bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function-driven single-cell genomics uncovers cellulose-degrading bacteria from the rare biosphere
Authors: Doud Devin F R , Bowers Robert M , Schulz Frederik , De Raad Markus , Deng Kai , Tarver Angela , Glasgow Evan , Vander Meulen Kirk , Fox Brian , Deutsch Sam , Yoshikuni Yasuo , Northen Trent , Hedlund Brian P , Singer Steven W , Ivanova Natalia , Woyke Tanja 
Published: November 2019

Abstract
Assigning a functional role to a microorganism has historically relied on cultivation of isolates or detection of environmental genome-based biomarkers using a posteriori knowledge of function. However, the emerging field of function-driven single-cell genomics aims to expand this paradigm by identifying and capturing individual microbes based on their in situ functions or traits. To identify and characterize yet uncultivated microbial taxa involved in cellulose degradation, we developed and benchmarked a function-driven single-cell screen, which we applied to a microbial community inhabiting the Great Boiling Spring (GBS) Geothermal Field, northwest Nevada. Our approach involved recruiting microbes to fluorescently labeled cellulose particles, and then isolating single microbe-bound particles via fluorescence-activated cell sorting. The microbial community profiles prior to sorting were determined via bulk sample 16S rRNA gene amplicon sequencing. The flow-sorted cellulose-bound microbes were subjected to whole genome amplification and shotgun sequencing, followed by phylogenetic placement. Next, putative cellulase genes were identified, expressed and tested for activity against derivatives of cellulose and xylose. Alongside typical cellulose degraders, including members of the Actinobacteria, Bacteroidetes, and Chloroflexi, we found divergent cellulases encoded in the genome of a recently described candidate phylum from the rare biosphere, Goldbacteria, and validated their cellulase activity. As this genome represents a species-level organism with novel and phylogenetically distinct cellulolytic activity, we propose the name Candidatus ‘Cellulosimonas argentiregionis’. We expect that this function-driven single-cell approach can be extended to a broad range of substrates, linking microbial taxonomy directly to in situ function.
NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
Authors: Fang Evandro F. , Hou Yujun , Lautrup Sofie , Jensen Martin Borch , Yang Beimeng , SenGupta Tanima , Caponio Domenica , Khezri Rojyar , Demarest Tyler G. , Aman Yahyah , Figueroa David , Morevati Marya , Lee Ho-Joon , Kato Hisaya , Kassahun Henok , Lee Jong-Hyuk , Filippelli Deborah , Okur Mustafa Nazir , Mangerich Aswin , Croteau Deborah L. , Maezawa Yoshiro , Lyssiotis Costas A. , Tao Jun , Yokote Koutaro , Rusten Tor Erik , Mattson Mark P. , Jasper Heinrich , Nilsen Hilde , Bohr Vilhelm A. 
Published: November 2019

AbstractMetabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.
Plasmon-enhanced stimulated Raman scattering microscopy with single-molecule detection sensitivity
Authors: Zong Cheng , Premasiri Ranjith , Lin Haonan , Huang Yimin , Zhang Chi , Yang Chen , Ren Bin , Ziegler Lawrence D. , Cheng Ji-Xin 
Published: November 2019

AbstractStimulated Raman scattering (SRS) microscopy allows for high-speed label-free chemical imaging of biomedical systems. The imaging sensitivity of SRS microscopy is limited to ~10 mM for endogenous biomolecules. Electronic pre-resonant SRS allows detection of sub-micromolar chromophores. However, label-free SRS detection of single biomolecules having extremely small Raman cross-sections (~10−30 cm2 sr−1) remains unreachable. Here, we demonstrate plasmon-enhanced stimulated Raman scattering (PESRS) microscopy with single-molecule detection sensitivity. Incorporating pico-Joule laser excitation, background subtraction, and a denoising algorithm, we obtain robust single-pixel SRS spectra exhibiting single-molecule events, verified by using two isotopologues of adenine and further confirmed by digital blinking and bleaching in the temporal domain. To demonstrate the capability of PESRS for biological applications, we utilize PESRS to map adenine released from bacteria due to starvation stress. PESRS microscopy holds the promise for ultrasensitive detection and rapid mapping of molecular events in chemical and biomedical systems.
The genome of a subterrestrial nematode reveals adaptations to heat
Authors: Weinstein Deborah J. , Allen Sarah E. , Lau Maggie C. Y. , Erasmus Mariana , Asalone Kathryn C. , Walters-Conte Kathryn , Deikus Gintaras , Sebra Robert , Borgonie Gaetan , van Heerden Esta , Onstott Tullis C. , Bracht John R. 
Published: November 2019

