinical assessments, and medication use in a large prospective cohort of patients with ankylosing spondylitis (AS) in daily clinical practice.

Methods

Consecutive AS patients from the Groningen Leeuwarden AS (GLAS) cohort with baseline and 2‐year lateral radiographs of the thoracic and lumbar spine were included. Radiographs were scored for vertebral fractures by 2 readers according to the method of Genant et al. Differences in baseline characteristics between patients with and without radiographic vertebral fractures were explored.

Results

Of 292 included AS patients, 59 (20%) had radiographic vertebral fractures at baseline, 15 (6%) developed new fractures, and 7 (2%) showed an increase in the severity of existing fractures during 2 years of follow‐up. Most fractures were mild and located in the midthoracic and thoracolumbar region of the spine. The presence of vertebral fractures was significantly associated with older age, higher body mass index, longer smoking duration, larger occiput‐to‐wall distance, more spinal radiographic damage, and lower hip bone mineral density (BMD). The development of new or progressive vertebral fractures was also associated with older age and low BMD. Patients using nonsteroidal antiinflammatory drugs (NSAIDs) at baseline showed less prevalent and incident vertebral fractures.

Conclusion

In this large AS cohort in daily clinical practice, radiographic vertebral fractures were frequently present in AS, especially in older patients with more advanced disease, low hip BMD, and a less healthy lifestyle. Interestingly, NSAID use was associated with a reduced vertebral fractures risk.
Depression and Progression of Subclinical Cardiovascular Disease in Systemic Lupus Erythematosus
Authors: Jorge April , Lertratanakul Apinya , Lee Jungwha , Pearce William , McPherson David , Thompson Trina , Barinas‐Mitchell Emma , Ramsey‐Goldman Rosalind
Published: July 2016

Objective

Women with systemic lupus erythematosus (SLE) have an increased incidence of premature cardiovascular disease (CVD). A relationship between depression and increased inflammation leading to CVD has been proposed. The aim of this study was to evaluate the relationship between depression and the progression of subclinical atherosclerosis in women with SLE.

Methods

In this prospective case–control study, 149 participants with SLE and 126 controls were followed over 5 years. Evaluation included laboratory studies, assessment of CVD risk factors, depression screening, ultrasound evaluations of carotid intima‐media thickness (CIMT) and carotid plaque, and assessment of SLE disease activity for the SLE cases.

Results

The SLE group had a higher rate of depression: 29% compared with 11% in the control group (P = 0.003). When controlling for traditional CVD risk factors, the presence of baseline depression correlated with increased progression of CIMT in the SLE group, but not in the control group. The mean increase in CIMT was 0.026 mm in the SLE group without depression versus 0.064 mm in the depressed SLE group (P = 0.0096). There was no association between depression and carotid plaque in either group, with a calculated odds ratio for plaque progression in the depressed SLE group of 1.118 (95% confidence interval 0.476, 2.623) in the adjusted model.

Conclusion

Women with SLE and concomitant depression have an increased risk of developing subclinical atherosclerosis, as measured by CIMT, but not by carotid plaque. The data suggest that depression, a potentially modifiable risk factor, may contribute to the increased risk of subclinical atherosclerosis in women with SLE.
Self‐Assembled Heterojunction Carbon Nanotubes Synergizing with Photoimmobilized IGF‐1 Inhibit Cellular Senescence
Authors: Chen Wu‐Ya , Yang Run‐Cai , Wang Hui‐Min , Zhang Li , Hu Kaikai , Li Chu‐Hua , You Rong , Yin Liang , Guan Yan‐Qing
Published: July 2016

