bluuebunny/crossref_metadata_2025_split huggingface dataset:
The origin of heterogeneous nanoparticle uptake by cells
Authors: Rees Paul , Wills John W. , Brown M. Rowan , Barnes Claire M. , Summers Huw D. 
Published: May 2019

AbstractUnderstanding nanoparticle uptake by biological cells is fundamentally important to wide-ranging fields from nanotoxicology to drug delivery. It is now accepted that the arrival of nanoparticles at the cell is an extremely complicated process, shaped by many factors including unique nanoparticle physico-chemical characteristics, protein-particle interactions and subsequent agglomeration, diffusion and sedimentation. Sequentially, the nanoparticle internalisation process itself is also complex, and controlled by multiple aspects of a cell’s state. Despite this multitude of factors, here we demonstrate that the statistical distribution of the nanoparticle dose per endosome is independent of the initial administered dose and exposure duration. Rather, it is the number of nanoparticle containing endosomes that are dependent on these initial dosing conditions. These observations explain the heterogeneity of nanoparticle delivery at the cellular level and allow the derivation of simple, yet powerful probabilistic distributions that accurately predict the nanoparticle dose delivered to individual cells across a population.
Tuning the permselectivity of polymeric desalination membranes via control of polymer crystallite size
Authors: Lu Xinglin , Feng Xunda , Yang Yi , Jiang Jin , Cheng Wei , Liu Caihong , Gopinadhan Manesh , Osuji Chinedum O. , Ma Jun , Elimelech Menachem 
Published: May 2019

AbstractMembrane desalination is a leading technology for treating saline waters to augment fresh water supply. The need for high-performance desalination membranes, particularly with high water/salt selectivity, has stimulated research into the fundamental structure-property-performance relationship of state-of-the-art membranes. In this study, we utilize a facile method for tuning properties of a polymeric desalination membrane to shed light on water and salt transport mechanisms of such membranes. A desalination membrane made of cellulose triacetate is treated in a plasticizer solution, followed by water rinsing. The modified membranes exhibit reduced salt flux without compromising water flux, indicating enhanced water/salt selectivity. An inspection of material characteristics using a model film system reveals a plasticizing-extracting process in changing the polymeric structure, which leads to the reduction of crystallite size in the polymer matrix, consequently affecting the transport properties of the membranes. Our findings highlight the potential of the plasticizing-extracting process in fabricating membranes with desired desalination performance.
FANCM limits ALT activity by restricting telomeric replication stress induced by deregulated BLM and R-loops
Authors: Silva Bruno , Pentz Richard , Figueira Ana Margarida , Arora Rajika , Lee Yong Woo , Hodson Charlotte , Wischnewski Harry , Deans Andrew J. , Azzalin Claus M. 
Published: May 2019

AbstractTelomerase negative immortal cancer cells elongate telomeres through the Alternative Lengthening of Telomeres (ALT) pathway. While sustained telomeric replicative stress is required to maintain ALT, it might also lead to cell death when excessive. Here, we show that the ATPase/translocase activity of FANCM keeps telomeric replicative stress in check specifically in ALT cells. When FANCM is depleted in ALT cells, telomeres become dysfunctional, and cells stop proliferating and die. FANCM depletion also increases ALT-associated marks and de novo synthesis of telomeric DNA. Depletion of the BLM helicase reduces the telomeric replication stress and cell proliferation defects induced by FANCM inactivation. Finally, FANCM unwinds telomeric R-loops in vitro and suppresses their accumulation in cells. Overexpression of RNaseH1 completely abolishes the replication stress remaining in cells codepleted for FANCM and BLM. Thus, FANCM allows controlled ALT activity and ALT cell proliferation by limiting the toxicity of uncontrolled BLM and telomeric R-loops.
The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT)
Authors: Lu Robert , O’Rourke Julienne J. , Sobinoff Alexander P. , Allen Joshua A. M. , Nelson Christopher B. , Tomlinson Christopher G. , Lee Michael , Reddel Roger R. , Deans Andrew J. , Pickett Hilda A. 
Published: May 2019

