bluuebunny/crossref_metadata_2025_split huggingface dataset:
Video-rate multi-color structured illumination microscopy with simultaneous real-time reconstruction
Authors: Markwirth Andreas , Lachetta Mario , Mönkemöller Viola , Heintzmann Rainer , Hübner Wolfgang , Huser Thomas , Müller Marcel 
Published: September 2019

AbstractSuper-resolved structured illumination microscopy (SR-SIM) is among the fastest fluorescence microscopy techniques capable of surpassing the optical diffraction limit. Current custom-build instruments are able to deliver two-fold resolution enhancement with high acquisition speed. SR-SIM is usually a two-step process, with raw-data acquisition and subsequent, time-consuming post-processing for image reconstruction. In contrast, wide-field and (multi-spot) confocal techniques produce high-resolution images instantly. Such immediacy is also possible with SR-SIM, by tight integration of a video-rate capable SIM with fast reconstruction software. Here we present instant SR-SIM by VIGOR (Video-rate Immediate GPU-accelerated Open-Source Reconstruction). We demonstrate multi-color SR-SIM at video frame-rates, with less than 250 ms delay between measurement and reconstructed image display. This is achieved by modifying and extending high-speed SR-SIM image acquisition with a new, GPU-enhanced, network-enabled image-reconstruction software. We demonstrate high-speed surveying of biological samples in multiple colors and live imaging of moving mitochondria as an example of intracellular dynamics.
Ran pathway-independent regulation of mitotic Golgi disassembly by Importin-α
Authors: Chang Chih-Chia , Chen Ching-Jou , Grauffel Cédric , Pien Yu-Chung , Lim Carmay , Tsai Su-Yi , Hsia Kuo-Chiang 
Published: September 2019

AbstractTo facilitate proper mitotic cell partitioning, the Golgi disassembles by suppressing vesicle fusion. However, the underlying mechanism has not been characterized previously. Here, we report a Ran pathway-independent attenuation mechanism that allows Importin-α (a nuclear transport factor) to suppress the vesicle fusion mediated by p115 (a vesicular tethering factor) and is required for mitotic Golgi disassembly. We demonstrate that Importin-α directly competes with p115 for interaction with the Golgi protein GM130. This interaction, promoted by a phosphate moiety on GM130, is independent of Importin-β and Ran. A GM130 K34A mutant, in which the Importin-α-GM130 interaction is specifically disrupted, exhibited abundant Golgi puncta during metaphase. Importantly, a mutant showing enhanced p115-GM130 interaction presented proliferative defects and G2/M arrest, demonstrating that Importin-α-GM130 binding modulates the Golgi disassembly that governs mitotic progression. Our findings illuminate that the Ran and kinase-phosphatase pathways regulate multiple aspects of mitosis coordinated by Importin-α (e.g. spindle assembly, Golgi disassembly).
Spin current generation in organic antiferromagnets
Authors: Naka Makoto , Hayami Satoru , Kusunose Hiroaki , Yanagi Yuki , Motome Yukitoshi , Seo Hitoshi 
Published: September 2019

AbstractSpin current–a flow of electron spins without a charge current–is an ideal information carrier free from Joule heating for electronic devices. The celebrated spin Hall effect, which arises from the relativistic spin-orbit coupling, enables us to generate and detect spin currents in inorganic materials and semiconductors, taking advantage of their constituent heavy atoms. In contrast, organic materials consisting of molecules with light elements have been believed to be unsuited for spin current generation. Here we show that a class of organic antiferromagnets with checker-plate type molecular arrangements can serve as a spin current generator by applying a thermal gradient or an electric field, even with vanishing spin-orbit coupling. Our findings provide another route to create a spin current distinct from the conventional spin Hall effect and open a new field of spintronics based on organic magnets having advantages of small spin scattering and long lifetime.
Structure of Csx1-cOA4 complex reveals the basis of RNA decay in Type III-B CRISPR-Cas
Authors: Molina Rafael , Stella Stefano , Feng Mingxia , Sofos Nicholas , Jauniskis Vykintas , Pozdnyakova Irina , López-Méndez Blanca , She Qunxin , Montoya Guillermo 
Published: September 2019

