bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics ofMycobacterium africanumLineage 5 and Lineage 6 from Ghana suggests different ecological niches
Authors: Otchere Isaac Darko , Coscollá Mireia , Sánchez-Busó Leonor , Asante-Poku Adwoa , Brites Daniela , Loiseau Chloe , Meehan Conor , Osei-Wusu Stephen , Forson Audrey , Laryea Clement , Yahayah Abdallah Iddrisu , Baddoo Akosua , Ansa Gloria Akosua , Aboagye Samuel Yaw , Asare Prince , Borrell Sonia , Gehre Florian , Beckert Patrick , Kohl Thomas A , N'dira Sanoussi , Beisel Christian , Antonio Martin , Niemann Stefan , de Jong Bouke C , Parkhill Julian , Harris Simon R , Gagneux Sebastien , Yeboah-Manu Dorothy 
Published: October 2017

AbstractMycobacterium africanum(Maf) causes up to half of human tuberculosis in West Africa, but little is known on this pathogen. We compared the genomes of 253Mafclinical isolates from Ghana, including both L5 and L6. We found that the genomic diversity of L6 was higher than in L5, and the selection pressures differed between both groups. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Conversely, human T cell epitopes were under purifying selection in L5, but under positive selection in L6. Although only 10% of the T cell epitopes were variable, mutations were mostly lineage-specific. Our findings indicate thatMafL5 and L6 are genomically distinct, possibly reflecting different ecological niches.
Deep profiling of mouse splenic architecture with CODEX multiplexed imaging
Authors: Goltsev Yury , Samusik Nikolay , Kennedy-Darling Julia , Bhate Salil , Hale Matthew , Vazquez Gustavo , Black Sarah , Nolan Garry P. 
Published: October 2017

SUMMARYA highly multiplexed cytometric imaging approach, termed CO-Detection by indEXing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an insitu polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.
Analysis of LRRC45 indicates cooperative functions of distal appendages at early steps of ciliogenesis
Authors: Kurtulmus Bahtiyar , Yuan Cheng , Schuy Jakob , Neuner Annett , Hata Shoji , Kalamakis Georgios , Martin-Villalba Ana , Pereira G. 
Published: October 2017

AbstractCilia perform essential signalling functions during development and tissue homeostasis. Ciliary malfunction causes a variety of diseases, named ciliopathies. The key role that the mother centriole plays in cilia formation can be attributed to appendage proteins that associate exclusively with the mother centriole. The distal appendages form a platform that docks early ciliary vesicles and removes CP110/Cep97 inhibitory complexes from the mother centriole. Here, we analysed the role played by LRRC45 in appendage formation and ciliogenesis. We show that the core appendage proteins Cep83 and SCLT1 recruit LRRC45 to the mother centriole. Once there LRRC45 recruits FBF1. The association of LRRC45 with the basal body of primary and motile cilia in differentiated and stem cells reveals a broad function in ciliogenesis. In contrast to the appendage components Cep164 and Cep123, LRRC45 was neither essential for docking of early ciliary vesicles nor for removal of CP110. Rather, LRRC45 promotes cilia biogenesis in CP110-uncapped centrioles by organising centriolar satellites and promoting the docking of Rab8 GTPase-positive vesicles. We propose that, instead of acting solely as a platform to recruit early vesicles, centriole appendages form discrete scaffolds of cooperating proteins that execute specific functions that promote the initial steps of ciliogenesis.
Two distinct mechanisms silencechinmoinDrosophilaneuroblasts and neuroepithelial cells to limit their self-renewal
Authors: Dillard Caroline , Narbonne-Reveau Karine , Foppolo Sophie , Lanet Elodie , Maurange Cédric 
Published: October 2017

