bluuebunny/crossref_metadata_2025 huggingface dataset:
Wave Controls on Deltaic Shoreline‐Channel Morphodynamics: Insights From a Coupled Model
Authors: Gao Weilun , Nienhuis Jaap , Nardin William , Wang Zheng Bing , Shao Dongdong , Sun Tao , Cui Baoshan
Published: August 2020

It is widely recognized that waves inhibit river mouth progradation and reduce the avulsion timescale of deltaic channels. Nevertheless, those effects may not apply to downdrift‐deflected channels. In this study, we developed a coupled model to explore the effects of wave climate asymmetry and alongshore sediment bypassing on shoreline‐channel morphodynamics. The shoreline position and channel trajectory are simulated using a “shoreline” module which drives the evolution of the river profile in a “channel” module by updating the position of river mouth boundary, whereas the channel module provides the sediment load to river mouth for the “shoreline” module. The numerical results show that regional alongshore sediment transport driven by an asymmetric wave climate can enhance the progradation of deltaic channels if sediment bypassing of the river mouth is limited, which is different from the common assumption that waves inhibit delta progradation. As such, waves can have a trade‐off effect on river mouth progradation that can further influence riverbed aggradation and channel avulsion. This trade‐off effect of waves is dictated by the net alongshore sediment transport, sediment bypassing at the river mouth, and wave diffusivity. Based on the numerical results, we further propose a dimensionless parameter that includes fluvial and alongshore sediment supply relative to wave diffusivity to predict the progradation and aggradation rates and avulsion timescale of deltaic channels. The improved understanding of progradation, aggradation, and avulsion timescale of deltaic channels has important implications for engineering and predicting deltaic wetland creation, particularly under changing water and sediment input to deltaic systems.
Gas Component Transport Across the Soil‐Atmosphere Interface for Gases of Different Density: Experiments and Modeling
Authors: Bahlmann L. M. , Smits K. M. , Heck K. , Coltman E. , Helmig R. , Neuweiler I.
Published: August 2020

We investigate the influence of near‐surface wind conditions on subsurface gas transport and on soil‐atmosphere gas exchange for gases of different density. Results of a sand tank experiment are supported by a numerical investigation with a fully coupled porous medium‐free flow model, which accounts for wind turbulence. The experiment consists of a two‐dimensional bench‐scale soil tank containing homogeneous sand and an overlying wind tunnel. A point source was installed at the bottom of the tank. Gas concentrations were measured at multiple horizontal and vertical locations. Tested conditions include four wind velocities (0.2/1.0/2.0/2.7 m/s), three different gases (helium: light, nitrogen: neutral, and carbon dioxide: heavy), and two transport cases (1: steady‐state gas supply from the point source; 2: transport under decreasing concentration gradient, subsequent to termination of gas supply). The model was used to assess flow patterns and gas fluxes across the soil surface. Results demonstrate that flow and transport in the vicinity of the surface are strongly coupled to the overlying wind field. An increase in wind velocity accelerates soil‐atmosphere gas exchange. This is due to the effect of the wind profile on soil surface concentrations and due to wind‐induced advection, which causes subsurface horizontal transport. The presence of gases with pronounced density difference to air adds additional complexity to the transport through the wind‐affected soil layers. Wind impact differs between tested gases. Observed transport is multidimensional and shows that heavy as well as light gases cannot be treated as inert tracers, which applies to many gases in environmental studies.
Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism
Authors: Matoba Nana , Liang Dan , Sun Huaigu , Aygün Nil , McAfee Jessica C. , Davis Jessica E. , Raffield Laura M. , Qian Huijun , Piven Joseph , Li Yun , Kosuri Sriam , Won Hyejung , Stein Jason L.
Published: August 2020

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder. Large genetically informative cohorts of individuals with ASD have led to the identification of a limited number of common genome-wide significant (GWS) risk loci to date. However, many more common genetic variants are expected to contribute to ASD risk given the high heritability. Here, we performed a genome-wide association study (GWAS) on 6222 case-pseudocontrol pairs from the Simons Foundation Powering Autism Research for Knowledge (SPARK) dataset to identify additional common genetic risk factors and molecular mechanisms underlying risk for ASD. We identified one novel GWS locus from the SPARK GWAS and four significant loci, including an additional novel locus from meta-analysis with a previous GWAS. We replicated the previous observation of significant enrichment of ASD heritability within regulatory regions of the developing cortex, indicating that disruption of gene regulation during neurodevelopment is critical for ASD risk. We further employed a massively parallel reporter assay (MPRA) and identified a putative causal variant at the novel locus from SPARK GWAS with strong impacts on gene regulation (rs7001340). Expression quantitative trait loci data demonstrated an association between the risk allele and decreased expression ofDDHD2(DDHD domain containing 2) in both adult and prenatal brains. In conclusion, by integrating genetic association data with multi-omic gene regulatory annotations and experimental validation, we fine-mapped a causal risk variant and demonstrated thatDDHD2is a novel gene associated with ASD risk.
Miliary breast cancer brain metastasis: a rare and aggressive form of central nervous system metastasis
Authors: Mills Matthew N. , Ahmed Kamran A.
Published: August 2020

