bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-based characterization and antifreeze properties of a hyperactive ice-binding protein from the Antarctic bacteriumFlavobacterium frigorisPS1
Authors: Do Hackwon , Kim Soon-Jong , Kim Hak Jun , Lee Jun Hyuck
Published: March 2014

Ice-binding proteins (IBPs) inhibit ice growth through direct interaction with ice crystals to permit the survival of polar organisms in extremely cold environments. FfIBP is an ice-binding protein encoded by the Antarctic bacteriumFlavobacterium frigorisPS1. The X-ray crystal structure of FfIBP was determined to 2.1 Å resolution to gain insight into its ice-binding mechanism. The refined structure of FfIBP shows an intramolecular disulfide bond, and analytical ultracentrifugation and analytical size-exclusion chromatography show that it behaves as a monomer in solution. Sequence alignments and structural comparisons of IBPs allowed two groups of IBPs to be defined, depending on sequence differences between the α2 and α4 loop regions and the presence of the disulfide bond. Although FfIBP closely resemblesLeucosporidium(recently re-classified asGlaciozyma) IBP (LeIBP) in its amino-acid sequence, the thermal hysteresis (TH) activity of FfIBP appears to be tenfold higher than that of LeIBP. A comparison of the FfIBP and LeIBP structures reveals that FfIBP has different ice-binding residues as well as a greater surface area in the ice-binding site. Notably, the ice-binding site of FfIBP is composed of a T-A/G-X-T/N motif, which is similar to the ice-binding residues of hyperactive antifreeze proteins. Thus, it is proposed that the difference in TH activity between FfIBP and LeIBP may arise from the amino-acid composition of the ice-binding site, which correlates with differences in affinity and surface complementarity to the ice crystal. In conclusion, this study provides a molecular basis for understanding the antifreeze mechanism of FfIBP and provides new insights into the reasons for the higher TH activity of FfIBP compared with LeIBP.
Bis(N-nitroso-N-pentylhydroxylaminato-κ2O,O′)copper(II)
Authors: Sheikh Bostanabad Ali , Kovalchukova Olga , Strashnova Svetlana , Stash Adam , Zyuzin Igor
Published: March 2014

In the centrosymmetric title compound, [Cu(C5H11N2O2)2], the Cu2+ion, located on an inversion centre (Wyckoff position 2b), is in a square-planar environment, surounded by four O atoms of the N—O groups of twoN-nitroso-N-pentylhydroxylaminate ligands [Cu—O = 1.9042 (17) and 1.9095 (16) Å]. The hydroxylaminate monoanions are bidentate chelating ligands. The Cu2+cations form stacks along [010], with intermolecular Cu...N contacts of 3.146 (2) and 3.653 (2) Å.
5,8-Bis[bis(pyridin-2-yl)amino]-1,3,4,6,7,9,9b-heptaazaphenalen-2(1H)-one dimethyl sulfoxide monosolvate dihydrate
Authors: Schwarzer Anke , Kroke Edwin
Published: March 2014

In the asymmetric unit of the title compound, C26H17N13O·C2H6OS·2H2O, there is one independent heptazine-based main molecule, one dimethyl sulfoxide molecule and two water molecules as solvents. The tri-s-triazine unit is substituted with two dipyridyl amine moieties and a carbonylic O atom. As indicated by the bond lengths in this acid unit of the heptazine derivative [C=O = 1.213 (2) Å, while the adjacent C—N(H) bond = 1.405 (2) Å] it is best described by the keto form. The cyameluric nucleus is close to planar (r.m.s. deviation = 0.061 Å) and the pyridine rings are inclined to its mean plane by dihedral angles varying from 47.47 (5) to 70.22 (5)°. The host and guest molecules are connectedviaN—H...O, O—H...O and O—H...N hydrogen bonds, forming a four-membered inversion dimer-like arrangement enclosing anR44(24) ring motif. These arrangements stack along [1-10] with a weak π–π interaction [inter-centroid distance = 3.8721 (12) Å] involving adjacent pyridine rings. There are also C—H...N and C—H...O hydrogen bonds and C—H...π interactions present within the host molecule and linking inversion-related molecules, forming a three-dimensional structure.
Combined fitting of small- and wide-angle X-ray total scattering data from nanoparticles: benefits and issues
Authors: Gagin Anton , Allen Andrew J. , Levin Igor
Published: March 2014

Simultaneous fitting of small- (SAS) and wide-angle (WAS) X-ray total scattering data for nanoparticles has been explored using both simulated and experimental signals. The nanoparticle types included core/shell metal and quantum-dot CdSe systems. Various combinations of reciprocal- and real-space representations of the scattering data have been considered. Incorporating SAS data into the fit consistently returned more accurate particle-size distribution parameters than those obtained by fitting the WAS data alone. A popular method for fitting the Fourier transform of the WAS data (i.e.a pair-distribution function), in which the omitted SAS part is represented using a parametric function, typically yielded significantly incorrect results. The Pareto optimization method combined with a genetic algorithm proved to be effective for simultaneous SAS/WAS analyses. An approach for identifying the most optimal solution from the Pareto set of solutions has been proposed.
Small-angle scattering from polydisperse particles with a diffusive surface
Authors: Tomchuk Olexandr V. , Bulavin Leonid A. , Aksenov Viktor L. , Garamus Vasil M. , Ivankov Oleksandr I. , Vul' Alexander Ya. , Dideikin Artur T. , Avdeev Mikhail V.
Published: March 2014

