bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling and Cost Benefit Analysis to Guide Deployment of POC Diagnostics for Non-typhoidalSalmonellaInfections with Antimicrobial Resistance
Authors: Manore Carrie , Graham Todd , Carr Alexa , Feryn Alicia , Jakhar Shailja , Mukundan Harshini , Highlander Hannah Callender 
Published: August 2018

ABSTRACTInvasive non-typhoidalSalmonella(NTS) is among the leading causes of blood stream infections in sub-Saharan Africa and other developing regions, especially among pediatric populations. Invasive NTS can be difficult to treat and have high case-fatality rates, in part due to emergence of strains resistant to broad-spectrum antibiotics. Furthermore, improper treatment contributes to increased antibiotic resistance and death. Point of care (POC) diagnostic tests that rapidly identify invasive NTS infection, and differentiate between resistant and non-resistant strains, may greatly improve patient outcomes and decrease resistance at the community level. Here we present for the first time a model for NTS dynamics in high risk populations that can analyze the potential advantages and disadvantages of four strategies involving POC diagnostic deployment, and the resulting impact on antimicrobial treatment for patients. Our analysis strongly supports the use of POC diagnostics coupled with targeted antibiotic use for patients upon arrival in the clinic for optimal patient and public health outcomes. We show that even the use of imperfect POC diagnostics can significantly reduce total costs and number of deaths, provided that the diagnostic gives results quickly enough that patients are likely to return or stay to receive targeted treatment.
3D Tissue elongation via ECM stiffness-cued junctional remodeling
Authors: Chen Dong-Yuan , Crest Justin , Streichan Sebastian J. , Bilder David 
Published: August 2018

ABSTRACTOrgans are sculpted by extracellular as well as cell-intrinsic forces, but how collective cell dynamics are orchestrated in response to microenvironmental cues is poorly understood. Here we apply advanced image analysis to reveal ECM-responsive cell behaviors that drive elongation of the Drosophila follicle, a model 3D system in which basement membrane stiffness instructs tissue morphogenesis. Throughin totomorphometric analyses of WT and ‘round egg’ mutants, we find that neither changes in average cell shape nor oriented cell division are required for appropriate organ shape. Instead, a major element is a reorientation of elongated cells at the follicle anterior. Polarized reorientation is regulated by mechanical cues from the basement membrane, which are transduced by the Src tyrosine kinase to alter junctional E-cadherin trafficking. This mechanosensitive cellular behavior represents a conserved mechanism that can elongate ‘edgeless’ tubular epithelia in a process distinct from those that elongate bounded, planar epithelia.
A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity
Authors: Muddapu Vignayanandam R. , Mandali Alekhya , Chakravarthy Srinivasa V. , Ramaswamy Srikanth 
Published: August 2018

AbstractParkinson’s disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). A full understanding of the underlying pathogenesis of this cell loss is unavailable, though a number of mechanisms have been indicated in the literature. A couple of these mechanisms, however, show potential for the development of radical and promising PD therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc cells by virtue of their excessive energy demands; the other is the excitotoxicity caused by excessive glutamate release onto SNc by an overactive Subthalamic Nucleus (STN). To investigate the latter hypothesis computationally, we developed a spiking neuron network model of the SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in a ‘stress’ variable; when the stress in a SNc neuron exceeds a stress threshold the neuron dies. The model shows that the interaction between SNc and STN involves a positive feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway effect that leads to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned PD mechanisms: metabolic vulnerability and glutamate excitotoxicity. Our simulation results show that the excitotoxic cause of SNc cell loss in PD might be initiated by weak excitotoxicity mediated by energy deficit, followed by strong excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies are simulated in the model to test their efficacy in slowing down or arresting SNc cell loss. Among the current therapeutics, glutamate inhibition, dopamine restoration, subthalamotomy and deep brain stimulation showed superior neuroprotective effects in the proposed model.
Comparison of environmental, biological and anthropogenic causes of wildlife–vehicle collisions among three large herbivore species
Authors: Christine Saint-Andrieux , Clément Calenge , Christophe Bonenfant 
Published: August 2018

