bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amplicon Sequencing of Single-copy Protein-coding Genes Reveals Accurate Diversity for Sequence-discrete Microbiome Populations
Authors: Yang Chengfeng , Su Qinzhi , Tang Min , Luo Shiqi , Zheng Hao , Zhang Xue , Zhou Xin 
Published: October 2021

ABSTRACTAn in-depth understanding of microbial function and the division of ecological niches requires accurate delineation and identification of microbes at a fine taxonomic resolution. Microbial phylotypes are typically defined using a 97% small subunit (16S) rRNA threshold. However, increasing evidence has demonstrated the ubiquitous presence of taxonomic units of distinct functions within phylotypes. These so-called sequence-discrete populations (SDPs) have used to be mainly delineated by disjunct sequence similarity at the whole-genome level. However, gene markers that could accurately identify and quantify SDPs are lacking in microbial community studies. Here we developed a pipeline to screen single-copy protein-coding genes that could accurately characterize SDP diversity via amplicon sequencing of microbial communities. Fifteen candidate marker genes were evaluated using three criteria (extent of sequence divergence, phylogenetic accuracy, and conservation of primer regions) and the selected genes were subject to test the efficiency in differentiating SDPs within Gilliamella, a core honeybee gut microbial phylotype, as a proof-of-concept. The results showed that the 16S V4 region failed to report accurate SDP diversities due to low taxonomic resolution and changing copy numbers. In contrast, the single-copy genes recommended by our pipeline were able to successfully quantify Gilliamella SDPs for both mock samples and honeybee guts, with results highly consistent with those of metagenomics. The pipeline developed in this study is expected to identify single-copy protein coding genes capable of accurately quantifying diverse bacterial communities at the SDP level.IMPORTANCEMicrobial communities can be distinguished by discrete genetic and ecological characteristics. These sequence-discrete populations are foundational for investigating the composition and functional structures of microbial communities at high resolution. In this study, we screened for reliable single-copy protein-coding marker genes to identify sequence-discrete populations through our pipeline. Using marker gene amplicon sequencing, we could accurately and efficiently delineate the population diversity in microbial communities. These results suggest that single copy protein-coding genes can be an accurate, quantitative and economical alternative for characterizing population diversity. Moreover, the feasibility of a gene as marker for any bacterial population identification can be quickly evaluated by the pipeline proposed here.
Transcriptional regulation of photoprotection in dark-to-light transition - more than just a matter of excess light energy
Authors: Redekop Petra , Sanz-Luque Emanuel , Yuan Yizhong , Villain Gaelle , Petroutsos Dimitris , Grossman Arthur R. 
Published: October 2021

ABSTRACTIn nature, photosynthetic organisms are exposed to different light spectra and intensities depending on the time of day and atmospheric and environmental conditions. When photosynthetic cells absorb excess light, they induce non-photochemical quenching to avoid photo-damage and trigger expression of ‘photoprotective’ genes. In this work, we used the green alga Chlamydomonas reinhardtii to assess the impact of light intensity, light quality, wavelength, photosynthetic electron transport and CO2 on induction of the ‘photoprotective’ genes (LHCSR1, LHCSR3 and PSBS) during dark-to-light transitions. Induction (mRNA accumulation) occurred at very low light intensity, was independently modulated by blue and UV-B radiation through specific photoreceptors, and only LHCSR3 was strongly controlled by CO2 levels through a putative enhancer function of CIA5, a transcription factor that controls genes of the carbon concentrating mechanism. We propose a model that integrates inputs of independent signaling pathways and how they may help the cells anticipate diel conditions and survive in a dynamic light environment.
Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times: A neuroimaging study
Authors: Andrushko Justin W. , Levenstein Jacob M. , Zich Catharina , Edmond Evan C. , Campbell Jon , Clarke William T. , Emir Uzay , Farthing Jonathan P. , Stagg Charlotte J. 
Published: October 2021

AbstractIn humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.Significance StatementEnhanced functional connectivity and decreased inhibition in sensorimotor areas of the brain underpin enhancements in motor performance and learning. In this study we investigated the impact of repeated right handgrip contractions at 50% MVC to improve behaviour, enhance functional connectivity and alter sensorimotor inhibition. We found that after nine minutes of repeated 50% MVC handgrip contractions with the right-hand, left-hand response times were significantly improved. This behavioural improvement was accompanied by altered interhemispheric functional connectivity and neurochemical changes across sensorimotor areas. Repeated unilateral handgrip contractions may be an effective method for enhancing contralateral limb motor performance in rehabilitation settings.
End-to-end learning of multiple sequence alignments with differentiable Smith-Waterman
Authors: Petti Samantha , Bhattacharya Nicholas , Rao Roshan , Dauparas Justas , Thomas Neil , Zhou Juannan , Rush Alexander M. , Koo Peter K. , Ovchinnikov Sergey 
Published: October 2021