Particles with a diffusive surface, characterized by a deviation from the Porod power-law asymptotic behavior in small-angle scattering towards an exponent below −4, are considered with respect to the polydispersity problem. The case of low diffusivity is emphasized, which allows the description of the scattering length density distribution within spherically isotropic particles in terms of a continuous profile. This significantly simplifies the analysis of the particle-size distribution function, as well as the change in the scattering invariants under contrast variation. The effect of the solvent scattering contribution on the apparent exponent value in power-law-type scattering and related restrictions in the analysis of the scattering curves are discussed. The principal features and possibilities of the developed approach are illustrated in the treatment of experimental small-angle neutron scattering data from liquid dispersions of detonation nanodiamond. The obtained scattering length density profile of the particles fits well with a transition of the diamond states of carbon inside the crystallites to graphite-like states at the surface, and it is possible to combine the diffusive properties of the surface with the experimental shift of the mean scattering length density of the particles compared with that of pure diamond. The moments of the particle-size distribution are derived and analyzed in terms of the lognormal approximation.
Absolute scale calibration with use of excess scattering length for small-angle X-ray scattering
Authors: Ohta Noboru , Sekiguchi Hiroshi , Sasaki Yuji C. , Yagi Naoto
Published: March 2014

For small-angle X-ray scattering (SAXS) in solution, absolute intensity calibration is an important step to estimate the number of electrons of the sample. In this study, the excess scattering length of 1-bromododecane dispersed in dodecane was determined using that of 1-chlorododecane in the same solvent. The deviation of the experimental values from theoretical calculations obtained using atomic factors was around 1%. It is suggested that the 1-chlorododecane–dodecane system constitutes a new calibration approach that is applicable to various materials over a large energy range generally used in SAXS measurements, and could be less complex and more reliable than conventional methods.
Simultaneous determination of several crystal structures from powder mixtures: the combination of powder X-ray diffraction, band-target entropy minimization and Rietveld methods
Authors: Schreyer Martin , Guo Liangfeng , Thirunahari Satyanarayana , Gao Feng , Garland Marc
Published: March 2014

Crystal structure determination is the key to a detailed understanding of crystalline materials and their properties. This requires either single crystals or high-quality single-phase powder X-ray diffraction data. The present contribution demonstrates a novel method to reconstruct single-phase powder diffraction data from diffraction patterns of mixtures of several components and subsequently to determine the individual crystal structures. The new method does not require recourse to any database of known materials but relies purely on numerical separation of the mixture data into individual component diffractograms. The resulting diffractograms can subsequently be treated like single-phase powder diffraction data,i.e.indexing, structure solution and Rietveld refinement. This development opens up a host of new opportunities in materials science and related areas. For example, crystal structures can now be determined at much earlier stages when only impure samples or polymorphic mixtures are available.
Patterson analysis for layer profile determination by neutron or X-ray reflectometry. II
Authors: Tun Zin
Published: March 2014

A data analysis technique based on the Patterson function is tested with simulated X-ray reflectometry data. In comparison to the case for neutron reflectometry, additional data manipulation is required because the scattering-length density of materials is generally much higher for X-rays than for neutrons. With this extra step duly performed, the technique yields a model layer profile accurate enough for least-squares refinement.
The role of the commonwealth environmental water holder in annual water allocation markets
Authors: Ancev Tiho
Published: March 2014

In recent years, the Government of Australia has bought back a significant amount of water entitlements in the Murray‐Darling Basin (MDB) through its Commonwealth Environmental Water Holder (CEWH) agency. This has been a welcome development, as it is an efficient way of securing water for the environment in the basin. However, the question of how to best manage water holdings held by the government is as yet unresolved. In particular, the question of whether and how should the CEWH engage in water markets is still grappling the government and academia alike. This paper addresses that question by evaluating total benefits to a range of water users, including the environment, under a variety of hydro‐climatic conditions. This is approached through running simulations based on environmental benefit function that varies with prevailing hydro‐climatic conditions. The findings indicate that the benefits are greater when CEWH actively participates in annual water allocation market and that such participation enables the CEWH to secure most water when it is needed the most by the environment. This suggests that policy should encourage the CEWH to further explore opportunities to engage with the water markets to the benefit of communities and the environment in the MDB.
Towards intensive parenting? Changes in the composition and determinants of mothers' and fathers' time with children 1992–2006
Authors: Craig Lyn , Powell Abigail , Smyth Ciara
Published: March 2014