AbstractWildlife–vehicle collisions are of increasing concern with regards to the continuous and accelerating anthropogenic development. Preventing and mitigating collisions with wildlife will require a better understanding of the environmental and biological drivers of collision risks. Because species of large mammals differ in terms of food requirements, habitat selection and movement behaviours we tested at the management unit level if the density of collisions with red deer, roe deer and wild boar differed in terms of spatial distribution and explanatory factors. From 20,275 documented collisions in France between years 1990 and 2006, we found marked differences in the most influential environmental factors accounting for the density of collisions among the three species. The effect of road density was higher for the red deer than for the two other species and did not level off at our spatial-scale of observation. As expected, the annual hunting harvest – interpreted as a proxy of population abundance – was positively associated with the density of collisions for all species, being the strongest for red deer. While the collision density decreased with the proportion of forest in a management unit for wild boar, it increased with the fragmentation of forests for red deer that commute among forest patches between day and night. To reduce the number of wildlife– vehicle collisions, our results suggest to generalise road fencing and/or a control of abundance of large herbivore populations. Mitigation measures should target units where the collision risk is the highest for the most problematic species.
Deciphering the roles of N-glycans on collagen-platelet interactions
Authors: Toonstra Christian , Hu Yingwei , Zhang Hui 
Published: August 2018

AbstractCollagen is a potent agonist for platelet activation, presenting itself as a key contributor to coagulation via interactions with platelet glycoproteins. The fine-details dictating platelet-collagen interactions are poorly understood. In particular, glycosylation could be a key determinant in the platelet-collagen interaction. Here we report an affinity purification coupled to mass spectrometry-based approach to elucidate the function of N-glycans in dictating platelet-collagen interactions. By integrative proteomic and glycoproteomic analysis of collagen-platelet interactive proteins with N-glycan manipulation, we demonstrate that the interaction of platelet adhesive receptors with collagen are highly N-glycan regulated, with glycans on many receptors playing positive roles on collagen binding, with glycans on other platelet glycoproteins exhibiting inhibitory roles on the binding to collagen. Our results significantly enhance our understanding of the details of glycans influencing the platelet-collagen interaction.
Nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
Authors: Agapova Aleksandra , Hunt Debbie M. , Petridis Michael , Garza-Garcia Acely , Sohaskey Charles D. , Carvalho Luiz Pedro S. de 
Published: August 2018

AbstractBacterial metabolism is fundamental to pathogenesis and has a dominant effect on bacterial killing by antibiotics. Here we explore how Mycobacterium tuberculosis utilises amino acids as nitrogen sources, using a combination of bacterial physiology and stable isotope tracing coupled to liquid chromatography mass spectrometry metabolomics methods. Our results define core properties of the nitrogen metabolic network from M. tuberculosis, such as: (i) the lack of homeostatic control of amino acid pool sizes; (ii) similar rates of utilisation of different amino acids as sole nitrogen sources; (iii) improved nitrogen utilisation from amino acids compared to ammonium; and (iv) co-metabolism of nitrogen sources. Finally, we discover that alanine dehydrogenase, is involved in ammonium assimilation in M. tuberculosis, in addition to its essential role in alanine utilisation. This study represents the first in-depth analysis of nitrogen source utilisation by metabolic generatlist M. tuberculosis and reveals a flexible metabolic network with characteristics that are likely product of evolution in the human host.
Palantir characterizes cell fate continuities in human hematopoiesis
Authors: Setty Manu , Kiseliovas Vaidotas , Levine Jacob , Gayoso Adam , Mazutis Linas , Pe’er Dana 
Published: August 2018

AbstractRecent studies using single cell RNA-seq (scRNA-seq) data derived from differentiating systems have raised fundamental questions regarding the discrete vs continuous nature of both differentiation and cell fate. Here we present Palantir, an algorithm that models trajectories of differentiating cells, which treats cell-fate as a probabilistic process, and leverages entropy to measure the changing nature of cell plasticity along the differentiation trajectory. Palantir generates a high resolution pseudotime ordering of cells, and assigns each cell state with its probability to differentiate into each terminal state. We apply Palantir to human bone marrow scRNA-seq data and detect key landmarks of hematopoietic differentiation. Palantir’s resolution enables identification of key transcription factors driving lineage fate choices, as these TFs closely track when cells lose plasticity. We demonstrate that Palantir is generalizable to diverse tissue types and well-suited to resolve less studied differentiating systems.
Active information maintenance in working memory by a sensory cortex
Authors: Zhang Xiaoxing , Yan Wenjun , Wang Wenliang , Fan Hongmei , Hou Ruiqing , Chen Yulei , Chen Zhaoqin , Duan Shumin , Compte Albert , Li Chengyu T. 
Published: August 2018