AbstractThe nematode Halicephalobus mephisto was originally discovered inhabiting a deep terrestrial aquifer 1.3 km underground. H. mephisto can thrive under conditions of abiotic stress including heat and minimal oxygen, where it feeds on a community of both chemolithotrophic and heterotrophic prokaryotes in an unusual ecosystem isolated from the surface biosphere. Here we report the comprehensive genome and transcriptome of this organism, identifying a signature of adaptation: an expanded repertoire of 70 kilodalton heat-shock proteins (Hsp70) and avrRpt2 induced gene 1 (AIG1) proteins. The expanded Hsp70 genes are transcriptionally induced upon growth under heat stress, and we find that positive selection is detectable in several members of this family. We further show that AIG1 may have been acquired by horizontal gene transfer (HGT) from a rhizobial fungus. Over one-third of the genes of H. mephisto are novel, highlighting the divergence of this nematode from other sequenced organisms. This work sheds light on the genomic basis of heat tolerance in a complete subterrestrial eukaryotic genome.
Phenotypic transitions enacted by simulated microgravity do not alter coherence in gene transcription profile
Authors: Po Agnese , Giuliani Alessandro , Masiello Maria Grazia , Cucina Alessandra , Catizone Angela , Ricci Giulia , Chiacchiarini Martina , Tafani Marco , Ferretti Elisabetta , Bizzarri Mariano 
Published: November 2019

AbstractCells in simulated microgravity undergo a reversible morphology switch, causing the appearance of two distinct phenotypes. Despite the dramatic splitting into an adherent-fusiform and a floating-spherical population, when looking at the gene-expression phase space, cell transition ends up in a largely invariant gene transcription profile characterized by only mild modifications in the respective Pearson’s correlation coefficients. Functional changes among the different phenotypes emerging in simulated microgravity using random positioning machine are adaptive modifications—as cells promptly recover their native phenotype when placed again into normal gravity—and do not alter the internal gene coherence. However, biophysical constraints are required to drive phenotypic commitment in an appropriate way, compatible with physiological requirements, given that absence of gravity foster cells to oscillate between different attractor states, thus preventing them to acquire a exclusive phenotype. This is a proof-of-concept of the adaptive properties of gene-expression networks supporting very different phenotypes by coordinated ‘profile preserving’ modifications.
A large-scale dataset for mitotic figure assessment on whole slide images of canine cutaneous mast cell tumor
Authors: Bertram Christof A. , Aubreville Marc , Marzahl Christian , Maier Andreas , Klopfleisch Robert 
Published: November 2019

AbstractWe introduce a novel, large-scale dataset for microscopy cell annotations. The dataset includes 32 whole slide images (WSI) of canine cutaneous mast cell tumors, selected to include both low grade cases as well as high grade cases. The slides have been completely annotated for mitotic figures and we provide secondary annotations for neoplastic mast cells, inflammatory granulocytes, and mitotic figure look-alikes. Additionally to a blinded two-expert manual annotation with consensus, we provide an algorithm-aided dataset, where potentially missed mitotic figures were detected by a deep neural network and subsequently assessed by two human experts. We included 262,481 annotations in total, out of which 44,880 represent mitotic figures. For algorithmic validation, we used a customized RetinaNet approach, followed by a cell classification network. We find F1-Scores of 0.786 and 0.820 for the manually labelled and the algorithm-aided dataset, respectively. The dataset provides, for the first time, WSIs completely annotated for mitotic figures and thus enables assessment of mitosis detection algorithms on complete WSIs as well as region of interest detection algorithms.
Full-length transcriptome sequencing from multiple tissues of duck, Anas platyrhynchos
Authors: Yin ZhongTao , Zhang Fan , Smith Jacqueline , Kuo Richard , Hou Zhuo-Cheng 
Published: November 2019

