bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA-seq reveals CD16-monocytes as key regulators of human monocyte transcriptional response toToxoplasma
Authors: Patir Anirudh , Gossner Anton , Ramachandran Prakash , Alves Joana , Freeman Tom C. , Henderson Neil C. , Watson Michael , Hassan Musa A. 
Published: December 2019

ABSTRACTMonocytes are among the major myeloid cells that respond toToxoplasma, a ubiquitous foodborne that infects ≥1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasmainteractions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasmainteractions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses toToxoplasmahave sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte response to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasmaencounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report thatToxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14++CD16-monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover theToxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed toToxoplasma.
Osteoblast-osteoclast co-culture amplifies inhibitory effects of FG-4592 on osteoclast formation and reduces bone resorption activity
Authors: Hulley Philippa A , Papadimitriou-Olivgeri Ioanna , Knowles Helen J 
Published: December 2019

AbstractThe link between bone and blood vessels is regulated by hypoxia and the hypoxia-inducible transcription factor, HIF, which drives both osteogenesis and angiogenesis. The recent clinical approval of PHD enzyme inhibitors, which stabilise HIF protein, introduces the potential for a new clinical strategy to treat osteolytic conditions such as osteoporosis, osteonecrosis and skeletal fracture and non-union. However, bone-resorbing osteoclasts also play a central role in bone remodelling and pathological osteolysis and HIF promotes osteoclast activation and bone loss in vitro. It is therefore likely that the final outcome of PHD enzyme inhibition in vivo would be mediated by a balance between increased bone formation and increased bone resorption. It is essential that we improve our understanding of the effects of HIF on osteoclast formation and function, and consider the potential contribution of inhibitory interactions with other musculoskeletal cells.The PHD enzyme inhibitor FG-4592 stabilised HIF protein and stimulated osteoclast-mediated bone resorption, but inhibited differentiation of human CD14+ monocytes into osteoclasts. Formation of osteoclasts in a more physiologically relevant 3D collagen gel did not affect the sensitivity of osteoclastogenesis to FG-4592, but increased sensitivity to reduced concentrations of RANKL. Co-culture with osteoblasts amplified inhibition of osteoclastogenesis by FG-4592, whether the osteoblasts were proliferating, differentiating or in the presence of exogenous M-CSF and RANKL. Osteoblast co-culture dampened the ability of high concentrations of FG-4592 to increase bone resorption.This data provides support for the therapeutic use of PHD enzyme inhibitors to improve bone formation and/or reduce bone loss for treatment of osteolytic pathologies, and indicates that FG-4592 might also act to inhibit the formation and activity of the osteoclasts that drive osteolysis.
Color tuning of neurons in face patches of macaque inferior temporal cortex
Authors: Duyck Marianne , Gruen Tessa J. , Tello Lawrence Y. , Eastman Serena , Fuller-Deets Joshua , Conway Bevil R. 
Published: December 2019

Previous work has shown that under viewing conditions that break retinal mechanisms for color, one class of objects appears paradoxically colored: faces, and they look green. Interpreted within a Bayesian-observer framework, this observation makes the surprising prediction that face-selective neurons are sensitive to color and weakly biased for colors that elicit L>M cone activity (warm colors). We tested this hypothesis by measuring color-tuning responses of face-selective cells in alert macaque monkey, using fMRI-guided microelectrode recording of the middle and anterior face patches and carefully color-calibrated stimuli. The population of face-selective neurons showed significant color tuning when assessed using images that preserved the luminance contrast relationships of the original face photographs. A Fourier analysis of the color-tuning responses uncovered two components. The first harmonic was biased towards the L>M colors, consistent with the prediction. Interestingly, the second harmonic aligned with the S-cone cardinal axis, which may relate to the computation of animacy by IT cells.SignificanceThe results provide the first quantitative measurements of the color tuning properties of face-selective neurons. The results provide insight into the neural mechanisms that could support the role of color in face perception.
Spatial, climate, and ploidy factors drive genomic diversity and resilience in the widespread grassThemeda triandra
Authors: Ahrens CW , James EA , Miller AD , Aitken NC , Borevitz JO , Cantrill DJ , Rymer PD 
Published: December 2019

