bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubule Lattice Spacing Governs Cohesive Envelope Formation of Tau Family Proteins
Authors: Siahaan Valerie , Tan Ruensern , Humhalova Tereza , Libusova Lenka , Lacey Samuel E. , Tan Tracy , Dacy Mariah , Ori-McKenney Kassandra M. , McKenney Richard J. , Braun Marcus , Lansky Zdenek 
Published: November 2021

AbstractTau is an intrinsically-disordered microtubule-associated protein (MAP) implicated in neurodegenerative disease. On microtubules, tau molecules segregate into two kinetically distinct phases, consisting of either independently diffusing molecules or interacting molecules that form cohesive “envelopes” around microtubules. Envelopes differentially regulate lattice accessibility for other MAPs, but the mechanism of envelope formation remains unclear. Here, we find that tau envelopes form cooperatively, locally altering the spacing of tubulin dimers within the microtubule lattice. Envelope formation compacted the underlying lattice, whereas lattice extension induced tau-envelope disassembly. Investigating other members of the tau-MAP family, we find MAP2 similarly forms envelopes governed by lattice-spacing, whereas MAP4 cannot. Envelopes differentially biased motor protein movement, suggesting that tau family members could spatially divide the microtubule surface into functionally distinct segments. We conclude that the interdependent allostery between lattice-spacing and cooperative envelope formation provides the molecular basis for spatial regulation of microtubule-based processes by tau and MAP2.
The evolutionary dynamics of genetic mutational load throughout tomato domestication history
Authors: Razifard Hamid , Visa Sofia , Tieman Denise , van der Knaap Esther , Caicedo Ana L. 
Published: November 2021

AbstractUnderstanding the evolution of deleterious mutations through domestication has fascinated evolutionary biologists and breeders alike. Some domesticated organisms have been reported to accumulate deleterious mutations, i.e. radical amino acid changes, through their domestication history (“cost of domestication”). However, more recent evidence paints a more complex picture of this phenomenon in different domesticated organisms. In this study, we used genomic sequences of 253 tomato accessions to investigate the evolution of deleterious mutations and genomic structural variants (SVs) through tomato domestication history. Specifically, we used phylogeny-based methods to identify deleterious mutations in the cultivated tomato as well as its closely related semi-wild and wild populations. We also explored a potential correlation between deleterious mutations and SVs. To create a functional link between deleterious alleles and phenotypes of interest for tomato breeding, we also conducted Genome-wide Association Studies (GWAS) on several fruit volatiles.Our results implicate a downward trend, throughout tomato domestication history, in diversity of most alleles, regardless of their functional impact. This suggests that demographic factors, such as bottleneck events and inbreeding, have reduced overall genetic diversity, leading to lower deleterious load and SVs as well as loss of some beneficial alleles during tomato domestication. We also detected an increase in proportions of nonsynonymous and deleterious alleles (relative to synonymous and neutral nonsynonymous alleles, respectively) during the initial stage of tomato domestication in Ecuador, although the final stage of tomato domestication in Mexico did not seem to involve such an increase. However, deleterious alleles in cultivated tomato seem to be more frequent than expected by neutral theory of molecular evolution. Additionally, for all tomato populations, we found a higher proportion of deleterious mutations in genomic regions impacted by SVs.Our analyses also revealed frequent deleterious alleles in several well-studied tomato genes, probably involved in response to biotic and abiotic stress as well as fruit development and flavor regulation. Also, through genome-wide association studies (GWAS), we discovered deleterious alleles associated with two volatiles: isobutyl acetate, which is important for tomato fruit flavor, and methyl salicylate, involved in disease resistance and regulating flowering time. To provide a practical guide for breeding experiments, we created TomDel, a public searchable database of 21,162 deleterious alleles identified in this study (https://github.com/hrazif/TomDel-0.1)
Competitive asymmetry confers polyploid advantage under environmental stress
Authors: Guo Wen , Wei Na , Hao Guang-You , Yang Shi-Jian , Zhu Zhi-Yong , Yang Yong-Ping , Duan Yuan-Wen 
Published: November 2021