AbstractDuck (Anas platyrhynchos), one of the most economically important waterfowl, is an ideal model for studying the immune protection mechanism of birds. An incomplete duck reference genome and very limited availability of full-length cDNAs has hindered the identification of alternatively spliced transcripts and slowed down many basic studies in ducks. We applied PacBio Iso-Seq technologies to multiple tissues from duck for use in transcriptome sequencing. We obtained 199,993 full-length transcripts and comprehensively annotated these transcripts. 23,755 lncRNAs were predicted from all identified transcripts and 35,031 alternative splicing events, which divided into 5 models, were accurately predicted from 3,346 genes. Our data constitute a large increase in the known number of both lncRNA, and alternatively spliced transcripts of duck and plays an important role in improving current genome annotation. In addition, the data will be extremely useful for functional studies in other birds.
Diversified Floral Resource Plantings Support Bee Communities after Apple Bloom in Commercial Orchards
Authors: Heller Sarah , Joshi Neelendra K. , Leslie Timothy , Rajotte Edwin G. , Biddinger David J. 
Published: November 2019

AbstractNatural habitats, comprised of various flowering plant species, provide food and nesting resources for pollinator species and other beneficial arthropods. Loss of such habitats in agricultural regions and in other human-modified landscapes could be a factor in recent bee declines. Artificially established floral plantings may offset these losses. A multi-year, season-long field study was conducted to examine how wildflower plantings near commercial apple orchards influenced bee communities. We examined bee abundance, species richness, diversity, and species assemblages in both the floral plantings and adjoining apple orchards. We also examined bee community subsets, such as known tree fruit pollinators, rare pollinator species, and bees collected during apple bloom. During this study, a total of 138 species of bees were collected, which included 100 species in the floral plantings and 116 species in the apple orchards. Abundance of rare bee species was not significantly different between apple orchards and the floral plantings. During apple bloom, the known tree fruit pollinators were more frequently captured in the orchards than the floral plantings. However, after apple bloom, the abundance of known tree fruit pollinating bees increased significantly in the floral plantings, indicating potential for floral plantings to provide additional food and nesting resources when apple flowers are not available.
Two Quenchers Formed During Photodamage of Phostosystem II and The Role of One Quencher in Preemptive Photoprotection
Authors: Zavafer Alonso , Iermak Ievgeniia , Cheah Mun Hon , Chow Wah Soon 
Published: November 2019

AbstractThe quenching of chlorophyll fluorescence caused by photodamage of Photosystem II (qI) is a well recognized phenomenon, where the nature and physiological role of which are still debatable. Paradoxically, photodamage to the reaction centre of Photosystem II is supposed to be alleviated by excitation quenching mechanisms which manifest as fluorescence quenchers. Here we investigated the time course of PSII photodamage in vivo and in vitro and that of picosecond time-resolved chlorophyll fluorescence (quencher formation). Two long-lived fluorescence quenching processes during photodamage were observed and were formed at different speeds. The slow-developing quenching process exhibited a time course similar to that of the accumulation of photodamaged PSII, while the fast-developing process took place faster than the light-induced PSII damage. We attribute the slow process to the accumulation of photodamaged PSII and the fast process to an independent quenching mechanism that precedes PSII photodamage and that alleviates the inactivation of the PSII reaction centre.
Impact of Sex on Office White Coat Effect Tail: Investigating Two Italian Residential Cohorts
Authors: Humbert Xavier , Fedrizzi Sophie , Alexandre Joachim , Menotti Alessandro , Manrique Alain , Laurenzi Martino , Touzé Emmanuel , Puddu Paolo E. 
Published: November 2019