ABSTRACTWhether common principles regulate the self-renewing potential of neural stem cells (NSCs) throughout the developing central nervous system is still unclear. In theDrosophilaventral nerve cord and central brain, asymmetrically dividing NSCs, called neuroblasts (NBs), progress through a series of sequentially expressed transcription factors that limits self-renewal by silencing a genetic module involving the transcription factor Chinmo. Here, we find that Chinmo also promotes neuroepithelium growth in the optic lobe during early larval stages by boosting symmetric self-renewing divisions while preventing differentiation. Neuroepithelium differentiation in late larvae requires the transcriptional silencing ofchinmoby ecdysone, the main steroid hormone, therefore allowing coordination of NSC self-renewal with organismal growth. In contrast,chinmosilencing in NBs is post-transcriptional and does not require ecdysone. Thus, duringDrosophiladevelopment, humoral cues or tissue-intrinsic temporal specification programs respectively limit self-renewal in different types of neural progenitors through the transcriptional and post-transcriptional regulation of the same transcription factor.SUMMARY STATEMENTHere, we demonstrate that the transcription factorchinmoacts as a master gene of NSC self-renewal in the different regions of the developingDrosophilabrain where it is controlled by distinct regulatory strategies.
Clearing the FoG: Antifungal tolerance is a subpopulation effect that is distinct from resistance and is associated with persistent candidemia
Authors: Rosenberg Alexander , Ene Iuliana V. , Bibi Maayan , Zakin Shiri , Segal Ella Shtifman , Ziv Naomi , Dahan Alon M. , Colombo Arnaldo L. , Bennett Richard J. , Berman Judith 
Published: October 2017

AbstractDrug susceptibility, defined by the minimal inhibitory concentration (MIC), often does not predict whether fungal infections will respond to therapy in the clinic. Tolerance at supra-MIC antifungal drug concentrations is rarely quantified and current clinical recommendations suggest it be ignored. Here, we measured and characterized drug-response variables that could influence the outcomes of fungal infections and be generalizable across major clades ofCandida albicans, one of the most frequently isolated human fungal pathogens. We quantified antifungal tolerance as the fraction of growth (FoG) above the MIC and found that it is clearly distinct from susceptibility/resistance measured as MIC. Instead, tolerance is due to the slow growth of subpopulations of cells that overcome drug stress more efficiently than the rest of the population, and correlates inversely with the accumulation of intracellular drug. Importantly, many adjuvant drugs used together with fluconazole, a fungistatic drug, reduce tolerance without affecting resistance. These include inhibitors of major stress response hubs such as Hsp90, calcineurin, PKC1 and TOR. Accordingly, in an invertebrate infection model, adjuvant combination therapy was significantly more effective than fluconazole alone in treating highly tolerant isolates and did not improve the treatment of isolates with low tolerance levels. Furthermore, isolates recovered from immunocompetent patients with persistent candidemia displayed significantly higher tolerance than isolates that were readily cleared by fluconazole. Thus, tolerance correlates with the response to fluconazole therapy in patients and may help predict whether infections will respond to fluconazole alone. Similarly, measuring tolerance may provide a useful clinical parameter for choosing appropriate therapeutic strategies to overcome persistent clinical candidemia.
Simulation of visual perception and learning with a retinal prosthesis
Authors: Golden James R. , Erickson-Davis Cordelia , Cottaris Nicolas P. , Parthasarathy Nikhil , Rieke Fred , Brainard David H. , Wandell Brian A. , Chichilnisky E.J. 
Published: October 2017

AbstractThe nature of artificial vision with a retinal prosthesis, and the degree to which the brain can adapt to the unnatural input from such a device, are poorly understood. Therefore, the development of current and future devices may be aided by theory and simulations that help to infer and understand what prosthesis patients see. A biologically-informed, extensible computational framework is presented here to predict visual perception and the potential effect of learning with a subretinal prosthesis. The framework relies on optimal linear reconstruction of the stimulus from retinal responses to infer the visual information available to the patient. A simulation of the physiological optics of the eye and light responses of the major retinal neurons was used to calculate the optimal linear transformation for reconstructing natural images from retinal activity. The result was then used to reconstruct the visual stimulus during the artificial activation expected from a subretinal prosthesis in a degenerated retina, as a proxy for inferred visual perception. Several simple observations reveal the potential utility of such a simulation framework. The inferred perception obtained with prosthesis activation was substantially degraded compared to the inferred perception obtained with normal retinal responses, as expected given the limited resolution and lack of cell type specificity of the prosthesis. Consistent with clinical findings and the importance of cell type specificity, reconstruction using only ON cells, and not OFF cells, was substantially more accurate. Finally, when reconstruction was re-optimized for prosthesis stimulation, simulating the greatest potential for learning by the patient, the accuracy of inferred perception was much closer to that of healthy vision. The reconstruction approach thus provides a more complete method for exploring the potential for treating blindness with retinal prostheses than has been available previously. It may also be useful for interpreting patient data in clinical trials, and for improving prosthesis design.
Explainable machine learning predictions to help anesthesiologists prevent hypoxemia during surgery
Authors: Lundberg Scott M. , Nair Bala , Vavilala Monica S. , Horibe Mayumi , Eisses Michael J. , Adams Trevor , Liston David E. , Low Daniel King-Wai , Newman Shu-Fang , Kim Jerry , Lee Su-In 
Published: October 2017

