bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic effects of whole-body vibration on fracture healing in ovariectomized rats: a systematic review and meta-analysis
Authors: Chen Jinman , Ruan Hongfeng , Liu Yang , Bao Jiamin , Xu Hao , Yao Min , Cui Xuejun , Liang Qianqian , Wang Yongjun
Published: December 2018

Objective:

Whole-body vibration (WBV), providing cyclic mechanical stimulation, has been used to accelerate fracture healing in preclinical studies. This study aimed to summarize and evaluate the effects of WBV on bone healing in ovariectomized rat models and then analyze its potential effects on fractures in human postmenopausal osteoporosis.

Methods:

PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, VIP, SinoMed, and WanFang databases were searched from their inception date to September 2017, and an updated search was conducted in January 2018. Studies that evaluated the effects of WBV on bone healing compared with control groups in ovariectomized rats were included. Two authors selected studies, extracted data, and assessed the methodological quality. Meta-analyses were performed when the same outcomes were reported in two or more studies.

Results:

Nine eligible studies were selected. In treatment groups, callus areas were significantly improved in the first 3 weeks, normalized total bone volume and total tissue volume values increased dramatically at 8 weeks, and the mechanical tests showed a significant difference at the end point of the study.

Conclusions:

This study suggested that WBV could accelerate callus formation in the early phase of bone healing, promote callus mineralization and maturity in the later phase, and restore mechanical properties of bones.
Variation of the Great Auricular Nerve and Prediction of the Facial Nerve Trunk Size
Authors: Kriengkraikasem Krist , Kowitwibool Kritsada , Chanpoo Malee
Published: December 2018

Background:

This study aimed to reveal the anatomical variation in the great auricular nerve (GAN) and the correlation between the size of the GAN and the facial nerve trunk (FNT), so as to aid surgeons to perform safe facelift surgery and parotidectomy.

Methods:

Sixteen human cadavers were studied on 16 left and 15 right facial sides. The GAN’s branching patterns, location, and the mean width of the GAN and FNT were measured.

Results:

The average distance where the nerve emerged from under the sternocleidomastoid muscle was 87.61 ± 12.13 mm when measured perpendicular to the Frankfort horizontal plane. The branching pattern of the GAN could be classified into 5 types of which the most common was type 3 (30.77%), where the GAN divided into the anterior (superficial) and posterior branches, and then the deep branch originated from the posterior branch of the GAN. The mean width of the GAN and FNT from all the dissections was 3.26 ± 0.67 mm and 3.36 ± 0.71 mm, respectively. There was a significant correlation between the width of the nerves on both facial sides (right: r =0.740, P =0.002; left: r = 0.839, P < 0.001).

Conclusions:

This study revealed the anatomical variation and the width of the GAN, which can strongly predict the width of the FNT. This should be taken into consideration during facelift surgery and parotidectomy, especially in patients with a small GAN to prevent iatrogenic injury to the small FNT.
Preventive Effect on Seroma of Use of PEAK PlasmaBlade after Latissimus Dorsi Breast Reconstruction
Authors: Sowa Yoshihiro , Inafuku Naoki , Kodama Takuya , Morita Daiki , Numajiri Toshiaki
Published: December 2018

Postoperative seroma is still the main complication after a latissimus dorsi (LD) flap procedure. The etiology of seroma is currently thought to comprise tissue fluids resulting from inflammatory reactions in affected tissue caused by the use of monopolar electrocautery (EC). It is possible that seroma formation can be reduced by using alternative devices such as the PEAK PlasmaBlade (PPB), which provides atraumatic scalpel-like cutting precision while the blade temperature remains close to body temperature. The subjects were 44 patients who underwent breast reconstruction with LD flaps from August 2015 to April 2017. They were retrospectively split into groups treated with a PPB (n = 21) and with conventional EC (n = 23). Outcomes such as rate of seroma formation, total drain discharge volume, indwelling period of drainage at the donor site, length of hospital stay, and operation time were compared between the 2 groups. The incidence of seroma was significantly lower in the PPB group (19.0%) than in the EC group (47.8%). The total drain discharge volume was significantly lower and the indwelling period of drainage and length of hospital stay were significantly shorter in the PPB group. In summary, use of PPB in an LD flap procedure can reduce seroma formation and the lengths of the drainage period and the hospital stay.
Complication Management following Rejuvenation Procedures with Hyaluronic Acid Fillers—an Algorithm-based Approach
Authors: Snozzi Philippe , van Loghem Jani A. J.
Published: December 2018

Background:

Hyaluronic acid is an ideal facial filler, however, although established as both safe and effective, complications do occur. Treatment recommendations that combine both expert opinions and clinical trial data are currently lacking, partly due to difficulties with diagnoses, nonspecific diagnostic investigations, and certain disorders presenting with similar symptoms, thereby confounding diagnosis and treatment.

