bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid, deep and precise profiling of the plasma proteome with multi-nanoparticle protein corona
Authors: Blume John E. , Manning William C. , Troiano Gregory , Hornburg Daniel , Figa Michael , Hesterberg Lyndal , Platt Theodore L. , Zhao Xiaoyan , Cuaresma Rea A. , Everley Patrick A. , Ko Marwin , Liou Hope , Mahoney Max , Ferdosi Shadi , Elgierari Eltaher M. , Stolarczyk Craig , Tangeysh Behzad , Xia Hongwei , Benz Ryan , Siddiqui Asim , Carr Steven A. , Ma Philip , Langer Robert , Farias Vivek , Farokhzad Omid C.
Published: July 2020

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined workflow combines depth of coverage and throughput with precise quantification based on unique interactions between proteins and NPs engineered for deep and scalable quantitative proteomic studies.
Transition to naïve human pluripotency mirrors pan-cancer DNA hypermethylation
Authors: Patani Hemalvi , Rushton Michael D. , Higham Jonathan , Teijeiro Saul A. , Oxley David , Cutillas Pedro , Sproul Duncan , Ficz Gabriella
Published: July 2020

Epigenetic reprogramming is a cancer hallmark, but how it unfolds during early neoplastic events and its role in carcinogenesis and cancer progression is not fully understood. Here we show that resetting from primed to naïve human pluripotency results in acquisition of a DNA methylation landscape mirroring the cancer DNA methylome, with gradual hypermethylation of bivalent developmental genes. We identify a dichotomy between bivalent genes that do and do not become hypermethylated, which is also mirrored in cancer. We find that loss of H3K4me3 at bivalent regions is associated with gain of methylation. Additionally, we observe that promoter CpG island hypermethylation is not restricted solely to emerging naïve cells, suggesting that it is a feature of a heterogeneous intermediate population during resetting. These results indicate that transition to naïve pluripotency and oncogenic transformation share common epigenetic trajectories, which implicates reprogramming and the pluripotency network as a central hub in cancer formation.
Mimicry of emergent traits amplifies coastal restoration success
Authors: Temmink Ralph J. M. , Christianen Marjolijn J. A. , Fivash Gregory S. , Angelini Christine , Boström Christoffer , Didderen Karin , Engel Sabine M. , Esteban Nicole , Gaeckle Jeffrey L. , Gagnon Karine , Govers Laura L. , Infantes Eduardo , van Katwijk Marieke M. , Kipson Silvija , Lamers Leon P. M. , Lengkeek Wouter , Silliman Brian R. , van Tussenbroek Brigitta I. , Unsworth Richard K. F. , Yaakub Siti Maryam , Bouma Tjeerd J. , van der Heide Tjisse
Published: July 2020

Restoration is becoming a vital tool to counteract coastal ecosystem degradation. Modifying transplant designs of habitat-forming organisms from dispersed to clumped can amplify coastal restoration yields as it generates self-facilitation from emergent traits, i.e. traits not expressed by individuals or small clones, but that emerge in clumped individuals or large clones. Here, we advance restoration science by mimicking key emergent traits that locally suppress physical stress using biodegradable establishment structures. Experiments across (sub)tropical and temperate seagrass and salt marsh systems demonstrate greatly enhanced yields when individuals are transplanted within structures mimicking emergent traits that suppress waves or sediment mobility. Specifically, belowground mimics of dense root mats most facilitate seagrasses via sediment stabilization, while mimics of aboveground plant structures most facilitate marsh grasses by reducing stem movement. Mimicking key emergent traits may allow upscaling of restoration in many ecosystems that depend on self-facilitation for persistence, by constraining biological material requirements and implementation costs.
Attosecond electronic timing with rising edges of photocurrent pulses
Authors: Hyun Minji , Ahn Changmin , Na Yongjin , Chung Hayun , Kim Jungwon
Published: July 2020

There has been remarkable progress in generating ultralow-noise microwaves from optical frequency combs in the last decade. While a combination of techniques has enabled tens to hundreds of attoseconds residual jitter in microwave extraction, so far most of research efforts have been focused on extracting single-tone microwaves from combs; there has been no study on the noise properties of photocurrent pulses directly extracted from the photodiode. Here, we reveal that the residual jitter between optical pulses and rising edges of photocurrent pulses can be in the tens of attoseconds regime. The rising-edge jitter is much lower than the falling-edge jitter, and further, this ultralow rising-edge jitter could be obtained by both p-i-n and (modified-)uni-travelling-carrier photodiodes. This finding can be directly used for various edge-sensitive timing applications, and further shows the potential for ultrahigh-precision timing using silicon-photonic-integrable on-chip p-i-n photodiodes.
Causality matters in medical imaging
Authors: Castro Daniel C. , Walker Ian , Glocker Ben
Published: July 2020

