bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of peptide-protein relationships in protein ambiguity groups via bipartite graphs
Authors: Schork Karin , Turewicz Michael , Uszkoreit Julian , Rahnenführer Jörg , Eisenacher Martin 
Published: July 2021

AbstractIn bottom-up proteomics, proteins are enzymatically digested into peptides before measurement with mass spectrometry. The relationship between proteins and their corresponding peptides can be represented by bipartite graphs. We conduct a comprehensive analysis of bipartite graphs using quantified peptides from measured data sets as well as theoretical peptides from an in silico digestion of the corresponding complete taxonomic protein sequence databases. The aim of this study is to characterize and structure the different types of graphs that occur and to compare them between data sets. We observed a large influence of the accepted minimum peptide length during in silico digestion. When changing from theoretical peptides to measured ones, the graph structures are subject to two opposite effects. On the one hand, the graphs based on measured peptides are on average smaller and less complex compared to graphs using theoretical peptides. On the other hand, the proportion of protein nodes without unique peptides, which are a complicated case for protein inference and quantification, is considerably larger for measured data. Additionally, the proportion of graphs containing at least one protein node without unique peptides rises when going from database to quantitative level. The fraction of shared peptides and proteins without unique peptides as well as the complexity and size of the graphs highly depends on the data set and organism. Large differences between the structures of bipartite peptide-protein graphs have been observed between database and quantitative level as well as between analyzed species. In the analyzed measured data sets, the proportion of protein nodes without unique peptides ranged from 6.4% to 55.0%. This highlights the need for novel methods that can quantify proteins without unique peptides. The knowledge about the structure of the bipartite peptide-protein graphs gained in this study will be useful for the development of such algorithms.
Cell-specific Bioorthogonal Tagging of Glycoproteins
Authors: Cioce Anna , Calle Beatriz , Rizou Tatiana , Lowery Sarah C. , Bridgeman Victoria , Mahoney Keira E. , Marchesi Andrea , Bineva-Todd Ganka , Flynn Helen , Li Zhen , Tastan Omur Y. , Roustan Chloe , Soro-Barrio Pablo , Wood Thomas M. , Keenan Tessa , Both Peter , Huang Kun , Parmeggiani Fabio , Snijders Ambrosius P. , Skehel Mark , Kjaer Svend , Fascione Martin A. , Bertozzi Carolyn R. , Flitsch Sabine , Malaker Stacy A. , Malanchi Ilaria , Schumann Benjamin 
Published: July 2021

ABSTRACTAltered glycosylation is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function.
Cross-species comparison of human and rodent primary reward consumption under budget constraints
Authors: Hu Yue , Nitsch Felix Jan , van Wingerden Marijn , Kalenscher Tobias 
Published: July 2021

AbstractOptimal use of resources is of great importance for survival of all species. Previous studies have shown that rats optimize their allocation of a limited number of operant responses (akin to a finite budget) to trade for food rewards. Here, we propose a novel human cost-benefit decision paradigm translated from an economic task initially developed for rodents, to conduct a cross-species comparison of primary reward consumption under budget constraints. Participants had a limited budget of effortful button-presses to obtain the opportunity to drink milk rewards or watch erotic pictures. Like rodents, they adapted their choice allocation when the price (i.e. fixed-ratio requirement for reward) and the budget changed when purchasing milk rewards. However, this was not the case when purchasing the opportunity to watch erotic pictures: compared to the milk and to the rodent task, participants made more internally inconsistent, hence, irrational choices, despite otherwise identical task structures. We found non-linear changes in arousal as a function of reward selection that might underlie the irrationality in the picture task. Our study shows that the type of reward matters not only for capturing the convergence in human and non-human economic decision-making, but also for understanding the factors behind compromised economic rationality.
Modeling habitat suitability of vulnerable Mollucan Babirusa Babyrousa babyrussa in small island of Buru, Indonesia
Authors: Wibowo Andri 
Published: July 2021