AbstractType III CRISPR-Cas multisubunit complexes cleave ssRNA and ssDNA. These activities promote the generation of cyclic oligoadenylate (cOA), which activates associated CRISPR-Cas RNases from the Csm/Csx families, triggering a massive RNA decay to provide immunity from genetic invaders. Here we present the structure of Sulfolobus islandicus (Sis) Csx1-cOA4 complex revealing the allosteric activation of its RNase activity. SisCsx1 is a hexamer built by a trimer of dimers. Each dimer forms a cOA4 binding site and a ssRNA catalytic pocket. cOA4 undergoes a conformational change upon binding in the second messenger binding site activating ssRNA degradation in the catalytic pockets. Activation is transmitted in an allosteric manner through an intermediate HTH domain, which joins the cOA4 and catalytic sites. The RNase functions in a sequential cooperative fashion, hydrolyzing phosphodiester bonds in 5′-C-C-3′. The degradation of cOA4 by Ring nucleases deactivates SisCsx1, suggesting that this enzyme could be employed in biotechnological applications.
Dual-phase nanostructuring of layered metal oxides for high-performance aqueous rechargeable potassium ion microbatteries
Authors: Li Ying-Qi , Shi Hang , Wang Sheng-Bo , Zhou Yi-Tong , Wen Zi , Lang Xing-You , Jiang Qing 
Published: September 2019

AbstractAqueous rechargeable microbatteries are promising on-chip micropower sources for a wide variety of miniaturized electronics. However, their development is plagued by state-of-the-art electrode materials due to low capacity and poor rate capability. Here we show that layered potassium vanadium oxides, KxV2O5·nH2O, have an amorphous/crystalline dual-phase nanostructure to show genuine potential as high-performance anode materials of aqueous rechargeable potassium-ion microbatteries. The dual-phase nanostructured KxV2O5·nH2O keeps large interlayer spacing while removing secondary-bound interlayer water to create sufficient channels and accommodation sites for hydrated potassium cations. This unique nanostructure facilitates accessibility/transport of guest hydrated potassium cations to significantly improve practical capacity and rate performance of the constituent KxV2O5·nH2O. The potassium-ion microbatteries with KxV2O5·nH2O anode and KxMnO2·nH2O cathode constructed on interdigital-patterned nanoporous metal current microcollectors exhibit ultrahigh energy density of 103 mWh cm−3 at electrical power comparable to carbon-based microsupercapacitors.
Time elapsed between Zika and dengue virus infections affects antibody and T cell responses
Authors: Pérez-Guzmán Erick X. , Pantoja Petraleigh , Serrano-Collazo Crisanta , Hassert Mariah A. , Ortiz-Rosa Alexandra , Rodríguez Idia V. , Giavedoni Luis , Hodara Vida , Parodi Laura , Cruz Lorna , Arana Teresa , White Laura J. , Martínez Melween I. , Weiskopf Daniela , Brien James D. , de Silva Aravinda , Pinto Amelia K. , Sariol Carlos A. 
Published: September 2019

AbstractZika virus (ZIKV) and dengue virus (DENV) are co-endemic in many parts of the world, but the impact of ZIKV infection on subsequent DENV infection is not well understood. Here we show in rhesus macaques that the time elapsed after ZIKV infection affects the immune response to DENV infection. We show that previous ZIKV exposure increases the magnitude of the antibody and T cell responses against DENV. The time interval between ZIKV and subsequent DENV infection further affects the immune response. A mid-convalescent period of 10 months after ZIKV infection results in higher and more durable antibody and T cell responses to DENV infection than a short period of 2 months. In contrast, previous ZIKV infection does not affect DENV viremia or pro-inflammatory status. Collectively, we find no evidence of a detrimental effect of ZIKV immunity in a subsequent DENV infection. This supports the implementation of ZIKV vaccines that could also boost immunity against future DENV epidemics.
Nanomechanics and co-transcriptional folding of Spinach and Mango
Authors: Mitra Jaba , Ha Taekjip 
Published: September 2019