Although breast cancer brain metastasis is an increasingly common occurrence, relatively little is known about miliary brain metastases, a rare subtype that presents unique diagnostic and management challenges. The present study from Bashour et al. proposes the first objective diagnostic imaging criteria, enabling improved future study.
Engineered immunological niches to monitor disease activity and treatment efficacy in relapsing multiple sclerosis
Authors: Morris Aaron H. , Hughes Kevin R. , Oakes Robert S. , Cai Michelle M. , Miller Stephen D. , Irani David N. , Shea Lonnie D.
Published: August 2020

Relapses in multiple sclerosis can result in irreversible nervous system tissue injury. If these events could be detected early, targeted immunotherapy could potentially slow disease progression. We describe the use of engineered biomaterial-based immunological niches amenable to biopsy to provide insights into the phenotype of innate immune cells that control disease activity in a mouse model of multiple sclerosis. Differential gene expression in cells from these niches allow monitoring of disease dynamics and gauging the effectiveness of treatment. A proactive treatment regimen, given in response to signal within the niche but before symptoms appeared, substantially reduced disease. This technology offers a new approach to monitor organ-specific autoimmunity, and represents a platform to analyze immune dysfunction within otherwise inaccessible target tissues.
Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography
Authors: Nakatsuka Nathan , Luisi Pierre , Motti Josefina M. B. , Salemme Mónica , Santiago Fernando , D’Angelo del Campo Manuel D. , Vecchi Rodrigo J. , Espinosa-Parrilla Yolanda , Prieto Alfredo , Adamski Nicole , Lawson Ann Marie , Harper Thomas K. , Culleton Brendan J. , Kennett Douglas J. , Lalueza-Fox Carles , Mallick Swapan , Rohland Nadin , Guichón Ricardo A. , Cabana Graciela S. , Nores Rodrigo , Reich David
Published: August 2020

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700–2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200–1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.
Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles
Authors: Kang Tengfei , Hou Liuzhen , Ruan Sai , Cao Weidi , Liu Xiaohua , Feng Xiaoming
Published: August 2020

The investigation of diverse reactivity of β,γ-unsaturated carbonyl compounds is of great value in asymmetric catalytic synthesis. Numerous enantioselective transformations have been well developed with β,γ-unsaturated carbonyl compounds as nucleophiles, however, few example were realized by utilizing them as not only nucleophiles but also electrophiles under a same catalytic system. Here we report a regioselective catalytic asymmetric tandem isomerization/α-Michael addition of β,γ-unsaturated 2-acyl imidazoles in the presence of chiral N,N′-dioxide metal complexes, delivering a broad range of optically pure 1,5-dicarbonyl compounds with two vicinal tertiary carbon stereocenters in up to >99% ee under mild conditions. Meanwhile, stereodivergent synthesis is disclosed to yield all four stereoisomers of products. Control experiments suggest an isomerization process involved in the reaction and give an insight into the role of NEt3. In addition, Mannich reaction and sulfur-Michael addition of β,γ-unsaturated 2-acyl imidazoles proceed smoothly as well under the same catalytic system.
The nucleosome acidic patch and H2A ubiquitination underlie mSWI/SNF recruitment in synovial sarcoma
Authors: McBride Matthew J. , Mashtalir Nazar , Winter Evan B. , Dao Hai T. , Filipovski Martin , D’Avino Andrew R. , Seo Hyuk-Soo , Umbreit Neil T. , St. Pierre Roodolph , Valencia Alfredo M. , Qian Kristin , Zullow Hayley J. , Jaffe Jacob D. , Dhe-Paganon Sirano , Muir Tom W. , Kadoch Cigall
Published: August 2020

Interactions between chromatin-associated proteins and the histone landscape play major roles in dictating genome topology and gene expression. Cancer-specific fusion oncoproteins, which display unique chromatin localization patterns, often lack classical DNA-binding domains, presenting challenges in identifying mechanisms governing their site-specific chromatin targeting and function. Here we identify a minimal region of the human SS18-SSX fusion oncoprotein (the hallmark driver of synovial sarcoma) that mediates a direct interaction between the mSWI/SNF complex and the nucleosome acidic patch. This binding results in altered mSWI/SNF composition and nucleosome engagement, driving cancer-specific mSWI/SNF complex targeting and gene expression. Furthermore, the C-terminal region of SSX confers preferential affinity to repressed, H2AK119Ub-marked nucleosomes, underlying the selective targeting to polycomb-marked genomic regions and synovial sarcoma–specific dependency on PRC1 function. Together, our results describe a functional interplay between a key nucleosome binding hub and a histone modification that underlies the disease-specific recruitment of a major chromatin remodeling complex.
Deep Learning-Based Quantification of Pulmonary Hemosiderophages in Cytology Slides
Authors: Marzahl Christian , Aubreville Marc , Bertram Christof A. , Stayt Jason , Jasensky Anne-Katherine , Bartenschlager Florian , Fragoso-Garcia Marco , Barton Ann K. , Elsemann Svenja , Jabari Samir , Krauth Jens , Madhu Prathmesh , Voigt Jörn , Hill Jenny , Klopfleisch Robert , Maier Andreas
Published: August 2020