Contemporary expectations of good parenting hold that focused, intensive parental attention is essential to children's development. Parental input is viewed as a key determinant in children's social, psychological and educational outcomes, with the early years particularly crucial. However, increased rates of maternal employment mean that more parents are juggling work and family commitments and have less non‐work time available to devote to children. Yet studies find that parental childcare time has increased over recent decades. In this paper, we explore the detail of this trend using data from the Australian Bureau of Statistics (ABS) Time Use Survey (TUS), 1992 and 2006. To investigate whether discourses on intensive parenting are reflected in behaviour, we examine a greater range of parent–child activities than has been undertaken to date, looking at trends in active childcare time (disaggregated into talk‐based, physical and accompanying care activities); time in childcare as a secondary activity; time spent in the company of children in leisure activities; and time spent in the company of children in total. We also investigate whether the influence of factors known to predict parental time with children (gender, education, employment status and the age of children) have changed over time. We contextualize our analyses within social and economic trends in Australia and find a compositional change in parental time, with more active childcare occurring within less overall time, which suggests more intensive, child‐centred parenting. Fathers' parent–child time, particularly in physical care, increased more than mothers' (from a much lower base), and tertiary education no longer predicts significantly higher childcare time.
Indirect causes of severe adverse maternal outcomes: a secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health
Authors: Lumbiganon P , Laopaiboon M , Intarut N , Vogel JP , Souza JP , Gülmezoglu AM , Mori R
Published: March 2014

Objective

To assess the proportion of severe maternal outcomes resulting from indirect causes, and to determine pregnancy outcomes of women with indirect causes.

Design

Secondary analysis of the WHO Multicountry Survey on Maternal and Newborn Health.

Setting

A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East.

Sample

A total of 314 623 pregnant women admitted to the participating facilities.

Methods

We identified the percentage of women with severe maternal outcomes arising from indirect causes. We evaluated the risk of severe maternal and perinatal outcomes in women with, versus without, underlying indirect causes, using adjusted odds ratios and 95% confidence intervals, by a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities.

Main outcome measures

Severe maternal outcomes and preterm birth, fetal mortality, early neonatal mortality, perinatal mortality, low birthweight, and neonatal intensive care unit admission.

Results

Amongst 314 623 included women, 2822 were reported to suffer from severe maternal outcomes, out of which 20.9% (589/2822; 95% CI 20.1–21.6%) were associated with indirect causes. The most common indirect cause was anaemia (50%). Women with underlying indirect causes showed significantly higher risk of obstetric complications (adjusted odds ratio, aOR, 7.0; 95% CI 6.6–7.4), severe maternal outcomes (aOR 27.9; 95% CI 24.7–31.6), and perinatal mortality (aOR 3.8; 95% CI 3.5–4.1).

Conclusions

Indirect causes were responsible for about one‐fifth of severe maternal outcomes. Women with underlying indirect causes had significantly increased risks of severe maternal and perinatal outcomes.
Advanced maternal age and pregnancy outcomes: a multicountry assessment
Authors: Laopaiboon M , Lumbiganon P , Intarut N , Mori R , Ganchimeg T , Vogel JP , Souza JP , Gülmezoglu AM ,   on behalf of the WHO Multicountry Survey on Maternal Newborn Health Research Network
Published: March 2014

Objective

To assess the association between advanced maternal age (AMA) and adverse pregnancy outcomes.

Design

Secondary analysis of the facility‐based, cross‐sectional data of the WHO Multicountry Survey on Maternal and Newborn Health.

Settings

A total of 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East.

Sample

A total of 308 149 singleton pregnant women admitted to the participating health facilities.

Methods

We estimated the prevalence of pregnant women with advanced age (35 years or older). We calculated adjusted odds ratios of individual severe maternal and perinatal outcomes in these women, compared with women aged 20–34 years, using a multilevel, multivariate logistic regression model, accounting for clustering effects within countries and health facilities. The confounding factors included facility and individual characteristics, as well as country (classified by maternal mortality ratio level).

Main outcome measures

Severe maternal adverse outcomes, including maternal near miss (MNM), maternal death (MD), and severe maternal outcome (SMO), and perinatal outcomes, including preterm birth (<37 weeks of gestation), stillbirths, early neonatal mortality, perinatal mortality, low birthweight (<2500 g), and neonatal intensive care unit (NICU) admission.

Results

The prevalence of pregnant women with AMA was 12.3% (37 787/308 149). Advanced maternal age significantly increased the risk of maternal adverse outcomes, including MNM, MD, and SMO, as well as the risk of stillbirths and perinatal mortalities.

Conclusions

Advanced maternal age predisposes women to adverse pregnancy outcomes. The findings of this study would facilitate antenatal counselling and management of women in this age category.
Is chronic kidney disease associated with diabetic retinopathy in Asian adults? 在亚洲成年人中慢性肾病与糖尿病视网膜病变相关吗？
Authors: Sabanayagam Charumathi , Foo Valencia Hui Xian , Ikram M Kamran , Huang Huiqi , Lim Su Chi , Lamoureux Ecosse L , Tai E Shyong , Wong Tien Yin
Published: March 2014

Background

Diabetic nephropathy (DN) is commonly associated with diabetic retinopathy (DR). Few studies have demonstrated that chronic kidney disease (CKD) is associated with DR. However, it is not clear if CKD in the absence of albuminuria is associated with DR.

Methods

We included 301 participants with diabetes (Chinese, Malay and Indian ethnicity aged ≥24 years who participated in the Singapore Prospective Study Program (2003–2007). Retinal photographs taken from both eyes were graded for DR using the modified Airlie House Classification. We examined the association of CKD defined by low estimated glomerular filtration rate (eGFR) (<60 mL/min per 1.73 m2, n = 54), and albuminuria (urinary albumin‐to‐creatinine ratio ≥30, n = 116) with any‐DR (n = 99) in logistic regression models. We replicated this analysis in another independent population‐based sample of Malay adults (n = 265) with similar methodology in Singapore.

