bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre- and peri-implantation Zika virus infection impairs fetal development by targeting trophectoderm cells
Authors: Tan Lei , Lacko Lauretta A. , Zhou Ting , Tomoiaga Delia , Hurtado Romulo , Zhang Tuo , Sevilla Ana , Zhong Aaron , Mason Christopher E , Noggle Scott , Evans Todd , Stuhlmann Heidi , Schwartz Robert E. , Chen Shuibing 
Published: September 2019

AbstractZika virus (ZIKV) infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the underlying mechanisms remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, at pre- and peri-implantation, because most current ZIKV pregnancy studies have focused on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be infected with ZIKV, and propagate virus causing neural progenitor cell death. These findings are corroborated by the dose-dependent nature of ZIKV susceptibility of hESC-derived trophectoderm cells. Single blastocyst RNA-seq reveals key transcriptional changes upon ZIKV infection, including nervous system development, prior to commitment to the neural lineage. The pregnancy rate of mice is >50% lower in pre-implantation infection than infection at E4.5, demonstrating that pre-implantation ZIKV infection leads to miscarriage. Cumulatively, these data elucidate a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.
Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes
Authors: Evangelopoulos Dimitrios , Prosser Gareth A. , Rodgers Angela , Dagg Belinda M. , Khatri Bhagwati , Ho Mei Mei , Gutierrez Maximiliano G. , Cortes Teresa , de Carvalho Luiz Pedro S. 
Published: September 2019

AbstractDrug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for six decades without significant appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We therefore investigated why Mycobacterium tuberculosis fails to become resistant to D-cycloserine. To address this question, we employed a combination of bacterial genetics, genomics, biochemistry and fitness analysis in vitro, in macrophages and in mice. Altogether, our results suggest that the ultra-low rate of emergence of D-cycloserine resistance mutations is the dominant biological factor delaying the appearance of clinical resistance to this antibiotic. Furthermore, we also identified potential compensatory mechanisms able to minimize the severe fitness costs of primary D-cycloserine resistance conferring mutations.
Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites
Authors: Holdgaard Søs Grønbæk , Cianfanelli Valentina , Pupo Emanuela , Lambrughi Matteo , Lubas Michal , Nielsen Julie C. , Eibes Susana , Maiani Emiliano , Harder Lea M. , Wesch Nicole , Foged Mads Møller , Maeda Kenji , Nazio Francesca , de la Ballina Laura R. , Dötsch Volker , Brech Andreas , Frankel Lisa B. , Jäättelä Marja , Locatelli Franco , Barisic Marin , Andersen Jens S. , Bekker-Jensen Simon , Lund Anders H. , Rogov Vladimir V. , Papaleo Elena , Lanzetti Letizia , De Zio Daniela , Cecconi Francesco 
Published: September 2019

AbstractThe centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity.
Structure of the thermo-sensitive TRP channel TRP1 from the alga Chlamydomonas reinhardtii
Authors: McGoldrick Luke L. , Singh Appu K. , Demirkhanyan Lusine , Lin Ting-Yu , Casner Ryan G. , Zakharian Eleonora , Sobolevsky Alexander I. 
Published: September 2019

AbstractAlgae produce the largest amount of oxygen on earth and are invaluable for human nutrition and biomedicine, as well as for the chemical industry, energy production and agriculture. The mechanisms by which algae can detect and respond to changes in their environments can rely on membrane receptors, including TRP ion channels. Here we present a 3.5-Å resolution cryo-EM structure of the transient receptor potential (TRP) channel crTRP1 from the alga Chlamydomonas reinhardtii that opens in response to increased temperature and is positively regulated by the membrane lipid PIP2. The structure of crTRP1 significantly deviates from the structures of other TRP channels and has a unique 2-fold symmetrical rose-shape architecture with elbow domains and ankyrin repeat domains submerged and dipping into the membrane, respectively. Our study provides a structure of a TRP channel from a micro-organism and a structural framework for better understanding algae biology and TRP channel evolution.
UPF1/SMG7-dependent microRNA-mediated gene regulation
Authors: Park Jungyun , Seo Jwa-Won , Ahn Narae , Park Seokju , Hwang Jungwook , Nam Jin-Wu 
Published: September 2019

