bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐translational modifications in effectors and plant proteins involved in host–pathogen conflicts
Authors: Tahir J. , Rashid M. , Afzal A. J.
Published: January 2019

Molecular interplay between two species is largely driven by protein–protein interactions and protein modifications that set the pace of co‐evolution in these species. During host–pathogen interactions, proteins involved in virulence and defence impart tempospatial dynamic post‐translational modifications (PTMs) to gain advantage for the causative species. Pathogens mainly cause disease in plant hosts by secreting elicitors (peptides and small molecules) or proteins in the inter‐ and intracellular space of host cells. These pathogen proteins have evolved a wide array of sophisticated mechanisms to manipulate host responses, including resistance. Through a set of diverse events ranging from PTMs to post‐translational oligomerization, these proteins are able to enhance virulence and suppress the otherwise elaborate plant immune system. Similarly, PTMs adapted by host proteins often lead to the activation of a robust defence response. Insights into the PTMs of pathogen and host proteins are therefore germane to the understanding of the co‐evolutionary arms race. This review summarizes the characterization of PTMs in pathogen effectors and their target host proteins. Based on this, a metaphorical view of host–pathogen conflicts is proposed, where PTMs act as molecular pivots in a 3D combinatorial game model – a novel abstraction of the arms race, where these molecular pivots restore the balance of competition between the two organisms.
Addition of lignin to lime materials for expedited pH increase and improved vertical mobility of lime in no‐till soils
Authors: Tao Haiying , Pan William L. , Carter Paul , Wang Ku
Published: January 2019

Soil acidification caused by long‐term nitrogen (N) fertilizer applications has been a growing concern for dryland crop production in both tilled and no‐till soils in the Pacific Northwest (PNW). Many no‐till soils have stratified soil pH in the 5–10 cm depth due to repeated N fertilizer applications at this depth. In the PNW, the practice of liming to correct low soil pH is complicated due to lack of affordable lime sources and because the inherent difficulty in ameliorating stratified soil acidity in no‐till systems. An intact soil‐column incubation study was conducted to investigate whether mixing lime materials with lignin‐containing black liquor—a by‐product from the pulp industry—could elevate soil pH change in both conventional and no‐till systems and expedite vertical downward movement of lime in no‐till system. Results indicate that mixing lime with black liquor has the potential to not only elevate the increase in soil pH in both conventional till and no‐till systems, but also accelerate downward movement of lime to correct soil pH below the soil surface. Mixing agricultural lime or super fine micro lime with black liquor increased soil pH to a depth of 25–30 cm within 147 days after surface application to a no‐till soil.
Identification of the novel allele, HLA‐B*40:379, by next‐generation sequencing
Authors: Seshasubramanian Vani , SathishKannan Aruna Devi , Naganathan Chandramouleeswaran , Nandakumar Yogesh , Narayan Saranya
Published: January 2019

Identification of the novel allele HLA‐B*40:379 carrying polymorphisms in an intron, exon and the 3′ untranslated region.
Sources of inequality in the Philippines: Insights from stochastic dominance tests for richness and poorness
Authors: Valenzuela Maria Rebecca , Wong Wing‐Keung , Zhu Zhen Zhen
Published: January 2019

New stochastic dominance (SD) tests of richness and poorness are applied to income and expenditure distributions in the Philippines to measure relative welfare levels and investigate sources of inequality from 2000 to 2012. We successfully demonstrate that welfare analyses based on ascending and descending SD principles offer a stronger characterisation of changing levels of welfare in a population than what could be obtained using standard SD approach alone. Empirically, our results show that large improvements in relative welfare over time in the Philippines favoured older and female‐headed households, mainly in the urban areas. Further, female headship and more years in education promoted higher welfare within and among the population groups. On the other hand, the growth of remittance incomes may have caused the greater imbalance in the distributions found in more recent years. Analysis by age groups meanwhile showed that over time, there are increasing concentrations of poorer households among the youngest cohort (30 and under), at the same time that there are also increasing concentrations of richer households among the over 60s. The combined impact of these factors provides a viable explanation as to why the gap between the rich and the poor has remained high in the Philippines for a very long time now.
Profinite detection of 3-manifold decompositions
Authors: Wilton Henry , Zalesskii Pavel
Published: January 2019

The profinite completion of the fundamental group of a closed, orientable$3$-manifold determines the Kneser–Milnor decomposition. If$M$is irreducible, then the profinite completion determines the Jaco–Shalen–Johannson decomposition of$M$.
125Iodide as a surrogate tracer for epithelial chloride transport by the mouse large intestine in vitro
Authors: Stephens Christine E. , Whittamore Jonathan M. , Hatch Marguerite
Published: January 2019

New Findings

What is the central question of this study?

The tracer 36Cl−, currently used to measure transepithelial Cl− fluxes, has become prohibitively expensive, threatening its future use. 125Iodide, previously validated alongside 36Cl− as a tracer of Cl− efflux by cells, has not been tested as a surrogate for 36Cl− across epithelia.

What is the main finding and its importance?

We demonstrate that 125I− can serve as an inexpensive replacement for measuring Cl− transport across mouse large intestine, tracking Cl− transport in response to cAMP stimulation (inducing Cl− secretion) in the presence and absence of the main gastrointestinal Cl−–HCO3− exchanger, DRA.

