bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic landscapes reveal how human genetic diversity aligns with geography
Authors: Peter Benjamin Marco , Petkova Desislava , Novembre John
Published: December 2017

Geographic patterns in human genetic diversity carry footprints of population history1,2and provide insights for genetic medicine and its application across human populations3,4. Summarizing and visually representing these patterns of diversity has been a persistent goal for human geneticists5–10, and has revealed that genetic differentiation is frequently correlated with geographic distance. However, most analytical methods to represent population structure11–15do not incorporate geography directly, and it must be consideredpost hocalongside a visual summary. Here, we use a recently developed spatially explicit method to estimate “effective migration” surfaces to visualize how human genetic diversity is geographically structured (the EEMS method16). The resulting surfaces are “rugged”, which indicates the relationship between genetic and geographic distance is heterogenous and distorted as a rule. Most prominently, topographic and marine features regularly align with increased genetic differentiation (e.g. the Sahara desert, Mediterranean Sea or Himalaya at large scales; the Adriatic, interisland straits in near Oceania at smaller scales). In other cases, the locations of historical migrations and boundaries of language families align with migration features. These results provide visualizations of human genetic diversity that reveal local patterns of differentiation in detail and emphasize that while genetic similarity generally decays with geographic distance, there have regularly been factors that subtly distort the underlying relationship across space observed today. The fine-scale population structure depicted here is relevant to understanding complex processes of human population history and may provide insights for geographic patterning in rare variants and heritable disease risk.
Saturation mutagenesis reveals manifold determinants of exon definition
Authors: Ke Shengdong , Anquetil Vincent , Zamalloa Jorge Rojas , Maity Alisha , Yang Anthony , Arias Mauricio A. , Kalachikov Sergey , Russo James J. , Ju Jingyue , Chasin Lawrence A.
Published: December 2017

To illuminate the extent and roles of exonic sequences in the splicing of human RNA transcripts, we conducted saturation mutagenesis of a 51-nt internal exon in a three-exon minigene. All possible single and tandem dinucleotide substitutions were surveyed. Using high-throughput genetics, 5560 minigene molecules were assayed for splicing in human HEK293 cells. Up to 70% of mutations produced substantial (greater than twofold) phenotypes of either increased or decreased splicing. Of all predicted secondary structural elements, only a single 15-nt stem–loop showed a strong correlation with splicing, acting negatively. The in vitro formation of exon-protein complexes between the mutant molecules and proteins associated with spliceosome formation (U2AF35, U2AF65, U1A, and U1-70K) correlated with splicing efficiencies, suggesting exon definition as the step affected by most mutations. The measured relative binding affinities of dozens of human RNA binding protein domains as reported in the CISBP-RNA database were found to correlate either positively or negatively with splicing efficiency, more than could fit on the 51-nt test exon simultaneously. The large number of these functional protein binding correlations point to a dynamic and heterogeneous population of pre-mRNA molecules, each responding to a particular collection of binding proteins.
DiSCaMB: a software library for aspherical atom model X-ray scattering factor calculations with CPUs and GPUs
Authors: Chodkiewicz Michał L. , Migacz Szymon , Rudnicki Witold , Makal Anna , Kalinowski Jarosław A. , Moriarty Nigel W. , Grosse-Kunstleve Ralf W. , Afonine Pavel V. , Adams Paul D. , Dominiak Paulina Maria
Published: December 2017

It has been recently established that the accuracy of structural parameters from X-ray refinement of crystal structures can be improved by using a bank of aspherical pseudoatoms instead of the classical spherical model of atomic form factors. This comes, however, at the cost of increased complexity of the underlying calculations. In order to facilitate the adoption of this more advanced electron density model by the broader community of crystallographers, a new software implementation calledDiSCaMB, `densities in structural chemistry and molecular biology', has been developed. It addresses the challenge of providing for high performance on modern computing architectures. With parallelization options for both multi-core processors and graphics processing units (using CUDA), the library features calculation of X-ray scattering factors and their derivatives with respect to structural parameters, gives access to intermediate steps of the scattering factor calculations (thus allowing for experimentation with modifications of the underlying electron density model), and provides tools for basic structural crystallographic operations. Permissively (MIT) licensed,DiSCaMBis an open-source C++ library that can be embedded in both academic and commercial tools for X-ray structure refinement.
CAPOW: a standalone program for the calculation of optimal weighting parameters for least-squares crystallographic refinements
Authors: Johnson Natalie T. , Ott Holger , Probert Michael R.
Published: December 2017

The rigorous analysis of crystallographic models, refined through the use of least-squares minimization, is founded on the expectation that the data provided have a normal distribution of residuals. Processed single-crystal diffraction data rarely exhibit this feature without a weighting scheme being applied. These schemes are designed to reflect the precision and accuracy of the measurement of observed reflection intensities. While many programs have the ability to calculate optimal parameters for applied weighting schemes, there are still programs that do not contain this functionality, particularly when moving beyond the spherical atom model. For this purpose, CAPOW (calculation and plotting of optimal weights), a new program for the calculation of optimal weighting parameters for a SHELXL weighting scheme, is presented and an example of its application in a multipole refinement is given.
Organizing a crystallization laboratory
Authors: Gu Allen , Marshall Bevan , Rosa Nicholas , Ristic Marko , Newman Janet
Published: December 2017

