bluuebunny/crossref_metadata_2025 huggingface dataset:
Solving the RNA polymerase I structural puzzle
Authors: Moreno-Morcillo María , Taylor Nicholas M. I. , Gruene Tim , Legrand Pierre , Rashid Umar J. , Ruiz Federico M. , Steuerwald Ulrich , Müller Christoph W. , Fernández-Tornero Carlos
Published: September 2014

Knowing the structure of multi-subunit complexes is critical to understand basic cellular functions. However, when crystals of these complexes can be obtained they rarely diffract beyond 3 Å resolution, which complicates X-ray structure determination and refinement. The crystal structure of RNA polymerase I, an essential cellular machine that synthesizes the precursor of ribosomal RNA in the nucleolus of eukaryotic cells, has recently been solved. Here, the crucial steps that were undertaken to build the atomic model of this multi-subunit enzyme are reported, emphasizing how simple crystallographic experiments can be used to extract relevant biological information. In particular, this report discusses the combination of poor molecular replacement and experimental phases, the application of multi-crystal averaging and the use of anomalous scatterers as sequence markers to guide tracing and to locate the active site. The methods outlined here will likely serve as a reference for future structural determination of large complexes at low resolution.
Structure of archaerhodopsin-2 at 1.8 Å resolution
Authors: Kouyama Tsutomu , Fujii Ryudo , Kanada Soun , Nakanishi Taichi , Chan Siu Kit , Murakami Midori
Published: September 2014

Archaerhodopsin-2 (aR2), the sole protein found in the claret membrane ofHalorubrumsp. Aus-2, functions as a light-driven proton pump. In this study, structural analysis of aR2 was performed using a novel three-dimensional crystal prepared by the successive fusion of claret membranes. The crystal is made up of stacked membranes, in each of which aR2 trimers are arranged on a hexagonal lattice. This lattice structure resembles that found in the purple membrane ofH. salinarum, except that lipid molecules trapped within the trimeric structure are not distributed with perfect threefold symmetry. Nonetheless, diffraction data at 1.8 Å resolution provide accurate structural information about functionally important residues. It is shown that two glutamates in the proton-release channel form a paired structure that is maintained by a low-barrier hydrogen bond. Although the structure of the proton-release pathway is highly conserved among proton-pumping archaeal rhodopsins, aR2 possesses the following peculiar structural features: (i) the motional freedom of the tryptophan residue that makes contact with the C13 methyl group of retinal is restricted, affecting the formation/decay kinetics of the L state, and (ii) the N-terminal polypeptide folds into an Ω-loop, which may play a role in organizing the higher-order structure.
Using textons to rank crystallization droplets by the likely presence of crystals
Authors: Ng Jia Tsing , Dekker Carien , Kroemer Markus , Osborne Michael , von Delft Frank
Published: September 2014

The visual inspection of crystallization experiments is an important yet time-consuming and subjective step in X-ray crystallography. Previously published studies have focused on automatically classifying crystallization droplets into distinct but ultimately arbitrary experiment outcomes; here, a method is described that instead ranks droplets by their likelihood of containing crystals or microcrystals, thereby prioritizing for visual inspection those images that are most likely to contain useful information. The use of textons is introduced to describe crystallization droplets objectively, allowing them to be scored with the posterior probability of a random forest classifier trained against droplets manually annotated for the presence or absence of crystals or microcrystals. Unlike multi-class classification, this two-class system lends itself naturally to unidirectional ranking, which is most useful for assisting sequential viewing because images can be arranged simply by using these scores: this places droplets with probable crystalline behaviour early in the viewing order. Using this approach, the top ten wells included at least one human-annotated crystal or microcrystal for 94% of the plates in a data set of 196 plates imaged with a Minstrel HT system. The algorithm is robustly transferable to at least one other imaging system: when the parameters trained from Minstrel HT images are applied to a data set imaged by the Rock Imager system, human-annotated crystals ranked in the top ten wells for 90% of the plates. Because rearranging images is fundamental to the approach, a custom viewer was written to seamlessly support such ranked viewing, along with another important output of the algorithm, namely the shape of the curve of scores, which is itself a useful overview of the behaviour of the plate; additional features with known usefulness were adopted from existing viewers. Evidence is presented that such ranked viewing of images allows faster but more accurate evaluation of drops, in particular for the identification of microcrystals.
Customer service in supply chain management: a case study
Authors: Naoui Fatiha
Published: September 2014

Purpose

– The purpose of this paper is to present a case study to assess the customer service within supply chain management (SCM). In particular, the paper emphasizes an interest in an integrated approach to considering customer service performance in an efficient way. Indeed, information systems as technical support play an essential role in the SCM of small- and medium-sized enterprises (SMEs). The reasons for pursuing such research can be explained by the fact that the customers are the first concern of any firm that seeks to be competitive. Indeed, the author seeks to answer the following question: Which are the main explaining factors of the customers’ service performance within Alpha SCM?

Design/methodology/approach

– A qualitative research methodology is used based on 11 semi-structured interviews with professionals and direct observation as part of a telecommunications network SME in France.