Synthesis of artificial and functional structures for bone tissue engineering has been well recognized but the associated cell senescence issue remains much less concerned so far. In this work, surface‐modified polycaprolactone‐polylactic acid scaffolds using self‐assembled heterojunction carbon nanotubes (sh‐CNTs) combined with insulin‐like growth factor‐1 are synthesized and a series of structural and biological characterizations are carried out, with particular attention to cell senescence mechanism. It is revealed that the modified scaffolds can up‐regulate the expressions of alkaline phosphates and bone morphogenetic proteins while down‐regulate the expressions of senescence‐related proteins in mesenchymal stem cells, demonstrating the highly preferred anti‐senescence functionality of the sh‐CNTs modified scaffolds in bone tissue engineering. Furthermore, it is also found that with sh‐CNTs, scaffolds can accelerate bone healing with extremely low toxicity in vivo.
Light Manipulation in Organic Photovoltaics
Authors: Ou Qing‐Dong , Li Yan‐Qing , Tang Jian‐Xin
Published: July 2016

Organic photovoltaics (OPVs) hold great promise for next‐generation photovoltaics in renewable energy because of the potential to realize low‐cost mass production via large‐area roll‐to‐roll printing technologies on flexible substrates. To achieve high‐efficiency OPVs, one key issue is to overcome the insufficient photon absorption in organic photoactive layers, since their low carrier mobility limits the film thickness for minimized charge recombination loss. To solve the inherent trade‐off between photon absorption and charge transport in OPVs, the optical manipulation of light with novel micro/nano‐structures has become an increasingly popular strategy to boost the light harvesting efficiency. In this Review, we make an attempt to capture the recent advances in this area. A survey of light trapping schemes implemented to various functional components and interfaces in OPVs is given and discussed from the viewpoint of plasmonic and photonic resonances, addressing the external antireflection coatings, substrate geometry‐induced trapping, the role of electrode design in optical enhancement, as well as optically modifying charge extraction and photoactive layers.
Convolution Operations on Coding Metasurface to Reach Flexible and Continuous Controls of Terahertz Beams
Authors: Liu Shuo , Cui Tie Jun , Zhang Lei , Xu Quan , Wang Qiu , Wan Xiang , Gu Jian Qiang , Tang Wen Xuan , Qing Qi Mei , Han Jia Guang , Zhang Wei Li , Zhou Xiao Yang , Cheng Qiang
Published: July 2016

The concept of coding metasurface makes a link between physically metamaterial particles and digital codes, and hence it is possible to perform digital signal processing on the coding metasurface to realize unusual physical phenomena. Here, this study presents to perform Fourier operations on coding metasurfaces and proposes a principle called as scattering‐pattern shift using the convolution theorem, which allows steering of the scattering pattern to an arbitrarily predesigned direction. Owing to the constant reflection amplitude of coding particles, the required coding pattern can be simply achieved by the modulus of two coding matrices. This study demonstrates that the scattering patterns that are directly calculated from the coding pattern using the Fourier transform have excellent agreements to the numerical simulations based on realistic coding structures, providing an efficient method in optimizing coding patterns to achieve predesigned scattering beams. The most important advantage of this approach over the previous schemes in producing anomalous single‐beam scattering is its flexible and continuous controls to arbitrary directions. This work opens a new route to study metamaterial from a fully digital perspective, predicting the possibility of combining conventional theorems in digital signal processing with the coding metasurface to realize more powerful manipulations of electromagnetic waves.
A phase II study of two dose levels of ofatumumab induction followed by maintenance therapy in symptomatic, previously untreated chronic lymphocytic leukemia
Authors: Flinn Ian W. , Ruppert Amy S. , Harwin William , Waterhouse David , Papish Steven , Jones Jeffrey A. , Hainsworth John , Byrd John C.
Published: July 2016