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition in sport horses with negative impact on performance. Cytology of bronchoalveolar lavage fluid by use of a scoring system is considered the most sensitive diagnostic method. Macrophages are classified depending on the degree of cytoplasmic hemosiderin content. The current gold standard is manual grading, which is however monotonous and time-consuming. We evaluated state-of-the-art deep learning-based methods for single cell macrophage classification and compared them against the performance of nine cytology experts and evaluated inter- and intra-observer variability. Additionally, we evaluated object detection methods on a novel data set of 17 completely annotated cytology whole slide images (WSI) containing 78,047 hemosiderophages. Our deep learning-based approach reached a concordance of 0.85, partially exceeding human expert concordance (0.68 to 0.86, mean of 0.73, SD of 0.04). Intra-observer variability was high (0.68 to 0.88) and inter-observer concordance was moderate (Fleiss’ kappa = 0.67). Our object detection approach has a mean average precision of 0.66 over the five classes from the whole slide gigapixel image and a computation time of below two minutes. To mitigate the high inter- and intra-rater variability, we propose our automated object detection pipeline, enabling accurate, reproducible and quick EIPH scoring in WSI.
Associations of PRKN–PACRG SNPs and G × G and G × E interactions with the risk of hyperlipidaemia
Authors: Zheng Peng-Fei , Yin Rui-Xing , Wei Bi-Liu , Liu Chun-Xiao , Deng Guo-Xiong , Guan Yao-Zong
Published: August 2020

This research aimed to assess the associations of 7 parkin RBR E3 ubiquitin protein ligase (PRKN) and 4 parkin coregulated gene (PACRG) single-nucleotide polymorphisms (SNPs), their haplotypes, gene–gene (G × G) and gene-environment (G × E) interactions with hyperlipidaemia in the Chinese Maonan minority. The genotypes of the 11 SNPs in 912 normal and 736 hyperlipidaemic subjects were detected with next-generation sequencing technology. The genotypic and allelic frequencies of the rs1105056, rs10755582, rs2155510, rs9365344, rs11966842, rs6904305 and rs11966948 SNPs were different between the normal and hyperlipidaemic groups (P < 0.05–0.001). Correlations between the above 7 SNPs and blood lipid levels were also observed (P < 0.0045–0.001, P < 0.0045 was considered statistically significant after Bonferroni correction). Strong linkage disequilibrium was found among the 11 SNPs (r2 = 0.01–0.64). The most common haplotypes were PRKN C-G-T-G-T-T-C (> 15%) and PACRG A-T-A-T (> 40%). The PRKN C-G-C-A-T-T-C and PRKN–PACRG C-G-T-G-T-T-C-A-T-A-T haplotypes were associated with an increased risk of hyperlipidaemia, whereas the PRKN–PACRG C-G-T-G-C-T-C-A-T-C-T and C-G-T-G-T-T-C-A-T-C-T haplotypes provided a protective effect. Association analysis based on the haplotypes and G × G interaction could improve the power to detect the risk of hyperlipidaemia over the analysis of any one SNP alone. The differences in serum lipid parameters between the hyperlipidaemic and normal groups might partly be due to the effects of the PRKN–PACRG SNPs and their haplotypes.
Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain
Authors: Palladino Claudia , Ezeonwumelu Ifeanyi Jude , Mate-Cano Irene , Borrego Pedro , Martínez-Román Paula , Arca-Lafuente Sonia , Resino Salvador , Taveira Nuno , Briz Verónica
Published: August 2020

Hepatitis C virus (HCV) infection remains a global health problem. Previously, the prevalence of NS5A resistance-associated substitutions (RASs) to elbasvir, a new direct-acting antiviral (DAA) against the NS5A viral protein was assessed by our group before its introduction into clinical use in Spain. However, the origin, epidemic history, transmission dynamics, diversity and baseline RASs to NS5A direct-acting agents of HCV-GT1a in Spain remain unknown. A nationwide cross-sectional survey of individuals chronically-infected with HCV-G1a and DAAs-naïve was performed. HCV population sequencing, phylogenetic analysis and Bayesian methods were used. GT1a clade II was more prevalent than clade I (82.3% vs. 17.7%; P < 0.001) and older (estimated origin in 1912 vs. 1952). Clade II epidemic is currently declining whereas clade I epidemic has reached equilibrium. A total of 58 single RASs were identified, which account for the moderate level (10%) of baseline resistance observed. When considering the regional data, marked differences were observed, with thirteen regions showing an intermediate level (5–15%) and one a high level (20%) of resistance. Current HCV-GT1a epidemic in Spain is driven by clade I which seem to have different dissemination routes relative to clade II. A moderate level of baseline RASs to NS5A-DAAs with marked differences among regions was observed. Close surveillance of response to treatment with DAAs will be important.
Correlative study of epigenetic regulation of tumor microenvironment in spindle cell melanomas and cutaneous malignant peripheral nerve sheath tumors
Authors: Vougiouklakis Theodore , Aung Phyu P. , Vasudevaraja Varshini , Prieto Victor G. , Torres-Cabala Carlos A. , Sulman Erik P. , Snuderl Matija , Jour George
Published: August 2020