SummaryFragmented grassland ecosystems, and the species that shape them, are under immense pressure. Restoration and management strategies should include genetic diversity and adaptive capacity to improve success but these data are generally unavailable. Therefore, we use the foundational grass,Themeda triandra, to test how spatial, environmental, and ploidy factors shape patterns of genetic variation.We used reduced-representation genome sequencing on 487 samples from 52 locations to answer fundamental questions about how the distribution of genomic diversity and ploidy polymorphism supports adaptation to harsher climates. We explicitly quantified isolation-by-distance (IBD), isolation-by-environment (IBE), and predicted population genomic vulnerability in 2070.We found that a majority (54%) of the genomic variation could be attributed to IBD, while 22% of the genomic variation could be explained by four climate variables showing IBE. Results indicate that heterogeneous patterns of vulnerability across populations are due to genetic variation, multiple climate factors, and ploidy polymorphism, which lessened genomic vulnerability in the most susceptible populations.These results indicate that restoration and management ofT. triandrashould incorporate knowledge of genomic diversity and ploidy polymorphisms to increase the likelihood of population persistence and restoration success in areas that will become hotter and more arid.
Attraction, Dynamics, and Phase Transitions in Fire Ant Tower-Building
Authors: Nave Gary K. , Mitchell Nelson T. , Dick Jordan A. Chan , Schuessler Tyler , Lagarrigue Joaquin A. , Peleg Orit 
Published: December 2019

AbstractMany insect species, and even some vertebrates, assemble their bodies to form multi-functional materials that combine sensing, computation, and actuation. The tower-building behavior of red imported fire ants, Solenopsis invicta, presents a key example of this phenomenon of collective construction. While biological studies of collective construction focus on behavioral assays to measure the dynamics of formation and studies of swarm robotics focus on developing hardware that can assemble and interact, algorithms for designing such collective aggregations have been mostly overlooked. We address this gap by formulating an agent-based model for collective tower-building with a set of behavioral rules that incorporate local sensing of neighboring agents. We find that an attractive force makes tower building possible. Next, we explore the trade-offs between attraction and random motion to characterize the dynamics and phase transition of the tower building process. Lastly, we provide an optimization tool that may be used to design towers of specific shapes, mechanical loads, and dynamical properties such as mechanical stability and mobility of the center of mass.
Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning
Authors: Smith Martin A. , Ersavas Tansel , Ferguson James M. , Liu Huanle , Lucas Morghan C , Begik Oguzhan , Bojarski Lilly , Barton Kirston , Novoa Eva Maria 
Published: December 2019

ABSTRACTNanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5’ and 3’ ends of reads, which complicates sequence-based barcode demultiplexing. Here, we propose a novel strategy to barcode and demultiplex direct RNA sequencing nanopore data, which does not rely on base-calling or additional library preparation steps. Specifically, custom DNA oligonucleotides are ligated to RNA transcripts during library preparation. Then, raw current signal corresponding to the DNA barcode is extracted and transformed into an array of pixels, which is used to determine the underlying barcode using a deep convolutional neural network classifier. Our method,DeePlexiCon, implements a 20-layer residual neural network model that can demultiplex 93% of the reads with 95.1% specificity, or 60% of reads with 99.9% specificity. The availability of an efficient and simple barcoding strategy for native RNA sequencing will enhance the use of direct RNA sequencing by making it more cost-effective to the entire community. Moreover, it will facilitate the applicability of direct RNA sequencing to samples where the RNA amounts are limited, such as patient-derived samples.
Variation of bacterial communities along the vertical gradient in Lake Issyk Kul, Kyrgyzstan
Authors: Rojas-Jimenez Keilor , Araya-Lobo Alex , Quesada-Perez Fabio , Akerman-Sanchez Johana , Delgado-Duran Brayan , Ganzert Lars , Zavialov Peter O. , Alymkulov Salmor , Kirillin Georgiy , Grossart Hans Peter 
Published: December 2019

