bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is There Any Clinical Value of Adding 123I-Metaiodobenzylguanidine Myocardial Scintigraphy to 123I-Ioflupane (DaTscan) in the Differential Diagnosis of Parkinsonism?
Authors: Stathaki Maria , Koukouraki Sophia , Simos Panagiotis , Boura Iro , Papadaki Emmanouela , Bourogianni Olga , Tsaroucha Angeliki , Kapsoritakis Nikolaos , Mitsias Panayiotis , Spanaki Cleanthe 
Published: May 2020

Purpose
The aim of the study is to evaluate the impact of myocardial 123I-metaiodobenzylguanidine (MIBG) in the diagnosis, clinical management, and differential diagnosis of Parkinson disease (PD) and non-PD parkinsonism.

Methods
The study enrolled 41 patients with parkinsonism. An initial diagnosis was reached after thorough clinical and imaging evaluation. After 2 to 5 years of follow-up, a final diagnosis was established. All patients underwent, soon after their initial visit, presynaptic striatal DaT scintigraphy with 123I-FP-CIT (DaTscan) and 123I-MIBG myocardial scintigraphy. DaTscan is not specific to distinguish among different types of neurodegenerative parkinsonism. 123I-MIBG myocardial scintigraphy displays the functional status of cardiac sympathetic nerves, which is reduced in PD/dementia with Lewy bodies (DLB) and normal in atypical parkinsonian syndromes and secondary or nondegenerative parkinsonism.

Results
No patients showed adverse effects during or after both scintigraphies. A positive DaTscan was found in all patients in the PD/DLB group (17/17) and in 15 of 24 patients in the non-PD group. Myocardial 123I-MIBG scintigraphy was associated with lower sensitivity (82% vs 100%) but higher specificity than DaTscan (79% vs 38%) in diagnosis PD/DLB from non-PD parkinsonism. A positive scan result on both techniques, to confirm diagnosis of PD/DLB, significantly improved the specificity of DaTscan, from 38% to 75%, with no reduction in sensitivity.

Conclusions
Myocardial 123I-MIBG imaging provides complementary value to 123I-FP-CIT in the proper diagnosis, treatment plan, and differential diagnosis between PD and other forms of parkinsonism.
The far side of the COVID-19 epidemic curve: local re-openings and re-closings based on globally coordinated triggers may work best
Authors: Karatayev Vadim A. , Anand Madhur , Bauch Chris T. 
Published: May 2020

AbstractIn the late stages of an epidemic, infections are often sporadic and geographically distributed. Spatially structured stochastic models can capture these important features of disease dynamics, thereby allowing a broader exploration of interventions. Here we develop a stochastic model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission amongst an interconnected group of population centres representing counties, municipalities and districts (collectively, “counties”). The model is parameterized with demographic, epidemiological, testing, and travel data from Ontario, Canada. We explore the effects of different control strategies after the epidemic curve has been flattened. We compare a local strategy of re-opening (and re-closing, as needed) schools and workplaces county-by-county according to triggers for county-specific infection prevalence, to a global strategy of province-wide re-opening and re-closing according to triggers for province-wide infection prevalence. We find that the local strategy results in a similar number coronavirus disease (COVID-19) cases but significantly fewer person-days of closure, even under high inter-county travel scenarios. However, both cases and person-days lost to closure rise when county triggers are not coordinated and when testing rates vary among counties. Finally, we show that local strategies can also do better in the early epidemic stage but only if testing rates are high and the trigger prevalence is low. Our results suggest that pandemic planning for the far side of the COVID-19 epidemic curve should consider local strategies for re-opening and re-closing.
Identification of antigen-specific TCR sequences using a strategy based on biological and statistical enrichment in unselected subjects
Authors: Smith Neal P. , Ruiter Bert , Virkud Yamini V. , Shreffler Wayne G. 
Published: May 2020

AbstractRecent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unrelated individuals. The biological enrichment entails fluorescence-activated cell sorting ofin vitroantigen-activated memory CD4+T cells followed by TCRβ sequencing. The resulting TCRβ sequences are then filtered by selecting those that are statistically enriched when compared to their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3 amino acid sequences that had similar characteristics to validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3s revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3s unveiled themselves as core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell mediated disorders, and to yield new biomarkers and biological insights.
Metabolic engineering ofEscherichia colifor optimized biosynthesis of nicotinamide mononucleotide, a noncanonical redox cofactor
Authors: Black William B. , Aspacio Derek , Bever Danielle , King Edward , Zhang Linyue , Li Han 
Published: May 2020