The tumor microenvironment (TME) plays critical roles in tumor growth and progression, however key regulators of gene expression in the TME of cutaneous malignant peripheral nerve sheath tumor (C-MPNST) and spindle cell melanoma (SCM) have not been well elucidated. Herein, we investigate the epigenetic regulation of promoters and gene bodies and their effect on the TME composition of C-MPNSTs and SCMs. A cohort of 30 patients was analyzed using differential gene expression (DGE) and gene set enrichment analysis (GSEA) using the Nanostring platform. Methylation analysis was carried out utilizing an Infinium Methylation EPIC array targeting 866,562 methylation site (CpG) islands. DGE revealed overexpression of genes related to mast cells in the TME of SCMs, and a predominance of exhausted CD8+ T cells and macrophages in the TME of C-MPNSTs. Interestingly, we further observed promoter hypermethylation in key overexpressed genes and corresponding gene body hypomethylation. Analysis using ENCODE ChIP-sequencing data identified CTCF as the common transcription factor at the site of the hypomethylated probe. These findings support that the TME composition of C-MPNSTs and SCMs is at least partially independent on promoter methylation status, suggesting a possible relationship between gene body enhancers and expression of key TME genes in both entities.
Different luminance- and texture-defined contrast sensitivity profiles for school-aged children
Authors: Silvestre Daphné , Guy Jacalyn , Hanck Julie , Cornish Kim , Bertone Armando
Published: August 2020

Our current understanding of how the visual brain develops is based largely on the study of luminance-defined information processing. This approach, however, is somewhat limiting, since everyday scenes are composed of complex images, consisting of information characterized by physical attributes relating to both luminance and texture. Few studies have explored how contrast sensitivity to texture-defined information develops, particularly throughout the school-aged years. The current study investigated how contrast sensitivity to luminance- (luminance-modulated noise) and texture-defined (contrast-modulated noise) static gratings develops in school-aged children. Contrast sensitivity functions identified distinct profiles for luminance- and texture-defined gratings across spatial frequencies (SFs) and age. Sensitivity to luminance-defined gratings reached maturity in childhood by the ages of 9–10 years for all SFs (0.5, 1, 2, 4 and 8 cycles/degree or cpd). Sensitivity to texture-defined gratings reached maturity at 5–6 years for low SFs and 7–8 years for high SFs (i.e., 4 cpd). These results establish that the processing of luminance- and texture-defined information develop differently as a function of SF and age.
A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories
Authors: Abdel-Latif Ghada A. , Elwahab Azza H. Abd , Hasan Rehab A. , ElMongy Noura F. , Ramzy Maggie M. , Louka Manal L. , Schaalan Mona F.
Published: August 2020

Cyclophosphamide (CP) is a chemotherapeutic agent that induces oxidative stress causing multiple organ damage. Sacubitril/valsartan, is a combined formulation of neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (valsartan), that induces the protective effect of brain natriuretic peptide. The aim of the current study is to investigate the prophylactic impacts of sacubitril/valsartan versus valsartan against CP-induced lung toxicity in rats. Rats were assigned randomly into 6 groups; control; received corn oil (2 ml/kg/day; p.o. for 6 days), sacubitril/valsartan (30 mg/kg; p.o. for 6 days), valsartan (15 mg/kg; p.o. for 6 days), CP (200 mg/kg; i.p. on day 5), sacubitril/valsartan + CP (30 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively), valsartan + CP (15 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively). Both sacubitril/valsartan and valsartan produced a significant decrease in the inflammation and fibrosis markers in the BALF, in comparison with the CP group. Both sacubitril/valsartan and valsartan produced an apparent decrease in the relative genes expression of miR-150-3p and NF-κB, as well as a significant decrease in the relative expression of P38 and ERK1/2 MAPKs and an increase in the relative gene expression of Nrf-2, compared to CP group. Intriguingly, sacubitril/valsartan , showed subtle superiority in almost all investigated parameters, compared to valsartan. In conclusion, sacubitril/valsartan effectively abrogated the CP induced lung inflammation and fibrosis, providing a potential promising protection that could be linked to their ability to inhibit miR-150-3p via inhibition of NF-κB and MAPK signaling pathways.
The diversification and lineage-specific expansion of nitric oxide signaling in Placozoa: insights in the evolution of gaseous transmission
Authors: Moroz Leonid L. , Romanova Daria Y. , Nikitin Mikhail A. , Sohn Dosung , Kohn Andrea B. , Neveu Emilie , Varoqueaux Frederique , Fasshauer Dirk
Published: August 2020

Nitric oxide (NO) is a ubiquitous gaseous messenger, but we know little about its early evolution. Here, we analyzed NO synthases (NOS) in four different species of placozoans—one of the early-branching animal lineages. In contrast to other invertebrates studied, Trichoplax and Hoilungia have three distinct NOS genes, including PDZ domain-containing NOS. Using ultra-sensitive capillary electrophoresis assays, we quantified nitrites (products of NO oxidation) and l-citrulline (co-product of NO synthesis from l-arginine), which were affected by NOS inhibitors confirming the presence of functional enzymes in Trichoplax. Using fluorescent single-molecule in situ hybridization, we showed that distinct NOSs are expressed in different subpopulations of cells, with a noticeable distribution close to the edge regions of Trichoplax. These data suggest both the compartmentalized release of NO and a greater diversity of cell types in placozoans than anticipated. NO receptor machinery includes both canonical and novel NIT-domain containing soluble guanylate cyclases as putative NO/nitrite/nitrate sensors. Thus, although Trichoplax and Hoilungia exemplify the morphologically simplest free-living animals, the complexity of NO-cGMP-mediated signaling in Placozoa is greater to those in vertebrates. This situation illuminates multiple lineage-specific diversifications of NOSs and NO/nitrite/nitrate sensors from the common ancestor of Metazoa and the preservation of conservative NOS architecture from prokaryotic ancestors.
A model for the geomagnetic field reversal rate and constraints on the heat flux variations at the core-mantle boundary
Authors: Carbone Vincenzo , Alberti Tommaso , Lepreti Fabio , Vecchio Antonio
Published: August 2020