Managing chemical stocks and samples in any laboratory is an arduous task; in a crystallization laboratory this is particularly burdensome, given the need for many stocks to facilitate optimization of crystal hits obtained from screening experiments. Although inventory management is widespread in retail and other arenas, most small academic laboratories do not adopt formal stock management systems. Without an overarching system for handling stocks and samples, problems such as stock duplication, inappropriate stock storage and insufficient labelling are rife. Two applications have been developed in the Collaborative Crystallization Centre, the first of which manages the hundreds of stocks used for crystallization, and a second which manages protein (and other) samples stored in the 193 K freezer. Both applications are built around a simple database, with a Python front end that allows samples or stocks to be scanned in or out. Information from a decade of crystallization stock usage allows a good estimation of what chemicals are used (and in what quantities) in a crystallization laboratory.
Double-grating monochromatic beamline with ultrafast response for FLASH2 at DESY
Authors: Poletto Luca , Frassetto Fabio , Brenner Günter , Kuhlmann Marion , Plönjes Elke
Published: December 2017

The preliminary design of a monochromatic beamline for FLASH2 at DESY is presented. The monochromator is tunable in the 50–1000 eV energy range with resolving power higher than 1000 and temporal response below 50 fs over the whole energy range. A time-delay-compensated configuration using the variable-line-spacing monochromator design with two gratings is adopted: the first grating disperses the radiation on its output plane, where the intermediate slit performs the spectral selection; the second grating compensates for the pulse-front tilt and for the spectral dispersion due to diffraction from the first grating.
Structure of aspartate β-semialdehyde dehydrogenase fromFrancisella tularensis
Authors: Mank N. J. , Pote S. , Majorek K.A. , Arnette A. K. , Klapper V. G. , Hurlburt B. K. , Chruszcz M.
Published: December 2017

Aspartate β-semialdehyde dehydrogenase (ASADH) is an enzyme involved in the diaminopimelate pathway of lysine biosynthesis. It is essential for the viability of many pathogenic bacteria and therefore has been the subject of considerable research for the generation of novel antibiotic compounds. This manuscript describes the first structure of ASADH fromFrancisella tularensis, the causative agent of tularemia and a potential bioterrorism agent. The structure was determined at 2.45 Å resolution and has a similar biological assembly to other bacterial homologs. ASADH is known to be dimeric in bacteria and have extensive interchain contacts, which are thought to create a half-sites reactivity enzyme. ASADH from higher organisms shows a tetrameric oligomerization, which also has implications for both reactivity and regulation. This work analyzes the apo form ofF. tularensisASADH, as well as the binding of the enzyme to its cofactor NADP+.
The impact of financial restatement on auditor changes: Iranian evidence
Authors: Eshagniya Azam , Salehi Mahdi
Published: December 2017

Purpose

This paper aims to examine the effect of financial restatement on changing the auditor in the following years.

Design/methodology/approach

The study uses data of 105 companies (735 company-years) listed on the Tehran Stock Exchange collected during the period 2008-2014. Logistic regression is used to test the hypotheses.

Findings

The results of hypotheses present that restatement does not cause auditor changes and that as the severity of a restatement increases, the auditor change in the following year of restatement also does not increase. Restating companies having strong governance do not go for auditor changes as compared with other companies. In addition, in companies that are restating, non-big auditor changes are not more likely than a big auditor. Also, in companies restating simultaneous with a CEO turnover, there is no possibility of auditor change. Furthermore, multinomial logistic regression showed that the adjustments resulting from the correction of errors and changes in procedures and the amount of adjustments do not cause auditor change in the following year. So, the results have shown that the restatement is not an important factor in changing auditor the next year.

Originality/value

The current study analyses the impact of financial restatement on auditor changes in a deep manner in a developing country like Iran.
Analysis of the impact of referral-based recruitment on job attitudes and turnover in temporary agency workers
Authors: González Luis , Rivarés Lorenzo
Published: December 2017

Purpose

The purpose of this paper is to analyse the referral-based recruitment process in temporary work agencies (TWA) and its influence on workers’ attitudes and turnover.

Design/methodology/approach

By means of a quasi-experimental design with equivalent groups and repeated measures, differences in attitudes -group commitment, task commitment, group satisfaction, general job satisfaction and job involvement- and turnover in a group of workers recruited by the TWA through the “bring a friend” procedure based on employee referrals and in another group comprising workers not recruited through employee referrals are studied.

Findings

The results obtained show that workers recruited through employee referrals by the TWA are characterized by having greater group commitment, task commitment, task satisfaction, general job satisfaction and turnover than employees not recruited through employee referrals. These differences are explained on the basis of expectations and the feeling of obligation generated in the recruitment process.

Research limitations/implications

The sample size is an element to take into account when valuing the obtained results. Moreover, the effects of the recruitment programs with employee referral on the TWA should be analyze on more qualified jobs. Furthermore, they should be also evaluated if the effects on the attitudes stay the same in longer periods.