Chloride transport is important for driving fluid secretion and absorption by the large intestine, with dysregulation resulting in diarrhoea‐associated pathologies. The radioisotope 36Cl− has long been used as a tracer to measure epithelial Cl− transport but is prohibitively expensive. 125Iodide has been used as an alternative to 36Cl− in some transport assays but has never been validated as an alternative for tracing bidirectional transepithelial Cl− fluxes. The goal of this study was to validate 125I− as an alternative to 36Cl− for measurement of Cl− transport by the intestine. Simultaneous fluxes of 36Cl− and 125I− were measured across the mouse caecum and distal colon. Net Cl− secretion was induced by the stimulation of cAMP with a cocktail of forskolin (FSK) and 3‐isobutyl‐1‐methylxanthine (IBMX). Unidirectional fluxes of 125I− correlated well with 36Cl− fluxes after cAMP‐induced net Cl− secretion, occurring predominantly through a reduction in the absorptive mucosal‐to‐serosal Cl− flux rather than by stimulation of the secretory serosal‐to‐mucosal Cl− flux. Correlations between 125I− fluxes and 36Cl− fluxes were maintained in epithelia from mice lacking DRA (Slc26a3), the main Cl−–HCO3− exchanger responsible for Cl− absorption by the large intestine. Lower rates of Cl− and I− absorption in the DRA knockout intestine suggest that DRA might have a previously unrecognized role in iodide uptake. This study validates that 125I− traces transepithelial Cl− fluxes across the mouse large intestine, provides insights into the mechanism of net Cl− secretion and suggests that DRA might be involved in intestinal iodide absorption.
Structural effects on the performance of epoxide-based negative-tone molecular resists
Authors: Sharp Brandon L. , Narcross Hannah L. , Ludovice Peter , Tolbert Laren M. , Henderson Clifford L.
Published: January 2019

Several 0.26N tetramethylammonium hydroxide (TMAH)-soluble epoxide molecular resists have been synthesized and are reported here. Previously, the patterning performance of 1,1,2,2-tetrakis(p-hydroxyphenyl)ethane-3 epoxide (TPOE-3Ep) was reported and resolved 26 nm lines using extreme ultraviolet lithography. Here, a deeper study is performed to determine the effects of various structural features on the lithographic performance of 0.26N TMAH-soluble molecular resists. Increasing the number of phenols resulted in a notable increase in the glass transition temperature (Tg) of these materials, which required high postexposure bake (PEB) temperatures to achieve normalized remaining thickness (NRT) values of 1 in methyl isobutyl ketone development. Such high PEB temperatures resulted in insoluble material (high NRT values) in unexposed regions in the 248 nm contrast curves. Methyl groups were introduced adjacent to the hydroxyl group of phenol in an attempt to lower the Tg of the resists to allow the use of lower PEB temperatures. The methyl groups only slightly lowered the Tg of the resists, while detrimentally reducing the final NRT. Thus, instead of using the TPOE core or its methylated analog, a smaller core was used, and the resist trihydroxyphenyl ethane (THPE)-2Ep was designed and synthesized to be a low-Tg base-soluble resist. THPE-2Ep has a Tg of 41 °C and showed promising early performance using e-beam lithography and resolves 30 nm lines in 0.26N TMAH developer at a dose of 72 μC/cm2 at a PEB of 50 °C.
Understanding flow-induced crystallization in polymers: A perspective on the role of molecular simulations
Authors: Graham Richard S.
Published: January 2019

Flow-induced crystallization in polymers is an important problem in both fundamental polymer science and industrial polymer processing. The key process of flow-induced nucleation occurs on a very rapid time scale and on a highly localized lengthscale and so is extremely difficult to observe directly in experiments. However, recent advances in molecular dynamics (MD) simulations mean that flow-induced nucleation can be simulated at an achievable computational cost. Such studies offer unrivalled time and lengthscale resolution of the nucleation process. Nevertheless, the computational cost of MD places considerable constraints on the range of molecular weights, temperature, and polydispersity that can be studied. In this review, I will discuss recent progress, describe how future work might resolve or work around the constraints of molecular simulation, and examine how multiscale modeling could translate molecular insight into improved polymer processing.
Two Novel α-
l
-Arabinofuranosidases from
Bifidobacterium longum
subsp.
longum
Belonging to Glycoside Hydrolase Family 43 Cooperatively Degrade Arabinan
Authors: Komeno Masahiro , Hayamizu Honoka , Fujita Kiyotaka , Ashida Hisashi
Published: January 2019

We identified two novel α-
l
-arabinofuranosidases, BlArafC and BlArafB, from
B. longum
subsp.
longum
JCM 1217, both of which are predicted to be extracellular membrane-bound enzymes. The former specifically acts on α1,2/3-
l
-arabinofuranosyl linkages, while the latter acts on the α1,5-
l
-arabinofuranosyl linkage. These enzymes cooperatively degrade arabinan and are required for the efficient growth of bifidobacteria in arabinan-containing medium. The genes encoding these enzymes are located side by side in a gene cluster involved in metabolic pathways for plant-derived polysaccharides, which may confer adaptability in adult intestines.
CD8
+
Cytotoxic-T-Lymphocyte Breadth Could Facilitate Early Immune Detection of Immunodeficiency Virus-Derived Epitopes with Limited Expression Levels
Authors: Tsukamoto Tetsuo , Yamamoto Hiroyuki , Matano Tetsuro
Published: January 2019

