bluuebunny/crossref_metadata_2025 huggingface dataset:
Russia – Measures Affecting the Importation of Railway Equipment and Parts Thereof, DS499
Authors: Sohlberg Marcus
Published: June 2020

The dispute concerns a challenge by Ukraine of certain measures imposed by Russia concerning conformity assessment procedures for railway products, produced in Ukraine and exported to Russia. Ukraine alleged that the Russian measures prevented imports from Ukraine into Russia. For example, Russia was accused of suspending Ukrainian suppliers’ certificates of conformity, as well as refusing to process new certificate applications, due to alleged impossibility of carrying out required annual on-site inspections in Ukraine due to security concerns. These measures were subject to challenge by Ukraine under the WTO Agreement on Technical Barriers to Trade (TBT Agreement), which applies to WTO Members’ technical regulations and related conformity assessment procedures. Two of the Appellate Body's most noteworthy findings reversing the Panel are addressed below.
Impact of reduced rates of 2,4-D and glyphosate on sweetpotato growth and yield
Authors: Batts Thomas M. , Miller Donnie K. , Griffin James L. , Villordon Arthur O. , Stephenson Daniel O. , Jennings Kathrine M. , Chaudhari Sushila , Blouin David C. , Copes Josh T. , Smith Tara P.
Published: June 2020

Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.
Detection of grassy weeds in bermudagrass with deep convolutional neural networks
Authors: Yu Jialin , Schumann Arnold W. , Sharpe Shaun M. , Li Xuehan , Boyd Nathan S.
Published: June 2020

Spot spraying POST herbicides is an effective approach to reduce herbicide input and weed control cost. Machine vision detection of grass or grass-like weeds in turfgrass systems is a challenging task due to the similarity in plant morphology. In this work, we explored the feasibility of using image classification with deep convolutional neural networks (DCNN), including AlexNet, GoogLeNet, and VGGNet, for detection of crabgrass species (Digitaria spp.), doveweed [Murdannia nudiflora (L.) Brenan], dallisgrass (Paspalum dilatatum Poir.), and tropical signalgrass [Urochloa distachya (L.) T.Q. Nguyen] in bermudagrass [Cynodon dactylon (L.) Pers.]. VGGNet generally outperformed AlexNet and GoogLeNet in detecting selected grassy weeds. For detection of P. dilatatum, VGGNet achieved high F1 scores (≥0.97) and recall values (≥0.99). A single VGGNet model exhibited high F1 scores (≥0.93) and recall values (1.00) that reliably detected Digitaria spp., M. nudiflora, P. dilatatum, and U. distachya. Low weed density reduced the recall values of AlexNet at detecting all weed species and GoogLeNet at detecting Digitaria spp. In comparison, VGGNet achieved excellent performances (overall accuracy = 1.00) at detecting all weed species in both high and low weed-density scenarios. These results demonstrate the feasibility of using DCNN for detection of grass or grass-like weeds in turfgrass systems.
Potential Predictability of Net Primary Production in the Ocean
Authors: Krumhardt K. M. , Lovenduski N. S. , Long M. C. , Luo J. Y. , Lindsay K. , Yeager S. , Harrison C.
Published: June 2020

Interannual variations in marine net primary production (NPP) contribute to the variability of available living marine resources, as well as influence critical carbon cycle processes. Here we provide a global overview of near‐term (1 to 10 years) potential predictability of marine NPP using a novel set of initialized retrospective decadal forecasts from an Earth System Model. Interannual variations in marine NPP are potentially predictable in many areas of the ocean 1 to 3 years in advance, from temperate waters to the tropics, showing a substantial improvement over a simple persistence forecast. However, some regions, such as the subpolar Southern Ocean, show low potential predictability. We analyze how bottom‐up drivers of marine NPP (nutrients, light, and temperature) contribute to its predictability. Regions where NPP is primarily driven by the physical supply of nutrients (e.g., subtropics) retain higher potential predictability than high‐latitude regions where NPP is controlled by light and/or temperature (e.g., the Southern Ocean). We further examine NPP predictability in the world's Large Marine Ecosystems. With a few exceptions, we show that initialized forecasts improve potential predictability of NPP in Large Marine Ecosystems over a persistence forecast and may aid to manage living marine resources.
Deoxycholic acid modulates the progression of gallbladder cancer through N6-methyladenosine-dependent microRNA maturation
Authors: Lin Ruirong , Zhan Ming , Yang Linhua , Wang Hui , Shen Hui , Huang Shuai , Huang Xince , Xu Sunwang , Zhang Zijie , Li Weijian , Liu Qiang , Shi Yongsheng , Chen Wei , Yu Jianxiu , Wang Jian
Published: June 2020

Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, deoxycholic acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. DCA plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized. Here, we analyzed human GBC samples and found that DCA was significantly downregulated in GBC, and reduced levels of DCA was associated with poor clinical outcome in patients with GBC. DCA treatment impeded tumor progression by halting cell proliferation. DCA decreased miR-92b-3p expression in an m6A-dependent posttranscriptional modification manner by facilitating dissociation of METTL3 from METTL3–METTL14–WTAP complex, which increased the protein level of the phosphatase and tensin homolog, a newly identified target of miR-92b-3p, and subsequently inactivated the PI3K/AKT signaling pathway. Our findings revealed that DCA might function as a tumor suppressive factor in GBC at least by interfering with miR-92b-3p maturation, and suggested that DCA treatment could provide a new therapeutic strategy for GBC.
Coexistence of genetically different Rhizophagus irregularis isolates induces genes involved in a putative fungal mating response
Authors: Mateus Ivan D , Rojas Edward C , Savary Romain , Dupuis Cindy , Masclaux Frédéric G , Aletti Consolée , Sanders Ian R
Published: June 2020

Arbuscular mycorrhizal fungi (AMF) are of great ecological importance because of their effects on plant growth. Closely related genotypes of the same AMF species coexist in plant roots. However, almost nothing is known about the molecular interactions occurring during such coexistence. We compared in planta AMF gene transcription in single and coinoculation treatments with two genetically different isolates of Rhizophagus irregularis in symbiosis independently on three genetically different cassava genotypes. Remarkably few genes were specifically upregulated when the two fungi coexisted. Strikingly, almost all of the genes with an identifiable putative function were known to be involved in mating in other fungal species. Several genes were consistent across host plant genotypes but more upregulated genes involved in putative mating were observed in host genotype (COL2215) compared with the two other host genotypes. The AMF genes that we observed to be specifically upregulated during coexistence were either involved in the mating pheromone response, in meiosis, sexual sporulation or were homologs of MAT-locus genes known in other fungal species. We did not observe the upregulation of the expected homeodomain genes contained in a putative AMF MAT-locus, but observed upregulation of HMG-box genes similar to those known to be involved in mating in Mucoromycotina species. Finally, we demonstrated that coexistence between the two fungal genotypes in the coinoculation treatments explained the number of putative mating response genes activated in the different plant host genotypes. This study demonstrates experimentally the activation of genes involved in a putative mating response and represents an important step towards the understanding of coexistence and sexual reproduction in these important plant symbionts.
Division of functional roles for termite gut protists revealed by single-cell transcriptomes
Authors: Nishimura Yuki , Otagiri Masato , Yuki Masahiro , Shimizu Michiru , Inoue Jun-ichi , Moriya Shigeharu , Ohkuma Moriya
Published: June 2020

The microbiome in the hindgut of wood-feeding termites comprises various species of bacteria, archaea, and protists. This gut community is indispensable for the termite, which thrives solely on recalcitrant and nitrogen-poor wood. However, the difficulty in culturing these microorganisms has hindered our understanding of the function of each species in the gut. Although protists predominate in the termite gut microbiome and play a major role in wood digestion, very few culture-independent studies have explored the contribution of each species to digestion. Here, we report single-cell transcriptomes of four protists species comprising the protist population in worldwide pest Coptotermes formosanus. Comparative transcriptomic analysis revealed that the expression patterns of the genes involved in wood digestion were different among species, reinforcing their division of roles in wood degradation. Transcriptomes, together with enzyme assays, also suggested that one of the protists, Cononympha leidyi, actively degrades chitin and assimilates it into amino acids. We propose that C. leidyi contributes to nitrogen recycling and inhibiting infection from entomopathogenic fungi through chitin degradation. Two of the genes for chitin degradation were further revealed to be acquired via lateral gene transfer (LGT) implying the importance of LGT in the evolution of symbiosis. Our single-cell-based approach successfully characterized the function of each protist in termite hindgut and explained why the gut community includes multiple species.
Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)
Authors: Agrati Chiara , Sacchi Alessandra , Bordoni Veronica , Cimini Eleonora , Notari Stefania , Grassi Germana , Casetti Rita , Tartaglia Eleonora , Lalle Eleonora , D’Abramo Alessandra , Castilletti Concetta , Marchioni Luisa , Shi Yufang , Mariano Andrea , Song Jin-Wen , Zhang Ji-Yuan , Wang Fu-Sheng , Zhang Chao , Fimia Gian Maria , Capobianchi Maria R. , Piacentini Mauro , Antinori Andrea , Nicastri Emanuele , Maeurer Markus , Zumla Alimuddin , Ippolito Giuseppe
Published: June 2020

SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.
Glucocorticoids can induce BIM to trigger apoptosis in the absence of BAX and BAK1
Authors: Dong Li , Vaux David L.
Published: June 2020

Cells from two murine lymphoid lines died 24–48 h after treatment with the glucocorticoid dexamethasone. Deletion ofBaxandBak1prevented rapid apoptosis, but treatment with dexamethasone for greater 6 days still led to cell death that was characterized by release of cytochrome c into the cytosol, activation of caspases, and loss of cell membrane integrity. In WEHI7 thymoma cells, this did not occur whenBcl2l11(Bim)was deleted in addition toBaxandBak1. When these triple mutant lines were exposed to dexamethasone for 10 days, they arrested, but after dexamethasone was removed, they had 10-fold higher clone forming efficiency thanBax/Bak1double knock-out cells. Although induced over-expression of BIMs alone was not sufficient to induce the death ofBax−/−Bak1−/−Bim−/−cells, they did die when BIMs was induced in the presence of dexamethasone. These results suggest that dexamethasone induces production of BIM together with other, as yet unidentified proteins, that cause release of cytochrome c and apoptosis in the absence of BAX and BAK1.
Circ-MMP2 (circ-0039411) induced by FOXM1 promotes the proliferation and migration of lung adenocarcinoma cells in vitro and in vivo
Authors: Lv Xin , Huang Hongping , Feng Hui , Wei Zhonghua
Published: June 2020

Numerous reports have stated the significance of cellular events such as proliferation, migration and EMT (epithelial-mesenchymal transition) for cancer development, but the related molecular mechanism remains elusive. FOXM1 (forkhead box transcription M1) is a nuclear co-activator participating in lung adenocarcinoma (LUAD). Thus, this study tried to explain the function of FOXM1 and its downstream molecular mechanism in LUAD. We uncovered FOXM1 upregulation in LUAD and demonstrated that FOXM1 facilitated β-catenin nuclear translocation to activate the transcription of downstream genes. Moreover, we discovered that FOXM1 transcriptionally activated circ0039411 which derived from matrix metallopeptidase 2 (MMP2) (also named as circ-MMP2), while MMP2 is a known downstream target of β-catenin. As for functional investigation, knockdown of circ-0039411 suppressed the proliferation, migration and EMT in LUAD cells and also hindered in vivo growth and metastasis of LUAD tumor. Mechanistically, circ-0039411 enhanced the stability of FOXM1 mRNA by recruiting IGF2BP3 (insulin like growth factor 2 mRNA binding protein 3), thus forming a positive feedback loop. In conclusion, this study revealed that FOXM1-induced circ-MMP2 (circ-0039411) contributes to malignant behaviors of LUAD cells via relying on FOXM1, potentially infusing inspirations for the search of new molecular targets for LUAD treatment.
NMMHC IIA triggers neuronal autophagic cell death by promoting F-actin-dependent ATG9A trafficking in cerebral ischemia/reperfusion
Authors: Wang Guangyun , Wang Tiezheng , Hu Yang , Wang Jieman , Wang Yan , Zhang Yuanyuan , Li Fang , Liu Wentao , Sun Yang , Yu Boyang , Kou Junping
Published: June 2020

Previous findings have shown that non-muscle myosin heavy-chain IIA (NMMHC IIA) is involved in autophagy induction triggered by starvation in D. melanogaster; however, its functional contribution to neuronal autophagy remains unclear. The aim of this study is to explore the function of NMMHC IIA in cerebral ischemia-induced neuronal autophagy and the underlying mechanism related to autophagy-related gene 9A (ATG9A) trafficking. Functional assays and molecular mechanism studies were used to investigate the role of NMMHC IIA in cerebral ischemia-induced neuronal autophagy in vivo and in vitro. A middle cerebral artery occlusion (MCAO) model in mice was used to evaluate the therapeutic effect of blebbistatin, a myosin II ATPase inhibitor. Herein, either depletion or knockdown of NMMHC IIA led to increased cell viability in both primary cultured cortical neurons and pheochromocytoma (PC12) cells exposed to oxygen–glucose deprivation/reoxygenation (OGD/R). In addition, NMMHC IIA and autophagic marker LC3B were upregulated by OGD/R, and inhibition of NMMHC IIA significantly reduced OGD-induced neuronal autophagy. Furthermore, NMMHC IIA-induced autophagy is through its interactions with F-actin and ATG9A in response to OGD/R. The NMMHC IIA–actin interaction contributes to ATG9A trafficking and autophagosome formation. Inhibition of the NMMHC IIA–actin interaction using blebbistatin and the F-actin polymerization inhibitor cytochalasin D significantly suppressed ATG9A trafficking and autophagy induction. Furthermore, blebbistatin significantly improved neurological deficits and infarct volume after ischemic attack in mice, accompanied by ATG9A trafficking and autophagy inhibition. These findings demonstrate neuroprotective effects of NMMHC IIA inhibition on regulating ATG9A trafficking-dependent autophagy activation in the context of cerebral ischemia/reperfusion.
Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy
Authors: Humeau Juliette , Leduc Marion , Cerrato Giulia , Loos Friedemann , Kepp Oliver , Kroemer Guido
Published: June 2020