Originality/value

This is the first paper to examine the impact of the employee-referral-based recruitment method known as “bring a friend” on attitudes – group commitment, task commitment, group satisfaction, general job satisfaction, and job involvement – and turnover of employees when used by TWA. Likewise, we want highlight the fact that this is a longitudinal research study.
Absorptive capacity, cluster linkages, and innovation
Authors: Chandrashekar Deepak , Mungila Hillemane Bala Subrahmanya
Published: December 2017

Purpose

The purpose of this paper is to outline the key determinants of innovation performance of a firm in a cluster. This paper probes the role of absorptive capacity in furthering the cluster linkages and thereby enhancing the innovation performance of a firm.

Design/methodology/approach

This study adopts stratified random sampling technique to choose sample firms from the identified population of firms in a cluster. Further, it employs primary data collection method to collect data from sample firms through a semi-structured questionnaire based in-depth interviews with the top level management of sample firms. It uses multiple linear regression (MLR) techniques to ascertain the influence of absorptive capacity on degree of cluster linkages (both intra-cluster and extra-cluster linkages), and degree of cluster linkages (both intra-cluster and extra-cluster linkages) on innovation performance of a firm.

Findings

On the one hand, internal factors of absorptive capacity of a firm have a significant positive influence on the degrees of both intra-cluster linkages and extra-cluster linkages. On the other hand, external factors of absorptive capacity of a firm significantly impact the degree of intra-cluster linkages (DICL). But, they have no significant influence on the degree of extra-cluster linkages (DECL). Further, both the DICL and the DECL drive innovation performance of a firm in a cluster. Notably, subsidiaries of externally based firms exhibit superior innovation performance compared to those firms based in a cluster.

Originality/value

This paper contributes to the extant literature in two ways. First, it empirically validates the effect of absorptive capacity of a firm on its degree of cluster linkages (both intra-cluster and extra-cluster linkages) taking into account both internal and external factors of absorptive capacity. Second, it ascertains the influence of degree of cluster linkages (both intra-cluster and extra-cluster linkages) on the innovation performance of a firm in a cluster.
Redefining Loyalty: Motivational Strategies and Employee Loyalty in an Era of Downsizing
Authors: Obilade Sandra
Published: December 2017

Retaining employee loyalty after restructuring is a problem for all types of businesses. The major issue concerns how management and employees can establish a new, mutually acceptable "psychological contract" which ensures employee loyalty but not lifelong employment. Eighteen small businesses in Fairfield County, Connecticut were surveyed to investigate loyalty and motivation after downsizing. A significant correlation was found between loyalty and motivation. Furthermore, several motivational techniques employed were inconsistent with employee needs. Suggestions are offered on how to retain employee loyalty.
Value Creation in New Firms: Evidence from the Biotechnology Industry
Authors: Coombs Joseph E. , Leeds David L.
Published: December 2017

The purpose of this study is to empirically examine those factors that enhance the value of newly public firms. The article presents a model for the market value of a newly public biotechnology firm. Explanatory variables include several intangible indicators of the scientific capabilities of the firm including firm citations, licenses, patents, products in the pipeline, and R&D intensity. Top management team variables are also examined. The results support the conclusion that scientific capabilities significantly impact the value of the firm as viewed by public equity markets.
Paint-Your-Own Pottery Case Study
Authors: Morin Lisa
Published: December 2017

There are currently more than seventy paint-your-own pottery shops in the United States. Although the concept of such studios is fairly new in New England, they have been in existence on the West Coast for years.
What happened to Çaction?
Authors: Letiche Hugo
Published: December 2017

Purpose

Although the epistemology of researcher reflexivity has been championed as crucial to research for some 30 years, it remains controversial and often ill-defined. In the 1980s, “reflexivity” was championed by the hermeneutically and epistemologically savvy to try and break the strangle hold of naïve positivism. Nowadays, reflexivity most often refers to the turn-to-affect and to the researcher’s ability and willingness to radically sensitivize “self” to others and circumstances. The purpose of this paper is to specify what non-representational research has brought to the reflexivity debate and then focus on Brosseau’s particular rendition of reflexivity, which is seen as far more demanding, problematic and valuable.

Design/methodology/approach

The approach followed in this paper is a hermeneutic reflection based on Thrift’s and Brosseau’s oeuvres. The perspective is historical, qua research methods’ take on reflexivity and qua Brosseau textual production.

Findings

Five differences between Thrift’s and Brosseau’s reflexivities are highlighted. Brosseau brings us much further in applying affective reflexivity to research writing than does Thrift.