Results

41% of those with low‐eGFR had normoalbuminuria. In separate models, while albuminuria was significantly associated with any‐DR, low‐eGFR was not significantly associated with any‐DR. In a model combining both markers, compared to the referent group (normal‐eGFR+normoalbuminuria), the odds ratio (OR) (95% confidence interval [CI]) of any‐DR were: 2.33 (1.27–4.27) for normal‐eGFR+albuminuria, 1.38 (0.49–3.91) for low‐eGFR + normoalbuminuria, and 2.64 (1.05–6.63) for low‐eGFR+albuminuria. Similar findings for any‐DR were observed in the replication cohort of Malay persons (3.56 [1.49–8.54] for normal‐eGFR+albuminuria, 1.69 (0.52–5.55) for low‐eGFR+normoalbuminuria, 4.34 [1.68–11.24] for low‐eGFR+albuminuria.

Conclusion

We demonstrated that CKD is associated with DR only in the presence of albuminuria suggesting that CKD is more likely related to diabetes in the presence of albuminuria.
Polysensitisation in a laboratory scientist associated with allergic contact dermatitis from methylisothiazolinone in skin cleansers
Authors: Palmer Matthew J , Nixon Rosemary
Published: March 2014

Polysensitisation refers to reactivity to three or more allergens on epicutaneous patch testing, and is likely to affect a distinct subgroup of individuals with allergic contact dermatitis (ACD). Methylisothiazolinone (MIT) is an increasingly prevalent allergen, recently having been described as occurring in epidemic proportions. We report a patient with ACD to 12 allergens, including MIT, and discuss the implications of polysensitisation and the likely need for repeat patch testing in such patients if they subsequently re‐present with dermatitis.
Incidence of clinically symptomatic pneumothorax in ultrasound‐guided infraclavicular and supraclavicular brachial plexus block
Authors: Gauss A. , Tugtekin I. , Georgieff M. , Dinse‐Lambracht A. , Keipke D. , Gorsewski G.
Published: March 2014

The use of periclavicular brachial plexus block as regional anaesthesia for surgical procedures on the upper extremity is common. However, the proximity of the pleura results in a risk of pneumothorax. Without ultrasound monitoring, the pneumothorax risk has been reported to be as high as 6.1%. We conducted a prospective, observational study to examine the risk of pneumothorax in 6366 ultrasound‐guided periclavicular plexus blocks. All patients with a clinically manifest and radiologically confirmed pneumothorax were analysed. Clinically symptomatic pneumothorax occurred in four patients (0.06%; 95% CI 0.001–0.124), in three of them after a two‐day latency period. Ultrasound guidance does therefore appear to reduce the risk of pneumothorax. Although all of the anaesthesiologists involved in the complications had previously performed fewer than 20 blocks, we are not able to confirm that a block experience ≤ 20 is a significant risk factor. Faulty image‐setting, inability to obtain a view of the needle tip and inadequate supervision are likely to be important risk factors.
Ear drainage and the role of sepsis evaluations in the neonatal intensive care unit
Authors: Khattab Mona , Cannon‐Heinrich Charlene , Bizzarro Matthew J.
Published: March 2014

Aim

To design and implement an intervention to reduce ear drainage and subsequent sepsis evaluation and treatment in the neonatal intensive care unit.

Methods

From 2008 to 2011, we observed an increase in the rates of ear drainage warranting investigation. Data collection was performed from 1991 to 2013 on 50 cases. Preliminary analysis revealed an association between timing of endotracheal tube tape changes and onset of drainage. We speculated that pooling of anti‐adhesive solution into the external auditory canal was precipitating an inflammatory process. Unit‐wide education was conducted to protect the ears during tape removal. Post‐initiative rates of drainage were collected and compared with pre‐initiative rates.

Results

Median gestational age and birthweight were 26 weeks and 754 g, respectively. In 64% of cases, an anti‐adhesive solution was used on the face within 48 h of the onset of drainage. Sepsis evaluation was performed in 68% of cases. Rates of ear drainage peaked from 2008 to 2011 at 9.18 per 1000 admissions when a new anti‐adhesive product was used, declining to 0.66 post‐initiative (rate difference: −8.52; 95% CI: −12.00, −5.03).

