bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder
Authors: Zhan Yanni , Zhou Yanling , Zheng Wei , Liu Weijian , Wang Chengyu , Lan Xiaofeng , Deng Xiurong , Xu Yan , Zhang Bin , Ning Yuping 
Published: July 2020

AbstractIncreasing evidence has demonstrated that inflammatory cytokines play an important role in major depressive disorder (MDD) and are associated with treatment outcomes. Few studies have explored the trajectories of multiple inflammatory cytokines after repeated ketamine infusions in MDD. In this study, we conducted a secondary analysis to investigate the impact of ketamine on the modulation of the inflammatory pathway in depression and whether this pathway contributes to the antidepressant properties of ketamine. A total of 60 patients with depression received six ketamine infusions (0.5 mg/kg) during a 12-day period. The Montgomery–Asberg Scale (MADRS) was administered, and blood samples were collected at baseline and 24 h and 14 days after the sixth infusion (days 0, 13, and 26). Plasma levels of the 19 cytokines were measured using the Luminex assay. At baseline, inflammatory cytokines were associated with the severity of depression. The concentrations of pro- and anti-inflammatory factors, including granulocyte macrophage colony-stimulating factor (GM-CSF), fractalkine, interferon gamma (IFN-γ), interleukin (IL)-10, IL-12p70, IL-17A, IL-1β, IL-2, IL-4, IL-23, IL-5, IL-6, IL-7, and tumor necrosis factor alpha (TNF-α), were downregulated after repeated ketamine administration (allp < 0.05). In addition, alterations in the levels of IL-17A (r = −0.259,p = 0.046) and IL-6 (r = −0.262,p = 0.043) were correlated with symptom improvement. A lower level of interferon-inducible T cell alpha chemoattractant (ITAC) at baseline was predictive of ketamine treatment response on day 13 according to a stepwise linear regression analysis (β = −0.296,p = 0.040). Our results suggest that the inflammatory pathway may be involved in the antidepressant effects of ketamine, which may be conducive to future treatment strategy optimization.
Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options
Authors: Wu Xiaowei , Luo Qingyu , Liu Zhihua 
Published: July 2020

AbstractMCL1 is an important antiapoptotic member of the BCL-2 family that is distinguishable from other family members based on its relatively short half-life. Emerging studies have revealed the crucial role of MCL1 in the chemoresistance of cancer cells. The antiapoptotic function of MCL1 makes it a popular therapeutic target, although specific inhibitors have begun to emerge only recently. Notably, emerging studies have reported that several E3 ligases and deubiquitinases modulate MCL1 stability, providing an alternate means of targeting MCL1 activity. In addition, the emergence and development of proteolysis-targeting chimeras, the function of which is based on ubiquitination-mediated degradation, has shown great potential. In this review, we provide an overview of the studies investigating the ubiquitination and deubiquitination of MCL1, summarize the latest evidence regarding the development of therapeutic strategies targeting MCL1 in cancer treatment, and discuss the promising future of targeting MCL1 via the ubiquitin–proteasome system in clinical practice.
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

AbstractLarge-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

AbstractEpigenetic 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

AbstractRestoration 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

AbstractThere 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

AbstractCausal 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.
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

AbstractFollowing 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

AbstractThe 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

AbstractDissection 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

AbstractIn 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

AbstractThis 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

AbstractAutophagy 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

AbstractMicroplastic 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

AbstractA 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.