Causal reasoning can shed new light on the major challenges in machine learning for medical imaging: scarcity of high-quality annotated data and mismatch between the development dataset and the target environment. A causal perspective on these issues allows decisions about data collection, annotation, preprocessing, and learning strategies to be made and scrutinized more transparently, while providing a detailed categorisation of potential biases and mitigation techniques. Along with worked clinical examples, we highlight the importance of establishing the causal relationship between images and their annotations, and offer step-by-step recommendations for future studies.
Author Correction: Locally-adapted reproductive photoperiodism determines population vulnerability to climate change in burying beetles
Authors: Tsai Hsiang-Yu , Rubenstein Dustin R. , Fan Yu-Meng , Yuan Tzu-Neng , Chen Bo-Fei , Tang Yezhong , Chen I-Ching , Shen Sheng-Feng
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Nuclear-mitochondrial DNA segments resemble paternally inherited mitochondrial DNA in humans
Authors: Wei Wei , Pagnamenta Alistair T. , Gleadall Nicholas , Sanchis-Juan Alba , Stephens Jonathan , Broxholme John , Tuna Salih , Odhams Christopher A. ,   Genomics England Research Consortium, Ambrose J. C. , Baple E. L. , Bleda M. , Boardman-Pretty F. , Boissiere J. M. , Boustred C. R. , Caulfield M. J. , Chan G. C. , Craig C. E. H. , Daugherty L. C. , de Burca A. , Devereau A. , Elgar G. , Foulger R. E. , Fowler T. , Furió-Tarí P. , Hackett J. M. , Halai D. , Holman J. E. , Hubbard T. J. P. , Jackson R. , Kasperaviciute D. , Kayikci M. , Lahnstein L. , Lawson K. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , Mason J. , McDonagh E. M. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , Odhams C. A. , Patch C. , Perez-Gil D. , Polychronopoulos D. , Pullinger J. , Rahim T. , Rendon A. , Riesgo-Ferreiro P. , Rogers T. , Ryten M. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smedley D. , Smith K. R. , Sosinsky A. , Spooner W. , Stevens H. E. , Stuckey A. , Sultana R. , Thomas E. R. A. , Thompson S. R. , Tregidgo C. , Tucci A. , Walsh E. , Watters S. A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. ,   NIHR BioResource, Sanchis-Juan Alba , Stephens Jonathan , Tuna Salih , Turro Ernest , Chinnery Patrick F. , Fratter Carl , Turro Ernest , Caulfield Mark J. , Taylor Jenny C. , Rahman Shamima , Chinnery Patrick F.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Long-term culture of human pancreatic slices as a model to study real-time islet regeneration
Authors: Qadir Mirza Muhammad Fahd , Álvarez-Cubela Silvia , Weitz Jonathan , Panzer Julia K. , Klein Dagmar , Moreno-Hernández Yaisa , Cechin Sirlene , Tamayo Alejandro , Almaça Joana , Hiller Helmut , Beery Maria , Kusmartseva Irina , Atkinson Mark , Speier Stephan , Ricordi Camillo , Pugliese Alberto , Caicedo Alejandro , Fraker Christopher A. , Pastori Ricardo Luis , Domínguez-Bendala Juan
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Effect of FeCoNiCrCu0.5 High-entropy-alloy Substrate on Sn Grain Size in Sn-3.0Ag-0.5Cu Solder
Authors: Shen Yu-An , Lin Chun-Ming , Li Jiahui , He Siliang , Nishikawa Hiroshi
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The role and function of IκKα/β in monocyte impairment
Authors: Galbraith Norman J. , Gardner Sarah A. , Walker Samuel P. , Trainor Patrick , Carter Jane V. , Bishop Campbell , Sarojini Harshini , O’Brien Stephen J. , Bhatnagar Aruni , Polk Hiram C. , Galandiuk Susan
Published: July 2020

Following major trauma, sepsis or surgery, some patients exhibit an impaired monocyte inflammatory response that is characterized by a decreased response to a subsequent bacterial challenge. To investigate this poorly understood phenomenon, we adopted an in-vitro model of endotoxin tolerance utilising primary human CD14 + monocytes to focus on the effect of impairment on IκKα/β, a critical part of the NFκB pathway. Impaired monocytes had decreased IκKα mRNA and protein expression and decreased phosphorylation of the IκKα/β complex. The impaired monocyte secretome demonstrated a distinct cytokine/chemokine footprint from the naïve monocyte, and that TNF-α was the most sensitive cytokine or chemokine in this setting of impairment. Inhibition of IκKα/β with a novel selective inhibitor reproduced the impaired monocyte phenotype with decreased production of TNF-α, IL-6, IL-12p70, IL-10, GM-CSF, VEGF, MIP-1β, TNF-β, IFN-α2 and IL-7 in response to an LPS challenge. Surgical patients with infection also exhibited an impaired monocyte phenotype and had decreased SITPEC, TAK1 and MEKK gene expression, which are important for IκKα/β activation. Our results emphasize that impaired monocyte function is, at least in part, related to dysregulated IκKα/β activation, and that IκKα/β is likely involved in mounting a sufficient monocyte inflammatory response. Future studies may wish to focus on adjuvant therapies that augment IκKα/β function to restore monocyte function in this clinically important problem.
Molecular markers from the chloroplast genome of rose provide a complementary tool for variety discrimination and profiling
Authors: Li Changhong , Zheng Yongqi , Huang Ping
Published: July 2020

