bluuebunny/crossref_metadata_2025 huggingface dataset:
A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging
Authors: An Hong-Wei , Li Li-Li , Wang Yi , Wang Ziqi , Hou Dayong , Lin Yao-Xin , Qiao Sheng-Lin , Wang Man-Di , Yang Chao , Cong Yong , Ma Yang , Zhao Xiao-Xiao , Cai Qian , Chen Wen-Ting , Lu Chu-Qi , Xu Wanhai , Wang Hao , Zhao Yuliang
Published: October 2019

Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.
Specific ion effects at graphitic interfaces
Authors: Zhan Cheng , Cerón Maira R. , Hawks Steven A. , Otani Minoru , Wood Brandon C. , Pham Tuan Anh , Stadermann Michael , Campbell Patrick G.
Published: October 2019

Improved understanding of aqueous solutions at graphitic interfaces is critical for energy storage and water desalination. However, many mechanistic details remain unclear, including how interfacial structure and response are dictated by intrinsic properties of solvated ions under applied voltage. In this work, we combine hybrid first-principles/continuum simulations with electrochemical measurements to investigate adsorption of several alkali-metal cations at the interface with graphene and within graphene slit-pores. We confirm that adsorption energy increases with ionic radius, while being highly dependent on the pore size. In addition, in contrast with conventional electrochemical models, we find that interfacial charge transfer contributes non-negligibly to this interaction and can be further enhanced by confinement. We conclude that the measured interfacial capacitance trends result from a complex interplay between voltage, confinement, and specific ion effects-including ion hydration and charge transfer.
Manipulating topological transformations of polar structures through real-time observation of the dynamic polarization evolution
Authors: Du K. , Zhang M. , Dai C. , Zhou Z. N. , Xie Y. W. , Ren Z. H. , Tian H. , Chen L. Q. , Van Tendeloo Gustaaf , Zhang Z.
Published: October 2019

Topological structures based on controllable ferroelectric or ferromagnetic domain configurations offer the opportunity to develop microelectronic devices such as high-density memories. Despite the increasing experimental and theoretical insights into various domain structures (such as polar spirals, polar wave, polar vortex) over the past decade, manipulating the topological transformations of polar structures and comprehensively understanding its underlying mechanism remains lacking. By conducting an in-situ non-contact bias technique, here we systematically investigate the real-time topological transformations of polar structures in PbTiO3/SrTiO3 multilayers at an atomic level. The procedure of vortex pair splitting and the transformation from polar vortex to polar wave and out-of-plane polarization are observed step by step. Furthermore, the redistribution of charge in various topological structures has been demonstrated under an external bias. This provides new insights for the symbiosis of polar and charge and offers an opportunity for a new generation of microelectronic devices.
Cellular sequestrases maintain basal Hsp70 capacity ensuring balanced proteostasis
Authors: Ho Chi-ting , Grousl Tomas , Shatz Oren , Jawed Areeb , Ruger-Herreros Carmen , Semmelink Marije , Zahn Regina , Richter Karsten , Bukau Bernd , Mogk Axel
Published: October 2019

Maintenance of cellular proteostasis is achieved by a multi-layered quality control network, which counteracts the accumulation of misfolded proteins by refolding and degradation pathways. The organized sequestration of misfolded proteins, actively promoted by cellular sequestrases, represents a third strategy of quality control. Here we determine the role of sequestration within the proteostasis network in Saccharomyces cerevisiae and the mechanism by which it occurs. The Hsp42 and Btn2 sequestrases are functionally intertwined with the refolding activity of the Hsp70 system. Sequestration of misfolded proteins by Hsp42 and Btn2 prevents proteostasis collapse and viability loss in cells with limited Hsp70 capacity, likely by shielding Hsp70 from misfolded protein overload. Btn2 has chaperone and sequestrase activity and shares features with small heat shock proteins. During stress recovery Btn2 recruits the Hsp70-Hsp104 disaggregase by directly interacting with the Hsp70 co-chaperone Sis1, thereby shunting sequestered proteins to the refolding pathway.
Semiarid climate and hyposaline lake on early Mars inferred from reconstructed water chemistry at Gale
Authors: Fukushi Keisuke , Sekine Yasuhito , Sakuma Hiroshi , Morida Koki , Wordsworth Robin
Published: October 2019

Salinity, pH, and redox states are fundamental properties that characterize natural waters. These properties of surface waters on early Mars reflect palaeoenvironments, and thus provide clues on the palaeoclimate and habitability. Here we constrain these properties of pore water within lacustrine sediments of Gale Crater, Mars, using smectite interlayer compositions. Regardless of formation conditions of smectite, the pore water that last interacted with the sediments was of Na-Cl type with mild salinity (~0.1–0.5 mol/kg) and circumneutral pH. To interpret this, multiple scenarios for post-depositional alterations are considered. The estimated Na-Cl concentrations would reflect hyposaline, early lakes developed in 104–106-year-long semiarid climates. Assuming that post-depositional sulfate-rich fluids interacted with the sediments, the redox disequilibria in secondary minerals suggest infiltration of oxidizing fluids into reducing sediments. Assuming no interactions, the redox disequilibria could have been generated by interactions of upwelling groundwater with oxidized sediments in early post-depositional stages.
Intestinal microbiome composition and its relation to joint pain and inflammation
Authors: Boer Cindy G. , Radjabzadeh Djawad , Medina-Gomez Carolina , Garmaeva Sanzhima , Schiphof Dieuwke , Arp Pascal , Koet Thomas , Kurilshikov Alexander , Fu Jingyuan , Ikram M. Arfan , Bierma-Zeinstra Sita , Uitterlinden André G. , Kraaij Robert , Zhernakova Alexandra , van Meurs Joyce B. J.
Published: October 2019

Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species. In addition, we replicate these results in 867 Caucasian adults of the Lifelines-DEEP study. Finally we show evidence that this association is driven by local inflammation in the knee joint. Our results indicate the microbiome is a possible therapeutic target for osteoarthritis-related knee pain.
Chloroplastic metabolic engineering coupled with isoprenoid pool enhancement for committed taxanes biosynthesis in Nicotiana benthamiana
Authors: Li Jianhua , Mutanda Ishmael , Wang Kaibo , Yang Lei , Wang Jiawei , Wang Yong
Published: October 2019

Production of the anticancer drug Taxol and its precursors in heterologous hosts is more sustainable than extraction from tissues of yew trees or chemical synthesis. Although attempts to engineer the Taxol pathway in microbes have made significant progress, challenges such as functional expression of plant P450 enzymes remain to be addressed. Here, we introduce taxadiene synthase, taxadiene-5α-hydroxylase, and cytochrome P450 reductase in a high biomass plant Nicotiana benthamiana. Using a chloroplastic compartmentalized metabolic engineering strategy, combined with enhancement of isoprenoid precursors, we show that the engineered plants can produce taxadiene and taxadiene-5α-ol, the committed taxol intermediates, at 56.6 μg g−1 FW and 1.3 μg g−1 FW, respectively. In addition to the tools and strategies reported here, this study highlights the potential of Nicotiana spp. as an alternative platform for Taxol production.
Three-dimensional open nano-netcage electrocatalysts for efficient pH-universal overall water splitting
Authors: Zhuang Zewen , Wang Yu , Xu Cong-Qiao , Liu Shoujie , Chen Chen , Peng Qing , Zhuang Zhongbin , Xiao Hai , Pan Yuan , Lu Siqi , Yu Rong , Cheong Weng-Chon , Cao Xing , Wu Konglin , Sun Kaian , Wang Yu , Wang Dingsheng , Li Jun , Li Yadong
Published: October 2019

High-efficiency water electrolysis is the key to sustainable energy. Here we report a highly active and durable RuIrOx (x ≥ 0) nano-netcage catalyst formed during electrochemical testing by in-situ etching to remove amphoteric ZnO from RuIrZnOx hollow nanobox. The dispersing-etching-holing strategy endowed the porous nano-netcage with a high exposure of active sites as well as a three-dimensional accessibility for substrate molecules, thereby drastically boosting the electrochemical surface area (ECSA). The nano-netcage catalyst achieved not only ultralow overpotentials at 10 mA cm−2 for hydrogen evolution reaction (HER; 12 mV, pH = 0; 13 mV, pH = 14), but also high-performance overall water electrolysis over a broad pH range (0 ~ 14), with a potential of mere 1.45 V (pH = 0) or 1.47 V (pH = 14) at 10 mA cm−2. With this universal applicability of our electrocatalyst, a variety of readily available electrolytes (even including waste water and sea water) could potentially be directly used for hydrogen production.
Dynamic oxygen adsorption on single-atomic Ruthenium catalyst with high performance for acidic oxygen evolution reaction
Authors: Cao Linlin , Luo Qiquan , Chen Jiajia , Wang Lan , Lin Yue , Wang Huijuan , Liu Xiaokang , Shen Xinyi , Zhang Wei , Liu Wei , Qi Zeming , Jiang Zheng , Yang Jinlong , Yao Tao
Published: October 2019

Achieving active and stable oxygen evolution reaction (OER) in acid media based on single-atom catalysts is highly promising for cost-effective and sustainable energy supply in proton electrolyte membrane electrolyzers. Here, we report an atomically dispersed Ru1-N4 site anchored on nitrogen-carbon support (Ru-N-C) as an efficient and durable electrocatalyst for acidic OER. The single-atom Ru-N-C catalyst delivers an exceptionally intrinsic activity, reaching a mass activity as high as 3571 A gmetal−1 and turnover frequency of 3348 O2 h−1 with a low overpotential of 267 mV at a current density of 10 mA cm−2. The catalyst shows no evident deactivation or decomposition after 30-hour operation in acidic environment. Operando synchrotron radiation X-ray absorption spectroscopy and infrared spectroscopy identify the dynamic adsorption of single oxygen atom on Ru site under working potentials, and theoretical calculations demonstrate that the O-Ru1-N4 site is responsible for the high OER activity and stability.
A merged copper(I/II) cluster isolated from Glaser coupling
Authors: Zhang Siqi , Zhao Liang
Published: October 2019