AbstractCompetitive asymmetry across heterogeneous environments is crucial for the success of polyploid plants, however, little is known about it. As the major force in plant evolution, polyploids are predicted to maintain the competitive dominance relative to diploids under increased stress conditions.To evaluate the hypothesis of competitive asymmetry, we competed tetraploid and diploid plants of perennial herbaceous Chrysanthemum indicum L. (Asteraceae) at different relative frequencies under low and high water stress. We quantified the interaction intensity between competing plants of the same (intraploidy) and different ploidy levels (interploidy), and measured functional traits related to gas exchange and plant water use to understand the underlying mechanisms.Stronger competitive effects of the tetraploid on diploid provided evidence for the competitive asymmetry between polyploid and diploid plants in C. indicum. Such competitive asymmetry was not only maintained under drought (increased water stress), but also translated into higher fitness of the tetraploid consistently across water stress conditions. Functional traits associated with fast growth and efficient water use likely explained the competitive dominance of the tetraploid.These results will advance our understanding of species interactions between polyploid and diploid plants, and provide insights into population dynamics and species distribution under environmental change.
Temporally robust occupancy frequency distributions in riverine metacommunities explained by local biodiversity regulation
Authors: O’Sullivan Jacob D. , Terry J. Christopher D. , Rossberg Axel G. 
Published: November 2021

AbstractThe mechanisms determining the distribution of the number of sites species occupy—the occupancy frequency distribution (OFD)—remain incompletely understood despite decades of research. Here we study OFD in fresh-water metacommunities in England. We show that OFD are largely time invariant despite continuous turnover in community composition and well described by log-series distributions. Both shape and temporal robustness are readily explained by a simple patch occupancy model with intrinsic regulation of local richness. The model is mathematically analogous to classical neutral theory, but concerns numbers of patches occupied instead of individuals present. The precise shape of the model’s log-series OFD is determined by a parameter representing the rate of colonisation from adjacent sites, which we estimate for the data. Our results support the view that meta-community structure reflects a dynamic steady state controlled by local ecological constraints. Interspecific trait differences underlie these constraints, but are unlikely to determine macroecological structure.
Distinct replay signatures for prospective decision-making and memory preservation
Authors: Wimmer G. Elliott , Liu Yunzhe , McNamee Daniel C. , Dolan Raymond J. 
Published: November 2021

AbstractTheories of neural replay propose that it supports a range of functions, most prominently planning and memory consolidation. Here, we test the hypothesis that distinct signatures of replay in the same task are related to model-based decisionmaking (‘planning’) and memory preservation. We designed a reward learning task wherein participants utilized structure knowledge for model-based evaluation, while at the same time had to maintain knowledge of two independent and randomly alternating task environments. Using magnetoencephalography (MEG) and multivariate analysis, we first identified temporally compressed sequential reactivation, or replay, both prior to choice and following reward feedback. Before choice, prospective replay strength was enhanced for the current task-relevant environment when a model-based planning strategy was beneficial. Following reward receipt, and consistent with a memory preservation role, replay for the alternative distal task environment was enhanced as a function of decreasing recency of experience with that environment. Critically, these planning and memory preservation relationships were selective to pre-choice and post-feedback periods. Our results provide new support for key theoretical proposals regarding the functional role of replay and demonstrate that the relative strength of planning and memory-related signals are modulated by on-going computational and task demands.Significance statementThe sequential neural reactivation of prior experience, known as replay, is considered to be an important mechanism for both future planning and preserving memories of the past. Whether, and how, replay supports both of these functions remains unknown. Here, in humans, we found that prior to a choice, rapid replay of potential future paths was enhanced when planning was more beneficial. By contrast, after choice feedback, when no future actions are imminent, we found evidence for a memory preservation signal evident in enhanced replay of paths that had been visited less in the recent past. The results demonstrate that distinct replay signatures, expressed at different times, relate to two dissociable cognitive functions.
Longitudinal immune cell profiling in early systemic lupus erythematosus
Authors: Sasaki Takanori , Bracero Sabrina , Keegan Joshua , Chen Lin , Cao Ye , Stevens Emma , Qu Yujie , Wang Guoxing , Nguyen Jennifer , Alves Stephen E. , Lederer James A. , Costenbader Karen H. , Rao Deepak A. 
Published: November 2021

AbstractObjectiveTo investigate the immune cell profiling and their longitudinal changes in systemic lupus erythematosus (SLE).MethodsWe employed mass cytometry with three different 38-39 marker panels (Immunophenotyping, T cell/monocyte, and B cell) in cryopreserved peripheral blood mononuclear cells (PBMCs) from nine patients with early SLE, 15 patients with established SLE, and 14 non-inflammatory controls. We used machine learning-driven clustering, FlowSOM (Flow Self-Organizing Maps) and dimensional reduction with tSNE (t-distributed Stochastic Neighbor Embedding) to identify unique cell populations in early and established SLE. For the nine early SLE patients, longitudinal mass cytometry analysis was applied to PBMCs at three time points (at enrollment, six months post-enrollment, and one year post-enrollment). Serum samples were also assayed for 65 cytokines by Luminex multiplex assay, and associations between cell types and cytokines/chemokines assessed.ResultsT peripheral helper cells (Tph cells), T follicular helper cells (Tfh cells) and several Ki67+proliferating subsets (ICOS+Ki67+CD8 T cells, Ki67+regulatory T cells, CD19intKi67hiplasmablasts, and Ki67hiPU.1himonocytes) were increased in early SLE. Longitudinal mass cytometry and multiplex serum cytokine assays of samples from early SLE patients revealed that Tfh cells and CXCL10 decreased at one year post-enrollment. CXCL13 correlated positively with several of the expanded cell populations in early SLE.ConclusionsTwo major helper T cell subsets and unique Ki67+proliferating immune cell subsets were expanded in the early phase of SLE, and the immunologic features characteristic of early SLE evolved over time.
Individual differences in frontoparietal plasticity in humans
Authors: Boroshok Austin L. , Park Anne T. , Fotiadis Panagiotis , Velasquez Gerardo H. , Tooley Ursula A. , Simon Katrina R. , Forde Jasmine C.P. , Delgado Reyes Lourdes M. , Tisdall M. Dylan , Bassett Dani S. , Cooper Emily A. , Mackey Allyson P. 
Published: November 2021