Cytotoxic-T-lymphocyte (CTL) responses are important to control the replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Accumulating evidence suggests that the ability of a few immunodominant T-cell populations to detect and kill HIV/SIV-infected cells is important in individuals with a protective major histocompatibility complex class I (MHC-I) allele.
“I don't go to Meetings”: understanding farmer perspectives on bovine TB and biosecurity training
Authors: Hamilton Lindsay , Evans Nick , Allcock James
Published: January 2019

In 2016, a veterinary service company, XL Farmcare UK, was awarded a Defra contract to manage a series of on‐farm demonstration workshops to raise biosecurity awareness. The workshops provided free training for cattle farmers in England on the practical measures that they could take to limit the threat of bovine tuberculosis (bTB). Despite communicating these events to farmers, the number who subsequently attended them was low and the company decided to conduct research to seek explanation. Farmers were interviewed at agricultural shows, their comments analysed and the frequency of words in use were measured to produce a set of common themes. This thematic analysis provides an illustrative rather than representative picture of farmer opinions yet holds significant explanatory value for understanding the apparent lack of engagement with biosecurity training. Broad‐ranging farmer perspectives can be understood through a ‘typology’ of feelings about bTB, particularly expressions of blame, loss, confusion, ignorance, resignation and fear. The cumulative effect amounts to one of overwhelming negativity, explaining why so many farmers disengaged from training provision; a finding with relevance and value for the way training providers plan future communication methods in relation to biosecurity risk mitigation.
Evaluating the role of data quality when sharing information in hierarchical multistock assessment models, with an application to Dover sole
Authors: Johnson Samuel D.N. , Cox Sean P.
Published: January 2019

An emerging approach to data-limited fisheries stock assessment uses hierarchical multistock assessment models to group stocks together, sharing information from data-rich to data-poor stocks. In this paper, we simulate data-rich and data-poor fishery and survey data scenarios for a complex of Dover sole (Microstomus pacificus) stocks. Simulated data for individual stocks were used to compare estimation performance for single-stock and hierarchical multistock versions of a Schaefer production model. The single-stock and best-performing multistock models were then used in stock assessments for the real Dover sole data. Multistock models often had lower estimation errors than single-stock models when assessment data had low statistical power. Relative errors for productivity and relative biomass parameters were lower for multistock assessment model configurations. In addition, multistock models that estimated hierarchical priors for survey catchability performed the best under data-poor scenarios. We conclude that hierarchical multistock assessment models are useful for data-limited stocks and could provide a more flexible alternative to data pooling and catch-only methods; however, these models are subject to nonlinear side effects of parameter shrinkage. Therefore, we recommend testing hierarchical multistock models in closed-loop simulations before application to real fishery management systems.
Prediction of diameter distributions and tree-lists in southwestern Oregon using LiDAR and stand-level auxiliary information
Authors: Mauro Francisco , Frank Bryce , Monleon Vicente J. , Temesgen Hailemariam , Ford Kevin R.
Published: January 2019

Diameter distributions and tree-lists provide information about forest stocks disaggregated by size and species and are key for informing forest management. Diameter distributions and tree-lists are multivariate responses, which makes the evaluation of methods for their prediction reliant on the use of dissimilarity metrics to summarize differences between observations and predictions. We compared four strategies for selection of k nearest neighbors (k-NN) methods to predict diameter distributions and tree-lists using LiDAR and stand-level auxiliary data and analyzed the effect of the k-NN distance and number of neighbors in the performance of the predictions. Strategies differed by the dissimilarity metric used to search for optimal k-NN configurations and the presence or absence of post-stratification. We also analyzed how alternative k-NN configurations ranked when tree-lists were aggregated using different DBH classes and species groupings. For all dissimilarity metrics, k-NN configurations using random-forest distance and three or more neighbors provided the best results. Rankings of k-NN configurations based on different dissimilarity metrics were relatively insensitive to changes on the width of the DBH classes and the definition of the species groups. The selection of the k-NN methods was clearly dependent on the choice of the dissimilarity metric. Further research is needed to find suitable ways to define dissimilarity metrics that reflect how forest managers evaluate differences between predicted and observed tree-lists and diameter distributions.
Period-1 Evolutions to Chaos in a Periodically Forced Brusselator
Authors: Luo Albert C. J. , Guo Siyu
Published: January 2019

In this paper, analytical solutions of periodic evolutions of the Brusselator with a harmonic diffusion are obtained through the generalized harmonic balance method. The stability and bifurcation of the periodic evolutions are determined. The bifurcation tree of period-1 to period-8 evolutions of the Brusselator is presented through frequency-amplitude characteristics. To illustrate the accuracy of the analytical periodic evolutions of the Brusselator, numerical simulations of the stable period-1 to period-8 evolutions are completed. The harmonic amplitude spectrums are presented for the accuracy of the analytical periodic evolution, and each harmonics contribution on the specific periodic evolution can be achieved. This study gives a better understanding of periodic evolutions to chaos in the slowly varying Brusselator system, and the bifurcation tree of period-1 evolution to chaos are clearly demonstrated, which can help one understand a route of periodic evolution to chaos in chemical reaction oscillators. From this study, the generalized harmonic balance method is a good method for slowly varying systems, and such a method provides very accurate solutions of periodic motions in such nonlinear systems.
Experimental and Numerical Observation of Successive Mixed-Mode Oscillation-Incrementing Bifurcations in an Extended Bonhoeffer–van der Pol Oscillator
Authors: Shimizu Kuniyasu , Inaba Naohiko
Published: January 2019