AbstractBabirusa is a mammal belongs to Suidae family. This mammal belongs to Babyrousa genus is known endemic to Indonesia. Recently there are 3 species of Babyrousa, one species is Babyrousa babyrussa, listed as ‘Vulnerable’ on the IUCN Red List of Threatened Species. Babyrousa occurs in Indonesia on Sulawesi island, Togian, Sula islands, and Taliabu, Mangole and Buru islands in the Molucca regions. The Moluccan Babirusa is now restricted to upland forests and mountainous terrain. Then this study aims to assess the suitability of Buru island as habitat for Moluccan Babirusa. The suitability analysis was based on GIS analysis using 4 determinant environmental variables required by B. babyrussa species including NDVI, barren soil, elevation, and river network. The particular location was a Batabual landscape sizing 292.60 km2 located in the east parts of Buru island. Based on NDVI, less vegetation covers were observed in north and east parts of Batabual. In contrast, NDVI values were higher in the central, west, and south indicating that half of the landscape was covered by intact primary forest. Batabual has a hilly landscape surrounded by coastal areas with hilly areas were observed in the south and west. There were 2 river streams in the east parts. The analysis has divided the landscape into several parts based on the habitat suitability levels. About one third of the landscape located in north was considered less and not suitable for Babirusa. Some areas in west were also considered moderate to be inhabited by Babirusa considering a presence of hilly landscape that may limit the vertical distribution of Babirusa. Most suitable habitats were estimated in central parts of the landscape spanning to the south. South parts of the landscape were characterized by high NDVI values and forest covers then these areas were considered as suitable habitats for Babirusa. The size of this suitable habitat was estimated around 188.62 km2 or more than half of the size (64.46%) of Batabual landscape.
The economical lifestyle of CPR bacteria in groundwater allows little preference for environmental drivers
Authors: Chaudhari Narendrakumar M. , Overholt Will A. , Figueroa-Gonzalez Perla Abigail , Taubert Martin , Bornemann Till L. V. , Probst Alexander J. , Hölzer Martin , Marz Manja , Küsel Kirsten 
Published: July 2021

AbstractThe highly diverseCand. Patescibacteria are predicted to have minimal biosynthetic and metabolic pathways, which hinders understanding of how their populations differentiate to environmental drivers or host organisms. Their metabolic traits to cope with oxidative stress are largely unknown. Here, we utilized genome-resolved metagenomics to investigate the adaptive genome repertoire of Patescibacteria in oxic and anoxic groundwaters, and to infer putative host ranges.Within six groundwater wells,Cand. Patescibacteria was the most dominant (up to 79%) super-phylum across 32 metagenomes obtained from sequential 0.2 and 0.1 µm filtration. Of the reconstructed 1275 metagenome-assembled genomes (MAGs), 291 high-quality MAGs were classified asCand. Patescibacteria.Cand. Paceibacteria andCand. Microgenomates were enriched exclusively in the 0.1 µm fractions, whereas candidate division ABY1 andCand. Gracilibacteria were enriched in the 0.2 µm fractions. Patescibacteria enriched in the smaller 0.1 µm filter fractions had 22% smaller genomes, 13.4% lower replication measures, higher fraction of rod-shape determining proteins, and genomic features suggesting type IV pili mediated cell-cell attachments. Near-surface wells harbored Patescibacteria with higher replication rates than anoxic downstream wells characterized by longer water residence time. Except prevalence of superoxide dismutase genes in Patescibacteria MAGs enriched in oxic groundwaters (83%), no major metabolic or phylogenetic differences were observed based on oxygen concentrations. The most abundant Patescibacteria MAG in oxic groundwater encoded a nitrate transporter, nitrite reductase, and F-type ATPase, suggesting an alternative energy conservation mechanism. Patescibacteria consistently co-occurred with one another or with members of phyla Nanoarchaeota, Bacteroidota, Nitrospirota, and Omnitrophota. However, only 8% of MAGs showed highly significant one-to-one association, mostly with Omnitrophota. Genes coding for motility and transport functions in certain Patescibacteria were highly similar to genes from other phyla (Omnitrophota, Proteobacteria and Nanoarchaeota).Other than genes to cope with oxidative stress, we found little genomic evidence for niche adaptation of Patescibacteria to oxic or anoxic groundwaters. Given that we could detect specific host preference only for a few MAGs, we propose that the majority of Patescibacteria can attach to multiple hosts just long enough to loot or exchange supplies with an economic lifestyle of little preference for geochemical conditions.
An atlas of healthy and injured cell states and niches in the human kidney
Authors: Lake Blue B. , Menon Rajasree , Winfree Seth , Hu Qiwen , Ferreira Ricardo Melo , Kalhor Kian , Barwinska Daria , Otto Edgar A. , Ferkowicz Michael , Diep Dinh , Plongthongkum Nongluk , Knoten Amanda , Urata Sarah , Naik Abhijit S. , Eddy Sean , Zhang Bo , Wu Yan , Salamon Diane , Williams James C. , Wang Xin , Balderrama Karol S. , Hoover Paul , Murray Evan , Vijayan Anitha , Chen Fei , Waikar Sushrut S. , Rosas Sylvia , Wilson Francis P. , Palevsky Paul M. , Kiryluk Krzysztof , Sedor John R. , Toto Robert D. , Parikh Chirag , Kim Eric H. , Macosko Evan Z. , Kharchenko Peter V. , Gaut Joseph P. , Hodgin Jeffrey B. , Eadon Michael T. , Dagher Pierre C. , El-Achkar Tarek M. , Zhang Kun , Kretzler Matthias , Jain Sanjay ,   for the KPMP consortium
Published: July 2021

AbstractUnderstanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of ∼1.2 million neighborhoods provided linkages to active immune responses. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.
PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade
Authors: Srour Nivine , Villarreal Oscar D. , Yu Zhenbao , Preston Samuel , Miller Wilson H. , Szewczyk Magdelena M. , Barsyte-Lovejoy Dalia , Xu Han , del Rincón Sonia V. , Richard Stéphane 
Published: July 2021

AbstractDespite the success of immune checkpoint inhibitor (ICI) therapy in different cancers, resistance and relapses are frequent. Thus, combination therapies are expected to enhance response rates and overcome resistance to ICIs. Herein, we report that combining protein arginine methyltransferase 7 (PRMT7) inhibition with ICIs triggers a strong anti-tumor T cell immunity and restrains tumor growth in vivo by increasing tumor immune cell infiltration. Consistently, TCGA database analysis showed an inverse correlation between PRMT7 expression and T cell infiltration in human melanomas. Mechanistically, we show that PRMT7 has a two-prong effect on melanoma tumor immunity. On one hand, it serves as a coactivator of IRF-1 for PD-L1 expression by upregulating promoter H4R3me2s levels in melanoma cells. Next, PRMT7 prevents repetitive element expression to avoid intracellular dsRNA accumulation or ‘viral mimicry’. PRMT7 deletion resulted in increased endogenous retroviral elements (ERVs), dsRNA, and genes implicated in interferon activation, antigen presentation and chemokine signaling. Our findings identify PRMT7 as factor used by melanoma to evade anti-tumor immunity and define the therapeutic potential of PRMT7 alone or in combination with PD-(L)1 blockade to enhance ICI efficiency.
Phage co-transport with hyphal-riding bacteria fuels bacterial invasion in water-unsaturated microbial ecosystems
Authors: You Xin , Kallies René , Kühn Ingolf , Schmidt Matthias , Harms Hauke , Chatzinotas Antonis , Wick Lukas Y. 
Published: July 2021

AbstractNon-motile microbes enter new habitats often by co-transport with motile microorganisms. Here, we report on the ability of hyphal-riding bacteria to co-transport lytic phages and utilize them as ‘weapons’ during colonization of new water-unsaturated habitats. This is comparable to the concept of biological invasions in macroecology. In analogy to invasion frameworks in plant and animal ecology, we tailored spatially organized, water-unsaturated model microcosms using hyphae of Pythium ultimum as invasion paths and flagellated soil-bacterium Pseudomonas putida KT2440 as carrier for co-transport of Escherichia virus T4. P. putida KT2440 efficiently dispersed along P. ultimum to new habitats and dispatched T4 phages across air gaps transporting ≈ 0.6 phages bacteria−1. No T4 displacement along hyphae was observed in the absence of carrier bacteria. If E. coli occupied the new habitat, T4 co-transport fueled the fitness of invading P. putida KT2440, while the absence of phage co-transport led to poor colonization followed by extinction. Our data emphasize the importance of hyphal transport of bacteria and associated phages in regulating fitness and composition of microbial populations in water-unsaturated systems. As such co-transport mirrors macroecological invasion processes, we recommend hyphosphere systems with motile bacteria and co-transported phages as models for testing hypotheses in invasion ecology.
Identification of cells expressing Calcitonins A and B, PDF and ACP in Locusta migratoria using cross-reacting antisera and in situ hybridization
Authors: Veenstra Jan A. 
Published: July 2021

AbstractThis work was initiated because an old publication suggested that electrocoagulation of four paraldehyde fuchsin positive cells in the brain of Locusta migratoria might produce a diuretic hormone, the identity of which remains unknown, since none of the antisera to the various putative Locusta diuretic hormones recognizes these cells. The paraldehyde fuchsin positive staining suggests a peptide with a disulfide bridge and the recently identified Locusta calcitonins have both a disulfide bridge and are structurally similar to calcitonin-like diuretic hormone.In situ hybridization and antisera raised to calcitonin-A and -B were used to show were these peptides are expressed in Locusta. Calcitonin-A is produced by neurons and neuroendocrine cells that were previously shown to be immunoreactive to an antiserum to pigment dispersing factor (PDF). The apparent PDF-immunoreactivity in these neurons and neuroendocrine cells is due to crossreactivity with the calcitonin-A precursor. As confirmed by both an PDF-precursor specific antiserum and in situ hybridisation, those calcitonin-A expressing cells do not express PDF.Calcitonin B is expressed by numerous enteroendocrine cells in the midgut as well as the midgut caeca. A guinea pig antiserum to calcitonin A seemed quite specific as it recognized only the calcitonin A expressing cells. However, rabbit antisera to calcitonin-A and-B both crossreacted with neuroendocrine cells in the brain that produce ACP, this is almost certainly due to the common C-terminal dipeptide SPamide that is shared between Locusta calcitonin-A, calcitonin-B and ACP.
Evolutionary dynamics of asexual hypermutators adapting to a novel environment
Authors: Ho Wei-Chin , Behringer Megan G. , Miller Samuel F. , Gonzales Jadon , Nguyen Amber , Allahwerdy Meriem , Boyer Gwyneth F. , Lynch Michael 
Published: July 2021

