bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tomato fruit susceptibility to fungal disease can be uncoupled from ripening by suppressing susceptibility factors
Authors: Silva Christian J. , van den Abeele Casper , Ortega-Salazar Isabel , Papin Victor , Adaskaveg Jaclyn A. , Wang Duoduo , Casteel Clare L. , Seymour Graham B. , Blanco-Ulate Barbara 
Published: June 2020

AbstractThe increased susceptibility of ripe fruit to fungal pathogens poses a substantial threat to crop production and marketability. Here, we coupled transcriptomic analyses with mutant studies to uncover critical processes associated with defenses and susceptibility in tomato (Solanum lycopersicum) fruit. Using unripe and ripe fruit inoculated with three fungal pathogens, we identified common pathogen responses reliant on chitinases, WRKY transcription factors, and reactive oxygen species detoxification. We established that the magnitude and diversity of defense responses do not significantly impact the interaction outcome, as susceptible ripe fruit mounted a strong defense response to pathogen infection. Then, to distinguish features of ripening that may be responsible for susceptibility, we utilized non-ripening tomato mutants that displayed different susceptibility patterns to fungal infection. Based on transcriptional and hormone profiling, susceptible tomato genotypes had losses in the maintenance of cellular redox homeostasis, while jasmonic acid accumulation and signaling coincided with defense activation in resistant fruit. We identified and validated a susceptibility factor, pectate lyase (PL). CRISPR-based knockouts ofPL, but not polygalacturonase (PG2a), reduced susceptibility of ripe fruit by >50%. This study suggests that targeting specific genes that drive susceptibility is a viable strategy to improve the resistance of tomato fruit against fungal disease.HighlightIncreased susceptibility to fungal disease during tomato ripening is driven by the accumulation of susceptibility factors and not the lack of defense responses.
Enhancing Colorimetric LAMP Amplification Speed and Sensitivity with Guanidine Chloride
Authors: Zhang Yinhua , Ren Guoping , Buss Jackson , Barry Andrew J. , Patton Gregory C. , Tanner Nathan A. 
Published: June 2020

AbstractLoop-mediated isothermal amplification (LAMP) is a versatile technique for detection of target DNA and RNA, enabling rapid molecular diagnostic assays with minimal equipment. The global SARS-CoV-2 pandemic has presented an urgent need for new and better diagnostic methods, with colorimetric LAMP utilized in numerous studies for SARS-CoV-2 detection. However, the sensitivity of colorimetric LAMP in early reports has been below that of the standard RT-qPCR tests, and we sought to improve performance. Here we report the use of guanidine hydrochloride and combined primer sets to increase speed and sensitivity in colorimetric LAMP, bringing this simple method up to the standards of sophisticated technique and enabling accurate and high-throughput diagnostics.
Direct colorimetric LAMP assay for in-field detection of African swine fever virus: a validation study during an outbreak in Vietnam
Authors: Tran Diem Hong , Tran Hau Thi , Le Uyen Phuong , Vu Xuan Dang , Trinh Thi Bich Ngoc , Do Hoang Dang Khoa , Than Van Thai , Bui Le Minh , Vu Van Van , Nguyen Thi Lan , Phung Huong Thi Thu , Le Van Phan 
Published: June 2020

ABSTRACTAfrican Swine Fever (ASF) is a highly infectious viral disease with high mortality. The most recent ASF outbreak in Vietnam occurred in 2019, posing a threat to spread to the neighboring Asian countries. Without a commercial vaccine or efficient chemotherapeutics successfully developed, rapid diagnosis and necessary biosecurity procedures are required to control the disease. While the diagnosis method of ASF recommended by the World Organization of Animal Health is real-time PCR, it is not suitable for in-field detection of the disease. In this study, a colorimetric Loop-Mediated Isothermal Amplification (LAMP) assay was developed and evaluated for ASF virus detection using crude serum samples collected from domestic pigs in Vietnam during the 2019 outbreak. The LAMP results can be readily visualized to naked eyes within 30 minutes without the requirement of DNA extraction and sophisticated equipment. The sensitivity, specificity, and limit of detection of colorimetric LAMP assay were comparable to a commercial diagnostic real-time PCR kit. Results strongly indicate that the developed colorimetric LAMP assay is highly recommended for the in-field diagnosis of ASF.
Implementation and evaluation of a novel real-time multiplex assay for SARS-CoV-2: In-field learnings from a clinical microbiology laboratory
Authors: Williams Eloise , Bond Katherine , Chong Brian , Giltrap Dawn , Eaton Malcolm , Kyriakou Peter , Calvert Peter , Zhang Bowen , Siwan Mahendra , Howden Benjamin , Druce Julian , Catton Mike , Williamson Deborah A 
Published: June 2020