Ubiquitous copper-oxygen species are pivotal in enabling multifarious oxidation reactions in biological and chemical transformations. We herein construct a macrocycle-protected mixed-valence cluster [(tBuC≡CCuI3)-(μ2-OH)-CuII] by merging a copper acetylide cluster with a copper-oxygen moiety formed in Glaser coupling. This merged Cu(I/II) cluster shows remarkably strong oxidation capacity, whose reduction potential is among the most positive for Cu(II) and even comparable with some Cu(III) species. Consequently, the cluster exhibits high hydrogen atom transfer (HAT) reactivity with inert hydrocarbons. In contrast, the degraded [CuII-(μ2-OH)-CuII] embedded in a small macrocyclic homologue shows no HAT reactivity. Theoretical calculations indicate that the strong oxidation ability of Cu(II) in [(tBuC≡CCuI3)-(μ2-OH)-CuII] is mainly ascribed to the uneven charge distribution of Cu(I) ions in the tBuC≡CCuI3 unit because of significant [dCu(I) → π*(C≡C)] back donation. The present study on in situ formed metal clusters opens a broad prospect for mechanistic studies of Cu-based catalytic reactions.
Photoinduced hydrogen release from hydrogen boride sheets
Authors: Kawamura Reiya , Cuong Nguyen Thanh , Fujita Takeshi , Ishibiki Ryota , Hirabayashi Toru , Yamaguchi Akira , Matsuda Iwao , Okada Susumu , Kondo Takahiro , Miyauchi Masahiro
Published: October 2019

Hydrogen boride nanosheets (HB sheets) are facilely synthesized via ion-exchange treatment on magnesium diboride (MgB2) in an acetonitrile solution. Optical absorption and fluorescence spectra of HB sheets indicate that their bandgap energy is 2.8 eV. According to first-principles calculations, optical absorption seen at 2.8 eV is assigned to the electron transition between the σ-bonding states of B and H orbitals. In addition, density functional theory (DFT) calculations suggest the other allowed transition from the σ-bonding state of B and H orbitals to the antibonding state with the gap of 3.8 eV. Significant gaseous H2 release is found to occur only under photoirradiation, which causes the electron transition from the σ-bonding state to the antibonding state even under mild ambient conditions. The amount of H2 released from the irradiated HB sheets is estimated to be 8 wt%, indicating that the sheets have a high H2-storage capacity compared with previously reported metal H2-storage materials.
Unexpected large evasion fluxes of carbon dioxide from turbulent streams draining the world’s mountains
Authors: Horgby Åsa , Segatto Pier Luigi , Bertuzzo Enrico , Lauerwald Ronny , Lehner Bernhard , Ulseth Amber J. , Vennemann Torsten W. , Battin Tom J.
Published: October 2019

Inland waters, including streams and rivers, are active components of the global carbon cycle. Despite the large areal extent of the world’s mountains, the role of mountain streams for global carbon fluxes remains elusive. Using recent insights from gas exchange in turbulent streams, we found that areal CO2evasion fluxes from mountain streams equal or exceed those reported from tropical and boreal streams, typically regarded as hotspots of aquatic carbon fluxes. At the regional scale of the Swiss Alps, we present evidence that emitted CO2derives from lithogenic and biogenic sources within the catchment and delivered by the groundwater to the streams. At a global scale, we estimate the CO2evasion from mountain streams to 167 ± 1.5 Tg C yr−1, which is high given their relatively low areal contribution to the global stream and river networks. Our findings shed new light on mountain streams for global carbon fluxes.
Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation
Authors: Kim Sukyeong , Han Sangbin , Kim Yeongjae , Kim Hyeon-Seop , Gu Young-Ran , Kang Donghyun , Cho Yongsik , Kim Hyeonkyeong , Lee Jeeyeon , Seo Yeyoung , Chang Moon Jong , Chang Chong Bum , Kang Seung-Baik , Kim Jin-Hong
Published: October 2019

Osteoarthritis (OA) is a prevalent degenerative disease, which involves progressive and irreversible destruction of cartilage matrix. Despite efforts to reconstruct cartilage matrix in osteoarthritic joints, it has been a difficult task as adult cartilage exhibits marginal repair capacity. Here we report the identification of tankyrase as a regulator of the cartilage anabolism axis based on systems-level factor analysis of mouse reference populations. Tankyrase inhibition drives the expression of a cartilage-signature matrisome and elicits a transcriptomic pattern that is inversely correlated with OA progression. Furthermore, tankyrase inhibitors ameliorate surgically induced OA in mice, and stem cell transplantation coupled with tankyrase knockdown results in superior regeneration of cartilage lesions. Mechanistically, the pro-regenerative features of tankyrase inhibition are mainly triggered by uncoupling SOX9 from a poly(ADP-ribosyl)ation (PARylation)-dependent protein degradation pathway. Our findings provide insights into the development of future OA therapies aimed at reconstruction of articular cartilage.
Biological process activity transformation of single cell gene expression for cross-species alignment
Authors: Ding Hongxu , Blair Andrew , Yang Ying , Stuart Joshua M.
Published: October 2019

The maintenance and transition of cellular states are controlled by biological processes. Here we present a gene set-based transformation of single cell RNA-Seq data into biological process activities that provides a robust description of cellular states. Moreover, as these activities represent species-independent descriptors, they facilitate the alignment of single cell states across different organisms.
Morphometrics of eight Chinese cavefish species
Authors: Lunghi Enrico , Zhao Yang , Sun Xueying , Zhao Yahui
Published: October 2019

