bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who infects Whom? - Reconstructing infection chains of Mycobacterium avium ssp. paratuberculosis in an endemically infected dairy herd by use of genomic data
Authors: Nigsch Annette , Robbe-Austerman Suelee , Stuber Tod P. , Bitar Paulina D. Pavinski , Gröhn Yrjö , Schukken Ynte H. 
Published: February 2021

AbstractRecent evidence of circulation of multiple strains within herds and mixed infections of cows marks the beginning of a rethink of our knowledge on Mycobacterium avium ssp. paratuberculosis (MAP) epidemiology. Strain typing opens new ways to investigate MAP transmission. This work presents a method for reconstructing infection chains in a setting of endemic Johne’s disease on a well-managed dairy farm. By linking genomic data with demographic field data, strain-specific differences in spreading patterns could be quantified for a densely sampled dairy herd. Mixed infections of dairy cows with MAP are common, and some strains spread more successfully. Infected cows remain susceptible for co-infections with other MAP genotypes. The model suggested that cows acquired infection from 1–4 other cows and spread infection to 0–17 individuals. Reconstructed infection chains supported the hypothesis that high shedding animals that started to shed at an early age and showed a progressive infection pattern represented a greater risk for spreading MAP. Transmission of more than one genotype between animals was recorded. In this farm with a good MAP control management program, adult-to-adult contact was proposed as the most important transmission route to explain the reconstructed networks. For each isolate, at least one more likely ancestor could be inferred. Our study results help to capture underlying transmission processes and to understand the challenges of tracing MAP spread within a herd. Only the combination of precise longitudinal field data and bacterial strain type information made it possible to trace infection in such detail.
Ground cover presence in organic olive orchards affects the interaction of natural enemies againstPrays oleae, promoting an effective egg predation
Authors: Álvarez Hugo Alejandro , Jiménez-Muñoz Raquel , Morente Marina , Campos Mercedes , Ruano Francisca 
Published: February 2021

AbstractThe olive moth,Prays oleae, is one of the most common insects that damages olives in the Mediterranean region. The establishment of ground cover within olive orchards has been promoted in this region in recent years to avoid erosion and soil degradation. Nevertheless, its role as a shelter for natural enemies of pests has been controversial. In this study, we have investigated the effectiveness of the biological control ofP. oleaein organic olive orchards with ground cover (mowed) and without ground cover (tilled). For this, (1) we assessed the relationship between predated eggs and the abundance of natural enemies in both types of orchards; (2) we compared both the potential damage of the pest and the egg hatching in the two types of orchards; and (3) we examined the interaction amongst families of natural enemies andP. oleae(as adults and as predated eggs). The results showed that there is a high rate of predation in the studied olive orchards, 81% of the eggs were predated, 12.2% hatched, and 6.9% were live eggs. However, mowed orchards were more effective for controllingP. oleaeby means of egg predation rather than tilled orchards, i.e., in mowed orchards, whilst the potential damage of the pest was higher, egg hatching was rather low. The structure of the adult arthropod community, i.e., the composition and abundance of families of natural enemies did not differ between the orchards, but the abundance of the families Anthocoridae, Miridae and Scelionidae was significantly higher in the mowed orchards. Finally, the interaction amongst natural enemies andP. oleaeshowed that the families that better explained the effects on egg predation were Aeolothripidae, Anthocoridae, Miridae, Chrysopidae (predators), and Formicidae (omnivore). We discuss the results in terms of ecological interactions of trophic guilds and we conclude that the establishment and maintenance of ground cover in organic olive orchards, at least in June and July, is of great significance because it positively affects the egg predation ofP. oleae. This effect is especially significant when there is a low abundance of natural enemies in the olive orchards.
Alien chromatin other than the GST-encodingFhb7candidate confers Fusarium head blight resistance in wheat breeding
Authors: Guo Xianrui , Shi Qinghua , Yuan Jing , Zhang Jing , Wang Mian , Wang Jing , Wang Chunhui , Fu Shulan , Su Handong , Liu Yang , Huang Yuhong , Liu Chang , Liu Qian , Sun Yishuang , Wang Long , Wang Ke , Jing Donglin , Zhang Pingzhi , Li Jinbang , Kang Houyang , Zhou Yonghong , Ye Xingguo , Han Fangpu 
Published: February 2021