Mixed-mode oscillation-incrementing bifurcations (MMOIBs) are a universal phenomenon appearing in a large class of mixed-mode oscillation (MMO)-generating dynamics that appear to be governed by asymmetric Farey arithmetic. This report presents experimental and numerical observations of the simplest MMOIBs generated by an extended Bonhoeffer–van der Pol circuit. The results indicate that maintaining a constant temperature during the circuit experiments is required to yield stable MMOs and MMOIBs. We also clarify how the firing number variations related to MMOIB phenomena follow asymmetric Farey arithmetic.
Distributed learning with indefinite kernels
Authors: Shi Lei
Published: January 2019

We investigate the distributed learning with coefficient-based regularization scheme under the framework of kernel regression methods. Compared with the classical kernel ridge regression (KRR), the algorithm under consideration does not require the kernel function to be positive semi-definite and hence provides a simple paradigm for designing indefinite kernel methods. The distributed learning approach partitions a massive data set into several disjoint data subsets, and then produces a global estimator by taking an average of the local estimator on each data subset. Easy exercisable partitions and performing algorithm on each subset in parallel lead to a substantial reduction in computation time versus the standard approach of performing the original algorithm on the entire samples. We establish the first mini-max optimal rates of convergence for distributed coefficient-based regularization scheme with indefinite kernels. We thus demonstrate that compared with distributed KRR, the concerned algorithm is more flexible and effective in regression problem for large-scale data sets.
Ocean ecosystem discrete time dynamics generated by ℓ-Volterra operators
Authors: Rozikov U. A. , Shoyimardonov S. K.
Published: January 2019

We consider a discrete-time dynamical system generated by a nonlinear operator (with four real parameters [Formula: see text]) of ocean ecosystem. We find conditions on the parameters under which the operator is reduced to a [Formula: see text]-Volterra quadratic stochastic operator mapping two-dimensional simplex to itself. We show that if [Formula: see text], then (under some conditions on [Formula: see text]) this [Formula: see text]-Volterra operator may have up to three or a countable set of fixed points; if [Formula: see text], then the operator has up to three fixed points. Depending on the parameters, the fixed points may be attracting, repelling or saddle points. The limit behaviors of trajectories of the dynamical system are studied. It is shown that independently on values of parameters and on initial (starting) point, all trajectories converge. Thus, the operator (dynamical system) is regular. We give some biological interpretations of our results.
ER stress contributes to high-fat diet-induced decrease of thyroglobulin and hypothyroidism
Authors: Zhang Xiaohan , Shao Shanshan , Zhao Lifang , Yang Rui , Zhao Meng , Fang Li , Li Mengzhu , Chen Wenbin , Song Yongfeng , Xu Chao , Zhou Xiaoming , Zhao Jiajun , Gao Ling
Published: January 2019

Recent studies revealed the emerging role of excess uptake of lipids in the development of hypothyroidism. However, the underlying mechanism is largely unknown. We investigated the effect of high-fat diet (HFD) on thyroid function and the role of endoplasmic reticulum (ER) in HFD-induced hypothyroidism. Male Sprague-Dawley rats were fed with HFD or control diet for 18 wk. HFD rats showed an impaired thyroid function, with decreased thyroglobulin (Tg) level. We found the ER stress was triggered in HFD rat thyroid glands and palmitate-treated thyrocytes. Luminal swelling of ER in thyroid epithelial cells of HFD rats was also observed. The rate of Tg degradation increased in palmitate-treated thyrocytes. In addition, applying 4-phenyl butyric acid to alleviate ER stress in HFD rats improved the decrease of Tg and thyroid function. Withdrawal of the HFD improved thyroid function . In conclusion, we demonstrate that ER stress mediates the HFD-induced hypothyroidism, probably by impairing the production of Tg, and attenuation of ER stress improves thyroid function. Our study provides the understanding of how HFD induces hypothyroidism.
Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans
Authors: Sachs Stephan , Zarini Simona , Kahn Darcy E. , Harrison Kathleen A. , Perreault Leigh , Phang Tzu , Newsom Sean A. , Strauss Allison , Kerege Anna , Schoen Jonathan A. , Bessesen Daniel H. , Schwarzmayr Thomas , Graf Elisabeth , Lutter Dominik , Krumsiek Jan , Hofmann Susanna M. , Bergman Bryan C.
Published: January 2019