AbstractThe collapse of stalled replication forks is a major driver of genomic instability. Several committed mechanisms exist to resolve replication stress. These pathways are particularly pertinent at telomeres. Cancer cells that use Alternative Lengthening of Telomeres (ALT) display heightened levels of telomere-specific replication stress, and co-opt stalled replication forks as substrates for break-induced telomere synthesis. FANCM is a DNA translocase that can form independent functional interactions with the BLM-TOP3A-RMI (BTR) complex and the Fanconi anemia (FA) core complex. Here, we demonstrate that FANCM depletion provokes ALT activity, evident by increased break-induced telomere synthesis, and the induction of ALT biomarkers. FANCM-mediated attenuation of ALT requires its inherent DNA translocase activity and interaction with the BTR complex, but does not require the FA core complex, indicative of FANCM functioning to restrain excessive ALT activity by ameliorating replication stress at telomeres. Synthetic inhibition of FANCM-BTR complex formation is selectively toxic to ALT cancer cells.
Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro
Authors: Feldman Alona , Mukha Dzmitry , Maor Itzhak I. , Sedov Egor , Koren Elle , Yosefzon Yahav , Shlomi Tomer , Fuchs Yaron 
Published: May 2019

AbstractMost studies on the skin focus primarily on the hair follicle and interfollicular epidermis, whereas little is known regarding the homeostasis of the sebaceous gland (SG). The SG has been proposed to be replenished by different pools of hair follicle stem cells and cells that resides in the SG base, marked by Blimp1. Here, we demonstrate that single Blimp1+ cells isolated from mice have the potential to generate SG organoids in vitro. Mimicking SG homeostasis, the outer layer of these organoids is composed of proliferating cells that migrate inward, undergo terminal differentiation and generating lipid-filled sebocytes. Performing confocal microscopy and mass-spectrometry, we report that these organoids exhibit known markers and a lipidomic profile similar to SGs in vivo. Furthermore, we identify a role for c-Myc in sebocyte proliferation and differentiation, and determine that SG organoids can serve as a platform for studying initial stages of acne vulgaris, making this a useful platform to identify potential therapeutic targets.
SORLA regulates endosomal trafficking and oncogenic fitness of HER2
Authors: Pietilä Mika , Sahgal Pranshu , Peuhu Emilia , Jäntti Niklas Z. , Paatero Ilkka , Närvä Elisa , Al-Akhrass Hussein , Lilja Johanna , Georgiadou Maria , Andersen Olav M. , Padzik Artur , Sihto Harri , Joensuu Heikki , Blomqvist Matias , Saarinen Irena , Boström Peter J. , Taimen Pekka , Ivaska Johanna 
Published: May 2019

AbstractThe human epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. While the endosomal trafficking of many other receptor tyrosine kinases is known to regulate their oncogenic signalling, the prevailing view on HER2 is that this receptor is predominantly retained on the cell surface. Here, we find that sortilin-related receptor 1 (SORLA; SORL1) co-precipitates with HER2 in cancer cells and regulates HER2 subcellular distribution by promoting recycling of the endosomal receptor back to the plasma membrane. SORLA protein levels in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA triggers HER2 targeting to late endosomal/lysosomal compartments and impairs HER2-driven signalling and in vivo tumour growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.
Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors
Authors: Kirchdoerfer Robert N. , Ward Andrew B. 
Published: May 2019

AbstractRecent history is punctuated by the emergence of highly pathogenic coronaviruses such as SARS- and MERS-CoV into human circulation. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Here, we present the 3.1 Å resolution structure of the SARS-CoV nsp12 polymerase bound to its essential co-factors, nsp7 and nsp8, using single particle cryo-electron microscopy. nsp12 possesses an architecture common to all viral polymerases as well as a large N-terminal extension containing a kinase-like fold and is bound by two nsp8 co-factors. This structure illuminates the assembly of the coronavirus core RNA-synthesis machinery, provides key insights into nsp12 polymerase catalysis and fidelity and acts as a template for the design of novel antiviral therapeutics.
Synergistic and antagonistic impacts of suspended sediments and thermal stress on corals
Authors: Fisher Rebecca , Bessell-Browne Pia , Jones Ross 
Published: May 2019