Methods:

The purpose of this article was to provide the aesthetic clinician with practical recommendations regarding complication diagnosis arising as a consequence of hyaluronic acid filler rejuvenation treatment. It also provides recommendations for their management using step-wise treatment algorithms that are based on published expert opinions, as well as the author’s clinical experience.

Results:

Algorithms are provided for the most common categories of complication associated with hyaluronic acid filler treatment, that is, skin discoloration, edema, nodules, infection, and vascular compromise.

Conclusions:

These guidelines are not intended to be complete or exhaustive but may prove informative for aesthetic clinicians who are responsible for treating patients with hyaluronic acid fillers. It may help to guide them on recognizing potential complications and it provides clear guidance on optimum treatment pathways.
Experience of Using a Semielemental Formula for Home Enteral Nutrition in Children
Authors: Leonard Marie , Caldari Dominique , Mas Emmanuel , Lambe Cécile , Comte Aurélie , Ley Delphine , Peretti Noël , Borderon Corinne , Marinier Evelyne , Coste Marie‐Edith , Lamireau Thierry , Rubio Amandine , Turquet Anne , Dubern Béatrice , Dabadie Alain , Gautry Julien , Kyheng Maeva , Guimber Dominique , Gottrand Frédéric
Published: December 2018

Objectives:

The use of semielemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product.

Methods:

We performed a retrospective multicenter survey on a cohort of patients receiving this semielemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6, and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events.

Results:

We recruited 136 patients ages 9.8 ± 4.4 years at baseline. Mean body mass index z score was −1.0 ± 1.8; mean height z score was −1.1 ± 1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and hematological (19.9%). The indications for a semielemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%), and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children.

Conclusions:

This semielemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet.
Reduction of Metal Artifacts and Improvement in Dose Efficiency Using Photon-Counting Detector Computed Tomography and Tin Filtration
Authors: Zhou Wei , Bartlett David J. , Diehn Felix E. , Glazebrook Katrina N. , Kotsenas Amy L. , Carter Rickey E. , Fletcher Joel G. , McCollough Cynthia H. , Leng Shuai
Published: December 2018

Objectives

The aim of this study was to investigate the impact on metal artifacts and dose efficiency of using a tin filter in combination with high-energy threshold (TH) images of a photon-counting detector (PCD) computed tomography (CT) system.

Materials and Methods

A 3D-printed spine with pedicle screws was scanned on a PCD-CT system with and without tin filtration. Image noise and severity of artifacts were measured for low-energy threshold (TL) and TH images. In a prospective, institutional review board–approved, Health Insurance Portability and Accountability Act-compliant study, 20 patients having a clinical energy-integrating detector (EID) CT were scanned on a PCD-CT system using tin filtration. Images were reviewed by 3 radiologists to evaluate visualization of anatomic structures, diagnostic confidence, and image preference. Artifact severity and image noise were measured. Wilcoxon signed rank was used to test differences between PCD-CT TH and EID-CT images.

Results

Phantom TH images with tin filtration reduced metal artifacts and had comparable noise (32 HU) to TL images (29 HU) acquired without tin filtration. Visualization scores for the cortex, trabeculae, and implant-trabecular interface from PCD-CT TH images (4.4 ± 0.9, 4.4 ± 1.0, and 4.4 ± 1.0) were significantly higher (P < 0.0001) than EID-CT images (3.3 ± 1.3, 3.3 ± 1.2, and 3.3 ± 1.6). A strong preference was shown for PCD-CT TH images due to improved diagnostic confidence and decreased artifact severity. Noise in PCD-CT TH images (93 ± 41 HU) was significantly lower than that in EID-CT images (133 ± 92 HU, P < 0.05).

Conclusions

Threshold high images acquired with tin filtration on PCD-CT demonstrated a substantial decrease in metal artifacts and an increase in dose efficiency compared with EID-CT.
Iodinated Contrast Agents and Risk of Hypothyroidism in Young Children in the United States
Authors: Jick Susan S. , Hedderson Monique , Xu Fei , Cheng Yingkai , Palkowitsch Petra , Michel Alexander
Published: December 2018

Background

Although it is generally acknowledged that exposure to iodine contrast agents can interfere with thyroid function, little is known about the incidence of iodine-induced hypothyroidism in young children (younger than the age of 4 years).

Study Objectives

This was a retrospective cohort study to estimate the incidence rate of detected hypothyroidism in a US-based general population of pediatric patients exposed to an iodinated contrast agent.

Setting

The study was conducted in Kaiser Permanente Northern California, an integrated health care delivery system.

Study Population

This study included 2320 pediatric patients younger than 4 years of age who had a diagnostic procedure with an iodinated contrast agent during years 2008 to 2016.

Results

Among 2320 young children who met our study criteria, we identified 34 who met the initial criteria to be a case of hypothyroidism. The incidence density ratio for all hypothyroidism in iodine contrast agent–exposed patients was 1.33 per 1000 person months (95% confidence interval, 0.9–1.8). Most cases appeared to have subclinical hypothyroidism. The rate was higher for the probably iodine-induced cases (0.90 per 1000 person months) compared with cases with a possible alternate etiology (0.43 per 1000 person months), for males compared with females, and among children who had a heart catheterization compared with those with a computed tomography scan. It was also highest among the youngest children (younger than 3 months old), and decreased with increasing age.