AbstractThe stability and quality of metazoan mRNAs are under microRNA (miRNA)-mediated and nonsense-mediated control. Although UPF1, a core mediator of nonsense-mediated mRNA decay (NMD), mediates the decay of target mRNA in a 3′UTR-length-dependent manner, the detailed mechanism remains unclear. Here, we suggest that 3′UTR-length-dependent mRNA decay is not mediated by nonsense mRNAs but rather by miRNAs that downregulate target mRNAs via Ago-associated UPF1/SMG7. Global analyses of mRNAs in response to UPF1 RNA interference in miRNA-deficient cells reveal that 3′UTR-length-dependent mRNA decay by UPF1 requires canonical miRNA targeting. The destabilization of miRNA targets is accomplished by the combination of Ago2 and UPF1/SMG7, which may recruit the CCR4-NOT deadenylase complex. Indeed, loss of the SMG7-deadenylase complex interaction increases the levels of transcripts regulated by UPF1-SMG7. This UPF1/SMG7-dependent miRNA-mediated mRNA decay pathway may enable miRNA targeting to become more predictable and expand the miRNA-mRNA regulatory network.
A highly dynamic F-actin network regulates transport and recycling of micronemes in Toxoplasma gondii vacuoles
Authors: Periz Javier , Del Rosario Mario , McStea Alexandra , Gras Simon , Loney Colin , Wang Lin , Martin-Fernandez Marisa L. , Meissner Markus 
Published: September 2019

AbstractThe obligate intracellular parasite Toxoplasma gondii replicates in an unusual process, described as internal budding. Multiple dausghter parasites are formed sequentially within a single mother cell, requiring replication and distribution of essential organelles such as micronemes. These organelles are thought to be formed de novo in the developing daughter cells. Using dual labelling of a microneme protein MIC2 and super-resolution microscopy, we show that micronemes are recycled from the mother to the forming daughter parasites using a highly dynamic F-actin network. While this recycling pathway is F-actin dependent, de novo synthesis of micronemes appears to be F-actin independent. The F-actin network connects individual parasites, supports long, multidirectional vesicular transport, and regulates transport, density and localisation of micronemal vesicles. The residual body acts as a storage and sorting station for these organelles. Our data describe an F-actin dependent mechanism in apicomplexans for transport and recycling of maternal organelles during intracellular development.
Materials tactile logic via innervated soft thermochromic elastomers
Authors: Jin Yang , Lin Yiliang , Kiani Abolfazl , Joshipura Ishan D. , Ge Mingqiao , Dickey Michael D. 
Published: September 2019

AbstractConventional machines rely on rigid, centralized electronic components to make decisions, which limits complexity and scaling. Here, we show that decision making can be realized on the material-level without relying on semiconductor-based logic. Inspired by the distributed decision making that exists in the arms of an octopus, we present a completely soft, stretchable silicone composite doped with thermochromic pigments and innervated with liquid metal. The ability to deform the liquid metal couples geometric changes to Joule heating, thus enabling tunable thermo-mechanochromic sensing of touch and strain. In more complex circuits, deformation of the metal can redistribute electrical energy to distal portions of the network in a way that converts analog tactile ‘inputs’ into digital colorimetric ‘outputs’. Using the material itself as the active player in the decision making process offers possibilities for creating entirely soft devices that respond locally to environmental interactions or act as embedded sensors for feedback loops.
The paleoclimatic footprint in the soil carbon stock of the Tibetan permafrost region
Authors: Ding Jinzhi , Wang Tao , Piao Shilong , Smith Pete , Zhang Ganlin , Yan Zhengjie , Ren Shuai , Liu Dan , Wang Shiping , Chen Shengyun , Dai Fuqiang , He Jinsheng , Li Yingnian , Liu Yongwen , Mao Jiafu , Arain Altaf , Tian Hanqin , Shi Xiaoying , Yang Yuanhe , Zeng Ning , Zhao Lin 
Published: September 2019