Conclusion

Protecting the ear from anti‐adhesive solutions during tape removal may reduce rates of noninfectious ear drainage and limit unnecessary interventions.
An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin
Authors: Carrancio Soraya , Markovics Jennifer , Wong Piu , Leisten Jim , Castiglioni Paola , Groza Matthew C. , Raymon Heather K. , Heise Carla , Daniel Tom , Chopra Rajesh , Sung Victoria
Published: March 2014

Sotatercept (ACE‐011), a recombinant human fusion protein containing the extracellular domain of the human Activin receptor IIA, binds to and inhibits activin and other members of the transforming growth factor ‐β (TGF‐β) superfamily. Administration of sotatercept led to a rapid and sustained increase in red blood cell (RBC) count and haemoglobin (Hb) in healthy volunteers (phase I clinical trials), but the mechanism is not fully understood. Mice treated with RAP‐011 (murine ortholog of ACE‐011) respond with a rapid (within 24 h) increase in haematocrit, Hb, and RBC count. These effects are accompanied by an equally rapid stimulation of late‐stage erythroid precursors in the bone marrow (BM). RAP‐011 also induces a significant increase in erythroid burst‐forming units and erythropoietin, which could contribute to additional, sustained effects on RBC production. Further in vitro co‐culture studies demonstrate that BM accessory cells are required for RAP‐011 effects. To better understand which TGF‐β family ligand(s) mediate RAP‐011 effects, we evaluated the impact of several of these ligands on erythroid differentiation. Our data suggest that RAP‐011 may act to rescue growth differentiation factor 11/Activin A‐induced inhibition of late‐stage erythropoiesis. These data define the mechanism of action of a novel agent that regulates RBC differentiation and provide the rationale to develop sotatercept for the treatment of anaemia and ineffective erythropoiesis.
High‐Throughput Screen of Natural Product Extracts in A Yeast Model of Polyglutamine Proteotoxicity
Authors: Walter Gladis M. , Raveh Avi , Mok Sue‐Ann , McQuade Thomas J. , Arevang Carl J. , Schultz Pamela J. , Smith Matthew C. , Asare Samuel , Cruz Patricia G. , Wisen Susanne , Matainaho Teatulohi , Sherman David H. , Gestwicki Jason E.
Published: March 2014

Proteins with expanded polyglutamine (polyQ) segments cause a number of fatal neurodegenerative disorders, including Huntington's disease (HD). Previous high‐throughput screens in cellular and biochemical models of HD have revealed compounds that mitigate polyQ aggregation and proteotoxicity, providing insight into the mechanisms of disease and leads for potential therapeutics. However, the structural diversity of natural products has not yet been fully mobilized toward these goals. Here, we have screened a collection of ~11 000 natural product extracts for the ability to recover the slow growth of ΔProQ103‐expressing yeast cells in 384‐well plates (Z' ~ 0.7, CV ~ 8%). This screen identified actinomycin D as a strong inhibitor of polyQ aggregation and proteotoxicity at nanomolar concentrations (~50–500 ng/mL). We found that a low dose of actinomycin D increased the levels of the heat‐shock proteins Hsp104, Hsp70 and Hsp26 and enhanced binding of Hsp70 to the polyQ in yeast. Actinomycin also suppressed aggregation of polyQ in mammalian cells, suggesting a conserved mechanism. These results establish natural products as a rich source of compounds with interesting mechanisms of action against polyQ disorders.
1,3‐Disubstituted‐4‐Aminopyrazolo [3, 4‐d] Pyrimidines, a New Class of Potent Inhibitors for Phospholipase D
Authors: Kulkarni Aditya , Quang Phong , Curry Victoriana , Keyes Renee , Zhou Weihong , Cho Hyejin , Baffoe Jonathan , Török Béla , Stieglitz Kimberly
Published: March 2014

Phospholipase D enzymes cleave lipid substrates to produce phosphatidic acid, an important precursor for many essential cellular molecules. Phospholipase D is a target to modulate cancer‐cell invasiveness. This study reports synthesis of a new class of phospholipase D inhibitors based on 1,3‐disubstituted‐4‐amino‐pyrazolopyrimidine core structure. These molecules were synthesized and used to perform initial screening for the inhibition of purified bacterial phospholipase D, which is highly homologous to the human PLD1. Initially tested with the bacterial phospholipase D enzyme, then confirmed with the recombinant human PLD1 and PLD2 enzymes, the molecules presented here exhibited inhibition of phospholipase D activity (IC50) in the low‐nanomolar to low‐micromolar range with both monomeric substrate diC4PC and phospholipid vesicles and micelles. The data strongly indicate that these inhibitory molecules directly block enzyme/vesicle substrate binding. Preliminary activity studies using recombinant human phospholipase Ds in in vivo cell assays measuring both transphosphatidylation and head‐group cleavage indicate inhibition in the mid‐ to low‐nanomolar range for these potent inhibitory novel molecules in a physiological environment.
Rational Design and Screening Study of Novel Lead Compound Based on Acetohydroxyacid Synthase Structure
Authors: Jin Jingnan , Qi Xiaojuan , Yao Dandan , Mao Bangqiang , Li Jianhong , Zhang Qingye , Chen Changshui
Published: March 2014

Acetohydroxyacid synthase (AHAS) is a key target and has extensive application in the process of herbicide discovery. However, the problem of weed resistance is gradually serious with long‐term excessive use of commercial AHAS‐inhibiting herbicides, and so, it is urgent to develop novel herbicides. In this study, a virtual screening was performed based on the active site of AHAS. Then, the hit‐10 compound with the IC50 value of 47.41 mg/L was selected as lead compound based on the biological testing. Subsequently, the optimization design and syntheses of lead compound were carried out according to the analyzing results of mechanism and receptor‐/ligand‐binding mode. Three novel 5‐substituted benzyl‐1,3,4‐thiadiazol‐2‐carbamic acid phenyl ester derivatives were designed and synthesized. Bioactive assay results of the three target compounds showed that all of them displayed the higher inhibition than lead compound to AHAS, with the IC50 values in the 23.54–32.05 mg/L range, and the inhibition rates were increased by 30–50%. Finally, we also analyzed the possible inhibitory mechanism of the three target compounds based on the molecular docking between AHAS and target compounds. This study would provide a novel chemical structure for the discovery of novel AHAS herbicides.
Developmental regulation of p53-dependent radiation-induced thymocyte apoptosis in mice
Authors: Gentil Dit Maurin A , Lemercier C , Collin-Faure V , Marche P N , Jouvin-Marche E , Candéias S M
Published: March 2014