SummaryWorking memory is a critical function of the brain to maintain and manipulate information over delay periods of seconds. Sensory areas have been implicated in working memory; however, it is debated whether the delay-period activity of sensory regions is actively maintaining information or passively reflecting top-down inputs. We hereby examined the anterior piriform cortex, an olfactory cortex, in head-fixed mice performing a series of olfactory working memory tasks. Information maintenance is necessary in these tasks, especially in a dual-task paradigm in which mice are required to perform another distracting task while actively maintaining information during the delay period. Optogenetic suppression of the piriform cortex activity during the delay period impaired performance in all the tasks.Furthermore, electrophysiological recordings revealed that the delay-period activity of the anterior piriform cortex encoded odor information with or without the distracting task.Thus, this sensory cortex is critical for active information maintenance in working memory.
Deep-learning-based flexible pipeline for segmenting and tracking cells in 3D image time series for whole brain imaging
Authors: Wen Chentao , Miura Takuya , Fujie Yukako , Teramoto Takayuki , Ishihara Takeshi , Kimura Koutarou D. 
Published: August 2018

AbstractThe brain is a complex system that operates based on coordinated neuronal activities. Brain-wide cellular calcium imaging techniques have quickly advanced in recent years and become powerful tools for understanding the neuronal activities of small animal models. The whole brain imaging generally requires to extract the neuronal activities from three-dimensional (3D) image series. Unfortunately, the 3D image series are obtained under imaging conditions different among laboratories and extracting neuronal activities from the data requires multiple processes. Therefore researchers need to develop their own software, which has prevented the application of whole-brain imaging experiments in more laboratories. Here, we combined traditional image processing techniques with the powerful deep-learning method which can be flexibly modified to fit 3D image data in the nematodeCaenorhabditis elegansobtained under different conditions. We first trained the 3D U-net deep network to classify each pixel into cell and non-cell categories. Cells merged as a whole region were further separated into individual cells by watershed segmentation. The cells were then tracked in 3D space over time with the combination of a feedforward network and a point set registration method to use local and global relative positions of the cells, respectively. Remarkably, one manually annotated 3D image combined with data augmentation was sufficient for training the deep networks to obtain satisfactory tracking results. Our method correctly tracked more than 98% of neurons in three different image datasets and successfully extracted brain-wide neuronal activities. Our method worked well even when the sampling rate was reduced: 86% correct in case 4/5 frames were removed, and when artificial noise was added into the raw images: 91% correct in case 35 times of background-level noise was added. Our results proved that deep learning is widely applicable to different datasets and can help us in establishing a flexible pipeline for extracting whole brain activities.
In vitro determination of the CB1 efficacy of illicit synthetic cannabinoids
Authors: Sachdev Shivani , Vemuri Kiran , Banister Samuel D. , Longworth Mitchell , Kassiou Michael , Santiago Marina , Makriyannis Alexandros , Connor Mark 
Published: August 2018

AbstractBACKGROUND AND PURPOSEThe morbidity and mortality associated with recreational use of synthetic cannabinoid receptor agonists (SCRAs) is a major health concern, and may involve over-activation of CB1 receptors. Thus, we sought to determine the efficacy of 13 SCRAs at CB1 using receptor depletion with the irreversible CB1 antagonist AM6544 followed by fitting the curve with the Black and Leff operational model to calculate efficacy.EXPERIMENTAL APPROACHReceptor depletion in mouse AtT-20 neuroblastoma cells stably expressing human CB1 was achieved by pre-treatment of cells with AM6544 (10 µM, 60 mins). The CB1-mediated hyperpolarisation of AtT20 cells was measured using membrane potential dye. From data fit to the operational model, the efficacy (tau) and affinity (KA) parameters were obtained for each drug.KEY RESULTSAM6544 did not affect the potency or maximal effect of native somatostatin receptor-induced hyperpolarisation (Control, pEC50 9.13 ± 0.05, Emax 38 ± 1%; AM6544 treated pEC50 9.18 ± 0.04, Emax 39 ± 0.7%). The tau value of ∆9-THC was 70-fold less than the reference CB-agonist CP55940, and 240-fold less than the highest efficacy SCRA, 5F-MDMB-PICA. Most of the SCRAs had about 50% of the efficacy of CP55940. There was no correlation between the tau and KA values for any SCRA.CONCLUSION AND IMPLICATIONSAll the SCRA tested showed substantially higher agonist activity at CB1 than ∆9-THC, which may contribute to the adverse effects seen with these drugs but not ∆9-THC, although the mechanisms underlying SCRA toxicity are still poorly defined.
Dopamine D1 receptor signalling differentially regulates action sequences and turning behaviour in freely movingDrosophila
Authors: Kottler Benjamin , Faville Richard , Bridi Jessika , Hirth Frank 
Published: August 2018

