bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbendazim-resistance associated β2-tubulin substitutions increase deoxynivalenol biosynthesis by reducing the interaction between β2-tubulin and IDH3 in Fusarium graminearum
Authors: Zhou Zehua , Duan Yabing , Zhou Mingguo
Published: September 2019

Microtubule is a well-known structural protein participating in cell division, motility and vesicle traffic. In this study, we found that β2-tubulin, one of the microtubule components, plays an important role in regulating secondary metabolite deoxynivalenol (DON) biosynthesis in Fusarium graminearum by interacting with isocitrate dehydrogenase subunit 3 (IDH3). We found IDH3 negatively regulate DON biosynthesis by reducing acetyl-CoA accumulation in F. graminearum and DON biosynthesis was stimulated by exogenous acetyl-CoA. In addition, the expression of IDH3 significantly decreased in the carbendazim-resistant mutant nt167 (Fgβ F167Y). Furthermore, we found that carbendazim-resistance associated β2-tubulin substitutions reducing the interaction intensity between β2-tubulin and IDH3. Interestingly, we demonstrated that β2-tubulin inhibitor carbendazim can disrupt the interaction between β2-tubulin and IDH3. The decreased interaction intensity between β2-tubulin and IDH3 resulted in the decreased expression of IDH3, which can cause the accumulation of acetyl-CoA, precursor of DON biosynthesis in F. graminearum. Thus, we revealed that carbendazim-resistance associated β2-tubulin substitutions or carbendazim treatment increases DON biosynthesis by reducing the interaction between β2-tubulin and IDH3 in F. graminearum. Taken together, the novel findings give the new perspectives of β2-tubulin in regulating secondary metabolism in phytopathogenic fungi.

Author Summary

The deoxynivalenol (DON) biosynthesis is increased in carbendazim-resistant strains in Fusarium graminearum. To date, the molecular mechanism between the carbendazim-resistant substitution and the increased DON production remained elusive. Here we found that acetyl-CoA-associated enzyme IDH3 negatively regulates acetyl-CoA and DON biosynthesis. Moreover, β2 tubulin interacted with IDH3 physically and increase its expression. We further found that carbendazim-resistant substitution in β2 tubulin reducing the interaction between β2 tubulin and IDH3, which resulted in the decreased expression of IDH3. In addition, we demonstrated that carbendazim disrupting the binding between β2 tubulin and IDH3, which also decreases the expression of IDH3. Taken together, our results give a newly insights into the mechanism of β2 tubulin and its carbendazim-resistant substitution in regulating DON biosynthesis.
Loss of pyrethroid resistance in newly established laboratory colonies of Aedes aegypti
Authors: Vera-Maloof Farah Z. , Saavedra-Rodriguez Karla , Penilla-Navarro Rosa P. , Rodriguez-Ramirez Americo D. , Dzul Felipe , Manrique Pablo , Black William C.
Published: September 2019

Background

Resistance to pyrethroid insecticides in Aedes aegypti has become widespread after almost two decades of their frequent use to reduce arbovirus transmission. Despite this, use of pyrethroids continues because they are relatively inexpensive and because of their low human toxicity. Resistance management has been proposed as a means to retain the use of pyrethroids in natural populations. A key component of resistance management assumes that there is a negative fitness associated with resistance alleles so that when insecticides are removed, resistance alleles will decline in frequency. At least three studies in Ae. aegypti have demonstrated a decrease in pyrethroid resistance once the insecticide is removed.

Methods/Principal Findings

The present study aims to evaluate variation in the loss of pyrethroid resistance among newly established laboratory populations of Ae. aegypti from Mexico. Eight field collections were maintained for up to eight generations and we recorded changes in the frequencies of mutations at the V1,016I locus and at the F1,534C locus in the voltage gated sodium channel (VGSC) gene. I1,016 and C1,534 confer resistance. We also examined resistance ratios (RR) with type 1 and 2 pyrethroids.

Conclusions/Significance

We demonstrate that, in general, the frequency of the Ae. aegypti pyrethroid resistance alleles I1,016 and C1,534 decline when they are freed from pyrethroid pressure in the laboratory. However, the pattern of decline is strain dependent. In agreement with earlier studies, RR was positively correlated with I1,016 resistant allele frequencies and showed significant protection against permethrin, and deltamethrin whereas F1534C showed protection against permethrin but not against deltamethrin.

