bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular retargeting of antibodies converts immune defense against oncolytic viruses into cancer immunotherapy
Authors: Niemann Julia , Woller Norman , Brooks Jennifer , Fleischmann-Mundt Bettina , Martin Nikolas T. , Kloos Arnold , Knocke Sarah , Ernst Amanda M. , Manns Michael P. , Kubicka Stefan , Wirth Thomas C. , Gerardy-Schahn Rita , Kühnel Florian
Published: July 2019

Virus-neutralizing antibodies are a severe obstacle in oncolytic virotherapy. Here, we present a strategy to convert this unfavorable immune response into an anticancer immunotherapy via molecular retargeting. Application of a bifunctional adapter harboring a tumor-specific ligand and the adenovirus hexon domain DE1 for engaging antiadenoviral antibodies, attenuates tumor growth and prolongs survival in adenovirus-immunized mice. The therapeutic benefit achieved by tumor retargeting of antiviral antibodies is largely due to NK cell-mediated triggering of tumor-directed CD8 T-cells. We further demonstrate that antibody-retargeting (Ab-retargeting) is a feasible method to sensitize tumors to PD-1 immune checkpoint blockade. In therapeutic settings, Ab-retargeting greatly improves the outcome of intratumor application of an oncolytic adenovirus and facilitates long-term survival in treated animals when combined with PD-1 checkpoint inhibition. Tumor-directed retargeting of preexisting or virotherapy-induced antiviral antibodies therefore represents a promising strategy to fully exploit the immunotherapeutic potential of oncolytic virotherapy and checkpoint inhibition.
Rapid inundation of southern Florida coastline despite low relative sea-level rise rates during the late-Holocene
Authors: Jones Miriam C. , Wingard G. Lynn , Stackhouse Bethany , Keller Katherine , Willard Debra , Marot Marci , Landacre Bryan , E. Bernhardt Christopher
Published: July 2019

Sediment cores from Florida Bay, Everglades National Park were examined to determine ecosystem response to relative sea-level rise (RSLR) over the Holocene. High-resolution multiproxy analysis from four sites show freshwater wetlands transitioned to mangrove environments 4–3.6 ka, followed by estuarine environments 3.4–2.8 ka, during a period of enhanced climate variability. We calculate a RSLR rate of 0.67 ± 0.1 mm yr−1 between ~4.2–2.8 ka, 4–6 times lower than current rates. Despite low RSLR rates, the rapid mangrove to estuarine transgression was facilitated by a period of prolonged droughts and frequent storms. These findings suggest that with higher and accelerating RSLR today, enhanced climate variability could further hasten the loss of mangrove-lined coastlines, compounded by the reductions in natural flow to the coast caused by water management. Climate variability is nonlinear, and when superimposed on increases in RSLR, can complicate estimated trajectories of coastal inundation for resource management and urban planning.
Active thrombin produced by the intestinal epithelium controls mucosal biofilms
Authors: Motta Jean-Paul , Denadai-Souza Alexandre , Sagnat David , Guiraud Laura , Edir Anissa , Bonnart Chrystelle , Sebbag Mireille , Rousset Perrine , Lapeyre Ariane , Seguy Carine , Mathurine-Thomas Noa , Galipeau Heather J. , Bonnet Delphine , Alric Laurent , Buret Andre G. , Wallace John L. , Dufour Antoine , Verdu Elena F. , Hollenberg Morley D. , Oswald Eric , Serino Matteo , Deraison Celine , Vergnolle Nathalie
Published: July 2019

Proteolytic homeostasis is important at mucosal surfaces, but its actors and their precise role in physiology are poorly understood. Here we report that healthy human and mouse colon epithelia are a major source of active thrombin. We show that mucosal thrombin is directly regulated by the presence of commensal microbiota. Specific inhibition of luminal thrombin activity causes macroscopic and microscopic damage as well as transcriptomic alterations of genes involved in host-microbiota interactions. Further, luminal thrombin inhibition impairs the spatial segregation of microbiota biofilms, allowing bacteria to invade the mucus layer and to translocate across the epithelium. Thrombin cleaves the biofilm matrix of reconstituted mucosa-associated human microbiota. Our results indicate that thrombin constrains biofilms at the intestinal mucosa. Further work is needed to test whether thrombin plays similar roles in other mucosal surfaces, given that lung, bladder and skin epithelia also express thrombin.
Antimalarial activity of primaquine operates via a two-step biochemical relay
Authors: Camarda Grazia , Jirawatcharadech Piyaporn , Priestley Richard S. , Saif Ahmed , March Sandra , Wong Michael H. L. , Leung Suet , Miller Alex B. , Baker David A. , Alano Pietro , Paine Mark J. I. , Bhatia Sangeeta N. , O’Neill Paul M. , Ward Stephen A. , Biagini Giancarlo A.
Published: July 2019

Primaquine (PQ) is an essential antimalarial drug but despite being developed over 70 years ago, its mode of action is unclear. Here, we demonstrate that hydroxylated-PQ metabolites (OH-PQm) are responsible for efficacy against liver and sexual transmission stages of Plasmodium falciparum. The antimalarial activity of PQ against liver stages depends on host CYP2D6 status, whilst OH-PQm display direct, CYP2D6-independent, activity. PQ requires hepatic metabolism to exert activity against gametocyte stages. OH-PQm exert modest antimalarial efficacy against parasite gametocytes; however, potency is enhanced ca.1000 fold in the presence of cytochrome P450 NADPH:oxidoreductase (CPR) from the liver and bone marrow. Enhancement of OH-PQm efficacy is due to the direct reduction of quinoneimine metabolites by CPR with the concomitant and excessive generation of H2O2, leading to parasite killing. This detailed understanding of the mechanism paves the way to rationally re-designed 8-aminoquinolines with improved pharmacological profiles.
Real-time optical and electronic sensing with a β-amino enone linked, triazine-containing 2D covalent organic framework
Authors: Kulkarni Ranjit , Noda Yu , Kumar Barange Deepak , Kochergin Yaroslav S. , Lyu Pengbo , Balcarova Barbora , Nachtigall Petr , Bojdys Michael J.
Published: July 2019

