bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic selection to optimize doubled haploid-based hybrid breeding in maize
Authors: Li Jinlong , Cheng Dehe , Guo Shuwei , Yang Zhikai , Chen Ming , Chen Chen , Jiao Yanyan , Li Wei , Liu Chenxu , Zhong Yu , Qi Xiaolong , Yang Jinliang , Chen Shaojiang 
Published: September 2020

ABSTRACTCrop improvement, as a long-term endeavor, requires continuous innovations in technique from multiple perspectives. Doubled haploid (DH) technology for pure inbred production, which shaves years off of the conventional selfing approach, has been widely used for breeding. However, the final success rate ofin vivomaternal DH production is determined by four factors: haploids induction, haploids identification, chromosome doubling, and successful selfing of the fertile haploid plants to produce DH seeds. Traits in each of these steps, if they can be accurately predicted using genomic selection methods, will help adjust the DH production protocol and simplify the logistics and save costs. Here, a hybrid population (N=158) was generated based on an incomplete half diallel design using 27 elite inbred lines. These hybrids were induced to create F1-derived haploid families. The hybrid materials, as well as the 27 inbreds, the inbred-derived haploids (N=200), and the F1-derived haploids (N=5,000) were planted in the field to collect four DH-production traits, three yield-related traits, and three developmental traits. Quantitative genetics analysis suggested that in both diploids and haploid families, most of the developmental traits showed high heritability, while the DH-production and developmental traits exhibited intermediate levels of heritability. By employing different genomic selection models, our results showed that the prediction accuracy ranged from 0.52 to 0.59 for the DH-production traits, 0.50 to 0.68 for the yield-related traits, and 0.44 to 0.87 for the developmental traits. Further analysis using index selection achieved the highest prediction accuracy when considering both DH production efficiency and the agronomic trait performance. Furthermore, the long-term responses through simulation confirmed that index selection would increase the genetic gain for targeted agronomic traits while maintaining the DH production efficiency. Therefore, our study provides an optimization strategy to integrate GS technology for DH-based hybrid breeding.
Genomic asymmetry of theBrassica napusseed: Epigenetic contributions of DNA methylation and small RNAs to subgenome bias
Authors: Ziegler Dylan J. , Khan Deirdre , Pulgar-Vidal Nadège , Parkin Isobel A.P. , Robinson Stephen J. , Belmonte Mark F. 
Published: September 2020

AbstractPolyploidy has predominated the genetic history of the angiosperms, and allopolyploidy is known to have contributed to the vast speciation of flowering plants.Brassica napus, one of the world’s most important oilseeds, is one such polyploid species originating from the interspecific hybridization ofBrassica rapa(An) andBrassica oleracea(Cn). Nascent amphidiploids must balance progenitor genomes during reproduction, though the role of epigenetic regulation in subgenome maintenance is unknown. The seed is the pivotal developmental transition into the new sporophytic generation and as such undergoes substantial epigenetic modifications. We investigated subgenome bias between the Anand Cnsubgenomes as well as across syntenic regions by profiling DNA methylation and siRNAs characteristic ofB. napusseed development. DNA methylation and siRNA accumulation were prevalent in the Cnsubgenome and most pronounced early during seed morphogenesis. Hypermethylation during seed maturation was most pronounced on non-coding elements, including promoters, repetitive elements, and siRNAs. Methylation on siRNA clusters was more prevalent in syntenic regions of the Cnsubgenome and implies selective silencing of genomic loci of the seed. Together, we find compelling evidence for the asymmetrical epigenetic regulation of the Anand Cnsubgenomes ofBrassica napusacross seed development.
Global Importance Analysis: An Interpretability Method to Quantify Importance of Genomic Features in Deep Neural Networks
Authors: Koo Peter K. , Majdandzic Antonio , Ploenzke Matthew , Anand Praveen , Paul Steffan B. 
Published: September 2020

ABSTRACTDeep neural networks have demonstrated improved performance at predicting the sequence specificities of DNA- and RNA-binding proteins compared to previous methods that rely onk-mers and position weight matrices. To gain insights into why a DNN makes a given prediction, model interpretability methods, such as attribution methods, can be employed to identify motif-like representations along a given sequence. Because explanations are given on an individual sequence basis and can vary substantially across sequences, deducing generalizable trends across the dataset and quantifying their effect size remains a challenge. Here we introduce global importance analysis (GIA), a model interpretability method that quantifies the population-level effect size that putative patterns have on model predictions. GIA provides an avenue to quantitatively test hypotheses of putative patterns and their interactions with other patterns, as well as map out specific functions the network has learned. As a case study, we demonstrate the utility of GIA on the computational task of predicting RNA-protein interactions from sequence. We first introduce a convolutional network, we call ResidualBind, and benchmark its performance against previous methods on RNAcompete data. Using GIA, we then demonstrate that in addition to sequence motifs, ResidualBind learns a model that considers the number of motifs, their spacing, and sequence context, such as RNA secondary structure and GC-bias.
Clostridium difficilebinary toxin (CDT) is recognized by the TLR2/6 heterodimer to induce an NF-κB response
Authors: Simpson Morgan , Frisbee Alyse , Kumar Pankaj , Schwan Carsten , Aktories Klaus , Petri William A. 
Published: September 2020