AbstractTibetan permafrost largely formed during the late Pleistocene glacial period and shrank in the Holocene Thermal Maximum period. Quantifying the impacts of paleoclimatic extremes on soil carbon stock can shed light on the vulnerability of permafrost carbon in the future. Here, we synthesize data from 1114 sites across the Tibetan permafrost region to report that paleoclimate is more important than modern climate in shaping current permafrost carbon distribution, and its importance increases with soil depth, mainly through forming the soilʼs physiochemical properties. We derive a new estimate of modern soil carbon stock to 3 m depth by including the paleoclimate effects, and find that the stock ($${\mathrm{36}}{\mathrm{.6}}_{{\mathrm{ - 2}}{\mathrm{.4}}}^{{\mathrm{ + 2}}.3}$$
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PgC) is triple that predicted by ecosystem models (11.5 ± 4.2 s.e.m PgC), which use pre-industrial climate to initialize the soil carbon pool. The discrepancy highlights the urgent need to incorporate paleoclimate information into model initialization for simulating permafrost soil carbon stocks.
Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes
Authors: Leslie Patrick L. , Chao Yvonne L. , Tsai Yi-Hsuan , Ghosh Subrata K. , Porrello Alessandro , Van Swearingen Amanda E. D. , Harrison Emily B. , Cooley Brian C. , Parker Joel S. , Carey Lisa A. , Pecot Chad V. 
Published: September 2019

AbstractLymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.
Label-free assessment of pre-implantation embryo quality by the Fluorescence Lifetime Imaging Microscopy (FLIM)-phasor approach
Authors: Ma Ning , Mochel Nabora Reyes de , Pham Paula Duyen , Yoo Tae Yeon , Cho Ken W. Y. , Digman Michelle A. 
Published: September 2019

AbstractDevelopment of quantitative, safe and rapid techniques for assessing embryo quality provides significant advances in Assisted Reproductive Technologies (ART). Instead of assessing the embryo quality by the standard morphologic evaluation, we apply the phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) method to capture endogenous fluorescent biomarkers of pre-implantation embryos as a non-morphological caliber for embryo quality. Here, we identify, under hypoxic and non-hypoxic conditions, the unique spectroscopic trajectories at different stages of mouse pre-implantation development, which is referred to as the developmental, or “D-trajectory”, that consists of fluorescence lifetime from different stages of mouse pre-implantation embryos. The D-trajectory correlates with intrinsic fluorescent species from a distinctive energy metabolism and oxidized lipids, as seen with Third Harmonic Generation (THG) that changes over time. In addition, we have defined a non-morphological Embryo Viability Index (EVI) to distinguish pre-implantation embryo quality using the Distance Analysis (DA), a machine learning algorithm to process the fluorescence lifetime distribution patterns. We show, under our experimental conditions, that the phasor-FLIM approach provides a much-needed non-invasive quantitative technology for identifying healthy embryos at the early compaction stage with 86% accuracy. The DA and phasor-FLIM method may provide the opportunity to improve implantation success rates forin vitrofertilization clinics.
Spatial and Temporal Variability of Ambient Underwater Sound in the Baltic Sea
Authors: Mustonen Mirko , Klauson Aleksander , Andersson Mathias , Clorennec Dominique , Folegot Thomas , Koza Radomił , Pajala Jukka , Persson Leif , Tegowski Jarosław , Tougaard Jakob , Wahlberg Magnus , Sigray Peter 
Published: September 2019