AbstractThe lack of resistance resources is a major bottleneck for wheat Fusarium head blight (FHB) resistance breeding. Three wheat-Th. elongatumFHB resistant translocation lines have been developed and used for wheat breeding without yield penalty. Transcriptomic analysis identified a derivative glutathione S-transferase transcript T26102, which was homologous toFhb7and induced dramatically byFusarium graminearum. Unlike other studies,Fhb7homologs were detected not only inThinopyrumbut also inElymus,Leymus,PseudoroegeriaandRoegeria. We also found that several wheat-Th. ponticumderivatives carryingFhb7and its homologs were highly susceptible to FHB. Moreover, the transgenic plants expressingFhb7and its homolog on different backgrounds did not improve the FHB resistance.One Sentence SummaryThe GST-encodingFhb7candidate cannot improve Fusarium head blight resistance in wheat breeding.
Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis
Authors: Cid Elena , Marquez-Galera Angel , Valero Manuel , Gal Beatriz , Medeiros Daniel C. , Navarron Carmen M. , Ballesteros-Esteban Luis , Reig-Viader Rita , Morales Aixa V. , Fernandez-Lamo Ivan , Gomez-Dominguez Daniel , Sato Masaaki , Hayashi Yasunori , Bayes Alex , Barco Angel , Lopez-Atalaya Jose P , de la Prida Liset M 
Published: February 2021

AbstractHippocampal sclerosis, the major neuropathological hallmark of temporal lobe epilepsy, is characterized by different patterns of neuronal loss. The mechanisms of cell-type specific vulnerability, their progression and histopathological classification remain controversial. Here using single-cell electrophysiology in vivo and immediate early gene expression, we reveal that superficial CA1 pyramidal neurons are overactive in epileptic rats and micein vivo. Bulk tissue and single-nucleus expression profiling disclosed sublayer-specific transcriptomic signatures and robust microglial pro-inflammatory responses. Transcripts regulating neuronal processes such as voltage-channels, synaptic signalling and cell adhesion molecules were deregulated by epilepsy differently across sublayers, while neurodegenerative signatures primarily involved superficial cells. Pseudotime analysis of gene expression in single-nuclei andin situvalidation revealed separated trajectories from health to epilepsy across cell types, and identified a subset of superficial cells undergoing a later stage in neurodegeneration. Our findings indicate sublayer- and cell type-specific changes associated with selective CA1 neuronal damage contributing to progression of hippocampal sclerosis.
Inhibiting glycogen synthase kinase 3 suppresses TDP-43-mediated neurotoxicity in a caspase-dependant manner
Authors: White Matthew A. , Massenzio Francesca , Li Xingli , Coleman Michael P. , Barmada Sami J. , Sreedharan Jemeen 
Published: February 2021

AbstractAmyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) is a progressive and ultimately fatal disease spectrum characterised by 43-kDa TAR DNA-binding protein (TDP-43) pathology. Current disease modifying drugs have modest effects and novel therapies are sorely needed. We previously showed that deletion of glycogen synthase kinase-3 (GSK3) suppresses TDP-43-mediated motor neuron degeneration inDrosophila.Here, we investigated the potential of GSK3 inhibition to ameliorate TDP43-mediated toxicity in mammalian neurons. Expression of TDP-43 was found to both activate GSK3 and promote caspase mediated cleavage of TDP-43. Inhibition of GSK3 reduced the abundance of full-length and cleaved TDP-43 in rodent neurons expressing wild-type or disease-associated mutant TDP-43 and also ameliorated neurotoxicity. Our results suggest that TDP-43 turnover is promoted by GSK3 inhibition in a caspase-dependent manner, and that targeting GSK3 activity could have therapeutic value.
Usingde novoassembly to identify structural variation of complex immune system gene regions
Authors: Zhang Jia-Yuan , Roberts Hannah , Flores David S. C. , Cutler Antony J. , Brown Andrew C. , Whalley Justin P. , Mielczarek Olga , Buck David , Lockstone Helen , Xella Barbara , Oliver Karen , Corton Craig , Betteridge Emma , Bashford-Rogers Rachael , Knight Julian C. , Todd John A. , Band Gavin 
Published: February 2021