AbstractRecent advances in fluorogen-binding “light-up” RNA aptamers have enabled protein-free detection of RNA in cells. Detailed biophysical characterization of folding of G-Quadruplex (GQ)-based light-up aptamers such as Spinach, Mango and Corn is still lacking despite the potential implications on their folding and function. In this work we employ single-molecule fluorescence-force spectroscopy to examine mechanical responses of Spinach2, iMangoIII and MangoIV. Spinach2 unfolds in four discrete steps as force is increased to 7 pN and refolds in reciprocal steps upon force relaxation. In contrast, GQ-core unfolding in iMangoIII and MangoIV occurs in one discrete step at forces >10 pN and refolding occurred at lower forces showing hysteresis. Co-transcriptional folding using superhelicases shows reduced misfolding propensity and allowed a folding pathway different from refolding. Under physiologically relevant pico-Newton levels of force, these aptamers may unfold in vivo and subsequently misfold. Understanding of the dynamics of RNA aptamers will aid engineering of improved fluorogenic modules for cellular applications.
Regulation of the endosomal SNX27-retromer by OTULIN
Authors: Stangl Aurelia , Elliott Paul R. , Pinto-Fernandez Adan , Bonham Sarah , Harrison Luke , Schaub Annalisa , Kutzner Kerstin , Keusekotten Kirstin , Pfluger Paul T. , El Oualid Farid , Kessler Benedikt M. , Komander David , Krappmann Daniel 
Published: September 2019

AbstractOTULIN (OTU Deubiquitinase With Linear Linkage Specificity) specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Here we report on the mass spectrometric identification of the OTULIN interactor SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ-binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27. By solving the structure of the OTU domain in complex with the PDZ domain, we demonstrate that a second interface contributes to the selective, high affinity interaction of OTULIN and SNX27. SNX27 does not affect OTULIN catalytic activity, OTULIN-LUBAC binding or Met1-linked ubiquitin chain homeostasis. However, via association, OTULIN antagonizes SNX27-dependent cargo loading, binding of SNX27 to the VPS26A-retromer subunit and endosome-to-plasma membrane trafficking. Thus, we define an additional, non-catalytic function of OTULIN in the regulation of SNX27-retromer assembly and recycling to the cell surface.
Open data on industry payments to healthcare providers reveal potential hidden costs to the public
Authors: Mejia Jorge , Mejia Amanda , Pestilli Franco 
Published: September 2019

AbstractHealthcare industry players make payments to medical providers for non-research expenses. While these payments may pose conflicts of interest, their relationship with overall healthcare costs remains largely unknown. In this study, we linked Open Payments data on providers’ industry payments with Medicare data on healthcare costs. We investigated 374,766 providers’ industry payments and healthcare costs. We demonstrate that providers receiving higher amounts of industry payments tend to bill higher drug and medical costs. Specifically, we find that a 10% increase in industry payments is associated with 1.3% higher medical and 1.8% higher drug costs. For a typical provider, for example, a 10% or $25 increase in annual industry payments would be associated with approximately $1,100 higher medical costs and $100 higher drug costs. Furthermore, the association between payments and healthcare costs varies markedly across states and correlates with political leaning, being stronger in more conservative states.
Agricultural land-uses consistently exacerbate infectious disease risks in Southeast Asia
Authors: Shah Hiral A. , Huxley Paul , Elmes Jocelyn , Murray Kris A. 
Published: September 2019

AbstractAgriculture has been implicated as a potential driver of human infectious diseases. However, the generality of disease-agriculture relationships has not been systematically assessed, hindering efforts to incorporate human health considerations into land-use and development policies. Here we perform a meta-analysis with 34 eligible studies and show that people who live or work in agricultural land in Southeast Asia are on average 1.74 (CI 1.47–2.07) times as likely to be infected with a pathogen than those unexposed. Effect sizes are greatest for exposure to oil palm, rubber, and non-poultry based livestock farming and for hookworm (OR 2.42, CI 1.56–3.75), malaria (OR 2.00, CI 1.46–2.73), scrub typhus (OR 2.37, CI 1.41–3.96) and spotted fever group diseases (OR 3.91, CI 2.61–5.85). In contrast, no change in infection risk is detected for faecal-oral route diseases. Although responses vary by land-use and disease types, results suggest that agricultural land-uses exacerbate many infectious diseases in Southeast Asia.
ImmGen report: sexual dimorphism in the immune system transcriptome
Authors: Gal-Oz Shani Talia , Maier Barbara , Yoshida Hideyuki , Seddu Kumba , Elbaz Nitzan , Czysz Charles , Zuk Or , Stranger Barbara E. , Ner-Gaon Hadas , Shay Tal 
Published: September 2019

AbstractSexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female immune cells except in macrophages from three different tissues. Accordingly, very few genomic regions display differences in accessibility between sexes. Transcriptional sexual dimorphism in macrophages is mediated by genes of innate immune pathways, and increases after interferon stimulation. Thus, the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion.
Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes
Authors: van Meer Berend J. , Krotenberg Ana , Sala Luca , Davis Richard P. , Eschenhagen Thomas , Denning Chris , Tertoolen Leon G. J. , Mummery Christine L. 
Published: September 2019

AbstractCardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are increasingly recognized as valuable for determining the effects of drugs on ion channels but they do not always accurately predict contractile responses of the human heart. This is in part attributable to their immaturity but the sensitivity of measurement tools may also be limiting. Measuring action potential, calcium flux or contraction individually misses critical information that is captured when interrogating the complete excitation-contraction coupling cascade simultaneously. Here, we develop an hypothesis-based statistical algorithm that identifies mechanisms of action. We design and build a high-speed optical system to measure action potential, cytosolic calcium and contraction simultaneously using fluorescent sensors. These measurements are automatically processed, quantified and then assessed by the algorithm. Multiplexing these three critical physical features of hiPSC-CMs allows identification of all major drug classes affecting contractility with detection sensitivities higher than individual measurement of action potential, cytosolic calcium or contraction.
Host transcriptome and microbiome interaction modulates physiology of full-sibs broilers with divergent feed conversion ratio
Authors: Shah Tejas M. , Patel Jignasha G. , Gohil Tejas P. , Blake Damer P. , Joshi Chaitanya G. 
Published: September 2019

AbstractEfficient livestock production relies on effective conversion of feed into body weight gain (BWG). High levels of feed conversion are especially important in production of broiler chickens, birds reared for meat, where economic margins are tight. Traits associated with improved broiler growth and feed efficiency have been subjected to intense genetic selection, but measures such as feed conversion ratio (FCR) remain variable, even between full siblings (sibs). Non-genetic factors such as the composition and function of microbial populations within different enteric compartments have been recognized to influence FCR, although the extent of interplay between hosts and their microbiomes is unclear. To examine host–microbiome interactions we investigated variation in the composition and functions of host intestinal-hepatic transcriptomes and the intestinal microbiota of full-sib broilers with divergent FCR. Progeny from 300 broiler families were assessed for divergent FCR set against shared genetic backgrounds and exposure to the same environmental factors. The seven most divergent full-sib pairs were chosen for analysis, exhibiting marked variation in transcription of genes as well as gut microbial diversity. Examination of enteric microbiota in low FCR sibs revealed variation in microbial community structure and function with no difference in feed intake compared to high FCR sibs. Gene transcription in low and high FCR sibs was significantly associated with the abundance of specific microbial taxa. Highly intertwined interactions between host transcriptomes and enteric microbiota are likely to modulate complex traits like FCR and may be amenable to selective modification with relevance to improving intestinal homeostasis and health.
Analysis of mutations leading to para-aminosalicylic acid resistance in Mycobacterium tuberculosis
Authors: Pandey Bharati , Grover Sonam , Kaur Jagdeep , Grover Abhinav 
Published: September 2019