AbstractHow microbes adapt to a novel environment is a central question in evolutionary biology. While adaptive evolution must be fueled by beneficial mutations, whether higher mutation rates facilitate the rate of adaptive evolution remains unclear. To address this question, we culturedEscherichia colihypermutating populations, in which a defective methyl-directed mismatch repair pathway causes a 140-fold increase in single-nucleotide mutation rates. In parallel with wild-typeE. coli, populations were cultured in tubes containing Luria-Bertani broth, a complex medium known to promote the evolution of subpopulation structure. After 900 days of evolution, in three transfer schemes with different population-size bottlenecks, hypermutators always exhibited similar levels of improved fitness as controls. Fluctuation tests revealed that the mutation rates of hypermutator lines converged evolutionarily on those of wild-type populations, which may have contributed to the absence of fitness differences. Further genome-sequence analysis revealed that, although hypermutator populations have higher rates of genomic evolution, this largely reflects the effects of genetic draft under strong linkage. Despite these linkage effects, the evolved populations exhibit parallelism in fixed mutations, including those potentially related to biofilm formation, transcription regulation, and mutation-rate evolution. Together, these results generally negate the presumed relationship between high mutation rates and high adaptive speed of evolution, providing insight into how clonal adaptation occurs in novel environments.Significance statementWhile mutations are critical source for the adaptation in a new environment, whether or not the elevated mutation rates can empirically lead to the elevated adaptation rates remains unclear, especially when the environment is more heterogenous. To answer this question, we evolvedE. colipopulations with different starting mutation rates in a complex medium for 900 days and then examined their fitness and genome profiles. In the populations that have a higher starting mutation rate, despite faster genome evolution, their fitness improvement is not significantly faster. Our results reveal that the effect of elevated mutation rates is only very limited, and the mutations accumulated in hypermutators are largely due to linkage effect.
Structural basis for recognition of two HLA-A2-restricted SARS-CoV-2 spike epitopes by public and private T cell receptors
Authors: Wu Daichao , Kolesnikov Alexander , Yin Rui , Guest Johnathan D. , Gowthaman Ragul , Shmelev Anton , Serdyuk Yana , Efimov Grigory A. , Pierce Brian G. , Mariuzza Roy A. 
Published: July 2021

AbstractT cells play a vital role in combatting SARS-CoV-2 and in forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T cell receptors (TCRs) bound to their peptide–MHC targets is lacking. We determined structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures revealed the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of both TCRs to recognize natural variants of YLQ and RLQ but not homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.
The timescale and magnitude of 1/f aperiodic activity decrease with cortical depth in humans, macaques, and mice
Authors: Halgren Mila , Kang Raphi , Voytek Bradley , Ulbert Istvan , Fabo Daniel , Eross Lorand , Wittner Lucia , Madsen Joseph , Doyle Werner K , Devinsky Orrin , Halgren Eric , Harnett Mark T. , Cash Sydney S. 
Published: July 2021

AbstractCortical dynamics obey a 1/f power law, exhibiting an exponential decay of spectral power with increasing frequency. The slope and offset of this 1/f decay reflect the timescale and magnitude of aperiodic neural activity, respectively. These properties are tightly linked to cellular and circuit mechanisms (e.g. excitation:inhibition balance and firing rates) as well as cognitive processes (e.g. perception, memory, and state). However, the physiology underlying the 1/f power law in cortical dynamics is not well understood. Here, we compared laminar recordings from human, macaque and mouse cortex to evaluate how 1/f aperiodic dynamics vary across cortical layers and species. We report that 1/f slope is steepest in superficial layers and flattest in deep layers in each species. Additionally, the magnitude of this 1/f decay is greatest in superficial cortex and decreases with depth. We could account for both of these findings with a simple model in which superficial cortical transmembrane currents had longer time constants and greater densities than those in deeper layers. Together, our results provide novel insight into the organization of cortical dynamics, suggesting that the amplitude and time constant of local currents control circuit processing as a function of laminar depth. This may represent a general mechanism to facilitate appropriate integration of fast sensory inputs (infragranular) with slow feedback-type inputs (supragranular) across cortical areas and species.