AbstractIn this study, we explored the diversity and community composition of bacteria along a vertical gradient in Lake Issyk Kul, Kyrgyzstan, one of the largest and deepest brackish lakes in in the world. We identified 4904 bacterial ASVs based on analysis of 16S rRNA gene sequences and determined significant changes in the composition responding mainly to the variables depth and salinity. A higher abundance of Proteobacteria and Bacteroidetes was observed in the surface waters and the lake tributaries. Cyanobacteria were more abundant in the deep chlorophyll maximum (28.5 to 128 m), while Planctomycetes and Chloroflexi were dominant at depths between 128 to 600 m. According to our machine learning analysis used for identifying the most critical environmental factors, depth and temperature revealed the strongest effect on members of Proteobacteria, Planctomycetes, and Chloroflexi, while oxygen is associated with the variations in Cyanobacteria. Also, a notable increase in alpha diversity estimations was observed with increasing water depth. This work evidences significant differences in the structure of bacterial communities along the depth gradient in deep, transparent lake ecosystems. Notably, there is a dominance of Planctomycetes and Chloroflexi in the deepest layers, which can only be seen in a few other lakes with similar characteristics as Lake Issyk Kul and raises questions about their ecological role.
Antibiograms and Molecular Characterization of Drug Resistance ofMycobacterium abscessuscomplex from Patients with Multidrug-Resistant Pulmonary Tuberculosis (MDR TB) Infection
Authors: Bongulto Kenneth A. , Ang Concepcion F. , Cabrera Esperanza C. 
Published: December 2019

ABSTRACTIn the Philippines, acid fast bacilli positive sputum samples commonly treated as TB due toMycobacterium tuberculosis(MTB) complex. However,Mycobacterium abscessus(MAB) complex is often found in MTB cultures, or in patients confirmed negative for TB through sputum microscopy and culture. Hence, patients with MAB infections are mistakenly prescribed six-month anti-TB treatments. In this study, MAB complex isolates from MDRTB patients were identified and further sub-speciated using themass3210 gene. Antimicrobial susceptibility was tested using broth microdilution and resistance geneserm(41),rrs, rrl, gyrA, andgyrB were studied for mutations. Majority were susceptible to amikacin, azithromycin, clarithromycin, and moxifloxacin [MAB: 100%, 100%, 100%, 81.8%, respectively;M. massiliense(MAM): 100%, 100%, 100%, 60%, respectively]. 50% MAM and 63.6% MAB were susceptible to cefoxitin; 60% MAM and 45.5% MAB were susceptible to ciprofloxacin; 72.7% MAB, and 10%MAM were susceptible to doxycycline. Inducible resistance to azithromycin and clarithromycin was found in 27.3%MAB and 30% MAM. 42.9% MAB complex isolates were MDR. Macrolide resistant MAB and MAM had T28 sequevar, showing functionalerm(41) responsible for inducible resistance. Unexpectedly, full lengtherm(41) was found in MAM. Therrlgene in these isolates showed no point mutations, indicating T28 sequevar as cause of inducible resistance. All fluoroquinolone resistant isolates showed Ala-83 ingyrA fluoroquinolone resistant-dependent region (QRDR) and Arg-447 and Asn-464 ingyrB QRDR. These are associated with resistance to the drug.
Twinfilin uncaps filament barbed ends to promote turnover of lamellipodial actin networks
Authors: Hakala Markku , Wioland Hugo , Tolonen Mari , Jegou Antoine , Romet-Lemonne Guillaume , Lappalainen Pekka 
Published: December 2019