ABSTRACTThe unprecedented scale of testing required to effectively control the coronavirus disease (COVID-19) pandemic has necessitated urgent implementation of rapid testing in clinical microbiology laboratories. To date, there are limited data available on the analytical performance of emerging commercially available assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and integration of these assays into laboratory workflows. Here, we performed a prospective validation study of a commercially available assay, the AusDiagnostics Coronavirus Typing (8-well) assay. Respiratory tract samples for SARS-CoV-2 testing were collected between 1st March and 25th March 2020. All positive samples and a random subset of negative samples were sent to a reference laboratory for confirmation. In total, 2,673 samples were analyzed using the Coronavirus Typing assay. The predominant sample type was a combined nasopharyngeal/throat swab (2,640/2,673; 98.8%). Fifty-four patients were positive for SARS-CoV-2 (0.02%) using the Coronavirus Typing assay; 53/54 (98.1%) positive results and 621/621 (100%) negative results were concordant with the reference laboratory. Compared to the reference standard, sensitivity of the Coronavirus Typing assay for SARS-CoV-2 was 100% [95% CI 93.2%-100%], specificity 99.8% [95% CI 99.1%-100%], positive predictive value 98.1% (95% CI 90.2%-99.7%] and negative predictive value 100% [95% CI 99.4%-100%]. In many countries, standard regulatory requirements for the introduction of new assays have been replaced by emergency authorizations and it is critical that laboratories share their post-market validation experiences, as the consequences of widespread introduction of a sub-optimal assay for SARS-CoV-2 are profound. Here, we share our in-field experience, and encourage other laboratories to follow suit.
fMRI and Transcranial Electrical Stimulation (tES): A systematic review of parameter space and outcomes
Authors: Ghobadi-Azbari Peyman , Jamil Asif , Yavari Fatemeh , Esmaeilpour Zeinab , Malmir Nastaran , Mahdavifar-Khayati Rasoul , Soleimani Ghazaleh , Cha Yoon-Hee , Shereen A. Duke , Nitsche Michael A. , Bikson Marom , Ekhtiari Hamed 
Published: June 2020

AbstractThe combination of non-invasive brain stimulation interventions with human brain mapping methods have supported research beyond correlational associations between brain activity and behavior. Functional MRI (fMRI) partnered with transcranial electrical stimulation (tES) methods, i.e., transcranial direct current (tDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation, explore the neuromodulatory effects of tES in the targeted brain regions and their interconnected networks and provide opportunities for individualized interventions. Advances in the field of tES-fMRI can be hampered by the methodological variability between studies that confounds comparability/replicability. In order to explore variability in the tES-fMRI methodological parameter space (MPS), we conducted a systematic review of 222 tES-fMRI experiments (181 tDCS, 39 tACS and 2 tRNS) published before February 1, 2019, and suggested a framework to systematically report main elements of MPS across studies. We have organized main findings in terms of fMRI modulation by tES. tES modulates activation and connectivity beyond the stimulated areas particularly with prefrontal stimulation. There were no two studies with the same MPS to replicate findings. We discuss how to harmonize the MPS to promote replication in future studies.
Assessment of effective isolation, safe burial and vaccination optimal controls for an Ebola epidemic model
Authors: Tassé Arsène Jaurès Ouemba , Tsanou Berge , Lubuma Jean M.-S. , Woukeng Jean Louis 
Published: June 2020