Author Summary

The author is interested in the evolution of genes that confer resistance to insecticides, especially when this evolution affects binding of insecticides to their target site. The Voltage Gated Sodium Channel gene represents an excellent opportunity to understand how mutations at the target site(s) affect the evolution of resistance in many different pest insect species including Aedes aegypti, the primary vector of Dengue Virus, Yellow Fever, Zika and Chikungunya arboviruses.
Mapping the S1 and S1’ subsites of cysteine proteases with new dipeptidyl nitrile inhibitors as trypanocidal agents
Authors: Cianni Lorenzo , Lemke Carina , Gilberg Erik , Feldmann Christian , Rosini Fabiana , dos Reis Rocho Fernanda , Ribeiro Jean F.R. , Tezuka Daiane Y. , Lopes Carla D. , de Albuquerque Sérgio , Bajorath Jürgen , Laufer Stefan , Leitão Andrei , Gütschow Michael , Montanari Carlos A.
Published: September 2019

The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. A series of 26 new compounds waswere designed, synthesized, and tested against the recombinant cruzain (Cz) to map its S1/S1′ subsites. The same series was evaluated on a panel of four human cysteine proteases (CatB, CatK, CatL, CatS) and Leishmania mexicana CPB, which is a potential target for the treatment of cutaneous leishmaniasis. The synthesized compounds are dipeptidyl nitriles designed based on the most promising combinations of different moieties in P1 (ten), P2 (six), and P3 (four different building blocks). Eight compounds exhibited a Ki smaller than 20.0 nM for Cz, whereas three compounds met these criteria for LmCPB. The three inhibitors had an EC50 value of ca. 4 μM, thus being equipotent to benznidazole according to the anti-trypanosomal effects. Our mapping approach and the respective structure-activity relationships provide insights into the specific ligand-target interactions for therapeutically relevant cysteine proteases.

Author Summary

Despite many achievements in identifying novel agents for the treatment of tropical and neglected diseases, further research continues to be of fundamental importance. Our research groups have been using the cruzipain cysteine protease in its recombinant form, cruzain (Cz), to identify new trypanocidal agents. Considering the possible interchangeability with other cysteine proteases, the same series of dipeptidyl nitriles was tested in Leishmania mexicana LmCPB. Other potential targets for such inhibitors are human cysteine cathepsins, which are involved in different disease states. Thus, the inhibitors were also tested against cathepsins B, L, K, and S. Our results demonstrate that inhibition of these cysteine proteases can be achieved by appropriate structural modifications of dipeptidyl nitriles. It was also possible to identify trypanocidal agents, equipotent to benznidazole, the current drug of choice used for the treatment of Chagas disease.
Bioinformatics analysis of endophytic bacteria related to berberine in the Chinese medicinal plant Coptis teeta Wall
Authors: Liu Tian-hao , Zhang Xiao-mei , Tian Shou-zheng , Chen Li-guo , Yuan Jia-li
Published: September 2019

Plant endophytic microorganisms absorb nutrients and prevent pathogen damage, supporting healthy plant growth. However, relationships between endophytic bacteria of the medicinal plant Coptis teeta Wall. and berberine production remain unclear. Herein, we explored the microbial composition of wild-type (WT) and cultivated Coptis teeta Wall. root, stem and leaf, and endophytic bacteria related to berberine. Microbial characteristics of were analyzed by 16S rDNA sequencing, and berberine in roots was analyzed by high-performance liquid chromatography (HPLC). Proteobacteria, Actinobacteria and Bacteroidetes were the major phyla, and Mycobacterium, Salmonella, Nocardioides, Burkholderia-Paraburkholderia and Rhizobium were the dominant genera. Berberine was positively correlated with total P (TP), total N (TN), total K (TK) and available K (AK) in rhizosphere soil, and with Microbacterium and norank_f_7B-8, whereas TK was positively correlated with Microbacterium, TN, AK and Burkholderia-Paraburkholderia. The findings will support further studies on endophytic bacteria and berberine in Coptis teeta Wall., and may promote berberine production.
Evolutionary and biochemical analyses reveal conservation of the Brassicaceae telomerase ribonucleoprotein complex
Authors: Dew-Budd Kelly , Cheung Julie , Palos Kyle , Forsythe Evan S. , Beilstein Mark A.
Published: September 2019

The telomerase ribonucleoprotein complex (RNP) is essential for genome stability and performs this role through the addition of repetitive DNA to the ends of chromosomes. The telomerase enzyme is composed of a reverse transcriptase (TERT), which utilizes a template domain in an RNA subunit (TER) to reiteratively add telomeric DNA at the ends of chromosomes. Multiple TERs have been identified in the model plant Arabidopsis thaliana. Here we combine a phylogenetic and biochemical approach to understand how the telomerase RNP has evolved in Brassicaceae, the family that includes A. thaliana. Because of the complex phylogenetic pattern of template domain loss and alteration at the previously characterized A. thaliana TER loci, TER1 and TER2, across the plant family Brassicaceae, we bred double mutants from plants with a template deletion at AtTER1 and T-DNA insertion at AtTER2. These double mutants exhibited no telomere length deficiency, a definitive indication that neither of these loci encode a functional telomerase RNA. Moreover, we determined that the telomerase components TERT, Dyskerin, and the KU heterodimer are under strong purifying selection, consistent with the idea that the TER with which they interact is also conserved. To test this hypothesis further, we analyzed the substrate specificity of telomerase from species across Brassicaceae and determined that telomerase from close relatives bind and extend substrates in a similar manner, supporting the idea that TERs in different species are highly similar to one another and are likely encoded from an orthologous locus. Lastly, TERT proteins from across Brassicaceae were able to complement loss of function tert mutants in vivo, indicating TERTs from other species have the ability to recognize the native TER of A. thaliana. Finally, we immunoprecipitated the telomerase complex and identified associated RNAs via RNA-seq. Using our evolutionary data we constrained our analyses to conserved RNAs within Brassicaceae that contained a template domain. These analyses revealed a highly expressed locus whose disruption by a T-DNA resulted in a telomeric phenotype similar to the loss of other telomerase core proteins, indicating that the RNA has an important function in telomere maintenance.
Structural changes in secondary, but not primary, sensory cortex in individuals with congenital olfactory sensory loss
Authors: Peter Moa G. , Mårtensson Gustav , Postma Elbrich M. , Nordin Love Engström , Westman Eric , Boesveldt Sanne , Lundström Johan N.
Published: September 2019