AbstractDriven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity, to which several factors contribute including inheritable structural polymorphism of the underlying genes. Characterizing this variation is challenging due to the complexity of these loci, which contain extensive regions of paralogy, segmental duplication and high copy-number repeats, but recent progress in long-read sequencing and optical mapping techniques suggests this problem may now be tractable. Here we assess this by using long-read sequencing platforms from PacBio and Oxford Nanopore, supplemented with short-read sequencing and Bionano optical mapping, to sequence DNA extracted from CD14+monocytes and peripheral blood mononuclear cells from a single European individual identified as HV31. We use this data to build ade novoassembly of eight genomic regions encoding four key components of the immune system, namely the human leukocyte antigen, immunoglobulins, T cell receptors, and killer-cell immunoglobulin-like receptors. Validation of our assembly using k-mer based and alignment approaches suggests that it has high accuracy, with estimated base-level error rates below 1 in 10 kb, although we identify a small number of remaining structural errors. We use the assembly to identify heterozygous and homozygous structural variation in comparison to GRCh38. Despite analyzing only a single individual, we find multiple large structural variants affecting core genes at all three immunoglobulin regions and at two of the three T cell receptor regions. Several of these variants are not accurately callable using current algorithms, implying that further methodological improvements are needed. Our results demonstrate that assessing haplotype variation in these regions is possible given sufficiently accurate long-read and associated data; application of these methods to larger samples would provide a broader catalogue of germline structural variation at these loci, an important step toward making these regions accessible to large-scale genetic association studies.
Multi-modal artificial dura for simultaneous large-scale optical access and large-scale electrophysiology in non-human primate cortex
Authors: Griggs Devon J. , Khateeb Karam , Zhou Jasmine , Liu Teng , Wang Ruikang , Yazdan-Shahmorad Azadeh 
Published: February 2021

AbstractObjectiveNon-human primates (NHPs) are critical for development of translational neural technologies because of their neurological and neuroanatomical similarities to humans. Large-scale neural interfaces in NHPs with multiple modalities for stimulation and data collection poise us to unveil network-scale dynamics of both healthy and unhealthy neural systems. We aim to develop a large-scale multi-modal interface for NHPs for the purpose of studying large-scale neural phenomena including neural disease, damage, and recovery.ApproachWe present a multi-modal artificial dura (MMAD) composed of flexible conductive traces printed into transparent medical grade polymer. Our MMAD provides simultaneous neurophysiological recordings and optical access to large areas of the cortex (~3 cm2) and is designed to mitigate photo-induced electrical artifacts. The MMAD is the centerpiece of the interfaces we have designed to support electrocorticographic recording and stimulation, cortical imaging, and optogenetic experiments, all at the large-scales afforded by the brains of NHPs. We performed electrical and optical experiments bench-side andin vivowith macaques to validate the utility of our MMAD.Main resultsUsing our MMAD we present large-scale electrocorticography from sensorimotor cortex of three macaques. Furthermore, we validated surface electrical stimulation in one of our animals. Our bench-side testing showed up to 90% reduction of photo-induced artifacts with our MMAD. The transparency of our MMAD was confirmed both via bench-side testing (87% transmittance) and viain vivoimaging of blood flow from the underlying microvasculature using optical coherence tomography angiography.SignificanceOur results indicate that our MMAD supports large-scale electrocorticography, large-scale cortical imaging, and, by extension, large-scale optical stimulation. The MMAD prepares the way for both acute and long-term chronic experiments with complimentary data collection and stimulation modalities. When paired with the complex behaviors and cognitive abilities of NHPs, these assets prepare us to study large-scale neural phenomena including neural disease, damage, and recovery.
Fibroblast activation protein regulates natural killer cell migration, extravasation and tumor infiltration
Authors: Fitzgerald Allison A. , Maynard Rachael E. , Marcisak Emily F. , Nasir Apsra , Glasgow Eric , Jablonski Sandra A. , Van Der Veken Pieter , Pearson Gray , Eisman Shira E. , Mace Emily M. , Fertig Elana J. , Weiner Louis M. 
Published: February 2021