Intermuscular adipose tissue (IMAT) is negatively related to insulin sensitivity, but a causal role of IMAT in the development of insulin resistance is unknown. IMAT was sampled in humans to test for the ability to induce insulin resistance in vitro and characterize gene expression to uncover how IMAT may promote skeletal muscle insulin resistance. Human primary muscle cells were incubated with conditioned media from IMAT, visceral (VAT), or subcutaneous adipose tissue (SAT) to evaluate changes in insulin sensitivity. RNAseq analysis was performed on IMAT with gene expression compared with skeletal muscle and SAT, and relationships to insulin sensitivity were determined in men and women spanning a wide range of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Conditioned media from IMAT and VAT decreased insulin sensitivity similarly compared with SAT. Multidimensional scaling analysis revealed distinct gene expression patterns in IMAT compared with SAT and muscle. Pathway analysis revealed that IMAT expression of genes in insulin signaling, oxidative phosphorylation, and peroxisomal metabolism related positively to donor insulin sensitivity, whereas expression of macrophage markers, inflammatory cytokines, and secreted extracellular matrix proteins were negatively related to insulin sensitivity. Perilipin 5 gene expression suggested greater IMAT lipolysis in insulin-resistant individuals. Combined, these data show that factors secreted from IMAT modulate muscle insulin sensitivity, possibly via secretion of inflammatory cytokines and extracellular matrix proteins, and by increasing local FFA concentration in humans. These data suggest IMAT may be an important regulator of skeletal muscle insulin sensitivity and could be a novel therapeutic target for skeletal muscle insulin resistance.
Chronic maternal cortisol excess during late gestation leads to metabolic alterations in the newborn heart
Authors: Walejko Jacquelyn M. , Antolic Andrew , Koelmel Jeremy P. , Garrett Timothy J. , Edison Arthur S. , Keller-Wood Maureen
Published: January 2019

Our laboratory has previously shown in an ovine model of pregnancy that abnormal elevations in maternal cortisol during late gestation lead to increased fetal cardiac arrhythmias and mortality during peripartum. Furthermore, transcriptomic analysis of the fetal heart suggested alterations in TCA cycle intermediates and lipid metabolites in animals exposed to excess cortisol in utero. Therefore, we utilized a sheep model of pregnancy to determine how chronic increases in maternal cortisol alter maternal and fetal serum before birth and neonatal cardiac metabolites and lipids at term. Ewes were either infused with 1 mg·kg−1·day−1of cortisol starting at gestational day 115 ( n = 9) or untreated ( n = 6). Serum was collected from the mother and fetus (gestational day 125), and hearts were collected following birth. Proton nuclear magnetic resonance (1H-NMR) spectroscopy was conducted to measure metabolic profiles of newborn heart specimens as well as fetal and maternal serum specimens. Mass spectrometry was conducted to measure lipid profiles of newborn heart specimens. We observed alterations in amino acid and TCA cycle metabolism as well as lipid and glycerophospholipid metabolism in newborn hearts after excess maternal cortisol in late gestation. In addition, we observed alterations in amino acid and TCA cycle metabolites in fetal but not in maternal serum during late gestation. These results suggest that fetal exposure to excess maternal cortisol alters placental and fetal metabolism before birth and limits normal cardiac metabolic maturation, which may contribute to increased risk of peripartum cardiac arrhythmias observed in these animals or later life cardiomyopathies.
ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme
Authors: Zhao Zheng , Zhang Ke-Nan , Chai Rui-Chao , Wang Kuan-Yu , Huang Ruo-Yu , Li Guan-Zhang , Wang Yong-Zhi , Chen Jing , Jiang Tao
Published: January 2019

Background. Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. Methods. A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. Results. We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. Conclusion. The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.
High-Titre Neutralizing Antibodies to H1N1 Influenza Virus after Mouse Immunization with Yeast Expressed H1 Antigen: A Promising Influenza Vaccine Candidate
Authors: Kopera Edyta , Zdanowski Konrad , Uranowska Karolina , Kosson Piotr , Sączyńska Violetta , Florys Katarzyna , Szewczyk Bogusław
Published: January 2019

H1N1 influenza virus is still regarded as a serious pandemic threat. The most effective method of protection against influenza virus and the way to reduce the risk of epidemic or pandemic spread is vaccination. Influenza vaccine manufactured in a traditional way, though well developed, has some drawbacks and limitations which have stimulated interest in developing alternative approaches. In this study, we demonstrate that the recombinant H1 vaccine based on the hydrophilic haemagglutinin (HA) domain and produced in the yeast system elicited high titres of serum haemagglutination-inhibiting antibodies in mice. Transmission electron microscopy showed that H1 antigen oligomerizes into functional higher molecular forms similar to rosette-like structures. Analysis of the N-linked glycans using mass spectrometry revealed that the H1 protein is glycosylated at the same sites as the native HA. The recombinant antigen was secreted into a culture medium reaching approximately 10 mg/l. These results suggest that H1 produced inPichia pastoriscan be considered as the vaccine candidate against H1N1 virus.
Inflammasomes, Autophagy, and Cell Death: The Trinity of Innate Host Defense against Intracellular Bacteria
Authors: Krakauer Teresa
Published: January 2019