Originality/value

A polemic calling for and warnings about the complexities of affective reflexivity, presented as demanding, dangerous and complex.
A Simple and Efficient Method of Extracting DNA from Aged Bones and Teeth
Authors: Liu Qiqi , Liu Liyan , Zhang Minli , Zhang Qingzhen , Wang Qiong , Ding Xiaoran , Shao Liting , Zhou Zhe , Wang Shengqi
Published: December 2017

DNA is often difficult to extract from old bones and teeth due to low levels of DNA and high levels of degradation. This study established a simple yet efficient method for extracting DNA from 20 aged bones and teeth (approximately 60 years old). Based on the concentration and STR typing results, the new method of DNA extraction (OM) developed in this study was compared with the PrepFiler™ BTA Forensic DNA Extraction Kit (BM). The total amount of DNA extracted using the OM method was not significantly different from that extracted using the commercial kit (p > 0.05). However, the number of STR loci detected was significantly higher in the samples processed using the OM method than using the BM method (p < 0.05). This study aimed to establish a DNA extraction method for aged bones and teeth to improve the detection rate of STR typing and reduce costs compared to the BM technique.
AudioMoth: Evaluation of a smart open acoustic device for monitoring biodiversity and the environment
Authors: Hill Andrew P. , Prince Peter , Piña Covarrubias Evelyn , Doncaster C. Patrick , Snaddon Jake L. , Rogers Alex
Published: December 2017

The cost, usability and power efficiency of available wildlife monitoring equipment currently inhibits full ground‐level coverage of many natural systems. Developments over the last decade in technology, open science, and the sharing economy promise to bring global access to more versatile and more affordable monitoring tools, to improve coverage for conservation researchers and managers.

Here we describe the development and proof‐of‐concept of a low‐cost, small‐sized and low‐energy acoustic detector: “AudioMoth.” The device is open‐source and programmable, with diverse applications for recording animal calls or human activity at sample rates of up to 384 kHz. We briefly outline two ongoing real‐world case studies of large‐scale, long‐term monitoring for biodiversity and exploitation of natural resources. These studies demonstrate the potential for AudioMoth to enable a substantial shift away from passive continuous recording by individual devices, towards smart detection by networks of devices flooding large and inaccessible ecosystems.

The case studies demonstrate one of the smart capabilities of AudioMoth, to trigger event logging on the basis of classification algorithms that identify specific acoustic events. An algorithm to trigger recordings of the New Forest cicada (Cicadetta montana) demonstrates the potential for AudioMoth to vastly improve the spatial and temporal coverage of surveys for the presence of cryptic animals. An algorithm for logging gunshot events has potential to identify a shotgun blast in tropical rainforest at distances of up to 500 m, extending to 1 km with continuous recording.

AudioMoth is more energy efficient than currently available passive acoustic monitoring devices, giving it considerably greater portability and longevity in the field with smaller batteries. At a build cost of ∼US$43 per unit, AudioMoth has potential for varied applications in large‐scale, long‐term acoustic surveys. With continuing developments in smart, energy‐efficient algorithms and diminishing component costs, we are approaching the milestone of local communities being able to afford to remotely monitor their own natural resources.
Insolvent trading and voluntary administration in Australia: economic winners and losers?
Authors: Brotchie James , Morrison David
Published: December 2017

Australian directors who incur debts while their companies are insolvent can be pursued by the corporate regulator for compensation when their companies fail. Under the Australian insolvent trading laws, directors no longer experience ‘true’ limited liability, and as expected, they adjust their behaviour as a result. Identifying director's rational behaviour in an insolvent trading world is difficult as there are no formal economic models of director decision‐making under Australian current corporate law. In this paper, we develop such a model primarily for private companies. We incorporate the threat of insolvent trading as well as director's tactical use of voluntary administration to avoid insolvent trading litigation. We show that neither a combination of insolvent trading or voluntary administration can simultaneously ensure creditors‐best outcomes, eliminate insolvent trading and reduce director underinvestment.
HUMAN RESOURCE MANAGEMENT PRACTICES AND EMPLOYEE JOB SATISFACTION IN NONPROFIT ORGANIZATIONS
Authors: BASTIDA Ramon , MARIMON Frederic , CARRERAS Lluís
Published: December 2017

The purpose of this study is to establish a measurement scale for human resource management (HRM) practices in nonprofit organizations and to analyze their impact on employee job satisfaction. An exploratory factor analysis (EFA) using a principal components was performed. The analyzed sample is composed of 62 organizations with 2,030 employees. The results demonstrate that 8 out of 20 analyzed variables determine the measurement scale of HRM practices in these organizations. These variables are related to psychological demands, active work and development possibilities, social relations and leadership, and the degree of coherence in the organization with its principles. According to the results, these practices have an impact on employee job satisfaction. We believe that these results are relevant due to the lack of similar studies and the relevance of nonprofit organizations as job creators in the European Union.
Okur‐Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion
Authors: Chiu A.T.G. , Pei S.L.C. , Mak C.C.Y. , Leung G.K.C. , Yu M.H.C. , Lee S.L. , Vreeburg M. , Pfundt R. , van der Burgt I. , Kleefstra T. , Frederic T.M.‐T. , Nambot S. , Faivre L. , Bruel A.‐L. , Rossi M. , Isidor B. , Küry S. , Cogne B. , Besnard T. , Willems M. , Reijnders M.R.F. , Chung B.H.Y.
Published: December 2017