AbstractNatural killer (NK) cells play a critical role in physiologic and pathologic conditions such as pregnancy, infection, autoimmune disease and cancer. In cancer, numerous strategies have been designed to exploit the cytolytic properties of NK cells, with variable success. A major hurdle to NK-cell focused therapies is NK cell recruitment and infiltration into tumors. While the chemotaxis pathways regulating NK recruitment to different tissues are well delineated, the mechanisms human NK cells employ to physically migrate are ill-defined. We show for the first time that human NK cells express fibroblast activation protein (FAP), a cell surface protease previously thought to be primarily expressed by activated fibroblasts. FAP degrades the extracellular matrix to facilitate cell migration and tissue remodeling. We used novelin vivozebrafish andin vitro3D culture models to demonstrate that FAP knock out and pharmacologic inhibition restrict NK cell migration, extravasation, and invasion through tissue matrix. Notably, forced overexpression of FAP promotes NK cell invasion through matrix in both transwell and tumor spheroid assays, ultimately increasing tumor cell lysis. Additionally, FAP overexpression enhances NK cells invasion into a human tumor in immunodeficient mice. These findings demonstrate the necessity of FAP in NK cell migration and present a new approach to modulate NK cell trafficking and enhance cell-based therapy in solid tumors.Graphical Abstract
Discovery of a first-in-class inhibitor of the PRMT5-substrate adaptor interaction
Authors: McKinney David C , McMillan Brian J , Ranaghan Matthew , Moroco Jamie A , Brousseau Merissa , Mullin-Bernstein Zachary , O’Keefe Meghan , McCarren Patrick , Mesleh Michael F. , Mulvaney Kathleen M. , Singh Ritu , Bajrami Besnik , Skepner Adam , Timm David E. , Porter Dale , Kaushik Virendar K. , Sellers William R. , Ianari Alessandra 
Published: February 2021

AbstractPRMT5 and its substrate adaptor proteins (SAPs), pICln and Riok1, are synthetic lethal dependencies in MTAP-deleted cancer cells. SAPs share a conserved PRMT5 binding motif (PBM) which mediates binding to a surface of PRMT5 distal to the catalytic site. This interaction is required for methylation of several PRMT5 substrates, including histone and spliceosome complexes. We screened for small molecule inhibitors of the PRMT5-PBM interaction and validated a compound series which binds to the PRMT5-PBM interface and directly inhibits binding of SAPs. Mode of action and structure determination studies revealed that these compounds form a covalent bond between a halogenated pyridazinone group and cysteine 278 of PRMT5. Optimization of the starting hit produced a lead compound, BRD0639, which engages the target in cells, disrupts the PRMT5-RIOK1 complex, and reduces substrate methylation. BRD0639 is a first-in-class PBM-competitive small molecule that can support studies of PBM-dependent PRMT5 activities and the development of novel PRMT5 inhibitors that selectively target these functions.
Cryptic microgeographic variation in responses of larval Atlantic cod to warmer temperatures
Authors: Oomen Rebekah A. , Juliussen Elisabeth , Olsen Esben M. , Knutsen Halvor , Jentoft Sissel , Hutchings Jeffrey A. 
Published: February 2021

AbstractAlthough temperature is known to drive species dynamics and distributions, our understanding of the extent to which thermal plasticity varies within species is poor. Differences in plasticity can arise through local adaptation to heterogeneous environments, hybridization, and the release of cryptic genetic variation in novel environments. Here, wild Atlantic cod (Gadus morhua) from contrasting environments inside and outside of a fjord system in southern Norway spawned freely in a semi-natural laboratory environment, generating pure crosses and reciprocal hybrids. A common-garden rearing experiment of the larvae at 6°C, 9.5°C, and 13°C revealed cryptic genetic variation in thermal responses of growth and survival at warmer temperatures. Variation in growth plasticity was greatest from 9.5°C to 13°C, the latter of which exceeds temperatures currently typical of larvae in their native environments. In contrast to our prediction of intermediate hybrid responses consistent with additive genetic effects, one reciprocal hybrid cross showed a 4% increase in size at the highest temperature, whereas most crosses exhibited 4-12% reductions in size. All crosses experienced severe (76-93%) reductions in survival from 9.5°C to 13°C. Variation in survival plasticity suggests a genetically variable basis for the severity with which survival declines with increasing temperature and the potential for an adaptive response to warming. Notably, we demonstrate the potential for hybridization between coexisting ‘fjord’ and ‘North Sea’ ecotypes that naturally inhabit the inner and outer fjord environments at contrasting frequencies. Yet, ecotype explained a minor (3-10%) component of growth reaction norm variation, suggesting it is insufficient for describing important biological variation. Current broad-scale management and lack of coastal monitoring impede the development of strategies to maintain the potential for adaptation to warming temperatures in systems with such phenotypic complexity resulting from cryptic genetic variation, coexisting ecotypes, and gene flow.
Assessing knowledge, concerns, and risk perceptions among Italian medical students during the SARS-CoV-2 pandemic
Authors: Greco Manfredi , Maietti Elisa , Rallo Flavia , Reno Chiara , Trerè Davide , Savoia Elena , Fantini Maria Pia , Gori Davide 
Published: February 2021