Fully-aromatic, two-dimensional covalent organic frameworks (2D COFs) are hailed as candidates for electronic and optical devices, yet to-date few applications emerged that make genuine use of their rational, predictive design principles and permanent pore structure. Here, we present a 2D COF made up of chemoresistant β-amino enone bridges and Lewis-basic triazine moieties that exhibits a dramatic real-time response in the visible spectrum and an increase in bulk conductivity by two orders of magnitude to a chemical trigger - corrosive HCl vapours. The optical and electronic response is fully reversible using a chemical switch (NH3 vapours) or physical triggers (temperature or vacuum). These findings demonstrate a useful application of fully-aromatic 2D COFs as real-time responsive chemosensors and switches.
Water-soluble polysaccharides from Grifola Frondosa fruiting bodies protect against immunosuppression in cyclophosphamide-induced mice via JAK2/STAT3/SOCS signal transduction pathways
Authors: Meng Meng , Guo Mingzhu , Feng Chengcheng , Wang Ruhua , Cheng Dai , Wang Chunling
Published: July 2019

Grifola Frondosa, the king of mushrooms, is one of the most valued traditional medicines and has been used as a health food for a long time in China, Japan, and other Asian countries.
Tetra-, hexa- and octanuclear copper hydride complexes supported by tridentate phosphine ligands
Authors: Nakajima Takayuki , Nakamae Kanako , Hatano Rika , Imai Kaho , Harada Masafumi , Ura Yasuyuki , Tanase Tomoaki
Published: July 2019

Tetra-, hexa-, and octanuclear copper hydride complexes were synthesized by using a triphosphine, Ph2PCH2P(Ph)CH2PPh2(dpmp), and were characterized by X-ray crystallographic analyses and theoretical calculations.
trans-Trismethoxy resveratrol decreased fat accumulation dependent on fat-6 and fat-7 in Caenorhabditis elegans
Authors: Yue Yiren , Shen Peiyi , Chang Amanda L. , Qi Weipeng , Kim Kee-Hong , Kim Daeyoung , Park Yeonhwa
Published: July 2019

trans-Trismethoxy resveratrol reduced fat accumulation via the regulation of FAT-6 and FAT-7, stearoyl-CoA desaturases homologs, in Caenorhabditis elegans.
Silicon nitride nanopore created by dielectric breakdown with a divalent cation: deceleration of translocation speed and identification of single nucleotides
Authors: Goto Yusuke , Matsui Kazuma , Yanagi Itaru , Takeda Ken-ichi
Published: July 2019

Controlled dielectric breakdown with a divalent metal cation provides a silicon nitride nanopore with the ability to decelerate single-stranded DNA speed.
Catalyst- and reagent-free 1,6-hydrophosphonylation of p-quinone methides: a practical approach for the synthesis of diarylmethyl phosphine oxides
Authors: Aher Yogesh N. , Pawar Amit B.
Published: July 2019

We have developed a catalyst-, reagent-, and additive-free protocol with 100% atom economy for the synthesis of diarylmethyl phosphine oxides via 1,6-hydrophosphonylation of p-quinone methides using water as a green solvent.
Photo-induced copper-RDRP in continuous flow without external deoxygenation
Authors: Marathianos Arkadios , Liarou Evelina , Anastasaki Athina , Whitfield Richard , Laurel Matthew , Wemyss Alan M. , Haddleton David M.
Published: July 2019

Photo-induced Cu-RDRP of acrylates in a continuous flow reactor without the need for deoxygenation or externally added reagents.
Éducation thérapeutique du patient en Côte d’Ivoire (Afrique de l’Ouest) : enjeux et défis face à l’indifférence
Authors: Konan Y.E. , Kivits J. , Tanguy M. , Benie J.
Published: July 2019

En Côte d’Ivoire, l’émergence des maladies chroniques ne suscite pas la mobilisation des principaux acteurs autour de l’éducation thérapeutique du patient (ETP). Pourtant, les enjeux d’équité, politiques, médico-économiques et d’amélioration de la qualité de vie des patients montrent qu’il est nécessaire que l’ETP devienne une priorité nationale. Par conséquent, face à ces enjeux, la Côte d’Ivoire se doit de relever un certain nombre de défis. Il s’agit des défis de la formation, de la recherche, du financement, de la démarche qualité, de la multidisciplinarité et du changement de posture éducative.
Autoimmunthyreoiditis
Authors: Bieger Wilfried P.
Published: July 2019

In Deutschland sind etwa 5 % der Bevölkerung an einer Autoimmunthyreoiditis (AITD) erkrankt, wobei die Hashimoto-Thyreoiditis häufiger ist als Morbus Basedow. Bei beiden Autoimmunerkrankungen sind Frauen deutlich häufiger betroffen als Männer, familiäre Häufungen sind bekannt und nicht selten leiden die Patienten gleichzeitig an weiteren Autoimmunopathien. Die Ätiologie der AIDT gilt als multifaktoriell, der Beitrag genetischer Faktoren wird auf 75 % geschätzt. Umweltfaktoren haben einen Anteil von 20 % an der Inzidenz. Als Trigger wurden u. a. Rauchen, Infektionen, Stress und Selenmangel identifiziert. Möglichkeiten der Diagnostik und Therapie werden zusammenfassend dargestellt.
Überleben bei ALS?
Authors: Mutter Joachim
Published: July 2019

Zahlreiche wissenschaftliche Arbeiten belegen einen Zusammenhang zwischen Schwermetallbelastungen und neurodegenerativen Erkrankungen wie ALS. Immer wieder in der Diskussion sind Zahnfüllungen aus Amalgam, die in Deutschland trotz vielzähliger gegenteiliger Belege noch immer als unschädlich eingestuft werden. Die WHO hat diese bereits 1991 als Hauptquelle für Quecksilberbelastungen eingestuft.