AbstractUnderstanding pressure pathways and their cumulative impacts is critical for developing effective environmental policy. For coral reefs, wide spread bleaching resulting from global warming is occurring concurrently with local pressures, such as increases in suspended sediments through coastal development. Here we examine the relative importance of suspended sediment pressure pathways for dredging impacts on corals and evidence for synergistic or antagonistic cumulative effects between suspended sediments and thermal stress. We show that low to moderate reductions in available light associated with dredging may lead to weak antagonistic (less than expected independently) cumulative effects. However, when sediment loads are high any reductions in mortality associated with reduced bleaching are outweighed by increased mortality associated with severe low light periods and high levels of sediment deposition and impacts become synergistic (greater than what would occur independently). The findings suggest efforts to assess global cumulative impacts need to consider how pressures interact to impact ecosystems, and that the cumulative outcome may vary across the range of realised pressure fields.
Infinitesimal sulfur fusion yields quasi-metallic bulk silicon for stable and fast energy storage
Authors: Ryu Jaegeon , Seo Ji Hui , Song Gyujin , Choi Keunsu , Hong Dongki , Wang Chongmin , Lee Hosik , Lee Jun Hee , Park Soojin 
Published: May 2019

AbstractA fast-charging battery that supplies maximum energy is a key element for vehicle electrification. High-capacity silicon anodes offer a viable alternative to carbonaceous materials, but they are vulnerable to fracture due to large volumetric changes during charge–discharge cycles. The low ionic and electronic transport across the silicon particles limits the charging rate of batteries. Here, as a three-in-one solution for the above issues, we show that small amounts of sulfur doping (<1 at%) render quasi-metallic silicon microparticles by substitutional doping and increase lithium ion conductivity through the flexible and robust self-supporting channels as demonstrated by microscopy observation and theoretical calculations. Such unusual doping characters are enabled by the simultaneous bottom-up assembly of dopants and silicon at the seed level in molten salts medium. This sulfur-doped silicon anode shows highly stable battery cycling at a fast-charging rate with a high energy density beyond those of a commercial standard anode.
Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
Authors: Genet Gael , Boyé Kevin , Mathivet Thomas , Ola Roxana , Zhang Feng , Dubrac Alexandre , Li Jinyu , Genet Nafiisha , Henrique Geraldo Luiz , Benedetti Lorena , Künzel Steffen , Pibouin-Fragner Laurence , Thomas Jean-Leon , Eichmann Anne 
Published: May 2019

AbstractEndothelial cell migration, proliferation and survival are triggered by VEGF-A activation of VEGFR2. However, how these cell behaviors are regulated individually is still unknown. Here we identify Endophilin-A2 (ENDOA2), a BAR-domain protein that orchestrates CLATHRIN-independent internalization, as a critical mediator of endothelial cell migration and sprouting angiogenesis. We show thatEndoA2knockout mice exhibit postnatal angiogenesis defects and impaired front-rear polarization of sprouting tip cells. ENDOA2 deficiency reduces VEGFR2 internalization and inhibits downstream activation of the signaling effector PAK but not ERK, thereby affecting front-rear polarity and migration but not proliferation or survival. Mechanistically, VEGFR2 is directed towards ENDOA2-mediated endocytosis by the SLIT2-ROBO pathway via SLIT-ROBO-GAP1 bridging of ENDOA2 and ROBO1. Blocking ENDOA2-mediated endothelial cell migration attenuates pathological angiogenesis in oxygen-induced retinopathy models. This work identifies a specific endocytic pathway controlling a subset of VEGFR2 mediated responses that could be targeted to prevent excessive sprouting angiogenesis in pathological conditions.
Assessing spirituality: is there a beneficial role in the management of COPD?
Authors: Gergianaki Irini , Kampouraki Maria , Williams Siân , Tsiligianni Ioanna 
Published: May 2019

AbstractHere,we report on the role of spirituality assessment in the management of chronic obstructive pulmonary disease (COPD). Although a positive effect of addressing spirituality in health care has been proved in a number of chronic diseases, its potential in COPD has received less attention. Although limited, available evidence suggests that spirituality may play an important role in improving quality of life of patients with COPD. The fruitful results in other long-term conditions may lay the foundation for further research on addressing spirituality in COPD. This should focus where the burden of COPD is greatest, including low-resource settings globally. Implementation research should include exploration of an acceptable consultation process to identify patients who would welcome spiritual discussions; how to integrate spiritual approaches into health care professional curricula so that they are aware of its importance and have the confidence to raise it with patients and how to integrate spiritual approaches into holistic COPD care.
Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Authors: Burgmaier Kathrin , Kilian Samuel , Bammens Bert , Benzing Thomas , Billing Heiko , Büscher Anja , Galiano Matthias , Grundmann Franziska , Klaus Günter , Mekahli Djalila , Michel-Calemard Laurence , Milosevski-Lomic Gordana , Ranchin Bruno , Sauerstein Katja , Schaefer Susanne , Shroff Rukshana , Sterenborg Rosalie , Verbeeck Sarah , Weber Lutz T. , Wicher Dorota , Wühl Elke , Dötsch Jörg , Schaefer Franz , Liebau Max C. 
Published: May 2019

AbstractAutosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric hepatorenal disorder with pronounced phenotypic variability. A substantial number of patients with early diagnosis reaches adulthood and some patients are not diagnosed until adulthood. Yet, clinical knowledge about adult ARPKD patients is scarce. Here, we describe forty-nine patients with longitudinal follow-up into young adulthood that were identified in the international ARPKD cohort study ARegPKD. Forty-five patients were evaluated in a cross-sectional analysis at a mean age of 21.4 (±3.3) years describing hepatorenal findings. Renal function of native kidneys was within CKD stages 1 to 3 in more than 50% of the patients. Symptoms of hepatic involvement were frequently detected. Fourteen (31%) patients had undergone kidney transplantation and six patients (13%) had undergone liver transplantation or combined liver and kidney transplantation prior to the visit revealing a wide variability of clinical courses. Hepatorenal involvement and preceding complications in other organs were also evaluated in a time-to-event analysis. In summary, we characterize the broad clinical spectrum of young adult ARPKD patients. Importantly, many patients have a stable renal and hepatic situation in young adulthood. ARPKD should also be considered as a differential diagnosis in young adults with fibrocystic hepatorenal disease.
Novel Genes and Metabolite Trends in Bifidobacterium longum subsp. infantis Bi-26 Metabolism of Human Milk Oligosaccharide 2′-fucosyllactose
Authors: Zabel Bryan , Yde Christian Clement , Roos Paige , Marcussen Jørn , Jensen Henrik Max , Salli Krista , Hirvonen Johanna , Ouwehand Arthur C. , Morovic Wesley 
Published: May 2019

AbstractHuman milk oligosaccharides (HMOs) function as prebiotics for beneficial bacteria in the developing gut, often dominated by Bifidobacterium spp. To understand the relationship between bifidobacteria utilizing HMOs and how the metabolites that are produced could affect the host, we analyzed the metabolism of HMO 2′-fucosyllactose (2′-FL) in Bifidobacterium longum subsp. infantis Bi-26. RNA-seq and metabolite analysis (NMR/GCMS) was performed on samples at early (A600 = 0.25), mid-log (0.5–0.7) and late-log phases (1.0–2.0) of growth. Transcriptomic analysis revealed many gene clusters including three novel ABC-type sugar transport clusters to be upregulated in Bi-26 involved in processing of 2′-FL along with metabolism of its monomers glucose, fucose and galactose. Metabolite data confirmed the production of formate, acetate, 1,2-propanediol, lactate and cleaving of fucose from 2′-FL. The formation of acetate, formate, and lactate showed how the cell uses metabolites during fermentation to produce higher levels of ATP (mid-log compared to other stages) or generate cofactors to balance redox. We concluded that 2′-FL metabolism is a complex process involving multiple gene clusters, that produce a more diverse metabolite profile compared to lactose. These results provide valuable insight on the mode-of-action of 2′-FL utilization by Bifidobacterium longum subsp. infantis Bi-26.
The role of stratospheric ozone for Arctic-midlatitude linkages
Authors: Romanowsky Erik , Handorf Dörthe , Jaiser Ralf , Wohltmann Ingo , Dorn Wolfgang , Ukita Jinro , Cohen Judah , Dethloff Klaus , Rex Markus 
Published: May 2019