Individuals with congenital sensory loss usually demonstrate altered brain morphology in areas associated with early processing of the lost sense. Here, we aimed to establish whether this also applies to individuals born without a sense of smell (congenital anosmia) by comparing cortical morphology between 33 individuals with isolated congenital anosmia and matched controls. We detected no structural alterations in the primary olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different plastic processes.
Epigenetic Memory Independent of Symmetric Histone Inheritance
Authors: Saxton Daniel S , Rine Jasper
Published: September 2019

Heterochromatic gene silencing is an important form of gene regulation that usually requires specific histone modifications. A popular model posits that inheritance of modified histones, especially in the form of H3-H4 tetramers, underlies inheritance of heterochromatin. Because H3-H4 tetramers are randomly distributed between daughter chromatids during DNA replication, rare occurrences of asymmetric tetramer inheritance within a heterochromatic domain would have the potential to destabilize heterochromatin. This model makes a prediction that shorter heterochromatic domains would experience unbalanced tetramer inheritance more frequently, and thereby be less stable. In contrast to this prediction, we found that shortening a heterochromatic domain in Saccharomyces had no impact on the strength of silencing nor its heritability. Additionally, we found that replisome mutations that disrupt inheritance of H3-H4 tetramers had only minor effects on heterochromatin stability. These findings suggest that histones carry little or no memory of the heterochromatin state through DNA replication.
Genetic diversity and haplotypic structure of a Saudi population sample using Investigator Argus X-12 amplification kit
Authors: Messaoudi Safia A. , Babu Saranya R. , Alsaleh Abrar B. , Albajjah Mohamed , AlSnan Noora , Chaudhary Abdul Rauf
Published: September 2019

X-chromosome short tandem repeat (X-STR) markers have shown a great capability in forensic identity investigations and paternity testing involving kinship analysis.

In the current study, the distribution of 12 X-STR loci located in four linkage groups was evaluated using Investigator® Argus X-12 Amplification Kit in 200 unrelated healthy individuals (105 males and 95 females) from the central region of the Saudi Arabia in order to create a DNA database.

Our results indicated that DXS10146 locus was the most informative with 21 alleles while DXS8378 locus was the least with five alleles. Forensic parameters showed that all X-STRs loci either as individual markers or as linkage groups provide genetic information with high discrimination that is appropriate for forensic purposes with Paternity Informed Consent (PIC), Power of exclusion (PE), and Paternity index (PI) varied from 0.61211 to 0.917979, 0.38722 to 0.842949, and 0.038416 to 0.16367, respectively. A significant Linkage disequilibrium (LD) with p-value after Bonferroni correction p ≤ 0.05/66= 0.0008 was observed for 17 pairs of loci in male samples and 4 pairs of loci in female. In the male group, LG3 showed relatively high values of Haplotype diversity. The pairwise genetic distance fixation index (Fst) results showed that the Saudi population is genetically close to the Egyptian and Emirati populations and distant to the Turkish population.

The current study revealed that Investigator® Argus 12 X-STR kit would support forensic application, kinship testing involving female offspring, and human identification in Saudi populations.
Sex differences in autoimmunity could be associated with altered regulatory T cell phenotype and lipoprotein metabolism
Authors: Robinson George A , Waddington Kirsty E , Adriani Marsilio , Radziszewska Anna , Peckham Hannah , Isenberg David. A , Ioannou Yiannis , Ciurtin Coziana , Pineda-Torra Ines , Jury Elizabeth C
Published: September 2019