The production of T cell receptor αβ+ (TCRαβ+) T lymphocytes in the thymus is a tightly regulated process that can be monitored by the regulated expression of several surface molecules, including CD4, CD8, cKit, CD25 and the TCR itself, after TCR genes have been assembled from discrete V, D (for TCR-β) and J gene segments by a site-directed genetic recombination. Thymocyte differentiation is the result of a delicate balance between cell death and survival: developing thymocytes die unless they receive a positive signal to proceed to the next stage. This equilibrium is altered in response to various physiological or physical stresses such as ionizing radiation, which induces a massive p53-dependent apoptosis of CD4+CD8+ double-positive (DP) thymocytes. Interestingly, these cells are actively rearranging their TCR-α chain genes. To unravel an eventual link between V(D)J recombination activity and thymocyte radio-sensitivity, we analysed the dynamics of thymocyte apoptosis and regeneration following exposure of wild-type and p53-deficient mice to different doses of γ-radiation. p53-dependent radio-sensitivity was already found to be high in immature CD4−CD8− (double-negative, DN) cKit+CD25+ thymocytes, where TCR-β gene rearrangement is initiated. However, TCR-αβ−CD8+ immature single-positive thymocytes, an actively cycling intermediate population between the DN and DP stages, are the most radio-sensitive cells in the thymus, even though their apoptosis is only partially p53-dependent. Within the DP population, TCR-αβ+ thymocytes that completed TCR-α gene recombination are more radio-resistant than their TCR-αβ− progenitors. Finally, we found no correlation between p53 activation and thymocyte sensitivity to radiation-induced apoptosis.
Object Concepts in the Chemical Senses
Authors: Stevenson Richard J.
Published: March 2014

This paper examines the applicability of the object concept to the chemical senses, by evaluating them against a set of criteria for object‐hood. Taste and chemesthesis do not generate objects. Their parts, perceptible from birth, never combine. Orthonasal olfaction (sniffing) presents a strong case for generating objects. Odorants have many parts yet they are perceived as wholes, this process is based on learning, and there is figure‐ground segregation. While flavors are multimodal representations bound together by learning, there is no functional need for flavor objects in the mouth. Rather, food identification occurs prior to ingestion using the eye and nose, with the latter retrieving multimodal flavor objects via sniffing (e.g.,sweetsmelling caramel). While there are differences in object perception between vision, audition, and orthonasal olfaction, the commonalities suggest that the brain has adopted the same basic solution when faced with extracting meaning from complex stimulus arrays.
Combined cutaneous smooth muscle hamartoma and nevus flammeus
Authors: Fernandez‐Flores Angel , Saeb‐Lima Marcela
Published: March 2014

We report on a combined cutaneous smooth muscle hamartoma and reticulate port‐wine stain on the thigh of a 26‐year‐old woman. The lesion measured 30 cm in longest diameter and presented clinically with a macular erythematous telangiectatic vascular appearance. It was focally ulcerated, which represented the patient's main complaint. Histopathological study demonstrated smooth muscle bundles closely intermingled with a vascular component comprised of capillaries and venules. Such a morphological presentation is, to the best of our knowledge, unique in the literature.
Association between vascular access type and patient mortality among elderly patients on hemodialysis in Canada
Authors: Zhang Joyce C. , Al‐Jaishi Ahmed A. , Na Yingbo , de Sa Eric , Moist Louise M.
Published: March 2014

Optimal vascular access in elderly patients requires consideration of the benefits and risks in a population with increased comorbidity and mortality. Our objective was to examine the association between vascular access type and patient mortality by age category among incident adult hemodialysis patients registered in the Canadian Organ Replacement Register between 2001 and 2010. We also describe the secular trend in incident and prevalent vascular access use. We used a Cox proportional hazards model to evaluate the overall mortality in patients aged less than 65, 65–74, 75–85, and greater than 85 years who initiated hemodialysis using a central venous catheter (catheter) or arteriovenous (AV)‐access (fistula or graft) using an intention‐to‐treat approach. The cohort of 39,721 patients consisted of 42%, 27%, 26%, and 5% of patients aged <65, 65–74, 75–85, and >85, respectively. Patients who initiated hemodialysis using an AV‐access constituted 21%, 22%, 20%, and 15% of each age category. AV access use was associated with lower adjusted mortality compared with catheter use in each age category (Hazard Ratios [HR], 0.67; 95% Confidence Interval [0.62–0.72]; HR, 0.76 [0.63–0.91]; HR, 0.77 [0.64–0.93], HR, 0.73 [0.56–0.96], respectively). In Canada, use of an AV‐access is associated with lower mortality across all age categories, even in the very elderly. Further studies are required to understand the patient preference, complications, and resource use when selecting access type in the elderly.
Chat-based telepharmacy in Denmark: design and early results
Authors: Ho Inger , Nielsen Line , Jacobsgaard Helle , Salmasi Hassan , Pottegård Anton
Published: March 2014

Objectives

Following the introduction of a nationwide online telepharmacy chat-service in Denmark in the spring of 2012, offering free counselling to all Danish citizens, we aimed to investigate the types of enquiries that are made to the telepharmacy.