AbstractSince 1976 many outbreaks of Ebola virus disease have occurred in Africa, and up to now, no treatment is available. Thus, to fight against this illness, several control strategies have been adopted. Among these measures, isolation, safe burial and vaccination occupy a prominent place. In this paper therefore, we present a model which takes into account these three control strategies as well as the difference in immunological responses of infected by distinguishing individuals with moderate and severe symptoms. The sensitivity analysis of the control reproduction number suggests that, the vaccination response works better than the two other control measures at the beginning of the disease, and there is no need to vaccinate people in order to overcome Ebola. The global asymptotic dynamic of the model with controls is completely achieved exhibiting a sharp threshold behavior. Consequently, the global stability of the endemic equilibrium when the control reproduction number is greater than one, calls for the implementation of the three responses optimally. Thus, we define, analyze and implement different optimal control problems which minimize the cost of controls and the number of infected individuals through vaccination, isolation and safe burial. The obtained results highlight that, in order to mitigate Ebola outbreaks, an optimal vaccination strategy has more impact than the combination of isolation and safe burial responses. Therefore, the broad recommendation is that: if for any disease outbreak, the vaccine can be available quickly, one should think of implementing large vaccination programs rather than any other control measures.
Predicting individual risk for COVID19 complications using EMR data
Authors: Kinar Yaron , Lanyado Alon , Shoshan Avi , Yesharim Rachel , Domany Tamar , Shalev Varda , Chodick Gabriel 
Published: June 2020

AbstractBackgroundThe global pandemic of COVID-19 has challenged healthcare organizations and caused numerous deaths and hospitalizations worldwide. The need for data-based decision support tools for many aspects of controlling and treating the disease is evident but has been hampered by the scarcity of real-world reliable data. Here we describe two approaches: a. the use of an existing EMR-based model for predicting complications due to influenza combined with available epidemiological data to create a model that identifies individuals at high risk to develop complications due to COVID-19 and b. a preliminary model that is trained using existing real world COVID-19 data.MethodsWe have utilized the computerized data of Maccabi Healthcare Services a 2.3 million member state-mandated health organization in Israel. The age and sex matched matrix used for training the XGBoost ILI-based model included, circa 690,000 rows and 900 features. The available dataset for COVID-based model included a total 2137 SARS-CoV-2 positive individuals who were either not hospitalized (n = 1658), or hospitalized and marked as mild (n = 332), or as having moderate (n = 83) or severe (n = 64) complications.FindingsThe AUC of our models and the priors on the 2137 COVID-19 patients for predicting moderate and severe complications as cases and all other as controls, the AUC for the ILI-based model was 0.852[0.824–0.879] for the COVID19-based model – 0.872[0.847–0.879].InterpretationThese models can effectively identify patients at high-risk for complication, thus allowing optimization of resources and more focused follow up and early triage these patients if once symptoms worsen.FundingThere was no funding for this studyResearch in contextEvidence before this studyWe have search PubMed for coronavirus[MeSH Major Topic] AND the following MeSH terms: risk score, predictive analytics, algorithm, predictive analytics. Only few studies were found on predictive analytics for developing COVID19 complications using real-world data. Many of the relevant works were based on self-reported information and are therefore difficult to implement at large scale and without patient or physician participation.Added value of this studyWe have described two models for assessing risk of COVID-19 complications and mortality, based on EMR data. One model was derived by combining a machine-learning model for influenza-complications with epidemiological data for age and sex dependent mortality rates due to COVID-19. The other was directly derived from initial COVID-19 complications data.Implications of all the available evidenceThe developed models may effectively identify patients at high-risk for developing COVID19 complications. Implementing such models into operational data systems may support COVID-19 care workflows and assist in triaging patients.
Ribosome rescue inhibitors clearNeisseria gonorrhoeae in vivousing a new mechanism
Authors: Aron Zachary D. , Mehrani Atousa , Hoffer Eric D. , Connolly Kristie L. , Torhan Matthew C. , Alumasa John N. , Srinivas Pooja , Cabrera Mynthia , Hosangadi Divya , Barbor Jay S. , Cardinale Steven C. , Kwasny Steven M. , Morin Lucas R. , Butler Michelle M. , Opperman Timothy J. , Bowlin Terry L. , Jerse Ann , Stagg Scott M. , Dunham Christine M. , Keiler Kenneth C. 
Published: June 2020