Inflammasome activation is an innate host defense mechanism initiated upon sensing pathogens or danger in the cytosol. Both autophagy and cell death are cell autonomous processes important in development, as well as in host defense against intracellular bacteria. Inflammasome, autophagy, and cell death pathways can be activated by pathogens, pathogen-associated molecular patterns (PAMPs), cell stress, and host-derived damage-associated molecular patterns (DAMPs). Phagocytosis and toll-like receptor (TLR) signaling induce reactive oxygen species (ROS), type I IFN, NFκB activation of proinflammatory cytokines, and the mitogen-activated protein kinase cascade. ROS and IFNγare also prominent inducers of autophagy. Pathogens, PAMPs, and DAMPs activate TLRs and intracellular inflammasomes, inducing apoptotic and inflammatory caspases in a context-dependent manner to promote various forms of cell death to eliminate pathogens. Common downstream signaling molecules of inflammasomes, autophagy, and cell death pathways interact to initiate appropriate measures against pathogens and determine host survival as well as pathological consequences of infection. The integration of inflammasome activation, autophagy, and cell death is central to pathogen clearance. Various pathogens produce virulence factors to control inflammasomes, subvert autophagy, and modulate host cell death in order to evade host defense. This review highlights the interaction of inflammasomes, autophagy, and host cell death pathways in counteractingBurkholderia pseudomallei, the causative agent of melioidosis. Contrasting evasion strategies used byB.pseudomallei,Mycobacterium tuberculosis, andLegionella pneumophilato avoid and dampen these innate immune responses will be discussed.
Achieving Complete Remission of Hepatocellular Carcinoma: A Significant Predictor for Recurrence-Free Survival after Liver Transplantation
Authors: Bürger Christin , Maschmeier Miriam , Hüsing-Kabar Anna , Wilms Christian , Köhler Michael , Schmidt Martina , Schmidt Hartmut H. , Kabar Iyad
Published: January 2019

Background. Liver transplantation (LT) is a curative treatment for hepatocellular carcinoma (HCC) and the underlying primary liver disease; however, tumor recurrence is still a major issue. Therefore, the aim of this study was to assess predictors and risk factors for HCC recurrence after LT in patients within and outside the Milan criteria with a special focus on the impact of different bridging strategies. Methods. All patients who underwent LT for HCC between 07/2002 and 09/2016 at the University Hospital of Muenster were consecutively included in this retrospective study. Database research was performed and a multivariable regression analysis was conducted to explore potential risk factors for HCC recurrence. Results. A total of 82 patients were eligible for the statistical analysis. Independent of bridging strategy, achieving complete remission (CR) was significantly associated with a lower risk for tumor recurrence (p = 0.029; OR = 0.426, 95% CI 0.198-0.918). A maximal diameter of lesion < 3 cm was also associated with lower recurrence rates (p = 0.040; OR = 0.140, 95% CI 0.022-0.914). Vascular invasion proved to be an independent risk factor for HCC recurrence (p = 0.004; OR = 11.357, 95% CI 2.142-60.199). Conclusion. Achieving CR prior to LT results in a significant risk reduction of HCC recurrence after LT independent of the treatment modalities applied.
Incentive Mechanism of R&D Firms’ Collaborative Innovation Based on Organisational Ambidexterity
Authors: Song Bo , Jin Penghao , Zhao Liangjie
Published: January 2019

From the perspective of organizational ambidexterity, we consider the choice of innovation strategy among R&D firms. By building on contractual arrangements and employing a dynamic game model, we focus on the incentive mechanism of R&D Firms’ collaborative innovation and analyze incentive contracts of benefits distribution and cost-sharing when two firms conduct market-driven innovation (exploitative innovation) strategy and technological research-driven innovation (exploratory innovation) strategy respectively, and collaborate for innovation with each other. We also discuss the influence of exploratory and exploitative innovation effects on decision-making of R&D firms regarding whether to choose collaborative innovation under different incentive contracts. The results show that the effects of exploratory innovation acts as the intrinsic motivation of collaborative innovation while exploratory innovation could be improved to some degree by exploitative innovation. In addition, both investment levels of exploratory and exploitative innovation would decrease (increase) when innovation cost (innovative efficiency) increases. Moreover, compared with a benefit-distribution contract, cost-sharing contracts would not only lead exploitative innovation to realize optimal revenue, but also provide incentives for exploratory innovation more effectively.
A Case Series of Breast Metastases from Different Extramammary Malignancies and Their Literature Review
Authors: Moreno-Astudillo Liliana , Villaseñor-Navarro Yolanda , Sánchez-Goytia Vyanka , Porras-Reyes Fany , Lara-Mercado Alfredo , Sollozo-Dupont Isabel
Published: January 2019

Metastasis to the breast from all other primary sites is unusual. Twelve patients were diagnosed between 2007 and 2017 at National Cancer Institute, Mexico. Solitary or multiple masses, round or oval, and hypoechoic and solid lesions with posterior acoustic shadowing were patterns commonly reported in these patients; other arrangements include diffuse involvement of the breast simulating an inflammatory carcinoma. The development of a breast metastasis is revealed, in our experience, as a negative prognostic factor. Thus, the radiologist should know about the varied appearance of metastatic breast lesions and provide radiopathological correlations when available.
Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response
Authors: Binder Pablo , Wang Shunyao , Radu Maria , Zin Min , Collins Lucy , Khan Saba , Li Yatong , Sekeres Karolina , Humphreys Neil , Swanton Eileithyia , Reid Adam , Pu Fay , Oceandy Delvac , Guan Kaomei , Hille Susanne S. , Frey Norbert , Müller Oliver J. , Cartwright Elizabeth J. , Chernoff Jonathan , Wang Xin , Liu Wei
Published: January 2019

Rationale:

Secreted and membrane-bound proteins, which account for 1/3 of all proteins, play critical roles in heart health and disease. The endoplasmic reticulum (ER) is the site for synthesis, folding, and quality control of these proteins. Loss of ER homeostasis and function underlies the pathogenesis of many forms of heart disease.