Findings

– This empirical case study is to delineate the concept dimensions. These dimensions allow the drawing up of a framework of actions to improve SME customer service performance evaluations in the SCM.

Research limitations/implications

– The paper is a single case study, not generalizable, but might be useful in general way. Another issue that the author can reflect on is the key performance indicators (KPIs). The KPIs selected are rather subjective and not generic relating to supply chain as “process”. The answers correspond to the managers’ perception and the international dimension is not taken into account in this work.

Practical implications

– The results contribute to the existing body of knowledge regarding services for improving the relationship with the customers; improve operational reporting; improve invoice control and indicator follow-ups with the project manager; and improve cost management.

Social implications

– The human factor is an important and current issue and is discussed in context of the case study.

Originality/value

– The paper adds to the understanding by showing that the human motivation and intellectual capital management are critical success factors in the Alpha SCM case study. It offers a new perspective that customers are among the major actors in the telecommunications market, along with the corporate customers and administration involved in implementation or service quality follow-up and telecommunications use. The group offers a wide range of skills to help the customers to make the most of technology.
An Observational Analysis of the Impact of Board Dynamics and Directors' Participation on Perceived Board Effectiveness
Authors: Pugliese Amedeo , Nicholson Gavin , Bezemer Pieter‐Jan
Published: September 2014

This study addresses calls for closer examination of board dynamics by offering an inside view of director interactions. Video observations of three board meetings at each of two Australian corporations matched with director interviews and secondary data reveal distinct patterns of director interactions, their sources of variation and their impact on perceived board effectiveness. The data reveal that director interactions are multidimensional and dynamic: while group interactions across agenda items are similar, with a few directors leading the discussion, the contributing directors change across items. Moreover, directors' inclusiveness and evenness of participation are associated with higher perceptions of board effectiveness. Lastly, the study found that director interactions change with the nature of the items, board climate and board meeting arrangements. The study contributes to the literature by moving beyond the individual‐level analysis of directors' skills or independence, and offering a detailed view of how the joint group and individual dimensions of board dynamics affect board functioning.
Negotiating Imagined Genetic Communities: Unity and Diversity in Brazilian Science and Society
Authors: Kent Michael , Santos Ricardo Ventura , Wade Peter
Published: September 2014

In this article, we explore the ways in which genetic research reconfigures historically rooted debates on race and national identity by analyzing the intense debates that have taken place in the past decade in Brazil around the genetic profile of the nation's population. Such debates have not only featured a significant variety of interpretations by different geneticists but also involved the media, policy makers, and social movements. Here we focus in particular on the ways in which genetic knowledge and the arguments it makes possible have reproduced, contested, or transformed pre existing narratives about race and national identity in Brazil. A central underlying tension in these debates is that between unity and diversity—between views that consider the Brazilian population as a single unit that cannot be differentiated except at the individual level and alternative interpretations that emphasize the multiplicity of its populations in terms of race, region, and genetic ancestry. [genetics, imagined communities, Brazil, identity politics]
British and Pakistani children's understanding of death: Cultural and developmental influences
Authors: Panagiotaki Georgia , Nobes Gavin , Ashraf Aisha , Aubby Herjit
Published: September 2014

This study explored British and Pakistani 4‐ to 7‐year‐olds’ (N = 188) understanding of death. The aim was to examine possible influences on the acquisition of the subcomponents of the death concept by investigating how they are understood by children of different ages and cultural and religious backgrounds. Three groups of children were compared: White British and British Muslim living in London, and Pakistani Muslim living in rural Pakistan. In line with previous research (Slaughter, 2005, Aust. Psychol., 40(3), 179), irreversibility of death was one of the first subcomponents to be acquired, while causality was the last. The two groups of British children shared many similarities in their understanding of inevitability, applicability, irreversibility, and cessation. Pakistani Muslim children understood irreversibility earlier than did children in both British groups. In all three cultural groups, children's responses demonstrated very limited understanding of causality. Our findings support the view that aspects of a mature understanding of death develop between the ages of 4 and 7 years and that the process of understanding death as a biological event is, to a great extent, universal. They also suggest that aspects of children's reasoning are influenced by culturally specific experiences, particularly those arising from living in rural versus urban settings.
Targeting the cis‐dimerization of LINGO‐1 with low MW compounds affects its downstream signalling
Authors: Cobret L , De Tauzia M L , Ferent J , Traiffort E , Hénaoui I , Godin F , Kellenberger E , Rognan D , Pantel J , Bénédetti H , Morisset‐Lopez S
Published: September 2014

Background and Purpose

The transmembrane protein LINGO‐1 is a negative regulator in the nervous system mainly affecting axonal regeneration, neuronal survival, oligodendrocyte differentiation and myelination. However, the molecular mechanisms regulating its functions are poorly understood. In the present study, we investigated the formation and the role of LINGO‐1 cis‐dimers in the regulation of its biological activity.

