bluuebunny/crossref_metadata_2025 huggingface dataset:
Talbot-Lau x-ray phase-contrast setup for fast scanning of large samples
Authors: Seifert Maria , Ludwig Veronika , Kaeppler Sebastian , Horn Florian , Meyer Pascal , Pelzer Georg , Rieger Jens , Sand Daniel , Michel Thilo , Mohr Jürgen , Riess Christian , Anton Gisela
Published: March 2019

Compared to conventional attenuation x-ray radiographic imaging, the x-ray Talbot-Lau technique provides further information about the scattering and the refractive properties of the object in the beam path. Hence, this additional information should improve the diagnostic process concerning medical applications and non-destructive testing. Nevertheless, until now, due to grating fabrication process, Talbot-Lau imaging suffers from small grating sizes (70 mm diameter). This leads to long acquisition times for imaging large objects. Stitching the gratings is one solution. Another one consists of scanning Talbot-Lau setups. In this publication, we present a compact and very fast scanning setup which enables imaging of large samples. With this setup a maximal scanning velocity of 71.7 mm/s is possible. A resolution of 4.1 lines/mm can be achieved. No complex alignment procedures are necessary while the field of view comprises 17.5 × 150 cm2. An improved reconstruction algorithm concerning the scanning approach, which increases robustness with respect to mechanical instabilities, has been developed and is presented. The resolution of the setup in dependence of the scanning velocity is evaluated. The setup imaging qualities are demonstrated using a human knee ex-vivo as an example for a high absorbing human sample.
Strong correlation of novel sleep electroencephalography coherence markers with diagnosis and severity of posttraumatic stress disorder
Authors: Modarres Mo H. , Opel Ryan A. , Weymann Kristianna B. , Lim Miranda M.
Published: March 2019

Objective biomarkers of the presence and severity of posttraumatic stress disorder (PTSD) are elusive, yet badly needed. Electroencephalographic (EEG) coherence represents a promising approach to identifying and understanding brain biomarker activity in PTSD. Overnight polysomnography data containing EEG across sleep and wake states was collected in n = 76 Veterans with and without PTSD from a single site under IRB approval. Brain coherence markers (BCM) were calculated from EEG signals using a novel approach to produce one index for PTSD diagnosis (PTSDdx), and another index for PTSD severity (PTSDsev). PTSDdx showed strong sensitivity to the presence of PTSD in the awake state, during non-rapid eye movement (NREM) stage N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. PTSDsev showed a strong correlation with PTSD symptom severity (using the PTSD Checklist 5, or PCL5 survey) in the awake state, during N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. Thus, sleep EEG-based brain coherence markers can be utilized as an objective means for determining the presence and severity of PTSD. This portable, inexpensive, and non-invasive tool holds promise for better understanding the physiological mechanisms underlying PTSD and for tracking objective responses to treatment.
Predicting protein-peptide interaction sites using distant protein complexes as structural templates
Authors: Johansson-Åkhe Isak , Mirabello Claudio , Wallner Björn
Published: March 2019

Protein-peptide interactions play an important role in major cellular processes, and are associated with several human diseases. To understand and potentially regulate these cellular function and diseases it is important to know the molecular details of the interactions. However, because of peptide flexibility and the transient nature of protein-peptide interactions, peptides are difficult to study experimentally. Thus, computational methods for predicting structural information about protein-peptide interactions are needed. Here we present InterPep, a pipeline for predicting protein-peptide interaction sites. It is a novel pipeline that, given a protein structure and a peptide sequence, utilizes structural template matches, sequence information, random forest machine learning, and hierarchical clustering to predict what region of the protein structure the peptide is most likely to bind. When tested on its ability to predict binding sites, InterPep successfully pinpointed 255 of 502 (50.7%) binding sites in experimentally determined structures at rank 1 and 348 of 502 (69.3%) among the top five predictions using only structures with no significant sequence similarity as templates. InterPep is a powerful tool for identifying peptide-binding sites; with a precision of 80% at a recall of 20% it should be an excellent starting point for docking protocols or experiments investigating peptide interactions. The source code for InterPred is available at http://wallnerlab.org/InterPep/.
Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene
Authors: Yong Jing , Tian Jide , Dang Hoa , Wu Ting-Ting , Atkinson Mark A. , Sun Ren , Kaufman Daniel L.
Published: March 2019

There has been considerable debate as to whether obesity can act as an accelerator of type 1 diabetes (T1D). We assessed this possibility using transgenic mice (MIP-TF mice) whose ß-cells express enhanced green fluorescent protein (EGFP). Infecting these mice with EGFP-expressing murine herpes virus-68 (MHV68-EGFP) caused occasional transient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not spread to other ß-cell antigens. We hypothesized that obesity-related systemic inflammation and ß-cell stress could exacerbate the MHV68-EGFP-induced ß-cell autoreactivity. We crossed MIP-TF mice with Avymice which develop obesity and provide models of metabolic disease alongside early stage T2D. Unlike their MIP-TF littermates, MHV68-EGFP–infected Avy/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia. MHV68-EGFP infection induced a more pronounced intra-insulitis in older, more obese, Avy/MIP-TF mice. Moreover, in MHV68-EGFP-infected Avy/MIP-TF mice, Th1 reactivity spread from EGFP to other ß-cell antigens. Thus, the spreading of autoreactivity among ß-cell antigens corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese Avy/MIP-TF mice but not lean MIP-TF mice. These observations are consistent with the notion that obesity-associated systemic inflammation and ß-cell stress lowers the threshold necessary for T cell autoreactivity to spread from EGFP to other ß-cell autoantigens.
Salvage Carbon-Ion Radiation Therapy For Locoregionally Recurrent Head and Neck Malignancies
Authors: Gao Jing , Hu Jiyi , Guan Xiyin , Yang Jing , Hu Weixu , Kong Lin , Lu Jiade J.
Published: March 2019