AbstractTo assess the impact of sex on office white-coat effect tail (OWCET), the waning of systolic blood pressure (SBP) after its waxing during office visit, on the incidence of long-term major fatal and non-fatal events in two Italian residential cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. There were 3565 persons (92 with missing data, 44% men, 54 ± 11 years) included in the Gubbio and 1712 men (49 ± 5 years) in the IRA studies. OWCET was defined as a decrease of ≥10 mmHg in SBP between successive measurements with slight measurement differences between the two cohorts. Cardiovascular (CVD), coronary heart disease (CHD) and stroke (STR) incidences were considered. Over an approximately 20-year follow-up, women with OWCET had an increased risk of CVD [HR: 1.591 (95%CI: 1.204–2.103)], CHD [HR: 1.614 (95%CI: 1.037–2.512)] and STR [HR: 1.696 (95%CI: 1.123–2.563)] events independently of age, serum and HDL cholesterol, cigarettes, BMI and SBP in the Gubbio study. However, there was no increased risk of CVD, CHD or STR in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. These results were not modified significantly by the correction of the regression dilutions bias between the first and the subsequent SBP measurements. Thus, in primary care, OWCET should be actively evaluated in women as it can improve stratification of long-term CVD, CHD and STR risks.
Chern and Z2 topological insulating phases in perovskite-derived 4d and 5d oxide buckled honeycomb lattices
Authors: Köksal Okan , Pentcheva Rossitza 
Published: November 2019

AbstractBased on density functional theory calculations including a Coulomb repulsion parameter U, we explore the topological properties of (LaXO3)2/(LaAlO3)4 (111) with X = 4d and 5d cations. The metastable ferromagnetic phases of LaTcO3 and LaPtO3 with preserved P321 symmetry emerge as Chern insulators (CI) with C = 2 and 1 and band gaps of 41 and 38 meV at the lateral lattice constant of LaAlO3, respectively. Berry curvatures, spin textures as well as edge states provide additional insight into the nature of the CI states. While for X = Tc the CI phase is further stabilized under tensile strain, for X = Pd and Pt a site disproportionation takes place when increasing the lateral lattice constant from aLAO to aLNO. The CI phase of X = Pt shows a strong dependence on the Hubbard U parameter with sign reversal for higher values associated with the change of band gap opening mechanism. Parallels to the previously studied (X2O3)1/(Al2O3)5 (0001) honeycomb corundum layers are discussed. Additionally, non-magnetic systems with X = Mo and W are identified as potential candidates for Z2 topological insulators at aLAO with band gaps of 26 and 60 meV, respectively. The computed edge states and Z2 invariants underpin the non-trivial topological properties.
Genome Wide Analysis Approach Suggests Chromosome 2 Locus to be Associated with Thiazide and Thiazide Like-Diuretics Blood Pressure Response
Authors: Singh Sonal , McDonough Caitrin W. , Gong Yan , Bailey Kent R. , Boerwinkle Eric , Chapman Arlene B. , Gums John G. , Turner Stephen T. , Cooper-DeHoff Rhonda M. , Johnson Julie A. 
Published: November 2019