Experimental Approach

LINGO‐1 homodimers were identified in both HEK293 and SH‐SY5Y cells using co‐immunoprecipitation experiments and BRET saturation analysis. We performed a hypothesis‐driven screen for identification of small‐molecule protein–protein interaction modulators of LINGO‐1 using a BRET‐based assay, adapted for screening. The compound identified was further assessed for effects on LINGO‐1 downstream signalling pathways using Western blotting analysis and AlphaScreen technology.

Key Results

LINGO‐1 was present as homodimers in primary neuronal cultures. LINGO‐1 interacted homotypically in cis‐orientation and LINGO‐1 cis‐dimers were formed early during LINGO‐1 biosynthesis. A BRET‐based assay allowed us to identify phenoxybenzamine as the first conformational modulator of LINGO‐1 dimers. In HEK‐293 cells, phenoxybenzamine was a positive modulator of LINGO‐1 function, increasing the LINGO‐1‐mediated inhibition of EGF receptor signalling and Erk phosphorylation.

Conclusions and Implications

Our data suggest that LINGO‐1 forms constitutive cis‐dimers at the plasma membrane and that low MW compounds affecting the conformational state of these dimers can regulate LINGO‐1 downstream signalling pathways. We propose that targeting the LINGO‐1 dimerization interface opens a new pharmacological approach to the modulation of its function and provides a new strategy for drug discovery.
Inhibition of monoacylglycerol lipase reduces nicotine withdrawal
Authors: Muldoon P P , Chen J , Harenza J L , Abdullah R A , Sim‐Selley L J , Cravatt B F , Miles M F , Chen X , Lichtman A H , Damaj M I
Published: September 2014

Background and Purpose

Abrupt discontinuation of nicotine, the main psychoactive component in tobacco, induces a withdrawal syndrome in nicotine‐dependent animals, consisting of somatic and affective signs, avoidance of which contributes to drug maintenance. While blockade of fatty acid amide hydrolase, the primary catabolic enzyme of the endocannabinoid arachidonoylethanolamine (anandamide), exacerbates withdrawal responses in nicotine‐dependent mice, the role of monoacylglycerol lipase (MAGL), the main hydrolytic enzyme of a second endocannabinoid 2‐arachidonylglycerol (2‐AG), in nicotine withdrawal remains unexplored.

Experimental Approach

To evaluate the role of MAGL enzyme inhibition in nicotine withdrawal, we initially performed a genetic correlation approach using the BXD recombinant inbred mouse panel. We then assessed nicotine withdrawal intensity in the mouse after treatment with the selective MAGL inhibitor, JZL184, and after genetic deletion of the enzyme. Lastly, we assessed the association between genotypes and smoking withdrawal phenotypes in two human data sets.

Key Results

BXD mice displayed significant positive correlations between basal MAGL mRNA expression and nicotine withdrawal responses, consistent with the idea that increased 2‐AG brain levels may attenuate withdrawal responses. Strikingly, the MAGL inhibitor, JZL184, dose‐dependently reduced somatic and aversive withdrawal signs, which was blocked by rimonabant, indicating a CB1 receptor‐dependent mechanism. MAGL‐knockout mice also showed attenuated nicotine withdrawal. Lastly, genetic analyses in humans revealed associations of the MAGL gene with smoking withdrawal in humans.

Conclusions and Implications

Overall, our findings suggest that MAGL inhibition maybe a promising target for treatment of nicotine dependence.
Activation of PPARδ: from computer modelling to biological effects
Authors: Kahremany Shirin , Livne Ariela , Gruzman Arie , Senderowitz Hanoch , Sasson Shlomo
Published: September 2014

PPARδ is a ligand‐activated receptor that dimerizes with another nuclear receptor of the retinoic acid receptor family. The dimers interact with other co‐activator proteins and form active complexes that bind to PPAR response elements and promote transcription of genes involved in lipid metabolism. It appears that various natural fatty acids and their metabolites serve as endogenous activators of PPARδ; however, there is no consensus in the literature on the nature of the prime activators of the receptor. In vitro and cell‐based assays of PPARδ activation by fatty acids and their derivatives often produce conflicting results. The search for synthetic and selective PPARδ agonists, which may be pharmacologically useful, is intense. Current rational modelling used to obtain such compounds relies mostly on crystal structures of synthetic PPARδ ligands with the recombinant ligand binding domain (LBD) of the receptor. Here, we introduce an original computational prediction model for ligand binding to PPARδ LBD. The model was built based on EC50 data of 16 ligands with available crystal structures and validated by calculating binding probabilities of 82 different natural and synthetic compounds from the literature. These compounds were independently tested in cell‐free and cell‐based assays for their capacity to bind or activate PPARδ, leading to prediction accuracy of between 70% and 93% (depending on ligand type). This new computational tool could therefore be used in the search for natural and synthetic agonists of the receptor.
The RBMX gene as a candidate for the Shashi X‐linked intellectual disability syndrome
Authors: Shashi V. , Xie P. , Schoch K. , Goldstein D.B. , Howard T.D. , Berry M.N. , Schwartz C.E. , Cronin K. , Sliwa S. , Allen A. , Need A.C.
Published: September 2014