Okur‐Chung syndrome is a neurodevelopmental condition attributed to germline CSNK2A1 pathogenic missense variants. We present 8 unreported subjects with the above syndrome, who have recognizable dysmorphism, varying degrees of developmental delay and multisystem involvement. Together with 6 previously reported cases, we present a case series of 7 female and 7 male subjects, highlighting the recognizable facial features of the syndrome (microcephaly, hypertelorism, epicanthic fold, ptosis, arched eyebrows, low set ears, ear fold abnormality, broad nasal bridge and round face) as well as frequently occurring clinical features including neurodevelopmental delay (93%), gastrointestinal (57%), musculoskeletal (57%) and immunological (43%) abnormalities. The variants reported in this study are evolutionary conserved and absent in the normal population. We observed that the CSNK2A1 gene is relatively intolerant to missense genetic changes, and most variants are within the protein kinase domain. All except 1 variant reported in this cohort are spatially located on the binding pocket of the holoenzyme. We further provide key recommendations on the management of Okur‐Chung syndrome. To conclude, this is the second case series on Okur‐Chung syndrome, and an in‐depth review of the phenotypic features and genomic findings of the condition with suggestions on clinical management.
An Implicit SPH Formulation for Incompressible Linearly Elastic Solids
Authors: Peer Andreas , Gissler Christoph , Band Stefan , Teschner Matthias
Published: December 2017

We propose a novel smoothed particle hydrodynamics (SPH) formulation for deformable solids. Key aspects of our method are implicit elastic forces and an adapted SPH formulation for the deformation gradient that—in contrast to previous work—allows a rotation extraction directly from the SPH deformation gradient. The proposed implicit concept is entirely based on linear formulations. As a linear strain tensor is used, a rotation‐aware computation of the deformation gradient is required. In contrast to existing work, the respective rotation estimation is entirely realized within the SPH concept using a novel formulation with incorporated kernel gradient correction for first‐order consistency. The proposed implicit formulation and the adapted rotation estimation allow for significantly larger time steps and higher stiffness compared to explicit forms. Performance gain factors of up to one hundred are presented. Incompressibility of deformable solids is accounted for with an ISPH pressure solver. This further allows for a pressure‐based boundary handling and a unified processing of deformables interacting with SPH fluids and rigids. Self‐collisions are implicitly handled by the pressure solver.
Diagnostic accuracy of high‐resolution T2‐weighted MRI vs contrast‐enhanced T1‐weighted MRI to screen for cerebellopontine angle lesions in symptomatic patients
Authors: Hentschel M.A. , Kunst H.P.M. , Rovers M.M. , Steens S.C.A.
Published: December 2017

Objective

To evaluate diagnostic accuracy of high‐resolution T2‐weighted MRI (T2w) for detecting cerebellopontine angle (CPA) lesions compared to a combined protocol including gadolinium enhanced T1‐weighted MRI (GdT1w).

Setting

Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.

Participants

A random sample of MRIs from 350 patients (700 CPAs) with asymmetrical audiovestibular complaints was used, acquired between 2013 and 2016.

Main outcome measures

Sensitivity, specificity, positive and negative predictive values of T2w results compared to GdT1w and, in patients with any suggestion of CPA pathology, to the complete examination (T1w, GdT1w and T2w). Inter‐rater agreement between an experienced neuroradiologist and a less experienced observer was calculated.

Results

Results of 678 CPAs in 340 patients were analysed. On T2w, the neuroradiologist identified all 27 lesions >2 mm in size out of a total of 30 CPA lesions (sensitivity: 90% [95% CI: 73.5%‐97.9%]). Negative predictive value reached 99.5% (95% CI: 98.7‐99.9). One missed lesion of 2 mm would have been detected in clinical practice, as this was one of 14 patients for which additional GdT1w would have been ordered based on T2w alone, increasing sensitivity to 93% (95% CI: 77.9%‐99.2%) and negative predictive value to 99.7% (95% CI: 98.9%‐100%). Inter‐rater agreement for T2w was 98% (95% CI: 96.4‐98.8).

Conclusion

T2w has a very high diagnostic accuracy for the presence of CPA lesions in patients with asymmetrical audiovestibular complaints. However, in a screening protocol with T2w only, smallest vestibular schwannomas as well as rare differential diagnoses that probably only would be detected on GdT1w may remain unnoticed.
Cytochemical flow analysis of intracellular G6PD and aggregate analysis of mosaic G6PD expression
Authors: Kalnoky Michael , Bancone Germana , Kahn Maria , Chu Cindy S. , Chowwiwat Nongnud , Wilaisrisak Pornpimon , Pal Sampa , LaRue Nicole , Leader Brandon , Nosten Francois , Domingo Gonzalo J.
Published: December 2017

Background

Medicines that exert oxidative pressure on red blood cells (RBC) can cause severe hemolysis in patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. Due to X‐chromosome inactivation, females heterozygous for G6PD with 1 allele encoding a G6PD‐deficient protein and the other a normal protein produce 2 RBC populations each expressing exclusively 1 allele. The G6PD mosaic is not captured with routine G6PD tests.