Discussion

Our finding of hypothyroidism in young children exposed to iodine contrast agents (1.33 per 1000 person months [95% confidence interval, 0.9–1.8]) is broadly consistent with the sparse literature on this outcome.
Integrative Medicine in Plastic Surgery
Authors: Ruan Qing Zhao , Chen Austin D. , Tran Bao Ngoc N. , Epstein Sherise , Fukudome Eugene Y. , Tobias Adam M. , Lin Samuel J. , Lee Bernard T. , Yeh Gloria Y. , Singhal Dhruv
Published: December 2018

Background

Surveys have reported that as high as 80% of plastic surgery patients utilize integrative medicine approaches including natural products (NPs) and mind-body practices (MBPs). Little is known regarding the evidence of benefit of these integrative therapies specifically in a plastic surgery patient population.

Methods

We conducted a systematic review of studies in MEDLINE, PubMed, and EMBASE (inception through December 2016) evaluating integrative medicine among plastic surgery patients. Search terms included 76 separate NP and MBP interventions as listed in the 2013 American Board of Integrative Health Medicine Curriculum. Two independent reviewers extracted data from each study, including study type, population, intervention, outcomes, conclusions (beneficial, harmful, or neutral), year of publication, and journal type. Level of evidence was assessed according to the American Society of Plastic Surgeons Rating Levels of Evidence and Grading Recommendations.

Results

Of 29 studies analyzed, 13 studies (45%) evaluated NPs and 16 (55%) studied MBPs. Level II reproducible evidence supports use of arnica to decrease postoperative edema after rhinoplasty, onion extract to improve scar pigmentation, hypnosis to alleviate perioperative anxiety, and acupuncture to improve perioperative nausea. Level V evidence reports on the risk of bleeding in gingko and kelp use and the risk of infection in acupuncture use. After year 2000, 92% of NP studies versus 44% of MBP studies were published (P = 0.008).

Conclusions

High-level evidence studies demonstrate promising results for the use of both NPs and MBPs in the care of plastic surgery patients. Further study in this field is warranted.
Communication skills training for healthcare professionals in oncology over the past decade: a systematic review of reviews
Authors: Bos – van den Hoek Danique W. , Visser Leonie N.C. , Brown Richard F. , Smets Ellen M.A. , Henselmans Inge
Published: December 2018

Purpose of review

Effective communication in cancer care requires complex communication skills of healthcare professionals (HCPs), which can be advanced by communication skills training (CST). The number of empirical studies on CST has grown steadily over the last decade. However, controversies on CST abound. The aim of this review of reviews is to summarize evidence for the effectiveness of CST in oncology as well as for effective CST features (intensity, format and content) and to synthesize the current opinion on CST.

Recent findings

The evidence synthesized from multiple reviews supported the effect of CST on HCPs’ communication skills. Yet, the certainty of evidence was limited as studies were diverse and effects heterogeneous. Furthermore, limited evidence was found for effective CST intensity, format and content. Authors of the reviews advocated further high-quality research with robust outcome measurement to establish the most essential features of CST and recommended implementation of CST in the standard training of HCPs with continuous supervision.

CST can probably improve some aspects of HCPs’ communication skills. Despite the uncertain evidence, implementation of CST into clinical practice is widely advocated and specific recommendations regarding intensity and format are provided. Evidence to justify and substantiate implementation efforts is needed.
White Matter Microstructure in Illiterate and Low-Literate Elderly Brazilians: Preliminary Findings
Authors: Resende Elisa de Paula França , Tovar-Moll Fernanda Freire , Ferreira Fernanda Meireles , Bramati Ivanei , de Souza Leonardo Cruz , Carmona Karoline Carvalho , Guimarães Henrique Cerqueira , Carvalho Viviane Amaral , Barbosa Maira Tonidandel , Caramelli Paulo
Published: December 2018

Objective:

To investigate differences in white matter microstructure between illiterate and low-literate elderly Brazilians.

Background:

High literacy levels are believed to partially counteract the negative effects of neurodegenerative diseases. Investigating the impact of low literacy versus illiteracy on brain structure can contribute knowledge about cognitive reserve in elderly populations with low educational attainment. Fractional anisotropy is a measure derived from diffusion tensor imaging sequences that positively correlate with the integrity of the brain’s white matter microstructure.

Methods:

Older adults who participated in an epidemiological study to investigate brain aging in Brazil and had magnetic resonance scans with the diffusion tensor imaging acquisition were selected (n=31). Participants were divided into two groups: (a) low-literate (n=21), with 3.4 (1.4) years of education, 79.8 (3.8) years of age, 17 cognitively healthy and four with cognitive impairment-no dementia; and (b) illiterate (n=10) with no formal schooling, 80.7 (4.1) years of age, six cognitively healthy and four with cognitive impairment-no dementia. We contrasted the two groups’ white matter microstructure measures using whole-brain and region of interest approaches.