A striking feature of many natural magnetic fields generated by dynamo action is the occurrence of polarity reversals. Paleomagnetic measurements revealed that the Earth’s magnetic field has been characterised by few hundred stochastic polarity switches during its history. The rate of reversals changes in time, maybe obeying some underlying regular pattern. While chaotic dynamical systems can describe the short-term behaviour of the switches of the Earth’s magnetic polarity, modelling the long-term variations of the reversal rate is somewhat problematic, as they occur on timescales of tens to hundreds of millions of years, of the order of mantle convection timescales. By investigating data of geomagnetic reversal rates, we find the presence of cycles with variable frequency and show that the transition towards periods where reversals do not occur for tens of million years (superchrons) can be described by a second-order phase transition that we interpret to be driven by variations of the heat flux at the core-mantle boundary (CMB). The model allows us to extract from the reversal sequence quantitative information on the susceptibility of the reversal rate caused by changes in the CMB heat flux amplitude, thus providing direct information on the deep inner layers of the Earth.
Age negatively impacts reproduction in high-ranking male rhesus macaques on Cayo Santiago, Puerto Rico
Authors: Milich Krista M. , Ruiz-Lambides Angelina , Maldonado Elizabeth , Maestripieri Dario
Published: August 2020

Based on sexual selection theory, the reproductive potential of male primates is expected to be limited by access to fertile females. Alpha males, the highest ranking males in a social group, are predicted to have better access to mates and produce more offspring until they are no longer dominant, which usually corresponds with age. Little is known about male reproductive senescence independent of rank changes in nonhuman primates. Here, we examine variation in the reproductive success of high-ranking male rhesus macaques on Cayo Santiago. We recorded behavioral data for 21 adult males across 9 social groups during the 2013 mating season. Additionally, we used paternity data from the long-term database to determine the number of offspring each subject sired over his lifetime and during the study period. Older high-ranking males in stable groups had fewer offspring than younger high-ranking males in stable groups in 2013. The low reproductive output for the older males was not a result of lower mating effort, and reproductive output in 2013 was not predicted by total prior reproductive success. Our results provide novel evidence of post-copulatory reproductive senescence in high-ranking male nonhuman primates.
Rapid microbial diversification of dissolved organic matter in oceanic surface waters leads to carbon sequestration
Authors: Hach Philipp F. , Marchant Hannah K. , Krupke Andreas , Riedel Thomas , Meier Dimitri V. , Lavik Gaute , Holtappels Moritz , Dittmar Thorsten , Kuypers Marcel M. M.
Published: August 2020

The pool of dissolved organic matter (DOM) in the deep ocean represents one of the largest carbon sinks on the planet. In recent years, studies have shown that most of this pool is recalcitrant, because individual compounds are present at low concentrations and because certain compounds seem resistant to microbial degradation. The formation of the diverse and recalcitrant deep ocean DOM pool has been attributed to repeated and successive processing of DOM by microorganisms over time scales of weeks to years. Little is known however, about the transformation and cycling that labile DOM undergoes in the first hours upon its release from phytoplankton. Here we provide direct experimental evidence showing that within hours of labile DOM release, its breakdown and recombination with ambient DOM leads to the formation of a diverse array of new molecules in oligotrophic North Atlantic surface waters. Furthermore, our results reveal a preferential breakdown of N and P containing molecules versus those containing only carbon. Hence, we show the preferential breakdown and molecular diversification are the crucial first steps in the eventual formation of carbon rich DOM that is resistant to microbial remineralization.
Global transcriptome analysis of subterranean pod and seed in peanut (Arachis hypogaea L.) unravels the complexity of fruit development under dark condition
Authors: Liu Hao , Liang Xuanqiang , Lu Qing , Li Haifen , Liu Haiyan , Li Shaoxiong , Varshney Rajeev , Hong Yanbin , Chen Xiaoping
Published: August 2020

Peanut pods develop underground, which is the most salient characteristic in peanut. However, its developmental transcriptome remains largely unknown. In the present study, we sequenced over one billion transcripts to explore the developmental transcriptome of peanut pod using Illumina sequencing. Moreover, we identified and quantified the abundances of 165,689 transcripts in seed and shell tissues along with a pod developmental gradient. The dynamic changes of differentially expressed transcripts (DETs) were described in seed and shell. Additionally, we found that photosynthetic genes were not only pronouncedly enriched in aerial pod, but also played roles in developing pod under dark condition. Genes functioning in photomorphogenesis showed distinct expression profiles along subterranean pod development. Clustering analysis unraveled a dynamic transcriptome, in which transcripts for DNA synthesis and cell division during pod expansion were transitioning to transcripts for cell expansion and storage activity during seed filling. Collectively, our study formed a transcriptional baseline for peanut fruit development under dark condition.
Immune outcomes of Zika virus infection in nonhuman primates
Authors: Schouest Blake , Fahlberg Marissa , Scheef Elizabeth A. , Ward Matthew J. , Headrick Kyra , Szeltner Dawn M. , Blair Robert V. , Gilbert Margaret H. , Doyle-Meyers Lara A. , Danner Victoria W. , Bonaldo Myrna C. , Wesson Dawn M. , Panganiban Antonito T. , Maness Nicholas J.
Published: August 2020

