bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th17 immunity in the colon is controlled by two novel subsets of colon-specific mononuclear phagocytes
Authors: Huang Hsin-I , Jewell Mark L. , Youssef Nourhan , Huang Min-Nung , Hauser Elizabeth R. , Fee Brian E. , Rudemiller Nathan P. , Privratsky Jamie R. , Zhang Junyi J. , Reyes Estefany , Wang Donghai , Taylor Gregory A. , Gunn Michael D. , Ko Dennis C. , Cook Donald N. , Chandramohan Vidyalakshmi , Crowley Steven D. , Hammer Gianna Elena 
Published: January 2021

AbstractIntestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.
BnaA03.WRKY28, interacting with BnaA09.VQ12, acts as a brake factor of activated BnWRKY33-mediated resistance outburst againstSclerotinia sclerotioruminBrassica napus
Authors: Zhang Ka , Liu Fei , Wang Zhixin , Zhuo Chenjian , Hu Kaining , Li Xiaoxia , Wen Jing , Yi Bin , Shen Jinxiong , Ma Chaozhi , Fu Tingdong , Tu Jinxing 
Published: January 2021

ABSTRACTSclerotinia sclerotiorumcauses substantial damage to the growth ofBrassica napus(rapeseed) and makes a significant loss of crop yield. The plant innate immune system may be the primary solution to defense againstS. sclerotiorumfor rapeseed. Here, we identify that BnWRKY33, a transcription factor in the innate immune pathway, can be rapidly phosphorylated and activated by the MAPK cascade after rapeseed is infected withS. sclerotiorum. In the MAPK cascade, activated BnaA03.MKK4 phosphorylates and activates BnaA06.MPK3 and BnaC03.MPK3. The activated BnMPK3 acts on the substrate BnWRKY33 to enhance its transcriptional activity and trigger a transcriptional burst ofBnWRKY33, which helps plants effectively resist the pathogenic fungi by enhancing the expression of phytoalexin synthesis-related genes. With constant infection,BnaA03.WRKY28andBnaA09.VQ12are induced, and BnaA03.WRKY28 physically interacts with BnaA09.VQ12 to form a protein complex. BnaA03.WRKY28 preferentially binds to the promoter ofBnWRKY33with the help of BnaA09.VQ12. Compared with activated BnWRKY33, BnaA03.WRKY28 has a lower transcriptional activity on downstreamBnWRKY33, which leads to weaker resistance againstS. sclerotiorumfor rapeseed in the later stage of infection. Furthermore, the inducedBnaA03.WRKY28may promote axillary bud activity and axillary meristem initiation by regulating the expression of branching-related genes (such asBnBRC1), thus promoting the formation of branches in the leaf axils.One-sentence summaryUnder constant infection bySclerotinia sclerotiorum, BnaA03.WRKY28 interacts with BnaA09.VQ12 and takes precedence over phosphorylated BnWRKY33 to bind to theBnWRKY33promoter, thereby weakening resistance but promoting branching.
Does insect herbivory suppress ecosystem productivity? Evidence from a temperate woodland
Authors: Visakorpi Kristiina , Gripenberg Sofia , Malhi Yadvinder , Riutta Terhi 
Published: January 2021

AbstractOur current understanding of the relationship between insect herbivory and ecosystem productivity is limited. Previous studies have typically quantified only leaf area loss, or have been conducted during outbreak years. These set-ups often ignore the physiological changes taking place in the remaining plant tissue after insect attack, or may not represent typical, non-outbreak herbivore densities. Here, we estimate the amount of carbon lost to insect herbivory in a temperate deciduous woodland both through leaf area loss and, notably, through changes in leaf gas exchange in non-consumed leaves under non-outbreak densities of insects. We calculate how net primary productivity changes with decreasing and increasing levels of herbivory, and estimate what proportion of the carbon involved in the leaf area loss is transferred further in the food web. We estimate that the net primary productivity of an oak stand under ambient levels of herbivory is 54 - 69% lower than that of a completely intact stand. The effect of herbivory quantified only as leaf area loss (0.1 Mg C ha−1yr−1) is considerably smaller than when the effects of herbivory on leaf physiology are included (8.5 Mg C ha−1yr−1). We propose that the effect of herbivory on primary productivity is non-linear and mainly determined by changes in leaf gas exchange. We call for replicated studies in other systems to validate the relationship between insect herbivory and ecosystem productivity described here.
Exploring the prognostic value of SCARF1 in non-small cell lung cancers
Authors: Patten Daniel A. , Shetty Shishir 
Published: January 2021

