bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIGHER LEVELS OF CEREBROSPINAL FLUID NITRITE AND NITRATE IN LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE
Authors: Santos-Lobato Bruno L. , Bortolanza Mariza , Batalhão Marcelo E. , Pimentel Ângela V. , Capellari-Carnio Evelin , Del-Bel Elaine A. , Tumas Vitor 
Published: June 2020

AbstractIntroductionLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID.MethodsWe measured CSF NOx levels in patients with PD with and without LID, and in healthy controls. The levels of CSF NOx levels were measured by ozone-based chemiluminescence.Results67 participants were enrolled. CSF NOx levels were higher in patients with PD with LID than in healthy controls (Kruskal-Wallis statistics = 7.24, p = 0.02). CSF NOx levels did not correlate with other clinical variables.ConclusionWe reported higher levels of nitric oxide in the CSF of patients with PD and LID.Highlights–Nitric oxide has a role on levodopa-induced dyskinesias in Parkinson’s disease–We measured CSF nitrite and nitrate in Parkinson’s disease patients with dyskinesias–CSF nitrite and nitrate were higher in Parkinson’s disease patients with dyskinesias
Optimal Control Measures to Combat COVID 19 Spread in Sri Lanka: A Mathematical Model Considering the Heterogeneity of Cases
Authors: Wickramaarachchi WPTM , Perera SSN 
Published: June 2020

AbstractThe COVID 19 pandemic caused by the novel corona virus (SARS-CoV-2) has been one of the major public health concerns across the globe, currently more than 3.5 million individuals have been infected, and the number of deaths has passed 250,000. The world wide burden of the disease has been massive, and the governments are in dilemma to protect the health system of the country while safeguarding the economy. There is no vaccine or antivirus drug found against this virus while multiple research groups are actively working on a suitable candidate. The only available mode of minimizing the disease burden has been to control its transmission among the population. Since the occurrence of first COVID 19 local case on 11 March 2020, the government of Sri Lanka introduced serious social distancing and public health interventions in its fullest capacity as a developing nation to effectively combat with the disease spread. This study focuses to develop a mathematical model to investigate the dynamic of this novel disease using an extended version of an SEIR compartmental structure considering the heterogeneity of cases such as asymptomatic, symptomatic with mild indications and the cases required intensive care treatments. All the measures and interventions are in progress with a significantly large social and economic cost, thus, optimal control techniques are used to identify the most appropriate strategies to minimize this cost. The results of the simulations prove that optimal control measures can be worked out as the epidemic curves are flattened while delaying the outbreak so that the health system might not be under pressure to treat and care the patients.
The neurodevelopment of anomalous perception: Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia
Authors: Rollins Colleen P.E. , Garrison Jane R. , Arribas Maite , Seyedsalehi Aida , Li Zhi , Chan Raymond C.K. , Yang Junwei , Wang Duo , Lio Pietro , Yan Chao , Yi Zheng-hui , Cachia Arnaud , Upthegrove Rachel , Deakin Bill , Simons Jon S. , Murray Graham K. , Suckling John 
Published: June 2020

AbstractBackgroundAll perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear.MethodsWe studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T structural magnetic resonance (MR) imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS) from MR images and constructed cortical folding covariance matrices organized by large-scale networks.ResultsIn both ethnic groups, we replicated a significantly shorter left PCS in patients with hallucinations compared to those without, and healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks.ConclusionThe discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.
Bayesian Networks in Healthcare: the chasm between research enthusiasm and clinical adoption
Authors: Kyrimi Evangelia , McLachlan Scott , Dube Kudakwashe , Fenton Norman 
Published: June 2020

AbstractProblemBayesian Networks (BN) can address real-world decision-making problems, and there is enormous and rapidly increasing interest in their use in healthcare. Yet, despite thousands of BNs in healthcare papers published yearly, evidence of their adoption in practice is extremely limited and there is no consensus on why.MethodA preliminary review was conducted to identify research gaps and justify the conduct of a broader scoping or systematic review of BNs in healthcareResultsWe highlight that: (1) there have been no significant attempts to systematically review the domain; (2) there are weaknesses in the way BN development processes are presented in the literature; and (3) in contrast to enthusiasm (including from clinicians) there has been negligible adoption of published BNs into clinical practice.ConclusionA systematic review of BNs in healthcare is needed to a) understand the chasm between research enthusiasm and clinical adoption; and b) improve clinical adoption.
The critical role of HDAC1 activates NSCLC growth by nicotine resistance Cisplatin
Authors: Peng Ching-Yi , Wu Jia-Ping 
Published: June 2020