AbstractNeuroplasticity, defined as the brain’s potential to change in response to its environment, has been extensively studied at the cellular and molecular levels. Work in animal models suggests that stimulation to the ventral tegmental area (VTA) enhances plasticity, and that myelination constrains plasticity. Little is known, however, about whether proxy measures of these properties in the human brain are associated with learning. Here, we investigated the plasticity of the frontoparietal system by asking whether VTA resting-state functional connectivity and myelin map values (T1w/T2w ratios) predicted learning after short-term training on the adaptive n-back (n = 46, ages 18-25). We found that stronger baseline connectivity between VTA and lateral prefrontal cortex predicted greater improvements in accuracy. Lower myelin map values predicted improvements in response times, but not accuracy. Our findings suggest that proxy markers of neural plasticity can predict learning in humans.
Structure-Activity Relationships in the Design of Mitochondria-Targeted Peptide Therapeutics
Authors: Mitchell Wayne , Tamucci Jeffrey D. , Ng Emery L. , Liu Shaoyi , Szeto Hazel H. , May Eric R. , Alexandrescu Andrei T. , Alder Nathan N. 
Published: November 2021

AbstractMitochondria play a central role in metabolic homeostasis; hence, dysfunction of this organelle underpins the etiology of many heritable and aging-related diseases. Mitochondria-targeted tetrapeptides with alternating cationic and aromatic residues, such as SS-31 (Elamipretide), show promise as therapeutic compounds. In this study, we conducted a quantitative structure-activity analysis of three alternative tetrapeptide analogs that differed with respect to aromatic side chain composition and sequence register, benchmarked against SS-31. Using NMR and molecular dynamics approaches, we obtained the first structural models for this class of compounds, showing that all analogs except for SS-31 form compact reverse turn conformations in the membrane-bound state. All peptide analogs bound cardiolipin-containing membranes, yet they had significant differences in equilibrium binding behavior and membrane interactions. Notably, the analogs had markedly different effects on membrane surface charge, supporting a mechanism in which modulation of membrane electrostatics is a key feature of their mechanism of action. All peptide analogs preserved survival and energy metabolism more effectively than SS-31 in cell stress models. Within our peptide set, the analog containing tryptophan side chains, SPN10, had the strongest impact on most membrane properties and showed greatest efficacy in cell culture studies. Taken together, these results show that side chain composition and register strongly influence the activity of these mitochondria-targeted peptides. Furthermore, this work helps provide a framework for the rational design of next-generation therapeutics with enhanced potency.
Comparison of materials for rapid passive collection of environmental DNA
Authors: Bessey Cindy , Gao Yuan , Truong Yen Bach , Miller Haylea , Jarman Simon Neil , Berry Oliver 
Published: November 2021

AbstractPassive collection is an emerging sampling method for environmental DNA (eDNA) in aquatic systems. Passive eDNA collection is inexpensive, efficient, and requires minimal equipment, making it suited to high density sampling and remote deployment. Here, we compare the effectiveness of nine membrane materials for passively collecting fish eDNA from a 3 million litre marine mesocosm. We submerged materials (cellulose, cellulose with 1% and 3% chitosan, cellulose overlayed with electrospun nanofibers and 1% chitosan, cotton fibres, hemp fibres and sponge with either zeolite or active carbon) for intervals between five and 1080 minutes. We show that for most materials, with as little as five minutes submersion, mitochondrial fish eDNA measured with qPCR, and fish species richness measured with metabarcoding, was comparable to that collected by conventional filtering. Furthermore, PCR template DNA concentrations and species richness were generally not improved significantly by longer submersion. Species richness detected for all materials ranged between 11 to 37 species, with a median of 27, which was comparable to the range for filtered eDNA (19-32). Using scanning electron microscopy, we visualised biological matter adhered to the surface of materials, rather than entrapped, with images also revealing a diversity in size and structure of putative eDNA particles.Environmental DNA can be collected rapidly from seawater with a passive approach and using a variety of materials. This will suit cost and time-sensitive biological surveys, and where access to equipment is limited.
Water column stability as an important factor controlling nitrite-dependent anaerobic methane oxidation in stratified lake basins
Authors: Su Guangyi , Lehmann Moritz F. , Tischer Jana , Weber Yuki , Walser Jean-Claude , Niemann Helge , Zopfi Jakob 
Published: November 2021

