bluuebunny/crossref_metadata_2025 huggingface dataset:
QSAR Modelling of Novel Coumarin Derivatives for MAO-B Inhibition
Authors: Kambo Konan René , Kouman Koffi Charles , Akonan Ludovic , Abou Akoun , Megnassan Eugene , Kakou-Yao Rita , Tenon Abodou Jules
Published: October 2024

We report here the design of new inhibitors against human monoamine oxidase (hMAO-B) as potential treatment of Parkinson’s disease. We have completed computer-aided molecular design of MAO-B inhibitors by In situ modification of the reference crystal structure of 7-(3-chlorobenzyloxy)-4-(methylamino) methyl-coumarin cocrystallized (COU1) in complex with MAO-B (Protein Data Bank (PDB) entry code: 2v61) using MM-PB approach. A QSAR model built for a training set of 29 COUs with reported inhibitory activities (IC50exp) displayed a significant correlation between the computed relative Gibbs free energies (rGFE, ∆∆Gcom) of MAO-B – inhibitor complex formation and IC50exp (pIC50exp = -0.22.∆∆Gcom +7.73; R2 = 0.93). With this QSAR model we were able to explain almost 93% of the variation of observed inhibition data. The predictive capability of the QSAR model was validate by generating the 3D QSAR MAO-B inhibition Pharmacophore (PH4) the estimated IC50pred of which displayed a non-less significant correlation with the observed IC50exp (R2 = 0.91) making this PH4 a reliable chemical space virtual screening tool. Deep analysis of MAO-B – inhibitor interactions at the enzyme active site suggested structural information about interesting building blocks for enumerating a large and diverse virtual combinatorial library (VCL) of 67,949 analogues of the reference inhibitor (COU1). The best PH4 mapping hit emerging from the virtual screening displays a half-maximal inhibitory concentration of 20 pM. Combining molecular modeling and PH4 model resulted in proposed novel potent anti-Parkinson’s agent candidates with favorable pharmacokinetic profiles. Despite the lack of Molecular Dynamics (MD) check of the conformational stability of novel predicted potent analogues, the resulting PH4, as virtual screening tool, can help processing larger databases in search of coumarin scaffold bearing MAO-B inhibitors.
Ancient water supports today's energy needs
Authors: D'Odorico Paolo , Natyzak Jennifer L. , Castner Elizabeth A. , Davis Kyle F. , Emery Kyle A. , Gephart Jessica A. , Leach Allison M. , Pace Michael L. , Galloway James N.
Published: April 2017

The water footprint for fossil fuels typically accounts for water utilized in mining and fuel processing, whereas the water footprint of biofuels assesses the agricultural water used by crops through their lifetime. Fossil fuels have an additional water footprint that is not easily accounted for: ancient water that was used by plants millions of years ago, before they were transformed into fossil fuel. How much water is mankind using from the past to sustain current energy needs? We evaluate the link between ancient water virtually embodied in fossil fuels to current global energy demands by determining the water demand required to replace fossil fuels with biomass produced with water from the present. Using equal energy units of wood, bioethanol, and biodiesel to replace coal, natural gas, and crude oil, respectively, the resulting water demand is 7.39 × 1013 m3 y−1, approximately the same as the total annual evaporation from all land masses and transpiration from all terrestrial vegetation. Thus, there are strong hydrologic constraints to a reliance on biofuel energy produced with water from the present because the conversion from fossil fuels to biofuels would have a disproportionate and unsustainable impact on the modern water. By using fossil fuels to meet today's energy needs, we are virtually using water from a geological past. The water cycle is insufficient to sustain the production of the fuel presently consumed by human societies. Thus, non‐fuel‐based renewable energy sources are needed to decrease mankind's reliance on fossil fuel energy without placing an overwhelming pressure on global freshwater resources.
The anatomy of a wrinkle ridge revealed in the wall of Melas Chasma, Mars
Authors: Cole Hank M. , Andrews‐Hanna Jeffrey C.
Published: April 2017

Wrinkle ridges are among the most common tectonic structures on the terrestrial planets and provide important records of the history of planetary strain and geodynamics. The observed broad arches and superposed narrow wrinkles are thought to be the surface manifestation of blind thrust faults, which terminate in near‐surface volcanic sequences and cause folding and layer‐parallel shear. However, the subsurface tectonic architecture associated with the ridges remains a matter of debate. Here we present direct observations of a wrinkle ridge thrust fault where it has been exposed by erosion in the southern wall of Melas Chasma on Mars. The thrust fault has been made resistant to erosion, likely due to volcanic intrusion, such that later erosional widening of the trough exposed the fault plane as a 70 km long ridge extending into the chasma. A plane fit to this ridge crest reveals a thrust fault with a dip of 13° (+8°, −7°) between 1 and 3.5 km depth below the plateau surface, with no evidence for listric character in this depth range. This dip is significantly lower than the commonly assumed value of 30°, which, if representative of other wrinkle ridges, indicates that global contraction on Mars may have been previously underestimated.
Screening of conventional anticonvulsants in a genetic mouse model of epilepsy
Authors: Hawkins Nicole A. , Anderson Lyndsey L. , Gertler Tracy S. , Laux Linda , George Alfred L. , Kearney Jennifer A.
Published: April 2017

Objective

Epilepsy is a common neurological disorder that affects 1% of the population. Approximately, 30% of individuals with epilepsy are refractory to treatment, highlighting the need for novel therapies. Conventional anticonvulsant screening relies predominantly on induced seizure models. However, these models may not be etiologically relevant for genetic epilepsies. Mutations in SCN1A are a common cause of Dravet Syndrome, a severe epileptic encephalopathy. Dravet syndrome typically begins in infancy with seizures provoked by fever and then progresses to include afebrile pleomorphic seizure types. Affected children respond poorly to available anticonvulsants. Scn1a+/− heterozygous knockout mice recapitulate features of Dravet syndrome and provide a potential screening platform to investigate novel therapeutics. In this study, we conducted a screening of conventional anticonvulsants in Scn1a+/− mice to establish assays that most closely correlate with human response data.