AbstractMultiple Sequence Alignments (MSAs) of homologous sequences contain information on structural and functional constraints and their evolutionary histories. Despite their importance for many downstream tasks, such as structure prediction, MSA generation is often treated as a separate pre-processing step, without any guidance from the application it will be used for. Here, we implement a smooth and differentiable version of the Smith-Waterman pairwise alignment algorithm that enables jointly learning an MSA and a downstream machine learning system in an end-to-end fashion. To demonstrate its utility, we introduce SMURF (Smooth Markov Unaligned Random Field), a new method that jointly learns an alignment and the parameters of a Markov Random Field for unsupervised contact prediction. We find that SMURF learns MSAs that mildly improve contact prediction on a diverse set of protein and RNA families. As a proof of concept, we demonstrate that by connecting our differentiable alignment module to AlphaFold and maximizing predicted confidence, we can learn MSAs that improve structure predictions over the initial MSAs. Interestingly, the alignments that improve AlphaFold predictions are self-inconsistent and can be viewed as adversarial. This work highlights the potential of differentiable dynamic programming to improve neural network pipelines that rely on an alignment and the potential dangers of relying on black-box methods for optimizing predictions of protein sequences.
The role of mitochondrial energetics in the origin and diversification of eukaryotes
Authors: Schavemaker Paul E. , Muñoz-Gómez Sergio A. 
Published: October 2021

AbstractThe origin of eukaryotic cell size and complexity is thought by some to have required an energy excess provided by mitochondria, whereas others claim that mitochondria provide no energetic boost to eukaryotes. Recent observations show that energy demand scales continuously and linearly with cell volume across both prokaryotes and eukaryotes, and thus suggest that eukaryotes do not have an increased energetic capacity over prokaryotes. However, amounts of respiratory membranes and ATP synthases scale super-linearly with cell surface area. Furthermore, the energetic consequences of the contrasting genomic architectures between prokaryotes and eukaryotes have yet to be precisely quantified. Here, we investigated (1) potential factors that affect the cell volumes at which prokaryotes become surface area-constrained, (2) the amount of energy that is divested to increasing amounts of DNA due to the contrasting genomic architectures of prokaryotes and eukaryotes, and (3) the costs and benefits of respiring symbionts for a host cell. Our analyses suggest that prokaryotes are not necessarily constrained by their cell surfaces at cell volumes of 100–103 μm3, and that the genomic architecture of eukaryotes is only slightly advantageous at genomes sizes of 106–107 bp. This suggests that eukaryotes may have first evolved without the need for mitochondria as these ranges hypothetically encompass the Last Eukaryote Common Ancestor and its proto-eukaryotic ancestors. At these slightly larger cell volumes, a host cell may also have derived a greater advantage (lower cost) from harboring a population of ATP-producing symbionts. However, our analyses also show that increasingly larger and fast-dividing prokaryotes would have a shortage of surface area devoted to respiration and would disproportionally divest more energy to DNA synthesis at larger genome sizes. We thus argue that, even though mitochondria may not have been required by the first eukaryotes, the successful diversification of eukaryotes into larger and faster-growing cells was ultimately contingent upon the origin of mitochondria.SignificanceThere has been a lot of theorizing about the evolution of eukaryotes from prokaryotes, but no consensus seems to be on the horizon. Our quantitative analyses on the required amount of respiratory membrane, and the amount of energy diverted to DNA synthesis, by both prokaryotes and eukaryotes, suggest that mitochondria provided rather small advantages to the first eukaryotes, but were advantageous for the macro-evolutionary diversification of eukaryotes. This conclusion provides a middle road in the debate between those that claim that the origin of eukaryotes required a massive energy boost provided by mitochondria, and those that argue that the origin of mitochondria did not represent a quantum leap in energetic advantages to eukaryotes.
Cancer cell-autonomous cGAS-STING response confers drug resistance
Authors: Lv Qian-Ming , Wang Shi-Yi , Lei Hui-Min , Zhang Ke-Ren , Tang Ya-Bin , Shen Ying , Lu Li-Ming , Chen Hong-Zhuan , Zhu Liang 
Published: October 2021