AbstractCoordinated polymerization of actin filaments provides force for cell migration, morphogenesis, and endocytosis. Capping Protein (CP) is central regulator of actin dynamics in all eukaryotes. It binds actin filament (F-actin) barbed ends with high affinity and slow dissociation kinetics to prevent filament polymerization and depolymerization. In cells, however, CP displays remarkably rapid dynamics within F-actin networks, but the underlying mechanism has remained enigmatic. We report that a conserved cytoskeletal regulator, twinfilin, is responsible for CP’s rapid dynamics and specific localization in cells. Depletion of twinfilin led to stable association of CP with cellular F-actin arrays and its treadmilling throughout leading-edge lamellipodium. These were accompanied by diminished F-actin disassembly rates. In vitro single filament imaging approaches revealed that twinfilin directly promotes dissociation of CP from filament barbed ends, while allowing subsequent filament depolymerization. These results uncover an evolutionary conserved bipartite mechanism that controls how actin cytoskeleton-mediated forces are generated in cells.
Correlated evolution between heat tolerance and thermal performance curves in Drosophila subobscura
Authors: Mesas Andrés , Jaramillo Angélica , Castañeda Luis E. 
Published: December 2019

AbstractGlobal warming imposes important challenges for ectotherm organisms, which can avoid the negative effects of thermal stress via evolutionary adaptation of their upper thermal limits (CTmax). In this sense, the estimation of CTmax and its evolutionary capacity is crucial to determine the vulnerability of natural populations to climate change. However, these estimates depend on the thermal stress intensity and it is not completely clear whether this thermal stress intensity can impact the evolutionary response of CTmax and thermal reaction norms (i.e. thermal performance curve, TPC). Here we performed an evolutionary experiment by selecting high heat tolerance using acute and chronic thermal stress in Drosophila subobscura. After artificial selection, we found that knockdown temperatures (a CTmax proxy) evolved in selected lines compared to control lines, whereas the realized heritability and evolutionary rate change of heat tolerance did not differ between acute-selected and chronic-selected lines. From TPC analysis, we found acute-selected lines evolved a higher optimal performance temperature (Topt) compared to acute-control lines, whereas this TPC parameter was not different between chronic-selected and chronic-control lines. The evolutionary response of Topt caused a displacement of entire TPC to high temperatures suggesting a shared genetic architecture between heat tolerance and high-temperature performance, which only arose in the acute-selected lines. In conclusion, thermal stress intensity has important effects on the evolution of thermal physiology in ectotherms, indicating that different thermal scenarios conduce to similar evolutionary responses of heat tolerance but do not for thermal performance. Therefore, thermal stress intensity could have important consequences on the estimations of the vulnerability of ectotherms to global warming.
Cultivation of Exoelectrogenic Bacteria in Conductive DNA Nanocomposite Hydrogels Yields a Programmable Biohybrid Materials System
Authors: Hu Yong , Rehnlund David , Klein Edina , Gescher Johannes , Niemeyer Christof M. 
Published: December 2019

AbstractThe use of living microorganisms integrated within electrochemical devices is an expanding field of research, with applications in microbial fuel cells, microbial biosensors or bioreactors. We describe the use of porous nanocomposite materials prepared by DNA polymerization of carbon nanotubes (CNT) and silica nanoparticles (SiNP) for the construction of a programmable biohybrid system containing the exoelectrogenic bacterium Shewanella oneidensis. We initially demonstrate the electrical conductivity of the CNT-containing DNA composite by employment of chronopotentiometry, electrochemical impedance spectroscopy, and cyclic voltammetry. Cultivation of Shewanella oneidensis in these materials shows that the exoelectrogenic bacteria populate the matrix of the composite, while non-exoelectrogenic Escherichia coli remain on its surface. Moreover, the ability to use extracellular electron transfer pathways is positively correlated with number of cells within the conductive synthetic biofilm matrix. The Shewanella containing composite remains stable for several days. Programmability of this biohybrid material system is demonstrated by on-demand release and degradation induced by a short-term enzymatic stimulus. The perspectives of this approach for technical applications are being discussed.
Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review
Authors: Onwuchekwa Chukwuemeka , Bassey Edem , Williams Victor , Oga Emmanuel 
Published: December 2019