AbstractNicotine is active in highly cisplatin-resistant cancer cells; however, there is little evidence for its resistant activity in lung cancer with cisplatin. Many mechanisms of cisplatin resistance have been proposed. The mechanisms of the nicotine treatment of cisplatin-resistant lung cancer for histone deacetylase 1 (HDAC1) activity is unknown. Nicotine was used to analyze cisplatin-resistant non-small cell lung cancer (NSCLC) cancer cell growth. Western blot was used to analyze cell cycle-related proteins. Cancer cell viability (cell survival) was measured with MTT assay. HDAC1 transfected NSCLC cells were used to analyze the direct binding between cytosol and nucleus distribution. Here, using cell viability and migration methods we firstly found nicotine regulated cisplatin-resistant NSCLC cells growth by targeting HDAC1. Expression of cisplatin was negatively correlated with HDAC1. And HDAC1 inhibitor, VPA, in the NSCLC cancer cells were predicted. Further experiments confirmed that HDAC1 directly targeted E2F and cisplatin. Besides, HDAC1 and cisplatin inhibited NSCLC cell growth and reduced expression of E2F and Cyclin E proteins. The use of nicotine compromised cisplatin-induced E2F suppression and cancer cell growth. NSCLC cancer cells co-transfected with nicotine and HDAC1 had a higher cell cycle proliferation. Taken all together, cisplatin interferes with DNA replication kills the cancer cell fastest proliferation; however, nicotine increased detoxification of cisplatin, inhibition of apoptosis and DNA repair, induced cisplatin resistance.
Negative frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures
Authors: Harrow Gabrielle L. , Lees John A. , Hanage William P. , Lipsitch Marc , Corander Jukka , Colijn Caroline , Croucher Nicholas J. 
Published: June 2020

AbstractStreptococcus pneumoniaecan be split into multiple strains, each with a characteristic combination of core and accessory genome variation, able to co-circulate and compete within the same hosts. Previous analyses of epidemiological datasets suggested the short-term vaccine-associated dynamics ofS. pneumoniaestrains may be mediated through multi-locus negative frequency-dependent selection (NFDS), acting to maintain accessory loci at equilibrium frequencies. To test whether this model could explain how such multi-strain populations were generated, it was modified to incorporate recombination. The outputs of simulations featuring symmetrical recombination were compared with genomic data on locus frequencies and distributions between genotypes, pairwise genetic distances and tree shape. These demonstrated NFDS prevented the loss of variation through neutral drift, but generated unstructured populations of diverse isolates. Making recombination asymmetrical, favouring deletion of accessory loci over insertion, alongside multi-locus NFDS significantly improved the fit to genomic data. In a population at equilibrium, structuring into multiple strains was stable due to outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. As many bacteria inhibit the integration of insertions into their chromosomes, this combination of asymmetrical recombination and multi-locus NFDS may underlie the co-existence of strains within a single ecological niche.
How Accurate Are Circular Dichroism Based Secondary Structure Estimates?
Authors: Nagy Gabor , Grubmüller Helmut 
Published: June 2020

AbstractCircular dichroism (CD) spectroscopy is highly sensitive to the secondary structure (SS) composition of proteins. Several methods exist to either estimate the SS composition of a protein or to validate existing structural models using its CD spectrum. The accuracy and precision of these methods depend on the quality of both the measured CD spectrum and the used reference structure. Using a large reference protein set with high quality CD spectra and synthetic data derived from this set, we quantified deviations from both ideal spectra and reference structures due to experimental limitations. We also determined the impact of these deviations on SS estimation, CD prediction, and SS validation methods of the SESCA analysis package. With regard to the CD spectra, our results suggest intensity scaling errors and non-SS contributions as the main causes of inaccuracies. These factors also can lead to overestimated model errors during validation. The errors of the used reference structures combine non-additively with errors caused by the CD spectrum, which increases the uncertainty of model validation. We have further shown that the effects of scaling errors in the CD spectrum can be nearly eliminated by appropriate re-scaling, and that the accuracy of model validation methods can be improved by accounting for typical non-SS contributions. These improvements have now been implemented within the SESCA package.
Cold induced chromatin compaction and nuclear retention of clock mRNAs resets the circadian rhythm
Authors: Fischl Harry , McManus David , Oldenkamp Roel , Schermelleh Lothar , Mellor Jane , Jagannath Aarti , Furger Andre 
Published: June 2020