AbstractThymidylate synthase A (ThyA) is the key enzyme involved in the folate pathway in Mycobacterium tuberculosis. Mutation of key residues of ThyA enzyme which are involved in interaction with substrate 2′-deoxyuridine-5′-monophosphate (dUMP), cofactor 5,10-methylenetetrahydrofolate (MTHF), and catalytic site have caused para-aminosalicylic acid (PAS) resistance in TB patients. Focusing on R127L, L143P, C146R, L172P, A182P, and V261G mutations, including wild-type, we performed long molecular dynamics (MD) simulations in explicit solvent to investigate the molecular principles underlying PAS resistance due to missense mutations. We found that these mutations lead to (i) extensive changes in the dUMP and MTHF binding sites, (ii) weak interaction of ThyA enzyme with dUMP and MTHF by inducing conformational changes in the structure, (iii) loss of the hydrogen bond and other atomic interactions and (iv) enhanced movement of protein atoms indicated by principal component analysis (PCA). In this study, MD simulations framework has provided considerable insight into mutation induced conformational changes in the ThyA enzyme of Mycobacterium.
Understanding pseudo-albinism in sole (Solea senegalensis): a transcriptomics and metagenomics approach
Authors: Pinto Patricia I. S. , Guerreiro Cláudia C. , Costa Rita A. , Martinez-Blanch Juan F. , Carballo Carlos , Codoñer Francisco M. , Manchado Manuel , Power Deborah M. 
Published: September 2019

AbstractPseudo-albinism is a pigmentation disorder observed in flatfish aquaculture with a complex, multi-factor aetiology. We tested the hypothesis that pigmentation abnormalities are an overt signal of more generalised modifications in tissue structure and function, using as a model the Senegalese sole and two important innate immune barriers, the skin and intestine, and their microbiomes. Stereological analyses in pseudo-albino sole revealed a significantly increased mucous cell number in skin (P < 0.001) and a significantly thicker muscle layer and lamina propria in gut (P < 0.001). RNA-seq transcriptome analysis of the skin and gut identified 573 differentially expressed transcripts (DETs, FDR < 0.05) between pseudo-albino and pigmented soles (one pool/tissue from 4 individuals/phenotype). DETs were mainly linked to pigment production, skin structure and regeneration and smooth muscle contraction. The microbiome (16 S rRNA analysis) was highly diverse in pigmented and pseudo-albino skin but in gut had low complexity and diverged between the two pigmentation phenotypes. Quantitative PCR revealed significantly lower loads of Mycoplasma (P < 0.05) and Vibrio bacteria (P < 0.01) in pseudo-albino compared to the control. The study revealed that pseudo-albinism in addition to pigmentation changes was associated with generalised changes in the skin and gut structure and a modification in the gut microbiome.
Cigarette Smoke Exposure Induces Retrograde Trafficking of CFTR to the Endoplasmic Reticulum
Authors: Marklew Abigail J. , Patel Waseema , Moore Patrick J. , Tan Chong D. , Smith Amanda J. , Sassano M. Flori , Gray Michael A. , Tarran Robert 
Published: September 2019

AbstractChronic obstructive pulmonary disease (COPD), which is most commonly caused by cigarette smoke (CS) exposure, is the third leading cause of death worldwide. The cystic fibrosis transmembrane conductance regulator (CFTR) is an apical membrane anion channel that is widely expressed in epithelia throughout the body. In the airways, CFTR plays an important role in fluid homeostasis and helps flush mucus and inhaled pathogens/toxicants out of the lung. Inhibition of CFTR leads to mucus stasis and severe airway disease. CS exposure also inhibits CFTR, leading to the decreased anion secretion/hydration seen in COPD patients. However, the underlying mechanism is poorly understood. Here, we report that CS causes CFTR to be internalized in a clathrin/dynamin-dependent fashion. This internalization is followed by retrograde trafficking of CFTR to the endoplasmic reticulum. Although this internalization pathway has been described for bacterial toxins and cargo machinery, it has never been reported for mammalian ion channels. Furthermore, the rapid internalization of CFTR is dependent on CFTR dephosphorylation by calcineurin, a protein phosphatase that is upregulated by CS. These results provide new insights into the mechanism of CFTR internalization, and may help in the development of new therapies for CFTR correction and lung rehydration in patients with debilitating airway diseases such as COPD.