A novel X‐linked intellectual disability (XLID) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26‐q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X‐linked (RBMX) gene at Xq26 in the affected males (n = 7), one carrier female, absent in unaffected males (n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non‐coding regions of RBMX; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.
Flow‐mediated dilation in the inactive limb following acute hypoxic exercise
Authors: Katayama Keisho , Yamashita Shin , Iwamoto Erika , Ishida Koji
Published: September 2014

The purpose of this study was to elucidate the effect of acute aerobic exercise performed under hypoxic conditions on flow‐mediated dilation (FMD) in the inactive limb. Seven males participated in the study. The subjects performed two submaximal leg cycling on a semirecumbent ergometer at the same relative intensity (60% peak oxygen uptake) in normoxia [inspired oxygen fraction (FIO2) = 0·21] and hypoxia (FIO2 = 0·12–0·13) for 30 min. The brachial artery diameter and blood velocity during exercise were measured via ultrasound, and the antegrade and retrograde shear rates were calculated. Before and 5, 30 and 60 min after exercise, brachial artery FMD was measured in normoxia. FMD was estimated as the percentage increase in peak diameter from the baseline diameter at prior occlusion (%FMD) and as the controlling changes in baseline diameter (the corrected‐%FMD). No difference in antegrade shear rate during exercise was detected between the normoxic and hypoxic conditions, whereas the retrograde shear rate was larger during hypoxic exercise. The %FMD decreased significantly at 5 min after exercise in both normoxia and hypoxia, and it returned to pre‐exercise levels within 60 min of recovery. Significant decreases in FMD at 5 min after exercise had disappeared when the baseline diameter was controlled using an analysis of covariance (the corrected‐%FMD). No significant differences were observed between the normoxic and hypoxic trials in the %FMD and corrected‐%FMD following exercise. These results suggest that hypoxia has no impact on endothelial function in the inactive limb following acute aerobic exercise.
Detection of mitotic figures and G2+ tumor nuclei with histone markers correlates with worse overall survival in patients with Merkel cell carcinoma
Authors: Henderson Samuel A. , Tetzlaff Michael T. , Pattanaprichakul Penvadee , Fox Patricia , Torres‐Cabala Carlos A. , Bassett Roland L. , Prieto Victor G. , Richards Hunter W. , Curry Jonathan L.
Published: September 2014

Background

High mitotic figure count (MFC) correlates with low survival rate in Merkel cell carcinoma (MCC). However, the prognostic impact of histone biomarkers as surrogates of MFC in MCC is unknown. We evaluated the prognostic significance of the immunodetection of mitotic figures and of G2+ tumor nuclei with histone‐associated mitotic markers H3K79me3T80ph (H3KT) and phosphohistone H3 (PHH3) in MCC.

Methods

Immunohistochemical analyses of H3KT and PHH3 and proliferative marker Ki‐67 were performed in a series of 21 cases of MCC. The significance of the pathologic data and immunoreactivity with these markers was evaluated with Pearson correlation and paired Student t‐test. Univariate Cox proportional hazards regression models were performed to assess the relationships between these markers and survival.

Results

H3KT detected a higher number of mitotic figure (p<0.0001) and G2+ tumor nuclei (p<0.0052) than did PHH3. Furthermore, the MFC combined with G2+ tumor nuclei detected with H3KT compared to PHH3 and manual MFC was a significant predictor of impaired survival in patients with MCC (p=0.035;HR=1.0172), corresponding to a 1.72% increased risk of death for each unit increase in H3KT.

Conclusions

Biomarker analysis of proliferative rates with histone markers may have relevance in stratifying risk in patients with MCC.
Morphology and ultrastructure of the alimentary canal of the cicada Platypleura kaempferi (Hemiptera: Cicadidae)
Authors: Zhong Haiying , Zhang Yalin , Wei Cong
Published: September 2014

The alimentary canal of cicada Platypleura kaempferi is described. It comprises the oesophagus, filter chamber, external midgut section and hindgut. The elongate oesophagus expands posteriorly, with its posterior end constricting to become a bulb. The filter chamber consists of two parts: a very thin sheath and a filter organ. The filter organ is composed of the anterior and posterior ends of the midgut (internal midgut section), and the internal proximal ends of the Malpighian tubules. The external midgut section differentiates into a collapsed sac and a midgut loop. The latter is divided into three distinct segments. The hindgut contains a dilated rectum and a long narrow ileum. The distal portions of the four Malpighian tubules are enclosed in a peritoneal sheath together with the distal ileum before reaching to the rectum. Ultrastructurally, the oesophagus and the hindgut are lined with a cuticle. The filter chamber sheath consists of cells with large irregular nuclei. Filamentous substances coat the microvilli of the cells of the internal midgut section. The posterior end of the midgut comprises two types of cells, with the first type of cells containing many vesicles and scattered elements of rough endoplasmic reticulum. The anterior and posterior segments of the midgut loop cells have ferritin‐like granules. The ileum cells have well‐developed apical leaflets associated with mitochondria. Accumulations of virus‐like particles enclosed in the membrane are observed in the esophagus, conical segment, mid‐ and posterior segments of the midgut loop.
Complex Relationships amongst Parasite Load and Escape Behaviour in an Insular Lizard
Authors: Garrido Mario , Pérez‐Mellado Valentín , Cooper William E.
Published: September 2014