The rose is one of the most important ornamental woody plants because of its extensive use and high economic value. Herein, we sequenced a complete chloroplast genome of the miniature rose variety Rosa ‘Margo Koster’ and performed comparative analyses with sequences previously published for other species in the Rosaceae family. The chloroplast genome of Rosa ‘Margo Koster’, with a size of 157,395 bp, has a circular quadripartite structure typical of angiosperm chloroplast genomes and contains a total of 81 protein-coding genes, 30 tRNA genes and 4 rRNA genes. Conjunction regions in the chloroplast genome of Rosa ‘Margo Koster’ were verified and manually corrected by Sanger sequencing. Comparative genome analysis showed that the IR contraction and expansion events resulted in rps19 and ycf1 pseudogenes. The phylogenetic analysis within the Rosa genus showed that Rosa ‘Margo Koster’ is closer to Rosa odorata than to other Rosa species. Additionally, we identified and screened highly divergent sequences and cpSSRs and compared their power to discriminate rose varieties by Sanger sequencing and capillary electrophoresis. The results showed that 15 cpSSRs are polymorphic, but their discriminating power is only moderate among a set of rose varieties. However, more than 150 single nucleotide variations (SNVs) were discovered in the flanking region of cpSSRs, and the results indicated that these SNVs have a higher divergence and stronger power for profiling rose varieties. These findings suggest that nucleotide mutations in the chloroplast genome may be an effective and powerful tool for rose variety discrimination and DNA profiling. These molecular markers in the chloroplast genome sequence of Rosa spp. will facilitate population and phylogenetic studies and other related studies of this species.
Long-range inputome of cortical neurons containing corticotropin-releasing hormone
Authors: Zhao Peilin , Zhao Mengting , Wang Huading , Jiang Tao , Jia Xueyan , Tian Jiaojiao , Li Anan , Gong Hui , Li Xiangning
Published: July 2020

Dissection of the neural circuits of the cerebral cortex is essential for studying mechanisms underlying brain function. Herein, combining a retrograde rabies tracing system with fluorescent micro-optical sectional tomography, we investigated long-range input neurons of corticotropin-releasing hormone containing neurons in the six main cortical areas, including the prefrontal, somatosensory, motor, auditory, and visual cortices. The whole brain distribution of input neurons showed similar patterns to input neurons distributed mainly in the adjacent cortical areas, thalamus, and basal forebrain. Reconstruction of continuous three-dimensional datasets showed the anterior and middle thalamus projected mainly to the rostral cortex whereas the posterior and lateral projected to the caudal cortex. In the basal forebrain, immunohistochemical staining showed these cortical areas received afferent information from cholinergic neurons in the substantia innominata and lateral globus pallidus, whereas cholinergic neurons in the diagonal band nucleus projected strongly to the prefrontal and visual cortex. Additionally, dense neurons in the zona incerta and ventral hippocampus were found to project to the prefrontal cortex. These results showed general patterns of cortical input circuits and unique connection patterns of each individual area, allowing for valuable comparisons among the organisation of different cortical areas and new insight into cortical functions.
Morphology and transport characterization of solution-processed rubrene thin films on polymer-modified substrates
Authors: Gao Xujing , Liu Wentao , Liu Hao , Huang Miaoming , He Suqin , Zhang Manman , Hua Zhengxia , Zhu Chengshen
Published: July 2020

In this report, the morpho-structural peculiarities and the crystallization mechanisms in solution-processed, solvent vapor annealed (SVA) thin films of rubrene (5,6,11,12-tetraphenylnaphthacene) on different substrates were investigated. The high-quality rubrene crystal films with a triclinic crystal structure were successfully prepared on the FTO substrates (glass slide coated with fluorine-tin-oxide) modified by PLA (polylactic acid) for the first time. The area coverage of rubrene crystal and the sizes of rubrene dendritic crystals increased with increasing thickness of PLA film and concentration of rubrene solution. For rubrene molecules, FTO wafers with rough surface provided the possibility of heterogeneous nucleation. During the SVA process, there were two kinds of forces acting on the diffusion of rubrene molecules: one force was provided by the residual chloroform solvent, which was perpendicular to the substrate, and the other force was provided by gaseous dichloromethane, which was parallel to the substrate. The synergy of these two forces was proposed to explain the nucleation and the crystallization processes of rubrene films. The higher nucleus of PLA/rubrene dendrites and the layer-by-layer stacking of needle-shaped nanocrystalline PLA/rubrene were important for exploring their kinetic formation process.
Mosquito proboscis-inspired needle insertion to reduce tissue deformation and organ displacement
Authors: Li Annie D. R. , Putra Ketut B. , Chen Lei , Montgomery Jeffrey S. , Shih Albert
Published: July 2020