Although the Zika virus (ZIKV) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. Nonhuman primate (NHP) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. Here, we infected a small group of male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques with a minimally passaged Brazilian ZIKV isolate and used multicolor flow cytometry and transcriptional profiling to describe early immune patterns following infection. We found evidence of strong innate antiviral responses together with induction of neutralizing antibodies and T cell responses. We also assessed the relative importance of CD8 T cells in controlling infection by carrying out CD8 T cell depletion in an additional two animals of each species. CD8 depletion appeared to dysregulate early antiviral responses and possibly increase viral persistence, but the absence of CD8 T cells ultimately did not impair control of the virus. Together, these data describe immunological trends in two NHP species during acute ZIKV infection, providing an account of early responses that may be important in controlling infection.
Direct and quantitative analysis of altered metabolic flux distributions and cellular ATP production pathway in fumarate hydratase-diminished cells
Authors: Noguchi Shingo , Ishikawa Hirokazu , Wakita Kenichi , Matsuda Fumio , Shimizu Hiroshi
Published: August 2020

Fumarate hydratase (FH) is an enzyme in the tricarboxylic acid (TCA) cycle, biallelic loss-of-function mutations of which are associated with hereditary leiomyomatosis and renal cell cancer. However, how FH defect modulates intracellular metabolic fluxes in human cells has remained unclear. This study aimed to reveal metabolic flux alterations induced by reduced FH activity. We applied 13C metabolic flux analysis (13C-MFA) to an established cell line with diminished FH activity (FHdim) and parental HEK293 cells. FHdim cells showed reduced pyruvate import flux into mitochondria and subsequent TCA cycle fluxes. Interestingly, the diminished FH activity decreased FH flux only by about 20%, suggesting a very low need for FH to maintain the oxidative TCA cycle. Cellular ATP production from the TCA cycle was dominantly suppressed compared with that from glycolysis in FHdim cells. Consistently, FHdim cells exhibited higher glucose dependence for ATP production and higher resistance to an ATP synthase inhibitor. In summary, using FHdim cells we demonstrated that FH defect led to suppressed pyruvate import into mitochondria, followed by downregulated TCA cycle activity and altered ATP production pathway balance from the TCA cycle to glycolysis. We confirmed that 13C-MFA can provide direct and quantitative information on metabolic alterations induced by FH defect.
Diatoms constrain forensic burial timelines: case study with DB Cooper money
Authors: Kaye Thomas G. , Meltzer Mark
Published: August 2020

Diatoms are found universally in waters around the world. Some diatom species such as Asterionella formosa have a broad variation in seasonal abundance leading to the possibility that diatoms could constrain the time of year when an object was immersed in water. Here we apply this technique to the cold case of DB Cooper’s money. Nine years after the crime, six thousand dollars in three bundles were found on the shore of the Columbia River near Portland, Oregon. This burial site was ~30 km from his reported jump location which gave no apparent reason for the money to end up there. This study found diatoms on a recovered bill which indicates that the money was immersed before burial. The species mix found on the bills was compared to a test bill submerged in the Columbia River in November which was the timeframe for the crime. The Cooper bill contained diatoms from summer bloom species suggesting that the money was not directly buried dry and the immersion happened months after the late November hijacking. This finding rules out of a majority of current theories related to the crime and proposes diatoms as a feasible methodology to constrain seasonal timelines in forensics.
Comparison of eight complete chloroplast genomes of the endangered Aquilaria tree species (Thymelaeaceae) and their phylogenetic relationships
Authors: Hishamuddin Muhammad Syahmi , Lee Shiou Yih , Ng Wei Lun , Ramlee Shairul Izan , Lamasudin Dhilia Udie , Mohamed Rozi
Published: August 2020

Aquilaria tree species are naturally distributed in the Indomalesian region and are protected against over-exploitation. They produce a fragrant non-timber product of high economic value, agarwood. Ambiguous species delimitation and limited genetic information within Aquilaria are among the impediments to conservation efforts. In this study, we conducted comparative analysis on eight Aquilaria species complete chloroplast (cp) genomes, of which seven were newly sequenced using Illumina HiSeq X Ten platform followed by de novo assembly. Aquilaria cp genomes possess a typical quadripartite structure including gene order and genomic structure. The length of each of the cp genome is about 174 kbp and encoded between 89 and 92 proteins, 38 tRNAs, and 8 rRNAs, with 27 duplicated in the IR (inverted repeat) region. Besides, 832 repeats (forward, reverse, palindrome and complement repeats) and nine highly variable regions were also identified. The phylogenetic analysis suggests that the topology structure of Aquilaria cp genomes were well presented with strong support values based on the cp genomes data set and matches their geographic distribution pattern. In summary, the complete cp genomes will facilitate development of species-specific molecular tools to discriminate Aquilaria species and resolve the evolutionary relationships of members of the Thymelaeaceae family.
The dynamics of free and phosphopeptide-bound Grb2-SH2 reveals two dynamically independent subdomains and an encounter complex with fuzzy interactions
Authors: Sanches Karoline , Caruso Icaro P. , Almeida Fabio C. L. , Melo Fernando A.
Published: August 2020