AbstractBackgroundNoncanonical redox cofactors are emerging as important tools in cell-free biosynthesis to increase the economic viability, to enable exquisite control, and to expand the range of chemistries accessible. However, these noncanonical redox cofactors need to be biologically synthesized to achieve full integration with renewable biomanufacturing processes.ResultsIn this work, we engineeredEscherichia colicells to biosynthesize the noncanonical cofactor nicotinamide mononucleotide (NMN+), which has been efficiently used in cell-free biosynthesis. First, we developed a growth-based screening platform to identify effective NMN+biosynthetic pathways inE. coli. Second, we explored various pathway combinations and host gene disruption to achieve an intracellular level of ~1.5 mM NMN+, a 130-fold increase over the cell’s basal level, in the best strain, which features a previously uncharacterized nicotinamide phosphoribosyltransferase (NadV) fromRalstonia solanacearum.Last, we revealed mechanisms through which NMN+accumulation impactsE. colicell fitness, which sheds light on future work aiming to improve the production of this noncanonical redox cofactor.ConclusionThese results further the understanding of effective production and integration of NMN+intoE. coli. This may enable the implementation of NMN+-directed biocatalysis without the need for exogenous cofactor supply.
The kinetic landscape of an RNA binding protein in cells
Authors: Sharma Deepak , Zagore Leah L. , Brister Matthew M. , Ye Xuan , Crespo-Hernández Carlos E. , Licatalosi Donny D. , Jankowsky Eckhard 
Published: May 2020

ABSTRACTGene expression in higher eukaryotic cells orchestrates interactions between thousands of RNA binding proteins (RBPs) and tens of thousands of RNAs1. The kinetics by which RBPs bind to and dissociate from their RNA sites are critical for the coordination of cellular RNA-protein interactions2. However, these kinetics were experimentally inaccessible in cells. Here we show that time-resolved RNA-protein crosslinking with a pulsed femtosecond UV laser, followed by immunoprecipitation and high throughput sequencing allows the determination of binding and dissociation kinetics of the RBP Dazl for thousands of individual RNA binding sites in cells. This kinetic crosslinking and immunoprecipitation (KIN-CLIP) approach reveals that Dazl resides at individual binding sites only seconds or shorter, while the sites remain Dazl-free markedly longer. The data further indicate that Dazl binds to many RNAs in clusters of multiple proximal sites. The impact of Dazl on mRNA levels and ribosome association correlates with the cumulative probability of Dazl binding in these clusters. Integrating kinetic data with mRNA features quantitatively connects Dazl-RNA binding to Dazl function. Our results show how previously inaccessible, kinetic parameters for RNA-protein interactions in cells can be measured and how these data quantitatively link RBP-RNA binding to cellular RBP function.
Anti-GPR56 monoclonal antibody potentiates GPR56-mediated Src-Fak signaling to modulate cell adhesion
Authors: Chatterjee Treena , Zhang Sheng , Posey Tressie A. , Wu Ling , Yu Wangsheng , Liu Qingyun J. , Carmon Kendra S. 
Published: May 2020

AbstractGPR56, also known as ADGRG1, is a member of the adhesion G protein-coupled receptor (aGPCR) family shown to play important roles in cell adhesion, brain development, immune system function, and tumorigenesis. GPR56 is upregulated in colorectal cancer and high expression correlates with poor prognosis. Several studies have shown that GPR56 couples to the Gα12/13class of heterotrimeric G-proteins to promote RhoA activation. However, due to its structural complexity and lack of a high affinity receptor-specific ligand, the complete GPR56 signaling mechanism still remains largely unknown. To delineate the activation mechanism and intracellular signaling functions of GPR56, we generated a monoclonal antibody (mAb) which binds GPR56 with high affinity and specificity to the extracellular domain (ECD). We show that overexpression of GPR56 in 293T cells lead to increased phosphorylation of Src, Fak, and paxillin adhesion proteins and activation of the Gα12/13-RhoA-mediated serum response factor (SRF) pathway. Treatment of cells with anti-GPR56 mAb potentiated Src-Fak phosphorylation, RhoA-SRF signaling, and cell adhesion. Consistently, knockdown of GPR56 in colorectal cancer cells decreased Src-Fak pathway phosphorylation and cell adhesion. Interestingly, GPR56-mediated activation of Src-Fak phosphorylation occurred independent of RhoA, yet mAb-induced potentiation of RhoA-SRF signaling was Src-dependent. Furthermore, we show that the Serine–Threonine–Proline-rich (STP) region of the ECD of GPR56 was not essential for mAb binding, yet was required for activation of Src-Fak signaling. These data support a new ECD-dependent mechanism by which GPR56 functions to regulate cell adhesion through activation of Src-Fak signaling.
Conspecific negative density dependence and why its study should not be abandoned
Authors: LaManna Joseph A. , Mangan Scott A. , Myers Jonathan A. 
Published: May 2020