Für ALS gibt es bislang keine kurative Therapie, die Prognose ist in den meisten Fällen sehr ungünstig. Eine Ausleitungstherapie mit Chelatbildnern hat sich als nicht schädlich, sondern vielmehr lebensrettend und ursächlich gezeigt, was internationale wissenschaftliche Arbeiten bestätigen.
Historical Inductions Meet the Material Theory
Authors: Shech Elay
Published: July 2019

Historical inductions, that is, the pessimistic metainduction and the problem of unconceived alternatives, are critically analyzed via John D. Norton’s material theory of induction and subsequently rejected as noncogent arguments. It is suggested that the material theory is amenable to a local version of the pessimistic metainduction, for example, in the context of some medical studies.
Distribution and temporal trends of temperature extremes over Antarctica
Authors: Wei Ting , Yan Qing , Ding Minghu
Published: July 2019

The spatiotemporal characteristics of temperature extremes over Antarctica remain largely unknown. Here, we use quality-controlled daily datasets from Antarctic weather stations to show that the annual maximum and minimum temperatures exhibit a decreasing pattern over Antarctica from the coast to inland regions. This feature holds for the warmest daily maximum and coldest daily minimum temperatures, which define the intensity of extremes, but not for the number of warm (cold) days measuring the frequency of extremes, which show limited dependence on latitude or elevation. During 1970–2000, the temperature extremes in the South Orkney islands and on the margins of East Antarctica show opposite trends, especially with a significant increasing and decreasing trend in warm events, respectively. During 1999–2013, the intensity and frequency of extreme temperatures decrease significantly over West Antarctica, but the trends vary greatly across sub-regions of Antarctica. Despite the limited number of stations and the potential time dependence of trends, these results not only help to decipher the climate regimes of Antarctica and fill current gaps in the map of global climate extremes, but also may guide the future design of Antarctic observational networks and be used to assess the capability of reanalysis datasets and climate models.
Steroidogenic acute regulatory protein and luteinizing hormone are required for normal ovarian steroidogenesis and oocyte maturation in zebrafish†
Authors: Shang Guohui , Peng Xuyan , Ji Cheng , Zhai Gang , Ruan Yonglin , Lou Qiyong , Jin Xia , He Jiangyan , Wang Han , Yin Zhan
Published: July 2019

In recent studies, luteinizing hormone (LH) was reported to play important roles in oocyte maturation. However, the mechanism by which LH signaling, especially regarding the steroidogenesis process, affects oocyte maturation has not been clarified. In this study, zebrafish models with a functional deficiency in luteinizing hormone beta (Lhb) or steroidogenic acute regulatory protein (Star), an enzyme that promotes the transport of cholesterol into the inner mitochondrial membrane for maturation-induced hormone (MIH) production, were generated using transcription activator-like effector nucleases (TALENs). Similar phenotypes of the maturation-arrested oocytes in both female mutants have been observed. The levels of MIH in the oocytes of the female mutants were clearly decreased in both the lhb and star knockout zebrafish. The expression of star was dramatically down-regulated in the lhb mutant follicles and was clearly promoted by forskolin and hCG in vitro. Furthermore, treatment with the MIH precursors, pregnenolone or progesterone, as well as with MIH itself rescued the maturation-arrested oocyte phenotypes in both lhb and star mutants. The plasma levels of other steroids, including testosterone, estradiol, and cortisol, were not affected in the lhb mutants, while the levels of gonad hormones testosterone and estradiol were significantly increased in the star mutants. The cortisol levels were decreased in the star mutants. Collectively, our results confirm that LH plays important roles in the initiation of MIH synthesis from cholesterol and maintains oocyte maturation in zebrafish, as well as provide evidence that Star might act downstream of LH signaling in steroidogenesis.
Association Between Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection in Early Life and Recurrent Wheeze and Asthma in Later Childhood
Authors: Shi Ting , Ooi Yujing , Zaw Ei Mon , Utjesanovic Natasa , Campbell Harry , Cunningham Steve , Bont Louis , Nair Harish ,   RESCEU Investigators, Nair Harish , Campbell Harry , Shi Ting , Zhang Shanshan , Li You , Openshaw Peter , Wedzicha Jadwicha , Falsey Ann , Miller Mark , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Mikolajczyk Rafael , Hackett Judy , Cai Bing , Knirsch Charles , Leach Amanda , Stoszek Sonia K , Gallichan Scott , Kieffer Alexia , Demont Clarisse , Cheret Arnaud , Gavart Sandra , Aerssens Jeroen , Wyffels Veronique , Cleenewerck Matthias , Fuentes Robert , Rosen Brian , Nair Harish , Campbell Harry , Shi Ting , Zhang Shanshan , Li You , Openshaw Peter , Wedzicha Jadwicha , Falsey Ann , Miller Mark , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Mikolajczyk Rafael , Hackett Judy , Cai Bing , Knirsch Charles , Leach Amanda , Stoszek Sonia K , Gallichan Scott , Kieffer Alexia , Demont Clarisse , Cheret Arnaud , Gavart Sandra , Aerssens Jeroen , Wyffels Veronique , Cleenewerck Matthias , Fuentes Robert , Rosen Brian
Published: July 2019

Background

Recurrent wheeze and asthma in childhood are commons causes of chronic respiratory morbidity globally. We aimed to explore the association between respiratory syncytial virus (RSV) infection in early life and subsequent respiratory sequelae up to age 12 years.