AbstractChlorthalidone (CTD) is more potent than hydrochlorothiazide (HCTZ) in reducing blood pressure (BP) in hypertensive patients, though both are plagued with BP response variability. However, there is a void in the literature regarding the genetic determinants contributing to the variability observed in BP response to CTD. We performed a discovery genome wide association analysis of BP response post CTD treatment in African Americans (AA) and European Americans (EA) from the Pharmacogenomic Evaluation of Antihypertensive Responses-2 (PEAR-2) study and replication in an independent cohort of AA and EA treated with HCTZ from the PEAR study, followed by a race specific meta-analysis of the two studies. Successfully replicated SNPs were further validated in beta-blocker treated participants from PEAR-2 and PEAR for opposite direction of association. The replicated and validated signals were further evaluated by protein-protein interaction network analysis. An intronic SNP rs79237970 in the WDR92 (eQTL for PPP3R1) was significantly associated with better DBP response to CTD (p = 5.76 × 10−6, β = −15.75) in the AA cohort. This SNP further replicated in PEAR (p = 0.00046, β = −9.815) with a genome wide significant meta-analysis p-value of 8.49 × 10−9. This variant was further validated for opposite association in two β-blockers treated cohorts from PEAR-2 metoprolol (p = 9.9 × 10−3, β = 7.47) and PEAR atenolol (p = 0.04, β = 4.36) for association with DBP. Studies have implicated WDR92 in coronary artery damage. PPP3R1 is the regulatory subunit of the calcineurin complex. Use of calcineurin inhibitors is associated with HTN. Studies have also shown polymorphisms in PPP3R1 to be associated with ventricular hypertrophy in AA hypertensive patients. Protein-protein interaction analysis further identified important hypertension related pathways such as inositol phosphate-mediated signaling and calcineurin-NFAT signaling cascade as important biological process associated with PPP3R1 which further strengthen the potential importance of this signal. These data collectively suggest that WDR92 and PPP3R1 are novel candidates that may help explain the genetic underpinnings of BP response of thiazide and thiazide-like diuretics and help identify the patients better suited for thiazide and thiazide-like diuretics compared to β-blockers for improved BP management. This may further help advance personalized approaches to antihypertensive therapy.
Phosphorylation of PD-1-Y248 is a marker of PD-1-mediated inhibitory function in human T cells
Authors: Bardhan Kankana , Aksoylar Halil-Ibrahim , Le Bourgeois Thibault , Strauss Laura , Weaver Jessica D. , Delcuze Bethany , Charest Alain , Patsoukis Nikolaos , Boussiotis Vassiliki A. 
Published: November 2019

AbstractPD-1 is a target of cancer immunotherapy but responses are limited to a fraction of patients. Identifying patients with T cells subjected to PD-1-mediated inhibition will allow selection of suitable candidates for PD-1-blocking therapy and will improve the therapeutic success. We sought to develop an approach to detect PD-1-mediated inhibitory signaling. The cytoplasmic tail of PD-1 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) encompassing Y223 and an immunoreceptor tyrosine-based switch motif (ITSM) encompassing Y248, which is indispensable for interaction of SHP-2 and delivery of PD-1 inhibitory function. We generated an antibody specific for phosphorylated PD-1-Y248 and examined PD-1pY248+ (pPD-1) expression in human T cells. pPD-1 was upregulated by TCR/CD3 + CD28 stimulation and simultaneous PD-1 ligation. pPD-1+CD8+ T cells were identified in human peripheral blood and had impaired effector function. pPD-1+ T cells were also detected in tumor-draining lymph nodes of tumor bearing mice and in biopsies of patients with glioblastoma multiform. Detection of pPD-1+ T cells might serve as a biomarker for identification of T cells subjected to PD-1-mediated immunosuppression.
Micro-scale patchiness enhances trophic transfer efficiency and potential plankton biodiversity
Authors: Priyadarshi Anupam , Smith S. Lan , Mandal Sandip , Tanaka Mamoru , Yamazaki Hidekatsu 
Published: November 2019

AbstractRather than spatial means of biomass, observed overlap in the intermittent spatial distributions of aquatic predators and prey is known to be more important for determining the flow of nutrients and energy up the food chain. A few previous studies have separately suggested that such intermittency enhances phytoplankton growth and trophic transfer to sustain zooplankton and ultimately fisheries. Recent observations have revealed that phytoplankton distributions display consistently high degrees of mm scale patchiness, increasing along a gradient from estuarine to open ocean waters. Using a generalized framework of plankton ecosystem models with different trophic configurations, each accounting for this intermittency, we show that it consistently enhances trophic transfer efficiency (TE), i.e. the transfer of energy up the food chain, and expands the model stability domain. Our results provide a new explanation for observation-based estimates of unexpectedly high TE in the vast oligotrophic ocean and suggest that by enhancing the viable trait space, micro-scale variability may potentially sustain plankton biodiversity.