AbstractScavenger receptor class F member 1 (SCARF1) has previously been shown to be highly expressed within the human liver, hold prognostic value in hepatocellular carcinoma and mediate the specific recruitment of leukocytes to liver sinusoidal endothelial cells; however, to date, the liver remains the only major organ in which SCARF1 has been explored in any detail. Here, we utilised publically-available RNA-sequencing data from The Cancer Genome Atlas (TGCA) to identify the lungs as a site of significantSCARF1expression and attribute the majority of its expression to endothelial cell populations. Next, we show thatSCARF1expression is significantly reduced in two histologically distinct types of non-small cell lung carcinoma cancers (NSCLCs), lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), compared to non-tumoural tissues. Interestingly, loss ofSCARF1expression was associated with aggressive tumour biology in LUAD tissues, but not in LUSC. Furthermore, increasedSCARF1expression was highly prognostic of better overall survival in LUAD tumour tissues, but this was again in contrast to LUSC tumours, in whichSCARF1held no prognostic value. Finally, we showed thatSCARF1is widely expressed in tumour endothelial cells of non-small cell lung cancers and that its total expression in LUAD tumour tissues correlated with immune score and CD4+T cell infiltration. This study represents the first detailed exploration ofSCARF1expression in normal and diseased human lung tissues and further highlights the prognostic value and therapeutic potential of SCARF1 in immunologically active cancers.
ssDNA recombineering boostsin vivoevolution of nanobodies displayed on bacterial surfaces
Authors: Al-ramahi Yamal , Nyerges Akos , Margolles Yago , Cerdán Lidia , Ferenc Gyorgyi , Pál Csaba , Fernández Luis Ángel , de Lorenzo Víctor 
Published: January 2021

SUMMARYIn vivoevolution of antibodies facilitates emergence of novel target specificities from pre-existing clones. In this work we show how mutagenic ssDNA recombineering of camel-derived nanobodies encoded in a bacterial genome enables clonal hyper-diversification and the rise of new properties. As a proof-of-principle we used a nanobody recognizing the antigen TirM from enterohaemorrhagicE. coli(EHEC) and evolved it towards the otherwise not recognized TirM antigen from enteropathogenicE. coli(EPEC). To this end,E. colicells displaying on their surface this nanobody fused to the intimin outer membrane anchor domain were subjected to multiple rounds of mutagenic ssDNA recombineering targeted to the CDR1, CDR2 and CDR3 regions of its genomically encoded VHHsequence. Binders to the new antigen (EPEC TirM) were then selected upon immunomagnetic capture of bacteria bearing the corresponding nanobody variants. As a result, several modified nanobodies were identified which maintained recognition of EHEC TirM but acquired the ability to bind the new antigen with high affinity (Kd ~20 nM). The results highlight the power of combining evolutionary properties of bacteriain vivowith oligonucleotide synthesisin vitrofor the sake of focusing diversification to specific segments of a gene (or protein thereof) of interest. Our experimental workflow empowers the evolution of nanobodies displayed on the surface of bacterial cells for a large number of potential applications in medical and industrial biotechnology.
Pervasive false brain connectivity from electrophysiological signals
Authors: Pascual-Marqui Roberto D. , Achermann Peter , Faber Pascal , Kinoshita Toshihiko , Kochi Kieko , Nishida Keiichiro , Yoshimura Masafumi 
Published: January 2021