To investigate the safety and efficacy of salvage carbon-ion radiation therapy (CIRT) in patients with locoregionally recurrent head and neck malignancies. One hundred and forty-one patients with locally recurrent head and neck malignancies previously treated with radiotherapy were salvaged using intensity-modulated carbon-ion radiation therapy (CIRT). The median dose was 60 Gray-Equivalent (GyE) (range 50–69 GyE, 2.0~3.5 GyE/daily fraction). All patients completed planned CIRT except for one. With a median follow-up time of 14.7 (range 1.6–36.4) months, the 1-year overall survival rate was 95.9%. Local, regional, and distant progression free survival rates were 84.9% and 97.7%, and 96%, respectively. Grade 3 or higher acute and late toxicities were observed in 7.1% of the patients. Ten patients developed mucosal necrosis and 4 of these patients deceased. Due to its physical and biological characteristics, CIRT appeared to be an acceptable treatment option for patients with locoregionally recurrent head and neck malignancies after previous radiotherapy. Treatment-induced adverse effects and early response to CIRT were both favorable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.
Manipulation of cell migration by laserporation-induced local wounding
Authors: Pervin Mst. Shaela , Yumura Shigehiko
Published: March 2019

Living organisms employ various mechanisms to escape harm. At the cellular level, mobile cells employ movement to avoid harmful chemicals or repellents. The present study is the first to report that cells move away from the site of injury in response to local wounding. When a migrating Dictyostelium cell was locally wounded at its anterior region by laserporation, the cell retracted its anterior pseudopods, extended a new pseudopod at the posterior region, and migrated in the opposite direction with increasing velocity. When wounded in the posterior region, the cell did not change its polarity and moved away from the site of wounding. Since the cells repair wounds within a short period, we successfully manipulated cell migration by applying multiple wounds. Herein, we discussed the signals that contributed to the wound-induced escape behavior of Dictyostelium cells. Our findings provide important insights into the mechanisms by which cells establish their polarity.
Developing attentional control in naturalistic dynamic road crossing situations
Authors: Nicholls Victoria I. , Jean-Charles Geraldine , Lao Junpeng , de Lissa Peter , Caldara Roberto , Miellet Sebastien
Published: March 2019

In the last 20 years, there has been increasing interest in studying visual attentional processes under more natural conditions. In the present study, we propose to determine the critical age at which children show similar to adult performance and attentional control in a visually guided task; in a naturalistic dynamic and socially relevant context: road crossing. We monitored visual exploration and crossing decisions in adults and children aged between 5 and 15 while they watched road traffic videos containing a range of traffic densities with or without pedestrians. 5–10 year old (y/o) children showed less systematic gaze patterns. More specifically, adults and 11–15 y/o children look mainly at the vehicles’ appearing point, which is an optimal location to sample diagnostic information for the task. In contrast, 5–10 y/os look more at socially relevant stimuli and attend to moving vehicles further down the trajectory when the traffic density is high. Critically, 5-10 y/o children also make an increased number of crossing decisions compared to 11–15 y/os and adults. Our findings reveal a critical shift around 10 y/o in attentional control and crossing decisions in a road crossing task.
Small vessel disease and intracoronary plaque composition: a single centre cross-sectional observational study
Authors: Wightman A. , Barlis P. , MacBain M. , Hodgson L. , Cheng L. , Gocuk S. , Hayat U. , Chow D. , Tacey M. , Hutchinson A. , Colville D. , Lamoureux E. , Savige J.
Published: March 2019

Cardiac events are commonly triggered by rupture of intracoronary plaque. Many studies have suggested that retinal small vessel abnormalities predict cardiac events. The present study examined retinal microvascular abnormalities associated with intracoronary plaque. This was a single centre cross-sectional observational study of consecutive subjects who underwent coronary angiography and intracoronary optical coherence tomography (OCT) of occlusive coronary artery disease. Subjects’ retinal images were deidentified and graded for microvascular retinopathy (Wong and Mitchell classification), and vessel calibre using a semiautomated method based on Knudtson’s modification of the Parr Hubbard formula. Control subjects had no significant plaque on angiography. Analysis used the Fisher’s exact test or student t-test. Thirty-two subjects with intracoronary plaque including 22 males (79%) had a mean age of 62.6 ± 9.4 years. Twenty-four (86%) had hypertension, 10 (36%) had diabetes, and 21 (75%) were current or former smokers. Their average mean arterial pressure was 90.5 ± 5.8 mm Hg, and mean eGFR was 74 ± 15/min/1.73 m2. On angiography, 23 (82%) had a left anterior descending artery (LAD) stenosis, their mean diseased vessel score was 1.86 ± 1.21, and mean total stent number was 1.04 ± 1.00. Plaque type was mainly (>50%) fibrous (n = 7), lipid (n = 7), calcific (n = 10), or mixed (n = 4). Control subjects had a lower mean diastolic BP (p = 0.01), were less likely to have an LAD stenosis (p < 0.001), a lower mean diseased vessel score (p < 0.001) and fewer stents (p = 0.02). Subjects with plaque were more likely to have a moderate microvascular retinopathy than those with none (p = 0.004). Moderate retinopathy was more common with lipid (p = 0.05) or calcific (p = 0.003) plaque. Individuals with calcific plaque had a larger arteriole calibre (158.4 ± 15.2 µm) than those with no plaque (143.8 ± 10.6 µm, p = 0.02), but calibre was not related to diabetes or smoking. Calibre did not correlate with plaque length, thickness or arc angle. Thus, subjects with intracoronary artery plaque are more likely to have a moderate microvascular retinopathy. Those with calcific plaque have larger retinal arterioles which is consistent with our previous finding of larger vessel calibre in triple coronary artery disease. Retinal microvascular imaging warrants further evaluation in identifying severe coronary artery disease.
A novel RT-QPCR-based assay for the relative quantification of residue specific m6A RNA methylation
Authors: Castellanos-Rubio Ainara , Santin Izortze , Olazagoitia-Garmendia Ane , Romero-Garmendia Irati , Jauregi-Miguel Amaia , Legarda Maria , Bilbao Jose Ramon
Published: March 2019