AbstractHypoxemia causes serious patient harm, and while anesthesiologists strive to avoid hypoxemia during surgery, anesthesiologists are not reliably able to predict which patients will have intraoperative hypoxemia. Using minute by minute EMR data from fifty thousand surgeries we developed and tested a machine learning based system called Prescience that predicts real-time hypoxemia risk and presents an explanation of factors contributing to that risk during general anesthesia. Prescience improved anesthesiologists’ performance when providing interpretable hypoxemia risks with contributing factors. The results suggest that if anesthesiologists currently anticipate 15% of events, then with Prescience assistance they could anticipate 30% of events or an estimated additional 2.4 million annually in the US, a large portion of which may be preventable because they are attributable to modifiable factors. The prediction explanations are broadly consistent with the literature and anesthesiologists’ prior knowledge. Prescience can also improve clinical understanding of hypoxemia risk during anesthesia by providing general insights into the exact changes in risk induced by certain patient or procedure characteristics. Making predictions of complex medical machine learning models (such as Prescience) interpretable has broad applicability to other data-driven prediction tasks in medicine.
Controlled iris radiance in a diurnal fish looking at prey
Authors: Michiels Nico K. , Seeburger Victoria C. , Kalb Nadine , Meadows Melissa G. , Anthes Nils , Mailli Amalia A. , Jack Colin B. 
Published: October 2017

1.SummaryActive sensing using light, or active photolocation, is only known from deep sea and nocturnal fish with chemiluminescent “search” lights. Bright irides in diurnal fish species have recently been proposed as a potential analogue. Here, we contribute to this discussion by testing whether iris radiance is actively modulated. The focus is on behaviourally controlled iris reflections, called “ocular sparks”. The triplefinTripterygion delaisican alternate between red and blue ocular sparks, allowing us to test the prediction that spark frequency and hue depend on background hue and prey presence. In a first experiment, we found that blue ocular sparks were significantly more often “on” against red backgrounds, and red ocular sparks against blue backgrounds, particularly when copepods were present. A second experiment tested whether hungry fish showed more ocular sparks, which was not the case. Again, background hue resulted in differential use of ocular spark types. We conclude that iris radiance through ocular sparks inT. delaisiis not a side effect of eye movement, but adaptively modulated in response to the context under which prey are detected. We discuss the possible alternative functions of ocular sparks, including an as yet speculative role in active photolocation.
Enumerating the Economic Cost of Antimicrobial Resistance Per Antibiotic Consumed to Inform the Evaluation of Interventions Affecting their Use
Authors: Shrestha Poojan , Cooper Ben S , Coast Joanna , Oppong Raymond , Do Nga T. T. , Podha Tuangrat , Celhay Olivier , Guerin Philippe J. , Wertheim Heiman , Lubell Yoel 
Published: October 2017