This study investigates mosquito proboscis-inspired (MPI) insertion applied to the clinically used biopsy needle to reduce tissue deformation and organ displacement. Advanced medical imagining has enabled early-stage identification of cancerous lesions that require needle biopsy for minimally invasive tissue sampling and pathological analysis. Accurate cancer diagnosis depends on the accuracy of needle deployment to the targeted cancerous lesion site. However, currently available needle delivery systems deform and move soft tissue and organs, leading to a non-diagnostic biopsy or undersampling of the target. Two features inspired by the mosquito proboscis were adopted for MPI insertion in prostate biopsy: (1) the harpoon-shape notches at the needle tip and (2) reciprocating needle-cannula motions for incremental insertion. The local tissue deformation and global prostate displacement during the MPI vs. traditional direct insertions were quantified by optically tracking the displacement of particle-embedded tissue-mimicking phantoms. Results show that the MPI needle insertion reduced both local tissue deformation and global prostate displacement because of the opposite needle-cannula motions and notches which stabilized and reduced the tissue deformation during insertion. Findings provide proof of concept for MPI insertion in the clinical biopsy procedures as well as insights of needle–tissue interaction for future biopsy technology development.
An improved method for high-throughput quantification of autophagy in mammalian cells
Authors: Koepke Lennart , Winter Benjamin , Grenzner Alexander , Regensburger Kerstin , Engelhart Susanne , van der Merwe Johannes A. , Krebs Stefan , Blum Helmut , Kirchhoff Frank , Sparrer Konstantin M. J.
Published: July 2020

Autophagy is a cellular homeostatic pathway with functions ranging from cytoplasmic protein turnover to immune defense. Therapeutic modulation of autophagy has been demonstrated to positively impact the outcome of autophagy-dysregulated diseases such as cancer or microbial infections. However, currently available agents lack specificity, and new candidates for drug development or potential cellular targets need to be identified. Here, we present an improved method to robustly detect changes in autophagy in a high-throughput manner on a single cell level, allowing effective screening. This method quantifies eGFP-LC3B positive vesicles to accurately monitor autophagy. We have significantly streamlined the protocol and optimized it for rapid quantification of large numbers of cells in little time, while retaining accuracy and sensitivity. Z scores up to 0.91 without a loss of sensitivity demonstrate the robustness and aptness of this approach. Three exemplary applications outline the value of our protocols and cell lines: (I) Examining autophagy modulating compounds on four different cell types. (II) Monitoring of autophagy upon infection with e.g. measles or influenza A virus. (III) CRISPR/Cas9 screening for autophagy modulating factors in T cells. In summary, we offer ready-to-use protocols to generate sensitive autophagy reporter cells and quantify autophagy in high-throughput assays.
Investigating the presence of microplastics in demersal sharks of the North-East Atlantic
Authors: Parton Kristian J. , Godley Brendan J. , Santillo David , Tausif Muhammad , Omeyer Lucy C. M. , Galloway Tamara S.
Published: July 2020

Microplastic pollution is ubiquitous in the marine environment and is ingested by numerous marine species. Sharks are an understudied group regarding their susceptibility to microplastic ingestion. Here, we provide evidence of ingestion of microplastic and other anthropogenic fibres in four demersal sharks species found in the waters of the United Kingdom and investigate whether body burdens of contamination vary according to species, sex or size. Sharks were collected from the North-East Atlantic. Stomachs and digestive tracts of 46 sharks of 4 species were examined and 67% of samples contained at least one contaminant particle. Although we acknowledge modest sample size, estimated particle burden increased with body size but did not vary systematically with sex or species. A total of 379 particles were identified, leading to median estimates ranging from 2 to 7.5 ingested contaminants per animal for the 4 species. The majority were fibrous in nature (95%) and blue (88%) or black (9%) in colour. A subsample of contaminants (N = 62) were subject to FT-IR spectroscopy and polymers identified as: synthetic cellulose (33.3%), polypropylene (25%), polyacrylamides (10%) and polyester (8.3%). The level of risk posed to shark species by this level of contamination is unknown. Nevertheless, this study presents the first empirical evidence and an important baseline for ingestion of microplastics and other anthropogenic fibres in native UK shark species and highlights the pervasive nature of these pollutants.
Promoting crystallization of intrinsic membrane proteins with conjugated micelles
Authors: Van Truong Thien , Ghosh Mihir , Wachtel Ellen , Friedman Noga , Jung Kwang-Hwan , Sheves Mordechai , Patchornik Guy
Published: July 2020