AbstractAs an evolutionarily conserved DNA-sensing machinery in innate immunity, the cGAS-STING pathway has been reported to play an important role in immune surveillance and tumor suppression. Recent evidence suggests an intriguing tumor- and metastasis-promoting effect of this signaling pathway, either in a cancer cell-autonomous or a cancer cell-nonautonomous, bystander cell-mediated manner. Here, we show a new face of cGAS-STING signaling whose activation in a cancer-cell-autonomous response manner confers drug resistance. Targeted or conventional chemotherapy drug treatment induced cancer cell cytosolic DNA accumulation and triggered subsequent cGAS-STING signaling activation in cancer cell lines and the human cell-derived xenograft tumors. This activation promoted an acquisition and maintenance of drug resistance which was prevented and overcome in vitro and in vivo by blockade of STING signaling. This finding highlights a new face of cGAS-STING signaling and an ability of cancer cells to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress and warrants a caution in combining STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.Statement of significancecGAS-STING signaling has long been recognized as playing a key role in triggering antitumor immunity. We reveal a new face of cGAS-STING signaling and an ability of cancer cells autonomously to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress.
SINBAD: a flexible tool for single cell DNA methylation data
Authors: Uzun Yasin , Yu Wenbao , Chen Changya , Tan Kai 
Published: October 2021

AbstractDNA methylation is an epigenetic mark that has vital importance in both development and disease. Single cell bisulfite sequencing technologies enable profiling of the methylome at high resolution, providing the basis for dissecting the heterogeneity and dynamics of DNA methylation in complex tissues and over time. Despite the rapid increase in the number of experimental protocols for methylome sequencing, analytical tools designed specifically for single-cell data are lacking. We developed a computational tool, SINBAD, for efficient and standardized pre-processing, quality assessment and analysis of single cell methylation data. Starting from multiplexed sequencing reads, major analysis modules of SINBAD include preprocessing, read mapping, methylation quantification, multivariate analysis, and gene signature profiling. SINBAD provides a flexible platform to implement interoperable and robust processing of single-cell methylome data.
Previously uncharacterized rectangular bacterial structures in the dolphin mouth
Authors: Dudek Natasha K. , Galaz-Montoya Jesus G. , Shi Handuo , Mayer Megan , Danita Cristina , Celis Arianna I. , Viehboeck Tobias , Wu Gong-Her , Behr Barry , Bulgheresi Silvia , Huang Kerwyn Casey , Chiu Wah , Relman David A. 
Published: October 2021

ABSTRACTMuch remains to be explored regarding the diversity of uncultured, host-associated microbes. Here, we report the discovery of unusual rectangular bacterial structures (RBSs) in the mouths of bottlenose dolphins. DNA staining revealed multiple paired bands within RBSs that suggested cells dividing along the longitudinal axis. Cryogenic transmission electron microscopy and tomography revealed parallel membrane-bound segments, suspected to be cells, encapsulated by an S-layer-like periodic surface covering. RBSs displayed novel pilus-like appendages with bundles of threads splayed at the tips. Multiple lines of evidence suggested that RBSs are bacterial and distinct from the Neisseriaceae generaSimonsiellaandConchiformibius, with which they share similar morphology and division patterning, including genomic DNA sequencing of micromanipulated RBSs, 16S rRNA gene sequencing, and fluorescencein situhybridization. Our findings highlight the diversity of novel microbial forms and lifestyles that await discovery and characterization using tools complementary to genomics such as microscopy.
Multiple paths lead to salt tolerance - pre-adaptation vs dynamic responses from two closely related extremophytes
Authors: Tran Kieu-Nga , Wang Guannan , Oh Dong-Ha , Larkin John C. , Smith Aaron P. , Dassanayake Maheshi 
Published: October 2021

