bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblasts – the neglected cell type in peripheral sensitization and chronic pain? - A systematic view on the current state of the literature
Authors: Shinotsuka Naomi , Denk Franziska 
Published: February 2021

AbstractChronic pain and its underlying biological mechanisms have been studied for many decades, with a myriad of molecules, receptors and cell types known to contribute to abnormal pain sensations. We now know that besides an obvious role for neuronal populations in the peripheral and central nervous system, immune cells like microglia, macrophages and T cells are also important drivers of persistent pain. While neuroinflammation has therefore been widely studied in pain research, there is one cell-type that appears to be rather neglected in this context: the humble fibroblast.Fibroblasts may seem unassuming, but actually play a major part in regulating immune cell function and driving chronic inflammation. What is known about them in the context chronic pain?Here we set out to analyze the literature on this topic – using systematic screening and data extraction methods to obtain a balanced view on what has been published. We found that there has been surprisingly little research in this area: 134 articles met our inclusion criteria, only a tiny minority of which directly investigated interactions between fibroblasts and peripheral neurons. We categorized the articles we included – stratifying them according to what was investigated, the estimated quality of results, and any common conclusions.Fibroblasts are a ubiquitous cell type and a prominent source of many pro-algesic mediators in a wide variety of tissues. We think that they deserve a more central role in pain research and propose a new, testable model of how fibroblasts might drive peripheral neuron sensitization.
Dynamic Electrode-to-Image (DETI) Mapping Reveals the Human Brain’s Spatiotemporal Code of Visual Information
Authors: Hansen Bruce C. , Greene Michelle R. , Field David J. 
Published: February 2021

AbstractA chief goal of systems neuroscience is to understand how the brain encodes information in our visual environments. Understanding that neural code is crucial to explaining how visual content is transformed via subsequent semantic representations to enable intelligent behavior. Although the visual code is not static, this reality is often obscured in voxel-wise encoding models of BOLD signals due to fMRI’s poor temporal resolution. We leveraged the high temporal resolution of EEG to develop an encoding technique based in state-space theory. This approach maps neural signals to each pixel within a given image and reveals location-specific transformations of the visual code, providing a spatiotemporal signature for the image at each electrode. This technique offers a spatiotemporal visualization of the evolution of the neural code of visual information thought impossible to obtain from EEG and promises to provide insight into how visual meaning is developed through dynamic feedforward and recurrent processes.
Circulating Low Density Neutrophils of Breast Cancer Patients are Associated with their Worse Prognosis due to the Impairment of T cell Responses
Authors: Saraiva Diana P. , Correia Bruna F. , Salvador Rute , de Sousa Nídia , Jacinto António , Braga Sofia , Cabral M. Guadalupe 
Published: February 2021

AbstractNeutrophils are prominent immune components of solid tumors, which can protect against the onset of cancer (N1) or have pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN, a rare subset in non-pathological conditions, have been extensively studied in cancer, due to their frequency in this disease and their pro-tumor phenotype. However, this has been mainly demonstrated in animal models and proper validation in humans is an urgent need. Here, we further enlighten the clinical impact of LDN in a cohort of breast cancer (BC) patients. We observed that LDN were practically absent in healthy donors’ blood, while were significantly increased in the blood of BC patients, particularly with metastatic disease. Relevant for a clinical translation, within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than in responders. The association of a higher incidence of circulating LDN and the worse prognosis of BC patients could be explained by the pro-tumor/immunosuppressive characteristics exhibited by these cells. Namely, there are more LDN expressing the immunosuppressive marker PD-L1, than HDN. Additionally, LDN also showed increased expression of activation markers; a robust formation of neutrophil extracellular traps; an augmented phagocytic activity; and a higher capacity to release reactive oxygen species, which may contribute for tumor development and metastization. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with the immunosuppressive CCR4+ regulatory T cells, corroborating their impairment on the anti-tumor immune responses, which was further demonstratedex vivo. Hence, this study reveals the potential of LDN as a clinical meaningful biomarker of BC response to treatment and opens new avenues for developing targeted immunotherapies.
Zooming into the genomic vicinity of the major locus for vicine and convicine in faba bean (Vicia fabaL.)
Authors: Tacke Rebecca , Ecke Wolfgang , Höfer Michael , Sass Olaf , Link Wolfgang 
Published: February 2021