Chinese cavefishes are a bizarre and interesting vertebrate taxa, but one with relatively little research. China holds the highest global cavefish diversity, accounting for about one-third of known species. Sinocyclocheilus is the largest genus of cavefishes in the world and is endemic to the south of China. The distribution of Sinocyclocheilus species is very narrow, and sometimes they inhabit just a single cave; this feature increases the vulnerability to extinction. With this study we provide the first comprehensive dataset related to the morphometrics of eight Sinocyclocheilus species. In addition to enhancing our knowledge on these poorly known species we aim to provide a dataset useful for future comparative analyses aiming to better understand the adaptive ability of cavefishes.
Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat
Authors: Smigielski Lukasz , Kometer Michael , Scheidegger Milan , Krähenmann Rainer , Huber Theo , Vollenweider Franz X.
Published: October 2019

Meditation and psychedelics have played key roles in humankind’s search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin’s positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications.
Author Correction: Evaluating analgesic efficacy and administration route following craniotomy in mice using the grimace scale
Authors: Cho Chulmin , Michailidis Vassilia , Lecker Irene , Collymore Chereen , Hanwell David , Loka Mary , Danesh Matthew , Pham Christine , Urban Paige , Bonin Robert P. , Martin Loren J.
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Genomic Prediction of 16 Complex Disease Risks Including Heart Attack, Diabetes, Breast and Prostate Cancer
Authors: Lello Louis , Raben Timothy G. , Yong Soke Yuen , Tellier Laurent C. A. M. , Hsu Stephen D. H.
Published: October 2019

We construct risk predictors using polygenic scores (PGS) computed from common Single Nucleotide Polymorphisms (SNPs) for a number of complex disease conditions, using L1-penalized regression (also known as LASSO) on case-control data from UK Biobank. Among the disease conditions studied are Hypothyroidism, (Resistant) Hypertension, Type 1 and 2 Diabetes, Breast Cancer, Prostate Cancer, Testicular Cancer, Gallstones, Glaucoma, Gout, Atrial Fibrillation, High Cholesterol, Asthma, Basal Cell Carcinoma, Malignant Melanoma, and Heart Attack. We obtain values for the area under the receiver operating characteristic curves (AUC) in the range ~0.58–0.71 using SNP data alone. Substantially higher predictor AUCs are obtained when incorporating additional variables such as age and sex. Some SNP predictors alone are sufficient to identify outliers (e.g., in the 99th percentile of polygenic score, or PGS) with 3–8 times higher risk than typical individuals. We validate predictors out-of-sample using the eMERGE dataset, and also with different ancestry subgroups within the UK Biobank population. Our results indicate that substantial improvements in predictive power are attainable using training sets with larger case populations. We anticipate rapid improvement in genomic prediction as more case-control data become available for analysis.
Development and application of affordable SNP typing approaches to genotype Mycobacterium tuberculosis complex strains in low and high burden countries
Authors: Cancino-Muñoz Irving , Gil-Brusola Ana , Torres-Puente Manuela , Mariner-Llicer Carla , Dogba John , Akinseye Victor , Adesokan Kehinde , Kwaghe Ayi , Ejeh Francis , Cadmus Simeon , Comas Iñaki
Published: October 2019

The Mycobacterium tuberculosis complex (MTBC) comprises the species that causes tuberculosis (TB) which affects 10 million people every year. A robust classification of species, lineages, and sub-lineages is important to explore associations with drug resistance, epidemiological patterns or clinical outcomes. We present a rapid and easy-to-follow methodology to classify clinical TB samples into the main MTBC clades. Approaches are based on the identification of lineage and sub-lineage diagnostic SNP using a real-time PCR high resolution melting assay and classic Sanger sequencing from low-concentrated, low quality DNA. Thus, suitable for implementation in middle and low-income countries. Once we validated our molecular procedures, we characterized a total of 491 biological samples from human and cattle hosts, representing countries with different TB burden. Overall, we managed to genotype ~95% of all samples despite coming from unpurified and low-concentrated DNA. Our approach also allowed us to detect zoonotic cases in eight human samples from Nigeria. To conclude, the molecular techniques we have developed, are accurate, discriminative and reproducible. Furthermore, it costs less than other classic typing methods, resulting in an affordable alternative method in TB laboratories.
The extent, frequency and ecological functions of food wasting by parrots
Authors: Sebastián-González Esther , Hiraldo Fernando , Blanco Guillermo , Hernández-Brito Dailos , Romero-Vidal Pedro , Carrete Martina , Gómez-Llanos Eduardo , Pacífico Erica C. , Díaz-Luque José A. , Dénes Francisco V. , Tella José L.
Published: October 2019

Anecdotic citations of food wasting have been described for parrots, but we lack a comprehensive knowledge about the extent of this behaviour, and its ecological and evolutionary implications. Here, we combine experimental and observational approaches to evaluate the spatial, temporal, typological and taxonomic extent of food wasting by parrots, to identify the ecological and evolutionary factors driving food wasting, and to assess the incidence of two ecological functions derived from food wasting, such as food facilitation to other animal species and secondary seed dispersal. We found that food wasting is a widespread behaviour found in all the studied parrot species. However, the proportion of food wasted differed among species and throughout the year. Parrots wasted more food during the non-breeding season, when they relied on exotic plants and on unripe fruits or seeds. We also recorded 86 animal species feeding on the food wasted by parrots, 27 of which potentially acted as secondary seed dispersers. Overall, our study emphasizes the universality of food wasting among parrots, and the important implications that this behaviour may have for the species involved (i.e., the parrot, the plant, the other species feeding on wasted food), and for the functioning of the whole ecosystem.
Genetic structure of Mycoplasma ovipneumoniae informs pathogen spillover dynamics between domestic and wild Caprinae in the western United States
Authors: Kamath Pauline L. , Manlove Kezia , Cassirer E. Frances , Cross Paul C. , Besser Thomas E.
Published: October 2019