Male and female immune responses are known to differ resulting in an increased prevalence of autoimmunity in women. Here sex differences in T-cell subset frequency and function during adolescence were examined in healthy donors and patients with the autoimmune disease juvenile (J)SLE; onset of JSLE commonly occurs during puberty suggesting a strong hormonal influence. Healthy adolescent males had increased regulatory T-cell (Treg) frequency, and increased Treg suppressive capacity and IL-4 production compared to healthy adolescent females. The T-helper 2-like profile in male Tregs was associated with increased expression of GATA3 which correlated significantly with elevated Treg plasma membrane glycosphingolipid expression. Differential Treg phenotype was associated with unique serum metabolomic profiles in males compared to female adolescents. Notably, very low density lipoprotein (VLDL) metabolomic signatures correlated positively with activated Tregs in males but with resting Tregs in females. Consistently, only VLDL isolated from male serum was able to induce increased Treg IL-4 production and glycosphingolipid expression following in cultured cells. Remarkably, gender differences in Treg frequency, phenotype and function and serum metabolomic profiles were lost in adolescents with JSLE. This work provides evidence that a combination of pubertal development, immune cell defects and dyslipidemia may contribute to JSLE pathogenesis.
Dysregulated cell signalling and reduced satellite cell potential in ageing muscle
Authors: Patel Ketan , Simbi Biggy , Ritvos Olli , Vaiyapuri Sakthivel , Dhoot Gurtej K
Published: September 2019

Aberrant activation of signalling pathways has been postulated to promote age related changes in skeletal muscle. Cell signalling activation requires not only the expression of ligands and receptors but also an appropriate environment that facilitates their interaction. Here we first examined the expression of SULF1/SULF2 and members of RTK and the Wnt family in skeletal muscle of normal and a mouse model of accelerated ageing. We show that SULF1/SULF2 and these signalling components, a feature of early muscle development are barely detectable in early postnatal muscle. Real time qPCR and immunocytochemical analysis showed gradual but progressive up-regulation of SULF1/SULF2 and RTK/Wnt proteins not only in the activated satellite cells but also on muscle fibres that gradually increased with age. Satellite cells on isolated muscle fibres showed spontaneous in vivo satellite cell activation and progressive reduction in proliferative potential and responsiveness to HGF and dysregulated myogenic differentiation with age. Finally, we show that SULF1/SULF2 and RTK/Wnt signalling components are expressed in progeric mouse muscles at earlier stage but their expression is attenuated by an intervention that promotes muscle repair and growth.
Design and assembly of DNA molecules using multi-objective optimisation
Authors: Gaeta Angelo , Zulkower Valentin , Stracquadanio Giovanni
Published: September 2019

Rapid engineering of biological systems is currently hindered by limited integration of manufacturing constraints into the design process, ultimately limiting the yield of many synthetic biology workflows.

Here we tackle DNA engineering as a multi-objective optimization problem aiming at finding the best tradeoff between design requirements and manufacturing constraints. We developed a new open-source algorithm for DNA engineering, called Multi-Objective Optimisation algorithm for DNA Design and Assembly (MOODA), available as a Python package and web application athttp://mooda.stracquadaniolab.org.

Experimental results show that our method provides near optimal constructs and scales linearly with design complexity, effectively paving the way to rational engineering of DNA molecules from genes to genomes.
NNT Regulates Mitochondrial Metabolism in NSCLC Through Maintenance of Fe-S Protein Function
Authors: Ward Nathan P. , Kang Yun Pyo , Falzone Aimee , Boyle Terry A. , DeNicola Gina M.
Published: September 2019

Human lung tumors exhibit robust and complex mitochondrial metabolism, likely precipitated by the highly oxygenated nature of pulmonary tissue. As ROS generation is a byproduct of this metabolism, reducing power in the form of nicotinamide adenine dinucleotide phosphate (NADPH) is required to mitigate oxidative stress in response to this heightened mitochondrial activity. Nicotinamide nucleotide transhydrogenase (NNT) is known to sustain mitochondrial antioxidant capacity through the generation of NADPH, however its function in non-small cell lung cancer (NSCLC) has not been established. We found that NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression. We further show that NNT loss elicits mitochondrial dysfunction independent of substantial increases in oxidative stress, but rather marked by the diminished activities of proteins dependent on resident iron-sulfur clusters. These defects were associated with both NADPH availability and ROS accumulation, suggesting that NNT serves a specific role in mitigating the oxidation of these critical protein cofactors.
Homeostatic recovery of embryonic spinal activity initiated by compensatory changes in resting membrane potential
Authors: Gonzalez-Islas Carlos , Garcia-Bereguiain Miguel Angel , Wenner Peter
Published: September 2019

When baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. We have previously shown that 2-day blockade of either excitatory GABAergic or glutamatergic transmission in the living embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, by 2 hours of persistent receptor blockade embryonic movements begin to recover, and by 12 hours we observe a complete homeostatic recovery in vivo. Compensatory changes in voltage-gated conductances in motoneurons were observed by 12 hours of blockade, but not changes in synaptic strength. It was unclear whether changes in voltage-gated conductances were observed by 2 hours of blockade when the recovery actually begins. Further, compensatory changes in voltage-gated conductances were not observed following glutamatergic blockade where embryonic movements were blocked but then recovered in a similar manner to GABAergic blockade. In this study, we discover a mechanism for homeostatic recovery in these first hours of neurotransmitter receptor blockade. In the first 6 hours of GABAergic or glutamatergic blockade there was a clear depolarization of resting membrane potential in both motoneurons and interneurons. These changes reduced action potential threshold and were mainly observed in the continued presence of the antagonist. Therefore, it appears that fast changes in resting membrane potential represent a key fast homeostatic mechanism for the maintenance of network activity in the living embryonic nervous system.