AbstractThe versatility of faba bean (Vicia fabaL.) seed as valuable protein feed is hampered by its relatively high level of the compounds vicine and convicine (VC), which are antinutritive factors in poultry and further non-ruminant feed. The objective here was to develop the first-ever genetically low-VC winter faba bean. Hence, the low VC allele vc-, that should be the basis of a known, major locus for VC, need verification and molecular identification and be based on appropriately developed DNA-markers; the low VC feature awaited its transfer into the high-performing winter faba bean germplams. Based on bi-parental F2-families and isogenic lines, we thus developed highly useful SNP markers exploiting transcriptomic data. Furthermore, we fine-mapped and, based on synteny toMedicago truncatulaandCicer arietinum, we identified a candidate gene for the VC locus. A novel, genetically low VC winter faba bean population was bred. The path is now well-prepared for further marker-based breeding progress.
Impacts of an urban sanitation intervention on fecal indicators and the prevalence of human fecal contamination in Mozambique
Authors: Holcomb David A. , Knee Jackie , Capone Drew , Sumner Trent , Adriano Zaida , Nalá Rassul , Cumming Oliver , Brown Joe , Stewart Jill R. 
Published: February 2021

ABSTRACTFecal source tracking (FST) may be useful to assess pathways of fecal contamination in domestic environments and to estimate the impacts of water, sanitation, and hygiene (WASH) interventions in low-income settings. We measured two non-specific and two human-associated fecal indicators in water, soil, and surfaces before and after a shared latrine intervention from low-income households in Maputo, Mozambique participating in the Maputo Sanitation (MapSan) trial. Up to a quarter of households were impacted by human fecal contamination, but trends were unaffected by improvements to shared sanitation facilities. The intervention reducedE. coligene concentrations in soil but did not impact culturableE. colior the prevalence of human FST markers in a difference-in-differences analysis. Using a novel Bayesian hierarchical modeling approach to account for human marker diagnostic sensitivity and specificity, we revealed a high amount of uncertainty associated with human FST measurements and intervention effect estimates. The field of microbial source tracking would benefit from adding measures of diagnostic accuracy to better interpret findings, particularly when FST analyses convey insufficient information for robust inference. With improved measures, FST could help identify dominant pathways of human and animal fecal contamination in communities and guide implementation of effective interventions to safeguard health.SYNOPSISAn urban sanitation intervention had minimal and highly uncertain effects on human fecal contamination after accounting for fecal indicator sensitivity and specificity.TOC GRAPHIC/ABSTRACT ART
Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception
Authors: Yang Shu , Zhang Ya , Yang Chuxuan , Wu Xuefeng , El Oud Sarah Maria , Chen Rongfang , Cai Xudong , Wu Xufeng S. , Lan Ganhui , Zheng Xiaoyan 
Published: February 2021

ABSTRACTHedgehog (Hh) signaling patterns embryonic tissues and contributes to homeostasis in adults. InDrosophila, Hh transport and signaling are thought to occur along a specialized class of actin-rich filopodia, termed cytonemes. Here, we report that Interference hedgehog (Ihog) not only forms a Hh receptor complex with Patched to mediate intracellular signaling, but Ihog also engages intrans-homophilic binding leading to cytoneme stabilization in a manner independent of its role as the Hh receptor. Both functions of Ihog (trans-homophilic binding for cytoneme stabilization and Hh binding for ligand sensing) involve a region of the first fibronectin repeat of the extracellular domain. Thus, the Ihog-Ihog interaction and the Hh-Ihog interaction cannot occur simultaneously for a single Ihog molecule. By combining experimental data and mathematical modeling, we determined that Hh-Ihog heterophilic interaction dominates and Hh can disrupt and displace Ihog molecules involved intrans-homophilic binding. Consequently, we proposed that the weaker Ihog-Ihogtransinteraction promotes and stabilizes direct membrane contacts along cytonemes and that, as the cytoneme encounters secreted Hh ligands, the ligands trigger release of Ihog fromtransIhog-Ihog complex enabling transport or internalization of the Hh ligand-Ihog-Patched -receptor complex. Thus, the seemingly incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate to assist Hh transport and reception along the cytonemes.One-sentence summaryApparently incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate in Hh transport and reception.
No evidence for short-term evolutionary response to a warming environment in Drosophila
Authors: Santos Marta A. , Carromeu-Santos Ana , Quina Ana S. , Santos Mauro , Matos Margarida , Simões Pedro 
Published: February 2021

AbstractAdaptive evolution is key in mediating responses to climate change. Such evolution will expectedly lead to changes in the populations’ thermal reaction norm and improve their ability to cope with stressful conditions. Conversely, constraints of different nature might limit the adaptive response. Here, we test these expectations by performing a real-time evolution experiment in historically differentiatedDrosophila subobscurapopulations. We address the phenotypic changes of flies evolving for nine generations in a daily fluctuating environment with average constant temperature, or a warming environment with increasing average and amplitude temperature across generations. Our results showed that (1) evolution under a global warming scenario has not led, so far, to a noticeable change in the thermal response; (2) historical background appears to be affecting the responses of populations under the warming environment, particularly at higher temperatures; (3) thermal reaction norms are trait-dependent: while lifelong exposure to low temperature decreases fecundity and productivity but not viability, high temperature causes negative transgenerational effects on productivity and viability, even though fecundity remains high. These findings raise concerns about the short-term efficiency of adaptive responses to the current changing climate.
Molecular basis for Ras suppressor-1 recruitment to focal adhesions and stabilization of consensus adhesome complex
Authors: Fukuda Koichi , Lu Fan , Qin Jun 
Published: February 2021