Methods

On the basis of clinical response data from a large, single center, retrospective survey of Dravet syndrome case records, we selected nine drugs for screening in Scn1a+/− mice to determine which phenotypic measures correlate best with human therapeutic response. We evaluated several screening paradigms and incorporated pharmacokinetic monitoring to establish drug exposure levels.

Results

Scn1a+/− mice exhibited responses to anticonvulsant treatment similar to those observed clinically. Sodium channel blockers were not effective or exacerbated seizures in Scn1a+/− mice. Overall, clobazam was the most effective anticonvulsant in Scn1a+/− mice, consistent with its effect in Dravet syndrome.

Interpretation

Genetic models of spontaneous epilepsy provide alternative screening platforms and may augment the AED development process. In this study, we established an effective screening platform that pharmacologically validated Scn1a+/− mice for preclinical screening of potential Dravet syndrome therapeutics.
Engineering Efficient p‐Type TMD/Metal Contacts Using Fluorographene as a Buffer Layer
Authors: Musso Tiziana , Kumar Priyank V. , Grossman Jeffrey C. , Foster Adam S.
Published: April 2017

P‐type transistors based on high work function transition metal dichalcogenide (TMD) monolayers such as MoS2 are to date difficult to produce, owing to the strong Fermi level pinning at the semiconductor/contact metal interfaces. In this work, the potential of halogenated graphenes is demonstrated as a new class of efficient hole injection layers to TMDs such as MoS2 and WSe2 by taking fluorographene (or GF) as a model buffer layer. Using first‐principles computations, two commonly obtained GF stoichiometries, C2F and CF, have been studied as buffer layers between MoS2 and Pt. In particular, for high work function TMDs such as MoS2, it has been shown that C2F forms an ohmic contact, while CF leads to a significant p‐SBH value. On the other hand, for low work function TMDs such as WSe2, both C2F and CF lead to p‐type ohmic contacts. This analysis shows that the ability of these buffer layers to form p‐type contacts depends crucially on the charge redistribution at the GF/metal interface, which is dictated by their chemical interaction and equilibrium geometry. The fundamental electronic structures between the different semiconductor/insulator/metal interfaces which are part of this study have also been investigated.
Domino Reaction of ortho‐Carbonylated Alkyne‐Substituted Arylaldehydes with Arylsulfinic Acids: Efficient Access to Sulfonyl‐Functionalized Indanones
Authors: Meng Xin , Zhu Hongbo , Chen Guang , Tian Laijin , Sun Xuejun , Cao Ziping , You Jinmao
Published: April 2017

An acid‐mediated domino reaction of ortho‐carbonylated alkynyl arylaldehydes with arylsulfinic acids provides rapid access to a variety of sulfonyl‐functionalized indanones in high yields. The proposed reaction mechanism involves a domino process that comprises the hydrolysis of an ynone motif, a Knoevenagel condensation reaction, and a thia‐Michael addition reaction. Thus, a one‐step operation enables the formation of C−C and C−S bonds. This transformation benefits from simple reaction conditions, readily available starting materials, and good substrate scope.
An easily organic–inorganic hybrid optical sensor based on dithizone impregnation on mesoporous SBA‐15 for simultaneous detection and removal of Pb(II) ions from water samples: Response‐surface methodology
Authors: Dashtian Kheibar , Zare‐Dorabei Rouholah
Published: April 2017

In this study, a novel organic–inorganic hybrid adsorbent for single‐step detection and removal of Pb(II) ions based on dithizone (DZ) anchored on mesoporous SBA‐15 was fabricated. The designed solid optical sensor revealed rapid colorimetric responses and high selectivity. Central composite design (CCD) combined with desirability function (DF) was applied to evaluate the interactive effects and optimization of important variables such as pH value, mesoporous SBA‐15 dosage, contact time and initial concentration of Pb(II) ions and optimum conditions for each of the factors were obtained 6.0, 25 mg, 30 min and 20 μg ml− 1, respectively. This adsorbent or solid optical chemo sensor exhibited a linear range of 1.0 to 100.0 μg ml−1 of Pb(II) ion concentration with a detection limit of 0.07 μg ml−1. This adsorbent was applied to determine and remove the Pb(II) in spiked samples. Various isotherm models such as Langmuir, Freundlich, Temkin and Dubinin–Radushkevich were studied for fitting the experimental equilibrium data. Langmuir model was chosen as an efficient model. Various kinetic models such as pseudo‐first, second order intraparticle, diffusion models were studied for analysis of experimental adsorption data and the pseudo second order model was chosen as an efficient model.
Stabilization of Hybrid Systems by Feedback Control Based on Discrete‐Time State and Mode Observations
Authors: Li Yuyuan , Lu Jianqiu , Mao Xuerong , Qiu Qinwei
Published: April 2017