Despite the recent advances in treatment of CLL with targeted agents such as ibrutinib, availability of nonchemotherapy based therapies is desired. Given the 58% response rate (1996 NCI‐WG criteria) of single agent ofatumumab in CLL refractory to fludarabine and alemtuzumab, we initiated a phase II trial examining response, safety, and progression‐free survival (PFS) of ofatumumab as front‐line monotherapy. Patients enrolled included untreated, symptomatic CLL patients over the age of 65 or those who were inappropriate/did not desire chemotherapy. Two cohorts were enrolled sequentially examining either 1 g (33 patients) or 2 g (44 patients) weekly for 8 weeks followed by maintenance dosing every 2 months for a total of 24 months. Patients receiving 1 g were older than those receiving 2 g, but there were no significant differences in other clinical characteristics. The best overall response rates in the 1 and 2 g patient cohorts were 72 and 89% (1996 NCI‐WG criteria), respectively (54 and 68%, respectively, using 2008 IWCLL criteria). All but two responses were partial. The 24‐month estimated PFS rates were 46 and 78%, respectively. Response and PFS was lower in del(17p) and del(11q) CLL patients. Differences in PFS between dose cohorts were statistically significant and remained so when adjusting for age or high‐risk cytogenetics. Toxicity of this treatment was mild with only six patients not completing therapy due to toxicity. Ofatumumab induction followed by maintenance therapy in untreated CLL represents a well‐tolerated and active regimen, particularly with the 2 g of ofatumumab. Am. J. Hematol. 91:1020–1025, 2016. © 2016 Wiley Periodicals, Inc.
A Typical Metal‐Ion‐Responsive Color‐Tunable Emitting Insulated π‐Conjugated Polymer Film
Authors: Hosomi Takuro , Masai Hiroshi , Fujihara Tetsuaki , Tsuji Yasushi , Terao Jun
Published: July 2016

We report the synthesis of an insulated π‐conjugated polymer containing 2,2′‐bipyridine moieties as metal coordination sites. Metal coordination to the polymer enabled easy and reversible tuning of the luminescent color without changes to the main chain skeleton. The permethylated α‐cyclodextrin (PM α‐CD)‐based insulation structure allowed the metalated polymers to demonstrate efficient emission even in the solid state, with identical spectral shapes to the dilute solutions. In addition, the coordination ability of the metal‐free polymer was maintained in the solid state, resulting in reversible changes in the luminescent color in response to the metal ions. The synthesized polymer is expected to be suitable for application in recyclable luminescent sensors to distinguish different metal ions.
Fluorodecarboxylation for the Synthesis of Trifluoromethyl Aryl Ethers
Authors: Zhang Qing‐Wei , Brusoe Andrew T. , Mascitti Vincent , Hesp Kevin D. , Blakemore David C. , Kohrt Jeffrey T. , Hartwig John F.
Published: July 2016

The synthesis of mono‐, di‐, and trifluoromethyl aryl ethers by fluorodecarboxylation of the corresponding carboxylic acids is reported. AgF2 induces decarboxylation of aryloxydifluoroacetic acids, and AgF, either generated in situ or added separately, serves as a source of fluorine to generate the fluorodecarboxylation products. The addition of 2,6‐difluoropyridine increased the reactivity of AgF2, thereby increasing the range of functional groups and electronic properties of the aryl groups that are tolerated. The reaction conditions used for the formation of trifluoromethyl aryl ethers also served to form difluoromethyl and monofluoromethyl aryl ethers.
Versatile Room‐Temperature‐Phosphorescent Materials Prepared from N‐Substituted Naphthalimides: Emission Enhancement and Chemical Conjugation
Authors: Chen Xiaofeng , Xu Cheng , Wang Tao , Zhou Cao , Du Jiajun , Wang Zhongping , Xu Hangxun , Xie Tongqing , Bi Guoqiang , Jiang Jun , Zhang Xuepeng , Demas James N. , Trindle Carl O. , Luo Yi , Zhang Guoqing
Published: July 2016

Purely organic materials with room‐temperature phosphorescence (RTP) are currently under intense investigation because of their potential applications in sensing, imaging, and displaying. Inspired by certain organometallic systems, where ligand‐localized phosphorescence (3π‐π*) is mediated by ligand‐to‐metal or metal‐to‐ligand charge transfer (CT) states, we now show that donor‐to‐acceptor CT states from the same organic molecule can also mediate π‐localized RTP. In the model system of N‐substituted naphthalimides (NNIs), the relatively large energy gap between the NNI‐localized 1π‐π* and 3π‐π* states of the aromatic ring can be bridged by intramolecular CT states when the NNI is chemically modified with an electron donor. These NNI‐based RTP materials can be easily conjugated to both synthetic and natural macromolecules, which can be used for RTP microscopy.
Tartrate‐Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus
Authors: An Jie , Briggs Tracy A. , Dumax‐Vorzet Audrey , Alarcón‐Riquelme Marta E. , Belot Alexandre , Beresford Michael , Bruce Ian N. , Carvalho Claudia , Chaperot Laurence , Frostegård Johan , Plumas Joel , Rice Gillian I. , Vyse Timothy J. , Wiedeman Alice , Crow Yanick J. , Elkon Keith B.
Published: July 2016