Results:

The low-literate participants had significantly higher fractional anisotropy values in the right superior longitudinal fasciculus than did the illiterate ones.

Conclusions:

Although our results are preliminary because of the sample size, they suggest that low literacy, versus illiteracy, is associated with higher fractional anisotropy values, which are indirect measurements of white matter microstructure. This finding provides insight into a possible mechanism by which literacy, even at low levels, may contribute to cognitive reserve.
Recombination in a natural population of the bdelloid rotiferAdineta vaga
Authors: Vakhrusheva Olga A. , Mnatsakanova Elena A. , Galimov Yan R. , Neretina Tatiana V. , Gerasimov Evgeny S. , Ozerova Svetlana G. , Zalevsky Arthur O. , Yushenova Irina A. , Arkhipova Irina R. , Penin Aleksey A. , Logacheva Maria D. , Bazykin Georgii A. , Kondrashov Alexey S.
Published: December 2018

Sexual reproduction which involves alternation of meiosis and syngamy is the ancestral condition of extant eukaryotes. Transitions to asexual reproduction were numerous, but most of the resulting eukaryotic lineages are rather short-lived. Still, there are several exceptions to this rule including darwinulid ostracods1,2and timema stick insects3. The most striking of them is bdelloid rotifers4–6, microscopic freshwater invertebrates which underwent an extensive adaptive radiation after apparently losing meiosis over 10 Mya. Indeed, both the lack of males in numerous bdelloid species and the lack of proper homology between chromosomes6rule out ordinary sex. However, this does not exclude the possibility of some other mode of interindividual genetic exchange and recombination in their populations7. Recent analyses based on a few loci suggested genetic exchanges in this group8,9, although this has been controversial10. Here, we compare complete genomes of 11 individuals from the wild population of the bdelloid rotiferAdineta vaga,and show that its genetic structure, which involves Hardy-Weinberg proportions of genotypes within loci and lack of linkage disequilibrium between distant loci, is incompatible with strictly clonal reproduction. Instead, it can emerge only under ongoing recombination between different individuals within this species, possibly through transformation. Such a genetic structure makes the population immune to negative long-term consequences of the loss of conventional meiosis11, although this does not necessarily imply that interindividual genetic exchanges inA. vagaare directly maintained by natural selection.
Rapid evolution by spontaneous mutation increases genetic diversity facilitating plant population survival
Authors: Nottebrock Henning , Weng Mao-Lun , Rutter Matthew T , Fenster Charles B.
Published: December 2018

Using a mechanistic eco-evolutionary trait-based neighborhood-model, we quantify the impact of mutations on spatial interactions to better understand the potential effect of niche evolution through mutations on the population dynamics of Arabidopsis thaliana. We use 100 twenty-fifth generation mutation accumulation (MA) lines (genotypes) derived from one founder genotype to study mutational effects on neighbor responses in a field experiment. We created individual-based maps (15,000 individuals), including phenotypic variation, to quantify mutational effects within genotypes versus between genotypes on reproduction and survival. At small-scale, survival is enhanced but reproduction is decreased when a genotype is surrounded by different genotypes. At large-scale, seed set is facilitated by different genotypes while the same genotype has either no effect or negative effects. Mutations may provide a mechanism for plants to quickly evolve niches and may drive competition, facilitation and selection with profound consequences for future population and community dynamics.
Accessory genome contributes to the virulence and resistance of the ocular isolate of Pseudomonas aeruginosa: A complete genome analysis
Authors: Subedi Dinesh , Kohli Gurjeet Singh , Vijay Ajay Kumar , Willcox Mark D. P. , Rice Scott A.
Published: December 2018

Bacteria can acquire an accessory genome through the horizontal transfer of genetic elements from non-parental lineages. This leads to rapid genetic evolution allowing traits such as antibiotic resistance and virulence to spread through bacterial communities. The study of complete genomes of bacterial strains helps to understand the genomic traits associated with virulence and antibiotic resistance. We aimed to investigate the complete accessory genome of an ocular isolate of P. aeruginosa. We obtained the complete genome of the ocular isolate strain PA34 of P. aeruginosa utilising genome sequence reads from Illumina and Oxford Nanopore Technology followed by PCR to close any identified gaps. In-depth genomic analysis was performed using various bioinformatics tools. The phenotypic properties of susceptibility to heavy metals and cytotoxicity were determined to confirm expression of certain traits. The complete genome of PA34 includes a chromosome of 6.8 Mbp and two plasmids of 95.4 Kbp (pMKPA34-1) and 26.8 Kbp (pMKPA34-2). PA34 had a large accessory genome of 1,213 genes and had 543 unique genes not present in other strains. These exclusive genes encoded features related to metal and antibiotic resistance, phage integrase and transposons. At least 24 GIs were predicated in the complete chromosome, of which two were integrated into novel sites. Eleven GIs carried virulence factors or replaced pathogenic genes. A bacteriophage carried the aminoglycoside resistance gene (aac(3)-IId). The two plasmids carried other six antibiotic resistance genes. The large accessory genome of this ocular isolate plays a large role in shaping its virulence and antibiotic resistance.
When can we trust population trends? Quantifying the effects of sampling interval and duration
Authors: Wauchope Hannah , Johnston Alison , Amano Tatsuya , Sutherland William
Published: December 2018