Spillover diseases have significant consequences for human and animal health, as well as wildlife conservation. We examined spillover and transmission of the pneumonia-associated bacterium Mycoplasma ovipneumoniae in domestic sheep, domestic goats, bighorn sheep, and mountain goats across the western United States using 594 isolates, collected from 1984 to 2017. Our results indicate high genetic diversity of M. ovipneumoniae strains within domestic sheep, whereas only one or a few strains tend to circulate in most populations of bighorn sheep or mountain goats. These data suggest domestic sheep are a reservoir, while the few spillovers to bighorn sheep and mountain goats can persist for extended periods. Domestic goat strains form a distinct clade from those in domestic sheep, and strains from both clades are found in bighorn sheep. The genetic structure of domestic sheep strains could not be explained by geography, whereas some strains are spatially clustered and shared among proximate bighorn sheep populations, supporting pathogen establishment and spread following spillover. These data suggest that the ability to predict M. ovipneumoniae spillover into wildlife populations may remain a challenge given the high strain diversity in domestic sheep and need for more comprehensive pathogen surveillance.
Modulating cellular cytotoxicity and phototoxicity of fluorescent organic salts through counterion pairing
Authors: Broadwater Deanna , Bates Matthew , Jayaram Mayank , Young Margaret , He Jianzhou , Raithel Austin L. , Hamann Thomas W. , Zhang Wei , Borhan Babak , Lunt Richard R. , Lunt Sophia Y.
Published: October 2019

Light-activated theranostics offer promising opportunities for disease diagnosis, image-guided surgery, and site-specific personalized therapy. However, current fluorescent dyes are limited by low brightness, high cytotoxicity, poor tissue penetration, and unwanted side effects. To overcome these limitations, we demonstrate a platform for optoelectronic tuning, which allows independent control of the optical properties from the electronic properties of fluorescent organic salts. This is achieved through cation-anion pairing of organic salts that can modulate the frontier molecular orbital without impacting the bandgap. Optoelectronic tuning enables decoupled control over the cytotoxicity and phototoxicity of fluorescent organic salts by selective generation of mitochondrial reactive oxygen species that control cell viability. We show that through counterion pairing, organic salt nanoparticles can be tuned to be either nontoxic for enhanced imaging, or phototoxic for improved photodynamic therapy.
Adsorptive removal of mercury from water by adsorbents derived from date pits
Authors: Al-Ghouti Mohammad A. , Da’ana Dana , Abu-Dieyeh Mohammed , Khraisheh Majeda
Published: October 2019

The current work presented here focuses on the remediation of mercury from water using modified low-cost materials. Modified date pits, low cost, minimal pretreatment steps and locally abundant agricultural waste materials were effectively employed as an adsorbent for remediating Hg2+ from aqueous media. Physical and chemical modification were developed such as thermal roasting (RDP), sulfur (SMRDP) and silane (SIMRDP) based modifications. Results showed that maximum adsorption by RDP was at pH 6, AC and both modifications was at pH 4. Furthermore, RDP has exothermic adsorption mechanism while AC, SMRDP, and SIMRDP have endothermic. All adsorbents except SIMRDP have spontaneous adsorption process. SEM analysis showed that the surface morphology of RDP was not significantly affected by different treatments while surface of AC was affected. The investigation for good adsorbents for Hg2+ uptake from different anthropogenic sources has been carried out by many investigators worldwide towards having a safe environment. In the current study, the highest Hg2+ adsorption of SMRDP was relatively high compared to other known adsorbents.
Bases of Bacterial Sodium Channel Selectivity Among Organic Cations
Authors: Wang Yibo , Finol-Urdaneta Rocio K. , Ngo Van Anh , French Robert J. , Noskov Sergei Yu.
Published: October 2019

Hille’s (1971) seminal study of organic cation selectivity of eukaryotic voltage-gated sodium channels showed a sharp size cut-off for ion permeation, such that no ion possessing a methyl group was permeant. Using the prokaryotic channel, NaChBac, we found some similarity and two peculiar differences in the selectivity profiles for small polyatomic cations. First, we identified a diverse group of minimally permeant cations for wildtype NaChBac, ranging in sizes from ammonium to guanidinium and tetramethylammonium; and second, for both ammonium and hydrazinium, the charge-conserving selectivity filter mutation (E191D) yielded substantial increases in relative permeability (PX/PNa). The relative permeabilities varied inversely with relative Kd calculated from 1D Potential of Mean Force profiles (PMFs) for the single cations traversing the channel. Several of the cations bound more strongly than Na+, and hence appear to act as blockers, as well as charge carriers. Consistent with experimental observations, the E191D mutation had little impact on Na+ binding to the selectivity filter, but disrupted the binding of ammonium and hydrazinium, consequently facilitating ion permeation across the NaChBac-like filter. We concluded that for prokaryotic sodium channels, a fine balance among filter size, binding affinity, occupancy, and flexibility seems to contribute to observed functional differences.
Abnormally Methylated FMR1 in Absence of a Detectable Full Mutation in a U.S.A Patient Cohort Referred for Fragile X Testing
Authors: Hensel Charles H. , Vanzo Rena J. , Martin Megan M. , Ling Ling , Aliaga Solange M. , Bui Minh , Francis David I. , Twede Hope , Field Michael H. , Morison Jonathon W. , Amor David J. , Godler David E.
Published: October 2019

