bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human-genome gut-microbiome interaction in Parkinson’s disease
Authors: Wallen Zachary D. , Stone William J. , Factor Stewart A. , Molho Eric , Zabetian Cyrus P. , Standaert David G. , Payami Haydeh 
Published: January 2021

AbstractThe causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we show that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. This is the first demonstration of interaction between genetic factors in the human genome and the dysbiosis of gut microbiome in PD.
IMPAIRED OLFACTORY NETWORK FUNCTIONAL CONNECTIVITY IN PARKINSON’S DISEASE: A NOVEL MARKER FOR DISEASE PROGRESSION
Authors: Karunanayaka Prasanna , Lu Jiaming , Lewis Mechelle M. , Elyan Rommy , Yang Qing X. , Eslinger Paul J. , Huang Xuemei 
Published: January 2021

ABSTRACTObjectiveDetermine the neural basis of olfactory impairment in akinetic-rigid (PDAR) and tremor predominant (PDT) Parkinson’s disease subtypes.MethodsWe combined resting-state fMRI (rs-fMRI) with seed based functional connectivity (FC) in order to delineate the olfactory network’s functional connectivity (ON FC) between PDARand PDTpatients. We then contrasted their ON FC patterns with cognitively normal (CN) subjects. All three groups were closely matched in age, demographic variables, and adjusted for relative cognitive performance. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT).ResultsUPSIT scores were lower in akinetic-rigid vs tremor subtypes; ON FC values were lower in PDARcompared to PDTand CN, and followed the trend observed in UPSIT scores. UPSIT scores and ON FC values were significantly correlated, reflecting the effects of PD pathologies.ConclusionsThe results show that olfactory function differs between PDARand PDTsuggesting a correlation between PD-related motor symptoms and olfactory deficits. ON FC differences accounts for the impaired olfactory functions observed between PDARand PDT. PDARis known to have worse clinical outcomes and faster cognitive decline compared to PDT; therefore, PD-related olfactory dysfunction may serve as a novel metric for enhancing PD prognosis.
Sharpened and mechanically durable carbon fiber electrode arrays for neural interfacing
Authors: Welle Elissa J. , Woods Joshua E. , Jiman Ahmad A. , Richie Julianna M. , Bottorff Elizabeth C. , Ouyang Zhonghua , Seymour John P. , Patel Paras R. , Bruns Tim M. , Chestek Cynthia A. 
Published: January 2021

AbstractBioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers were sharpened using a reproducible blowtorch method that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 ± 33.5 degree tip angle with 146.8 ± 17.7 μm exposed carbon. Silicone-embedded carbon fiber arrays were durable with 87.5% of fibers remaining after 50,000 passes. Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat CVN (41.8 μVpp), feline DRG (101.1 μVpp), and rat brain (80.7 μVpp). Recordings from the feline DRG included physiologically-relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recording device. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.
Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms
Authors: Iv Francois , Martins Carla Silva , Castro-Linares Gerard , Taveneau Cyntia , Barbier Pascale , Verdier-Pinard Pascal , Camoin Luc , Audebert Stéphane , Tsai Feng-Ching , Ramond Laurie , Llewellyn Alex , Belhabib Mayssa , Nakazawa Koyomi , Cicco Aurélie Di , Vincentelli Renaud , Wenger Jerome , Cabantous Stéphanie , Koenderink Gijsje H. , Bertin Aurélie , Mavrakis Manos 
Published: January 2021

AbstractSeptin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9. Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9 thus not recapitulating its native assembly into hetero-octameric complexes. We established a protocol that enabled the first-time isolation of recombinant human septin octamers containing distinct SEPT9 isoforms. A combination of biochemical and biophysical assays confirmed the octameric nature of the isolated complexes in solution. Reconstitution studies showed that octamers with either a long or a short SEPT9 isoform form filament assemblies, and can directly bind and cross-link actin filaments, raising the possibility that septin-decorated actin structures in cells reflect direct actin-septin interactions. Recombinant SEPT9-containing octamers will make it possible to design cell-free assays to dissect the complex interactions of septins with cell membranes and the actin/microtubule cytoskeleton.SummaryHuman septins in cells form hetero-octameric complexes containing the ubiquitously expressed SEPT9. Iv et al. describe the first-time isolation of recombinant human septin octamers with distinct SEPT9 isoforms. Reconstitution studies show that octamers with either a long or a short SEPT9 isoform form higher-order filament assemblies and directly bind and cross-link actin filaments.
RNAi screening reveals requirement for PDGFRβ in JEV infection
Authors: Zhou Minmin , Wang Shaobo , Guo Jiao , Liu Yang , Cao Junyuan , Lan Xiaohao , Jia Xiaoying , Zhang Bo , Xiao Gengfu , Wang Wei 
Published: January 2021

AbstractMosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide and is associated with high morbidity and mortality. To identify potential host therapeutic targets, a high-throughput receptor tyrosine kinase small interfering RNA library screening was performed with recombinant JEV particles. Platelet-derived growth factor receptor beta (PDGFRβ) was identified as a hit after two rounds of screening. Knockdown ofPDGFRβblocked JEV infection, and trans-complementation of PDGFRβ could partly restore its infectivity. The PDGFRβ inhibitor imatinib, which has been approved for the treatment of malignant metastatic cancer, protected mice against JEV-induced lethality by decreasing the viral load in the brain, while abrogating the histopathological changes associated with JEV infection. These findings demonstrated that PDGFRβ is important in viral infection and provided evidence for the potential to develop imatinib as a therapeutic intervention against JEV infection.
Detection of SARS-CoV-2 infection by rapid antigen test in comparison with RT-PCR in a public setting
Authors: Jakobsen Kathrine Kronberg , Jensen Jakob Schmidt , Todsen Tobias , Lippert Freddy , Martel Cyril Jean-Marie , Klokker Mads , von Buchwald Christian 
Published: January 2021

AbstractBackgroundRapid and accurate detection of SARS-CoV-2 infection is essential in limiting the spread of infection during the ongoing COVID-19 pandemic. The aim of this study was to determine the accuracy of the STANDARD Q COVID-19 Ag test (SD BIOSENSOR) by comparison with RT-PCR in a public setting.MethodIndividuals aged 18 years or older who had booked an appointment for a RT-PCR test on December 26-31, 2020 at a public test center in Copenhagen, Denmark, were invited to participate. An oropharyngeal swab was collected for RT-PCR analysis, immediately followed by a nasopharyngeal swab examined by the STANDARD Q COVID-19 Ag test (SD BIOSENSOR). Sensitivity, specificity, positive and negative predictive values of the antigen test were calculated with test results from RT-PCR as reference.ResultsOverall, 4697 individuals were included (female n=2456, 53.3%; mean age: 44.7 years, SD: 16.9 years); 196 individuals were tested twice or more. Among 4811 paired conclusive test results from the RT-PCR and antigen tests, 221 (4.6%) RT-PCR tests were positive. The overall sensitivity and specificity of the antigen test were 69.7% and 99.5%, the positive and negative predictive values were 87.0% and 98.5%. Ct values were significantly higher among individuals with false negative antigen tests compared to true positives.ConclusionThe sensitivity, specificity, and predictive values found indicate that the STANDARD Q COVID-19 Ag is a good supplement to RT-PCR testing.
Adult porcine (Sus scrofa) derived inner ear cells possessing multipotent stem/progenitor cell characteristics inin vitrocultures
Authors: Wijesinghe Printha , Sastry Anand , Hui Elizabeth , Cogan Tristan A. , Zheng Boyuan , Ho Germain , Kakal Juzer , Nunez Desmond A. 
Published: January 2021