AbstractClostridioides difficileinfection (CDI) represents a significant burden on the health care system, one that is exacerbated by the emergence of binary toxin (CDT)-producing hypervirulentC. difficilestrains. Previous work from our lab has shown that TLR2 recognizes CDT to induce inflammation. Here we explore the interactions of CDT with TLR2 and the impact on host immunity during CDI. We found that the TLR2/6 heterodimer, not TLR2/1, is responsible for CDT recognition, and that gene pathways including NF-κB and MAPK downstream of TLR2/6 are upregulated in mice with intact TLR2/6 signaling during CDI.
Retinal circuits driving a non-image forming visual behavior
Authors: Beier Corinne , Bocchero Ulisse , Zhang Zhijing , Jin Nange , Massey Stephen C. , Ribelayga Christophe P. , Martemyanov Kirill , Hattar Samer , Pahlberg Johan 
Published: September 2020

AbstractOuter retinal circuits that drive non-image forming vision in mammals are unknown. Rods and cones signal light increments and decrements to the brain through the ON and OFF pathways, respectively. Although their contribution to image-forming vision is known, the contributions of the ON and OFF pathway to the pupillary light response (PLR), a non-image forming behavior, are unexplored. Here we use genetically modified mouse lines, to comprehensively define the outer retinal circuits driving the PLR. The OFF pathway, which mirrors the ON pathway in image-forming vision, plays no role in the PLR. We found that rods use the primary rod pathway to drive the PLR at scotopic light levels. At photopic light levels, the primary and secondary rod pathways drive normal PLR. Importantly, we find that cones are unable to compensate for rods. Thus, retinal circuit dynamics allow rods to drive the PLR across a wide range of light intensities.
Lateralized decrease of parvalbumin+cells in the somatosensory cortex of ASD models is correlated with unilateral tactile hypersensitivity
Authors: Deemyad Tara , Puig Stephanie , Papale Andrew , Qi Hang , LaRocca Gregory M , Aravind Deepthi , LaNoce Emma , Urban Nathaniel N 
Published: September 2020

AbstractInhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin expressing (PV+) basket cells (BC) are a major player in maintaining the balance between excitation (E) and inhibition (I) in the cortex. Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorders (ASD) and may contribute to sensory alterations seen in ASD. Here, we report a lateralized decrease in the number of PV+BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of adult Shank3-/-and Cntnap2-/-mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animal’s dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (i.e., VVA) showed that the number of BCs was not different but rather, some BCs did not express detectable levels of PV (PV-), resulting in an elevated number of PV-VVA+basket cells. This lateralized reduction was not observed in the number of interneurons from the other two major groups that express somatostatin or the serotonergic receptor 5HT3a. Finally, we showed that dominant hind paws had higher mechanical sensitivity (i.e., lower mechanical thresholds measured with von Frey test) but no difference in thermal sensitivity (measured with Hargreaves test) when compared to the other hind paw. This mechanical hypersensitivity in the dominant paw correlated with the decrease in the number of PV+interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the sensory hypersensitivity in ASD could be due to decreased inhibitory inputs to the dominant somatosensory cortex.
Repeated Decision Stumping Distils Simple Rules from Single Cell Data
Authors: Croydon Veleslavov Ivan A. , Stumpf Michael P.H. 
Published: September 2020

AbstractHere we introduce repeated decision stumping, to distill simple models from single cell data. We develop decision trees of depth one – hence ‘stumps’ – to identify in an inductive manner, gene products involved in driving cell fate transitions, and in applications to published data we are able to discover the key-players involved in these processes in an unbiased manner without prior knowledge. The approach is computationally efficient, has remarkable predictive power, and yields robust and statistically stable predictors: the same set of candidates is generated by applying the algorithm to different subsamples of the data.
Neonatal enteropathogenicEscherichia coliinfection disrupts microbiota-gut-brain axis signaling
Authors: Hennessey Carly , Barboza Mariana , Brust-Mascher Ingrid , Knotts Trina A , Sladek Jessica A. , Pusceddu Matteo M , Stokes Patricia , Rabasa Gonzalo , Honeycutt Mackenzie , Walsh Olivia , Reardon Colin , Gareau Mélanie G. 
Published: September 2020