A new technique for promoting nucleation and growth of membrane protein (MP) crystals from micellar environments is reported. It relies on the conjugation of micelles that sequester MPs in protein detergent complexes (PDCs). Conjugation via amphiphilic [metal:chelator] complexes presumably takes place at the micelle/water interface, thereby bringing the PDCs into proximity, promoting crystal nucleation and growth. We have successfully applied this approach to two light-driven proton pumps: bacteriorhodopsin (bR) and the recently discovered King Sejong 1–2 (KS1–2), using the amphiphilic 4,4′-dinonyl-2,2′-dipyridyl (Dinonyl) (0.7 mM) chelator in combination with Zn2+, Fe2+, or Ni2+(0.1 mM). Crystal growth in the presence of the [metal–chelator] complexes leads to purple, hexagonal crystals (50–75 µm in size) of bR or pink, rectangular/square crystals (5–15 µm) of KS1–2. The effects of divalent cation identity and concentration, chelator structure and concentration, ionic strength and pH on crystal size, morphology and process kinetics, are described.
Genetic characteristics and pathogenesis of H5 low pathogenic avian influenza viruses from wild birds and domestic ducks in South Korea
Authors: Lee Yu-Na , Lee Dong-Hun , Cheon Sun-Ha , Park Yu-Ri , Baek Yoon-Gi , Si Young-Jae , Kye Soo-Jeong , Lee Eun-Kyoung , Heo Gyeong-Beom , Bae You-Chan , Lee Myoung-Heon , Lee Youn-Jeong
Published: July 2020

H5 and H7 subtypes of low pathogenic avian influenza viruses (LPAIVs) can mutate to highly pathogenic forms and are therefore subject to stringent controls. We characterized H5 LPAIVs isolated from wild-bird habitats and duck farms in South Korea from 2010 to 2017. Through nationwide active surveillance for AIVs, 59 H5 LPAIVs were isolated from wild-bird habitats (a mean annual rate of 5.3% of AIV isolations). In 2015, one LPAI H5N3 strain was isolated on a duck farm. Phylogenetic analysis revealed that the hemagglutinin (HA) gene of H5 isolates belonged to the Eurasian lineage, classified into three subgroups (HA-II, HA-III, and HA-IV). The H5 LPAIVs of the HA-III and HA-IV subgroups appeared in 2015 and 2017 in unusually high proportions (13.1% and 14.4%, respectively). In gene-constellation analysis, H5 LPAIVs isolated from 2015 to 2017 constituted ≥ 35 distinct genotypes, representing high levels of genetic diversity. Representative strains of three HA subgroups replicated restrictively in specific-pathogen-free chickens. Among the 11 isolates that were tested, 10 infected and replicated in mice without prior adaptation. The frequency of recent H5 LPAIV isolates with high genetic diversity indicates the importance of continued surveillance in both wild birds and poultry to monitor genetic and pathobiological changes.
A somatic evolutionary model of the dynamics of aneuploid cells during hematopoietic reconstitution
Authors: Rozhok Andrii I. , Silberman Rebecca E. , Higa Kelly C. , Liggett L. Alex , Amon Angelika , DeGregori James
Published: July 2020

Aneuploidy is a feature of many cancers. Recent studies demonstrate that in the hematopoietic stem and progenitor cell (HSPC) compartment aneuploid cells have reduced fitness and are efficiently purged from the bone marrow. However, early phases of hematopoietic reconstitution following bone marrow transplantation provide a window of opportunity whereby aneuploid cells rise in frequency, only to decline to basal levels thereafter. Here we demonstrate by Monte Carlo modeling that two mechanisms could underlie this aneuploidy peak: rapid expansion of the engrafted HSPC population and bone marrow microenvironment degradation caused by pre-transplantation radiation treatment. Both mechanisms reduce the strength of purifying selection acting in early post-transplantation bone marrow. We explore the contribution of other factors such as alterations in cell division rates that affect the strength of purifying selection, the balance of drift and selection imposed by the HSPC population size, and the mutation-selection balance dependent on the rate of aneuploidy generation per cell division. We propose a somatic evolutionary model for the dynamics of cells with aneuploidy or other fitness-reducing mutations during hematopoietic reconstitution following bone marrow transplantation. Similar alterations in the strength of purifying selection during cancer development could help explain the paradox of aneuploidy abundance in tumors despite somatic fitness costs.
Mining whole genome sequence data to efficiently attribute individuals to source populations
Authors: Pérez-Reche Francisco J. , Rotariu Ovidiu , Lopes Bruno S. , Forbes Ken J. , Strachan Norval J. C.
Published: July 2020

Whole genome sequence (WGS) data could transform our ability to attribute individuals to source populations. However, methods that efficiently mine these data are yet to be developed. We present a minimal multilocus distance (MMD) method which rapidly deals with these large data sets as well as methods for optimally selecting loci. This was applied on WGS data to determine the source of human campylobacteriosis, the geographical origin of diverse biological species including humans and proteomic data to classify breast cancer tumours. The MMD method provides a highly accurate attribution which is computationally efficient for extended genotypes. These methods are generic, easy to implement for WGS and proteomic data and have wide application.
Author Correction: Transcriptomic changes in the pre-implantation uterus highlight histotrophic nutrition of the developing marsupial embryo
Authors: Whittington Camilla M. , O’Meally Denis , Laird Melanie K. , Belov Katherine , Thompson Michael B. , McAllan Bronwyn M.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
HIV-1 and HIV-2 prevalence, risk factors and birth outcomes among pregnant women in Bissau, Guinea-Bissau: a retrospective cross-sectional hospital study
Authors: Rasmussen Dlama Nggida , Vieira Noel , Hønge Bo Langhoff , da Silva Té David , Jespersen Sanne , Bjerregaard-Andersen Morten , Oliveira Inés , Furtado Alcino , Gomes Magarida Alfredo , Sodemann Morten , Wejse Christian , Unger Holger Werner
Published: July 2020