Objective:

To investigate mechanisms responsible for regulating cardiac ER function, and to explore therapeutic potentials of strengthening ER function to treat heart disease.

Methods and Results:

Screening a range of signaling molecules led to the discovery that Pak (p21-activated kinase)2 is a stress-responsive kinase localized in close proximity to the ER membrane in cardiomyocytes. We found that Pak2 cardiac deleted mice (Pak2-CKO) under tunicamycin stress or pressure overload manifested a defective ER response, cardiac dysfunction, and profound cell death. Small chemical chaperone tauroursodeoxycholic acid treatment of Pak2-CKO mice substantiated that Pak2 loss-induced cardiac damage is an ER-dependent pathology. Gene array analysis prompted a detailed mechanistic study, which revealed that Pak2 regulation of protective ER function was via the IRE (inositol-requiring enzyme)-1/XBP (X-box–binding protein)-1–dependent pathway. We further discovered that this regulation was conferred by Pak2 inhibition of PP2A (protein phosphatase 2A) activity. Moreover, IRE-1 activator, Quercetin, and adeno-associated virus serotype-9–delivered XBP-1s were able to relieve ER dysfunction in Pak2-CKO hearts. This provides functional evidence, which supports the mechanism underlying Pak2 regulation of IRE-1/XBP-1s signaling. Therapeutically, inducing Pak2 activation by genetic overexpression or adeno-associated virus serotype-9–based gene delivery was capable of strengthening ER function, improving cardiac performance, and diminishing apoptosis, thus protecting the heart from failure.

Conclusions:

Our findings uncover a new cardioprotective mechanism, which promotes a protective ER stress response via the modulation of Pak2. This novel therapeutic strategy may present as a promising option for treating cardiac disease and heart failure.
miR‐15a/15b Cluster Modulates Survival of Mesenchymal Stem Cells to Improve Its Therapeutic Efficacy of Myocardial Infarction
Authors: Tu Yingfeng , Qiu Yan , Liu Li , Huang Tao , Tang Hao , Liu Youbin , Guo Wenguang , Jiang Hongchi , Fan Yuhua , Yu Bo
Published: January 2019

Background

The poor viability of transplanted mesenchymal stem cells (MSCs) hampers their therapeutic efficacy for ischemic heart disease. Micro
RNA
s are involved in regulation of
MSC
survival and function. The present study was designed to investigate the molecular effects of mi
R
‐15a/15b on
MSC
survival, focusing on the role of vascular endothelial growth factor receptor 2.

Methods and Results

We first harvested donor luc(Luciferase)‐
MSC
s (5×10
5
) isolated from the luciferase transgenic mice with
FVB
background. Luc‐
MSC
s were transfected with miR‐15a/15b mimics or inhibitors and cultured under oxygen glucose deprivation condition for 12 hours to mimics the harsh microenvironment in infarcted heart; they were subjected to MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide?Thiazolyl Blue Tetrazolium Bromide) assay, bioluminescence imaging, quantitative reverse transcription–polymerase chain reaction, transferase‐mediated deoxyuridine triphosphate–digoxigenin nick‐end labeling assay, and flow cytometry. Furthermore, the levels of vascular endothelial growth factor receptor 2, protein kinase B, p(Phosphorylate)‐protein kinase B, Bcl‐2, Bax, and caspase‐3 proteins were available by Western blotting assay. In vivo, acute myocardial infarction was induced in 24 mice by coronary ligation, with subsequent receipt of Luc‐
MSC
s, Luc‐
MSC
s+miR‐15a/15b inhibitors, or
PBS
treatment. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging and echocardiographic measurement. Next, ex vivo imaging and immunohistochemistry were conducted to verify the distribution of
MSC
s. We demonstrated that miR‐15a/15b targeted vascular endothelial growth factor receptor 2 to modulate
MSC
survival, possibly via phosphatidylinositol 3‐kinase/protein kinase B signaling pathway, which was proved by bioluminescence imaging, immunohistochemistry analysis, and echocardiographic measurement.

Conclusions

Luc‐
MSC
s could be followed dynamically in vitro and in vivo by bioluminescence imaging, and the role of mi
R
‐15a/b could be inferred from the loss of signals from luc‐
MSC
s. This finding may have practical clinical implications in mi
R
‐15a/15b–modified
MSC
transplantation in treating myocardial infarction.
Aspidistra luochengensis (Asparagaceae), a new species from Guangxi, China

Authors: PAN BO , QIN YING , LIN CHUN-RUI
Published: January 2019

Aspidistra louchengensis (Asparagaceae) is described and illustrated from limestone areas in northern Guangxi Zhuang Autonomous Region, China. It is similar to A. obconica C.R.Lin & Yan Liu with the perianth obconical campanulate, stamens inserted at upper third of perianth tube, but it can be clearly distinguished by leaf blade narrower and longer, perigone lobes longer (6–8 mm), adaxial densely papillose and scabrous, apex acuminate and outcurved, and stigma upper surface slightly concave. This new species is only known from Luocheng Mulao Autonomous County in Guangxi, China.
DNA Barcoding of Endangered Paphiopedilum species (Orchidaceae) of Peninsular Malaysia