AbstractDuring last decades, anthropogenic underwater sound and its chronic impact on marine species have been recognised as an environmental protection challenge. At the same time, studies on the spatial and temporal variability of ambient sound, and how it is affected by biotic, abiotic and anthropogenic factors are lacking. This paper presents analysis of a large-scale and long-term underwater sound monitoring in the Baltic Sea. Throughout the year 2014, sound was monitored in 36 Baltic Sea locations. Selected locations covered different natural conditions and ship traffic intensities. The 63 Hz, 125 Hz and 2 kHz one-third octave band sound pressure levels were calculated and analysed. The levels varied significantly from one monitoring location to another. The annual median sound pressure level of the quietest and the loudest location differed almost 50 dB in the 63 Hz one-third octave band. Largest difference in the monthly medians was 15 dB in 63 Hz one-third octave band. The same monitoring locations annual estimated probability density functions for two yearly periods show strong similarity. The data variability grows as the averaging time period is reduced. Maritime traffic elevates the ambient sound levels in many areas of the Baltic Sea during extensive time periods.
Artificial neural network analysis of the oxygen saturation signal enables accurate diagnostics of sleep apnea
Authors: Nikkonen Sami , Afara Isaac O. , Leppänen Timo , Töyräs Juha 
Published: September 2019

AbstractThe severity of obstructive sleep apnea (OSA) is classified using apnea-hypopnea index (AHI). Accurate determination of AHI currently requires manual analysis and complicated registration setup making it expensive and labor intensive. Partially for these reasons, OSA is a heavily underdiagnosed disease as only 7% of women and 18% of men suffering from OSA have diagnosis. To resolve these issues, we introduce an artificial neural network (ANN) that estimates AHI and oxygen desaturation index (ODI) using only the blood oxygen saturation signal (SpO2), recorded during ambulatory polygraphy, as an input. Therefore, hypopneas associated only with an arousal were not considered in this study. SpO2 signals from 1692 patients were used for training and 99 for validation. Two test sets were used consisting of 198 and 1959 patients. In the primary test set, the median absolute errors of ANN estimated AHI and ODI were 0.78 events/hour and 0.68 events/hour respectively. Based on the ANN estimated AHI and ODI, 90.9% and 94.4% of the test patients were classified into the correct OSA severity category. In conclusion, AHI and ODI can be reliably determined using neural network analysis of SpO2 signal. The developed method may enable a more affordable screening of OSA.
Deep-Learning-Based Segmentation of Small Extracellular Vesicles in Transmission Electron Microscopy Images
Authors: Gómez-de-Mariscal Estibaliz , Maška Martin , Kotrbová Anna , Pospíchalová Vendula , Matula Pavel , Muñoz-Barrutia Arrate 
Published: September 2019

AbstractSmall extracellular vesicles (sEVs) are cell-derived vesicles of nanoscale size (~30–200 nm) that function as conveyors of information between cells, reflecting the cell of their origin and its physiological condition in their content. Valuable information on the shape and even on the composition of individual sEVs can be recorded using transmission electron microscopy (TEM). Unfortunately, sample preparation for TEM image acquisition is a complex procedure, which often leads to noisy images and renders automatic quantification of sEVs an extremely difficult task. We present a completely deep-learning-based pipeline for the segmentation of sEVs in TEM images. Our method applies a residual convolutional neural network to obtain fine masks and use the Radon transform for splitting clustered sEVs. Using three manually annotated datasets that cover a natural variability typical for sEV studies, we show that the proposed method outperforms two different state-of-the-art approaches in terms of detection and segmentation performance. Furthermore, the diameter and roundness of the segmented vesicles are estimated with an error of less than 10%, which supports the high potential of our method in biological applications.
Mimicking in-vivo exposures to drug combinations in-vitro: anti-tuberculosis drugs in lung lesions and the hollow fiber model of infection
Authors: Kloprogge Frank , Hammond Robert , Kipper Karin , Gillespie Stephen H. , Della Pasqua Oscar 
Published: September 2019