AbstractThetrans-translation pathway for rescuing stalled ribosomes is conserved and essential in bacterial pathogens but has no mammalian homolog, making it an ideal target for new antibiotics. We previously reported the discovery of a family of acylaminooxadiazoles that selectively inhibittrans-translation, resulting in broad-spectrum antibiotic activity. Optimization of the pharmacokinetic and antibiotic properties of the acylaminooxadiazoles produced MBX-4132, which cleared multiple-drug resistantNeisseria gonorrhoeaeinfection in mice after a single oral dose. Cryo-EM studies of non-stop ribosomes showed that acylaminooxadiazoles bind to a unique site near the peptidyl-transfer center and significantly alter the conformation of ribosomal protein L27, suggesting a novel mechanism for specific inhibition oftrans-translation by these molecules.One Sentence SummaryRibosome rescue inhibitors reveal a new conformation of the ribosome and kill drug-resistantNeisseria gonorrhoeae in vivo.
CHMP2B regulates TDP-43 phosphorylation and proteotoxicity via modulating CK1 turnover independent of the autophagy-lysosomal pathway
Authors: Sun Xing , Deng Xue , Hu Rirong , Duan Yongjia , Zhang Kai , Cui Jihong , Ni Jiangxia , Wang Qiangqiang , Chen Yelin , Li Ang , Fang Yanshan 
Published: June 2020

ABSTRACTProtein inclusions containing phosphorylated TDP-43 are a shared pathology in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, most ALS/FTD patients do not have a mutation in TDP-43 or the enzymes directly regulating its phosphorylation. It is intriguing how TDP-43 becomes hyperphosphorylated in each disease condition. In a genetic screen for novel TDP-43 modifiers, we found that knockdown (KD) ofCHMP2B, a key component of the endosomal sorting complex required for transport (ESCRT) machinery, suppressed TDP-43-mediated neurodegeneration inDrosophila. Further investigation using mammalian cells indicated thatCHMP2BKD decreased whereas its overexpression (OE) increased TDP-43 phosphorylation levels. Moreover, a known FTD-causing mutationCHMP2Bintron5promoted hyperphosphorylation, insolubility and cytoplasmic accumulation of TDP-43. Interestingly, CHMP2B did not manifest these effects by its well-known function in the autophagy-lysosomal pathway. Instead, the kinase CK1 tightly regulated TDP-43 phosphorylation level in cells, and CHMP2B OE or CHMP2BIntron5significantly decreased ubiquitination and the turnover of CK1 via the ubiquitin-proteasome (UPS) pathway. Finally, we showed that CHMP2B protein levels increased in the cerebral cortices of aged mice, which might underlie the age-associated TDP-43 pathology and disease onset. Together, our findings reveal a molecular link between the two ALS/FTD-pathogenic proteins CHMP2B and TDP-43, and provide an autophagy-independent mechanism for CHMP2B in pathogenesis.SIGNIFICANCE STATEMENTTDP-43 and CHMP2B are both ALS/FTD-associated proteins. Protein aggregations containing phosphorylated TDP-43 are a pathological hallmark of ALS/FTD; however, it is unclear how increased phosphorylation of TDP-43 occurs in diseases. The pathogenesis of CHMP2B has mainly been considered as a consequence of autophagy-lysosomal dysfunction. Here, we reveal that increase of CHMP2B levels (which occurs in aged mouse brains) or expression of the disease-causing mutation CHMP2BIntron5promotes TDP-43 hyperphosphorylation, insolubility and cytoplasmic mislocalization. This effect is independent of the autophagy-lysosomal pathway but rather relies on the proteasome-mediated turnover of the kinase CK1 that phosphorylates TDP-43. Together, we provide a new molecular mechanism of CHMP2B pathogenesis by linking it to TDP-43 pathology via CK1.
Influence of the microenvironment on the modulation of the host response by the typhoid toxin
Authors: Martin Océane C.B. , Butter Deborah , Paparouna Eleni , Theodorou Sofia D.P. , Haykal Maria M. , Boutet-Robinet Elisa , Tebaldi Toma , Bergonzini Anna , Chiloeches Maria Lopez , Wakeham Andrew , Rhen Mikael , Gorgoulis Vassilis G. , Mak Tak , Pateras Ioannis S. , Frisan Teresa 
Published: June 2020

SummaryBacterial genotoxins cause DNA damage in eukaryotic cells, resulting in activation of the DNA damage response (DDR)in vitro. These toxins are produced by Gram negative bacteria, enriched in the microbiota of Inflammatory Bowel Disease (IBD) and colorectal cancer (CRC) patients. However, their role in infection remains poorly characterized. We have addressed the role of the typhoid toxin in the modulation of the host-microbial interaction in health and disease.Infection with a genotoxigenicSalmonellaprotected mice from intestinal inflammation. The toxin-induced DNA damage caused senescencein vivo, which was uncoupled from the inflammatory response, and associated with the maintenance of an anti-inflammatory environment. This effect was lost when infection occurred in mice suffering from inflammatory conditions that mimic Ulcerative Colitis, a form of IBD.These data highlight a complex context-dependent crosstalk between bacterial genotoxins-induced DDR and the host immune response, underlining an unexpected role for bacterial genotoxins.
Signal sequences encode information for protein folding in the endoplasmic reticulum
Authors: Sun Sha , Li Xia , Mariappan Malaiyalam 
Published: June 2020