Species’ population trends are fundamental to conservation, underpinning lUCN red-list classifications, many national lists of threatened species and are also used globally to convey to policy makers the state of nature. Clearly, it’s crucial to quantify how much we can trust population trend data. Yet many studies analyzing large numbers of population time series lack a straightforward way to estimate confidence in each trend. Here we artificially degrade 27,930 waterbird population time series to see how often subsets of the data correctly estimate the direction and magnitude of each population’s true trend. We find you need to sample many years to be confident that there is no significant trend in a population. Conversely, if a significant trend is detected, even from only a small subset of years, this is likely to be representative of the population’s true trend. This means that if a significant decline is detected in a population, it is likely to be correct and conservation action should be taken immediately, but if the trend is insignificant, confidence in this can only be high with many samples. Our full results provide a clear and quantitative way to assign confidence to species trends, and lays the foundation for similar studies of other taxa that can help to add rigor to large-scale population analyses.
A novel mechanosensitive channel controls osmoregulation, differentiation and infectivity inTrypanosoma cruzi
Authors: Dave N , Cetiner U , Arroyo D , Fonbuena J , Tiwari M , Barrera P , Lander N , Anishkin A , Sukharev S , Jimenez V
Published: December 2018

Trypanosoma cruzi, the causative agent of Chagas disease, undergoes drastic morphological and biochemical modifications as it passes between hosts and transitions from extracellular to intracellular stages. The osmotic and mechanical aspects of these cellular transformations are not understood. Here we identify and characterize a novel mechanosensitive channel in T.cruzi(TcMscS) belonging to the superfamily of small conductance mechanosensitive channels (MscS). TcMscS is activated by membrane tension and forms a large pore permeable to anions, cations, and small osmolytes. The channel changes its location from the contractile vacuole complex in epimastigotes to the plasma membrane as the parasites develop into intracellular amastigotes. TcMscS knockout parasites show significant fitness defects, including increased cell volume, calcium dysregulation, impaired differentiation, and a dramatic decrease in infectivity. Our work provides mechanistic insights into components supporting pathogen adaptation inside the host thus opening the exploration of mechanosensation as a prerequisite of protozoan infectivity.
Beyond SNP Heritability: Polygenicity and Discoverability of Phenotypes Estimated with a Univariate Gaussian Mixture Model
Authors: Holland Dominic , Frei Oleksandr , Desikan Rahul , Fan Chun-Chieh , Shadrin Alexey A. , Smeland Olav B. , Sundar V. S. , Thompson Paul , Andreassen Ole A. , Dale Anders M.
Published: December 2018

Of signal interest in the genetics of human traits is estimating their polygenicity (the proportion of causally associated single nucleotide polymorphisms (SNPs)) and the discoverability (or effect size variance) of the causal SNPs. Narrow-sense heritability is proportional to the product of these quantities. We present a basic model, using detailed linkage disequilibrium structure from an extensive reference panel, to estimate these quantities from genome-wide association studies (GWAS) summary statistics for SNPs with minor allele frequency >1%. We apply the model to diverse phenotypes and validate the implementation with simulations. We find model polygenicities ranging from ≃ 2 × 10−5to ≃ 4 × 10−3, with discoverabilities similarly ranging over two orders of magnitude. A power analysis allows us to estimate the proportions of phenotypic variance explained additively by causal SNPs at current sample sizes, and map out sample sizes required to explain larger portions of additive SNP heritability. The model also allows for estimating residual inflation.
Reconciling DNA replication and transcription in a hyphal organism: Spatial dynamics of transcription complexes in live Streptomyces coelicolor A3(2)
Authors: Nieminen Leena , Hoskisson Paul A
Published: December 2018

Reconciling transcription and DNA replication in the growing hyphae of the filamentous bacterium Streptomyces presents several physical constraints on growth due to their apically extending and branching, multigenomic cells and chromosome replication being independent of cell division. Using a GFP translational fusion to the β`-subunit of RNA polymerase (rpoC-egfp), in its native chromosomal location, we observed growing Streptomyces hyphae using time-lapse microscopy throughout the lifecycle and under different growth conditions. The RpoC-eGFP fusion co-localised with DNA around 1.8 μm behind the extending tip, whereas replisomes localise around 4-5 μm behind the tip, indicating that at the growing tip, transcription and chromosome replication are to some degree spatially separated. Dual-labeled RpoC-egfp/DnaN-mCherry strains also indicate that there is limited co-localisation of transcription and chromosome replication at the extending hyphal tip. This likely facilitates the use of the same DNA molecule for active transcription and chromosome replication in growing cells, independent of cell division. This represents a novel, but hitherto unknown mechanism for reconciling two fundamental processes that utilise the same macromolecular template that allows for rapid growth without compromising chromosome replication in filamentous bacteria and may have implications for evolution of filamentous growth in microorganisms, where uncoupling of DNA replication from cell division is required.
Dissociable laminar profiles of concurrent bottom-up and top-down modulation in the human visual cortex
Authors: Lawrence Samuel J. D. , Norris David G. , de Lange Floris P.
Published: December 2018