AbstractBackground– Antimicrobial resistance (AMR) poses a colossal threat to global health and incurs high economic costs to society. Economic evaluations of antimicrobials and interventions such as diagnostics and vaccines that affect their consumption rarely include the costs of AMR, resulting in sub-optimal policy recommendations. We estimate the economic cost of AMR per antibiotic consumed, stratified by drug class and national income level.Methods– The model is comprised of three components: correlation coefficients between human antibiotic consumption and subsequent resistance; the economic costs of AMR for five key pathogens; and consumption data for antibiotic classes driving resistance in these organisms. These were used to calculate the economic cost of AMR per antibiotic consumed for different drug classes, using data from Thailand and the United States (US) to represent low/middle and high-income countries.Results– The correlation coefficients between consumption of antibiotics that drive resistance in S. aureus, E. coli, K. pneumoniae, A. baumanii, and P. aeruginosa and resistance rates were 0.37, 0.27, 0.35, 0.45, and 0.52, respectively. The total economic cost of AMR due to resistance in these five pathogens was $0.5 billion and $2.8 billion in Thailand and the US, respectively. The cost of AMR associated with the consumption of one standard unit (SU) of antibiotics ranged from $0.1 for macrolides to $0.7 for quinolones, cephalosporins and broad-spectrum penicillins in the Thai context. In the US context, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for carbapenems to $0.6 for quinolones, cephalosporins and broad spectrum penicillins.Conclusion– The economic costs of AMR per antibiotic consumed were considerable, often exceeding their purchase cost. Differences between Thailand and the US were apparent, corresponding with variation in the overall burden of AMR and relative prevalence of different pathogens. Notwithstanding their limitations, use of these estimates in economic evaluations can make better-informed policy recommendations regarding interventions that affect antimicrobial consumption and those aimed specifically at reducing the burden of AMR.
The molecular genetics of participation in the Avon Longitudinal Study of Parents and Children
Authors: Taylor Amy E. , Jones Hannah J. , Sallis Hannah , Euesden Jack , Stergiakouli Evie , Davies Neil M. , Zammit Stanley , Lawlor Debbie A. , Munafò Marcus R. , Davey Smith George , Tilling Kate 
Published: October 2017

AbstractBackgroundIt is often assumed that selection (including participation and dropout) does not represent an important source of bias in genetic studies. However, there is little evidence to date on the effect of genetic factors on participation.MethodsUsing data on mothers (N=7,486) and children (N=7,508) from the Avon Longitudinal Study of Parents and Children, we 1) examined the association of polygenic risk scores for a range of socio-demographic, lifestyle characteristics and health conditions related to continued participation, 2) investigated whether associations of polygenic scores with body mass index (BMI; derived from self-reported weight and height) and self-reported smoking differed in the largest sample with genetic data and a sub-sample who participated in a recent follow-up and 3) determined the proportion of variation in participation explained by common genetic variants using genome-wide data.ResultsWe found evidence that polygenic scores for higher education, agreeableness and openness were associated with higher participation and polygenic scores for smoking initiation, higher BMI, neuroticism, schizophrenia, ADHD and depression were associated with lower participation. Associations between the polygenic score for education and self-reported smoking differed between the largest sample with genetic data (OR for ever smoking per SD increase in polygenic score:0.85, 95% CI:0.81,0.89) and sub-sample (OR:0.95, 95% CI:0.88,1.02). In genome-wide analysis, single nucleotide polymorphism based heritability explained 17-31% of variability in participation.ConclusionsGenetic association studies, including Mendelian randomization, can be biased by selection, including loss to follow-up. Genetic risk for dropout should be considered in all analyses of studies with selective participation.
Overnight memory consolidation facilitates rather than interferes with new learning of similar materials - a study probing NMDA-receptors
Authors: Alizadeh Asfestani M , Braganza E , Schwidetzky J , Santiago J , Soekadar S , Born J , Feld GB 
Published: October 2017