Recently, a kind of feedback control based on discrete‐time state observations was proposed to stabilize continuous‐time hybrid stochastic systems in the mean‐square sense. We find that the feedback control there still depends on the continuous‐time observations of the mode. However, it usually costs to identify the current mode of the system in practice. So we can further improve the control to reduce the control cost by identifying the mode at discrete times when we make observations for the state. In this paper, we aim to design such a type of feedback control based on the discrete‐time observations of both state and mode to stabilize the given hybrid stochastic differential equations (SDEs) in the sense of mean‐square exponential stability. Moreover, a numerical example is given to illustrate our results.
Lyme carditis with complete heart block: management with an external pacemaker
Authors: Chaudhry Muhammad Ali , Satti Srinivasa D. , Friedlander Ira R.
Published: April 2017

Key Clinical Message

Timely diagnosis and prompt initiation of treatment is essential in Lyme carditis to achieve favorable prognosis. Externalized permanent pacemaker with an active fixation lead as supportive pacing modality is a feasible option till complete resolution of conduction block with continued antibiotic therapy.
Effects of Solution Composition and Polymer Additive on the Crystallization of Struvite
Authors: Liu Yi , Qu Haiyan
Published: April 2017

Reject water from a wastewater treatment plant contains a large amount of phosphorus that can be recovered and used as phosphate fertilizer. However, the quality of the final products is affected by the variation of wastewater composition. This work focuses on the effects of the nitrogen/phosphorus (N/P) molar ratio, which is a mutable variable in the reject water, and a polymer additive on the crystallization of struvite from an artificial reject water system. The obtained results suggest that crystallization at a low pH (7.5) resulted in a narrow size distribution, over 93 % P could be recovered. The presence of the polymer Aquaflok 414C led to a slightly narrower crystal size distribution at a lower supersaturation index.
Liquid‐Crystalline Elastomers with Gold Nanoparticle Cross‐Linkers
Authors: Wójcik Michał M. , Wróbel Jarosław , Jańczuk Zuzanna Z. , Mieczkowski Józef , Górecka Ewa , Choi Joonmyung , Cho Maenghyo , Pociecha Damian
Published: April 2017

Embedding nanoparticles in a responsive polymer matrix is a formidable way to fabricate hybrid materials with predesigned properties and prospective applications in actuators, mechanically tunable optical elements, and electroclinic films. However, achieving chemical compatibility between nanoparticles and organic matter is not trivial and often results in disordered structures. Herein, it is shown that using nanoparticles as exclusive cross‐linkers in the preparation of liquid‐crystalline polymers can yield long‐range‐ordered liquid‐crystalline elastomers with high loadings of well‐dispersed nanoparticles, as confirmed by small‐angle XRD measurements. Moreover, the strategy of incorporating NPs as cross‐linking units does not result in disruption of mechanical properties of the polymer, and this phenomenon was explained by the means of all‐atom molecular dynamics simulations. Such materials can exhibit switchable behavior under thermal stimulus with stability spanning over multiple heating/cooling cycles. The presented strategy has proven to be a promising approach for the preparation of new types of hybrid liquid‐crystalline elastomers that can be of value for future photonic applications.
Murai Reaction on Furfural Derivatives Enabled by Removable N,N′‐Bidentate Directing Groups
Authors: Pezzetta Cristofer , Veiros Luis F. , Oble Julie , Poli Giovanni
Published: April 2017

Furfural and related compounds are industrially relevant building blocks obtained from lignocellulosic biomass. To enhance the added value of these renewable resources, a Ru‐catalyzed hydrofurylation of alkenes, involving a directed C−H activation at C3 of the furan ring, was developed. A thorough experimental study revealed that a bidentate amino‐imine directing group enabled the desired coupling. Removal of the directing group occurred during the purification step, directly releasing the C3‐functionalized furfurals. Development of the reaction as well as optimization and scope of the method were described. A mechanism was proposed on the basis of DFT calculations.
Efficacy of postoperative prophylactic antibiotics in reducing permanent pacemaker infections
Authors: Lee Wen‐Huang , Huang Ting‐Chun , Lin Li‐Jen , Lee Po‐Tseng , Lin Chih‐Chan , Lee Cheng‐Han , Chao Ting‐Hsing , Li Yi‐Heng , Chen Ju‐Yi
Published: April 2017

Background

Despite limited evidence, postoperative prophylactic antibiotics are often used in the setting of permanent pacemaker implantation or replacement. The aim of this study is to investigate the efficacy of postoperative antibiotics.

Hypothesis

Postoperative prophylactic antibiotics may be not clinically useful.

Methods

We recruited 367 consecutive patients undergoing permanent pacemaker implantation or generator replacement at a tertiary referral center. Baseline demographics, clinical characteristics, and procedure information were collected, and all patients received preoperative prophylactic antibiotics. Postoperative prophylactic antibiotics were administered at the discretion of the treating physician, and all patients were seen in follow‐up every 3 to 6 months for an average follow‐up period of 16 months. The primary endpoint was device‐related infection.