Methods

We estimated the strength of association by 3 control groups and 3 follow-up age groups, with data from studies published between January 1995 and May 2018. We also estimated associations by diagnostic criteria, age at infection, and high-risk population.

Results

Overall, we included 41 studies. A statistically significant association was observed between early life RSV infection and subsequent childhood recurrent wheeze, in comparison to those who were healthy or those without respiratory symptoms: OR 3.05 (95% confidence interval [CI], 2.50–3.71) for 0 to <36 months follow-up age; OR 2.60 (95% CI, 1.67–4.04) for 36–72 months; and OR 2.14 (95% CI, 1.33–3.45) for 73–144 months. For the subsequent development of asthma, a statistically significant association was observed only in relation to those aged 73–144 months at follow-up: OR 2.95 (95% CI, 1.96–4.46).

Conclusions

Further studies using standardized definitions and from diverse settings are needed to elucidate the role of confounders and provide more robust estimates.
An Updated Conceptual Model on the Pathogenesis of Bacterial Vaginosis
Authors: Muzny Christina A , Taylor Christopher M , Swords W Edward , Tamhane Ashutosh , Chattopadhyay Debasish , Cerca Nuno , Schwebke Jane R
Published: July 2019

Bacterial vaginosis (BV) is the most common cause of vaginal discharge. It is associated with an increased risk of preterm delivery, pelvic inflammatory disease, and an increased risk of acquisition of sexually transmitted infections including human immunodeficiency virus (HIV). The epidemiology of BV supports sexual transmission. However, its etiology remains unknown. At the center of the debate is whether BV is caused by a primary pathogen or a polymicrobial consortium of microorganisms that are sexually transmitted. We previously published a conceptual model hypothesizing that BV is initiated by sexual transmission of Gardnerella vaginalis. Critics of this model have iterated that G. vaginalis is found in virginal women and in sexually active women with a normal vaginal microbiota. In addition, colonization does not always lead to BV. However, recent advances in BV pathogenesis research have determined the existence of 13 different species within the genus Gardnerella. It may be that healthy women are colonized by nonpathogenic Gardnerella species, whereas virulent strains are involved in BV development. Based on our results from a recent prospective study, in addition to an extensive literature review, we present an updated conceptual model for the pathogenesis of BV that centers on the roles of virulent strains of G. vaginalis, as well as Prevotella bivia and Atopobium vaginae.
cis-12-Oxo-phytodienoic acid represses Arabidopsis seed germination in shade conditions
Authors: Barros-Galvão Thiago , Dave Anuja , Cole Adama , Harvey David , Langer Swen , Larson Tony R , Vaistij Fabián E , Graham Ian A
Published: July 2019

Light-dependent seed germination is induced by gibberellins (GA) and inhibited by abscisic acid (ABA). The widely accepted view of the GA/ABA ratio controlling germination does not, however, explain the fact that seeds deficient in ABA still germinate poorly under shade conditions that repress germination. In Arabidopsis, MOTHER-OF-FT-AND-TFL1 (MFT) acts as a key negative regulator of germination, modulating GA and ABA responses under shade conditions. Under full light the oxylipin cis-12-oxo-phytodienoic acid (OPDA), a precursor of the stress-related phytohormone jasmonic acid, interacts with ABA and MFT to repress germination. Here, we show that under shade conditions both OPDA and ABA repress germination to varying extents. We demonstrate that the level of shade-induced MFT expression influences the ability of OPDA and/or ABA to fully repress germination. We also found that MFT expression decreases with seed age and this again correlates with the response of seeds to OPDA and ABA. We conclude that OPDA plays an essential role alongside ABA in repressing germination in response to shade and the combined effect of these phytohormones is integrated to a significant extent through MFT.
Cosmic ray acceleration by shocks: spectral steepening due to turbulent magnetic field amplification
Authors: Bell A R , Matthews J H , Blundell K M
Published: July 2019

We show that the energy required to turbulently amplify magnetic field during cosmic ray (CR) acceleration by shocks extracts energy from the CR and steepens the CR energy spectrum.
Magnifications of paired micro-images emerging from a micro-lensing critical curve
Authors: Weisenbach Luke , Schechter Paul , Wambsganss Joachim
Published: July 2019

Studies of the inner regions of micro-lensed active galactic nucleus during caustic crossing events have often relied upon the approximation that the magnification near a fold caustic is inversely proportional to the square root of the source-caustic distance. We examine here the behaviour of the individual micro-images (one a micro-minimum of the light traveltime, the other a micro-saddle) that emerge as a point source crosses a micro-fold caustic. We provide a variety of statistics on both the behaviour of the two newly created micro-images and some parameters that appear in higher order approximations for the magnification. We compare the predictions of these higher order approximations to the actual image magnifications of our simulations.
Dietary vitamin D interacts with high phosphate-induced cardiac remodeling in rats with normal renal function
Authors: Hu Ming Chang , Scanni Roberto , Ye Jianfeng , Zhang Jianning , Shi Mingjun , Maique Jenny , Flores Brianna , Moe Orson W , Krapf Reto
Published: July 2019

Background

Vitamin D (VD) and phosphate (Pi) load are considered as contributors to cardiovascular disease in chronic kidney disease and the general population, but interactive effects of VD and Pi intake on the heart are not clearly illustrated.