AbstractRecent studies showing bias in the measurement of density dependence have the potential to sow confusion in the field of ecology. We provide clarity by elucidating key conceptual and statistical errors with the null-model approach used in Detto et al. (2019). We show that neither their null model nor a more biologically-appropriate null model reproduces differences in density-dependent recruitment between forests, indicating that the latitudinal gradient in negative density dependence is not an artefact of statistical bias. Finally, we suggest a path forward that combines observational comparisons of density dependence in multiple fitness components across localities with mechanistic and geographically-replicated experiments.
Phage-DMS: a comprehensive method for fine mapping of antibody epitopes
Authors: Garrett Meghan E. , Itell Hannah L. , Crawford Katharine H.D. , Basom Ryan , Bloom Jesse D. , Overbaugh Julie 
Published: May 2020

ABSTRACTUnderstanding the antibody response is critical to developing vaccine and antibody-based therapies and has inspired the recent development of new methods to isolate antibodies. However, methods to define the antibody-antigen interactions that determine specificity or allow escape have not kept pace. We developed Phage-DMS, a method which combines two powerful approaches – immunoprecipitation of phage peptide libraries and deep mutational scanning (DMS) – to enable high-throughput fine mapping of antibody epitopes. As an example, we designed sequences encoding all possible amino acid variants of HIV Envelope to create phage display libraries. Using Phage-DMS, we identified sites of escape predicted using other approaches for four well characterized HIV monoclonal antibodies with known linear epitopes. In some cases, the results of Phage-DMS refined the epitope beyond what was determined in previous studies. This method has the potential to rapidly and comprehensively screen many antibodies in a single experiment to define sites essential for binding to antigen.
Spatial inhibition of return is impaired in mild cognitive impairment and mild Alzheimer’s disease
Authors: Jiang Xiong , Howard James H. , Rebeck G. Wiliam , Turner R. Scott 
Published: May 2020

ABSTRACTSpatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here we provide evidence supporting that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD), and the impairment is readily detectable using a novel double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the novel double cue spatial IOR paradigm may be useful in detecting MCI and early AD.SIGNIFICANCE STATEMENTNovel double cue spatial inhibition of return (IOR) paradigm revealed a robust effect IOR deficits in individuals with mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD)Spatial IOR effect correlates with memory performance in healthy older adults at a elevated risk of Alzheimer’s disease (with a family history or APOE e4 allele)The data suggests that double cue spatial IOR may be sensitive to detect early AD pathological changes, which may be linked to disease progress at the posterior brain regions (rather than the medial temporal lobe)
Neurokinin 1 receptor activation in the rat spinal cord maintains latent sensitization, a model of inflammatory and neuropathic chronic pain
Authors: Chen Wenling , Marvizon Juan Carlos 
Published: May 2020

AbstractLatent sensitization is a model of chronic pain in which a persistent state of pain hypersensitivity is suppressed by opioid receptors, as evidenced by the ability of opioid antagonists to induce a period of mechanical allodynia. Our objective was to determine if substance P and its neurokinin 1 receptor (NK1R) mediate the maintenance of latent sensitization. Latent sensitization was induced by injecting rats in the hindpaw with complete Freund’s adjuvant (CFA), or by spared nerve injury (SNI). When responses to von Frey filaments returned to baseline (day 28), the rats were injected intrathecally with saline or the NK1R antagonist RP67580, followed 15 min later by intrathecal naltrexone. In both pain models, the saline-injected rats developed allodynia for 2 h after naltrexone, but not the RP67580-injected rats. Saline or RP67580 were injected daily for two more days. Five days later (day 35), naltrexone was injected intrathecally. Again, the saline-injected rats, but not the RP67580-injected rats, developed allodynia in response to naltrexone. To determine if there is sustained activation of NK1Rs during latent sensitization, NK1R internalization was measured in lamina I neurons in rats injected in the paw with saline or CFA, and then injected intrathecally with saline or naltrexone on day 28. The rats injected with CFA had a small amount of NK1R internalization that was significantly higher than in the saline-injected rats. Naltrexone increased NK1R internalization in the CFA-injected rats but nor in the saline-injected rats. Therefore, sustained activation of NK1Rs maintains pain hypersensitivity during latent sensitization.
Exotic Hobos: Release, escape, and potential secondary dispersal of African red-headed agamas (Agama picticaudaPETERS, 1877) through the Florida railway systems
Authors: Gray Russell J. 
Published: May 2020