Significance

Homeostatic plasticity represents a set of mechanisms that act to recover cellular or network activity following a challenge to that activity and is thought to be critical for the developmental construction of the nervous system. The chick embryo afforded us the opportunity to observe in a living developing system the timing of the homeostatic recovery of network activity following 2 distinct perturbations. Because of this advantage, we have identified a novel homeostatic mechanism that actually occurs as the network recovers and is therefore likely to contribute to nervous system homeostasis. We found that a depolarization of the resting membrane potential in the first hour of the perturbations enhances excitability and supports the recovery of embryonic spinal network activity.
Improved metagenomic analysis with Kraken 2
Authors: Wood Derrick E. , Lu Jennifer , Langmead Ben
Published: September 2019

Although Kraken’sk-mer-based approach provides fast taxonomic classification of metagenomic sequence data, its large memory requirements can be limiting for some applications. Kraken 2 improves upon Kraken 1 by reducing memory usage by 85%, allowing greater amounts of reference genomic data to be used, while maintaining high accuracy and increasing speed five-fold. Kraken 2 also introduces a translated search mode, providing increased sensitivity in viral metagenomics analysis.
A novel xenograft model of human HCC in immunocompetent mouse
Authors: Bi Yanzhen , Shi Jun , Li Shanshan , Wang Quanyi , Wang Quanquan , Wen Xinyuan , Yang Feng , Duan Zhongping , Yang Yonghong , Zhang Xiaobei , Zhang Yongchao , Shu Zhenfeng , Chen Yu , Hong Feng
Published: September 2019

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human liver cancer is of important practical significance. Taking advantage of the novel microcarrier-6, human HCC cells was injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh liver cancer tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry. The success rate was 60% (6/10) in the establishment of liver cancer PDX mouse model, and the total tumor formation rate of the tumor-forming model is 80-100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced. Through the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC.
Intraspecific niche partitioning in macrodetritivores enhances mixed leaf litter decomposition
Authors: Fontana Simone , Berg Matty P. , Moretti Marco
Published: September 2019

In biodiversity and ecosystem functioning research, the consideration of intraspecific trait variation and multiple trophic levels – both largely overlooked so far – has been proposed as a promising step towards a consensus about causal relationships and mechanisms.

Soil invertebrates contribute crucially to leaf litter decomposition and thus to the functioning of one of the most diverse ecosystem components on Earth. On the one hand, a positive effect of leaf litter diversity on decomposition was shown by several studies. On the other hand, at the interspecific level, differences in body size and feeding traits of consumers influence this process by interacting with leaf litter traits that define decomposability, such as nutrient content and physical properties. It is also known that the feeding niche of consumers can vary during their ontogeny as it depends on individual body size, metabolism and physiology. However, whether and how intraspecific trait variation of macrodetritivores contributes through niche partitioning to the positive effect of litter combinations on decomposition was never investigated.

Here, we tested experimentally the effect of intraspecific body size differences in the common terrestrial isopod species Oniscus asellus on the decomposition of the two co‐occurring litter species Acer platanoides and Betula pendula. We hypothesized complementary resource use by two distinct isopod body size classes, leading to decreased competition and higher overall litter decomposition.

In a full factorial design with all possible combinations of litter species and isopod body size classes, litter mixtures enhanced decomposition beyond the additive effect of each single species, especially in isopod mixed‐body size treatments. Our results suggest an interaction between litter and consumer diversity driving intraspecific feeding niche partitioning. Although the focus on a single detritivore species does not allow for generalizations, our results should stimulate the investigation of the mechanisms of biotic interactions among individual organisms.

A free Plain Language Summary can be found within the Supporting Information of this article.
Warm and out of breath: Thermal phenotypic plasticity in oxygen supply
Authors: Kielland Øystein Nordeide , Bech Claus , Einum Sigurd
Published: September 2019

Aquatic ectotherms face a challenge of obtaining sufficient oxygen, and it is commonly claimed that this challenge increases with increasing environmental temperature, causing concerns about the fate of aquatic ecosystems under climate change.

However, the oxygen challenge hypothesis often ignores the effect of known phenotypic plastic responses. These can occur on either a within‐ or multigenerational scale, where multiple reactions act in concert to increase oxygen supply in response to increased temperature in a wide range of traits (molecular, egg content, behavioural, cell structure, morphological).

Here, we combine a novel modelling approach with empirical measurements that enable quantification of how both the oxygen supply (maximum oxygen diffusion rate) and demand (metabolic rate) are affected by temperature while allowing for phenotypic plasticity.

We exposed the aquatic ectotherm Daphnia magna to a range of temperatures (17–28°C) over several asexual generations and confirm that phenotypic plasticity contributes to an increased ability to obtain oxygen on the whole‐organism level at high temperatures.