Methods

We fed normal male rats with three levels of dietary VD (100, 1100 or 5000 IU/kg chow) and Pi (0.2, 0.6 or 1.6%) (3X3 design) for 8 weeks and examined renal and cardiac function and histology.

Results

High dietary Pi decreased plasma and renal Klotho and plasma 25-hydroxyvitamin D, and increased plasma Pi, fibroblast growth factor 23 and parathyroid hormone without affecting renal function, while low Pi increased plasma and renal Klotho. Both low and high VD diets enhanced high Pi-reduced Klotho expression. Low dietary VD reduced-plasma Klotho was rescued by a low Pi diet. High dietary Pi reduced-cardiac ejection fraction was not modified by a low or high VD diet, but the dietary VD effects on cardiac pathologic changes were more complex. High dietary Pi-induced cardiac hypertrophy was attenuated by a low VD and exacerbated by a high VD diet. In contrast, high dietary Pi -induced cardiac fibrosis was magnified by a low VD and attenuated by a high VD diet.

Conclusions

High Pi diet induces hypertrophy and fibrosis in left ventricles, a low VD diet accelerates high Pi-induced fibrosis, and a high VD diet exacerbated high Pi -induced hypertrophy. Therefore, cardiac phosphotoxicity is exacerbated by either high or low dietary VD in rats with normal kidney function.
Incidence of Root-Knot Nematode (Meloidogyne graminicola) and Resulting Crop Losses in Paddy Rice in Northern India
Authors: Khan Mujeebur Rahman , Ahamad Faheem
Published: July 2019

Surveys of major rice growing districts in the state of Uttar Pradesh in Northern India were conducted for 3 consecutive years during 2013 to 2015 under a government-funded major research project to determine the frequency of occurrence and disease incidence of the rice root-knot nematode, Meloidogyne graminicola, in rice paddy fields. More than 800 paddy fields from 88 Tehsils (divisions within a district) in 18 major rice growing districts in Uttar Pradesh were surveyed, where M. graminicola was associated with root-knot disease in rice paddy fields based on morphological and molecular characterization of juveniles and adults. The highest frequency of disease in rice fields was observed in Aligarh (44.6%), followed by Muzaffarnagar, Shahjahanpur, and Kheri Lakhimpur (29.3, 28.0, and 27.4%, respectively). Maximum disease incidence was also recorded in Aligarh (44.6%), followed by Sultanpur, Mainpuri, and Muzaffarnagar (5.7, 5.2, and 4.5, respectively). Gall index and egg mass index values (on a 0 to 10 scale) were highest in Aligarh (3.5 and 2.1, respectively), followed by Muzaffarnagar (2.6 and 2.0) and Mainpuri (2.3 and 1.8). The average soil population of M. graminicola was highest in Aligarh (3,851 ± 297 second-stage juveniles [J2]/kg of soil), followed by Muzaffarnagar (2,855 ± 602 J2/kg of soil), whereas the lowest population was recorded in Barabanki (695 ± 400 J2/kg of soil) at the time of harvesting. Relative yield losses were also determined, and the highest yield loss attributed to M. graminicola infestation was recorded in Aligarh (47%). The yield loss was linearly correlated with the soil population density of M. graminicola and disease incidence.
Prioritizing transcriptomic and epigenomic experiments by using an optimization strategy that leverages imputed data
Authors: Schreiber Jacob , Bilmes Jeffrey , Noble William Stafford
Published: July 2019

Successful science often involves not only performing experiments well, but also choosing well among many possible experiments. In a hypothesis generation setting, choosing an experiment well means choosing an experiment whose results are interesting or novel. In this work, we formalize this selection procedure in the context of genomics and epigenomics data generation. Specifically, we consider the task faced by a scientific consortium such as the National Institutes of Health ENCODE Consortium, whose goal is to characterize all of the functional elements in the human genome. Given a list of possible cell types or tissue types (“biosamples”) and a list of possible high throughput sequencing assays, we ask “Which experiments should ENCODE perform next?” We demonstrate how to represent this task as an optimization problem, where the goal is to maximize the information gained in each successive experiment. Compared with previous work that has addressed a similar problem, our approach has the advantage that it can use imputed data to tailor the selected list of experiments based on data collected previously by the consortium. We demonstrate the utility of our proposed method in simulations, and we provide a general software framework, named Kiwano, for selecting genomic and epigenomic experiments.
STAT5-dependent regulation of CDC25A by miR-16 controls proliferation and differentiation in FLT3-ITD acute myeloid leukemia
Authors: Sueur Gabrielle , Boutet Alison , Gotanègre Mathilde , Mansat-De Mas Véronique , Besson Arnaud , Manenti Stéphane , Bertoli Sarah
Published: July 2019