Methods

An open‐source software tool for G6PD cytofluorometric data interpretation is described. The tool interprets data in terms of % bright RBC, or cells with normal G6PD activity in specimens collected from 2 geographically and ethnically distinct populations, an African American cohort (USA) and a Karen and Burman ethnic cohort (Thailand) comprising 242 specimens including 89 heterozygous females.

Results

The tool allowed comparison of data across 2 laboratories and both populations. Hemizygous normal or deficient males and homozygous normal or deficient females cluster at narrow % bright cells with mean values of 96%, or 6% (males) and 97%, or 2% (females), respectively. Heterozygous females show a distribution of 10‐85% bright cells and a mean of 50%. The distributions are associated with the severity of the G6PD mutation.

Conclusions

Consistent cytofluorometric G6PD analysis facilitates interlaboratory comparison of cellular G6PD profiles and contributes to understanding primaquine‐associated hemolytic risk.
Posaconazole oral dose and plasma levels in pediatric hematology‐oncology patients
Authors: Vicenzi Edoardo Bruno , Calore Elisabetta , Decembrino Nunzia , Berger Massimo , Perruccio Katia , Carraro Francesca , Rossin Sara , Putti Maria Caterina , Molinaro Mariadelfina , Tridello Gloria , Cesaro Simone
Published: December 2017

Background

Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level.

Methods

A total of 97 hematology‐oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included.

Results

Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 μg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 μg/mL at the first/second and the third determination, respectively. Posaconazole‐related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton‐pump inhibitors was significantly associated with a lower PPC, P = 0.04.

Conclusions

Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.
ER stress in skeletal muscle remodeling and myopathies
Authors: Afroze Dil , Kumar Ashok
Published: December 2017

Skeletal muscle is a highly plastic tissue in the human body that undergoes extensive adaptation in response to environmental cues, such as physical activity, metabolic perturbation, and disease conditions. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many mammalian cell types, including skeletal muscle. However, overload of misfolded or unfolded proteins in the ER lumen cause stress, which results in the activation of a signaling network called the unfolded protein response (UPR). The UPR is initiated by three ER transmembrane sensors: protein kinase R‐like endoplasmic reticulum kinase, inositol‐requiring protein 1α, and activating transcription factor 6. The UPR restores ER homeostasis through modulating the rate of protein synthesis and augmenting the gene expression of many ER chaperones and regulatory proteins. However, chronic heightened ER stress can also lead to many pathological consequences including cell death. Accumulating evidence suggests that ER stress‐induced UPR pathways play pivotal roles in the regulation of skeletal muscle mass and metabolic function in multiple conditions. They have also been found to be activated in skeletal muscle under catabolic states, degenerative muscle disorders, and various types of myopathies. In this article, we have discussed the recent advancements toward understanding the role and mechanisms through which ER stress and individual arms of the UPR regulate skeletal muscle physiology and pathology.
A comparative study of the physico‐chemical properties affecting the organoleptic quality of fresh and thermally treated yellow tomato ecotype fruit
Authors: Raiola Assunta , Pizzolongo Fabiana , Manzo Nadia , Montefusco Immacolata , Spigno Patrizia , Romano Raffaele , Barone Amalia
Published: December 2017

In recent years, yellow commercial tomatoes have attracted great interest from consumers. The goal of this work was to characterise the parameters of three yellow genotypes that affect the fruit quality, in comparison with those of a red fruit genotype. Compared to the other genotypes, the GiaGiù ecotype was characterised as having the highest titratable acidity, organic acids content and pectin content before and after a thermal treatment simulating industrial pasteurisation. Most of the analysed parameters influence the taste and aroma of fresh fruit and processed products, particularly the high glutamic acid content measured in the GiaGiù ecotype. This genotype was also distinctive for its higher pectin content, which influences the texture. These features might allow the development of new food products that require a specific viscosity, such as sauces and ketchup. Interestingly, the beneficial properties of GiaGiù were preserved after thermal processing.
Around the Mediterranean: an extreme example of loop migration in a long‐distance migratory passerine
Authors: Klvaňa Petr , Cepák Jaroslav , Munclinger Pavel , Michálková Romana , Tomášek Oldřich , Albrecht Tomáš
Published: December 2017