This response is strongest within the highest temperature range (22–28°C), where the change in oxygen challenge is expected to be most pronounced. However, the observed thermal plasticity in oxygen supply failed to compensate for the increased demand.

Thus, we provide empirical evidence that the oxygen challenge in aquatic ectotherms increases with increasing temperature, even in the presence of phenotypic plasticity in oxygen supply.

A free Plain Language Summary can be found within the Supporting Information of this article.
Field exclusion of large soil predators impacts lower trophic levels and decreases leaf‐litter decomposition in dry forests
Authors: Melguizo‐Ruiz Nereida , Jiménez‐Navarro Gerardo , De Mas Eva , Pato Joaquina , Scheu Stefan , Austin Amy T. , Wise David H. , Moya‐Laraño Jordi
Published: September 2019

Shifts in densities of apex predators may indirectly affect fundamental ecosystem processes, such as decomposition, by altering patterns of cascading effects propagating through lower trophic levels. These top–down effects may interact with anthropogenic impacts, such as climate change, in largely unknown ways.

We investigated how changes in densities of large predatory arthropods in forest leaf‐litter communities altered lower trophic levels and litter decomposition. We conducted our experiment in soil communities that had experienced different levels of long‐term average precipitation. We hypothesized that altering abundances of apex predators would have stronger effects on soil communities inhabiting dry forests, due to lower secondary productivity and greater resource overexploitation by lower trophic levels compared to wet forests.

We experimentally manipulated abundances of the largest arthropod predators (apex predators) in field mesocosms replicated in the leaf‐litter community of Iberian beech forests that differed in long‐term mean annual precipitation by 25% (three dry forests with MAP < 1,250 mm and four wet forests with MAP > 1,400 mm). After one year, we assessed abundances of soil fauna in lower trophic levels and indirect impacts on leaf‐litter decomposition using litter of understorey hazel, Corylus avellana.

Reducing densities of large predators had a consistently negative effect on final abundances of the different trophic groups and several taxa within each group. Moreover, large predatory arthropods strongly impacted litter decomposition, and their effect interacted with the long‐term annual rainfall experienced by the soil community. In the dry forests, a 50% reduction in the densities of apex predators was associated with a 50% reduction in decomposition. In wet forests, the same reduction in densities of apex soil predators did not alter the rate of litter decomposition.

Our results suggest that predators may facilitate lower trophic levels by indirectly reducing competition and resource overexploitation, cascading effects that may be more pronounced in drier forests where conditions have selected for greater competitive ability and more rapid resource utilization. These findings thus provide insights into the functioning of soil invertebrate communities and their role in decomposition, as well as potential consequences of soil community responses to climate change.
Glycyrrhizin treatment ameliorates post‐traumatic stress disorder‐like behaviours and restores circadian oscillation of intracranial serotonin
Authors: Lai Shuhua , Shi Liangpan , Jiang Zhixian , Lin Zhihang
Published: September 2019

Post‐traumatic stress disorder (PTSD) has become a major disease that threatens human health. Neurotransmitters and the amygdala are found to be critical in the development and maintenance of PTSD. We aim to investigate the role of glycyrrhizin in treating PTSD. Contextual fear extinction and elevated plus maze test were applied to evaluate the anxiety and fear memory. Microdialysis and high‐performance liquid chromatography were used to analyze the expression of amygdala neurotransmitters in PTSD animal models and to verify the effects of glycyrrhizin on major neurotransmitters. The protein levels of tryptophan hydroxylase 2 (TPH2) were examined by western bolt. Glycyrrhizin treatment significantly reduced anxiety and fear memory after 1 and 7 days of PTSD modelling. In addition, glycyrrhizin treatment restored the circadian rhythm changes of serotonin and TPH2. The present study found a significant circadian rhythm change of serotonin in the amygdala in PTSD rats. Besides, glycyrrhizin treatment restored the altered serotonin diurnal fluctuations, which raises important implications for PTSD treatment.
The Behaviour of Banking Financial Stability in ASEAN‐5
Authors: Oktaviyanti Dwi , Purnawan Muhammad Edhie
Published: September 2019

This research is aimed at analysing the cyclicality of banking financial stability, the impact of bank ownership status, bank size group and macroprudential policies on banking financial stability (Z‐score) of ASEAN‐5 countries. The study implements generalised method of moments system estimator and bank‐level data (2011:Q1–2017:Q1). The result indicates that the banking financial stability shows countercyclical behaviour. While government ownership does not affect financial stability, it tends to increase credit risk. Large and small bank group do not have significant different risk‐taking behaviour. Loan‐to‐Value ratio does not affect financial stability but significantly mitigates credit risk. An increase in reserve requirement lowers financial stability.
VoCC: An r package for calculating the velocity of climate change and related climatic metrics
Authors: García Molinos Jorge , Schoeman David S. , Brown Christopher J. , Burrows Michael T.
Published: September 2019

Climate change is a primary global driver of biodiversity reorganization. The velocity of clisecondary functions, or to produce output for display (see mate change and related metrics describe the spatial change of climatic variables over time, allowing quantification of climate change exposure and connectivity, facilitating insights into the potential scope of species’ range‐shift responses. These metrics have been extensively used in climate‐change ecology research and provide useful information for conservation. Multiple extensions to the original concept of climate velocity have been proposed since first presented nearly a decade ago. However, despite its utility, no software application is currently available that brings all these methods together.