AbstractHere, we introduce a novel behavioural paradigm to study neural circuits and mechanisms underlying action selection and decision-making in freely movingDrosophila. We first validate our approach by studyingFoxPmutants and show that normally invariant patterns of motor activity and turning behaviour are altered in these flies, reminiscent of indecision. Then, focusing on central complex (CX) circuits known to integrate different sensory modalities and controlling premotor regions, we show that action sequences and turning behaviour are regulated by dopamine D1 (Dop1R1) receptor signalling. Dop1R1 inputs onto CX columnar wedge and ellipsoid body R2/R4m ring neuron circuits both negatively gate motor activity but inversely control turning behaviour. While flies deficient of D1 receptor signalling present normal turning behaviour despite decreased activity, restoring Dop1R1 level in R2/R4m-specific circuitry affects the temporal organisation of motor actions and turning. These findings suggest that columnar wedge and ring neuron circuits of the CX differentially modulate patterns of motor action sequences and turning behaviour by comparative Dop1R1 signalling for goal-directed locomotion.
Adaptive metabolic strategies in consumer-resource models
Authors: Pacciani-Mori Leonardo , Giometto Andrea , Suweis Samir , Maritan Amos 
Published: August 2018

AbstractBacteria are able to adapt to different environments by changing their “metabolic strategies”, i.e. the ways in which they uptake available resources from the environment. For example, in a celebrated experiment Jacques Monod showed that bacteria cultured in media containing two different sugars consume them sequentially, resulting in bi-phasic growth curves called “diauxic shifts”. From the theoretical point of view, microbial communities are commonly described using MacArthur’s consumer-resource model, which describes the population dynamics of species competing for a given set of resources. In this model, however, metabolic strategies are treated as constant parameters. Here, we introduce adaptive metabolic strategies in the framework of consumer-resource models, allowing the strategies to evolve to maximize each species’ relative fitness. By doing so, we are able to describe quantitatively, and without invoking any specific molecular mechanisms for the metabolism of the microbial species, growth curves of the baker’s yeastSaccharomyces cerevisiaemeasured in a controlled experimental set-up, with galactose as the primary carbon source. We also show that metabolic adaptation enables the community to self-organize, allowing species to coexist even in the presence of few resources, and to respond optimally to a time-dependent environment. A connection between the Competitive Exclusion Principle and the metabolic theory of ecology is also discussed.
Epidemiological impact of hepatitis B vaccination (Monastir_ Tunisia ; 2000-17)
Authors: Dhouib Wafa , Kacem Meriem , Samia Grira , Maalel Issam , Zemni Imen , Abroug Hela , fredj Manel Ben , Salah Arwa Ben , Chelly Souhir , Green Essia , Djobbi Amira , Belguith Asma Sriha 
Published: August 2018

AbstractBackground: In 2016, the first global health sector strategy on viral hepatitis was endorsed with the goal of eliminating viral hepatitis as a public health threat by 2030. In Tunisia, effective vaccines for hepatitis B (HBV) have been added to the expanded programme of immunization (EPI) since July 1995 for new borns. We expected to have a decreasing trend in the prevalence rate of reported HBV. Our study aimed to address the epidemiological profile of HBV, to assess trends by age and gender in Monastir governorate over a period of 18 years according to immunization status and to estimate the burden (years lived with disability YLDs) of this pathology. Methods: We performed a descriptive cross sectional study of declared HBV from January 1, 2000 to December 31, 2017 defined as having positive serologic markers for HBs Ag. All declared patients were residents of Monastir’s Governorate. EPI included two periods, the first between 1995 and 2006 following a three-dose schedule (3, 4, 9 months). The second PI cohort after 2006 following a three-dose schedule (0, 2, 6 months). Results: During 18 years, 1526 cases of HBV were declared in Monastir with a mean of 85 cases per year. We estimated a mean of 1699 declared cases per year of HBV in Tunisia. CPR was 16.85/100,000 inh being the higher in age group of 20-39 years and in men .ASR was 15.99/100,000 inh, being 35.5 in men and 8.69 in women. During the study period, declared cases among presumed immunized (PI) person against HBV were 32(2.0%). Among PI cases, 29 were from the first period and 3 were from the second. We established a negative trend over 18 years of hepatitis B. The age group of 20 to 39 was the most common with a sharply decline. Presumed not immunized (PNI) HBV cases are decreasing by years with a prediction of 35 cases in 2024. Reported HBV contributed to 1.26 YLDs per 100,000 inh. The highest rate of YLDs occurred at the age 20-39 (2.73 YLDs per 100,000 inh). During 18 years, YLDs were 114.45 in Monastir with a mean of 2293.65 YLDs of HBV in Tunisia. Conclusion, this study showed a law prevalence rate and a decreasing trend of HBV during 18 years showing an efficacy of immunization and confirming that the universal hepatitis B vaccination in Tunisia has resulted in progress towards the prevention and control of hepatitis B infection. These findings should be demonstrated in other Tunisian regions with a standardized serological profile.