AbstractOne-third of newly synthesized proteins in mammals are translocated into the endoplasmic reticulum (ER) through the Sec61 translocon. It remains unclear how protein translocation coordinates with the chaperone availability to promote protein folding in the ER. We find that signal sequences cause a translocation pause at the Sec61 translocon until nascent chains engage with luminal chaperones for efficient translocation and folding in the ER. Using a substrate-trapping proteomic approach, we identify that nascent proteins with marginally hydrophobic signal sequences accumulate on the cytosolic side of the Sec61 translocon, which recruits BiP chaperone through Sec63 to bind onto nascent chains. Surprisingly, BiP binding not only releases translocationally paused nascent chains into the ER lumen but also ensures protein folding. Increasing hydrophobicity of signal sequences bypasses Sec63/BiP-dependent protein translocation but translocated nascent chains misfold and aggregate under conditions of limited BiP availability in the ER. Thus, signal sequence-dependent protein folding explains why signal sequences are diverse and use multiple protein translocation pathways.
The myosin regulatory light chain Myl5 localizes to mitotic spindle poles and is required for proper cell division
Authors: Ramirez Ivan , Gholkar Ankur A. , Velasquez Erick F. , Guo Xiao , Torres Jorge Z. 
Published: June 2020

ABSTRACTMyosins are ATP-dependent actin-based molecular motors critical for diverse cellular processes like intracellular trafficking, cell motility and cell invasion. During cell division, myosin MYO10 is important for proper mitotic spindle assembly, the anchoring of the spindle to the cortex, and positioning of the spindle to the cell mid-plane, while myosin MYO2 functions in actomyosin ring contraction to promote cytokinesis. However, myosins are regulated by myosin regulatory light chains (RLCs), and whether RLCs are important for cell division has remained unexplored. Here, we have determined that the previously uncharacterized myosin RLC Myl5 associates with the mitotic spindle and is required for cell division. Myl5 localized to the mitotic spindle poles and spindle microtubules during early mitosis, an area overlapping with MYO10 localization. Depletion of Myl5 led to defects in chromosome congression and to a slower progression through mitosis. We propose that Myl5 is a novel myosin RLC that is important for cell division.
Olfactory transmucosal SARS-CoV-2 invasion as port of Central Nervous System entry in COVID-19 patients
Authors: Meinhardt Jenny , Radke Josefine , Dittmayer Carsten , Mothes Ronja , Franz Jonas , Laue Michael , Schneider Julia , Brünink Sebastian , Hassan Olga , Stenzel Werner , Windgassen Marc , Rößler Larissa , Goebel Hans-Hilmar , Martin Hubert , Nitsche Andreas , Schulz-Schaeffer Walter J. , Hakroush Samy , Winkler Martin S. , Tampe Björn , Elezkurtaj Sefer , Horst David , Oesterhelweg Lars , Tsokos Michael , Heppner Barbara Ingold , Stadelmann Christine , Drosten Christian , Corman Victor Max , Radbruch Helena , Heppner Frank L. 
Published: June 2020

AbstractThe newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease presenting with fever, cough, and often pneumonia. Moreover, thromboembolic events throughout the body including the central nervous system (CNS) have been described. Given first indication for viral RNA presence in the brain and cerebrospinal fluid and in light of neurological symptoms in a large majority of COVID-19 patients, SARS-CoV-2-penetrance of the CNS is likely. By precisely investigating and anatomically mapping oro- and pharyngeal regions and brains of 32 patients dying from COVID-19, we not only describe CNS infarction due to cerebral thromboembolism, but also demonstrate SARS-CoV-2 neurotropism. SARS-CoV-2 enters the nervous system via trespassing the neuro-mucosal interface in the olfactory mucosa by exploiting the close vicinity of olfactory mucosal and nervous tissue including delicate olfactory and sensitive nerve endings. Subsequently, SARS-CoV-2 follows defined neuroanatomical structures, penetrating defined neuroanatomical areas, including the primary respiratory and cardiovascular control center in the medulla oblongata.