Results

A total of 110 patients were treated with preoperative antibiotics only (group 1), whereas 257 patients received both preoperative and postoperative antibiotics (group 2). After a mean follow‐up period of 16 months, 1 patient in group 1 (0.9%) and 4 patients in group 2 (1.5%) experienced a device‐related infection. There was no significant difference in the rate of infection between the 2 groups (P = 0.624). In the univariate analysis, only the age (60 ± 11 vs 75 ± 12 years, P < 0.001) was significantly different between the infected and noninfected groups. In the multivariate analysis, younger age was an independent risk factor for infective complications (odds ratio = 1.08, P = 0.016).

Conclusions

Patients treated with preoperative and postoperative antibiotics had a similar rate of infection as those treated with preoperative antibiotics alone. Further studies are needed to confirm these preliminary findings.
A holistic view of the effects of episiotomy on pelvic floor
Authors: Oliveira Dulce A. , Parente Marco P.L. , Calvo Begoña , Mascarenhas Teresa , Natal Jorge Renato M.
Published: April 2017

Vaginal delivery is commonly accepted as a risk factor in pelvic floor dysfunction; however, other obstetric procedures (episiotomy) are still controversial. In this work, to analyze the relationship between episiotomy and pelvic floor function, a finite element model of the pelvic cavity is used considering the pelvic floor muscles (PFMs) with damaged regions from spontaneous vaginal delivery and from deliveries with episiotomy. Common features assessed at screening of pelvic floor dysfunction are evaluated during numerical simulations of both Valsalva maneuver and contraction.

As stated in literature, a weakening of the PFM, represented by damaged regions in the finite element model, would lead to a bladder neck hypermobility measured as a variation between the α angle (angle between the bladder neck and the symphysis pubis line and the midline of the symphysis) during straining and withholding.

However, the present work does not associate bladder neck hypermobility to a more damaged muscle, suggesting that other supportive structures also play an important role in the stabilization of the pelvic organs. Furthermore, considering passive behavior of the PFM, independently of the amount of damage considered, the resultant displacements of the pelvic structures are the same.

Regarding the PFM contraction, the less the muscle is damaged, the greater the movements of the pelvic organs. Furthermore, the internal organs of the female genital system are the most affected by the unhealthy of the PFM. Additionally, the present study shows that the muscle damage affects more the active muscle component than the passive.
Using Twitter and the mobile cloud for delivering medical help in emergencies
Authors: Alshareef Hazzaa Naif , Grigoras Dan
Published: April 2017

Emergency events require a fast response and decisions based on first‐hand information. This paper presents a mobile cloud service that makes the best use of social media applications, such as Twitter, in emergency and risk management. Here, risk and emergency teams can receive data that can inform their decisions in a matter of seconds when an emergency has affected areas under their management. The proposed service allows users to provide on‐the‐ground information regarding such an event, as well as early notification to people who are in the vicinity of an emergency situation. The service matches users' requests to a set of predefined labels that will help rescuers to understand the situation more clearly. The service was implemented and tested with Android devices and a cloud‐computing instance hosted on an Amazon platform. A cloud‐based tool is also provided for risk and emergency management teams to interact with users' requests. The experimental results show that the proposed mobile cloud service enhanced the early detection of emergencies. This paper also provides a review of research papers on the use of social media in risk and emergency management and the benefits of integrating social media with mobile cloud computing to provide a better healthcare service in emergencies.
The prevalence of type 2 diabetes in urban Bo, Sierra Leone, and in the 16 countries of the West Africa region
Authors: Sundufu Abu James , Bockarie Cecil N. , Jacobsen Kathryn H.
Published: April 2017

Background

The goal of this study was to measure the prevalence of diabetes among adults in urban Bo, Sierra Leone, and to compare the new results to the diabetes prevalence rates reported from studies across West Africa.

Methods

A total of 694 outpatients ages 18 and older at Bo Government Hospital were tested for diabetes between January 2012 and December 2014. Diabetes was defined as a fasting blood sugar level of ≥126 mg/dL (≥7.0 mmol/L).

Results

The overall prevalence of diabetes was 6.2% (43/694). Diabetes prevalence increased from 0.8% (2/256) among patients ages 18 to 29 years to 3.9% (8/204) among patients ages 30 to 39, 8.4% (11/131) among patients ages 40 to 49, 19.0% (12/63) among patients ages 50 to 59, and 25.0% (10/40) among patients ages 60 and older. The prevalence of diabetes was 5.2% among females and 7.4% among males. After adjusting the study population to the age and sex distribution of the national population, the standardized prevalence of diabetes was 7.0%. The only previously published study of diabetes in Sierra Leone found a much lower 2.4% prevalence rate in 1997. A comprehensive literature search identified studies from across West Africa (including Benin, Burkina Faso, Cabo Verde, Côte d'Ivoire, the Gambia, Ghana, Guinea, Guinea‐Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, and Togo) that illustrate an increasing rate of diabetes and impaired glucose tolerance in the region.

Conclusions

It is important for hospitals and clinics across West Africa to increase their ability to diagnose, monitor, and treat type 2 diabetes in urban and rural areas.
Serum uric acid levels are associated with increased risk of newly developed diabetic retinopathy among Japanese male patients with type 2 diabetes: A prospective cohort study (diabetes distress and care registry at Tenri [DDCRT13])
Authors: Kuwata Hirohito , Okamura Shintaro , Hayashino Yasuaki , Tsujii Satoru , Ishii Hitoshi ,   for the Diabetes Distress and Care Registry at Tenri Study Group
Published: April 2017

Objective

We assessed the prospective association between baseline serum uric acid levels and consequent risk of developing diabetic retinopathy.