AbstractBackgroundThe impact of pneumococcal conjugate vaccine introduction in reducing the incidence of childhood pneumonia has not been well documented in sub-Saharan Africa. Many studies evaluating vaccine impact have used invasive pneumococcal disease or pneumococcal pneumonia as an outcome.ObjectiveTo estimate the impact of routine administration of 10-valent and 13-valent PCV on the incidence of pneumonia in children under five years of age in sub-Saharan Africa.Data sourcesA systematic review was conducted between 16 and 31 July 2019. The review was registered on PROSPERO with registration number CRD42019142369. The literature search was conducted in indexed databases including Medline and Embase, grey literature databases and online libraries of two universities. Manual search of the references of included studies was performed to identify additional relevant studies. The search strategy combined pneumococcal conjugate vaccine, pneumonia and child as search concepts.Study selectionStudies investigating the impact of 10- or13-valent PCV on childhood pneumonia in a sub-Saharan African country were eligible for inclusion. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Exclusion criteria were use of 7- or 9-valent PCV, systematic review studies, clinical trials and record publication prior to 2009.Data extractionIndependent data extraction was conducted. Key variables include year study conducted, type of study design, type of PCV used and year of introduction, reported PCV coverage, outcome measure evaluated and the effect measure.Data synthesisEight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact measured as percentage reduction in risk (%RR) of clinical pneumonia was mostly small and non-significant. The risk reduction was more significant and consistent on radiological and pneumococcal pneumonia. Vaccine effectiveness reported in case-control studies was mostly non-significant.ConclusionEvidence of the positive impact of routine infant pneumococcal vaccination on pneumonia in sub-Saharan Africa is weak. There is a need for more research in this area to evaluate the influence of pathogen or serotype replacement in pneumonia after PCV introduction. Ongoing surveillance is also required to establish the long term trend in pneumonia epidemiology after PCV introduction.
Glial cell mechanosensitivity is reversed by adhesion cues
Authors: Tomba C. , Migdal C. , Fuard D. , Villard C. , Nicolas A. 
Published: December 2019

ABSTRACTBrain tissues demonstrate heterogeneous mechanical properties, which evolve with aging and pathologies. The observation in these tissues of smooth to sharp rigidity gradients raises the question of brain cells responses to both different values of rigidity and their spatial variations. Here, we use recent techniques of hydrogel photopolymerization to achieve stiffness structuration down to micrometer resolution. We investigate primary neuron adhesion and orientation as well as glial cell adhesive and proliferative properties on multi-rigidity polyacrylamide hydrogels presenting a uniform density of adhesive molecules. We first observed that neurons grow following rigidity gradients. Then, our main observation is that glial cell adhesion and proliferation can be enhanced on stiff or on soft regions depending on the adhesive coating of the hydrogel, i. e. fibronectin or poly-L-lysine/laminin. This behavior was unchanged in the presence or not of neuronal cells. In addition, and contrarily to other cell types, glial cells were not confined by sharp, micron-scaled gradients of rigidity. Our observations suggest that their mechanosensitivity could involve adheison-related mechanosensitive pathways that are specific to brain tissues.SIGNIFICANCEBy growing primary brain cells on 2D multi-rigidity polyacrylamide hydrogels, we show that favorable culture conditions for glial cells switch from stiff to soft substrates when changing the adhesive ligands from fibronectin to poly-L-lysine/laminin. Together with neurons, glial cells thus provide a unique example where soft is preferred to stiff, but unlike neurons, this preference can be reversed by changing the nature of the coating. We additionally show that contrarily to other cell types, glial cells are deformed by subcellular gradients of rigidity but cannot be confined by these rigidity gradients. These observations point that glial cell use a very specific, integrin-related machinery for rigidity sensing.