Economic escape models predict escape decisions of prey which are approached by predators. Flight initiation distance (FID, predator–prey distance when prey begins to flee) and distance fled (DF) are major variables used to characterize escape responses. In optimal escape theory, FID increases as cost of not fleeing also increases. Moreover, FID decreases as cost of fleeing increases, due to lost opportunities to perform activities that may increase fitness. Finally, FID further increases as the prey's fitness increases. Some factors, including parasitism, may affect more than one of these predictors of FID. Initially, parasitized prey may have lower fitness as well as impaired locomotor ability, which would avoid predation and/or reduce their foraging ability, further decreasing the opportunity of fleeing. For example, if parasites decrease body condition, prey fitness is reduced and escape ability may be impaired. Hence, the overall influence of parasitism on FID is difficult to predict. We examined relationships between escape decisions and different traits: parasite load, body size and body condition in the Balearic lizard,Podarcis lilfordi. Lizards that showed higher haemogregarines load had longer FID and shorter DF. Although results did not confirm our initial predictions made on the basis of optimal escape theory, our findings suggest that parasites can alter several aspects of escape behaviour in a complex way.
Neck manipulation, stroke and the precautionary principle
Authors: Homola Samuel
Published: September 2014

In view of the increasing number of case reports associating stroke with neck manipulation, it is essential that patients and providers alike be made aware of the risk involved when undergoing or providing such treatment. A plausible explanation of how upper neck manipulation can cause stroke by damaging vertebral or internal carotid arteries begs for use of the precautionary principle when considering use of neck manipulation for any reason.
Screening of biomass production of cultivated forage grasses in response to mycorrhizal symbiosis under nutritional deficit conditions
Authors: Cavagnaro Romina A. , Oyarzabal Mariano , Oesterheld Martín , Grimoldi Agustín A.
Published: September 2014

Arbuscular mycorrhizal fungi (AMF) colonize the root systems of most natural grassland species and usually increase plant growth by enhancing nutrients provision. This effect on growth responses of cultivated forage grasses is scarcely known, particularly under nutritional deficit conditions. We examined total biomass production, aboveground and belowground biomass and tillering of three temperate and three tropical cultivated forage grasses. Seedlings of each species were inoculated with a mixture of mycorrhizal fungi and later grown for 5 months under nutritional deficit conditions. The mycorrhizal symbiosis promoted aboveground and belowground biomass production in five out of six grass species. Grass species differed in their mycorrhizal responsiveness: tropical grasses (Panicum coloratum cv. Klein = Brachiaria brizantha cv. Marandú > Paspalum dilatatum cv. Primo) responded better than temperate (Festuca arundinacea cv. Royal > Agropyron elongatum cv. Hulk), while the temperate Dactylis glomerata cv. Porto did not respond to AMF inoculation. In four of the species, the changes observed in aboveground biomass were explained by the total number of tillers, while, in P. dilatatum, changes were accounted for by the individual weight of mature tillers. On the whole, the screening of cultivated forage grasses revealed that tropical grasses were highly responsive to mycorrhizae, in contrast to a lower effect on the growth of temperate grasses.
Initiation of antiretroviral therapy in HIV‐infected adults with skin complaints in northern Tanzania
Authors: Mavura Daudi R. , Masenga E. John , Minja Eli , Grossmann Henning , Crump John A. , Bartlett John A.
Published: September 2014

Abnormal skin findings are identified in over 90% of human immunodeficiency virus (HIV)‐infected persons globally. A prospective cohort study of HIV‐infected patients with skin complaints commencing antiretroviral therapy (ART) in northern Tanzania was undertaken. Consecutive HIV‐infected subjects presenting with skin complaints, who met criteria for ART initiation, were recruited at a Tanzanian Regional Dermatology Training Center. A single dermatologist evaluated all subjects; baseline skin biopsies were performed, and CD4+ cell counts and plasma HIV RNA levels were measured. All subjects received a fixed‐dose combination of stavudine, lamivudine, and nevirapine. A total of 100 subjects were enrolled; 86 subjects completed six months of follow‐up. Median baseline CD4+ cell counts and plasma HIV RNA levels were 120 cells/μl and 5.2 log10 copies/ml. The most common dermatologic condition was papular pruritic eruption (47%). The median baseline score on the Burn Scale was 38%. After six months, 10 subjects had achieved the complete resolution of skin abnormalities. In those without complete resolution, the median Burn Scale score improved to 7%. Five patients developed new eruptions by month 3, which in two cases were attributed to drug reactions. In the 86 subjects remaining on ART after six months, the median CD4+ cell count had increased to 474 cells/μl, and plasma HIV RNA levels were <400 copies/ml in 85 (99%) subjects. Patients with HIV infection with skin complaints experienced marked clinical improvements following ART initiation.
The spectrum of genodermatoses and congenital cutaneous conditions in northern Ethiopia
Authors: Dassoni Federica , Morrone Aldo , Padovese Valeska
Published: September 2014