Research Design and Methods

Data for 1839 type 2 diabetes patients without diabetic retinopathy were obtained from a Japanese diabetes registry. A Cox proportional hazards model with time‐varying exposure information by sex was used and adjusted for potential confounders to assess the independent correlations between baseline serum uric acid levels and incidence rate of diabetic retinopathy.

Results

Newly developed diabetic retinopathy was recognized in 188 patients (10.2%) during the observation period of 2 years. Compared to the first serum uric acid quartile level, the multivariate adjusted hazards ratio for diabetic retinopathy development in male patients was 1.97 (95% CI, 1.14‐3.41;P = .015), 1.92 (95% CI, 1.18‐3.13;P = .008), and 2.17 (95% CI, 1.40‐3.37;P = .001) for the second, third, and fourth serum uric acid quartile levels, respectively. But this was not the case with female patients.

Conclusion

Higher serum uric acid levels were associated with increased risk of developing diabetic retinopathy in male patients with type 2 diabetes, but not in female patients. Serum uric acid may be a useful biomarker for predicting the future risk of developing diabetic retinopathy in male patients with type 2 diabetes.
Ephedra alkaloid contents of Chinese herbal formulae sold in Taiwan
Authors: Chang Chih‐Wei , Hsu Szu‐Yun , Huang Guan‐Qian , Hsu Mei‐Chich
Published: April 2017

Consumption of Ephedra alkaloids is prohibited in‐competition by the World Anti‐Doping Agency (WADA). In Taiwan, colds are often treated with Chinese herbal formulae containing Herba Ephedrae. We screened products sold in Taiwan and preliminarily assessed their relationships with WADA threshold violations. Fifty‐six concentrated powder products, including 19 Chinese herbal formulae that contained Herba Ephedrae, were collected. The content of Ephedra alkaloids, namely ephedrine (E), methylephedrine (ME), norpseudoephedrine (NPE; cathine), pseudoephedrine (PE), and norephedrine (NE; phenylpropanolamine), was determined using a validated high‐performance liquid chromatography method. The results revealed that the phenotypic indicators of the collected products, E/PE and E/total ratios, were 1.52–4.70 and 0.49–0.72, respectively, indicating that the Herba Ephedrae species in these products was probably E. sinica or E. equisetina, but not E. intermedia. The contents of E, ME, NPE, PE, and NE and the total alkaloid contents in the daily doses of the products were 0.45–34.97, 0.05–4.87, 0.04–3.61, 0.15–12.09, and 0.01–2.00 mg and 0.68–53.64 mg, respectively. The alkaloid contents followed a relatively consistent order (E > PE > ME ≈ NPE > NE), even for products from different manufacturers. We calculated that single doses of 50.0% and 3.6% of the products would result in the WADA thresholds of E and NPE being exceeded, respectively. Our data provide critical information for athletes and medical personnel, who should be wary of using complex Chinese herbal formulae in addition to over‐the‐counter products.
Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites
Authors: González Eduardo , Sher Anna A. , Anderson Robert M. , Bay Robin F. , Bean Daniel W. , Bissonnete Gabriel J. , Bourgeois Bérenger , Cooper David J. , Dohrenwend Kara , Eichhorst Kim D. , El Waer Hisham , Kennard Deborah K. , Harms‐Weissinger Rebecca , Henry Annie L. , Makarick Lori J. , Ostoja Steven M. , Reynolds Lindsay V. , Robinson W. Wright , Shafroth Patrick B.
Published: April 2017

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial‐temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain‐saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow‐up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix‐infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species.
Assessing vulnerability of giant pandas to climate change in the Qinling Mountains of China
Authors: Li Jia , Liu Fang , Xue Yadong , Zhang Yu , Li Diqiang
Published: April 2017

Climate change might pose an additional threat to the already vulnerable giant panda (Ailuropoda melanoleuca). Effective conservation efforts require projections of vulnerability of the giant panda in facing climate change and proactive strategies to reduce emerging climate‐related threats. We used the maximum entropy model to assess the vulnerability of giant panda to climate change in the Qinling Mountains of China. The results of modeling included the following findings: (1) the area of suitable habitat for giant pandas was projected to decrease by 281 km2from climate change by the 2050s; (2) the mean elevation of suitable habitat of giant panda was predicted to shift 30 m higher due to climate change over this period; (3) the network of nature reserves protect 61.73% of current suitable habitat for the species, and 59.23% of future suitable habitat; (4) current suitable habitat mainly located in Chenggu, Taibai, and Yangxian counties (with a total area of 987 km2) was predicted to be vulnerable. Assessing the vulnerability of giant panda provided adaptive strategies for conservation programs and national park construction. We proposed adaptation strategies to ameliorate the predicted impacts of climate change on giant panda, including establishing and adjusting reserves, establishing habitat corridors, improving adaptive capacity to climate change, and strengthening monitoring of giant panda.
In vitro and in vivo analyses of Morus alba Polish var. wielkolistna zolwinska leaf ethanol–water extract—antioxidant and hypocholesterolemic activities in hyperlipideamic rats
Authors: Jeszka‐Skowron Magdalena , Flaczyk Ewa , Podgórski Tomasz
Published: April 2017