N6-methyladenosine (m6A) is the most common and abundant RNA modification. Recent studies have shown its importance in the regulation of several biological processes, including the immune response, and different approaches have been developed in order to map and quantify m6A marks. However, site specific detection of m6A methylation has been technically challenging, and existing protocols are long and tedious and often involve next-generation sequencing. Here, we describe a simple RT-QPCR based approach for the relative quantification of candidate m6A regions that takes advantage of the diminished capacity of BstI enzyme to retrotranscribe m6A residues. Using this technique, we have been able to confirm the recently described m6A methylation in the 3′UTR of SOCS1 and SOCS3 transcripts. Moreover, using the method presented here, we have also observed alterations in the relative levels of m6A in specific motifs of SOCS genes in celiac disease patients and in pancreatic β-cells exposed to inflammatory stimuli.
Transcriptome analysis of the curry tree (Bergera koenigii L., Rutaceae) during leaf development
Authors: Shivakumar Vikram S. , Johnson Gabriel , Zimmer Elizabeth A.
Published: March 2019

The curry tree (Bergera koenigii L.) is a widely cultivated plant used in South Asian cooking. Next-generation sequencing was used to generate the transcriptome of the curry leaf to detect changes in gene expression during leaf development, such as those genes involved in the production of oils which lend the leaf its characteristic taste, aroma, and medicinal properties. Using abundance estimation (RSEM) and differential expression analysis, genes that were significantly differentially expressed were identified. The transcriptome was annotated with BLASTx using the non-redundant (nr) protein database, and Gene Ontology (GO) terms were assigned based on the top BLAST hit using Blast2GO. Lastly, functional enrichment of the assigned GO terms was analyzed for genes that were significantly differentially expressed. Of the most enriched GO categories, pathways involved in cell wall, membrane, and lignin synthesis were found to be most upregulated in immature leaf tissue, possibly due to the growth and expansion of the leaf tissue. Terpene synthases, which synthesize monoterpenes and sesquiterpenes, which comprise much of the curry essential oil, were found to be significantly upregulated in mature leaf tissue, suggesting that oil production increases later in leaf development. Enzymes involved in pigment production were also significantly upregulated in mature leaves. The findings were based on computational estimates of gene expression from RNA-seq data, and further study is warranted to validate these results using targeted techniques, such as quantitative PCR.
Effects of iron spin transition on the electronic structure, thermal expansivity and lattice thermal conductivity of ferropericlase: a first principles study
Authors: Song Yalan , He Kaihua , Sun Jian , Ma Chaojie , Wan Miao , Wang Qingbo , Chen Qili
Published: March 2019

The effects of the spin transition on the electronic structure, thermal expansivity and lattice thermal conductivity of ferropericlase are studied by first principles calculations at high pressures. The electronic structures indicate that ferropericlase is an insulator for high-spin and low-spin states. Combined with the quasiharmonic approximation, our calculations show that the thermal expansivity is larger in the high-spin state than in the low-spin state at ambient pressure, while the magnitude exhibits a crossover between high-spin and low-spin with increasing pressure. The calculated lattice thermal conductivity exhibits a drastic reduction upon the inclusion of ferrous iron, which is consistent with previous experimental studies. However, a subsequent enhancement in the thermal conductivity is obtained, which is associated with the spin transition. Mechanisms are discussed for the variation in thermal conductivity by the inclusion of ferrous iron and the spin transition.
Forest litter and shrubs act as an understory filter for the survival of Quercus mongolica seedlings in Mt. Kwan-ak, South Korea
Authors: Song Uhram
Published: March 2019

Forest succession fromPinustoQuercushas often been observed in temperate forest, although the succession mechanism is not clearly understood. This study investigated factors that affect the succession of forests from pine to oak, using forest vegetation inventory data at plots at Kwan-ak mountain in Korea. Analyses of understory canopy coverage, light intensity, and tree numbers and ages inP. densifloraforests indicate thatQ. mongolicacan only invade these forests before understory shrub establishment. The results from analyses of all environmental factors indicate that similar adverse effects from environmental factors occur in establishedP. densifloraandQ. mongolicaforests that inhibitQ. mongolicaseedling survival. However, the observed survival rate ofQ. mongolicaseedlings underP. densifloraduring winter were much higher thanQ. mongolicaseedlings underQ. mongolicatrees, and it is due to accumulated snow overQ. mongolicaforest litter which breaks or inhibits the emergence ofQ. mongolicaseedlings. Protecting seedlings with plastic cups significantly increased the survival rate which confirms that forest floor litter acts as a filter for the regeneration and succession ofQ. mongolicaforests. This paper thus concludes that understory shrubs and forest litter affect the succession dynamics ofP. densifloraandQ. mongolicaforests.
Measurement of Glomerular Filtration Rate using Quantitative SPECT/CT and Deep-learning-based Kidney Segmentation
Authors: Park Junyoung , Bae Sungwoo , Seo Seongho , Park Sohyun , Bang Ji-In , Han Jeong Hee , Lee Won Woo , Lee Jae Sung
Published: March 2019