Reports of congenital diseases in Africa are scanty, probably because of their rarity, the lack of knowledge among health workers, and the difficult political and social situation in different African countries. We describe here the spectrum of genetic and rare congenital cutaneous conditions encountered at the Italian Dermatological Center of Ayder referral hospital of Mekele, Ethiopia, over a 3‐year period. All patients attending the Italian Dermatological Center were registered in a database, and medical records of genetic and congenital disorders diagnosed from January 2008 to December 2010 were retrospectively analyzed. Over the total, 24 different genetic and congenital disorders affecting 122 individuals (0.4% of the total case load) were observed. In our case series, we did not report any patient affected by albinism, in contrast with literature from other African countries. To our knowledge, this is the first report from northern Ethiopia. A brief update on the commonest disorders is included.
Refining of edible oils: a critical appraisal of current and potential technologies
Authors: Vaisali Chandrasekar , Charanyaa Sampath , Belur Prasanna D. , Regupathi I.
Published: September 2014

The major sources of dietary lipids are edible oils, which include both vegetable and fish oils. Crude oil extracted from vegetable and fish sources contain mono‐, di‐, triacylglycerols along with impurities, which necessitates refining. The main objective of refining is to remove the contaminants that adversely affect the quality of oil, thereby reducing the shelf life and consumer acceptance. However, this refining process needs to be tailored as the composition of crude oil is highly variable, depending upon the plant/fish species, geographical location of the source and method of oil extraction. Recently, extensive efforts have been made to develop refining technology, using either conventional physical/chemical processes or several unconventional processes including biological and membrane processes. The first section of this review gives a brief description of general composition of some commonly used vegetable and fish oils, followed by the review of various refining methods and their effects on the oil constituents. Finally, an effort is made to understand the technological gaps in the existing methods and possible directions of research to overcome the said gaps.
Microwave Dielectric Properties of (Li0.5Ln0.5)MoO4 (Ln = Nd, Er, Gd, Y, Yb, Sm, and Ce) Ceramics
Authors: Pang Li‐Xia , Zhou Di , Guo Jing , Yue Zhen‐Xing , Yao Xi
Published: September 2014

In the present work, a series of scheelite‐related (Li0.5Ln0.5)MoO4 (Ln = Nd, Er, Gd, Y, Yb, Sm, and Ce) ceramics were prepared by using the solid‐state reaction method. Except for the (Li0.5Yb0.5)MoO4, the other compositions were found to have a scheelite structure. Among all the compositions, the (Li0.5Sm0.5)MoO4, (Li0.5Nd0.5)MoO4, and (Li0.5Ce0.5)MoO4 ceramics were found to possess low sintering temperatures below melting point of aluminum (660°C) and be chemically compatible with Al. The relation between microwave dielectric properties and structure was analyzed by using the Shannon additive rule and bond‐valence theory. This series of microwave dielectric ceramics might be candidate for low temperature co‐fired ceramics technology.
Photoperiod control of downstream movements of Atlantic salmon Salmo salar smolts
Authors: Zydlewski G. B. , Stich D. S. , McCormick S. D.
Published: September 2014

This study provides the first direct observations that photoperiod controls the initiation of downstream movement in Atlantic salmon Salmo salar smolts. Under simulated natural day length (LDN) conditions and seasonal increases in temperature, smolts increased their downstream movements five‐fold for a period of 1 month in late spring. Under the same conditions, parr did not show changes in downstream movement behaviour. When given a shortened day length (10L:14D) beginning in late winter, smolts did not increase the number of downstream movements. An early increase in day length (16L:8D) in late winter resulted in earlier initiation and termination of downstream movements compared to the LDN group. Physiological status and behaviour were related but not completely coincident: gill Na+/K+‐ATPase activity increased in all treatments and thyroid hormone was elevated prior to movement in 16L:8D treatment. The most parsimonious model describing downstream movement of smolts included synergistic effects of photoperiod treatment and temperature, indicating that peak movements occurred at colder temperatures in the 16L:8D treatment than in LDN, and temperature did not influence movement of smolts in the 10L:14D treatment. The complicated interactions of photoperiod and temperature are not surprising since many organisms have evolved to rely on correlations among environmental cues and windows of opportunity to time behaviours associated with life‐history transitions. These complicated interactions, however, have serious implications for phenological adjustments and persistence of S. salar populations in response to climate change.
Effects of feeding regimes and early maturation on migratory behaviour of landlocked hatchery‐reared Atlantic salmon Salmo salar smolts
Authors: Norrgård J. R. , Bergman E. , Schmitz M. , Greenberg L. A.
Published: September 2014