The human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau’s largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau.
Microenvironment-triggered dual-activation of a photosensitizer- fluorophore conjugate for tumor specific imaging and photodynamic therapy
Authors: Wang Chang , Wang Shengdan , Wang Yuan , Wu Honghai , Bao Kun , Sheng Rong , Li Xin
Published: July 2020

Photodynamic therapy is attracting increasing attention, but how to increase its tumor-specificity remains a daunting challenge. Herein we report a theranostic probe (azo-PDT) that integrates pyropheophorbide α as a photosensitizer and a NIR fluorophore for tumor imaging. The two functionalities are linked with a hypoxic-sensitive azo group. Under normal conditions, both the phototoxicity of the photosensitizer and the fluorescence of the fluorophore are inhibited. While under hypoxic condition, the reductive cleavage of the azo group will restore both functions, leading to tumor specific fluorescence imaging and phototoxicity. The results showed that azo-PDT selectively images BEL-7402 cells under hypoxia, and simultaneously inhibits BEL-7402 cell proliferation after near-infrared irradiation under hypoxia, while little effect on BEL-7402 cell viability was observed under normoxia. These results confirm the feasibility of our design strategy to improve the tumor-targeting ability of photodynamic therapy, and presents azo-PDT probe as a promising dual functional agent.
Size resolved characteristics of urban and suburban bacterial bioaerosols in Japan as assessed by 16S rRNA amplicon sequencing
Authors: Tanaka Daisuke , Fujiyoshi So , Maruyama Fumito , Goto Motoshi , Koyama Shinichi , Kanatani Jun-ichi , Isobe Junko , Watahiki Masanori , Sakatoku Akihiro , Kagaya Shigehiro , Nakamura Shogo
Published: July 2020

To study the size-resolved characteristics of airborne bacterial community composition, diversity, and abundance, outdoor aerosol samples were analysed by 16S rRNA gene-targeted quantitative PCR and amplicon sequencing with Illumina MiSeq. The samples were collected using size-resolved samplers between August and October 2016, at a suburban site in Toyama City and an urban site in Yokohama City, Japan. The bacterial communities were found to be dominated by Actinobacteria, Firmicutes, and Proteobacteria. At the genus level, we found a high abundance of human skin-associated bacteria, such as Propionibacterium, Staphylococcus, and Corynebacterium, in the urban site. Whereas, a high abundance of bacteria associated with soil and plants, such as Methylobacterium and Sphingomonas, was observed in the suburban site. Furthermore, our data revealed a shift in the bacterial community structure, diversity, and abundance of total bacteria at a threshold of 1.1-µm diameter. Interestingly, we observed that Legionella spp., the causal agents of legionellosis in humans, were mainly detected in > 2.1 µm coarse particles. Our data indicate that local environmental factors including built environments could influence the outdoor airborne bacterial community at each site. These results provide a basis for understanding the size-resolved properties of bacterial community composition, diversity, and abundance in outdoor aerosol samples and their potential influence on human health.
Conditional and unconditional genome-wide association study reveal complicate genetic architecture of human body weight and impacts of smoking
Authors: Xu Ting , Monir Md. Mamun , Lou Xiang-Yang , Xu Haiming , Zhu Jun
Published: July 2020

To reveal the impacts of smoking on genetic architecture of human body weight, we conducted a genome-wide association study on 5,336 subjects in four ethnic populations from MESA (The Multi-Ethnic Study of Atherosclerosis) data. A full genetic model was applied to association mapping for analyzing genetic effects of additive, dominance, epistasis, and their ethnicity-specific effects. Both the unconditional model (base) and conditional model including smoking as a cofactor were investigated. There were 10 SNPs involved in 96 significant genetic effects detected by the base model, which accounted for a high heritability (61.78%). Gene ontology analysis revealed that a number of genetic factors are related to the metabolic pathway of benzopyrene, a main compound in cigarettes. Smoking may play important roles in genetic effects of dominance, dominance-related epistasis, and gene-ethnicity interactions on human body weight. Gene effect prediction shows that the genetic effects of smoking cessation on body weight vary from different populations.
Unique genomic and neoepitope landscapes across tumors: a study across time, tissues, and space within a single lynch syndrome patient
Authors: Phung Tanya N. , Lenkiewicz Elizabeth , Malasi Smriti , Sharma Amit , Anderson Karen S. , Wilson Melissa A. , Pockaj Barbara A. , Barrett Michael T.
Published: July 2020