Quantitative SPECT/CT is potentially useful for more accurate and reliable measurement of glomerular filtration rate (GFR) than conventional planar scintigraphy. However, manual drawing of a volume of interest (VOI) on renal parenchyma in CT images is a labor-intensive and time-consuming task. The aim of this study is to develop a fully automated GFR quantification method based on a deep learning approach to the 3D segmentation of kidney parenchyma in CT. We automatically segmented the kidneys in CT images using the proposed method with remarkably high Dice similarity coefficient relative to the manual segmentation (mean = 0.89). The GFR values derived using manual and automatic segmentation methods were strongly correlated (R2 = 0.96). The absolute difference between the individual GFR values using manual and automatic methods was only 2.90%. Moreover, the two segmentation methods had comparable performance in the urolithiasis patients and kidney donors. Furthermore, both segmentation modalities showed significantly decreased individual GFR in symptomatic kidneys compared with the normal or asymptomatic kidney groups. The proposed approach enables fast and accurate GFR measurement.
Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host
Authors: Cohen Aviad , Troib Shani , Dotan Shahar , Najmuldeen Hastyar , Yesilkaya Hasan , Kushnir Tatyana , Shagan Marilou , Portnoi Maxim , Nachmani Hannie , Benisty Rachel , Tal Michael , Ellis Ronald , Chalifa-Caspi Vered , Dagan Ron , Nebenzahl Yaffa Mizrachi
Published: March 2019

Trigger factor (TF) has a known cytoplasmic function as a chaperone. In a previous study we showed that pneumococcal TF is also cell-wall localized and this finding combined with the immunogenic characteristic of TF, has led us to determine the vaccine potential of TF and decipher its involvement in pneumococcal pathogenesis. Bioinformatic analysis revealed that TF is conserved among pneumococci and has no human homologue. Immunization of mice with recombinant (r)TF elicited a protective immune response against a pneumococcal challenge, suggesting that TF contributes to pneumococcal pathogenesis. Indeed, rTF and an anti-rTF antiserum inhibited bacterial adhesion to human lung derived epithelial cells, indicating that TF contributes to the bacterial adhesion to the host. Moreover, bacteria lacking TF demonstrated reduced adhesion, in vitro, to lung-derived epithelial cells, neural cells and glial cells. The reduced adhesion could be restored by chromosomal complementation. Furthermore, bacteria lacking TF demonstrated significantly reduced virulence in a mouse model. Taken together, the ability of rTF to elicit a protective immune response, involvement of TF in bacterial adhesion, conservation of the protein among pneumococcal strains and the lack of human homologue, all suggest that rTF can be considered as a future candidate vaccine with a much broader coverage as compared to the currently available pneumococcal vaccines.
Widespread shifts in the coastal biota of northern California during the 2014–2016 marine heatwaves
Authors: Sanford Eric , Sones Jacqueline L. , García-Reyes Marisol , Goddard Jeffrey H. R. , Largier John L.
Published: March 2019

During 2014–2016, severe marine heatwaves in the northeast Pacific triggered well-documented disturbances including mass mortalities, harmful algal blooms, and declines in subtidal kelp beds. However, less attention has been directed towards understanding how changes in sea surface temperature (SST) and alongshore currents during this period influenced the geographic distribution of coastal taxa. Here, we examine these effects in northern California, USA, with a focus on the region between Point Reyes and Point Arena. This region represents an important biogeographic transition zone that lies <150 km north of Monterey Bay, California, where numerous southern species have historically reached their northern (poleward) range limits. We report substantial changes in geographic distributions and/or abundances across a diverse suite of 67 southern species, including an unprecedented number of poleward range extensions (37) and striking increases in the recruitment of owl limpets (Lottia gigantea) and volcano barnacles (Tetraclita rubescens). These ecological responses likely arose through the combined effects of extreme SST, periods of anomalous poleward flow, and the unusually long duration of heatwave events. Prolonged marine heatwaves and enhanced poleward dispersal may play an important role in longer-term shifts in the composition of coastal communities in northern California and other biogeographic transition zones.
Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures
Authors: Schroeder Michael P. , Bastian Lorenz , Eckert Cornelia , Gökbuget Nicola , James Alva Rani , Tanchez Jutta Ortiz , Schlee Cornelia , Isaakidis Konstandina , Häupl Björn , Baum Katharina , Migueles Lozano Oscar Arturo , Kouidri Khouloud , Pan Kuan-Ting , Urlaub Henning , Schwartz Stefan , Burmeister Thomas , von Stackelberg Arend , Hoelzer Dieter , Pfeiffer Heike , Rieger Michael A. , Göllner Stefanie , Oellerich Thomas , Horstman Martin , Schrappe Martin , Wolf Jana , Kirschner-Schwabe Renate , Brüggemann Monika , Müller-Tidow Carsten , Serve Hubert , Neumann Martin , Baldus Claudia D.
Published: March 2019