AbstractCooling patients to sub-physiological temperatures is an integral part of modern medicine. We show that cold exposure induces temperature-specific changes to the higher-order chromatin and gene expression profiles of human cells. These changes are particularly dramatic at 18°C, a temperature synonymous with that experienced by patients undergoing controlled deep-hypothermia during surgery. Cells exposed to 18°C exhibit largely nuclear-restricted transcriptome changes. These include the nuclear accumulation of core circadian clock suppressor gene transcripts, most notablyREV-ERBα. This response is accompanied by compaction of higher-order chromatin and hindrance of mRNPs from engaging nuclear pores. Rewarming reverses chromatin compaction and releases the transcripts into the cytoplasm, triggering a pulse of suppressor gene proteins that resets the circadian clock. We show that cold-induced upregulation of REV-ERBα alone is sufficient to trigger this resetting. Our findings uncover principles of the cellular cold-response that must be considered for current and future applications involving therapeutic deep-hypothermia.
Molecular phylogenetics and micromorphology of Australasian Stipeae (Poaceae), and the interrelation of whole-genome duplication and evolutionary radiations in this grass tribe
Authors: Tkach Natalia , Nobis Marcin , Schneider Julia , Becher Hannes , Winterfeld Grit , Barkworth Mary E. , Jacobs Surrey W. L. , Röser Martin 
Published: June 2020

ABSTRACTThe mainly Australian grass genusAustrostipawith ca. 64 species represents a remarkable example of an evolutionary radiation. To investigate aspects of diversification, macro- and micromorphological variation in this genus we conducted a molecular phylogenetic and scanning electron microscopy (SEM) analysis including representatives from all of its accepted subgenera.Plastid DNA variation withinAustrostipawas low and only few lineages were resolved. Nuclear ITS andAcc1yielded comparable groupings of taxa and resolved subgeneraArbuscula,Petaurista,Bambusinain a common clade and as monophyletic. In summary, we suggest recognizing nine subgenera inAustrostipa.Because of its taxonomic significance in Stipeae, we studied the lemma epidermal structure in 34 representatives ofAustrostipa.In most species, the lemma epidermal pattern (LEP) was relatively uniform (maize-like LEP), but in six species it was more similar to that ofStipas.str.,Neotrinia,PtilagrostisandOrthoraphium.The species representing subgeneraLobatae,Petaurista,BambusinaandA. muellerifrom subg.Tuberculataewere well-separated from all the other species included in the analysis.Two different sequence copies ofAcc1were found in polyploidAustrostipaandAnemanthele. Each of the copy types formed a single clade. This was also true of the sampled species ofStipas.str., but their clades were strongly separated from those ofAustrostipaandAnemanthele. This underlines the statement of Tzvelev (1977) that most if not all contemporary Stipeae are of hybrid origin and demonstrates it for the first time unambiguously on the molecular level.Chromosome number variation is surveyed and reviewed for the whole tribe Stipeae and interpreted in a molecular phylogenetic framework. The rather coherent picture of chromosome number variation underlines the phylogenetic and evolutionary significance of this character.The closest extant relatives ofAustrostipaandAnemantheleare in the clade ofAchnatherums.str.,Celtica,OloptumandStipellula. These genera are most abundant in Central and Eastern Asia, which makes a colonization of Australian and New Zealand from this region more likely, perhaps via long-distance dispersal, than colonization of Australia from southern South America via Antarctica as previously invoked.Supporting Informationmay be found online in the Supporting Information section at the end of the article.
Ultra-sensitive nanozyme-based chemiluminescence paper test for rapid diagnosis of SARS-CoV-2 infection
Authors: Liu Dan , Ju Chenhui , Han Chao , Shi Rui , Chen Xuehui , Duan Demin , Yan Jinghua , Yan Xiyun 
Published: June 2020