AbstractRas suppressor-1 (Rsu-1) is a leucine-rich repeat (LRR)-containing protein that is crucial for regulating fundamental cell adhesion processes and tumor development. Rsu-1 interacts with a zinc-finger type multi LIM domain-containing adaptor protein PINCH-1 involved in the integrin-mediated consensus adhesome but not with highly homologous isoform PINCH-2. However, the structural basis for such specific interaction and regulatory mechanism remains unclear. Here, we determined the crystal structures of Rsu-1 and its complex with the PINCH-1 LIM4-5 domains. Rsu-1 displays an arc-shaped solenoid architecture with eight LRRs shielded by the N- and C-terminal capping modules. We show that a large conserved concave surface of the Rsu-1 LRR domain recognizes the PINCH-1 LIM5 domain, and that the C-terminal non-LIM region of PINCH-2 but not PINCH-1 sterically disfavors the Rsu-1 binding. We further show that Rsu-1 can be assembled, via PINCH-1-binding, into a tight hetero-pentamer complex comprising Rsu-1, PINCH-1, ILK, Parvin, and Kindlin-2 that constitute a major consensus integrin adhesome crucial for focal adhesion assembly. Consistently, our mutagenesis and cell biological data consolidate the significance of the Rsu-1/PINCH-1 interaction in focal adhesion assembly and cell spreading. Our results provide a crucial molecular insight into Rsu-1-mediated cell adhesion with implication on how it may regulate tumorigenic growth.
Vesicular stomatitis virus chimeras expressing the Oropouche virus glycoproteins elicit protective immune responses in mice
Authors: Stubbs Sarah Hulsey , Pontelli Marjorie Cornejo , Mishra Nischay , Zhou Changhong , de Paula Souza Juliano , Mendes Viana Rosa Maria , Lipkin W. Ian , Knipe David M. , Arruda Eurico , Whelan Sean P. J. 
Published: February 2021

AbstractOropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections. Like other members of the family Peribunyaviridae, the viral genome exists as 3 single-stranded negative-sense RNA segments. The medium sized segment encodes a viral glycoprotein complex (GPC) that is proteolytically processed into two viral envelope proteins Gn and Gc responsible for attachment and membrane fusion. There are no therapeutics or vaccines to combat OROV infection, and we have little understanding of protective immunity to infection. Here we generated a replication competent chimeric vesicular stomatitis virus (VSV), in which the endogenous glycoprotein was replaced by the GPC of OROV. Serum from mice immunized with VSV-OROV specifically neutralized wild type OROV, and using peptide arrays we mapped multiple epitopes within an N-terminal variable region of Gc recognized by the immune sera. VSV-OROV lacking this variable region of Gc was also immunogenic in mice producing neutralizing sera that recognize additional regions of Gc. Challenge of both sets of immunized mice with wild type OROV shows that the VSV-OROV chimeras reduce wild type viral infection and suggest that antibodies that recognize the variable N-terminus of Gc afford less protection than those that target more conserved regions of Gc.ImportanceOropouche virus (OROV), an orthobunyavirus found in Central and South America, is an emerging public health challenge that causes debilitating febrile illness. OROV is transmitted by arthropods, and increasing mobilization has the potential to significantly increase the spread of OROV globally. Despite this, no therapeutics or vaccines have been developed to combat infection. Using vesicular stomatitis (VSV) as a backbone, we developed a chimeric virus bearing the OROV glycoproteins (VSV-OROV) and tested its ability to elicit a neutralizing antibody response. Our results demonstrate that VSV-OROV produces a strong neutralizing antibody response that is at least partially targeted to the N-terminal region of Gc. Importantly, vaccination with VSV-OROV reduces viral loads in mice challenged with wildtype virus. This data provides the first evidence that targeting the OROV glycoproteins may be an effective vaccination strategy to combat OROV infection.
Four large indels detected by cpTILLING in barley chloroplast mutator seedlings
Authors: Lencina F. , Landau A.M. , Pacheco M.G. , Kobayashi K. , Prina A.R. 
Published: February 2021