The migratory behaviour of hatchery‐reared landlocked Atlantic salmon Salmo salar raised under three different feeding regimes was monitored through the lower part of the River Klarälven, Sweden. The smolts were implanted with acoustic transmitters and released into the River Klarälven, 25 km upstream of the outlet in Lake Vänern. Early mature males, which had matured the previous autumn, were also tagged and released. To monitor migration of the fish, acoustic receivers were deployed along the migratory route. The proportion of S. salar that reached Lake Vänern was significantly greater for fish fed fat‐reduced feed than for fish given rations with higher fat content, regardless of ration size. Fish from the early mature male group remained in the river to a greater extent than fish from the three feeding regimes. Smolt status (degree of silvering), as visually assessed, did not differ among the feeding regime groups, and moreover, fully‐silvered fish, regardless of feeding regime, migrated faster and had a greater migration success than fish with less developed smolt characteristics. Also, successful migrants had a lower condition factor than unsuccessful ones. These results indicate that the migration success of hatchery‐reared S. smolts released to the wild can be enhanced by relatively simple changes in feeding regimes and by matching stocking time with smolt development.
Genetic differentiation among distinct karyomorphs of the wolf fish Hoplias malabaricus species complex (Characiformes, Erythrinidae) and report of unusual hybridization with natural triploidy
Authors: Utsunomia R. , Pansonato Alves J. C. , Paiva L. R. S. , Costa Silva G. J. , Oliveira C. , Bertollo L. A. C. , Foresti F.
Published: September 2014

In this study, genetic differentiation between karyomorphs A (2n = 42) and D (2n = 39/40) of the wolf fish Hoplias malabaricus, which is comprised of several cryptic species that present a wide variety of diploid chromosome numbers and sex chromosome systems, resulting in the identification of seven distinct karyomorphs (A–G), was investigated using a combination of molecular and cytogenetic tools. Deep sequence divergences for both karyomorphs were observed and indicate a long period of reproductive isolation between karyomorphs A and D. Additionally, one individual with 61 chromosomes was identified, which, as far as is known, is the first case of natural triploidy resulting from the hybridization between these highly differentiated karyomorphs of H. malabaricus. Molecular and cytogenetic analyses revealed that this allotriploid specimen carries two sets of maternal chromosomes from karyomorph D (2n = 40) and one set of chromosomes from karyomorph A (n = 21). Moreover, ribosomal sites and active nucleolus organizer regions from both parental contributors were found in the triploid hybrid. Considering the significant genetic distances between karyomorphs A and D, one of the primary reasons for the lack of recurrent reports of hybridization in the H. malabaricus species complex may be due to post‐zygotic barriers, such as hybrid sterility or unviability.
A SURVEY OF THE ECONOMICS OF FAIR TRADE
Authors: Dammert Ana C. , Mohan Sarah
Published: September 2014

Fair Trade has spread in developing countries as an initiative aimed at lifting poor smallholder farmers out of poverty by providing them with premium prices, availability of credit, and improved community development and social goods. Fair Trade is also viewed as a niche market for high value products in a context of globalization and trade liberalization policies that affect smallholder farmers in developing countries. This paper provides an overview of the potential effects of Fair Trade, both theoretical and empirical, on small‐scale producers in developing countries. Our review discusses the empirical evidence on prices and income, as well as the importance of limited market access and productivity. We discuss evidence on labor markets and human capital investments as well.
Vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and genistein‐induced changes in the vascular reactivity of rat's aorta
Authors: Fernandez Anne R. , Husain Ruby
Published: September 2014

Aim

During preeclampsia (PE), the excessive circulation of soluble fms‐like tyrosine kinase 1 (sFLT1) hinders the vasodilatory effect of vascular endothelial growth factor (VEGF). This effect has been proven in vitro in the renal artery of rats. The endothelium of the blood vessels is also said to be dysfunctional in PE. Genistein has shown the ability to antagonize the vascular contractions caused by a wide range of contractile agents. We conducted vascular reactivity studies to demonstrate the effect of: (i) sFLT1 on the vasodilatory effect of VEGF; and (ii) genistein on the vasodilatory effect of VEGF and its effects on denuded blood vessels (dysfunctional endothelium).

Material and Methods

Isolated aortas of male Sprague–Dawley rats were exposed to sFLT1 or genistein and then subjected to increasing doses of VEGF.

Results

The presence of sFLT1 inhibited the vasodilatory effect of VEGF in the rats' aortas. Genistein significantly potentiated the vasodilatory effect by the VEGF.

Conclusion

The results suggest that genistein may help overcome the vasospasm in PE. It may be a promising therapeutic approach to PE.
Maternal and neonatal outcomes in vacuum‐assisted delivery with the Kiwi OmniCup and Malmström metal cup
Authors: Turkmen Sahruh
Published: September 2014

Aim

To evaluate the effects of different types of vacuum cups on maternal and neonatal outcomes following assisted vaginal delivery.