AbstractThe human inner ear compared with that of other mammalian species is very complex. Although the mouse’s cochlea is frequently studied the mouse’s inner ear continues to develop postnatally whilst the human inner ear is fully developed by the third month of gestation which leads one to question the applicability of findings based on research on mice to human regenerative therapies. Here, we report a novelin vitroculture of adult porcine (Sus scrofa) inner ear cells developed from post-mortem labyrinth specimens. Anatomical findings based on maximal transverse and vertical axial diameters and the length of the cochlear duct suggest that the pig’s cochlea is similar to the human cochlea.In vitrocultures of porcine cochlear and vestibular cells showed the persistence of both inner ear hair cell (HC), supporting cell (SC) and stem/progenitor cell characteristics across passages up to 6 based on scanning electron microscopy, fluorescence immunocytochemistry and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Our findings showed that porcine cochlear and vestibular epithelia maintained multipotent stem/progenitor cell populations into adulthood although their regenerative capacities differed across the passages. The development of a viable and reproducible method to culture porcine inner ear cells provides an important investigative tool that can be utilized to study and evaluate the pathophysiological causes and cellular consequences of human inner ear disorders.
Bispecific antibody neutralizes circulating SARS-CoV-2 variants, prevents escape and protects mice from disease
Authors: De Gasparo Raoul , Pedotti Mattia , Simonelli Luca , Nickl Petr , Muecksch Frauke , Cassaniti Irene , Percivalle Elena , Lorenzi Julio C. C. , Mazzola Federica , Magrì Davide , Michalcikova Tereza , Haviernik Jan , Honig Vaclav , Mrazkova Blanka , Polakova Natalie , Fortova Andrea , Tureckova Jolana , Iatsiuk Veronika , Girolamo Salvatore Di , Palus Martin , Zudova Dagmar , Bednar Petr , Bukova Ivana , Bianchini Filippo , Mehn Dora , Nencka Radim , Strakova Petra , Pavlis Oto , Rozman Jan , Gioria Sabrina , Camilla Sammartino Josè , Giardina Federica , Gaiarsa Stefano , Hammarström Qiang Pan , Barnes Christopher O. , Bjorkman Pamela J. , Calzolai Luigi , Piralla Antonio , Baldanti Fausto , Nussenzweig Michel C. , Bieniasz Paul D. , Hatziioannou Theodora , Prochazka Jan , Sedlacek Radislav , Robbiani Davide F. , Ruzek Daniel , Varani Luca 
Published: January 2021

SummaryNeutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.
Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity
Authors: Tesfagiorgis Yodit , Craig Heather C , Parham Kate A , Kerfoot Steven M 
Published: January 2021

AbstractAnti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not known, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgHMOGspontaneous experimental autoimmune encephalomyelitis mice in the chronic phase of disease, after the establishment of meningeal B cell clusters. Compared to the circulation, lymph nodes, and spleen, B cell depletion from the CNS was delayed and not evident until 7d post administration of anti-CD20. Further, we did not find evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. The reduction of B cell numbers in the CNS coincided with less demyelination of the spinal cord white matter and also, surprisingly, an increase in the number of T cells recruited to the meninges but not parenchyma.
Improvements in the Sequencing and Assembly of Plant Genomes
Authors: Sharma Priyanka , Al-Dossary Othman , Alsubaie Bader , Al-Mssallem Ibrahim , Nath Onkar , Mitter Neena , Alves Margarido Gabriel Rodrigues , Topp Bruce , Murigneux Valentine , Masouleh Ardy Kharabian , Furtado Agnelo , Henry Robert J 
Published: January 2021

AbstractBackgroundAdvances in DNA sequencing have reduced the difficulty of sequencing and assembling plant genomes. A range of methods for long read sequencing and assembly have been recently compared and we now extend the earlier study and report a comparison with more recent methods.ResultsUpdated Oxford Nanopore Technology software supported improved assemblies. The use of more accurate sequences produced by repeated sequencing of the same molecule (PacBio HiFi) resulted in much less fragmented assembly of sequencing reads. The use of more data to give increased genome coverage resulted in longer contigs (higher N50) but reduced the total length of the assemblies and improved genome completeness (BUSCO). The original model species, Macadamia jansenii, a basal eudicot, was also compared with the 3 other Macadamia species and with avocado (Persea americana), a magnoliid, and jojoba (Simmondsia chinensis) a core eudicot. In these phylogenetically diverse angiosperms, increasing sequence data volumes also caused a highly linear increase in contig size, decreased assembly length and further improved already high completeness. Differences in genome size and sequence complexity apparently influenced the success of assembly from these different species.ConclusionsAdvances in long read sequencing technology have continued to significantly improve the results of sequencing and assembly of plant genomes. However, results were consistently improved by greater genome coverage (using an increased number of reads) with the amount needed to achieve a particular level of assembly being species dependant.
Measuring gas vesicle dimensions by electron microscopy
Authors: Dutka Przemysław , Malounda Dina , Metskas Lauren Ann , Chen Songye , Hurt Robert C. , Lu George J. , Jensen Grant J. , Shapiro Mikhail G. 
Published: January 2021