AbstractThe recently emerged coronavirus disease COVID-19 has now evolved into a global pandemic. Early detection is crucial for its effective control. Nucleic acid testing for viral pathogen and serological testing for host antibodies are playing important roles in current COVID-19 diagnosis. However, while nucleic acid testing is complicated, facility-restricted and time-consuming, antibody testing may result in high rates of false-negative diagnoses, especially during the early stages of viral infection. Thus, a more rapid and reliable test for both early COVID-19 diagnosis and whole-population screening is urgently needed. Here, we developed a novel nanozyme-based chemiluminescence paper assay for rapid and high-sensitive testing of SARS-CoV-2 spike antigen. Our paper test uses a newly established peroxidase-mimic Co-Fe@hemin nanozyme instead of natural HRP that catalytically amplifies the chemiluminescent signal, allowing for target concentrations to be as low as 0.1 ng/ml. Furthermore, our nanozyme-based chemiluminescence test exhibits a linear range that is 32-fold wider compared to ELISA tests. Importantly, testing is completed in less than 16 min, compared to 1-2 h required for ELISA or nucleic acid tests. Critically, signal detection is feasible using a smartphone camera. Ingredients for our test are simple and readily available, rendering overall cost considerably lower than those used in current diagnoses. In conclusion, our novel test provides a high-sensitive, point-of-care testing (POCT) approach for SARS-CoV-2 antigen detection, which should greatly increase current early screening capacities for suspected infections, and considerably lower demand for national healthcare resources.
Iron Supplementation Eliminates Antagonistic Interactions Between Root Associated Bacteria
Authors: Eng Thomas , Herbert Robin A. , Martinez Uriel , Wang Brenda , Chen Joseph , Brown Ben , Deutschbauer Adam , Bissell Mina , Mortimer Jenny C. , Mukhopadhyay Aindrila 
Published: June 2020

AbstractThe rhizosphere microbiome (rhizobiome) plays a critical role in plant health and development. However the processes by which the constituent microbes interact to form and maintain a community are not well understood. To investigate these molecular processes, we examined pairwise interactions between 11 different microbial isolates under selected nutrient-rich and nutrient-limited conditions. We observed that when grown with media supplemented with 56 mM glucose, 2 microbial isolates were able to inhibit the growth of 6 out of 11 other microbes tested. The interaction between microbes persisted even after the antagonistic microbe was removed, upon exposure to spent media. To probe the genetic basis for these antagonistic interactions, we used a barcoded transposon library in a proxy bacterium,Pseudomonas putida, to identify genes which showed enhanced sensitivity to the antagonistic factor(s) secreted byAcinetobactersp. 02. Iron metabolism-related gene clusters inP. putidawere implicated by this systems-level analysis. The supplementation of iron prevented the antagonistic interaction in the original microbial pair supporting the hypothesis that iron limitation drives antagonistic microbial interactions between rhizobionts. We conclude that rhizobiome community composition is influenced by competition for limiting nutrients with implications for growth and development of the plant.
The Mechanism of Vesicle Solubilization by the Detergent Sodium Dodecyl Sulfate
Authors: Juan-Colás José , Dresser Lara , Morris Katie , Lagadou Hugo , Ward Rebecca H. , Burns Amy , Tear Steve , Johnson Steven , Leake Mark C. , Quinn Steven D. 
Published: June 2020

AbstractMembrane solubilization by sodium dodecyl sulfate (SDS) is indispensable for many established biotech-nological applications, including viral inactivation and protein extraction. Although the ensemble thermo-dynamics have been thoroughly explored, the underlying molecular dynamics have remained inaccessible, owing to major limitations of traditional measurement tools. Here, we integrate multiple advanced biophysical approaches to gain multi-angle insight into the time-dependence and fundamental kinetic steps associated with the solubilization of single sub-micron sized vesicles in response to SDS. We find that the accumulation of SDS molecules on in-tact vesicles triggers biphasic solubilization kinetics comprising an initial vesicle expansion event followed by rapid lipid loss and micellization. Our findings support a general mechanism of detergent-induced membrane solubilization and we expect the framework of correlative biophysical technologies presented here will form a general platform for elucidating the complex kinetics of membrane perturbation induced by a wide variety of surfactants and disrupting agents.
High quality single amplicon sequencing method for illumina platforms using ‘N’ (0-10) spacer primer pool without PhiX spik-in
Authors: Naik Tejali , Sharda Mohak , Pandit Awadhesh 
Published: June 2020

AbstractIllumina sequencing platform requires base diversity in initial 11 cycles for efficient cluster identification and color matrix estimation. This limitation yields low quality data for amplicon libraries having homogeneous base composition. Spike-in of PhiX library ensures base diversity but overall reduces the number of sequencing reads for data analysis. To overcome such low diversity issues during amplicon sequencing on illumina platforms we developed high throughput single amplicon sequencing method by introducing ‘N’ spacers in target gene amplification primers that are pooled for simple handling. We evaluated the efficiency of ‘N’ spacer primers by targeting bacterial 16S V3-V4 region, demonstrating heterogonous base library construction. Addition of ‘N’ spacer causes sequencing frame shift at every base that leads to base diversity and produces heterogenous high quality reads within single amplicon library. We have written a python script “MetReTrim” to trim the heterogenous ‘N’ spacers from the pre-processed reads. This method terminates the need for PhiX spike-in and allows for multiplexing of multiple samples, greatly reducing the overall cost and yields improved sequence quality.