ABSTRACTContextInvasive reptile species are introduced and established through a variety of distribution channels (e.g. accidental/intentional release by pet owners, hitchhiking on imported goods), and can be detrimental to native ecosystems. Understanding the origins and spread of non-native species can help land managers to make informed decisions when attempting to prevent future introductions and remove established populations.AimsThe objectives of this study were to employ modelling techniques with open-source observational data to confirm putative local origins of African red-headed agamas in Florida and to locate potential distribution channels in which they are spreading throughout the state.MethodsGeographic profiling, a technique commonly used for criminal investigations, was used along with suspected origin locations of introduced African red-headed agamas (Agama picticauda) from the literature and observations from the Early Detection and Distribution Mapping System (EDDMapS). Anchor points and their immediate surroundings were investigated for potential patterns of origination and dispersal.Key resultsThe results of this study provide evidence that African red-headed agamas likely established themselves through both intentional releases and unintentional escapes from the pet owners and breeders, while also potentially hitchhiking on plant exports, and dispersing throughout Florida via the railway systems.ConclusionsGiven the potential for railways as a method of assisted dispersal, and given the potential exports they may be hitchhiking on, the results of this study suggest that railcars and railway export facilities should be included in future management of non-native African red-headed agamas in Florida.ImplicationsThe implications of this study builds on prior evidence that geographic profiling is an effective modelling tool in regards to biological invasions, which can accurately confirm suspected origins while also effectively mapping previously unknown epicenters of population clusters to be investigated by managers.
Individual Resting-state alpha peak frequency and within-trial changes in alpha peak frequency both predict visual flash segregation performance
Authors: Drewes Jan , Muschter Evelyn , Zhu Weina , Melcher David 
Published: May 2020

AbstractAlthough sensory input is continuous, information must be combined over time to guide action and cognition, leading to the proposal of temporal sampling windows. A number of studies have suggested that a 10Hz sampling window might be involved in the “frame rate” of visual processing. To investigate this, we tested the ability of participants to localize and enumerate 1 or 2 visual flashes presented either at near-threshold (NT) or full contrast intensities, while recording magnetoencephalography (MEG). Performance was linked to the alpha frequency both at the individual level and trial-by-trial. Participants with a higher resting state alpha peak frequency showed the greatest improvement in performance as a function of ISI within the 100ms time window, while those with slower alpha improved more when ISI exceeded 100ms. On each trial, correct enumeration (1 vs. 2) performance was paired with faster pre-stimulus instantaneous alpha frequency. The effect of the timing of the NT stimulus on the perception was consistent with visual temporal integration windows being embedded in a sampling rhythm. Our results suggest that visual sampling/processing speed, linked to peak alpha frequency, is both an individual trait and varies in a state-dependent manner.Significance StatementA fundamental question in sensory and cognitive neuroscience is how the brain makes sense of the continuous flow of sensory input, parsing it into meaningful objects and events. The speed of cortical alpha rhythms is hypothesized to predict the temporal resolution of visual perception. We present a magnetoencephalography study investigating whether this temporal resolution is an individual trait or, in contrast, depends on fluctuations in brain state. Our results show that both individual resting state alpha frequency, a relatively stable trait, and trial-by-trial fluctuations of the instantaneous alpha frequency determine temporal segregation performance. These results have important implications for how our moment-by-moment perceptual experience is shaped as well as future intervention strategies to improve visual processing for specific tasks.
CTLA-4 blockade reverses the Foxp3+ T-regulatory-cell suppression of anti-tuberculosis T-cell effector responses
Authors: Shao Lingyun , Gao Yan , Shao Xiaoyi , Ou Qingfang , Zhang Shu , Liu Qianqian , Zhang Bingyan , Wu Jing , Ruan Qiaoling , Shen Ling , Weng Xinhua , Zhang Wenhong , Chen Zheng W. 
Published: May 2020

AbstractBackgroundsIt has been well described that Foxp3+ T regulatory (Treg) cells suppress immune responses and that murine cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can control the function of Foxp3+Treg cells. However, it remains unknown about the role of CTLA-4 pathway in Treg suppression of T cell responses in tuberculosis (TB).MethodsWe assessed TB-driven changes in CTLA-4-expressing Foxp3+ Treg and conducted CTLA-4 blocking mechanistic studies ex vivo in 126 subjects with active TB, latent TB or uninfected statuses.ResultsFrequencies of CTLA-4-expressing Treg cells were increased in the circulation of pulmonary TB patients and in the pleural compartment of TB pleuritis. Six-month anti-TB treatment significantly reduced CTLA-4+ Treg subset. Notably, antibody blocking of CTLA-4 pathway (CTLA-4 blockade) reversed the ability of Treg cells to suppress anti-TB Th1 responses and abrogated the Treg-mediated suppression of TB antigen-stimulated proliferative response. The CTLA-4 blockade reversed the Treg suppression of the ability of T cells to restrict intracellular BCG andM. tuberculosisgrowth in macrophages.InterpretationThe study uncovered previously-unreported observations implicating that the CTLA-4 blockade abrogates the capability of Treg cells to suppress anti-TB immune responses or immunity. Findings support the rationale for exploring the CTLA-4 blockade as potential host-directed therapy against TB.FundThis work is supported in part by the National Natural Science Foundation of China (30901277, 81671553, 81501359), and the Key Technologies Research and Development Program for Infectious Diseases of China (2017ZX10201302-004).