ABSTRACTBackgroundDiarrheal diseases are a leading cause of death in children under age five worldwide. Repeated early life exposures to diarrheal pathogens can result in co-morbidities including stunted growth and cognitive deficits suggesting an impairment in the microbiota-gut-brain (MGB) axis.MethodsNeonatal C57BL/6 mice were infected with EPEC (strain e2348/69; ΔescV [T3SS mutant]), or vehicle (LB broth) via orogastric gavage (105CFU) at post-natal day (P7). Behavior (novel object recognition [NOR] task, light/dark [L/D] box, and open field test [OFT]), intestinal physiology (Ussing chambers), and the microbiota (16S Illumina sequencing) were assessed in adulthood (6-8 weeks).ResultsNeonatal infection of mice with EPEC impaired recognition memory (NOR task), coupled with increased neurogenesis (Ki67 and doublecortin immunostaining) and neuroinflammation (increased microglia activation [Iba1]) in adulthood. Intestinal pathophysiology was characterized by increased secretory state (short circuit current; Isc) and permeability (conductance; FITC-dextran flux) in the ileum and colon of neonatally EPEC-infected mice, along with increased expression of pro-inflammatory cytokines (Tnfα, Il12, Il6) and pattern recognition receptors (Nlr, Tlr). Finally, neonatal EPEC infection caused significant dysbiosis of the gut microbiota, including decreased Firmicutes, in adulthood.ConclusionsTogether these findings demonstrate that infection in early life can significantly impair the MGB axis in adulthood.
Metagenomic sequencing to detect respiratory viruses in persons under investigation for COVID-19
Authors: Babiker Ahmed , Bradley Heath L. , Stittleburg Victoria D. , Key Autum , Kraft Colleen S. , Waggoner Jesse J. , Piantadosi Anne 
Published: September 2020

AbstractWe used metagenomic next-generation sequencing (mNGS) to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR negative persons under investigations (PUIs) (n=30) and viral co-infections in SARS-CoV-2 RT-PCR positive PUIs (n=45). mNGS identified both co-infections and alternative viral infections that were not detected by routine clinical workup.
Adherence to COVID-19 pandemic prescribed recommendations, source of information and lockdown psychological impact of Nigeria social media users
Authors: Bolarinwa Obasanjo Afolabi , Olagunju Olalekan , Babalola Tesleem 
Published: September 2020

AbstractBackgroundCOVID-19 is a highly infectious viral disease that has spread to over one hundred and eight countries, including Nigeria. Countries across the globe have been implementing preventive measures towards curbing the spread and impact of the virus. Thus, the present study was aimed at assessing compliance to prescribe preventive recommendations, the psychological effect of lockdown, and the source of information among Nigeria social media users.MethodsThis research implemented an online cross-sectional survey using an unidentified online Google based questionnaire to elicit required information from potential respondents via social media channels such as WhatsApp, Twitter, Instagram, Telegram and Facebook. On these forums, an external link with google based questionnaire was shared with Nigerians social media users to participate from 1st to 31st April 2020 and we had 1,131 respondents who participated in the survey.ResultsAge and respondents’ scientific or non-scientific backgrounds were the socio-demographic variables associated with respondents having psychological challenges as P<0.05. However, none of the socio-demographic variables of the respondents were associated with compliance with the recommendations as P>0.05. Also, most (63.4%) of the respondents were stressed by the feelings associated with the COVID-19 pandemic, as the expected majority (80.1%) sources information about the epidemics through social media platforms.ConclusionGiven numerous uncertainties surrounding the global COVID-19 pandemics, there is a need to continuously increase awareness through various media and ensure that people are highly complying with the preventive measures being put in place by relevant authorities. Also, palliative measures should be put in place to reduce the psychological impact of the pandemic.
Evaluation of Safety and Immunogenicity of an Adjuvanted, TH-1 Skewed, Whole Virion InactivatedSARS-CoV-2 Vaccine - BBV152
Authors: Ganneru Brunda , Jogdand Harsh , Dharam Vijaya Kumar , Molugu Narasimha Reddy , Prasad Sai D , Vellimudu Srinivas , Ella Krishna M , Ravikrishnan Rajaram , Awasthi Amit , Jose Jomy , Rao Panduranga , Kumar Deepak , Ella Raches , Abraham Priya , Yadav Pragya , Sapkal Gajanan N , Shete Anita , Desphande Gururaj Rao , Mohandas Sreelekshmy , Basu Atanu , Gupta Nivedita , Vadrevu Krishna Mohan 
Published: September 2020