We recently identified the CDC25A phosphatase as a key actor in proliferation and differentiation in acute myeloid leukemia which expresses the FLT3-ITD mutation. In this paper we demonstrate that CDC25A level is controlled by a complex STAT5/miR-16 transcription and translation pathway working downstream of this receptor. First, we established by CHIP analysis that STAT5 is directly involved in FLT3-ITD-dependentCDC25Agene transcription. In addition, we determined that miR-16 expression is repressed by FLT3-ITD activity, and that STAT5 participates in this repression. In accordance with these results, miR-16 expression was significantly reduced in a panel of AML primary samples carrying the FLT3-ITD mutation when compared with FLT3wt cells. The expression of a miR-16 mimic reduced CDC25A protein and mRNA levels, and RNA interference-mediated down modulation of miR-16 restored CDC25A expression in response to FLT3-ITD inhibition. Finally, decreasing miR-16 expression partially restored the proliferation of cells treated with the FLT3 inhibitor AC220, while the expression of miR-16 mimic stopped this proliferation and induced monocytic differentiation of AML cells. In summary, we identified a FLT3-ITD/STAT5/miR-16/CDC25A axis essential for AML cell proliferation and differentiation.
The in vivo endothelial cell translatome is highly heterogeneous across vascular beds
Authors: Cleuren Audrey C.A. , van der Ent Martijn A. , Jiang Hui , Hunker Kristina L. , Yee Andrew , Siemieniak David R. , Molema Grietje , Aird William C. , Ganesh Santhi K. , Ginsburg David
Published: July 2019

Endothelial cells (ECs) are highly specialized across vascular beds. However, given their interspersed anatomic distribution, comprehensive characterization of the molecular basis for this heterogeneity in vivo has been limited. By applying endothelial-specific translating ribosome affinity purification (EC-TRAP) combined with high-throughput RNA sequencing analysis, we identified pan EC-enriched genes and tissue-specific EC transcripts, which include both established markers and genes previously unappreciated for their presence in ECs. In addition, EC-TRAP limits changes in gene expression following EC isolation and in vitro expansion, as well as rapid vascular bed-specific shifts in EC gene expression profiles as a result of the enzymatic tissue dissociation required to generate single cell suspensions for fluorescence-activated cell sorting (FACS) or single cell RNA sequencing analysis. Comparison of our EC-TRAP to published single cell RNA sequencing data further demonstrates considerably greater sensitivity of EC-TRAP for the detection of low abundant transcripts. Application of EC-TRAP to examine the in vivo host response to lipopolysaccharide (LPS) revealed the induction of gene expression programs associated with a native defense response, with marked differences across vascular beds. Furthermore, comparative analysis of whole tissue and TRAP-selected mRNAs identified LPS-induced differences that would not have been detected by whole tissue analysis alone. Together, these data provide a resource for the analysis of EC-specific gene expression programs across heterogeneous vascular beds under both physiologic and pathologic conditions.

Significance

Endothelial cells (ECs), which line all vertebrate blood vessels, are highly heterogeneous across different tissues. The present study uses a genetic approach to specifically tag mRNAs within ECs of the mouse, thereby allowing recovery and sequence analysis to evaluate the EC-specific gene expression program directly from intact organs. Our findings demonstrate marked heterogeneity in EC gene expression across different vascular beds under both normal and disease conditions, with a more accurate picture than can be achieved using other methods. The data generated in these studies advance our understanding of EC function in different blood vessels and provide a valuable resource for future studies.
Evolved for success in novel environments: The round goby genome
Authors: Adrian-Kalchhauser Irene , Blomberg Anders , Larsson Tomas , Musilova Zuzana , Peart Claire R , Pippel Martin , Solbakken Monica Hongroe , Suurväli Jaanus , Walser Jean-Claude , Wilson Joanna Yvonne , Rosenblad Magnus Alm , Burguera Demian , Gutnik Silvia , Michiels Nico , Töpel Mats , Pankov Kirill , Schloissnig Siegfried , Winkler Sylke
Published: July 2019

Since the beginning of global trade, hundreds of species have colonized territories outside of their native range. Some of these species proliferate at the expense of native ecosystems, i.e., have become invasive. Invasive species constitute powerfulin situexperimental systems to study fast adaptation and directional selection on short ecological timescales. They also present promising case studies for ecological and evolutionary success in novel environments.

We seize this unique opportunity to study genomic substrates for ecological success and adaptability to novel environments in a vertebrate. We report a highly contiguous long-read based genome assembly for the most successful temperate invasive fish, the benthic round goby (Neogobius melanostomus), and analyse gene families that may promote its impressive ecological success.

Our approach provides novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns in epigenetic regulators, and the presence of genes that may have contributed to the round goby’s capacity to invade cold and salty waters.

A recurring theme across all analyzed gene families are gene expansions. This suggests that gene duplications may promote ecological flexibility, superior performance in novel environments, and underlie the impressive colonization success of the round goby.Gobiidaegenerally feature fascinating adaptations and are excellent colonizers. Further long-read genome approaches across the goby family may reveal whether the ability to conquer new habitats relates more generally to gene copy number expansions.
H3K4me3 is neither instructive for, nor informed by, transcription
Authors: Murray Struan C , Lorenz Philipp , Howe Françoise S , Wouters Meredith , Brown Thomas , Xi Shidong , Fischl Harry , Khushaim Walaa , Rayappu Joseph Regish , Angel Andrew , Mellor Jane
Published: July 2019