Methods

A retrospective cohort study was undertaken of all vacuum‐assisted deliveries performed over a period of 2 years. Patients were divided into two groups according to whether a Kiwi OmniCup (n = 230) or Malmström metal cup (n = 98) was used. Maternal outcomes included maternal genital tract injury and total blood loss. Neonatal outcomes included Apgar score, umbilical cord blood gases, neonatal scalp injury and time spent in the neonatal unit.

Results

Maternal or neonatal outcomes and failure rates did not differ between the two groups, however, the duration of the procedure and the fundal pressure maneuver was more frequent in the Malmström group.

Conclusion

The results of this study suggest that the Kiwi OmniCup and Malmström metal cup vacuum extractors are safe and functionally effective for vacuum‐assisted delivery.
Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model
Authors: Rawas-Qalaji Mutasem , Rachid Ousama , Mendez Belacryst A , Losada Annette , Simons F Estelle R , Simons Keith J
Published: September 2014

Objectives

For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model.

Methods

The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively.

Key findings

Epimean(standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels).

Conclusion

Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings.
Identification of disulfide bond isomerase substrates reveals bacterial virulence factors
Authors: Ren Guoping , Champion Matthew M. , Huntley Jason F.
Published: September 2014

Bacterial pathogens are exposed to toxic molecules inside the host and require efficient systems to form and maintain correct disulfide bonds for protein stability and function. The intracellular pathogen Francisella tularensis encodes a disulfide bond formation protein ortholog, DsbA, which previously was reported to be required for infection of macrophages and mice. However, the molecular mechanisms by which F. tularensis DsbA contributes to virulence are unknown. Here, we demonstrate that F. tularensis DsbA is a bifunctional protein that oxidizes and, more importantly, isomerizes complex disulfide connectivity in substrates. A single amino acid in the conserved cis‐proline loop of the DsbA thioredoxin domain was shown to modulate both isomerase activity and F. tularensis virulence. Trapping experiments in F. tularensis identified over 50 F. tularensis DsbA substrates, including outer membrane proteins, virulence factors, and many hypothetical proteins. Six of these hypothetical proteins were randomly selected and deleted, revealing two novel proteins, FTL_1548 and FTL_1709, which are required for F. tularensis virulence. We propose that the extreme virulence of F. tularensis is partially due to the bifunctional nature of DsbA, that many of the newly identified substrates are required for virulence, and that the development of future DsbA inhibitors could have broad anti‐bacterial implications.
A CASE OF PARTIAL CONVERGENCE: THE EUROPEANIZATION OF CENTRAL GOVERNMENT IN CENTRAL AND EASTERN EUROPE
Authors: MEYER‐SAHLING JAN‐HINRIK , VAN STOLK CHRISTIAN
Published: September 2014

This article compares the Europeanization of central government in four Central and Eastern European countries (CEECs): Estonia, Latvia, Poland, and Slovakia. Using a large N survey of ministerial civil servants, it finds that the Europeanization of central government is characterized by partial convergence. The scope of Europeanization is large and similar among CEECs, reaching widely and deeply into government ministries. Moreover, patterns of Europeanization are similar among CEECs: the same ministries form the ‘inner core’ and ‘outer circle’ of Europeanized ministries; only a small proportion of civil servants work full‐time on EU issues and routinely engage in activities that ‘project’ national policies at EU level. Compared to old member states, patterns of Europeanization show signs of convergence, while the scope of Europeanization is larger in CEECs.
International survey of knowledge of food‐induced anaphylaxis
Authors: Wang Julie , Young Michael C. , Nowak‐Węgrzyn Anna
Published: September 2014

Background

Studies show that anaphylaxis is under‐recognized and epinephrine (adrenaline) is under‐used by medical personnel as well as patients and their families. This study assesses the knowledge of food‐induced anaphylaxis diagnosis and management across different populations of providers and caregivers and other interested respondents.

Methods

An online survey embedded in a case discussion of food‐induced anaphylaxis was distributed by Medscape to registered members.

Results

A total of 7822 responders who started the activity chose to answer at least some of the questions presented (response rate 39.5%). Over 80% of responders in all groups correctly identified the case of anaphylaxis with prominent skin and respiratory symptoms; however, only 55% correctly recognized the case without skin symptoms as anaphylaxis. Only 23% of responders correctly selected risk factors for anaphylaxis, with physicians significantly more likely to choose the correct answers as compared to allied health, other health professionals, and medical students (p < 0.001). Ninety‐five percent selected epinephrine (adrenaline) as the most appropriate treatment for anaphylaxis, and 81% correctly indicated that there are no absolute contraindications for epinephrine (adrenaline) in the setting of anaphylaxis. When presented a case of a child with no documented history of allergies who has symptoms of anaphylaxis, more physicians than any other group chose to administer stock epinephrine (adrenaline) (73% vs. 60%, p < 0.001).

Conclusion

Specific knowledge deficits for food‐induced anaphylaxis persist across all groups. Further educational efforts should be aimed not only at the medical community but also for the entire caregiver community and general public, to optimize care for food allergic individuals.