Recent efforts reclassified B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) into more refined subtypes. Nevertheless, outcomes of relapsed BCP-ALL remain unsatisfactory, particularly in adult patients where the molecular basis of relapse is still poorly understood. To elucidate the evolution of relapse in BCP-ALL, we established a comprehensive multi-omics dataset including DNA-sequencing, RNA-sequencing, DNA methylation array and proteome MASS-spec data from matched diagnosis and relapse samples of BCP-ALL patients (n = 50) including the subtypes DUX4, Ph-like and two aneuploid subtypes. Relapse-specific alterations were enriched for chromatin modifiers, nucleotide and steroid metabolism including the novel candidates FPGS, AGBL and ZNF483. The proteome expression analysis unraveled deregulation of metabolic pathways at relapse including the key proteins G6PD, TKT, GPI and PGD. Moreover, we identified a novel relapse-specific gene signature specific for DUX4 BCP-ALL patients highlighting chemotaxis and cytokine environment as a possible driver event at relapse. This study presents novel insights at distinct molecular levels of relapsed BCP-ALL based on a comprehensive multi-omics integrated data set including a valuable proteomics data set. The relapse specific aberrations reveal metabolic signatures on genomic and proteomic levels in BCP-ALL relapse. Furthermore, the chemokine expression signature in DUX4 relapse underscores the distinct status of DUX4-fusion BCP-ALL.
The source effect as a natural function of disgust in interpersonal context and its impairment in mental disorders
Authors: Lenk Maria , Ritschel Gerhard , Abele Marion , Roever Peggy , Schellong Julia , Joraschky Peter , Weidner Kerstin , Croy Ilona
Published: March 2019

Disgust affects interpersonal relationships and regulates hygienic, sexual and distance behaviour. Its intensity in the interpersonal context depends on the character of the relationship. Strangers normally evoke more disgust than intimates (known as the source effect). General disgust sensitivity is increased in various mental diseases. It is unclear how disgust in the interpersonal context is affected and whether the source effect is preserved. 460 inpatients with mental disorders and 463 healthy subjects answered a newly developed Questionnaire (DIRQ) that covers disgust in the interpersonal context on content categories (hygiene, physical proximity, sexuality) and on source categories (self, partner, parent, stranger). Mental disorders were diagnosed with structured interviews. Healthy controls exhibited a pronounced source effect, with strangers evoking more disgust than intimates. In patients, this source effect was reduced (Cohen’s d = 0.3), especially for sexual disgust, while general disgust sensitivity was increased (d = 0.5). High disgust in patients was best predicted by a history of sexual abuse and by the presence of post-traumatic stress disorder. In conclusion, mentally impaired patients show increased and trauma-associated disgust sensitivity. Their downregulation of sexual disgust in intimate relationships is hindered, which may have a boundary protective function but might also fuel difficulties engaging in relationships or intimacy.
Honey bee-collected pollen is a potential source of Ascosphaera apis infection in managed bumble bees
Authors: Pereira Kleber de Sousa , Meeus Ivan , Smagghe Guy
Published: March 2019

The trade of bumble bees started in the early nineties for pollinator-dependent greenhouse plants. Nowadays, its rearing and transport have received public attention, since managed bees can transfer pathogens to wild bee populations. Therefore, guaranteeing pathogen-free bumble bees is fundamental. The major protein source used in rearing facilities is honey bee-collected pollen. This can carry pathogens, however to date, solid data on the risk of this food source to the health of bumble bees is lacking. Here we performed a large pathogen screening of non-irradiated honey bee-collected pollen to discover particles infective to Bombus terrestris. We identified seven parasites (Apicystis bombi, Ascosphaera apis, Crithidia mellificae, Nosema ceranae, Paenibacillus larvae and two parasites resembling Nosema thomsoni and Microsporidium sp. Oise) and four viruses (CBPV, DWV, IAPV and SBV) in 17 pollen batches from two major European pollen source regions (Spain and Romania). Ascosphaera apis was capable of infecting bumble bees; the larvae showed similar symptoms to chalkbrood disease reported in honey bees. Bumble bee breeding facilities need to be cautious about the potential presence of this disease, which was originally reported in honey bees. Thorough diagnostic and control methods are needed, as risk of spillover to wild bee species is possible.
Growth-inhibition of cell lines derived from B cell lymphomas through antagonism of serotonin receptor signaling
Authors: Kolan Shrikant S. , Lidström Tommy , Mediavilla Tomás , Dernstedt Andy , Degerman Sofie , Hultdin Magnus , Björk Karl , Marcellino Daniel , Forsell Mattias N. E.
Published: March 2019

A majority of lymphomas are derived from B cells and novel treatments are required to treat refractory disease. Neurotransmitters such as serotonin and dopamine influence activation of B cells and the effects of a selective serotonin 1A receptor (5HT1A) antagonist on growth of a number of B cell-derived lymphoma cell lines were investigated. We confirmed the expression of 5HT1A in human lymphoma tissue and in several well-defined experimental cell lines. We discovered that the pharmacological inhibition of 5HT1A led to the reduced proliferation of B cell-derived lymphoma cell lines together with DNA damage, ROS-independent caspase activation and apoptosis in a large fraction of cells. Residual live cells were found ‘locked’ in a non-proliferative state in which a selective transcriptional and translational shutdown of genes important for cell proliferation and metabolism occurred (e.g., AKT, GSK-3β, cMYC and p53). Strikingly, inhibition of 5HT1A regulated mitochondrial activity through a rapid reduction of mitochondrial membrane potential and reducing dehydrogenase activity. Collectively, our data suggest 5HT1A antagonism as a novel adjuvant to established cancer treatment regimens to further inhibit lymphoma growth.
Genome-wide Identification of Tebufenozide Resistant Genes in the smaller tea tortrix, Adoxophyes honmai (Lepidoptera: Tortricidae)
Authors: Uchibori-Asano Miwa , Jouraku Akiya , Uchiyama Toru , Yokoi Kakeru , Akiduki Gaku , Suetsugu Yoshitaka , Kobayashi Tetsuya , Ozawa Akihito , Minami Saki , Ishizuka Chiharu , Nakagawa Yoshiaki , Daimon Takaaki , Shinoda Tetsuro
Published: March 2019