1.AbstractSignals of brain electric neuronal activity, either invasively measured or non-invasively estimated, are commonly used for connectivity inference. One popular methodology assumes that the neural dynamics follow a multivariate autoregression, where the autoregressive coefficients represent the couplings among regions. If observation noise is present and ignored, as is common in practice, the estimated couplings are biased, affecting all forms of Granger-causality inference, both in time and in frequency domains. Significant nonsense coupling, i.e., nonsense connectivity, can appear when in reality there is none, since there is always observation noise in two possible forms: measurement noise, and activity from other brain regions due to volume conduction and low spatial resolution. This problem is critical, and is currently not being addressed, calling into question the validity of many Granger-causality reports in the literature. An estimation method that accounts for noise is based on an overdetermined system of high-order multivariate Yule-Walker equations, which give reduced variance estimators for the coupling coefficients of the unobserved signals. Simulation-based comparisons to other published methods are presented, demonstrating its adequate performance. In addition, simulation results are presented for a zero connectivity case with noisy observations, where the new method correctly reports no connectivity while classical analyses (as found in most software packages) report nonsense connectivity. For the sake of reproducible research, the supplementary material includes, in human readable format, all the time series data used here.
Macaque V1 responses to 2nd-order contrast-modulated stimuli and the possible subcortical and cortical contributions
Authors: Ju Nian-Sheng , Guan Shu-Chen , Tang Shi-Ming , Yu Cong 
Published: January 2021

AbstractV1 neurons as linear filters supposedly only respond to 1st-order luminance-modulated (LM) stimuli, but not 2nd-order contrast-modulated (CM) ones. To solve this difficulty, filter-rectify-filter models are proposed, in which first-stage filters respond to CM stimulus elements, and the nonlinear-rectified outputs are summed by a second-stage filter for CM stimulus representation. Correspondingly, neurophysiological evidence shows V1/A17 neurons less responsive to CM stimuli than V2/A18 neurons. Here we used two-photon calcium imaging to demonstrate substantial V1 responses to CM gratings with unimodally distributed LM/CM preferences. Moreover, LM responses are suppressed by LM and CM adaptations regardless of orientation, but CM responses are more suppressed by same-orientation LM and CM adaptations than by orthogonal ones. While LM adaptation results agree with the Hubel-Wiesel view of LGN contributions to V1 orientation responses, CM adaptation results, which include both orientation-unspecific and specific components, may suggest similar subcortical contributions plus additional refinement by recurrent intracortical interactions.
Angular and Linear Speed Cells in the Parahippocampal Circuits
Authors: Spalla Davide , Treves Alessandro , Boccara Charlotte N. 
Published: January 2021

AbstractAn essential role of the hippocampal region is to integrate information to compute and update representations. How this transpires is highly debated. Many theories hinge on the integration of self-motion signals and the existence of continuous attractor networks (CAN). CAN models hypothesise that neurons coding for navigational correlates – such as position and direction – receive inputs from cells conjunctively coding for position, direction and self-motion. As yet, such conjunctive coding had not been found in the hippocampal region. Here, we report neurons coding for angular and linear velocity, distributed across the medial entorhinal cortex, the presubiculum and the parasubiculum. These self-motion neurons often conjunctively encoded position and/or direction, yet lacked a structured organisation, calling for the revision of current CAN models. These results offer insights as to how linear/angular speed – derivative in time of position/direction – may allow the updating of spatial representations, possibly uncovering a generalised algorithm to update any representation.
Estimating repeat spectra and genome length from low-coverage genome skims with RESPECT
Authors: Sarmashghi Shahab , Balaban Metin , Rachtman Eleonora , Touri Behrouz , Mirarab Siavash , Bafna Vineet 
Published: January 2021