In 2016, Methylation-Specific Quantitative Melt Analysis (MS-QMA) on 3,340 male probands increased diagnostic yield from 1.60% to 1.84% for fragile X syndrome (FXS) using a pooling approach. In this study probands from Lineagen (UT, U.S.A.) of both sexes were screened using MS-QMA without sample pooling. The cohorts included: (i) 279 probands with no FXS full mutation (FM: CGG > 200) detected by AmplideX CGG sizing; (ii) 374 negative and 47 positive controls. MS-QMA sensitivity and specificity in controls approached 100% for both sexes. For male probands with no FM detected by standard testing (n = 189), MS-QMA identified abnormal DNA methylation (mDNA) in 4% normal size (NS: < 44 CGGs), 6% grey zone (CGG 45–54) and 12% premutation (CGG 54–199) alleles. The abnormal mDNA was confirmed by AmplideX methylation sensitive (m)PCR and EpiTYPER tests. In contrast, no abnormal mDNA was detected in 89 males with NS alleles from the general population. For females, 11% of 43 probands with NS alleles by the AmplideX sizing assay had abnormal mDNA by MS-QMA, with FM / NS mosaicism confirmed by AmplideX mPCR. FMR1 MS-QMA analysis can cost-effectively screen probands of both sexes for methylation and FM mosaicism that may be missed by standard testing.
Clostridium difficile clade 3 (RT023) have a modified cell surface and contain a large transposable island with novel cargo
Authors: Shaw Helen Alexandra , Khodadoost Ladan , Preston Mark D. , Corver Jeroen , Mullany Peter , Wren Brendan W.
Published: October 2019

The major global pathogen Clostridium difficile (recently renamed Clostridioides difficile) has large genetic diversity including multiple mobile genetic elements. In this study, whole genome sequencing of 86 strains from the poorly characterised clade 3, predominantly PCR ribotype (RT)023, of C. difficile revealed distinctive surface architecture characteristics and a large mobile genetic island. These strains have a unique sortase substrate phenotype compared with well-characterised strains of C. difficile, and loss of the phage protection protein CwpV. A large genetic insertion (023_CTnT) comprised of three smaller elements (023_CTn1-3) is present in 80/86 strains analysed in this study, with genes common among other bacterial strains in the gut microbiome. Novel cargo regions of 023_CTnT include genes encoding a sortase, putative sortase substrates, lantibiotic ABC transporters and a putative siderophore biosynthetic cluster. We demonstrate the excision of 023_CTnT and sub-elements 023_CTn2 and 023_CTn3 from the genome of RT023 reference strain CD305 and the transfer of 023_CTn3 to a non-toxigenic C. difficile strain, which may have implications for the use of non-toxigenic C. difficile strains as live attenuated vaccines. Finally, we show that the genes within the island are expressed in a regulated manner in C. difficile RT023 strains conferring a distinct “niche adaptation”.
Sex determination using circulating cell-free fetal DNA in small volume of maternal plasma in elephants
Authors: Vincze Boglárka , Gáspárdy András , Biácsi Alexandra , Papp Endre Ákos , Garamvölgyi László , Sós Endre , Cseh Sándor , Kovács Gábor , Pádár Zsolt , Zenke Petra
Published: October 2019

The genetic sexing of animals having long gestation periods offers significant benefits in regard to breeding management among their populations living in captivity. In our study, a new increased-sensitivity PCR method for fetal sexing was developed and tested successfully on elephants, from only a small volume of maternal plasma. Suitable sensitivity was obtained by using short, reduced amplicon lengths with fluorescent labelling for capillary electrophoresis detection. The fundamental principle for this technique was based on the detection of two Y-specific markers (AmelYandSRY), the presence of which indicates the mother is carrying a male fetus and the absence of these markers designates a female fetus. As a reaction control, the X-chromosomal marker (PlpX) was used. To the best of our knowledge, this is the first report on this topic, confirming the presence of fetal cell-free DNA from the plasma of a pregnant captive elephant, and demonstrating a new opportunity for non-invasive assessment in fetal sex determination.
Complex interactions between sperm viability and female fertility
Authors: Tourmente Maximiliano , Archer C. Ruth , Hosken David J.
Published: October 2019

Sperm viability is a major male fitness component, with higher sperm viability associated with enhanced sperm competitiveness. While many studies have focussed on sperm viability from the male fitness standpoint, its impact on female fitness is less clear. Here we used a panel of 32 isogenic Drosophila simulans lines to test for genetic variation in sperm viability (percentage of viable cells). We then tested whether sperm viability affected female fitness by mating females to males from low or high sperm viability genotypes. We found significant variation in sperm viability among genotypes, and consistent with this, sperm viability was highly repeatable within genotypes. Additionally, females mated to high sperm viability males laid more eggs in the first seven hours after mating, and produced more offspring in total. However, the early increase in oviposition did not result in more offspring in the 8 hours following mating, suggesting that mating with high sperm-viability genotypes leads to egg wastage for females shortly after copulation. Although mating with high sperm-viability males resulted in higher female fitness in the long term, high quality ejaculates would result in a short-term female fitness penalty, or at least lower realised fitness, potentially generating sexual conflict over optimal sperm viability.
Evaluations of Acute and Sub-Acute Biological Effects of Narrowband and Moderate-Band High Power Electromagnetic Waves on Cellular Spheroids
Authors: Gibot Laure , Kolosnjaj-Tabi Jelena , Bellard Elisabeth , Chretiennot Thomas , Saurin Quentin , Catrain Alexandre , Golzio Muriel , Vézinet René , Rols Marie-Pierre
Published: October 2019