The smaller tea tortrix, Adoxophyes honmai, has developed strong resistance to tebufenozide, a diacylhydrazine-type (DAH) insecticide. Here, we investigated its mechanism by identifying genes responsible for the tebufenozide resistance using various next generation sequencing techniques. First, double-digest restriction site-associated DNA sequencing (ddRAD-seq) identified two candidate loci. Then, synteny analyses using A. honmai draft genome sequences revealed that one locus contained the ecdysone receptor gene (EcR) and the other multiple CYP9A subfamily P450 genes. RNA-seq and direct sequencing of EcR cDNAs found a single nucleotide polymorphism (SNP), which was tightly linked to tebufenozide resistance and generated an amino acid substitution in the ligand-binding domain. The binding affinity to tebufenozide was about 4 times lower in in vitro translated EcR of the resistant strain than in the susceptible strain. RNA-seq analyses identified commonly up-regulated genes in resistant strains, including CYP9A and choline/carboxylesterase (CCE) genes. RT-qPCR analysis and bioassays showed that the expression levels of several CYP9A and CCE genes were moderately correlated with tebufenozide resistance. Collectively, these results suggest that the reduced binding affinity of EcR is the main factor and the enhanced detoxification activity by some CYP9As and CCEs plays a supplementary role in tebufenozide resistance in A. honmai.
Custom fabrication and mode-locked operation of a femtosecond fiber laser for multiphoton microscopy
Authors: Davoudzadeh Nima , Ducourthial Guillaume , Spring Bryan Q.
Published: March 2019

Solid-state femtosecond lasers have stimulated the broad adoption of multiphoton microscopy in the modern laboratory. However, these devices remain costly. Fiber lasers offer promise as a means to inexpensively produce ultrashort pulses of light suitable for nonlinear microscopy in compact, robust and portable devices. Although encouraging, the initial methods reported in the biomedical engineering community to construct home-built femtosecond fiber laser systems overlooked fundamental aspects that compromised performance and misrepresented the significant financial and intellectual investments required to build these devices. Here, we present a practical protocol to fabricate an all-normal-dispersion ytterbium (Yb)-doped femtosecond fiber laser oscillator using commercially-available parts (plus standard optical components and extra-cavity accessories) as well as basic fiber splicing and laser pulse characterization equipment. We also provide a synthesis of established protocols in the laser physics community, but often overlooked in other fields, to verify true versus seemingly (partial or noise-like) mode-locked performance. The approaches described here make custom fabrication of femtosecond fiber lasers more accessible to a wide range of investigators and better represent the investments required for the proper laser design, fabrication and operation.
Association between HOMA-IR and Frailty among U.S. Middle-aged and Elderly Population
Authors: Peng Po-Sen , Kao Tung-Wei , Chang Pi-Kai , Chen Wei-Liang , Peng Po-Jui , Wu Li-Wei
Published: March 2019

Previous literatures revealed that homeostasis model assessment-estimated insulin resistance (HOMA-IR) was one of the cardio-metabolic risk factors. This study was conducted to access the association between HOMA-IR and frailty in the United States of America (U.S.) middle-aged and elderly high-risk insulin-resistant population. In the National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994, the study included 3,893 participants. In order to exam the association between HOMA-IR and frailty in the middle-aged and elderly population through the regression model adjusted for multiple covariates, we divided the participants into middle aged group (Age <65 years) and elderly group (Age > = 65 years) in this study. Each group was then divided into tertiles depending on their HOMA-IR levels. Higher level of HOMA-IR was significantly associated with frailty in the elderly group, but this association was not seen in the middle-aged population. These results demonstrated that the HOMA-IR level can be a novel risk assessment of frailty in elderly high-risk insulin-resistant individuals (Age > = 65 years).
Thermal tolerance and range expansion of invasive foraminifera under climate changes
Authors: Titelboim Danna , Almogi-Labin Ahuva , Herut Barak , Kucera Michal , Asckenazi-Polivoda Sarit , Abramovich Sigal
Published: March 2019

The Eastern Mediterranean is experiencing a large-scale invasion of alien tropical species from the Red Sea. This “Lessepsian invasion” began with the opening of the Suez Canal and is promoted by the ongoing oceanic warming. The environmental differences between the Red Sea and the Mediterranean act as a buffer allowing the invasion of certain species. This provides an opportunity to study the differences in temperature sensitivity between two sibling species of the cosmopolitian foraminifera Amphistegina. Both species are very common in the Red Sea. Whilest, only one is a successful invader and the other is absent in the Eastern Mediterranean. Here we show that the two species are different in their temperature sensitivity, which explains their selective invasion into the Mediterranean. These differences demonstrate that in respect to climate change resilient marine species can be distinguished by their ability to compensate for temperature changes by adjusting their physiological performance and by having tolerance to a wider temperature range. Moreover, we demonstrate that selective filtering mechanisms during invasion can prefer species that are more resilient to colder rather than expected warmer temperatures.
Investigating spontaneous retinal venous pulsation using Doppler optical coherence tomography
Authors: Wartak Andreas , Beer Florian , Desissaire Sylvia , Baumann Bernhard , Pircher Michael , Hitzenberger Christoph K.
Published: March 2019