AbstractThe cost of sequencing the genome is dropping at a much faster rate compared to assembling and finishing the genome. The use of lightly sampled genomes (genome-skims) could be transformative for genomic ecology, and results usingk-mers have shown the advantage of this approach in identification and phylogenetic placement of eukaryotic species. Here, we revisit the basic question of estimating genomic parameters such as genome length, coverage, and repeat structure, focusing specifically on estimating thek-mer repeat spectrum. We show using a mix of theoretical and empirical analysis that there are fundamental limitations to estimating thek-mer spectra due to ill-conditioned systems, and that has implications for other genomic parameters. We get around this problem using a novel constrained optimization approach (Spline Linear Programming), where the constraints are learned empirically. On reads simulated at 1X coverage from 66 genomes, our method, REPeat SPECTra Estimation (RESPECT), had<1.5% error in length estimation compared to 34% error previously achieved. In shotgun sequenced read samples with contaminants, RESPECT length estimates had median error 4%, in contrast to other methods that had median error 80%. Together, the results suggest that low-pass genomic sequencing can yield reliable estimates of the length and repeat content of the genome. The RESPECT software will be publicly available athttps://github.com/shahab-sarmashghi/RESPECT.git
SUFI:An automated approach to spectral unmixing of fluorescent multiplex images captured in mouse and postmortem human brain tissues
Authors: Sadashivaiah Vijay , Tippani Madhavi , Page Stephanie C. , Kwon Sang Ho. , Bach Svitlana V. , Bharadwaj Rahul A. , Hyde Thomas M. , Kleinman Joel E. , Jaffe Andrew E. , Maynard Kristen R. 
Published: January 2021

AbstractMultispectral fluorescence imaging coupled with linear unmixing is a form of image data collection and analysis that uses multiple fluorescent dyes - each measuring a specific biological signal - that are simultaneously measured and subsequently “unmixed” to provide a read-out for each individual signal. This strategy allows for measuring multiple signals in a single data capture session - for example, multiple proteins or RNAs in tissue slices or cultured cells, but can often result in mixed signals and bleed-through problems across dyes. Existing spectral unmixing algorithms are not optimized for challenging biological specimens such as postmortem human brain tissue, and often require manual intervention to extract spectral signatures. We therefore developed an intuitive, automated, and flexible package calledSUFI: spectral unmixing of fluorescent images (https://github.com/LieberInstitute/SUFI). This package unmixes multispectral fluorescence images by automating the extraction of spectral signatures using Vertex Component Analysis, and then performs one of three unmixing algorithms derived from remote sensing. We demonstrate these remote sensing algorithms’ performance on four unique biological datasets and compare the results to unmixing results obtained using ZEN Black software (Zeiss). We lastly integrate our unmixing pipeline into the computational tooldotdotdotthat is used to quantify individual RNA transcripts at single cell resolution in intact tissues and perform differential expression analysis of smFISH data, and thereby provide a one-stop solution for multispectral fluorescence image analysis and quantification. In summary, we provide a robust, automated pipeline to assist biologists with improved spectral unmixing of multispectral fluorescence images.
Coronavirus-associated molecular mimicry through homology to a SARS-CoV-2 peptide could be leading to susceptibility in patients with HLA-A*02:01 and HLA-A*24:02 serotypes
Authors: Adiguzel Yekbun 
Published: January 2021

AbstractThis study aims to predict autoimmunity-related pathological mechanisms that possess risk for individuals with specific human leukocyte antigen (HLA) serotypes and shared by certain coronaviruses including SARS-CoV-2, based on homology to a SARS-CoV-2 peptide. With the given aim, 1-) coronavirus-associated sequences, which are homologous to the 15mer SARS-CoV-2 peptide CFLGYFCTCYFGLFC, are obtained. 2-) Human peptides that have at least 7 residue matches with those coronavirus sequences, and the SARS-CoV-2 15mer, are found. 3-) Epitope pairs, which are sourced by those aligned coronavirus and human sequences are identified. 4-) Epitope pairs that are predicted to bind strongly not only to the same HLA allele with each other but also to the same HLA allele as those of the respective alignment of the SARS-CoV-2 peptide are selected. Following are the identified proteins or peptides (with HLA-A*02:01 or HLA-A*24:02 epitopes), as described in 1-to-4: Immunoglobulin heavy chain junction regions, CRB1 isoform I precursor, slit homolog 2 protein, hCG1995581, hCG2028737, phospholipid phosphatase-related protein type 2. Among those, CRB1 isoform I precursor sequence with the predicted HLA-A*24:02 epitope aligns with the highest number of different sequences. Results imply autoimmunity risk in COVID-19 patients with HLA-A*02:01 and HLA-A*24:02 serotypes, through molecular mimicry, as a shared pathogenicity risk that can be prevalent upon getting infected with certain coronaviruses. These can pave way to improved risk groups’ assessment and autoimmunity treatment options, for COVID-19 and its associated diseases. Also, the approach in this study can be used to predict prospective pathologies of the transmissible variants in susceptible humans.
Human brain organoid networks
Authors: Sharf Tal , van der Molen Tjitse , Glasauer Stella M.K. , Guzman Elmer , Buccino Alessio P. , Luna Gabriel , Cheng Zhouwei , Audouard Morgane , Ranasinghe Kamalini G. , Kudo Kiwamu , Nagarajan Srikantan S. , Tovar Kenneth R. , Petzold Linda R. , Hierlemann Andreas , Hansma Paul K. , Kosik Kenneth S. 
Published: January 2021