ABSTRACTWe report the development and evaluation of safety and immunogenicity of a whole virion inactivated SARS-COV-2 vaccine (BBV152), adjuvanted with aluminium hydroxide gel (Algel), or a novel TLR7/8 agonist adsorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established vero cell platform to produce large-scale GMP grade highly purified inactivated antigen, BBV152. Product development and manufacturing were carried out in a BSL-3 facility. Immunogenicity was determined at two antigen concentrations (3μg and 6μg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers, at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation containing TLR7/8 agonist adjuvant-induced Th1 biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2 specific IFN-γ+ CD4 T lymphocyte response. Our results support further development for Phase I/II clinical trials in humans.
Newly regenerated axons through a cell-containing biomaterial scaffold promote reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation
Authors: Siddiqui Ahad M. , Islam Riazul , Cuellar Carlos A. , Silvernail Jodi L. , Knudsen Bruce , Curley Dallece E. , Strickland Tammy , Manske Emilee , Suwan Parita T , Latypov Timur , Akhmetov Nafis , Zhang Shuya , Summer Priska , Nesbitt Jarred J. , Chen Bingkun K. , Grahn Peter J. , Madigan Nicolas N. , Yaszemski Michael J. , Windebank Anthony J. , Lavrov Igor 
Published: September 2020

AbstractWe report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES.
The effects of multi-day rTMS and cardiorespiratory fitness on working memory and local GABA concentration
Authors: Hendrikse Joshua , Thompson Sarah , Suo Chao , Yücel Murat , Rogasch Nigel C. , Coxon James P. 
Published: September 2020

AbstractWorking memory (WM) refers to the capacity to temporarily retain and manipulate finite amounts of information; a critical process in complex behaviours such as reasoning, comprehension, and learning. This cognitive function is supported by a parietal-prefrontal network and linked to the activity of key neurotransmitters, such as gamma-aminobutyric acid (GABA). Impairments in WM are seen in a range of psychiatric and neurological disorders, and there are currently no effective treatments. In this study, we analysed secondary outcome measures from a trial investigating the effects of multi-day rTMS on cognition. Participants received four days of 20 Hz rTMS to an individualised region of left parietal cortex in one week, and an individualised region of pre-supplementary motor area (pre-SMA) in a separate week. We assessed changes to WM function before and after each week of stimulation (N = 39), and changes to GABA concentration before and after stimulation in week one using MR spectroscopy (N = 18 per stimulation condition). We hypothesised that parietal rTMS would enhance WM and alter GABA concentration at the site of stimulation, but this was not observed. Instead, we report some evidence of improved WM function following the first week of pre-SMA rTMS stimulation, and a generalised increase in GABA concentration across both parietal and pre-SMA voxels following pre-SMA rTMS. Additionally, we found that higher cardiorespiratory fitness was associated with greater WM improvement following pre-SMA stimulation. This study does not support the use of parietal multi-day rTMS for the enhancement of working memory. In contrast, the results suggest that increasing cardiorespiratory fitness may provide a novel approach to enhance the effects of pre-SMA rTMS on cognition.
Cytosolic sequestration of spatacsin by Protein Kinase A and 14-3-3 proteins
Authors: Cogo Susanna , Tomkins James E. , Vavouraki Nikoleta , Giusti Veronica , Forcellato Federica , Franchin Cinzia , Tessari Isabella , Arrigoni Giorgio , Cendron Laura , Manzoni Claudia , Civiero Laura , Lewis Patrick A. , Greggio Elisa 
Published: September 2020

AbstractMutations in SPG11, encoding spatacsin, constitute the major cause of autosomal recessive Hereditary Spastic Paraplegia (HSP) with thinning of the corpus callosum. Previous studies showed that spatacsin orchestrates cellular traffic events through the formation of a coat-like complex and its loss of function results in lysosomal and axonal transport impairments. However, the upstream mechanisms that regulate spatacsin trafficking are unknown. Here, using proteomics and CRISPR/Cas9-mediated tagging of endogenous spatacsin, we identified a subset of 14-3-3 proteins as physiological interactors of spatacsin. The interaction is modulated by Protein Kinase A (PKA)-dependent phosphorylation of spatacsin at Ser1955, which initiates spatacsin trafficking from the plasma membrane to the intracellular space. Our study provides novel insight in understanding spatacsin physio-pathological roles with mechanistic dissection of its associated pathways.