We demonstrate the advantages of optical coherence tomography (OCT) imaging for investigation of spontaneous retinal venous pulsation (SRVP). The pulsatile changes in venous vessel caliber are analyzed qualitatively and quantitatively using conventional intensity-based OCT as well as the functional extension Doppler OCT (DOCT). Single-channel and double-channel line scanning protocols of our multi-channel OCT prototype are employed to investigate venous pulsatile caliber oscillations as well as venous flow pulsatility in the eyes of healthy volunteers. A comparison to recordings of scanning laser ophthalmoscopy (SLO) – a standard en-face imaging modality for evaluation of SRVP – is provided, emphasizing the advantages of tomographic image acquisition. To the best of our knowledge, this is the first quantitative time-resolved investigation of SRVP and associated retinal perfusion characteristics using OCT.
G-protein Gα13 functions as a cytoskeletal and mitochondrial regulator to restrain osteoclast function
Authors: Nakano Shinichi , Inoue Kazuki , Xu Cheng , Deng Zhonghao , Syrovatkina Viktoriya , Vitone Gregory , Zhao Liang , Huang Xin-Yun , Zhao Baohong
Published: March 2019

Excessive osteoclastic bone erosion disrupts normal bone remodeling and leads to bone loss in many skeletal diseases, including inflammatory arthritis, such as rheumatoid arthritis (RA) and psoriatic arthritis, periodontitis and peri-prosthetic loosening. Functional control of osteoclasts is critical for the maintenance of bone homeostasis. However, the mechanisms that restrain osteoclast resorptive function are not fully understood. In this study, we identify a previously unrecognized role for G-protein Gα13 in inhibition of osteoclast adhesion, fusion and bone resorptive function. Gα13 is highly expressed in mature multinucleated osteoclasts, but not during early differentiation. Deficiency of Gα13 in myeloid osteoclast lineage (Gα13ΔM/ΔM mice) leads to super spread morphology of multinucleated giant osteoclasts with elevated bone resorptive capacity, corroborated with an osteoporotic bone phenotype in the Gα13ΔM/ΔM mice. Mechanistically, Gα13 functions as a brake that restrains the c-Src, Pyk2, RhoA-Rock2 mediated signaling pathways and related gene expressions to control the ability of osteoclasts in fusion, adhesion, actin cytoskeletal remodeling and resorption. Genome wide analysis reveals cytoskeleton related genes that are suppressed by Gα13, identifying Gα13 as a critical cytoskeletal regulator in osteoclasts. We also identify a genome wide regulation of genes responsible for mitochondrial biogenesis and function by Gα13 in osteoclasts. Furthermore, the significant correlation between Gα13 expression levels, TNF activity and RA disease activity in RA patients suggests that the Gα13 mediated mechanisms represent attractive therapeutic targets for diseases associated with excessive bone resorption.
Socialisation and its effect on play behaviour and aggression in the domestic pig (Sus scrofa)
Authors: Weller Jennifer E. , Camerlink Irene , Turner Simon P. , Farish Marianne , Arnott Gareth
Published: March 2019

There is considerable interest in how early life experiences shape behavioural development. For example, the socialisation of unfamiliar pigs pre-weaning has been suggested to decrease aggression during later life. However, the behavioural mechanisms behind this socialisation effect remain unexplored. We allowed 12 litters of domestic pigs (Sus scrofa) to move freely between their home pen and a neighbouring pen (socialisation) during the lactation period, while keeping 12 litters isolated in their home pen (control). Contrary to predictions, socialisation did not result in higher levels of social play. However, control individuals engaged in more sow directed play than those that underwent socialisation. Consistent with predictions, males performed more piglet directed play than females. Social play behaviour pre-weaning was found to be highly concordant within individuals from both treatments. Post-weaning, 148 pigs were selected to perform two resident-intruder tests to assay aggressiveness. As predicted, socialised individuals were quicker to attack than controls, although females were more aggressive than males. Additionally, play fighting experience was found to negatively correlate with attack latency in females, supporting the hypothesis that early-life play experience is likely to be sexually dimorphic when males and females show pronounced differences in their later-life social behaviour.
Pattern analysis of 532- and 1,064-nm picosecond-domain laser-induced immediate tissue reactions in ex vivo pigmented micropig skin
Authors: Lee Hee Chul , Childs James , Chung Hye Jin , Park Jinyoung , Hong Jumi , Cho Sung Bin
Published: March 2019