We previously reported that mulberry leaf extracts possess in vitro antioxidant activity and show antihypergliceamic activity in diabetic rats. The aim of this study was to: quantify bioactive components of Morus alba (Polish variety: wielkolistna zolwinska) ethanol–water extract and to examine the effect of different doses of extract on plasma lipids and plasma antioxidant capacity in rats fed high‐fat diet for 6 weeks. The composition of phenolic compounds and DNJ content by chromatography analyses in the ethanol–water extract from M. alba L. leaves as well as the results of ABTS and DPPH assays were determined. The effect of the extract addition to the diet of hyperlipidaemic Wistar rats was also measured. In the in vivo study, conducted in rats fed high‐fat (∼45% energy from fat) diet for 6 weeks, we found that M. alba leaf extract supplement ingested with food (6 g/kg) decreased total cholesterol (24.1%) and LDL‐c fraction (21.0%). M. alba ethanol–water extract showed a significant effect on lowering plasma total and LDL cholesterol and antioxidant activity measured by the ferric reducing ability of plasma. The extract is a good source of natural antioxidants and could be potentially used as a dietary supplement in future human studies.

Practical applications: M. alba L. (Polish variety: wielkolistna zolwinska) leaf ethanol–water extract with high antioxidant activity and rich in chlorogenic acids and flavonols in in vitro analyses and shows an effect on lowering plasma total and LDL cholesterol and antioxidant activity in hyperlipideamic rats could be a dietary supplement in food for hypercholesterolemic individuals.

The Morus alba (Polish variety: wielkolistna zolwinska) leaf ethanol–water extract, rich in flavonols and phenolic acids, ingested with high‐fat diet by hyperlipideamic rats effectively lowers plasma total and LDL cholesterol and improves oxidative status.
Interinstrumental transfer of a fast short‐end injection capillary electrophoresis method: Application to the separation of niobium, tantalum, and their substituted ions
Authors: De Cock Bart , Oliver James D. , Delaunay Nathalie , Deblonde Gauthier , Mangelings Debby , Vander Heyden Yvan
Published: April 2017

The interinstrumental transfer of a short‐end CE method was studied. A model separation of the hexameric forms of niobium, tantalum, and their substituted ions (Nb6−xTax with 0 ≤ x ≤ 6) was selected as test case. The method was first optimized on a Beckman instrument and in a second step transferred to an Agilent instrument. The transfer needed updated guidelines that tackled differences in effective capillary length, 8.5 (Agilent) versus 10 cm (Beckman), because of instrumental different capillary cartridges. Differences in effective length lead to migration time and separation efficiency inequalities, illustrated by a decrease in resolution between the substituted ions. The difference in effective length was overcome by adapting the lift offset parameter of the Agilent instrument. The lift offset default setting is 4 mm and by increasing this parameter both the inlet and outlet lifts are lowered and thus the detection window can be displaced and consequently the effective length was increased. The decrease in effective length difference and the effect on the separation efficiency was investigated and led finally to a restored separation of the substituted ions. The adaptation of the lift offset parameter during short‐end injection methods was added to earlier developed guidelines to facilitate interinstrumental method transfer of CE methods.
Polo‐like‐kinase 1 is a proviral host factor for hepatitis B virus replication
Authors: Diab Ahmed , Foca Adrien , Fusil Floriane , Lahlali Thomas , Jalaguier Pascal , Amirache Fouzia , N'Guyen Lia , Isorce Nathalie , Cosset François‐Loïc , Zoulim Fabien , Andrisani Ourania , Durantel David
Published: April 2017

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC) and current treatments for chronic hepatitis B and HCC are suboptimal. Herein, we identified cellular serine/threonine Polo‐like‐kinase 1 (PLK1) as a positive effector of HBV replication. The aim of this study was to demonstrate the proviral role of PLK1 in HBV biosynthesis and validate PLK1 inhibition a potential antiviral strategy. To this end, we employed physiologically relevant HBV infection models of primary human hepatocytes (PHHs) and differentiated HepaRG cells in conjunction with pharmacologic PLK1 inhibitors, small interfering RNA (siRNA)‐mediated knockdown, and overexpression of constitutively active PLK1 (PLK1CA). In addition, a humanized liver Fah−/−/Rag2−/−/Il2rg−/− (FRG) mouse model was used to determine the antiviral effect of PLK1 inhibitor BI‐2536 on HBV infection in vivo. Finally, in vitro PLK1 kinase assays and site‐directed mutagenesis were employed to demonstrate that HBV core protein (HBc) is a PLK1 substrate. We demonstrated that HBV infection activated cellular PLK1 in PHHs and differentiated HepaRG cells. PLK1 inhibition by BI‐2536 or siRNA‐mediated knockdown suppressed HBV DNA biosynthesis, whereas overexpression of PLK1CA increased it, suggesting that the PLK1 effects on viral biosynthesis are specific and that PLK1 is a proviral cellular factor. Significantly, BI‐2536 administration to HBV‐infected humanized liver FRG mice strongly inhibited HBV infection, validating PLK1 as an antiviral target in vivo. The proviral action of PLK1 is associated with the biogenesis of the nucleocapsid, as BI‐2536 leads to its decreased intracellular formation/accumulation. In this respect, our studies identified HBc as a PLK1 substrate in vitro, and mapped PLK1 phosphorylation sites on this protein. Conclusion: PLK1 is a proviral host factor that could be envisaged as a target for combined antiviral and antitumoral strategies against HBV infection and HBV‐mediated carcinogenesis. (Hepatology 2017;66:1750–1765)
Investigating the effect of fibulin‐1 on the differentiation of human nasal inferior turbinate‐derived mesenchymal stem cells into osteoblasts
Authors: Hang Pham Le B. , Yoo Yie‐Ri , Park Sun Hwa , Back Sang A. , Kim Sung Won , Bjørge Isabel , Mano João , Jang Jun‐Hyeog
Published: April 2017