Lynch syndrome (LS) arises in patients with pathogenic germline variants in DNA mismatch repair genes. LS is the most common inherited cancer predisposition condition and confers an elevated lifetime risk of multiple cancers notably colorectal and endometrial carcinomas. A distinguishing feature of LS associated tumors is accumulation of variants targeting microsatellite repeats and the potential for high tumor specific neoepitope levels. Recurrent somatic variants targeting a small subset of genes have been identified in tumors with microsatellite instability. Notably these include frameshifts that can activate immune responses and provide vaccine targets to affect the lifetime cancer risk associated with LS. However the presence and persistence of targeted neoepitopes across multiple tumors in single LS patients has not been rigorously studied. Here we profiled the genomic landscapes of five distinct treatment naïve tumors, a papillary transitional cell renal cell carcinoma, a duodenal carcinoma, two metachronous colorectal carcinomas, and multi-regional sampling in a triple-negative breast tumor, arising in a LS patient over 10 years. Our analyses suggest each tumor evolves a unique complement of variants and that vaccines based on potential neoepitopes from one tissue may not be effective across all tumors that can arise during the lifetime of LS patients.
A G-quadruplex-binding compound shows potent activity in human gemcitabine-resistant pancreatic cancer cells
Authors: Ahmed Ahmed Abdullah , Marchetti Chiara , Ohnmacht Stephan A. , Neidle Stephen
Published: July 2020

Gemcitabine is a drug of choice in the treatment of human pancreatic cancer. Chemo-resistance to this drug is common and has been attributed to a variety of distinct mechanisms, involving > 100 genes. A recently developed small-molecule G-quadruplex ligand, the trisubstituted naphthalene diimide compound CM03, has previously been shown to have equivalent potency to gemcitabine in the pancreatic cancer cell line MIA PaCa-2. We report here on cell lines of increased resistance to gemcitabine that have been generated from this line, with the most resistant having 1,000-fold reduced sensitivity to gemcitabine. These resistant lines retain nM sensitivity to CM03. The molecular basis for the retention of potency by this G-quadruplex ligand has been examined using whole transcriptome data analysis with RNA-seq. This has revealed that the pattern of pathways down regulated by CM03 in the parental MIA PaCa-2 cell line is largely unaffected in the gemcitabine-resistant line. The analysis has also shown that the expression patterns of numerous genes involved in gemcitabine sensitivity are down regulated in the resistant line upon CM03 treatment. These results are supportive of the concept that G-quadruplex small molecules such as CM03 have potential for clinical use in the treatment of gemcitabine-resistant human pancreatic cancer.
Inherited variations in human pigmentation-related genes modulate cutaneous melanoma risk and clinicopathological features in Brazilian population
Authors: Lourenço Gustavo Jacob , Oliveira Cristiane , Carvalho Benilton Sá , Torricelli Caroline , Silva Janet Keller , Gomez Gabriela Vilas Bôas , Rinck-Junior José Augusto , Oliveira Wesley Lima , Vazquez Vinicius Lima , Serrano Sergio Vicente , Moraes Aparecida Machado , Lima Carmen Silvia Passos
Published: July 2020

Ultraviolet light exposure and cutaneous pigmentation are important host risk factors for cutaneous melanoma (CM), and it is well known that inherited ability to produce melanin varies in humans. The study aimed to identify single-nucleotide variants (SNVs) on pigmentation-related genes with importance in risk and clinicopathological aspects of CM. The study was conducted in two stages. In stage 1, 103 CM patients and 103 controls were analyzed using Genome-Wide Human SNV Arrays in order to identify SNVs in pigmentation-related genes, and the most important SNVs were selected for data validation in stage 2 by real-time polymerase-chain reaction in 247 CM patients and 280 controls. ADCY3 c.675+9196T>G, CREB1 c.303+373G>A, and MITF c.938-325G>A were selected for data validation among 74 SNVs. Individuals with CREB1 GA or AA genotype and allele “A” were under 1.79 and 1.47-fold increased risks of CM than others, respectively. Excesses of CREB1 AA and MITF AA genotype were seen in patients with tumors at Clark levels III to V (27.8% versus 13.7%) and at III or IV stages (46.1% versus 24.9%) compared to others, respectively. When compared to others, patients with ADCY3 TT had 1.89 more chances of presenting CM progression, and those with MITF GA or AA had 2.20 more chances of evolving to death by CM. Our data provide, for the first time, preliminary evidence that inherited abnormalities in ADCY3, CREB1, and MITF pigmentation-related genes, not only can increase the risk to CM, but also influence CM patients’ clinicopathological features.
DNA damage and antioxidant properties of CORM-2 in normal and cancer cells
Authors: Juszczak Michał , Kluska Magdalena , Wysokiński Daniel , Woźniak Katarzyna
Published: July 2020