AbstractAnaerobic oxidation of methane (AOM) with nitrate/nitrite as the terminal electron acceptor may play an important role in mitigating methane emissions from lacustrine environments to the atmosphere. We investigated AOM in the water column of two connected but hydrodynamically contrasting basins of a south-alpine lake in Switzerland (Lake Lugano). The North Basin is permanently stratified with year-round anoxic conditions below 120 m water depth, while the South Basin undergoes seasonal stratification with the development of bottom water anoxia during summer. We show that below the redoxcline of the North Basin a substantial fraction of methane was oxidized coupled to nitrite reduction by Candidatus Methylomirabilis. Incubation experiments with 14CH4 and concentrated biomass from showed at least 43-52%-enhanced AOM rates with added nitrate/nitrite as electron acceptor. Multiannual time series data on the population dynamics of Candidatus Methylomirabilis in the North Basin following an exceptional mixing event in 2005/2006 revealed their requirement for lasting stable low redox-conditions to establish. In the South Basin, on the other hand, we did not find molecular evidence for nitrite-dependent methane oxidizing bacteria. Our data suggest that here the dynamic mixing regime with fluctuating redox conditions is not conducive to the development of a stable population of relatively slow-growing Candidatus Methylomirabilis, despite a hydrochemical framework that seems more favorable for nitrite-dependent AOM than in the North Basin. We predict that the importance of N-dependent AOM in freshwater lakes will likely increase in future because of longer thermal stratification periods and reduced mixing caused by global warming.
PRMT5 epigenetically regulates the E3 ubiquitin ligase ITCH to influence lipid accumulation during mycobacterial infection
Authors: Borbora Salik Miskat , Rajmani R.S. , Balaji Kithiganahalli Narayanaswamy 
Published: November 2021

AbstractMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), triggers enhanced accumulation of lipids to generate foamy macrophages (FMs). This process has been often attributed to the surge in the expression of lipid influx genes with a concomitant decrease in those involved in lipid efflux genes. Here, we define an Mtb-orchestrated modulation of the ubiquitination mechanism of lipid accumulation markers to enhance lipid accretion during infection. We find that Mtb infection represses the expression of the E3 ubiquitin ligase, ITCH, resulting in the sustenance of key lipid accrual molecules viz. ADRP and CD36, that are otherwise targeted by ITCH for proteasomal degradation. In line, overexpressing ITCH in Mtb-infected cells was found to suppress Mtb-induced lipid accumulation. Molecular analyses including loss-of-function and ChIP assays demonstrated a role for the concerted action of the transcription factor YY1 and the arginine methyl transferase PRMT5 in restricting the expression of Itch gene by conferring repressive symmetrical H4R3me2 marks on its promoter. Consequently, siRNA-mediated depletion of YY1 or PRMT5 rescued ITCH expression, thereby compromising the levels of Mtb-induced ADRP and CD36 and limiting FM formation during infection. Accumulation of lipids within the host has been implicated as a pro-mycobacterial process that aids in pathogen persistence and dormancy. In our study, perturbation of PRMT5 enzyme activity resulted in compromised lipid levels and reduced mycobacterial survival in primary murine macrophages (ex vivo) and in a therapeutic mouse model of TB infection (in vivo). These findings provide new insights on the role of PRMT5 and YY1 in augmenting mycobacterial pathogenesis. Thus, we posit that our observations could help design novel adjunct therapies and combinatorial drug regimen for effective anti-TB strategies.Author SummaryMycobacterium tuberculosis generates lipid-laden cells (foamy macrophages-FMs) that offer a favorable shelter for its persistence. During infection, we observe a significant reduction in the expression of the E3 ubiquitin ligase, ITCH. This repression allows the sustenance of key lipid accretion molecules (ADRP and CD36), by curbing their proteasomal degradation. Further, we show the repression of ITCH to be dependent on the concerted action of the bifunctional transcription factor, YY1 and the arginine methyl transferase, PRMT5. NOTCH signaling pathway was identified as a master-regulator of YY1 expression. In vitro and in vivo analyses revealed the significance of PRMT5 in regulating FM formation and consequently mycobacterial burden.