Methods

We extracted 500 consecutive chat transcripts and categorised them in four categories: drug-related, symptom, technical and other. These categories were further divided into 28 prespecified subcategories. After the categorisation of the 500 transcripts, 7 new subcategories were added and the material was reanalysed. For drug-related enquiries, the drug in question was registered according to the anatomical-therapeutic-chemical system developed by World Health Organization. Veterinary and empty (nonresponding) enquiries were excluded.

Key findings

Four hundred seventy-six eligible enquiries were identified and categorised. The enquiries were found to be diverse: 170 enquiries (35.7%) were drug-related, 124 (26.1%) were technical in nature, 91 (19.1%) were related to symptoms and 91 (19.1%) of the enquiries were categorised as other. The most common drug class was ‘drugs related to the genitourinary system and sex hormones’. Only 50 (10.5%) of the enquiries happened in connection with an actual purchase at the online pharmacy. Of all enquiries, 28.6% led to a referral to a medical doctor. Of the customers, 89.2% were satisfied with the online counselling.

Conclusion

The diverse enquiries require professional chat operators with broad experience. Some subjects are overrepresented when compared with regular pharmacy counselling and should receive special attention. Continued monitoring is considered essential.
When Should Physical Rehabilitation Commence after Stroke: A Systematic Review
Authors: Lynch Elizabeth , Hillier Susan , Cadilhac Dominique
Published: March 2014

Background

Knowing when to commence physical rehabilitation after stroke is important to ensure optimal benefit for stroke survivors and efficient health care. The aims of this review were to: determine the effects on mortality, function and complications when physical rehabilitation commences ‘early’ (within seven days of stroke); and describe the effects of early transfer to rehabilitation wards/hospitals when sustained rehabilitation is unavailable in acute stroke units.

Review summary

From 3751 potential articles we included 5 randomized controlled trials and 38 cohort studies. Meta-analysis was performed with 3 randomized controlled trials involving 159 people to investigate the effects of commencing physical rehabilitation within 24 h of stroke compared to 48 h. Commencing physical rehabilitation within 24 h trended towards greater mortality (Mantel-Haenszel odds ratio 2·58; 95% confidence interval 0·98 to 6·79, P = 0·06), with no differences in complications or health outcomes. The cohort studies provided evidence of benefits when physical rehabilitation was commenced on the day of admission ( n = 1), within 3 days of stroke ( n = 3), or ‘sooner rather than later’ (3 of 4 studies). The effect of earlier transfer to rehabilitation was reported in 32 cohort studies. In 23/26 (88%) cohort studies that accounted for age and stroke severity, results favored earlier transfer for improving post-stroke function, with no consensus on timeframes.

Conclusion

In summary, the benefits of commencing physical rehabilitation within 24 h of stroke remain unclear from the current literature. Commencing physical rehabilitation or transferring to rehabilitation services ‘early’ may provide better functional outcomes.
Differences in Ischemic and Hemorrhagic Recurrence Rates among Race-Ethnic Groups in the PRoFESS Secondary Stroke Prevention Trial
Authors: Estol Conrado J. , Bath Philip M. W. , Gorelick Philip B. , Cotton Daniel , Martin Renee Hebert ,   PRoFESS Publications Committee and PRoFESS Investigators
Published: March 2014

Background and Aims

Epidemiological studies show that vascular risk factors are the same across the world but their effect vary between different race-ethnic groups. However, few studies have evaluated differences in recurrent stroke rates in various race-ethnicities. In >20 000 patients spanning 35 countries encompassing most race-ethnicities, we evaluated the incidence of ischemic and hemorrhagic strokes and myocardial infarction in patients within the context of the largest secondary stroke prevention trial (Prevention Regimen for Effectively Avoiding Secondary Strokes) to identify any significant differences.

Methods

There were 20 332 patients with a recent ischemic stroke randomized in a factorial design to receive the antiplatelet agent clopidogrel vs. aspirin plus extended-release dipyridamole, and 80 mg of the anthypertensive telmisartan vs. placebo. The primary outcome for the trial was the time to any recurrent stroke. Statistical analysis was used to detect race-ethnic differences in recurrent vascular events.

Results

Mean patient age was 66 (±8·6) years and 36% were women. The study included 58% European/Caucasian, 33% Asians, 5% Latin/Hispanic, and 4% Black African. There were 74% of patients that were hypertensive, and average systolic and diastolic blood pressure was 144·1/83·8 mmHg. There was at least one significant difference in the overall test of all race-ethnic groups in myocardial infarction and symptomatic intracerebral hemorrhage occurrence. In the Kaplan–Meier hemorrhage and stroke-free survival curves, Asians showed a significantly higher recurrence of ischemic stroke risk in the 135–150 mmHg and greater than 150 mm Hg blood pressure groups, and a greater risk of hemorrhage recurrence in the greater than 150 mmHg blood pressure group.