The growth factor receptor-bound protein 2 (Grb2) is a key factor in the regulation of cell survival, proliferation, differentiation, and metabolism. In its structure, the central Src homology 2 (SH2) domain is flanked by two Src homology 3 (SH3). SH2 is the most important domain in the recognition of phosphotyrosines. Here, we present the first dynamical characterization of Grb2-SH2 domain in the free state and in the presence of phosphopeptide EpYINSQV at multiple timescales, which revealed valuable information to the understanding of phophotyrosine sensing mechanism. Grb2-SH2 presented two dynamically independent subdomains, subdomain I involved in pY recognition and subdomain II is the pY + 2 specificity pocket. Under semi-saturated concentrations of pY-pep we observed fuzzy interactions, which led to chemical exchange observed by NMR. This information was used to describe the encounter complex. The association with pY-pep is dynamic, involving fuzzy interactions and multiple conformations of pY-pep with negative and hydrophobic residues, creating an electrostatic-potential that drives the binding of pY-pep. The recognition face is wider than the binding site, with many residues beyond the central SH2 binding site participating in the association complex, which contribute to explain previously reported capability of Grb2 to recognize remote pY.
Fabrication of fluorescent pH-responsive protein–textile composites
Authors: Saldanha Dalia Jane , Abdali Zahra , Modafferi Daniel , Janfeshan Bita , Dorval Courchesne Noémie-Manuelle
Published: August 2020

Wearable pH sensors are useful tools in the healthcare and fitness industries, allowing consumers to access information related to their health in a convenient manner via the monitoring of body fluids. In this work, we tailored novel protein–textile composites to fluorescently respond to changing pH. To do so, we used amyloid curli fibers, a key component in the extracellular matrix ofEscherichia coli, as genetic scaffold to fuse a pH-responsive fluorescent protein, pHuji. Engineered amyloids form macroscopic and environmentally resistant aggregates that we isolated to use as stand-alone hydrogel-based sensors, and that we trapped within textile matrices to create responsive bio-composites. We showed that these composites were mechanically robust and vapor-permeable, thus exhibiting favorable characteristics for wearable platforms. CsgA–pHuji fibers integrated in the textile allowed the final device to respond to pH changes and distinguish between alkaline and acidic solutions. We demonstrated that the resulting composites could sustain their fluorescence response over days, and that their sensing ability was reversible for at least 10 high/low pH cycles, highlighting their potential for continuous monitoring. Overall, we introduced a biosynthesized amyloid-based textile composite that could be used as biosensing patch for a variety of applications in the smart textile industry.
Upcycling of Fe-bearing sludge: preparation of erdite-bearing particles for treating pharmaceutical manufacture wastewater
Authors: Hu Tongke , Wang Huaimin , Ning Ruyan , Qiao Xueling , Liu Yanwen , Dong Wenqing , Zhu Suiyi
Published: August 2020

Groundwater treatment sludge is a type of solid waste with 9.0–28.9% wt.% Fe content and is precipitated in large quantity from backwash wastewater in groundwater treatment. The sludge is mainly composed of fine particles containing Fe, Si and Al oxides, such as ferrihydrite, quartz and boehmite. The Fe oxides mostly originate from the oxidation of ferrous Fe in groundwater, whilst the silicate/aluminium compounds mainly originate from the broken quartz sand filter in the backwash step. In general, the sludge is firstly coagulated, dewatered by filter pressing and finally undergoes harmless solidification before it is sent to landfills. However, this process is costly (approximately US$66.1/t) and complicated. In this study, groundwater treatment sludge was effectively recycled to prepare novel erdite-bearing particles via a one-step hydrothermal method by adding only Na2S·9H2O. After hydrothermal treatment, the quartz and boehmite of the sludge were dissolved and recrystallised to sodalite, whilst ferrihydrite was converted to an erdite nanorod at 160 °C and a hematite at 240 °C. SP160 was prepared as fine nanorod particles with 200 nm diameter and 2–5 μm length at a hydrothermal temperature of 160 °C. Nearly 100% OTC and its derivatives in pharmaceutical manufacture wastewater were removed by adding 0.1 g SP160. The major mechanism for the removal was the spontaneous hydrolysis of erdite in SP160 to generate Fe oxyhydroxide and use many hydroxyl groups for coordinating OTC and its derivatives. This study presents a novel method for the resource reutilisation of waste groundwater treatment sludge and reports efficient erdite-bearing particles for pharmaceutical manufacture wastewater treatment.
Author Correction: Genome-wide identification of and functional insights into the late embryogenesis abundant (LEA) gene family in bread wheat (Triticum aestivum)
Authors: Liu Hao , Xing Mingyan , Yang Wenbo , Mu Xiaoqian , Wang Xin , Lu Feng , Wang Yao , Zhang Linsheng
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Vasoactive intestinal peptide axis is dysfunctional in patients with Graves’ disease
Authors: Carrión M. , Ramos-Leví A. M. , Seoane I. V. , Martínez-Hernández R. , Serrano-Somavilla A. , Castro D. , Juarranz Y. , González-Álvaro I. , Gomariz Rosa P. , Marazuela Mónica
Published: August 2020