Recent developments in human neuroimaging make it possible to non-invasively measure neural activity from different cortical layers. This can potentially reveal not only which brain areas are engaged by a task, but also how. Specifically, bottom-up and top-down responses are associated with distinct laminar profiles. Here, we measured lamina-resolved fMRI responses during a visual task designed to induce concurrent bottom-up and top-down modulations via orthogonal manipulations of stimulus contrast and feature-based attention. BOLD responses were modulated by both stimulus contrast (bottom-up) and by engaging feature-based attention (top-down). Crucially, these effects operated at different cortical depths: Bottom-up modulations were strongest in the middle cortical layer, while top-down modulations were strong at all depths, being significantly stronger in deep and superficial layers compared to bottom-up effects. As such, we demonstrate that laminar activity profiles can discriminate between concurrent top-down and bottom-up processing, and are diagnostic of how a brain region is activated.
The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli
Authors: Kucharczyk Mateusz W. , Chisholm Kim I. , Denk Franziska , Dickenson Anthony H. , Bannister Kirsty , McMahon Stephen B.
Published: December 2018

Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature and not easily managed by available therapies. The peripheral sensory profile of primary afferents responsible for transmitting the pain-related messages from cancerous bone to central sites is investigated here. We imaged thousands of primary sensory dorsal root ganglion neurons in vivo in healthy (sham-operated) and cancer-induced bone pain (CIBP) rats in order to analyse and compare their function. Utilising Markov Cluster Analysis we identified distinct clusters of primary afferent responses to limb compression and position. In CIBP rats, three times as many sensory afferents responded to knee compression in the leg ipsilateral to the tumour compared to sham-operated rats. We present evidence that the observed increase in sensory afferent response was not due to increased individual afferent activity but rather represents activation of ‘silent’ nociceptors, whose origin we propose is largely from outside of the bone.
Deconvoluting Stress-Responsive Proteostasis Signaling Pathways for Pharmacologic Activation using Targeted RNA-sequencing
Authors: Grandjean Julia M.D. , Plate Lars , Morimoto Richard I. , Bollong Michael J. , Powers Evan T. , Wiseman R. Luke
Published: December 2018

Cellular proteostasis is maintained by stress-responsive signaling pathways such as the heat shock response (HSR), the oxidative stress response (OSR), and the unfolded protein response (UPR). Activation of these pathways results in the transcriptional upregulation of select subsets of stress-responsive genes that restore proteostasis and adapt cellular physiology to promote recovery following various types of acute insult. The capacity for these pathways to regulate cellular proteostasis makes them attractive therapeutic targets to correct proteostasis defects associated with diverse diseases. High-throughput screening (HTS) using cell-based reporter assays is highly effective for identifying putative activators of stress-responsive signaling pathways. However, the development of these compounds is hampered by the lack of medium-throughput assays to define compound potency and selectivity for a given pathway. Here, we describe a targeted RNA sequencing (RNAseq) assay that allows cost effective, medium-throughput screening of stress-responsive signaling pathway activation. We demonstrate that this assay allows deconvolution of stress-responsive signaling activated by chemical genetic or pharmacologic agents. Furthermore, we use this assay to define the selectivity of putative OSR and HSR activating compounds previously identified by HTS. Our results demonstrate the potential for integrating this adaptable targeted RNAseq assay into screening programs focused on developing pharmacologic activators of stress-responsive signaling pathways.
Antigen receptor control of methionine metabolism in T cells
Authors: Sinclair Linda V , Howden Andrew JM , Brenes-Murillo Alejandro J , Spinelli Laura , Hukelmann Jens L , Macintyre Andrew N , Liu Xiaojing , Thomson Sarah , Taylor Peter M , Rathmell Jeffrey C , Locasale Jason W , Lamond Angus I , Cantrell Doreen A
Published: December 2018

Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation. The present study uses high resolution mass spectrometry and metabolic labelling to explore how T cells control the methionine cycle to produce methyl donors for protein and nucleotide methylations. We show that antigen receptor engagement controls flux through the methionine cycle and also controls RNA and histone methylations. We establish that the main rate limiting step for the methionine cycle is control of methionine transporter expression by antigen receptors. Only T cells that respond to antigen to upregulate and sustain methionine transport are supplied with the methyl donors that permit the dynamic nucleotide methylations and epigenetic reprogramming that drives T cell differentiation.
Reference genes for RT-qPCR normalisation in different tissues, developmental stages and stress conditions of Hypericum perforatum
Authors: Wang Zhezhi , Zhou Wen , Yang Lei , Sun Yan , Zhang Qian , Li Bin , Wang Bin , Li Lin , Wang Donghao , Wang Shiqiang
Published: December 2018