Conclusions

We found a significant difference in myocardial infarction and symptomatic intracerebral hemorrhage recurrence among different race-ethnic groups. The risk of recurrent ischemic and hemorrhagic stroke was greater in Asians with high blood pressure.
Current approaches to fine mapping of antigen–antibody interactions
Authors: Abbott W. Mark , Damschroder Melissa M. , Lowe David C.
Published: March 2014

A number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X‐ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA‐based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity.
IMF Conditionality and the Intertemporal Allocation of Resources
Authors: Naqvi Hassan
Published: March 2014

This article analyzes the impact of IMF (International Monetary Fund) conditionality on the intertemporal allocation of resources in an emerging market economy. The study identifies a principal‐agent problem between the government of the emerging market and its citizens and shows that conditionality has the potential to mitigate the resulting misallocation of resources. Nevertheless, the analysis indicates that if IMF lending were influenced by geopolitical motives then the suboptimal allocation of resources would remain notwithstanding IMF conditionality.
Extending social security coverage to the rural sector in China
Authors: Chen Tianhong , Turner John A.
Published: March 2014

In late 2009 China launched an innovative, voluntary programme that by 2011 had extended pension coverage to 326.4 million people in the rural sector, including contributors and beneficiaries. It requires one contribution per year and provides a flat‐rate benefit and a contributions‐related benefit through a contributory individual account, with a government guarantee that the benefit will continue for life. The programme encourages participation of persons who do not pay income taxes, and thus have no tax incentive to participate, by providing substantial government subsidies. As a further incentive, old‐age benefits are provided to older parents when all their adult children participate in the contributory programme.
The Significance of Erythrocyte Sedimentation Rate as a Prognostic Factor for Patients with Prostate Cancer: Gunma Urological Oncology Study Group Investigation
Authors: Imai Kyoichi , Suzuki Takanori , Kobayashi Mikio , Yamanaka Hidetoshi , Tomaru Yukio , Sato Jin
Published: March 2014

The Gunma Urological Oncology Study Group has performed a multivariate statistical analysis of prognostic factors based on 353 patients with prostate cancer diagnosed between 1974 and 1984. This paper discusses the prognostic significance of erythrocyte sedimentation rate (ESR) in these patients with prostate cancer. Based on three ranges (<20, >20‐ <50, >50 mm/h) of ESR, a significant difference of survival rates among the patients was found by means of univariate analysis. ESR apparently includes components which represent anemia or infection. Hemoglobin, frequently used as a prognostic factor, was compared with ESR by means of multivariate analysis, and ESR was found to be a more useful prognostic factor than hemoglobin. Moreover ESR showed the highest partial coefficient value among the items studied (clinical stage, pathological differentiation, age, acid phosphatase, gait disturbance). It seems that ESR includes not only anemia and infection components but also provides a clue to the degree of bone metastasis or the degree of prostate cancer progression.
Effects of Interleukin‐6 and Granulocyte Colony‐stimulating Factor on the Proliferation of Leukemic Blast Progenitors from Acute Myeloblastic Leukemia Patients
Authors: Suzuki Toshiya , Morio Tomohiro , Tohda Shuji , Nagata Kaoru , Yamashita Yoko , Imai Yasufumi , Aoki Nobuo , Hirashima Kunitake , Nara Nobuo
Published: March 2014

The effects of recombinant human interleukin‐6 (rh IL‐6), which has homology with rh granulocyte colony‐stimulating factor (rh G‐CSF) at the amino acid sequence level, and rh G‐CSF on normal human bone marrow cells, fresh leukemic blast progenitors from 16 acute myeloblastic leukemia (AML) patients, and G‐CSF‐dependent human AML cell line (OCI/AML 1a) were investigated. rh G‐CSF stimulated the proliferation of leukemic blast progenitors from 13 out of 16 AML patients tested. rh IL‐6 stimulated the proliferation of blasts from eight AML patients and enhanced the G‐CSF‐dependent proliferation of the fresh AML blasts from two out of eight patients tested. On the other hand, rh IL‐6 suppressed the blast colony formation from two AML patients and OCI/AML 1a cells and also reduced the G‐CSF‐dependent proliferation of the blast progenitors from one of the two patients and the cell line. rh IL‐6 had no effect on the colony formation of normal granulocyte‐macrophage colony‐forming units (CFU‐GM) with or without rh G‐CSF. Differentiation‐induction by rh IL‐6 was not observed in the fresh AML blasts but was observed in OCI/AML 1a. The effect of IL‐6 on the blast colony formation and G‐CSF‐dependent blast cell growth was complicated and heterogenous among the AML cases; IL‐6 stimulated blast colony formation in some cases and suppressed it in others. The heterogeneity of the response was supposed to be derived from the heterogeneity of the characteristics of AML cells. Although G‐CSF simply stimulated the blast colony formation, IL‐6 had a bimodulatory effect on the proliferation of leukemic blast progenitors from AML patients. IL‐6 might be involved in the regulation of the proliferation of AML cells in vivo as well as in vitro.