The r package VoCC fills this gap by providing a comprehensive collection of functions that calculate climate velocity and related metrics from their initial formulation to the latest developments. Here, we introduce the core package functionality through a series of applied examples.

The collection of functions in the VoCC package represents a new, useful addition to the existing portfolio of tools with which to assess risks posed by climate change to species and ecosystems.
Taking a closer look at invasive alien plant research: A review of the current state, opportunities, and future directions for UAVs
Authors: Dash Jonathan P. , Watt Michael S. , Paul Thomas S. H. , Morgenroth Justin , Hartley Robin
Published: September 2019

The development and proliferation of unmanned aerial vehicles (UAV) in recent years presents a new data collection opportunity for invasive alien plant (IAP) research. The flexibility and cost‐efficiency of these craft offers a valuable solution where high‐spatial or high‐temporal resolution remotely sensed data are required.

In this paper, we review all published studies using UAV for remote data collection in IAP research.

We have systematically identified the taxonomy and habitat characteristics of the system studied, classified the UAV configuration, analytical methods and the limitations of each study.

We used this synthesis to identify research gaps, suggest directions for future research, and identify opportunities for practical application of the technology.
Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD‐L1)‐mediated immunosuppression
Authors: Xu Qixia , Long Qilai , Zhu Dexiang , Fu Da , Zhang Boyi , Han Liu , Qian Min , Guo Jianming , Xu Jianmin , Cao Liu , Chin Y. Eugene , Coppé Jean‐Philippe , Lam Eric W.‐F. , Campisi Judith , Sun Yu
Published: September 2019

Aging is characterized by a progressive loss of physiological integrity, while cancer represents one of the primary pathological factors that severely threaten human lifespan and healthspan. In clinical oncology, drug resistance limits the efficacy of most anticancer treatments, and identification of major mechanisms remains a key to solve this challenging issue. Here, we highlight the multifaceted senescence‐associated secretory phenotype (SASP), which comprises numerous soluble factors including amphiregulin (AREG). Production of AREG is triggered by DNA damage to stromal cells, which passively enter senescence in the tumor microenvironment (TME), a process that remarkably enhances cancer malignancy including acquired resistance mediated by EGFR. Furthermore, paracrine AREG induces programmed cell death 1 ligand (PD‐L1) expression in recipient cancer cells and creates an immunosuppressive TME via immune checkpoint activation against cytotoxic lymphocytes. Targeting AREG not only minimized chemoresistance of cancer cells, but also restored immunocompetency when combined with classical chemotherapy in humanized animals. Our study underscores the potential of in vivo SASP in driving the TME‐mediated drug resistance and shaping an immunosuppressive niche, and provides the proof of principle of targeting major SASP factors to improve therapeutic outcome in cancer medicine, the success of which can substantially reduce aging‐related morbidity and mortality.
Root coverage with coronally advanced flap:6‐year follow‐up
Authors: Kanmaz B , Kanmaz MG , Kaval B , Buduneli N
Published: September 2019

Aim

The aim of this study was to evaluate the long‐term stability of root coverage without a regular control programme after coronally advanced flap (CAF) procedures in isolated gingival recessions.

Material and Methods

Recession defects were treated with CAF using microsurgery technique. Probing depth, clinical attachment level, keratinized gingival width, plaque index, papilla bleeding index, recession depth, recession width and root surface area was evaluated at baseline, and then postoperative 6‐month and 6‐year follow‐up sessions. Percentages of root coverage and complete root coverage rates were also calculated.

Results

In total, 12 defects in 12 patients of the 36 defects in 30 patients were available for analysis at the 6‐year follow‐up examination (66.7% of the initial sites could be reached). Percentage of mean root coverage was 95.06% at 6‐month and 69.27% at 6‐year and the difference was statistically significant (P < 0.05). Complete root coverage rate decreased from 75% (at 6‐month) to 50% (at 6‐year), but the difference was not statistically significant (P > 0.05).

Conclusion

Within the limits of this long‐term follow‐up study, there seems to be a rather high risk for relapse after root coverage with CAF possibly due to the lack of regular recalls and persistent traumatic tooth brushing habits.
The tracking of lipopolysaccharide through the feto‐maternal compartment and the involvement of maternal TLR4 in inflammation‐induced fetal brain injury
Authors: Brown Amy G. , Maubert Monique E. , Anton Lauren , Heiser Laura M. , Elovitz Michal A.
Published: September 2019

Problem

Exposure to intrauterine inflammation (IUI) has been shown to induce fetal brain injury and increase the risk of acquiring a neurobehavioral disorder. The trafficking of the inflammatory mediator, lipopolysaccharide (LPS), in the pregnant female reproductive tract in the setting of IUI and the precise mechanisms by which inflammation induces fetal brain injury are not fully understood.