In this study, we compared the effect of tricarbonyldichlororuthenium (II) dimer (CORM-2) and its CO-depleted molecule (iCORM-2) on human peripheral blood mononuclear cells (PBMCs) and human promyelocytic leukemia HL-60 cells. We determined cell viability, DNA damage and DNA repair kinetics. We also studied the effect of both compounds on DNA oxidative damage, free radical level and HO-1 gene expression. We showed that at low concentrations both CORM-2 and iCORM-2 stimulate PBMCs viability. After 24-h incubation, CORM-2 and iCORM-2, at the concentration of 100 µM, reduce the viability of both PBMCs and HL-60 cells. We also demonstrated that CORM-2 and iCORM-2, in the 0.01–100 µM concentration range, cause DNA damage such as strand breaks and alkaline labile sites. DNA damage was repaired efficiently only in HL-60 cells. CORM-2 significantly reduces oxidative stress induced by 1 mM H2O2 in normal and cancer cells. On the contrary, iCORM-2 in HL-60 cells increases the level of free radicals in the presence of 1 and 5 mM H2O2. We also revealed that both CORM-2 and iCORM-2 induce HO-1 gene expression. However, CORM-2 induces this gene to a greater extent than iCORM-2, especially in HL-60 cells at 100 µM. Finally, we showed that CORM-2 and iCORM-2 reduce H2O2-induced DNA oxidative damage. Furthermore, CORM-2 proved to be a compound with stronger antioxidant properties than iCORM-2. Our results suggest that both active CORM-2 and inactive iCORM-2 exert biological effects such as cyto- and genotoxicity, antioxidant properties and the ability to induce the HO-1 gene. The released CO as well as iCORM-2 can be responsible for these effects.
Correlation of electroretinography components with visual function and prognosis of central retinal artery occlusion
Authors: Kim Hyeong Min , Park Kyu Hyung , Woo Se Joon
Published: July 2020

We investigated the full-field electroretinographic (ERG) parameters with visual function and prognosis in central retinal artery occlusion (CRAO), according to its severity. 110 affected eyes of CRAO patients were enrolled and compared with fellow uninvolved eyes (N = 110) and normal control eyes (N = 30). B/A ratio and photopic negative response amplitude (PhNR) resulted in statistically significant differences among the CRAO subgroups according to the severity of retinal ischemia. Amplitudes of PhNR indicating ganglion cell function showed a more marked decline in mild to severe ischemia than those of the B-wave. In terms of visual function and outcome, baseline visual acuity and visual field defects were correlated with B/A ratio only (both, P < .001), whereas improvements in visual acuity and visual field were correlated with B-wave amplitude in dark-adapted 3.0 (P = .004 and .006), B/A ratio (P = .023 and .008), and PhNR amplitude (P < .001 and .004). These three ERG parameters were found to be credible predictive factors of visual prognosis. In conclusion, B-wave amplitude in dark-adapted 3.0, B/A ratio, and PhNR amplitude changes in eyes with CRAO are associated with baseline features related to the severity of retinal ischemia, and these are correlated with visual function and prognosis.
Improved understanding of biofilm development by Piscirickettsia salmonis reveals potential risks for the persistence and dissemination of piscirickettsiosis
Authors: Levipan Héctor A. , Irgang Rute , Yáñez Alejandro , Avendaño-Herrera Ruben
Published: July 2020

Piscirickettsia salmonis is the causative agent of piscirickettsiosis, a disease with high socio-economic impacts for Chilean salmonid aquaculture. The identification of major environmental reservoirs for P. salmonis has long been ignored. Most microbial life occurs in biofilms, with possible implications in disease outbreaks as pathogen seed banks. Herein, we report on an in vitro analysis of biofilm formation by P. salmonis Psal-103 (LF-89-like genotype) and Psal-104 (EM-90-like genotype), the aim of which was to gain new insights into the ecological role of biofilms using multiple approaches. The cytotoxic response of the salmon head kidney cell line to P. salmonis showed interisolate differences, depending on the source of the bacterial inoculum (biofilm or planktonic). Biofilm formation showed a variable-length lag-phase, which was associated with wider fluctuations in biofilm viability. Interisolate differences in the lag phase emerged regardless of the nutritional content of the medium, but both isolates formed mature biofilms from 288 h onwards. Psal-103 biofilms were sensitive to Atlantic salmon skin mucus during early formation, whereas Psal-104 biofilms were more tolerant. The ability of P. salmonis to form viable and mucus-tolerant biofilms on plastic surfaces in seawater represents a potentially important environmental risk for the persistence and dissemination of piscirickettsiosis.
Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
Authors: Gaiani Federica , Rotoli Bianca Maria , Ferrari Francesca , Barilli Amelia , Visigalli Rossana , Carra Maria Clotilde , de’Angelis Gian Luigi , de’Angelis Nicola , Dall’Asta Valeria
Published: July 2020

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30–40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes’ cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.
Impact of individual actions on the collective response of social systems
Authors: Martin-Gutierrez Samuel , Losada Juan C. , Benito Rosa M.
Published: July 2020

In a social system individual actions have the potential to trigger spontaneous collective reactions. The way and extent to which the activity (number of actions—A) of an individual causes or is connected to the response (number of reactions—R) of the system is still an open question. We measure the relationship between activity and response with the distribution of efficiency, a metric defined as $$\eta =R/A$$η=R/A. Generalizing previous results, we show that the efficiency distribution presents a universal structure in three systems of different nature: Twitter, Wikipedia and the scientific citations network. To understand this phenomenon, we develop a theoretical framework composed of three minimal statistical models that contemplate different levels of dependence between A and R. The models not only are able to reproduce the empirical activity-response data but also can serve as baselines or null models for more elaborated and domain-specific approaches.