Optical pulses from picosecond lasers can be delivered to the skin as single, flat-top beams or fractionated beams using a beam splitter or microlens array (MLA). In this study, picosecond neodymium:yttrium aluminum garnet laser treatment using a single flat-top beam and an MLA-type beam at the wavelengths of 532 nm and 1,064 nm were delivered on ex vivo genotype-regulated, pigmented micropig skin. Skin specimens were obtained immediately after treatment and microscopically analyzed. Single flat-top beam treatment at a wavelength of 532 nm and a fluence of 0.05-J/cm2 reduced melanin pigments in epidermal keratinocytes and melanocytes, compared to untreated controls. Additionally, 0.1 J/cm2- and 1.3 J/cm2-fluenced laser treatment at 532 nm elicited noticeable vacuolation of keratinocytes and melanocytes within all epidermal layers. Single flat-top beam picosecond laser treatment at a wavelength of 1,064 nm and a fluence of 0.18 J/cm2 also reduced melanin pigments in keratinocytes and melanocytes. Treatment at 1,064-nm and fluences of 1.4 J/cm2 and 2.8 J/cm2 generated increasing degrees of vacuolated keratinocytes and melanocytes. Meanwhile, 532- and 1,064-nm MLA-type, picosecond laser treatment elicited fractionated zones of laser-induced micro-vacuolization in the epidermis and dermis. Therein, the sizes and degrees of tissue reactions differed according to wavelength, fluence, and distance between the microlens and skin.
Electrochemotherapy in the treatment of locally advanced or recurrent eyelid-periocular basal cell carcinomas
Authors: Kis Erika Gabriella , Baltás Eszter , Ócsai Henriette , Vass Attila , Németh István Balázs , Varga Erika , Oláh Judit , Kemény Lajos , Tóth-Molnár Edit
Published: March 2019

There is increasing evidence about the effectiveness of electrochemotherapy (ECT) in the treatment of basal cell carcinomas in the head and neck region, although its role in the management of eyelid-periocular skin tumors has to be clarified. The aim of the present study is to evaluate the results of ECT in the treatment of locally advanced primary and recurrent eyelid-periocular skin basal cell carcinomas. Twelve patients with basal cell carcinoma involving the eyelid-periocular skin region were treated with ECT. Three patients had locally advanced primary tumors, while 9 patients had recurrent tumors. All treatments were performed according to the ESOPE guidelines, using Cliniporator TM device. All patients received bleomycin based ECT. The route of administration was intratumoral in 3 patients and intravenous in 9 patients. Tumor response was evaluated using the RECIST 1.1. criteria. ECT resulted in complete response of the periocular skin tumors in all patients. Lower eyelid ectropion was developed in 3 patients which had to be corrected surgically. ECT can be used effectively in the treatment of locally advanced or recurrent basal cell carcinomas in the eyelid-periocular skin region. Excellent tumor control can be achieved with good functional and cosmetic results without systemic adverse events with short interval follow-up.
Global Ubiquitome Profiling Revealed the Roles of Ubiquitinated Proteins in Metabolic Pathways of Tea Leaves in Responding to Drought Stress
Authors: Xie Hui , Wang Yu , Ding Yiqian , Qiu Chen , Sun Litao , Gai Zhongshuai , Gu Honglian , Ding Zhaotang
Published: March 2019

Drought stress often affects the expression of genes and proteins in tea plants. However, the global profiling of ubiquitinated (Kub) proteins in tea plants remains unearthed. Here, we performed the ubiquitome in tea leaves under drought stress using antibody-based affinity enrichment coupled with LC-MS/MS analysis. In total, 1,409 lysine Kub sites in 781 proteins were identified, of which 14 sites in 12 proteins were up-regulated and 123 sites in 91 proteins down-regulated under drought stress. The identified Kub proteins were mainly located in the cytosol (31%), chloroplast (27%) and nuclear (19%). Moreover, 5 conserved motifs in EKub, EXXXKub, KubD, KubE and KubA were extracted. Several Kub sites in ubiquitin-mediated proteolysis-related proteins, including RGLG2, UBC36, UEV1D, RPN10 and PSMC2, might affect protein degradation and DNA repair. Plenty of Kub proteins related to catechins biosynthesis, including PAL, CHS, CHI and F3H, were positively correlated with each other due to their co-expression and co-localization. Furthermore, some Kub proteins involved in carbohydrate and amino acid metabolism, including FBPase, FBA and GAD1, might promote sucrose, fructose and GABA accumulation in tea leaves under drought stress. Our study preliminarily revealed the global profiling of Kub proteins in metabolic pathways and provided an important resource for further study on the functions of Kub proteins in tea plants.
Evidence for Escherichia coli DcuD carrier dependent FOF1-ATPase activity during fermentation of glycerol
Authors: Karapetyan L. , Valle A. , Bolivar J. , Trchounian A. , Trchounian K.
Published: March 2019

During fermentation Escherichia coli excrete succinate mainly via Dcu family carriers. Current work reveals the total and N,N’-dicyclohexylcarbodiimide (DCCD) inhibited ATPase activity at pH 7.5 and 5.5 in E. coli wild type and dcu mutants upon glycerol fermentation. The overall ATPase activity was highest at pH 7.5 in dcuABCD mutant. In wild type cells 50% of the activity came from the FOF1-ATPase but in dcuD mutant it reached ~80%. K+ (100 mM) stimulate total but not DCCD inhibited ATPase activity 40% and 20% in wild type and dcuD mutant, respectively. 90% of overall ATPase activity was inhibited by DCCD at pH 5.5 only in dcuABC mutant. At pH 7.5 the H+ fluxes in E. coli wild type, dcuD and dcuABCD mutants was similar but in dcuABC triple mutant the H+ flux decreased 1.4 fold reaching 1.15 mM/min when glycerol was supplemented. In succinate assays the H+ flux was higher in the strains where DcuD is absent. No significant differences were determined in wild type and mutants specific growth rate except dcuD strain. Taken together it is suggested that during glycerol fermentation DcuD has impact on H+ fluxes, FOF1-ATPase activity and depends on potassium ions.