Method of study

FITC‐labeled LPS was utilized to induce IUI on E15, tissues were collected, and fluorescence was visualized via the Spectrum IVIS. Embryo transfer was utilized to create divergent maternal and fetal genotypes. Wild‐type (WT) embryos were transferred into TLR4−/− pseudopregnant dams (TLR4−/−mat/WTfet). On E15, TLR4−/−mat/WTfet dams or their WT controls (WTmat/WTfet) received an intrauterine injection of LPS or phosphate‐buffered saline (PBS). Endotoxin and IL‐6 levels were assessed in amniotic fluid, and cytokine expression was measured via QPCR.

Results

Lipopolysaccharide trafficked to the uterus, fetal membranes, placenta, and the fetus and was undetectable in other tissues. Endotoxin was present in the amniotic fluid of all animals exposed to LPS. However, the immune response was blunted in TLR4−/−mat/WTfet compared with WT controls.

Conclusion

Intrauterine administered LPS is capable of accessing the entire feto‐placental unit with or without a functional maternal TLR4. Thus, bacteria or bacterial byproducts in the uterus may negatively impact fetal development regardless of the maternal genotype or endotoxin response. Despite the blunted immune response in the TLR4‐deficient dams, an inflammatory response is still ignited in the amniotic cavity and may negatively impact the fetus.
Alum impairs tolerogenic properties induced by allergoid‐mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs
Authors: Benito‐Villalvilla Cristina , Soria Irene , Pérez‐Diego Mario , Fernández‐Caldas Enrique , Subiza José Luis , Palomares Oscar
Published: September 2019

Background

Polymerized allergoids conjugated to mannan (PM) are suitable vaccines for allergen‐specific immunotherapy (AIT). Alum remains the most widely used adjuvant in AIT, but its way of action is not completely elucidated. The better understanding of the mechanisms underlying alum adjuvanticity could help to improve AIT vaccine formulations.

Objective

We sought to investigate the potential influence of alum in the tolerogenic properties imprinted by PM at the molecular level.

Methods

Flow cytometry, ELISAs, cocultures, intracellular staining and suppression assays were performed to assess alum and PM effects in human dendritic cells (DCs). BALB/c mice were immunized with PM alone or adsorbed to alum. Allergen‐specific antibodies, splenocyte cytokine production and splenic forkhead box P3 (FOXP3)+ regulatory T (Treg) cells were quantified. Metabolic and immune pathways were also studied in human DCs.

Results

Alum decreases PD‐L1 expression and IL‐10 production induced by PM in human DCs and increases pro‐inflammatory cytokine production. Alum impairs PM‐induced functional FOXP3+ Treg cells and promotes Th1/Th2/Th17 responses. Subcutaneous immunization of mice with PM plus alum inhibits in vivo induction of Treg cells promoted by PM without altering the capacity to induce functional allergen‐specific blocking antibodies. Alum inhibits mTOR activation and alters metabolic reprogramming by shifting glycolytic pathways and inhibiting reactive oxygen species (ROS) production in PM‐activated DCs, impairing their capacity to generate functional Treg cells.

Conclusion

We uncover novel mechanisms by which alum impairs the tolerogenic properties induced by PM, which might well contribute to improve the formulation of novel vaccines for AIT.
Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta‐analysis
Authors: Fricke Julia , Ávila Gabriela , Keller Theresa , Weller Karsten , Lau Susanne , Maurer Marcus , Zuberbier Torsten , Keil Thomas
Published: September 2019

Background and objectives

Urticaria is a frequent skin condition, but reliable prevalence estimates from population studies particularly of the chronic form are scarce. The objective of this study was to systematically evaluate and summarize the prevalence of chronic urticaria by evaluating population‐based studies worldwide.

Methods

We performed a systematic search in PUBMED and EMBASE for population‐based studies of cross‐sectional or cohort design and studies based on health insurance/system databases. Risk of bias was assessed using a specific tool for prevalence studies. For meta‐analysis, we used a random effects model.

Results

Eighteen studies were included in the systematic evaluation and 11 in the meta‐analysis including data from over 86 000 000 participants. Risk of bias was mainly moderate, whereas the statistical heterogeneity (I2) between the studies was high. Asian studies combined showed a higher point prevalence of chronic urticaria (1.4%, 95%‐CI 0.5‐2.9) than those from Europe (0.5%, 0.2‐1.0) and Northern American (0.1%, 0.1‐0.1). Women were slightly more affected than men, whereas in children < 15 years we did not find a sex‐specific difference in the prevalence. The four studies that examined time trends indicated an increasing prevalence of chronic urticaria over time.

Conclusions

On a global level, the prevalence of chronic urticaria showed considerable regional differences. There is a need to obtain more sex‐specific population‐based and standardized international data particularly for children and adolescents, different chronic urticaria subtypes and potential risk and protective factors.