High power electromagnetic signals can disrupt the functioning of electronic devices. As electromagnetism plays a role in cells homeostasis, such electromagnetic signals could potentially also alter some physiological processes. Herein we report on distinct biological parameters assessment after cellular spheroids exposure to high power electromagnetic signals, such as the ones used for defense applications. Signals effects were assessed in tumor cells spheroids and in normal human dermal fibroblasts spheroids, where macroscopic aspect, growth, plasma membrane integrity, induction of apoptosis, ATP content, and mitochondrial potential were investigated after spheroids exposure to high power electromagnetic signals. No significant effects were observed, indicating that 1.5 GHz narrowband electromagnetic fields with incident amplitude level of 40 kV/m, and 150 MHz moderate-band electric fields with an amplitude of 72.5 to approximately 200 kV/m, do not cause any significant alterations of assessed parameters.
Relative Fat Mass as an estimator of whole-body fat percentage among children and adolescents: A cross-sectional study using NHANES
Authors: Woolcott Orison O. , Bergman Richard N.
Published: October 2019

We evaluated the ability of the Relative Fat Mass (RFM) to estimate whole-body fat percentage among children and adolescents who participated in the National Health and Nutrition Examination Survey from 1999 through 2006 (n = 10,390). The RFM equation for adults (64 − (20 × height/waist circumference) + (12 × sex)) may be used for adolescents 15 to 19 years of age. For children and adolescents 8 to 14 years of age, we suggest a modified RFM equation, named as the RFMp (RFM pediatric): 74 − (22 × height/waist circumference) + (5 × sex). In both equations, sex equals 0 for boys and 1 for girls. RFMp was more accurate than BMI to estimate whole-body fat percentage (measured by dual energy X-ray absorptiometry, DXA) among girls (percentage of estimates that were <20% of measured body fat percentage, 88.2% vs. 85.7%; P = 0.027) and boys 8 to 14 years of age (83.4% vs. 71.0%; P < 0.001). RFM was more accurate than BMI among boys 15 to 19 years of age (82.3% vs. 73.9%; P < 0.001) but slightly less accurate among girls (89.0% vs. 92.6%; P = 0.002). Compared with BMI-for-age percentiles, RFMp had lower misclassification error of overweight or obesity (defined as a DXA-measured body fat percentage at the 85th percentile or higher) among boys 8 to 14 years of age (6.5% vs. 7.9%; P = 0.018) but not girls (RFMp: 8.2%; BMI-for-age: 7.9%; P = 0.681). Misclassification error of overweight or obesity was similar for RFM and BMI-for-age percentiles among girls (RFM: 8.0%; BMI-for-age: 6.6%; P = 0.076) and boys 15 to 19 years of age (RFM: 6.9%; BMI-for-age: 7.8%; P = 0.11). RFMp for children and adolescents 8 to 14 years of age and RFM for adolescents 15 to 19 years of age were useful to estimate whole-body fat percentage and diagnose body fat-defined overweight or obesity.
Doxycycline reduces osteopenia in female rats
Authors: de Figueiredo Fellipe A. T. , Shimano Roberta C. , Ervolino Edilson , Pitol Dimitrius L. , Gerlach Raquel F. , Issa Joao Paulo M.
Published: October 2019

Doxycycline, a member of the tetracycline family, is a drug used as an antibiotic (dosage of 100 mg/day) and as an anti-inflammatory drug on the dosage of 20 mg twice a day, this use has Matrix Metalloproteinases (MMP) inhibitor action. Doxycycline is a calcium chelator and therefore interferes in bone remodeling. The main objective of this study was to evaluate the action of the drug doxycycline in the control of osteopenia. Sixty three Wistars rats were divided into 9 groups with n = 7 each, as follow: the control group with doxycycline 10 mg/kg/day (C10), control with doxycycline 30 mg/kg/day (C30) and control (C), ovariectomized group with doxycycline 10 mg/kg/day (OVX10), ovariectomized with doxycycline 30 mg/kg/day (OVX30), and ovariectomized with water (OVX), sedentary group with 10 mg/kg/day (Se10), sedentary with doxycycline 30 mg/kg/day (Se30), and sedentary group with water (Se). Left femoral bone was used for bone densitometry, right femoral bone for histological analysis. The right tibia was intended for chemical quantifications, the total serum was used for cholesterol and calcium quantification. The length of the left femoral bone was measured after the densitometry analysis. Statistical analysis was performed using multivariate general linear model (ANOVA two factors with Bonferroni adjustment) and the TRAP analysis was subjected to normality test and then were subjected to nonparametric test, both with p < 0.05 significance. Statistically significant differences were found, with better results for the groups exposed to the medication (10 and 30 mg/kg/day): Se vs. Se10 and Se vs. Se30 for BMC, quantification of magnesium, amount of cancellous bone in the distal portion; OVX vs. OVX10 for BMC, BMD and calcium in serum; OVX vs. OVX10 and OVX30 for quantification in proximal and distal portion of cancellous bone; Se vs. Se30 and OVX vs. OVX30 for immunostaining for TRAP, all results with minimum of p ≤ 0.05. Doxycycline had a deleterious effect on control groups and positive action for bone organization on female rats affected by bilateral ovariectomy-induced osteopenia and sedentary lifestyle.
Let-7 regulates cell cycle dynamics in the developing cerebral
cortex and retina
Authors: Fairchild Corinne L. A. , Cheema Simranjeet K. , Wong Joanna , Hino Keiko , Simó Sergi , La Torre Anna
Published: October 2019