AbstractWhereas sleep-dependent consolidation and its neurochemical underpinnings have been strongly researched, less is known about how consolidation during sleep affects subsequent learning. Since sleep enhances memory, it can be expected to pro-actively interfere with learning after sleep, in particular of similar materials. This pro-active interference should be enhanced by substances that benefit consolidation during sleep, such as D-cycloserine. We tested this hypothesis in two groups (Sleep, Wake) of young healthy participants receiving on one occasion D-cycloserine (175 mg) and on another occasion placebo, according to a double-blind balanced cross-over design. Treatment was administered after participants had learned a set of word-pairs (A-B list) and before nocturnal retention periods of sleep vs. wakefulness. After D-cycloserine blood plasma levels had dropped to negligible amounts, i.e., the next day in the evening, participants learned, in three sequential runs, new sets of word-pairs. One list – to enhance interference – consisted of the same cue words as the original set paired with a new target word (A-C list) and the other of completely new cue words (D-E set). Unexpectedly, during post-retention learning the A-C interference list was generally better learned than the completely new D-E list, which suggests that consolidation of previously encoded similar material enhances memory integration rather than pro-active interference. Consistent with this view, new learning of word-pairs was better after sleep than wakefulness. Similarly, D-cycloserine generally enhanced learning of new word-pairs, compared to placebo. This effect being independent of sleep or wakefulness, leads us to speculate that D-cycloserine, in addition to enhancing sleep-dependent consolidation, might mediate a time-dependent process of active forgetting.
Transcriptional control and exploitation of an immune-responsive family of plant retrotransposons
Authors: Zervudacki Jérôme , Yu Agnès , Amesefe Delase , Wang Jingyu , Drouaud Jan , Navarro Lionel , Deleris Angélique 
Published: October 2017

ABSTRACTMobilization of transposable elements (TEs) in plants has been recognized as a driving force of evolution and adaptation, in particular by providing genes with regulatory modules that impact their transcription. In this study, we employed anATCOPIA93Long terminal repeats (LTR) promoter-GUSfusion to show that this retrotransposon behaves like an immune-responsive gene during plant defense in Arabidopsis. We also showed that the reactivation of the endogenousATCOPIA93copy“EVD”, in the presence of bacterial stress, is not only negatively regulated by DNA methylation but also by Polycomb-mediated silencing—a mode of repression typically found at protein-coding and microRNA genes. Interestingly, one of theATCOPIA93-derived soloLTRs is located upstream of the disease resistance geneRPP4and is devoid of either DNA methylation or H3K27m3 marks. Through loss-of-function experiments, we demonstrated that this soloLTR is required for proper expression ofRPP4during plant defense, thus linking the responsiveness ofATCOPIA93to biotic stress and the co-option of its LTR for plant immunity.
The Wisconsin Registry for Alzheimer’s Prevention: A Review of findings and current directions
Authors: Johnson Sterling C. , Koscik Rebecca L. , Jonaitis Erin M. , Clark Lindsay R. , Mueller Kimberly D. , Berman Sara E. , Bendlin Barbara B. , Engelman Corinne D. , Okonkwo Ozioma C. , Hogan Kirk J. , Asthana Sanjay , Carlsson Cynthia M. , Hermann Bruce P. , Sager Mark A. 
Published: October 2017

ABSTRACTThe Wisconsin Registry for Alzheimer’s Prevention (WRAP) is a longitudinal observational cohort study enriched with persons with a parental history (PH) of probable Alzheimer’s Disease (AD) dementia. Since late 2001, WRAP has enrolled 1,561 people at a mean baseline age of 54. Participants return for a second visit four years after baseline and subsequent visits occur every two years. Eighty-one percent (1270) of participants remain active in the study at a current mean age of 64 and 9 years of follow-up. Serially assessed cognition, self-reported medical and lifestyle histories (e.g. diet, physical and cognitive activity, sleep, and mood), laboratory tests, genetics, and linked studies comprising molecular imaging, structural imaging and cerebrospinal fluid data, have yielded many important findings. In this cohort, PH of probable AD is associated with 46%APOEε4 positivity, more than twice the rate of 22% among persons without PH. Subclinical or worse cognitive decline relative to internal normative data has been observed in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau positivity. Biomarker elevations, but notAPOEor PH status, are associated with cognitive decline. Salutary health and lifestyle factors are associated with better cognition and brain structure, and lower AD pathophysiologic burden. Of paramount importance is establishing the amyloid and tau AD endophenotypes to which cognitive outcomes can be linked. Such data will provide new knowledge on the early temporal course of AD pathophysiology and inform the design of secondary prevention clinical trials.