An important issue in migration research is how small‐bodied passerines pass over vast geographical barriers; in European–African avian migration, these are represented by the Mediterranean Sea and the Sahara Desert. Eastern (passing eastern Mediterranean), central (passing Apennine Peninsula) and western (via western Mediterranean) major migration flyways are distinguished for European migratory birds. The autumn and spring migration routes may differ (loop migration) and there could be a certain level of individual flexibility in how individuals navigate themselves during a single migration cycle. We used light‐level loggers to map migration routes of barn swallowsHirundo rusticabreeding in the centre of a wide putative contact zone between the northeastern and southernwestern European populations that differ in migration flyways utilised and wintering grounds. Our data documented high variation in migration patterns and wintering sites of tracked birds (n = 19 individuals) from a single breeding colony, with evidence for loop migration in all but one of the tracked swallows. In general, two migratory strategies were distinguished. In the first, birds wintering in a belt stretching from southcentral to southern Africa that used an eastern route for both the spring and autumn migration, then shifted their spring migration eastwards (anti‐clockwise loops, n = 12). In the second, birds used an eastern or central route to their wintering grounds in central Africa, shifting the spring migration route westward (clockwise loops, n = 7). In addition, we observed an extremely wide clockwise loop migration encompassing the entire Mediterranean, with one individual utilising both the eastern (autumn) and western (spring) migratory flyway during a single annual migration cycle. Further investigation is needed to ascertain whether clockwise migratory loops encircling the entire Mediterranean also occur other small long‐distance passerine species.
SERPINH1 overexpression in clear cell renal cell carcinoma: association with poor clinical outcome and its potential as a novel prognostic marker
Authors: Qi Yijun , Zhang Yue , Peng Zhiqiang , Wang Lei , Wang Kaizhen , Feng Duiping , He Junqi , Zheng Junfang
Published: December 2017

Precision therapy for clear cell renal cell carcinoma (ccRCC) requires molecular biomarkers ascertaining disease prognosis. In this study, we performed integrated proteomic and transcriptomic screening in all four tumour‐node‐metastasis stages of ccRCC and adjacent normal tissues (n = 18) to investigate differentially expressed genes. Most identified differentially expressed genes revealed a strong association with transforming growth factor‐β level and the epithelial‐to‐mesenchymal transition process. Of them, Serpin peptidase inhibitor clade H member 1 (SERPINH1) revealed the strongest association with poor prognosis and regulation on the expression levels of epithelial‐to‐mesenchymal transition markers. Subsequently, two independent sets (n = 532 and 105) verified the high level of SERPINH1 in ccRCC tissues and its association with reduced overall survival and disease‐free survival in all tumour‐node‐metastasis stages and patients with von Hippel–Lindau wild‐type (VHL‐WT). SERPINH1 was an independent predictor of poor overall survival (hazard ratio 0.696 for all patients) and disease‐free survival (hazard ratio 0.433 for all patients and 0.362 for patients with VHL‐WT) in ccRCC. We have thus shown for the first time that SERPINH1 is an independent precision predictor for unfavourable prognosis in ccRCC. This could assist in identifying patients who need early aggressive management and deepen our understanding of the pathogenesis of VHL‐WT ccRCC.
Quantifying the damage susceptibility to extreme events of mountain stream check dams using Rough Set Analysis
Authors: Mazzorana B. , Trenkwalder‐Platzer H. , Heiser M. , Hübl J.
Published: December 2017

In this work, a Rough Set Analysis‐based approach is proposed to quantify the damage susceptibility of check dams through specific indexes, which all require expert judgment to be quantified. The indexes are the Post‐Event Damage Condition (DamPost), the induced Condition Change (DamCh), the Residual Condition (RC), and the Post‐Event Functionality (FPost). Preliminarily, an existing data set, containing a quantification of the damage indexes, the associated characterisation of the flow process type of three torrential hazard events occurred in South Tyrol (Italy), the identification of construction material and the determination of age of the structure, was statistically analysed. To predict the damage indexes based on Rough Set Analysis, a general model, which considered all check dams regardless of their construction material, two specific models, for concrete and for masonry structures respectively, and a simplified version of the general model were set up. The derived rule bases exhibited satisfactory prediction accuracies only when the post‐event functionality, FPost, was chosen. Prediction accuracies were 68% for the general model, 79% for the material category concrete, 60% for the material category masonry, and 86% could be obtained by simplifying the decision attribute to a binary form (functionality given or not).
Comparison of robotic‐assisted versus laparoscopy for transperitoneal infrarenal para‐aortic lymphadenectomy in patients with endometrial cancer
Authors: Lee Hyun Jung , Lee Yoon Hee , Chong Gun Oh , Hong Dae Gy , Lee Yoon Soon
Published: December 2017

Aim

This study was conducted to evaluate the clinical feasibility of robotic‐assisted transperitoneal infrarenal para‐aortic lymphadenectomy (TIPAL) in patients with endometrial cancer.

Methods

From June 2006 to October 2016, we retrospectively analyzed 42 patients who underwent laparoscopic (n = 16) or robotic‐assisted (n = 26) staging operations, including TIPAL for endometrial cancer. Perioperative data including age; body mass index; operation duration; the number of lymph nodes retrieved and the ratio of time to lymph node retrieval during pelvic, infrarenal para‐aortic and total lymphadenectomy; estimated blood loss and postoperative complications were compared.

Results

The operative duration of pelvic (21.7 ± 5.31 vs 30.7 ± 10.8 min; P = 0.002), and total (62.6 ± 14.0 vs 87.0 ± 30.4 min; P = 0.010) lymphadenectomy was significantly shorter in the robotic‐assisted than the laparoscopic group, whereas there was no statistical difference in the duration of infrarenal para‐aortic lymphadenectomy. By contrast, the number of infrarenal para‐aortic lymph nodes retreived was significantly higher (29.4 ± 10.7 vs 23.3 ± 9.16; P = 0.016) in the robotic‐assisted group. Consequently, the ratio of time to number of lymph nodes retrieved during infrarenal (1.51 ± 0.49 vs 2.62 ± 1.34; P = 0.002) and total (1.43 ± 0.48 vs 2.15 ± 0.93; P = 0.014) lymphadenectomy was lower in the robotic‐assisted compared to the laparoscopic group.