The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51. Second, the modulation of autophagy by >30 chemically unrelated agents was partially inhibited in cells expressing a non-phosphorylable (S51A) mutant of eIF2α or lacking all four eIF2α kinases, although distinct kinases were involved in the response to different autophagy inducers. Third, inhibition of eIF2α phosphatases was sufficient to stimulate autophagy. In synthesis, it appears that eIF2α phosphorylation is a central event for the stimulation of autophagy.
LncRNA ANRIL acts as a modular scaffold of WDR5 and HDAC3 complexes and promotes alteration of the vascular smooth muscle cell phenotype
Authors: Zhang Chengxin , Ge Shangqing , Gong Wenhui , Xu Jinguo , Guo Zhixiang , Liu Zhuang , Gao Xiaotian , Wei Xiaoyong , Ge Shenglin
Published: June 2020

Many studies have shown that long-noncoding RNA (lncRNA) is associated with cardiovascular disease, but its molecular mechanism is still unclear. In this study, we explored the role of lncRNA ANRIL in ox-LDL-induced phenotypic transition of human aortic smooth muscle cells (HASMC). The results of quantitative fluorescence PCR showed that the expression of ANRIL in patients with coronary atherosclerotic heart disease (CAD) was significantly higher than that in normal subjects. RNA-FISH detection showed that the ANRIL expression increased in HASMC treated by ox-LDL. Ox-LDL could upregulate the expression of ANRIL and ROS and promote the phenotypic transition of HASMC. After downregulation of ANRIL by siRNA, ROS level decreased and HASMC phenotypic transition alleviated. ANRIL could act as a molecular scaffold to promote the binding of WDR5 and HDAC3 to form WDR5 and HDAC3 complexes, they regulated target genes such as NOX1 expression by histone modification, upregulated ROS level and promote HASMC phenotype transition. Therefore, we found a new epigenetic regulatory mechanism for phenotype transition of VSMC, ANRIL was a treatment target of occlusive vascular diseases.
MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells
Authors: Mukherjee Nabanita , Skees Jenette , Todd Kaleb J. , West Drake A. , Lambert Karoline A. , Robinson William A. , Amato Carol M. , Couts Kasey L. , Van Gulick Robert , MacBeth Morgan , Nassar Kelsey , Tan Aik-Choon , Zhai Zili , Fujita Mayumi , Bagby Stacey M. , Dart Chiara R. , Lambert James R. , Norris David A. , Shellman Yiqun G.
Published: June 2020

Current treatment for patients with metastatic melanoma include molecular-targeted therapies and immune checkpoint inhibitors. However, a subset of melanomas are difficult-to-treat. These melanomas include those without the genetic markers for targeted therapy, non-responsive to immunotherapy, and those who have relapsed or exhausted their therapeutic options. Therefore, it is necessary to understand and explore other biological processes that may provide new therapeutic approaches. One of most appealing is targeting the apoptotic/anti-apoptotic system that is effective against leukemia. We used genetic knockdown and pharmacologic approaches of BH3 mimetics to target anti-apoptotic BCL2 family members and identified MCL1 and BCLXL as crucial pro-survival members in melanoma. We then examined the effects of combining BH3 mimetics to target MCL1 and BCLXL in vitro and in vivo. These include clinical-trial-ready compounds such as ABT-263 (Navitoclax) and S63845/S64315 (MIK655). We used cell lines derived from patients with difficult-to-treat melanomas. In vitro, the combined inhibition of MCL1 and BCLXL resulted in significantly effective cell killing compared to single-agent treatment (p < 0.05) in multiple assays, including sphere assays. The combination-induced cell death was independent of BIM, and NOXA. Recapitulated in our mouse xenograft model, the combination inhibited tumor growth, reduced sphere-forming capacity (p < 0.01 and 0.05, respectively), and had tolerable toxicity (p > 0.40). Taken together, this study suggests that dual targeting of MCL1 and BCLXL should be considered as a treatment option for difficult-to-treat melanoma patients.
Professional duties are now considered legal duties of care within genomic medicine
Authors: Anna Middleton , Christine Patch , Jonathan Roberts , Richard Milne , Alessia Costa , Lauren Robarts , Jerome Atutornu
Published: June 2020