H3K4me3 is a near-universal histone modification found predominantly at the 5’ region of genes, with a well-documented association with gene activity. H3K4me3 has been ascribed roles as both an instructor of gene expression and also a downstream consequence of expression, yet neither has been convincingly proven on a genome-wide scale. Here we test these relationships using a combination of bioinformatics, modelling and experimental data from budding yeast in which the levels of H3K4me3 have been massively ablated. We find that loss of H3K4me3 has no effect on the levels of nascent transcription or transcript in the population. Moreover, we observe no change in the rates of transcription initiation, elongation, mRNA export or turnover, or in protein levels, or cell-to-cell variation of mRNA. Loss of H3K4me3 also has no effect on the large changes in gene expression patterns that follow galactose induction. Conversely, loss of RNA polymerase from the nucleus has no effect on the pattern of H3K4me3 deposition and little effect on its levels, despite much larger changes to other chromatin features. Furthermore, large genome-wide changes in transcription, both in response to environmental stress and during metabolic cycling, are not accompanied by corresponding changes in H3K4me3. Thus, despite the correlation between H3K4me3 and gene activity, neither appear to be necessary to maintain levels of the other, nor to influence their changes in response to environmental stimuli. When we compare gene classes with very different levels of H3K4me3 but highly similar transcription levels we find that H3K4me3-marked genes are those whose expression is unresponsive to environmental changes, and that their histones are less acetylated and dynamically turned-over. Constitutive genes are generally well-expressed, which may alone explain the correlation between H3K4me3 and gene expression, while the biological role of H3K4me3 may have more to do with this distinction in gene class.
Analysis and correction on frictional temperature rise testing of brake based on preset thermometry method
Authors: Zhao Shaodi , Yin Yan , Bao Jiusheng , Xiao Xingming , Li Zengsong , Chen Guoan
Published: July 2019

Purpose

The friction between brake pair causes an intense temperature rise on interface during braking, which affects the braking performance seriously. Therefore, building an accurate testing method for frictional temperature rise (FTR) is a prerequisite.

Design/methodology/approach

Facing braking conditions of automobiles, an experimental system for testing of FTR based on preset thermometry method (PTM) was established. The FTR was collected by the PTM and the variation laws as well as the cause of errors were analyzed by experiments. The deviations between tested and real temperature were corrected based on tribology and heat theories. Finally, an online prediction method for FTR was pointed out.

Findings

After correction, the temperature curve accords well with the laws of tribology and thermal theories. The corrected FTR at braking end point is approximately equal to the authentic temperature test by hand thermometer.

Originality/value

This study eliminated the hysteresis phenomenon of temperature rise sequence and lays a foundation for online accurate monitoring and warning of brake friction temperature rise. It has important theoretical and practical value for expanding the monitoring and improvement of brake performance.
Ninety and not out—Understanding our oldest old
Authors: Gibson Diane , Goss John
Published: July 2019

Objective

This paper draws attention to the rapidly growing number of Australian nonagenarians, presents previously unpublished information on this sub‐group of older people and explores the implications for future patterns of service delivery, planning and policy.

Methods

Statistical analyses of Census data and other Australian Bureau of Statistics Surveys using Table Builder Pro, combined with analysis of de‐identified Australian Institute of Health and Welfare (AIHW) unit record data on aged care and AIHW GRIM (mortality) data.

Results

Male nonagenarians almost doubled from 2006 to 2016, while their female counterparts grew by 55%. This cohort is the first to reap cumulative advantage from the dramatic reduction in death rates from 1970. Their demographic circumstances reveal both changes and continuities compared to the previous cohort.

Conclusion

Men and women aged 90 and over use a substantial proportion of aged care services, and their characteristics and circumstances are highly relevant to planning current and future aged care services.
Cellular immune responses in amniotic fluid of women with preterm labor and intra‐amniotic infection or intra‐amniotic inflammation
Authors: Gomez‐Lopez Nardhy , Romero Roberto , Galaz Jose , Xu Yi , Panaitescu Bogdan , Slutsky Rebecca , Motomura Kenichiro , Gill Navleen , Para Robert , Pacora Percy , Jung Eunjung , Hsu Chaur‐Dong
Published: July 2019

Problem

Preterm birth is commonly preceded by preterm labor, a syndrome that is causally linked to both intra‐amniotic infection and intra‐amniotic inflammation. However, the stereotypical cellular immune responses in these two clinical conditions are poorly understood.

Method of study

Amniotic fluid samples (n = 26) were collected from women diagnosed with preterm labor and intra‐amniotic infection (amniotic fluid IL‐6 concentrations ≥2.6 ng/mL and culturable microorganisms, n = 10) or intra‐amniotic inflammation (amniotic fluid IL‐6 concentrations ≥2.6 ng/mL without culturable microorganisms, n = 16). Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. Amniotic fluid concentrations of classical pro‐inflammatory cytokines, type 1 and type 2 cytokines, and T‐cell chemokines were determined using immunoassays.

Results

Women with spontaneous preterm labor and intra‐amniotic infection had (a) a greater number of total leukocytes, including neutrophils and monocytes/macrophages, in amniotic fluid; (b) a higher number of total T cells and CD4+ T cells, but not CD8+ T cells or B cells, in amniotic fluid; and (c) increased amniotic fluid concentrations of IL‐6, IL‐1β, and IL‐10, compared to those with intra‐amniotic inflammation. However, no differences in amniotic fluid concentrations of T‐cell cytokines and chemokines were observed between these two clinical conditions.

Conclusion

The cellular immune responses observed in women with preterm labor and intra‐amniotic infection are more severe than in those with intra‐amniotic inflammation, and neutrophils, monocytes/macrophages, and CD4+ T cells are the main immune cells responding to microorganisms that invade the amniotic cavity. These findings provide insights into the intra‐amniotic immune mechanisms underlying the human syndrome of preterm labor.
Effects of Lonicera japonica extract supplementation on in vitro ruminal fermentation, methane emission, and microbial population
Authors: Yejun Lee , Su Kyoung Lee , Shin Ja Lee , Jong‐Su Eun , Sung Sill Lee
Published: July 2019