Objective

Mutations in the ACP5 gene, which encodes tartrate‐resistant acid phosphatase (TRAP), cause the immuno‐osseous disorder spondyloenchondrodysplasia, which includes as disease features systemic lupus erythematosus (SLE) and a type I interferon (IFN) signature. Our aims were to identify TRAP substrates, determine the consequences of TRAP deficiency in immune cells, and assess whether ACP5 mutations are enriched in sporadic cases of SLE.

Methods

Interaction between TRAP and its binding partners was tested by a yeast 2‐hybrid screening, confocal microscopy, and immunoprecipitation/Western blotting. TRAP knockdown was performed using small interfering RNA. Phosphorylation of osteopontin (OPN) was analyzed by mass spectrometry. Nucleotide sequence analysis of ACP5 was performed by Sanger sequencing or next‐generation sequencing.

Results

TRAP and OPN colocalized and interacted in human macrophages and plasmacytoid dendritic cells (PDCs). TRAP dephosphorylated 3 serine residues on specific OPN peptides. TRAP knockdown resulted in increased OPN phosphorylation and increased nuclear translocation of IRF7 and P65, with resultant heightened expression of IFN‐stimulated genes and IL6 and TNF following Toll‐like receptor 9 stimulation. An excess of heterozygous ACP5 missense variants was observed in SLE compared to controls (P = 0.04), and transfection experiments revealed a significant reduction in TRAP activity in a number of variants.

Conclusion

Our findings indicate that TRAP and OPN colocalize and that OPN is a substrate for TRAP in human immune cells. TRAP deficiency in PDCs leads to increased IFNα production, providing at least a partial explanation for how ACP5 mutations cause lupus in the context of spondyloenchondrodysplasia. Detection of ACP5 missense variants in a lupus cohort suggests that impaired TRAP functioning may increase susceptibility to sporadic lupus.
Efficient Iterative Synthesis of O‐Acetylated Tri‐ to Pentadecasaccharides Related to the Lipopolysaccharide of Shigella flexneri Type 3 a through Di‐ and Trisaccharide Glycosyl Donors
Authors: Hu Zhaoyu , Bongat White Aileen F. , Mulard Laurence A.
Published: July 2016

Protection against bacterial infections, including shigellosis, can be achieved by antibodies against the bacterial surface polysaccharide. In line with our efforts to develop vaccine candidates for shigellosis, we report herein the synthesis of penta‐, deca‐, and pentadecasaccharides as well as tri‐, octa‐, and tridecasaccharides as the endchain and intrachain fragments, respectively, of the surface polysaccharide of Shigella flexneri 3 a, a prevalent serotype. The syntheses relied on the efficiency of the trichloroacetimidate glycosylation chemistry, whereby iteration with di‐ and trisaccharide building blocks provided fragments made of up to three mono‐O‐acetylated polysaccharide repeating units. Pd(OH)2‐mediated hydrogenation/hydrogenolysis enabled the concomitant removal or conversion of up to 31 protecting groups of 4 different origins to provide the targets as propyl glycosides. Oligosaccharides comprising the octasaccharide segment were shown to display high conformational similarities in solution.
Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data‐driven method
Authors: Bora Emre , Aydın Aydan , Saraç Tuğba , Kadak Muhammed Tayyib , Köse Sezen
Published: July 2016

Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first‐degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low‐scoring" and a "high‐scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low‐scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321–326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
In utero exposure to venlafaxine, a serotonin–norepinephrine reuptake inhibitor, increases cardiac anomalies and alters placental and heart serotonin signaling in the rat
Authors: Laurent Laetitia , Huang Chunwei , Ernest Sheila R. , Berard Anick , Vaillancourt Cathy , Hales Barbara F.
Published: July 2016

Background

Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin–norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat.