The legal duty to protect patient confidentiality is common knowledge amongst healthcare professionals. However, what may not be widely known, is that this duty is not always absolute. In the United Kingdom, both the General Medical Council governing the practice of all doctors, as well as many other professional codes of practice recognise that, under certain circumstances, it may be appropriate to break confidentiality. This arises when there is a wider duty to protect the health of others, and when the risk of non-disclosure outweighs the potential harm from breaking confidentiality. We discuss this situation specifically in relation to genomic medicine where relatives in a family may have differing views on the sharing of familial genetic information. Overruling a patient’s wishes is predicated on balancing the duty of care towards the patient versus protecting their relative from serious harm. We discuss the practice implications of a pivotal legal case that concluded recently in the High Court of Justice in England and Wales, ABC v St Georges Healthcare NHS Trust & Ors. Professional guidance is already clear that genetic healthcare professionals must undertake a balancing exercise to weigh up contradictory duties of care. However, the judge has provided a new legal weighting to these professional duties: ‘The scope of the duty extends not only to conducting the necessary balancing exercise but also to acting in accordance with its outcome’ [1: 189]. In the context of genomic medicine, this has important consequences for clinical practice.
A foundation for complex oxide electronics -low temperature perovskite epitaxy
Authors: Sønsteby Henrik H. , Skaar Erik , Fjellvåg Øystein S. , Bratvold Jon E. , Fjellvåg Helmer , Nilsen Ola
Published: June 2020

As traditional silicon technology is moving fast towards its fundamental limits, all-oxide electronics is emerging as a challenger offering principally different electronic behavior and switching mechanisms. This technology can be utilized to fabricate devices with enhanced and exotic functionality. One of the challenges for integration of complex oxides in electronics is the availability of appreciable low-temperature synthesis routes. Herein we provide a fundamental extension of the materials toolbox for oxide electronics by reporting a facile route for deposition of highly electrically conductive thin films of LaNiO3 by atomic layer deposition at low temperatures. The films grow epitaxial on SrTiO3 and LaAlO3 as deposited at 225 °C, with no annealing required to obtain the attractive electronic properties. The films exhibit resistivity below 100 µΩ cm with carrier densities as high as 3.6 · 1022 cm−3. This marks an important step in the realization of all-oxide electronics for emerging technological devices.
Self-filtering narrowband high performance organic photodetectors enabled by manipulating localized Frenkel exciton dissociation
Authors: Xie Boming , Xie Ruihao , Zhang Kai , Yin Qingwu , Hu Zhicheng , Yu Gang , Huang Fei , Cao Yong
Published: June 2020

The high binding energy and low diffusion length of photogenerated Frenkel excitons have long been viewed as major drawbacks of organic semiconductors. Therefore, bulk heterojunction structure has been widely adopted to assist exciton dissociation in organic photon-electron conversion devices. Here, we demonstrate that these intrinsically “poor” properties of Frenkel excitons, in fact, offer great opportunities to achieve self-filtering narrowband organic photodetectors with the help of a hierarchical device structure to intentionally manipulate the dissociation of Frenkel excitons. With this strategy, filter-free narrowband organic photodetector centered at 860 nm with full-width-at-half-maximum of around 50 nm, peak external quantum efficiency around 65% and peak specific detectivity over 1013 Jones are obtained, which is one the best performed no-gain type narrowband organic photodetectors ever reported and comparable to commercialized silicon photodetectors. This novel device structure along with its design concept may help create low cost and reliable narrowband organic photodetectors for practical applications.
Transition-metal-free formal cross-coupling of aryl methyl sulfoxides and alcohols via nucleophilic activation of C-S bond
Authors: Li Guolin , Nieves-Quinones Yexenia , Zhang Hui , Liang Qingjin , Su Shuaisong , Liu Qingchao , Kozlowski Marisa C. , Jia Tiezheng
Published: June 2020

Employment of sulfoxides as electrophiles in cross-coupling reactions remains underexplored. Herein we report a transition-metal-free cross-coupling strategy utilizing aryl(heteroaryl) methyl sulfoxides and alcohols to afford alkyl aryl(heteroaryl) ethers. Two drug molecules were successfully prepared using this protocol as a key step, emphasizing its potential utility in medicinal chemistry. A DFT computational study suggests that the reaction proceeds via initial addition of the alkoxide to the sulfoxide. This adduct facilitates further intramolecular addition of the alkoxide to the aromatic ring wherein charge on the aromatic system is stabilized by the nearby potassium cation. Rate-determining fragmentation then delivers methyl sulfenate and the aryl or heteroaryl ether. This study establishes the feasibility of nucleophilic addition to an appended sulfoxide as a means to form a bond to aryl(heteroaryl) systems and this modality is expected to find use with many other electrophiles and nucleophiles leading to new cross-coupling processes.
Chromosomal toxin-antitoxin systems in Pseudomonas putida are rather selfish than beneficial
Authors: Rosendahl Sirli , Tamman Hedvig , Brauer Age , Remm Maido , Hõrak Rita
Published: June 2020