ABSTRACTINTRODUCTIONDuring the first phase of COVID-19 pandemic, Italian medical students transitioned from in-person to remote learning. This study was carried out to early assess students’ sources of information, perceived risk of infection, knowledge and preventive practices in order to resume academic activity. The impact of training and volunteer work was also assessed.METHODSA cross-sectional online survey was conducted in May 2020 among medical students enrolled in the School of Medicine and Surgery, Bologna University.RESULTSThe analysis included 537 responses. On average students used seven sources of information on COVID-19. Scientific journals were considered the most trustworthy but they ranked only 6th in the frequency of use. Perceived risk of infection was higher for academic activities, especially in the hospital than daily living activities. Less than 50% of students reported being trained on biological risk and use of PPE. Training received was significantly associated with both perceived risk of infection and confidence in the use of PPE. Students engaged in volunteer work had higher confidence in PPE usage.DISCUSSIONAccessible scientific information and students’ engagement in spreading correct knowledge play an important role in challenging misinformation during the pandemic crisis. Students showed suboptimal knowledge about PPE use, calling for additional training. We found a moderate-high perceived risk of infection that could be mitigated with specific educational programs and by promoting voluntary work. Students’ engagement in public health emergencies (PHE) could potentially be beneficial for their training and as well as for the healthcare system.
Tuberculostearic acid (TSA)-containing phosphatidylinositols as reliable marker to determineMycobacterium tuberculosisbacterial burden
Authors: Brandenburg Julius , Heyckendorf Jan , Waldow Franziska , Zehethofer Nicole , Linnemann Lara , Gisch Nicolas , Karaköse Hande , Reimann Maja , Kranzer Katharina , Kalsdorf Barbara , Sanchez-Carballo Patricia , Weinkauf Michael , Scholz Verena , Malm Sven , Homolka Susanne , Gaede Karoline I. , Herzmann Christian , Schaible Ulrich E. , Hölscher Christoph , Reiling Norbert , Schwudke Dominik 
Published: February 2021

AbstractIt is estimated that approximately one-fourth of the world's population is infected with strains of theMycobacterium tuberculosiscomplex (MTBC), the causative agents of tuberculosis (TB). In this study, we present rationally developed molecular markers for bacterial burden, which are derived from mycobacterial phospholipids. Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PI) are present in all clinically relevant MTBC lineages investigated. For the major abundant lipid PI 16:0_19:0 (TSA), a detection limit equivalent to 102colony forming units (CFU) was determined for bacterial cultures and approximately 103for cell culture systems. We further developed a mass spectrometry based targeted lipid assay, which – in contrast to bacterial quantification on solid medium – can be performed within several hours including sample preparation. Translation of this indirect and culture-free detection approach allowed the determination of pathogen loads in infected murine macrophages, human neutrophils and murine lung tissue. We show that marker lipids inferred from the mycobacterial PIs are increased in peripheral blood mononuclear cells (PBMCs) of TB patients beyond the lipid metabolic background in comparison to healthy controls. In a small cohort of drug-susceptible TB patients elevated levels of these marker molecules were detected at therapy start and declined following successful anti-tuberculosis treatment. The concentration of TSA-containing PIs can be used as correlate for reliable and rapid quantification ofMycobacterium tuberculosis (Mtb)burden in experimentalin vitromodel systems and may also provide a clinically relevant tool for monitoring TB therapy.One Sentence SummaryTuberculostearic acid containing phosphatidylinositols represent a novel, fast to measure, reliable correlate ofMycobacterium tuberculosisbacterial burden in experimental model systems, which makes a future clinical application conceivable.