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves’ disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto’s thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.
Small cell transformation of ROS1 fusion-positive lung cancer resistant to ROS1 inhibition
Authors: Lin Jessica J. , Langenbucher Adam , Gupta Pranav , Yoda Satoshi , Fetter Isobel J. , Rooney Marguerite , Do Andrew , Kem Marina , Chang Kylie Prutisto , Oh Audris Y. , Chin Emily , Juric Dejan , Corcoran Ryan B. , Dagogo-Jack Ibiayi , Gainor Justin F. , Stone James R. , Lennerz Jochen K. , Lawrence Michael S. , Hata Aaron N. , Mino-Kenudson Mari , Shaw Alice T.
Published: August 2020

Histologic transformation from non-small cell to small cell lung cancer has been reported as a resistance mechanism to targeted therapy in EGFR-mutant and ALK fusion-positive lung cancers. Whether small cell transformation occurs in other oncogene-driven lung cancers remains unknown. Here we analyzed the genomic landscape of two pre-mortem and 11 post-mortem metastatic tumors collected from an advanced, ROS1 fusion-positive lung cancer patient, who had received sequential ROS1 inhibitors. Evidence of small cell transformation was observed in all metastatic sites at autopsy, with inactivation of RB1 and TP53, and loss of ROS1 fusion expression. Whole-exome sequencing revealed minimal mutational and copy number heterogeneity, suggestive of “hard” clonal sweep. Patient-derived models generated from autopsy retained features consistent with small cell lung cancer and demonstrated resistance to ROS1 inhibitors. This case supports small cell transformation as a recurring resistance mechanism, and underscores the importance of elucidating its biology to expand therapeutic opportunities.
Microfluidic self-assembly of high cabazitaxel loading albumin nanoparticles
Authors: Sun Yating , Lee Robert J. , Meng Fanchao , Wang Guiyuan , Zheng Xiaolong , Dong Shiyan , Teng Lesheng
Published: August 2020

Microfluidic technology for the preparation of human serum albumin nanoparticles is a promising method.
Multi pH-sensitive polymer–drug conjugate mixed micelles for efficient co-delivery of doxorubicin and curcumin to synergistically suppress tumor metastasis
Authors: Zhou Yuanhang , Zhou Chuhang , Zou Yang , Jin Yao , Han Shidi , Liu Qi , Hu Xinping , Wang Leqi , Ma Yining , Liu Yan
Published: August 2020

Multi pH-responsive polymer-drug conjugate mixed micelles were fabricated to co-deliver doxorubicin and curcumin for synergistic suppression tumor metastasis via inhibiting the invasion, migration, intravasation and extravasation of tumor cells.
Structural characterization of a peptoid-inspired conformationally constrained oligomer (PICCO) bound to streptavidin
Authors: McEnaney Patrick , Balzarini Madeline , Park Hajeung , Kodadek Thomas
Published: August 2020

A screen of a DNA-encoded library of PICCOs was screened against streptavidin (SA) resulting in the isolation of a high affinity ligand.
All good things come in threes: first example of a trimorphic, ternary molecular salt complex
Authors: Lemmerer Andreas
Published: August 2020

A ternary complex made up of trinitrobenzene, 2-aminopyridinium and 9-anthracenecarboxylate crystallizes out in three polymorphic forms, giving yellow, orange and red coloured crystals.
Graph convolutional neural networks with global attention for improved materials property prediction
Authors: Louis Steph-Yves , Zhao Yong , Nasiri Alireza , Wang Xiran , Song Yuqi , Liu Fei , Hu Jianjun
Published: August 2020

Graph neural networks with local and global attention mechanisms help to extract better features for materials property prediction.
Length-scales of dynamic heterogeneity in a driven binary colloid
Authors: Dutta Suman , Chakrabarti J.
Published: August 2020

Here we study the characteristic length scales in an aqueous suspension of a symmetric oppositely charged colloid subjected to a uniform electric field by Brownian dynamics simulations.
Superhard sp2–sp3 hybridized B2C3N2 with 2D metallicity
Authors: Li Baozhong , Zhang Yang , Luo Kun , Xie Chenlong , Gao Yufei , Hao Lingjuan , Wu Yingju , Zhang Shuangshuang , Ma Mengdong , Zhao Zhisheng , He Julong
Published: August 2020

t-B2C3N2 possesses superhigh hardness exceeding 40 GPa and unique 2D metallicity in a strong 3D network.
Reactions of a photoactivatable diazido Pt(iv) anticancer complex with a single-stranded oligodeoxynucleotide
Authors: Liang Zujun , Lin Jiafan , Gong Xianxian , Cheng Yiyu , Huang Chao , Zhang Jishuai , Wu Xiaoqin , Wang Fuyi , Zhao Yao , Wu Kui
Published: August 2020

Platination sites and oxidative adducts on a single-stranded oligodeoxynucleotide by photoactivatable diazido Pt(iv) anticancer complex were characterized by mass spectrometry.