In the neural progenitors of the developing central nervous system
(CNS), cell proliferation is tightly controlled and coordinated with cell fate
decisions. Progenitors divide rapidly during early development and their cell cycle
lengthens progressively as development advances to eventually give rise to a tissue
of the correct size and cellular composition. However, our understanding of the
molecules linking cell cycle progression to developmental time is incomplete. Here,
we show that the microRNA (miRNA) let-7 accumulates in neural progenitors over time
throughout the developing CNS. Intriguingly, we find that the level and activity of
let-7 oscillate as neural progenitors progress through the cell cycle by in situ hybridization and fluorescent miRNA sensor
analyses. We also show that let-7 mediates cell cycle dynamics: increasing the level
of let-7 promotes cell cycle exit and lengthens the S/G2 phase of the cell cycle,
while let-7 knock down shortens the cell cycle in neural progenitors. Together, our
findings suggest that let-7 may link cell proliferation to developmental time and
regulate the progressive cell cycle lengthening that occurs during
development.
High HDL-C levels reduce the risk of obstructive coronary artery disease in asymptomatic diabetics who achieved optimal glycemic control
Authors: Park Gyung-Min , Lee Yongjik , Won Ki-Bum , Yang Yu Jin , Park Sangwoo , Ann Soe Hee , Kim Yong-Giun , Yang Dong Hyun , Kang Joon-Won , Lim Tae-Hwan , Kim Hong-Kyu , Choe Jaewon , Lee Seung-Whan , Kim Young-Hak , Kim Shin-Jae , Lee Sang-Gon
Published: October 2019

The benefit of a high level of high-density lipoprotein cholesterol (HDL-C) against coronary atherosclerosis risk after achieving optimal glycemic control (OGC) in diabetics remains uncertain. We aimed to evaluate the association between HDL-C and obstructive coronary artery disease (CAD) according to OGC status in diabetics. We analyzed 1,114 asymptomatic diabetics who underwent coronary computed tomographic angiography in a health examination. OGC was defined as hemoglobin A1C <7.0%. Obstructive CAD was defined as the presence of plaques with ≥50% stenosis. Patients with a high HDL-C level (≥40 mg/dL and ≥50 mg/dL in males and females, respectively) showed a lower prevalence of obstructive CAD than those with a low HDL-C level in the OGC group (8.9% vs. 14.4%; p = 0.046), but not in the non-OGC group (22.3% vs. 23.2%, p = 0.850). Multiple logistic regression models showed that the risk for obstructive CAD was lower in patients with a high HDL-C level than in those with a low HDL-C level in the OGC group (odds ratio: 0.584, 95% confidence interval: 0.343–0.995; p = 0.048), but not in the non-OGC group. In conclusion, it may be necessary to maintain a high HDL-C level to reduce the risk of obstructive CAD in asymptomatic diabetics after OGC is achieved.
Asymmetrical middle cerebral artery bifurcations are more vulnerable to aneurysm formation
Authors: Zhang Xue-Jing , Hao Wei-Li , Zhang Dong-Hai , Gao Bu-Lang
Published: October 2019

The objective of this study was to elucidate possible relationship between middle cerebral artery (MCA) bifurcation aneurysms and bifurcation morphology. In the present study, 799 patients with three-dimensional angiography were enrolled, including 115 patients with MCA bifurcation aneurysms and 684 subjects without aneurysms. The MCA bifurcation geometry, including angles formed between two M2 segments (φ1) and between M1 and M2 segments, vessel diameters and aneurysm sizes were measured. DA ratio (larger/smaller M2 in diameter) and LA ratio (larger/smaller lateral angle) were also analyzed. The LA and DA ratios and angle φ1 were significantly (P < 0.0001) greater in patients harboring MCA bifurcation aneurysms than in the control, whereas lateral angles and bifurcation branch diameters were significantly smaller (P < 0.01) in patients with than without bifurcation aneurysms. Angle φ1 was significantly increased (P < 0.0001) while both lateral angles significantly decreased (P < 0.0001 and P = 0.0005, respectively) with increase of patients’ age. The size of MCA bifurcation aneurysms was significantly (P < 0.05) positively correlated with the bifurcation vascular diameter and aneurysm neck at the MCA bifurcation. A significantly positive correlation existed between aneurysm neck and DA ratio (P = 0.0075), whereas an inverse correlation between aneurysm neck and LA ratio (P = 0.0219). MCA bifurcation aneurysms were mostly deviated toward the smaller lateral angles and smaller M2 branch. In conclusion, aneurysmal MCA bifurcations have asymmetrical bifurcation structures with widened bifurcation angles, narrowed lateral angles, decreased M1 diameter, imbalanced lateral angles and M2 segments, with the cutoff bifurcation angle of 125.0° and cutoff lateral angle ratio of 1.57 for predicting MCA bifurcation aneurysms, whereas normal MCA bifurcations show close to symmetrical structures in the lateral angles and M2 branches.