Many extracellular matrix proteins have positive influences on the adhesion, proliferation, and differentiation of stem cells into specific cell linages. Fibulin‐1 (FBLN1), a member of a growing family of extracellular glycoproteins, contributes to the structure of the extracellular matrix. Here, we investigated the effect of FBLN1 on the ability of human nasal inferior turbinate‐derived mesenchymal stem cells (hTMSCs) to undergo osteogenic differentiation. After we generated recombinant FBLN1, the characteristics of FBLN1‐treated hTMSCs were evaluated using MTT assay, ALP and mineralization activities, and quantitative real‐time PCR. FBLN1 significantly enhanced the adhesion activity (p < 0.001) and proliferation of hTMSCs (p < 0.05). The ALP and mineralization activities of cells were dramatically increased (p < 0.01) after 9 and 12 days of FBLN1 treatment, respectively. This indicated the ability of FBLN1 to induce hTMSCs to differentiate into osteoblasts. Furthermore, increasing the mRNA levels of osteogenic marker genes, such as a transcriptional coactivator with a PDZ‐binding motif (TAZ), alkaline phosphatase (ALP), collagen type I (Col I), and osteocalcin (OCN), improved bone repair and regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2291–2298, 2017.
An Isoquinolin‐1(2H)‐Imine Derivative Induces Cell Death via Generation of Reactive Oxygen Species and Activation of JNK in Human A549 Cancer Cells
Authors: Liu Jing , Liu Tongyang , Mou Hanchuan , Jia Shuting , Huang Chao , Yan Shengjiao , Lin Jun , Luo Ying , Zhang Jihong
Published: April 2017

Compound 11‐benzoyl‐10‐chloro‐7,9‐difluoro‐6‐imino‐2,3,4,6‐tetrahydro‐1H‐pyrimido[1,2‐b]isoquinoline‐8‐carbonitrile (HC6h) is a novel polyhalo 1,3‐diazaheterocycle fused isoquinolin‐1(2H)‐imines derivative, which displays good anticancer activity and low toxicity in vivo. However, the underlying anticancer mechanisms have not previously been identified. The proliferation of A549 was assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in A549 with a H2DCFDA probe. Mitochondrial membrane potential was measured using the JC‐1 staining. Apoptosis were measured by annexin‐V/PI assay and autophagy by acridine orange staining and GFP‐LC3 fluorescence assay. The expression of autophagic and apoptotic proteins was determined by Western blot. The compound HC6h increased accumulation of vesicles, acridine orange‐stained cells and LC3‐II in A549 cells. Inhibition of compound HC6h‐induced autophagy by bafilomycin A1 increased apoptosis. Compound HC6h enhanced activation of caspase‐3, caspase‐9 and PARP cleavage in A549 cells. Compound HC6h leads to the rapid generation of intracellular ROS. Moreover, compound HC6h induced phosphorylation of JNK and was conferred by the increased ROS levels. Furthermore, down‐regulation of JNK attenuated autophagic and apoptotic effect in response to HC6h. The induction of ROS upon HC6h treatment leads to the activation of JNK that mediates autophagy and apoptosis in human A549 cancer cells. J. Cell. Biochem. 118: 4394–4403, 2017. © 2017 Wiley Periodicals, Inc.
BacteRiophage EXclusion (BREX): A novel anti‐phage mechanism in the arsenal of bacterial defense system
Authors: Bhushan Kul
Published: April 2017

The arm race between bacteria and phages leads to the development of many phage resistance mechanisms. Bacteria are perpetually changing their strategy to avert phage infection and killing. Recently, a study published that shed light on a novel bacterial defense system called bacteriophage exclusion (BREX). BREX system is a six‐gene cassette in Bacillus cereus which provides complete phage resistance to a broad range of phages, including lytic and temperate ones. It is a novel defense strategy which involves DNA methylation of the host cell and block phage DNA replication.
Pathways in the offending process of sex offenders who target marginalised victims
Authors: Horan Loren , Beauregard Eric
Published: April 2017

Prior literature shows that although marginalised populations are at a high risk of severe violence and homicide, research has focused on their offenders as if they constituted a homogeneous group. On the basis of a sample of 213 sex offenders who targeted marginalised individuals (i.e., sex trade worker, homeless individual, and severe drug user), we investigate the different pathways that these offenders take both prior to and during the commission of their crimes. Results of 2‐step cluster analysis regarding the offender's development, criminal history, crime context, and modus operandi revealed 3 distinct pathways of the offending process. The coercive pathway was characterised by the amount of violence used against the victim. The explosive pathway was defined by offenders who were in a state of rage at the time of the offence. Finally, offenders in the situational pathway committed their crimes out of opportunity and used very little violence. Differences between pathways were investigated with regard to characteristics of the index offence.
MALDI‐MS profiling of serum O‐glycosylation and N‐glycosylation in COG5‐CDG
Authors: Palmigiano A. , Bua R. O. , Barone R. , Rymen D. , Régal L. , Deconinck N. , Dionisi‐Vici C. , Fung C.‐W. , Garozzo D. , Jaeken J. , Sturiale L.
Published: April 2017