Chromosomal toxin-antitoxin (TA) systems are widespread genetic elements among bacteria, yet, despite extensive studies in the last decade, their biological importance remains ambivalent. The ability of TA-encoded toxins to affect stress tolerance when overexpressed supports the hypothesis of TA systems being associated with stress adaptation. However, the deletion of TA genes has usually no effects on stress tolerance, supporting the selfish elements hypothesis. Here, we aimed to evaluate the cost and benefits of chromosomal TA systems to Pseudomonas putida. We show that multiple TA systems do not confer fitness benefits to this bacterium as deletion of 13 TA loci does not influence stress tolerance, persistence or biofilm formation. Our results instead show that TA loci are costly and decrease the competitive fitness of P. putida. Still, the cost of multiple TA systems is low and detectable in certain conditions only. Construction of antitoxin deletion strains showed that only five TA systems code for toxic proteins, while other TA loci have evolved towards reduced toxicity and encode non-toxic or moderately potent proteins. Analysis of P. putida TA systems’ homologs among fully sequenced Pseudomonads suggests that the TA loci have been subjected to purifying selection and that TA systems spread among bacteria by horizontal gene transfer.
Thickness measurement of transparent liquid films with Paraxial Self-Reference Interferometry
Authors: Razzaghi Ahmad , Amjad Jafar Mostafavi , Maleki Maniya
Published: June 2020

In this paper, we introduce a non-invasive optical method, named Paraxial Self-Reference Interferometry (PSRI) for thickness measurement of liquid films. The method can be used for thin or thick layers (from μm to mm) of solids or liquids, with a high precision. The method is first applied to solid plates with known thickness and is verified to be accurate. Then we use it for the thickness measurement of liquid films in two experiments. The first experiment is spin coating and the second is dip coating. In both experiments, the results are in agreement with theoretical and experimental results of previous works. In the dip coating experiment, the Landau-Levich-Derjaguin law (LLD) is observed in low capillary numbers, and a deviation from this law due to gravity is seen in higher capillary numbers. The thinning due to the drainage is also observed and is consistent with theoretical predictions.
PAWI-2 overcomes tumor stemness and drug resistance via cell cycle arrest in integrin β3-KRAS-dependent pancreatic cancer stem cells
Authors: Cheng Jiongjia , Cashman John R.
Published: June 2020

Today, pancreatic cancer (PC) remains a major health problem in the US. The fact that cancer stem cells (CSCs) become enriched in humans following anti-cancer therapy implicates CSCs as key contributors to tumor dormancy, metastasis, and relapse in PC. A highly validated CSC model (FGβ3 cells) was used to test a novel compound (PAWI-2) to eradicate CSCs. Compared to parental bulk FG cells, PAWI-2 showed greater potency to inhibit cell viability and self-renewal capacity of FGβ3 cells. For FGβ3 cells, dysregulated integrin β3-KRAS signaling drives tumor progression. PAWI-2 inhibited β3-KRAS signaling independent of KRAS. This is clinically relevant. PAWI-2 targeted the downstream TBK1 phosphorylation cascade that was negatively regulated by optineurin phosphorylation via a feedback mechanism. This was confirmed by TBK1 genetic knockdown or co-treatment with TBK1-specific inhibitor (MRT67307). PAWI-2 also overcame erlotinib (an EGFR inhibitor) resistance in FGβ3 cells more potently than bortezomib. In the proposed working model, optineurin acts as a key regulator to link inhibition of KRAS signaling and cell cycle arrest (G2/M). The findings show PAWI-2 is a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.
The monoclonal antibody Ca37, developed against Candida albicans alcohol dehydrogenase, inhibits the yeast in vitro and in vivo
Authors: Antoran Aitziber , Aparicio-Fernandez Leire , Pellon Aize , Buldain Idoia , Martin-Souto Leire , Rementeria Aitor , Ghannoum Mahmoud A. , Fuchs Beth Burgwyn , Mylonakis Eleftherios , Hernando Fernando L. , Ramirez-Garcia Andoni
Published: June 2020