Lonicera japonica (LJ; honeysuckle) is used in traditional folk medicine in Korea and is a rich source of ascorbic acid and phenolic components that are reported to have antioxidant and antibiotic properties. We performed an in vitro experiment to assess the effects of LJ extracts (LJE) on ruminal fermentation. Timothy hay (0.3 g dry matter [DM]) was incubated with buffer, ruminal fluid, and 0%, 3%, 5%, 7%, and 9% LJE. Batch culture fermentation was conducted separately for 12, 24, and 48 hr to determine gas production (GP), ruminal fermentation characteristics, and microbial population characteristics. The effects on GP were generally similar to those on DM degradability, with a linear decrease observed at 9% extract at 24 hr. NH3‐N showed a linear increase with increasing extract concentrations at 12 hr, whereas a decrease was observed at 24 hr. Extract supplementation decreased methane (CH4) production at 12, 24, and 48 hr. In addition, the abundance of fibrolytic bacteria and ciliate‐associated methanogen was reduced at all concentrations of extracts. These results indicate that LJE have the potential to serve as a ruminal fermentation modifier to suppress CH4 production with minimal effects on nutrient digestion in the rumen.
Endometriosis infiltrating the pelvic floor muscles with histopathological correlation—A case report
Authors: Crispi Jr Claudio P. , Crispi Claudio P. , de Paula Crispi Fernanda , Cardeman Leon , Salomao Alice C. C. Brandão , de Freitas Fonseca Marlon
Published: July 2019

We report the case of a 29‐year‐old woman with deep infiltrating endometriosis who underwent robotic nerve‐sparing surgery for resection of all visible lesions infiltrating pelvic and extrapelvic sites. Painful symptoms included severe dysmenorrhea, menstrual dyschezia and stranguria, with no improvement in response to hormonal treatment. The location on physical examination of a painful retrocervical nodule was identified by magnetic resonance imaging to be infiltrating the right parametrium/paracervix. During surgery, this nodule was recognized as an important retrocervical/rectovaginal lesion infiltrating the pelvic floor (i.e. levator ani and coccygeus), and was histopathologically confirmed as endometriosis infiltrating the skeletal pelvic floor muscles. A Pubmed search of the MEDLINE database in March (2019) found no publication reporting histopathologic confirmation of endometriosis infiltrating the pelvic floor muscles.
HLA‐DQB1*03:01:01:21Q, a novel HLA‐DQB1 allele, detected in a Spanish volunteer bone marrow donor
Authors: Marin Rubio Luis A. , Rada Ramon , Ontañon Jesús
Published: July 2019

HLA‐DQB1*03:01:01:21Q differs from HLA‐DQB1*03:01:01:03 by a single‐nucleotide substitution (G → A) at position 1 of intron 3.
Forum on teaching Asian religions in the American South
Authors: Mikles Natasha L. , Esaki Brett J. , Battaglia Lisa
Published: July 2019

This series of three essays by educators from Georgia, Texas, and Alabama examines teaching Asian Religions in the American South. Through reflection on individual experience, each essay offers concrete strategies for the classroom that can be utilized by fellow educators working in the American South, but can also inform pedagogy in other North American regions. Introducing the idea of the “imagined student,” Esaki discusses teaching African American students and tailoring Asian religions courses towards their interests by producing positive buy‐in, while also acknowledging their potential isolation from White peers interested in similar topics. Mikles builds on Esaki's idea of the imagined student to discuss her own experience teaching Mexican and Vietnamese American students in Texas, while presenting specific strategies to overcome preconceived educator bias about students in Southern classrooms. Battaglia closes out the series by suggesting the use of a phenomenological approach for students to sympathetically enter into an Asian religious worldview. She offers specific exercises that can help students unpack their own assumptions – their “invisible backpack” – and approach Asian religions on their own terms.
The Impact of Patient-Specific Vascular Structure on Localized Cooling in the Human Heart
Authors: Spangenberg Nathan , Merrill Thomas , Mitchell Jennifer , Attaluri Anilchandra
Published: July 2019

Acute Myocardial Infarction (AMI) is the leading cause of worldwide death and disability, and approximately 720,000 Americans will experience an AMI in 2018. Studies have shown that rapid hypothermia therapy (< 35°C) before reperfusion in patients with AMI can reduce infarct size by 37%. Localized therapeutic hypothermia has proven the potential to cool heart tissue rapidly following AMI, 3°C in 5 minutes. Using digital imaging software and the finite volume method we analyzed temperature distributions in six patient-specific LCX artery models. A mock circulatory loop was used to determine the exiting temperatures of a standard 7 Fr catheter with flow rates ranging from 9.1 ml/min to 88.9 ml/min for input into our model. The said flow rates were fed into our model using 0.45 W and 128.4 W of cooling, respectively. Our work showed typical exit temperatures were between 35.8°C and 36.9°C using a 29.2 ml/min catheter infusion flow rate in all six heart models. Additionally, results of this study indicate that biovariability in patient-specific vascular structures significantly impacts Therapeutic Hypothermia (TH) treatment methods. These results indicate that further research is needed to examine more accurate physiological effects, such as pulsatile flow. Future models will be used to provide insight to guide more efficient TH device designs and operational parameters to optimize patient outcomes following AMI.
Development for Clinical Use of a Multiplexed Immunoassay Using Sputum Samples for Streptococcus pneumoniae: a Non-Culture-Based Approach for Serotype-Specific Detection
Authors: Kim Sun Jin , Jeong Yoo Jung , Kim Jong Hun , Yoon Young Kyung , Sohn Jang Wook , Nahm Moon Hee , Kim Min Ja
Published: July 2019

The multiplexed immunoassay (MIA) is an automated, monoclonal antibody-based serotyping assay that uses culture lysates of
Streptococcus pneumoniae
. This study describes the development and validation of applying MIA directly to sputum samples for the serotype-specific detection of
S. pneumoniae
. Sputum optimization involved liquefaction and fractionation.