ABSTRACTGas vesicles (GVs) are cylindrical or spindle-shaped protein nanostructures filled with air and used for flotation by various cyanobacteria, heterotrophic bacteria, and Archaea. Recently, GVs have gained interest in biotechnology applications due to their ability to serve as imaging agents and actuators for ultrasound, magnetic resonance and several optical techniques. The diameter of GVs is a crucial parameter contributing to their mechanical stability, buoyancy function and evolution in host cells, as well as their properties in imaging applications. Despite its importance, reported diameters for the same types of GV differ depending on the method used for its assessment. Here, we provide an explanation for these discrepancies and utilize electron microscopy (EM) techniques to accurately estimate the diameter of the most commonly studied types of GVs. We show that during air drying on the EM grid, GVs flatten, leading to a ~1.5-fold increase in their apparent diameter. We demonstrate that GVs’ diameter can be accurately determined by direct measurements from cryo-EM samples or alternatively indirectly derived from widths of flat collapsed and negatively stained GVs. Our findings help explain the inconsistency in previously reported data and provide accurate methods to measure GV dimensions.
Abundant secreted hydrolytic enzymes and secondary metabolite gene clusters in genomes of theBotryosphaeriaceaereflect their role as important plant pathogens
Authors: Nagel JH , Wingfield MJ , Slippers B 
Published: January 2021

AbstractTheBotryosphaeriaceaeare important plant pathogens, but unique in their ability to establish asymptomatic infections that persist for extended periods in a latent state. In this study, we used comparative analyses to consider elements that might shed light on the genetic basis of the interactions of these fungi with their plant hosts. For this purpose, we characterised secreted hydrolytic enzymes, secondary metabolite biosynthetic gene clusters and considered general trends in genomic architecture using all availableBotryosphaeriaceaegenomes, and selected Dothideomycetes genomes. TheBotryosphaeriaceaegenomes were rich in carbohydrate-active enzymes (CAZymes), proteases, lipases and secondary metabolic biosynthetic gene clusters (BGCs) compared to other Dothideomycete genomes. The genomes ofBotryosphaeria, Macrophomina, LasiodiplodiaandNeofusicoccum, in particular, had gene expansions of the major constituents of the secretome, notably CAZymes involved in plant cell wall degradation. TheBotryosphaeriaceaegenomes were shown to have moderate to high GC contents and most had low levels of repetitive DNA. The genomes were not compartmentalized based on gene and repeat densities, but genes of secreted enzymes were slightly more abundant in gene-sparse regions. The abundance of secreted hydrolytic enzymes and secondary metabolite BGCs in the genomes ofBotryosphaeria, Macrophomina, Lasiodiplodia, andNeofusicoccumwere similar to those in necrotrophic plant pathogens, but also endophytes of woody plants. The results provide a foundation for future comparative genomic analyses and hypothesis to explore the mechanisms underlyingBotryosphaeriaceaehost-plant interactions.
Inspiratory muscle training for enhancing repeated-sprint ability: A pilot study
Authors: Rodriguez Ramón F. , Aughey Robert J. , Billaut François , Townsend Nathan E. 
Published: January 2021

AbstractThis pilot study examined the effect of inspiratory muscle training (IMT) on repeated-sprint ability and vastus lateralis reoxygenation. Ten recreationally trained subjects were randomly divided into two groups to complete 4 weeks of IMT or Sham (placebo) training. Pre- and post-intervention, a repeated-sprint ability (RSA) test was performed in both normoxia and hypoxia (FiO2 ≈ 14.5%). Vastus lateralis reoxygenation (VLreoxy), defined as peak to minimum amplitude deoxyhaemoglobin for each sprint/recovery cycle, was assessed during all trials using near-infrared spectroscopy. For total work performed, power analysis revealed that for small, medium and large effects (Cohen’s f), sample sizes of n = 8, 16 and 90 respectively, are required to achieve a power of 80% at an α level of 0.05. Maximal inspiratory mouth pressure increased in IMT by 36.5%, 95% CI [20.9, 61.6] and by 2.7%, 95% CI [−4.46, 8.8] in Sham. No clear difference in the change of work completed during the sprints between groups were observed in normoxia (Sham −0.805 kJ, 95% CI [−3.92, 0.39]; IMT −2.06 kJ, 95% CI [−11.5, 4.96]; P = 0.802), or hypoxia (Sham −3.09 kJ, 95% CI [−7, 0.396]; IMT 0.354 kJ, 95% CI [−1.49, 2.1]; P = 0.802). VLreoxy in IMT increased by 9.34%, 95% CI [5.15, 13.7] in normoxia only. In conclusion, despite a large increase in IMT, this was only associated with a small effect on RSA in our pilot study cohort. Owing to a potentially relevant impact of training the inspiratory musculature, future studies should include a sample size of at least 16-20 to detect moderate to large effects on RSA.