Candida albicans is a commensal yeast able to cause life threatening invasive infections particularly in immunocompromised patients. Despite the availability of antifungal treatments, mortality rates are still unacceptably high and drug resistance is increasing. We, therefore, generated the Ca37 monoclonal antibody against the C. albicans alcohol dehydrogenase (Adh) 1. Our data showed that Ca37 was able to detect C. albicans cells, and it bound to Adh1 in yeast and Adh2 in hyphae among the cell wall-associated proteins. Moreover, Ca37 was able to inhibit candidal growth following 18 h incubation time and reduced the minimal inhibitory concentration of amphotericin B or fluconazole when used in combination with those antifungals. In addition, the antibody prolonged the survival of C. albicans infected-Galleria mellonella larvae, when C. albicans was exposed to antibody prior to inoculating G. mellonella or by direct application as a therapeutic agent on infected larvae. In conclusion, the Ca37 monoclonal antibody proved to be effective against C. albicans, both in vitro and in vivo, and to act together with antifungal drugs, suggesting Adh proteins could be interesting therapeutic targets against this pathogen.
Importance of Thyroid Hormone level and Genetic Variations in Deiodinases for Patients after Acute Myocardial Infarction: A Longitudinal Observational Study
Authors: Kazukauskiene Nijole , Skiriute Daina , Gustiene Olivija , Burkauskas Julius , Zaliunaite Violeta , Mickuviene Narseta , Brozaitiene Julija
Published: June 2020

This study aimed to examine the influence of thyroid hormone (TH) levels and genetic polymorphisms of deiodinases on long-term outcomes after acute myocardial infarction (AMI). In total, 290 patients who have experienced AMI were evaluated for demographic, clinical characteristics, risk factors, TH and NT-pro-BNP. Polymorphisms of TH related genes were included deiodinase 1 (DIO1) (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), deiodinase 2 (DIO2) (rs225015-G/A, rs225014-T/C) and deiodinase 3 (DIO3) (rs945006-T/G). Both all-cause and cardiac mortality was considered key outcomes. Cox regression model showed that NT-pro-BNP (HR = 2.11; 95% CI = 1.18– 3.78; p = 0.012), the first quartile of fT3, andDIO1gene rs12095080 were independent predictors of cardiac-related mortality (HR = 1.74; 95% CI = 1.04–2.91; p = 0.034). TheDIO1gene rs12095080 AG genotype (OR = 3.97; 95% CI = 1.45–10.89; p = 0.005) increased the risk for cardiac mortality. Lower fT3 levels and theDIO1gene rs12095080 are both associated with cardiac-related mortality after AMI.
Network Localisation of White Matter Damage in Cerebral Small Vessel Disease
Authors: Petersen Marvin , Frey Benedikt M. , Schlemm Eckhard , Mayer Carola , Hanning Uta , Engelke Kristin , Fiehler Jens , Borof Katrin , Jagodzinski Annika , Gerloff Christian , Thomalla Götz , Cheng Bastian
Published: June 2020

Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group’s connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.
Unique age-related transcriptional signature in the nervous system of the long-lived red sea urchin Mesocentrotus franciscanus
Authors: Polinski Jennifer M. , Kron Nicholas , Smith Douglas R. , Bodnar Andrea G.
Published: June 2020

The red sea urchin, Mesocentrotus franciscanus, is one the earth’s longest-lived animals, reported to live more than 100 years with indeterminate growth, life-long reproduction and no increase in mortality rate with age. To gain insight into mechanisms associated with longevity and negligible senescence, age-related transcriptional profiles were examined in tissues of the red sea urchin. Genome-wide transcriptional profiling using RNA-Seq revealed few age-related changes in gene expression in muscle and esophagus tissue. In contrast, radial nerve showed an unexpected level of complexity with the expression of 3,370 genes significantly altered more than two-fold with age, including genes involved in nerve function, signaling, metabolism, transcriptional regulation and chromatin modification. There was an age-related upregulation in expression of genes involved in synaptogenesis, axonogenesis and neuroprotection suggesting preservation of neuronal processes with age. There was also an upregulation in expression of positive regulators and key components of the AMPK pathway, autophagy, proteasome function, and the unfolded protein response. This unique age-related gene expression profile in the red sea urchin nervous system may play a role in mitigating the detrimental effects of aging in this long-lived animal.
AMF communities associated to Vitis vinifera in an Italian vineyard subjected to integrated pest management at two different phenological stages
Authors: Massa N. , Bona E. , Novello G. , Todeschini V. , Boatti L. , Mignone F. , Gamalero E. , Lingua G. , Berta G. , Cesaro P.
Published: June 2020