AbstractHuman brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiological behavior of neuronal circuits within organoids remains relatively under-explored. With high-density CMOS microelectrode arrays (26,400 electrodes) and shank electrodes (960 electrodes), we probed broadband and three-dimensional extracellular field recordings generated by spontaneous activity of human brain organoids. These recordings simultaneously captured local field potentials (LFPs) and single-unit activity extracted through spike sorting. From spiking activity, we estimated a directed functional connectivity graph of synchronous neural network activity, which showed a large number of weak functional connections enmeshed within a network skeleton of significantly fewer strong connections. Treatment of the organoid with a benzodiazepine induced a reproducible signature response that shortened the inter-burst intervals, increased the uniformity of the firing pattern within each burst and decreased the population of weakly connected edges. Simultaneously examining the spontaneous LFPs and their phase alignment to spiking showed that spike bursts were coherent with theta oscillations in the LFPs. Our results demonstrate that human brain organoids have self-organized neuronal assemblies of sufficient size, cellular orientation, and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug mechanisms, and the effects of external stimuli upon neuronal networks.
Immune elicitation by sensing the conserved signature from phytocytokines and microbes via theArabidopsisMIK2 receptor
Authors: Hou Shuguo , Liu Derui , Huang Shijia , Luo Dexian , Liu Zunyong , Wang Ping , Mu Ruimin , Han Zhifu , Chai Jijie , Shan Libo , He Ping 
Published: January 2021

ABSTRACTSessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that theArabidopsisreceptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE RICH ENDOGENOUS PEPTIDEs (SCOOPs) from plants as well as proteins present in fungalFusariumspp. and bacterialComamonadaceae, and elicits potent immune responses. SCOOP signature peptides trigger diverse immune and physiological responses in a MIK2-dependent manner with a sub-nanomolar sensitivity and directly bind to the extracellular leucine rich-repeat domain of MIK2in vivoandin vitro, indicating that MIK2 is the receptor of SCOOP peptides. Perception of SCOOP peptides induces the association of MIK2 and the coreceptors SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (SERK3) and SERK4 and relays the signaling through the cytosolic receptor-like kinasesBOTRYTIS-INDUCED KINASE 1 (BIK1) and AVRPPHB SUSCEPTIBLE1 (PBS1)-LIKE 1 (PBL1). Our study identified a unique plant receptor that bears a dual recognition capability sensing the conserved peptide motif from phytocytokines and microbial proteins via a convergent signaling relay to ensure a robust immune response.
PredicTF: a tool to predict bacterial transcription factors in complex microbial communities
Authors: Oliveira Monteiro Lummy Maria , Saraiva Joao , Toscan Rodolfo Brizola , Stadler Peter F , Silva-Rocha Rafael , da Rocha Ulisses Nunes 
Published: January 2021

AbstractTranscription Factors (TFs) are proteins that control the flow of genetic information by regulating cellular gene expression. Here we describe PredicTF, a first platform supporting the prediction and classification of novel bacterial TF in complex microbial communities. We evaluated PredicTF using a two-step approach. First, we tested PredictTF’s ability to predict TFs for the genome of an environmental isolate. In the second evaluation step, PredicTF was used to predict TFs in a metagenome and 11 metatranscriptomes recovered from a community performing anaerobic ammonium oxidation (anammox) in a bioreactor. PredicTF is open source pipeline available athttps://github.com/mdsufz/PredicTF.