Hypericum perforatum is a widely known medicinal herb used mostly as a remedy for depression because of its abundant secondary metabolites. Quantitative real-time PCR (qRT-PCR) is an optimized method for the efficient and reliable quantification of gene expression studies. In general, reference genes are used in qRT-PCR analysis because of their known or suspected housekeeping roles. However, their expression level cannot be assumed to remain stable under all possible experimental conditions. Thus, the identification of high quality reference genes is very necessary for the interpretation of qRT-PCR data. In this study, we investigated the expression of fourteen candidate genes, including nine housekeeping genes and five potential candidate genes. Additionally, the HpHYP1 gene, belonging to the PR-10 family associated with stress control, was used for validation of the candidate reference genes. Three programs were applied to evaluate the gene expression stability across four different plant tissues, three developmental stages and a set of abiotic stress and hormonal treatments. The candidate genes showed a wide range of Ct values in all samples, indicating that they are differentially expressed. Integrating all of the algorithms and evaluations, ACT2 and TUB-β were the most stable combination overall and for different developmental stages samples. Moreover, ACT2 and EF1-α were considered to be the two most applicable reference genes for different tissues and for stress samples. Majority of the conventional housekeeping genes exhibited better than the potential reference genes. The obtained results will contribute to improving credibility of standardization and quantification of transcription levels in future expression research of H. perforatum.
ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease
Authors: Wallace Daniel F. , Dooley James S.
Published: December 2018

Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the copper transporting P-type ATPase gene ATP7B. Estimates for WD population prevalence vary with 1 in 30,000 generally quoted. However, some genetic studies have reported much higher prevalence rates. The aim of this study was to estimate the population prevalence of WD and the pathogenicity/penetrance of WD variants by determining the frequency of ATP7B variants in a genomic sequence database. A catalogue of WD-associated ATP7B variants was constructed and then frequency information for these was extracted from the gnomAD dataset. Pathogenicity of variants was assessed by (a) comparing gnomAD allele frequencies against the number of reports for variants in the WD literature and (b) using variant effect prediction algorithms. 231 WD-associated ATP7B variants were identified in the gnomAD dataset, giving an initial estimated population prevalence of around 1 in 2400. After exclusion of WD-associated ATP7B variants with predicted low penetrance, the revised estimate showed a prevalence of around 1 in 20,000, with higher rates in the Asian and Ashkenazi Jewish populations. Reanalysis of other recent genetic studies using our penetrance criteria also predicted lower population prevalences for WD in the UK and France than had been reported. Our results suggest that differences in variant penetrance can explain the discrepancy between reported epidemiological and genetic prevalences of WD. They also highlight the challenge in defining penetrance when assigning causality to some ATP7B variants.
Rotational switches in the two-dimensional fullerene quasicrystal
Authors: Paßens M. , Karthäuser S.
Published: December 2018

One of the essential components of molecular electronic circuits are switching elements that are stable in two different states and can ideally be switched on and off many times. Here, distinct buckminsterfullerenes within a self-assembled monolayer, forming a two-dimensional dodecagonal quasicrystal on a Pt-terminated Pt3Ti(111) surface, are identified to form well separated molecular rotational switching elements. Employing scanning tunneling microscopy, the molecular-orbital appearance of the fullerenes in the quasicrystalline monolayer is resolved. Thus, fullerenes adsorbed on the 36vertex configuration are identified to exhibit a distinctly increased mobility. In addition, this finding is verified by differential conductance measurements. The rotation of these mobile fullerenes can be triggered frequently by applied voltage pulses, while keeping the neighboring molecules immobile. An extensive analysis reveals that crystallographic and energetic constraints at the molecule/metal interface induce an inequality of the local potentials for the 36and 32.4.3.4 vertex sites and this accounts for the switching ability of fullerenes on the 36vertex sites. Consequently, a local area of the 8/3 approximant in the two-dimensional fullerene quasicrystal consists of single rotational switching fullerenes embedded in a matrix of inert molecules. Furthermore, it is deduced that optimization of the intermolecular interactions between neighboring fullerenes hinders the realization of translational periodicity in the fullerene monolayer on the Pt-terminated Pt3Ti(111) surface.
Crystal structures of 2,3-bis(thiophen-2-yl)pyrido[2,3-b]pyrazine and 7-bromo-2,3-bis(thiophen-2-yl)pyrido[2,3-b]pyrazine
Authors: Popek Rafal , Crundwell Guy
Published: December 2018