Congenital disorders of glycosylation (CDG) are due to defective glycosylation of glycoconjugates. Conserved oligomeric Golgi (COG)‐CDG are genetic diseases due to defects of the COG complex subunits 1–8 causing N‐glycan and O‐glycan processing abnormalities. In COG‐CDG, isoelectric focusing separation of undersialylated glycoforms of serum transferrin and apolipoprotein C‐III (apoC‐III) allows to detect N‐glycosylation and O‐glycosylation defects, respectively. COG5‐CDG (COG5 subunit deficiency) is a multisystem disease with dysmorphic features, intellectual disability of variable degree, seizures, acquired microcephaly, sensory defects and autistic behavior. We applied matrix‐assisted laser desorption/ionization‐MS for a high‐throughput screening of differential serum O‐glycoform and N‐glycoform in five patients with COG5‐CDG. When compared with age‐matched controls, COG5‐CDG showed a significant increase of apoC‐III0a (aglycosylated glycoform), whereas apoC‐III1 (mono‐sialylated glycoform) decreased significantly. Serum N‐glycome of COG5‐CDG patients was characterized by the relative abundance of undersialylated and undergalactosylated biantennary and triantennary glycans as well as slight increase of high‐mannose structures and hybrid glycans. Using advanced and well‐established MS‐based approaches, the present findings reveal novel aspects on O‐glycan and N‐glycan profiling in COG5‐CDG patients, thus providing an increase of current knowledge on glycosylation defects caused by impairment of COG subunits, in support of clinical diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.
Quantifying spatial and temporal variations in phytoplankton and kelp isotopic signatures to estimate the distribution of kelp‐derived detritus off the west coast of Vancouver Island, Canada
Authors: Ramshaw Brock C. , Pakhomov Evgeny A. , Markel Russell W. , Kaehler Sven
Published: April 2017

We used stable isotopes to determine spatial and temporal patterns of suspended kelp‐derived detritus (KDD) along a Macrocystis kelp abundance gradient driven by recovering sea otter (Enhydra lutris) populations along the west coast of Vancouver Island. Three dominant kelp species (order Laminariales) and surface marine size‐fractionated particulate organic matter (POM) were sampled along offshore transects (0–30 km) within three regions during summer and winter. Nearshore phytoplankton isotope values were identified in regions with high chlorophyll a concentrations. Summer blooming phytoplankton δ13C values were enriched by 2.4‰ and 0.8‰ and δ15N was enriched by 1.2‰ and 0.3‰ for 20–63 μm and 0.7–20 μm POM, respectively. Macrophyte stable isotope values varied significantly within and among regions, as well as between seasons. Primary producer values were used in a Bayesian isotope mixing model (MixSIR) to estimate the KDD contribution to POM. In general, the kelp abundant region had a greater contribution of KDD to POM further away (from 4 km to 30 km) from the kelp forest (range of medians 7–58%) compared to the kelp sparse region (4–30%). Seasonally, the KDD contribution to 20–63 μm POM size fractions was greater during summer (33% average) compared to winter (16% average). These results indicated that kelp abundance is not the only driver of KDD dispersal spatially and temporally. Factors such as local oceanography, large variation in kelp isotope values, and similarity between kelp and shelf phytoplankton isotope values affect these patterns and lead to high uncertainty in modeled KDD contributions.
Bringing methanotrophy in rivers out of the shadows
Authors: Shelley Felicity , Ings Nicola , Hildrew Alan G. , Trimmer Mark , Grey Jonathan
Published: April 2017

Methane oxidation produces biomass that is a potential source of particulate carbon for consumers, and is in addition to photosynthetic production. We assessed methanotrophy and photosynthetic production under differing conditions of light and methane concentration. We measured methane oxidation and photosynthesis in gravel sediments from adjacent shaded and unshaded stretches of 15 chalk rivers in southern England, and also in 30 artificial channels in which we manipulated light and methane experimentally. The capacity for methane oxidation was 78% higher in the shade than unshaded areas, indicating a denser, or more active, methanotrophic assemblage on shaded riverbeds, and the difference was most pronounced when methane concentration was high. Across the 15 rivers, methanotrophic production ranged from 16 to 650 nmol C cm−2 d−1 and net photosynthetic production from 256 to 35,750 nmol C cm−2 d−1. The relative importance of methanotrophy to their total production (i.e., photosynthetic and methanotrophic) increased with methane concentration and ranged from 0.1–2.4% and 0.2–13% in unshaded and shaded areas, respectively. Over an annual cycle in one river, the response of the methanotrophs in the shade to a high summer methane concentration was ∼ five times greater than in the open; in winter, there was no effect of shading on methane oxidation. The response of methanotrophy to shading and methane concentration in the artificial channels resembled that found in the rivers. Methanotrophy makes a non‐negligible (here up to ∼ 13%) contribution to particulate carbon production in these streams, is disproportionately greater in the shade, and constitutes a distinct carbon pathway available for their food webs.