Vitis viniferaL. is an economically important crop that can be influenced by soil microorganisms, including arbuscular mycorrhizal fungi (AMF), that establish symbiotic associations with its roots. AMF have beneficial effects on grapevine performance improving water use efficiency and replant success. Most grapevine varieties are susceptible to various diseases, and integrated pest management (IPM) is one of the emerging approaches to perform pest control. In the present study, we examined the AMF communities present in the soil associated to the roots ofV. viniferacv. Pinot Noir (comparing them to those present in a soil not affected by grapevine roots), in a vineyard subjected to IPM at two different phenological stages, using 454 Roche sequencing technology. We proposed a new approach to analyze sequencing data. Most of the taxa were included in the family Glomeraceae. In particular,Glomussp.Rhizophagussp. andSeptoglomus viscosumwere present. The family Archeosporaceae was represented only by the genusArcheosporasp. Different AMF communities were found in the two soils and the importance of the phenological stage in regulating AMF biodiversity was assessed.
Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders
Authors: Delaby C. , Alcolea D. , Carmona-Iragui M. , Illán-Gala I. , Morenas-Rodríguez E. , Barroeta I. , Altuna M. , Estellés T. , Santos-Santos M. , Turon-Sans J. , Muñoz L. , Ribosa-Nogué R. , Sala-Matavera I. , Sánchez-Saudinos B. , Subirana A. , Videla L. , Benejam B. , Sirisi S. , Lehmann S. , Belbin O. , Clarimon J. , Blesa R. , Pagonabarraga J. , Rojas-Garcia R. , Fortea J. , Lleó A.
Published: June 2020

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.
Generation of Q-switched Pulses in Thulium-doped and Thulium/Holmium-co-doped Fiber Lasers using MAX phase (Ti3AlC2)
Authors: Ahmad H. , Kamely A. A. , Yusoff N. , Bayang L. , Samion M. Z.
Published: June 2020

A MAX phase Ti3AlC2 thin film is demonstrated as a saturable absorber (SA) to induce Q-switching in the 2.0 μm region. The Ti3AlC2 thin film is sandwiched between two fiber ferrules and integrated into thulium doped fiber laser (TDFL) and thulium-holmium doped fiber laser (THDFL) cavities. Stable Q-switched pulses are observed at 1980.79 nm and 1959.3 nm in the TDFL and THDFL cavities respectively, with repetition rates of 32.57 kHz and 21.94 kHz and corresponding pulse widths of 2.72 μs and 3.9 μs for both cavities. The performance of the Ti3AlC2 based SA for Q-switching operation indicates the high potential of other MAX phase materials to serve as SAs in future photonics systems.
Bioremediation of oil contaminated soil using agricultural wastes via microbial consortium
Authors: Zhang Chao , Wu Daoji , Ren Huixue
Published: June 2020

Agricultural wastes, such as wheat bran and swine wastewater, were used for bioremediation of oil-contaminated soil. Two optimised strains that could degrade oil efficiently were selected. The result showed that the best ratio of strain A to strain B was 7:3. Swine wastewater could be a replacement for nitrogen source and process water for bioremediation. Next, the Box-Behnken design was used to optimise the culture medium, and the optimal medium was as follows: microbial dosage of 97 mL/kg, wheat bran of 158 g/kg and swine wastewater of 232 mL/kg. Under the optimal medium, the oil degradation rate reached 68.27 ± 0.71% after 40 d. The urease, catalase, and dehydrogenase activities in oil-contaminated soil all increased, and the microbe quantity increased significantly with manual composting. These investigations might lay a foundation for reducing the pollution of agricultural wastes, exploring a late model for bioremediation of oil-contaminated soil.
Fuelling walking and cycling: human powered locomotion is associated with non-negligible greenhouse gas emissions
Authors: Mizdrak Anja , Cobiac Linda J , Cleghorn Christine L , Woodward Alistair , Blakely Tony
Published: June 2020

Reducing motorized transport and increasing active transport (i.e. transport by walking, cycling and other active modes) may reduce greenhouse gas (GHG) emissions and improve health. But, active modes of transport are not zero emitters. We aimed to quantify GHG emissions from food production required to fuel extra physical activity for walking and cycling. We estimate the emissions (in kgCO2e) per kilometre travelled for walking and cycling from energy intake required to compensate for increased energy expenditure, and data on food-related GHG emissions. We assume that persons who shift from passive modes of transport (e.g. driving) have increased energy expenditure that may be compensated with increased food consumption. The GHG emissions associated with food intake required to fuel a kilometre of walking range between 0.05 kgCO2e/km in the least economically developed countries to 0.26 kgCO2e/km in the most economically developed countries. Emissions for cycling are approximately half those of walking. Emissions from food required for walking and cycling are not negligible in economically developed countries which have high dietary-related emissions. There is high uncertainty about the actual emissions associated with walking and cycling, and high variability based on country economic development. Our study highlights the need to consider emissions from other sectors when estimating net-emissions impacts from transport interventions.