Authors: RAJARAM MICHEAL C. , YONG CHRISTINA S.Y. , GANSAU JUALANG A. , GO RUSEA
Published: January 2019

In this study, the efficacy of four DNA markers and their combinations (rbcL, matK, ITS, trnH-psbA) as barcode markers were tested across the endangered Paphiopedilum species from Peninsular Malaysia. Four species of Paphiopedilum were sampled and barcoded. The DNA barcodes reliabilities were evaluated using NCBI BLASTn program, phylogenetic tree via Neighbour-Joining method with 1000 bootstrap replicates in MEGA 6 and barcoding gap assessment. matK is the most promising barcode with high sequence quality (100%), high accuracy in BLASTn (100%), clear resolution of species in Neighbour-Joining phylogenetic tree (100%) and a distinct barcoding gap followed by ITS, trnH-psbA and rbcL. The combination of barcode regions revealed the lack of variation in rbcL and trnH-psbA but they are still useful for preliminary identification followed up by matK for accurate identification.
Systematic significance of seed morphology in Acanthophyllum (Caryophyllaceae: tribe Caryophylleae) in Iran

Authors: PIRANI ATEFEH , ZARRE SHAHIN , RABELER RICHARD , ASSADI MOSTAFA , JOHARCHI MOHAMMAD REZA , OXELMAN BENGT
Published: January 2019

Acanthophyllum, with ca. 90 spiny cushion-forming species, is one of the largest genera of Caryophyllaceae. Although taxonomic utility of seed morphology has already been highlighted in different genera of Caryophyllaceae, the systematic value of seed characters in Acanthophyllum has not been adequately addressed. In order to evaluate the application of seed morphology in infrageneric classification of Acanthophyllum, we surveyed seed characters in the five Iranian sections of Acanthophyllum. Seed morphology of 32 accessions of Acanthophyllum representing 21 species and four sections were investigated using scanning electron microscopy. Seed morphological characters of two species from one additional section were included based on previous studies in the Caryophyllaceae. Seeds in the majority of examined species are oblong in outline. Five types of seed surface can be considered: reticulate, reticulate-papillate, colliculate, colliculate-papillate, and colliculate-columellate. Papillae type is a reliable character for separation of certain natural groups within Acanthophyllum. Seed features provided strong evidences for separating sections, especially the following ones: Acanthophyllum, Macrostegia and Pleiosperma, whose seeds showed a high degree of uniformity among the sampled species. Morphological characteristics of seeds were less useful for discriminating Acanthophyllum species. While seed characters are consistent within individual populations, they can vary among different populations of an individual species. Our results show that variation in seed morphological characters are in agreement with phylogenetic patterns within Acanthophyllum.
Microtropis cerocarpa (Celastraceae), a new species from southern Vietnam

Authors: SAVINOV IVAN A. , NURALIEV MAXIM S. , KUZNETSOV ANDREY N. , KUZNETSOVA SVETLANA P. , LUU HONG TRUONG , TRAN HUU DANG , LUONG HUU THANH
Published: January 2019

Microtropis cerocarpa, a new species of Celastraceae, is described and illustrated. The species was discovered in 2012 during a botanical survey of the Chu Yang Sin National Park (Dak Lak province, southern Vietnam); additional collections were obtained there in 2018. Microtropis cerocarpa possesses dense glomerate sessile inflorescence with sessile flowers which allows placing this species into sect. Microtropis. Within this section it is most similar to M. obscurinervia, M. rhynchocarpa and M. wui. The new species differs from related species mainly by large thick leaves 23.5–39 cm long and 13–22 cm wide with very short petiole (subsessile) and cordate base, fruit with short rostrum of 1–2 mm long at apex, and immature fruit surface with a pronounced white wax coating in the form of granules. Microtropis cerocarpa is an easily recognized tree with remarkable robust habit and large leaves. A description of the vegetation in the area inhabited by M. cerocarpa is provided. The data on species diversity of Microtropis in Vietnam are summarized and an identification key is compiled.
Podoscypha yunnanensis sp. nov. (Polyporales, Basidiomycota) evidenced by morphological characters and phylogenetic analyses
Authors: WU YA-XING , SHEN SHAN , ZHAO CHANG-LIN
Published: January 2019

A new wood-inhabiting fungal species, Podoscypha yunnanensis sp. nov., is proposed based on morphological and molecular characters. The species is characterized by annual, gregarious basidiocarps with spathulate to flabelliform pilei, a dimitic hyphal system with clamped generative hyphae, caulocystidia cylindrical with an apex, and ellipsoid to subglobose basidiospores measuring 3–3.5(–4) × 2.5–3(–3.5) µm. The internal transcribed spacer (ITS) and the large subunit (LSU) regions of the nuclear ribosomal RNA gene sequences of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and bayesian inference methods. The phylogenetic analyses based on molecular data of ITS sequences showed that P. yunnanensis belonged to the genus Podoscypha and was closely related to P. fulvonitens and P. mellissii. Phylogeny based on ITS+nLSU sequences demonstrated that the new species formed a monophyletic lineage with a high support (100% BS, 100% BP, 1.00 BPP).