AbstractArctic warming was more pronounced than warming in midlatitudes in the last decades making this region a hotspot of climate change. Associated with this, a rapid decline of sea-ice extent and a decrease of its thickness has been observed. Sea-ice retreat allows for an increased transport of heat and momentum from the ocean up to the tropo- and stratosphere by enhanced upward propagation of planetary-scale atmospheric waves. In the upper atmosphere, these waves deposit the momentum transported, disturbing the stratospheric polar vortex, which can lead to a breakdown of this circulation with the potential to also significantly impact the troposphere in mid- to late-winter and early spring. Therefore, an accurate representation of stratospheric processes in climate models is necessary to improve the understanding of the impact of retreating sea ice on the atmospheric circulation. By modeling the atmospheric response to a prescribed decline in Arctic sea ice, we show that including interactive stratospheric ozone chemistry in atmospheric model calculations leads to an improvement in tropo-stratospheric interactions compared to simulations without interactive chemistry. This suggests that stratospheric ozone chemistry is important for the understanding of sea ice related impacts on atmospheric dynamics.
Gut microbiome differences between wild and captive black rhinoceros – implications for rhino health
Authors: Gibson Keylie M. , Nguyen Bryan N. , Neumann Laura M. , Miller Michele , Buss Peter , Daniels Savel , Ahn Michelle J. , Crandall Keith A. , Pukazhenthi Budhan 
Published: May 2019

AbstractA number of recent studies have shown the importance of the mammalian gut microbiome in host health. In the context of endangered species, a few studies have examined the relationship between the gut microbiome in wild versus captive populations due to digestive and other health issues. Unfortunately, the results seem to vary across taxa in terms of captive animals having higher, lower, or equivalent microbiome diversity relative to their wild counterparts. Here, we focus on the black rhinoceros as captive animals suffer from a number of potentially dietary related health effects. We compared gut microbiomes of wild and captive black rhinos to test for differences in taxonomic diversity (alpha and beta) and in functional diversity of the microbiome. We incorporated a more powerful metagenomic shotgun sequencing approach rather than a targeted amplification of the 16S gene for taxonomic assignment of the microbiome. Our results showed no significant differences in the alpha diversity levels between wild and captive black rhinos, but significant differences in beta diversity. We found that bacterial taxa traditionally associated with ruminant guts of domesticated animals had higher relative abundances in captive rhinos. Our metagenomic sequencing results suggest that unknown gut microbes of wild rhinos are being replaced by those found in conventional human-domesticated livestock. Wild rhinos have significantly different functional bacterial communities compared to their captive counterparts. Functional profiling results showed greater abundance of glycolysis and amino acid synthesis pathways in captive rhino microbiomes, representing an animal receiving sub-optimal nutrition with a readily available source of glucose but possibly an imbalance of necessary macro and micronutrients. Given the differences observed between wild and captive rhino gut microbiomes, we make a number of recommendations for potentially modifying captive gut microbiome to better reflect their wild counterparts and thereby hopefully improve overall rhino health in captivity.
A hydrofluoric acid-free method to dissolve and quantify silica nanoparticles in aqueous and solid matrices
Authors: Bossert David , Urban Dominic A. , Maceroni Mattia , Ackermann-Hirschi Liliane , Haeni Laetitia , Yajan Phattadon , Spuch-Calvar Miguel , Rothen-Rutishauser Barbara , Rodriguez-Lorenzo Laura , Petri-Fink Alke , Schwab Fabienne 
Published: May 2019

AbstractAs the commercial use of synthetic amorphous silica nanomaterials (SiO2-NPs) increases, their effects on the environment and human health have still not been explored in detail. An often-insurmountable obstacle for SiO2-NP fate and hazard research is the challenging analytics of solid particulate silica species, which involves toxic and corrosive hydrofluoric acid (HF). We therefore developed and validated a set of simple hydrofluoric acid-free sample preparation methods for the quantification of amorphous SiO2 micro- and nanoparticles. To circumvent HF, we dissolved the SiO2-NPs by base-catalyzed hydrolysis at room temperature or under microwave irradiation using potassium hydroxide, replacing the stabilizing fluoride ions with OH−, and exploiting the stability of the orthosilicic acid monomer under a strongly basic pH. Inductively coupled plasma – optical emission spectroscopy (ICP-OES) or a colorimetric assay served to quantify silicon. The lowest KOH: SiO2 molar ratio to effectively dissolve and quantify SiO2-NPs was 1.2 for colloidal Stöber SiO2-NPs at a pH >12. Fumed SiO2-NPs (Aerosil®) or food grade SiO2 (E551) containing SiO2-NPs were degradable at higher KOH: SiO2 ratios >8000. Thus, hydrofluoric acid-free SiO2-NP digestion protocols based on KOH present an effective (recoveries of >84%), less hazardous, and easy to implement alternative to current methods.