AbstractIn a previous work, a polymorphism detection strategy based on mismatch digestion was applied to the chloroplast genome of barley seedlings that carried the chloroplast mutator (cpm) genotype through many generations. Sixty-two different one- or two-nucleotide-polymorphisms were detected along with four large indels: an insertion of 15 bp in the intergenic region between tRNAHis and rps19 genes, a deletion of 620 bp in the psbA gene, a deletion of 79 bp in the intergenic region between rpl33 and rps18 genes and a deletion of 45 bp in the rps3 gene. In the present investigation, we analyzed direct repeats located at the borders of those four large indels. Furthermore, we investigated the consequences of protein expression of large indels located in coding regions. The deletion of 620 bp in the psbA gene was lethal at the second leaf stage when homoplastomic. The deletion of 45 bp in the rps3 gene, which eliminates 15 amino acids, did not affect the viability of the seedlings in homoplastomy. Interestingly, the deleted segment is also lacking in the wild type version of the rps3 gene of maize and sorghum. The presence of direct repeats at the borders of the four large indels suggests that they could have originated by illegitimate recombination. This would be in agreement with a previous hypothesis that the Cpm gene product would correspond to a mismatch repair (MMR) protein devoted to maintain plastome stability by playing fundamental roles in mismatch repair during replication and avoiding illegitimate recombination.
The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors
Authors: Baranovic Jelena , Braunbeck Sebastian , Zaki Nikolai , Minniberger Sonja , Chebli Miriam , Plested Andrew J.R. 
Published: February 2021

SummaryConotoxins are a large group of naturally occurring toxic peptides produced by the predatory sea snails of the genus Conus. Many of these toxins target ion channels, often with high specificity and affinity. As such, they have proven to be invaluable for basic research as well as acting as leads for therapeutic strategies. Con-ikot-ikot is the only conotoxin so far identified that targets AMPA-type glutamate receptors, the main mediators of excitatory neurotransmission in the vertebrate brain. Here, we describe how the toxin modifies the activity of AMPA receptors at the single-channel level. The toxin binds to the AMPA receptor with high affinity (EC50 = 5 nM) and once bound, takes minutes to wash out. As shown previously, it effectively blocks desensitization of AMPA receptors, however, compared to other desensitisation blockers, it is a poor stabiliser of the open channel because toxin-bound AMPA receptors undergo frequent, brief closures. We propose this is a direct consequence of the toxin’s unique binding mode to the ligand binding domains. Unlike other blockers of desensitization, which stabilise individual dimers within an AMPA receptor tetramer, the toxin immobilizes all four ligand binding domains of the tetramer. This result further emphasises that quaternary reorganization of independent LBD dimers is essential for the full activity of AMPA receptors.
Designing efficient genetic code expansion in Bacillus subtilis to gain biological insights
Authors: Stork Devon A. , Squyres Georgia R. , Kuru Erkin , Gromek Katarzyna A. , Rittichier Jonathan , Jog Aditya , Burton Briana M. , Church George M. , Garner Ethan C. , Kunjapur Aditya M. 
Published: February 2021

AbstractBacillus subtilis is a model Gram-positive bacterium, commonly used to explore questions across bacterial cell biology and for industrial uses. To enable greater understanding and control of proteins in B. subtilis, we demonstrate broad and efficient genetic code expansion in B. subtilis by incorporating 20 distinct non-standard amino acids within proteins using 3 different families of genetic code expansion systems and two choices of codons. We use these systems to achieve click-labelling, photo-crosslinking, and translational titration. These tools allow us to demonstrate differences between E. coli and B. subtilis stop codon suppression, validate a predicted protein-protein binding interface, and begin to interrogate properties underlying bacterial cytokinesis by precisely modulating cell division dynamics in vivo. We expect that the establishment of this simple and easily accessible chemical biology system in B. subtilis will help uncover an abundance of biological insights and aid genetic code expansion in other organisms.
Interacting brains revisited: A cross-brain network neuroscience perspective
Authors: Gerloff C. , Konrad K. , Bzdok D. , Büsing C. , Reindl V. 
Published: February 2021

AbstractElucidating the neural basis of social behavior is a long-standing challenge in neuroscience. Such endeavors are driven by attempts to extend the isolated perspective on the human brain by considering interacting persons’ brain activities, but a theoretical and computational framework for this purpose is still in its infancy. Here, we posit a comprehensive framework based on bipartite graphs for interbrain networks and address whether they provide meaningful insights into the neural underpinnings of social interactions. First, we show that the nodal density of such graphs exhibits nonrandom properties. While the current analyses mostly rely on global metrics, we encode the regions’ roles via matrix decomposition to obtain an interpretable network representation yielding both global and local insights. With Bayesian modeling, we reveal how synchrony patterns seeded in specific brain regions contribute to global effects. Beyond inferential inquiries, we demonstrate that graph representations can be used to predict individual social characteristics, outperforming functional connectivity estimators for this purpose. In the future, this may provide a means of characterizing individual variations in social behavior or identifying biomarkers for social interaction and disorders.