Methods

Timed‐pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression.

Results

Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5‐HT2B/Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts.

Conclusion

In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044–1055, 2016. © 2016 Wiley Periodicals, Inc.
Dy3+‐, Sm3+‐, Ce3+‐ and Tb3+‐activated optical properties of microcrystalline BaMgP2O7 phosphors
Authors: Wani J. A. , Dhoble N. S. , Kokode N. S. , Singh Vijay , Dhoble S. J.
Published: July 2016

Photoluminescence (PL) and thermoluminescence (TL) properties of rare earth (RE) ion (RE = Dy3+, Sm3+, Ce3+, Tb3+) activated microcrystalline BaMgP2O7 phosphors are presented in this work. Non‐doped and doped samples of BaMgP2O7 were prepared using a solid state diffusion method and characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), PL and TL. The XRD measurement confirmed the phase purity of the BaMgP2O7 host matrix. The average particle size was found through SEM measurement to be around 2 μm. All activators using the PL technique displayed characteristic excitation and emission spectra that corresponded to their typical f → f and f → d transitions respectively. Thermoluminescence measurements showed that BaMgP2O7:RE (RE = Dy3+, Sm3+, Tb3+, Ce3+) and co‐doped BaMgP2O7:Ce3+,Tb3+ phosphors have also TL behaviour.
Activist Theatre: The Effects of Community Performance on System Justification and Willingness to Engage in Activism
Authors: Vogel Autumn M. , Jackson Lydia Eckstein
Published: July 2016

System justification is a motivation to legitimize the status quo that disables individuals from changing oppressive social systems. Community performance has long been used as a tool to illuminate and challenge such systems of power. The goal of the present study was to provide an empirical test of the effectiveness of community performance in the context of gender‐based oppression. Specifically, the present study tested whether a community performance could decrease audience members' system justification and increase intentions to engage in collective and virtual action to correct these oppressive systems. The performance consisted of 18 community‐created pieces performed by 11 actresses before an audience of 165 members of the college and local communities across three days. A total of 153 audience members participated in the study. Results indicated that a 50‐min performance reduced system justification while increasing willingness to take collective and virtual‐based action. Limitations and implications are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Understanding perspectives of signalling mechanisms regulating PEBP1 function
Authors: Rajkumar Karthik , Nichita Aare , Anoor Pawan Kumar , Raju Swathi , Singh Surya Satyanarayana , Burgula Sandeepta
Published: July 2016

Phosphatidylethanolamine‐binding protein 1 (PEBP1), also known as Raf kinase inhibitor protein, belongs to PEBP family of proteins. It is known to interact with many proteins that are mainly involved in pathways that monitor cell proliferation and differentiation. PEBP1 in many cells interacts with several pathways, namely MAPK, GRK2, NF‐кB, etc. that keeps the cell proliferation and differentiation in check. This protein is expressed by many cells in humans, including neurons where it is predominantly involved in production of choline acetyltransferase. Deregulated PEBP1 is known to cause cancer, diabetic nephropathy and neurodegenerative diseases like Alzheimer's and dementia. Recent research led to the discovery of many drugs that mainly target the interaction of PEBP1 with its partners. These compounds are known to bind PEBP1 in its conserved domain which abrogate its association with interacting partners in several different pathways. We outline here the latest developments in understanding of PEBP1 function in maintaining cell integrity. Copyright © 2016 John Wiley & Sons, Ltd.