The crystal structures of 2,3-bis(thiophen-2-yl)pyrido[2,3-b]pyrazine, C15H9N3S2 (1), and 7-bromo-2,3-bis(thiophen-2-yl)pyrido[2,3-b]pyrazine, C15H8BrN3S2 (2), are discussed. Both molecules crystallize in space group P21/c. In 1, the thienyl rings are inclined to the mean plane of the pyridopyrazine moiety by 6.16 (7) and 86.66 (8)°, where as in 2 the corresponding dihedral angles are 33.29 (11) and 19.84 (9)°. The pyridopyrazine moiety is relatively planar in 1 with the two rings being inclined to each other by 1.33 (7)°. In 2, however, the pyridopyrazine moiety is buckled with the corresponding dihedral angle being larger at 8.78 (10)°. In the crystal of 1, the packing creates intersecting bilayers; the layering results from the pyridopyrazine moieties being engaged in offset π-stacking, where the interplanar distance is 3.431 (9) Å with an offset 1.14 Å. In the crystal of 2, the molecules pack head-to-head and are linked by a series of C—H...Br and C—H...N intermolecular interactions, forming layers parallel to the ab plane.
Crystal structure of 3,6-bis(pyridin-2-yl)-1,4-dihydro-1,2,4,5-tetrazine
Authors: Wzgarda-Raj Kinga , Rybarczyk-Pirek Agnieszka J. , Wojtulewski Sławomir , Palusiak Marcin
Published: December 2018

The structure of the title compound, C12H10N6, at 100 K has monoclinic (P21/n) symmetry. Crystals were obtained as a yellow solid by reduction of 3,6-bis(pyridin-2-yl)-1,2,4,5-tetrazine. The structure displays intermolecular hydrogen bonding of the N—H...N type, ordering molecules into infinite ribbons extending along the [100] direction.
Assessment of a small UAV speed polar graph by conducting flight tests
Authors: Tomaszewski Adam , Goraj Zdobyslaw Jan
Published: December 2018

Purpose

The purpose of this paper is to present an approach to a polar graph measurement by a flight testing technique and to propose a baseline research method for future tests of UAV polar graphs. The method presented can be used to demonstrate a conceptual and preliminary design process using a scaled, unmanned configuration. This shows how results of experimental flight tests using a scaled flying airframe may be described and analysed before manufacturing the full scale aircraft.

Design/methodology/approach

During the research, the flight tests were conducted for two aerodynamic configurations of a small UAV. This allowed the investigation of the influence of winglets and classic vertical stabilizers on the platform stability, performance and therefore polar graphs of a small unmanned aircraft.

Findings

A methodology of flight tests for the assessment of a small UAV’s polar graph has been proposed, performed and assessed. Two aerodynamic configurations were tested, and it was found that directional stability had a large influence on the UAV’s performance. A correlation between the speed and inclination of the altitude graph was found – i.e. the higher the flight speed, the steeper the altitude graph (higher descent speed, steeper flight path angle). This could be considered as a basic verification that the recorded data have a physical sense.

Practical implications

The polar graph and therefore glide ratio of the aircraft is a major factor for determining its performance and power required for flight. Using the right flight test procedure can speed-up the process of measuring glide ratio, making it easier, faster, robust, more effective and accurate in future research of novel, especially unorthodox configurations. This paper also can be useful for the proper selection of requirements and preliminary design parameters for making the design process more economically effective.

Originality/value

This paper presents a very efficient method of assessing the design parameters of UAVs, especially the polar graph, in an early stage of the design process. Aircraft designers and producers have been widely performing flight testing for years. However, these procedures and practical customs are usually not wide spread and very often are treated as the company’s “know how”. Results presented in this paper are original, relatively easily be repeated and checked. They may be used either by professionals, highly motivated individuals and representatives of small companies or also by ambitious amateurs.
New design for reducing interfacial stresses of reinforced structures with FRP plates
Authors: Belabed Youssouf , Kerboua Bachir , Tarfaoui Mostapha
Published: December 2018

Purpose

The sustainability of the structures is not only a technical goal, but also a matter of social and environmental values. This requires the researchers to use very rigid, highly durable and corrosion-resistant composite structures in order to achieve the technical, environmental and social goals. The purpose of this paper is to present an original work on reducing the interfacial stresses of bonded structures with fibre-reinforced polymers (FRP) plates based on new taper design.

Design/methodology/approach

In this proposed concept, the effect of combined taper is investigated on reducing interfacial stresses, attempting to enhance the structure performance and address the debonding problem that comes with reinforcing techniques. This research is carried out by using finite element analysis, incorporating many new parameters.

Findings

As a result, a new solution is discovered that combined taper in both adhesive layer and composite laminate, which significantly reduces the interfacial stresses at the end of the FRP plate. Additionally, a parametric study is carried out in order to determine the optimal configurations of taper dimensions as well as other parameters that influence the stress concentration distribution at the edge of the adherends.

Practical implications

This new design regarding the reduction of interfacial stresses will help in increasing the lifespan of damaged structures reinforced by FRP composites, preserving thus its technical, historical and social values.

Originality/value

The paper uses straight, concave and convex fillets with inverse taper as a new design solution with new parameters including thermo-mechanical loads and pre-stressed FRP plate with multi-layer, fibre orientation and shear-lag effects.