Conclusions

The robotic‐assisted approach took less time per infrarenal para‐aortic and total lymph nodes retrieved compared to the conventional laparoscopic approach. Robotic‐assisted TIPAL could be feasible and effective for the staging and treatment of patients with endometrial cancer.
Functional limitation of the masticatory system in patients with bulbar involvement in amyotrophic lateral sclerosis
Authors: Riera‐Punet N. , Martinez‐Gomis J. , Willaert E. , Povedano M. , Peraire M.
Published: December 2017

Amyotrophic lateral sclerosis (ALS) with bulbar dysfunction affects the motor neurons responsible for controlling the muscles in the jaw, face, soft palate, pharynx, larynx and tongue. This cross‐sectional study aimed to determine the functional limitation of the jaw in patients with ALS and bulbar dysfunction who had upper motor neuron (UMN), lower motor neuron (LMN) or balanced involvement. One hundred and fifty‐three patients with ALS and 23 controls were included. All participants answered using the 8‐item Jaw Functional Limitation Scale (JFLS‐8). Patients with ALS were grouped by neurologic examination as follows: non‐bulbar ALS, bulbar UMN‐predominant ALS; bulbar LMN‐predominant ALS; and bulbar balanced (UMN + LMN) ALS. Jaw limitation between the different groups was compared using the Kruskal‐Wallis test. Patients with non‐bulbar ALS had similar mandibular limitations to healthy participants. Only patients with balanced UMN and LMN bulbar manifestations reported greater difficulties in chewing soft food or in jaw mobility compared to the non‐bulbar ALS group. Patients with bulbar involvement also had greater difficulties in chewing tough food or chicken and in swallowing and talking compared to the non‐bulbar group, regardless of whether UMN or LMN predominant. No significant differences were found between the groups in smiling and yawning difficulties. Bulbar involvement in patients with ALS is associated with functional limitation of the masticatory system. However, balanced bulbar UMN and LMN involvement is associated with the worst impairments in chewing soft food and in opening the jaw widely.
Chromatin‐level regulation of the fragmented dothistromin gene cluster in the forest pathogen Dothistroma septosporum
Authors: Chettri Pranav , Dupont Pierre‐Yves , Bradshaw Rosie E.
Published: December 2017

Genes required for fungal secondary metabolite production are usually clustered, co‐regulated and expressed in stationary growth phase. Chromatin modification has an important role in co‐regulation of secondary metabolite genes. The virulence factor dothistromin, a relative of aflatoxin, provided a unique opportunity to study chromatin level regulation in a highly fragmented gene cluster that is switched on during early exponential growth phase. We analysed three histone modification marks by ChIP‐qPCR and gene deletion in the pine pathogen Dothistroma septosporum to determine their effects on dothistromin gene expression across a time course and at different loci of the dispersed gene cluster. Changes in gene expression and dothistromin production were associated with changes in histone marks, with higher acetylation (H3K9ac) and lower methylation (H3K9me3, H3K27me3) during early exponential phase at the onset of dothistromin production. But while H3K27me3 directly influenced dothistromin genes dispersed across chromosome 12, effects of H3K9 acetylation and methylation were orchestrated mainly through a centrally located pathway regulator gene DsAflR. These results revealed that secondary metabolite production can be controlled at the chromatin‐level despite the genes being dispersed. They also suggest that patterns of chromatin modification are important in adaptation of a virulence factor for a specific role in planta.
Does the mosquito Culex pipiens represent a potential vector of hepatitis C virus?
Authors: EL‐KHOLY S. E. , EL‐HUSSEINY I. M. , MESHRIF W. S. , EL‐AZM A. ABOU , SALEM M. L.
Published: December 2017

Infection with hepatitis C virus (HCV) is a public health burden in several countries. Although transmission through blood is the most likely potential route of HCV infection, other sources warrant exploration. This study was designed to examine the possibility that the mosquito Culex pipiens (Diptera: Culicidae) might serve as a vector of HCV. A series of laboratory experiments were conducted in female Cx. pipiens that were fed on blood taken from HCV patients and tested for the presence of HCV RNAs using a reverse transcription polymerase chain reaction technique. In addition, the ability of the female mosquito to transmit HCV to human blood through membrane feeding or to its offspring (larvae) was tested. Although positive strand RNA was detected on days 1,7 and 14, negative strand HCV RNA was detected in mosquito body homogenate on days 7 and 14. Positive strands were also detected in the head, alimentary canal and salivary glands of mosquito adults at 1 week post‐feeding, as well as in their offspring (larvae). An ex vivo assay demonstrated that HCV‐infected mosquitoes were able to transmit the virus RNA into naive human blood samples via a membrane feeder. The present data indicate that the mosquito Cx. pipiens may be a potential vector of HCV.