Significance of the Study

Phosphatidylethanolamine‐binding protein is crucial in regulation of MAPK and PKC pathways. Its diverse roles, including regulating these pathways keep cell differentiation and proliferation in check. This review outlines some latest findings which greatly add to our current knowledge of phosphatidylethanolamine‐binding protein.
Trifluoroselenomethionine: A New Unnatural Amino Acid
Authors: Block Eric , Booker Squire J. , Flores‐Penalba Sonia , George Graham N. , Gundala Sivaji , Landgraf Bradley J. , Liu Jun , Lodge Stephene N. , Pushie M. Jake , Rozovsky Sharon , Vattekkatte Abith , Yaghi Rama , Zeng Huawei
Published: July 2016

Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N‐(tert‐butoxycarbonyl)‐l‐aspartic acid tert‐butyl ester. TFSeM shows enhanced methioninase‐induced cytotoxicity, relative to selenomethionine (SeM), toward HCT‐116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. Nonetheless, when two different variants of the protein GB1 were expressed in an Escherichia coli methionine auxotroph cell line in the presence of TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85 % of the proteins contained SeM residues, even though no SeM had been added, thus implying loss of the trifluoromethyl group from TFSeM. The transformation of TFSeM into SeM is enzymatically catalyzed by E. coli extracts, but TFSeM is not a substrate of E. coli methionine adenosyltransferase.
Laboratory‐Evolved Enzymes Provide Snapshots of the Development of Enantioconvergence in Enzyme‐Catalyzed Epoxide Hydrolysis
Authors: Janfalk Carlsson Åsa , Bauer Paul , Dobritzsch Doreen , Nilsson Mikael , Kamerlin S. C. Lynn , Widersten Mikael
Published: July 2016

Engineered enzyme variants of potato epoxide hydrolase (StEH1) display varying degrees of enrichment of (2R)‐3‐phenylpropane‐1,2‐diol from racemic benzyloxirane. Curiously, the observed increase in the enantiomeric excess of the (R)‐diol is not only a consequence of changes in enantioselectivity for the preferred epoxide enantiomer, but also to changes in the regioselectivity of the epoxide ring opening of (S)‐benzyloxirane. In order to probe the structural origin of these differences in substrate selectivity and catalytic regiopreference, we solved the crystal structures for the evolved StEH1 variants. We used these structures as a starting point for molecular docking studies of the epoxide enantiomers into the respective active sites. Interestingly, despite the simplicity of our docking analysis, the apparent preferred binding modes appear to rationalize the experimentally determined regioselectivities. The analysis also identifies an active site residue (F33) as a potentially important interaction partner, a role that could explain the high conservation of this residue during evolution. Overall, our experimental, structural, and computational studies provide snapshots into the evolution of enantioconvergence in StEH1‐catalyzed epoxide hydrolysis.
Electro‐assisted Deposition of Binary Self‐Assembled 1,2‐Dithiolane Monolayers on Gold with Predictable Composition
Authors: Capitao Dany , Sahli Rihab , Raouafi Noureddine , Limoges Benoit , Fave Claire , Schöllhorn Bernd
Published: July 2016

A reproducible electro‐assisted method was proposed for the fast and well‐controlled formation of mixed binary 1,2‐dithiolane‐based self‐assembled monolayers (SAMs) on a gold electrode from micromolar adsorbate solution concentrations. This was made possible by the combined use of 1,2‐dithiolane derivatives having comparable surface binding affinities and the application of a moderate cathodic potential to the electrode until an equilibrium binary SAM coverage was reached. Dithiolane derivatives containing distinct redox‐active ferrocenyl groups were synthesized and used for simultaneous and quantitative electrochemical monitoring of the formation of the binary SAMs. The corresponding separate electrochemical responses of each component in the mixed layer allowed for the determination of the adsorbate ratio, which afforded the overall and the individual chemisorption kinetics. Regardless of the different adsorption kinetics, the resulting adsorbate ratios at equilibrium in the SAM were found to be the same as those in solution. Upon reporting the equilibrium surface concentration of the adsorbate as a function of its mole fraction in solution, a clear‐cut linear relationship was obtained, which makes this method particularly useful for controlling and predicting the chemical composition of functional binary SAMs on gold surfaces.
Biocatalysis and Biomass Conversion in Alternative Reaction Media
Authors: Sheldon Roger A.
Published: July 2016