AbstractHere, we evaluate protocol requirements to mimic therapeutically relevant drug concentrations at the site of infection (i.e. lung lesion) in an in-vitro hollow fibre model of infection using pulmonary tuberculosis as a paradigm. Steady-state pharmacokinetic profiles in plasma, lung tissue and lung lesion homogenate were simulated for isoniazid, rifampicin and pyrazinamide and moxifloxacin. An R-shiny User Interface was developed to support conversion of in-vivo pharmacokinetic CMAX, TMAX and T1/2 estimates into pump settings. A monotherapy protocol mimicking isoniazid in lung lesion homogenate (isoniazid CMAX = 1,200 ng/ml, TMAX = 2.2 hr and T1/2 = 4.7 hr), and two combination therapy protocols including drugs with similar (isoniazid and rifampicin (CMAX = 400 ng/ml)) and different half-lives (isoniazid and pyrazinamide (CMAX = 28,900 ng/ml and T1/2 = 8.0 hr)) were implemented in a hollow-fiber system. Drug levels in the perfusate were analysed using ultra-high-performance liquid chromatographic-tandem mass spectrometric detection. Steady state pharmacokinetic profiles measured in the hollow fiber model were similar to the predicted in-vivo steady-state lung lesion homogenate pharmacokinetic profiles. The presented approach offers the possibility to use pharmacological data to study the effect of target tissue exposure for drug combinations. Integration with pharmacokinetics modelling principles through a web interface will provide access to a wider community interested in the evaluation of efficacy of anti-tubercular drugs.
Differential brain mechanisms during reading human vs. machine translated fiction and news texts
Authors: Lin Fa-Hsuan , Liu Yun-Fei , Lee Hsin-Ju , Chang Claire H. C. , Jaaskelainen Iiro P. , Yeh Jyh-Neng , Kuo Wen-Jui 
Published: September 2019

AbstractFew neuroimaigng studies on reading comprehension have been conducted under natural reading settings. In this study, we showed texts presented in a natural way during functional MRI (fMRI) measurements to reveal brain areas sensitive to reading comprehension. Specifically, this paradigm independently manipulated two holistic features of article style: text genre and translation style, a qualitative index of how typical word choices and arrangements are made in daily use of the language. Specifically, articles from The New York Times (news) and Reader’s Digest (fiction) translated from English to Mandarin Chinese either by human experts or machine (Google Translate) were used to investigate the correlation of brain activity across participants during article reading. We found that bi-hemispheric visual cortex, precuneus, and occipito-parietal junction show significantly correlated hemodynamics across participants regardless of translation style and article genre. Compared to machine translation, reading human expert translation elicited more reliable fMRI signals across participants at precuneus, potentially because narrative representations and contents can be coherently presented over tens of seconds. We also found significantly stronger inter-subject correlated fMRI signals at temporal poles and fusiform gyri in fiction reading than in news reading. This may be attributed to more stable empathy processing across participants in fiction reading. The degree of stability of brain responses across subjects at extra-linguistic areas was found correlated with subjective rating on the text fluency. The functional connectivity between these areas was modulated by text genre and translation style. Taken together, our imaging results suggested stable and selective neural substrates associated with comprehending holistic features of written narratives.
Automated tracking and analysis of ant trajectories shows variation in forager exploration
Authors: Imirzian Natalie , Zhang Yizhe , Kurze Christoph , Loreto Raquel G. , Chen Danny Z. , Hughes David P. 
Published: September 2019

AbstractDetermining how ant colonies optimize foraging while mitigating pathogen and predator risks provides insight into how the ants have achieved ecological success. Ants must respond to changing resource conditions, but exploration comes at a cost of higher potential exposure to threats. Fungal infected cadavers surround the main foraging trails of the carpenter antCamponotus rufipes, offering a system to study how foragers behave given the persistent occurrence of disease threats. Studies on social insect foraging behavior typically require many hours of human labor due to the high density of individuals. To overcome this, we developed deep learning based computer vision algorithms to track foraging ants, frame-by-frame, from video footage shot under the natural conditions of a tropical forest floor at night. We found that most foragers walk in straight lines overlapping the same areas as other ants, but there is a subset of foragers with greater exploration. Consistency in walking behavior may protect most ants from infection, while foragers that explore unique portions of the trail may be more likely to encounter fungal spores implying a trade-off between resource discovery and risk avoidance.