In this Minireview, the state of the art in the use of ionic liquids (ILs) and deep eutectic solvents (DESs) as alternative reaction media for biocatalytic processes and biomass conversion is presented. Initial, proof‐of‐concept studies, more than a decade ago, involved first‐generation ILs based on dialkylimidazolium cations and non‐coordinating anions, such as tetrafluoroborate and hexafluorophosphate. More recently, emphasis has switched to more environmentally acceptable second‐generation ILs comprising cations, which are designed to be compatible with enzymes and, in many cases are derived from readily available, renewable resources, such as cholinium salts. Protic ionic liquids (PILs), prepared simply by mixing inexpensive amines and acids, are particularly attractive from both an environmental and economic viewpoint. DESs, prepared by mixing inexpensive salts with, preferably renewable, hydrogen‐bond donors such as glycerol and amino acids, have also proved suitable reaction media for biocatalytic conversions. A broad range of enzymes can be used in ILs, PILs and DESs, for example lipases in biodiesel production. These neoteric solvents are of particular interest, however, as reaction media for biocatalytic conversions of substrates that have limited solubility in common organic solvents, such as carbohydrates, nucleosides, steroids and polysaccharides. This has culminated in the recent focus of attention on their use as (co)solvents in the pretreatment and saccharification of lignocellulose as the initial steps in the conversion of second‐generation renewable biomass into biofuels and chemicals. They can similarly be used as reaction media in subsequent conversions of hexoses and pentoses into platform chemicals.
ChemInform Abstract: 3D Transition Metal Ordering and Rietveld Stacking Fault Quantification in the New Oxychalcogenides La2O2Cu2—4xCd2xSe2 .
Authors: Ainsworth Chris M. , Lewis James W. , Wang Chun‐Hai , Coelho Alan A. , Johnston Hannah E. , Brand Helen E. A. , Evans John S. O.
Published: July 2016

Polycrystalline samples of La2O2Cu2‐4xCd2xSe2 (x = 0—0.5) are prepared by solid state reaction of La2O3 and the elements in the presence of Al powder as O2 getter (Al2O3 crucible in evacuated silica tubes, 1100 °C, 12 h).
ChemInform Abstract: Baromagnetic Effect in Antiperovskite Mn3Ga0.95N0.94 by Neutron Powder Diffraction Analysis.
Authors: Wang Cong , et al.
Published: July 2016

Polycrystalline samples of the Mn3GaN antiperovskite are prepared by sintering stoichiometric amounts of Mn2N and Ga (evacuated quartz tubes, 800 °C, several days).
ChemInform Abstract: Effect of the [Ba2BO3F]∞ Layer on the Band Gap: Synthesis, Characterization, and Theoretical Studies of BaZn2B2O6·nBa2 BO3F (n = 0, 1, 2).
Authors: Wu Hongping , Su Xin , Han Shujuan , Yang Zhihua , Pan Shilie
Published: July 2016

Single crystals of Ba3Zn2B3O9F (I) and Ba5Zn2B4O12F2 (II) are synthesized from mixtures of BaF2, PbO, ZnO, and H3BO3 (850—900 °C, 10 h, 30% and 80% yield for (I) and (II), respectively).
ChemInform Abstract: Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes.
Authors: Liu Yangbin , Liu Xiaohua , Hu Haipeng , Guo Jing , Xia Yong , Lin Lili , Feng Xiaoming
Published: July 2016

The kinetic resolution of racemic propargyl vinyl ethers (I) through an enantioselective Claisen rearrangement affords chiral allenes (II) and enantiopure ethers (S)‐(I).
ChemInform Abstract: A Novel Coupling Reaction of α‐Halo Ketones Promoted by SmI3/CuI.
Authors: Liu Yongjun , Zhao Hengmin , Tian Guang , Du Feng , Qi Yan , Wen Yonghong
Published: July 2016

In the presented approach DMF plays a dual role both as a hydroxyl source and as a solvent.