AbstractSalt tolerance is a complex trait with much of the underlying genetic variation and integrated response strategies yet to be discovered from stress adapted plants.Schrenkiella parvulaandEutrema salsugineumare salt-tolerant extremophytes related toArabidopsis thalianain Brassicaceae. We investigated their response strategies contrasted against the salt-sensitive model,A. thalianato cope with salt stresses via transcriptomic, metabolomic, and ionomic adjustments. The extremophytes exemplified divergent routes to achieve nutrient balance, build osmotolerance, boost antioxidant capacity, and extend transcriptomic support for modified ion transport and stress signaling. Those led to similar molecular phenotypes adapted to salt stress in the extremophytes, absent inA. thaliana. The predominant transcriptomic signals in all three species were associated with salt stress. However, root architecture modulation mediated by negative regulation of auxin and ABA signaling supported minimally-affected root growth unique to each extremophyte during salt treatments. Overall,E. salsugineumexhibited pre-adapted responses at the metabolome level, whereasS. parvulashowed dynamic metabolomic responses coupled to a pre-adapted transcriptome to survive salt stress. Our work shows that the two extremophytes share common salt tolerance features, but differ substantially in pathways leading to the convergent, adaptive traits.
The SKBR3 Cell-Membrane Proteome: Role in Aberrant Cancer Cell Proliferation and Resource for Precision Medicine Applications
Authors: Karcini Arba , Lazar Iulia M. 
Published: October 2021

AbstractThe plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell-cell and cell-matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the landscape of the cancer cell-membrane proteome responsible for sustaining uncontrolled cell proliferation, and its intrinsic resources for enabling detection and therapeutic interventions. SKBR3/HER2+ breast cancer cells were used as a model system and mass spectrometry for characterizing the proteome. The number of identified cell-membrane proteins exceeded 2,000, with ~1,300 being matched by two or more unique peptides. Classification in four major categories, i.e., proteins with receptor or enzymatic activity, CD antigens, transporters, and cell adhesion proteins, uncovered overlapping roles in biological processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as capabilities for signaling crosstalk and alternate pathways for proliferation. The large number of tumor markers (>50) and putative drug targets (>100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal the vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.
PU.1 expression defines distinct functional activities in the phenotypic HSC compartment in a mouse model of inflammatory stress
Authors: Chavez James S. , Rabe Jennifer L. , Hernandez Giovanny , Mills Taylor S. , Niño Katia E. , Davizon-Castillo Pavel , Pietras Eric M. 
Published: October 2021

AbstractThe transcription factor PU.1 is a critical regulator of lineage fate in blood-forming hematopoietic stem cells (HSC). In response to inflammatory signals, PU.1 expression is increased in HSC, activating myeloid differentiation genes while repressing cell cycle and protein synthesis genes. To address potential functional heterogeneity arising in the phenotypic HSC compartment due to changes in PU.1 expression, here we fractionated phenotypic HSC using the SLAM code in conjunction with PU.1 expression levels using the PU.1-EYFP reporter mouse strain. While PU.1lo SLAM cells contain extensive long-term repopulating activity and a molecular signature corresponding to HSC activity at steady state, under inflammatory conditions the PU.1lo SLAM fraction is comprised almost entirely of HSC-like cells containing extensive short-term megakaryocytic potential. Our data demonstrate that the phenotypic HSC gate is heterogenous, and that similar PU.1 transcription factor levels can be tied to distinct functional activities under steady-state and inflammatory conditions.
A preliminary investigation into senior management skills: the context of third-party logistics (3PLs) providers
Authors: Midgley James , Bak Ozlem 
Published: October 2021

PurposeThe third-party logistics (3PL) provider has faced significant change since containerisation with the broadening scope of supply chains and technological developments. With these changes, the required supply chain skills discussions have covered mostly graduate skills or employees' skills with a limited discussion to what extent and whether senior management skills were changing. Hence, 3PL senior management skill requirements will be compiled based on existing studies and assessed to check whether these are still relevant and if so to what extent for today's 3PL senior managers.Design/methodology/approachA questionnaire has been devised based on 3PL senior management skills identified in the academic literature and sent out to senior managers via professional social networks of 3PL. Based on the previous literature, the senior managers selected had to fulfil the selection criteria of a minimum five years' managerial experience in a 3PL, and a minimum of ten years' experience in general, which limited the sample size to twenty-seven senior managers in the 3PL sector.FindingsThe findings indicated that 3PL senior managers’ skills highlighted an increasing dependence on and importance of relational and behavioural skills, particularly when compared with the more traditional functional and managerial skills. The study indicated that the 3PL senior managers highlighted an increasing dependence and importance upon relational and behavioural skills, particularly when compared with the more traditional functional skills.Research limitations/implicationsThe study has explored the senior management skills in 3PL in the UK, albeit the respondents possessing diverse backgrounds. Therefore, it would be beneficial to test whether these findings are exemplary across the wider 3PL sector, not only in the UK but also across Europe to see how corporate agenda for executive supply chain skills could be devised.Practical implicationsCorporate supply chain training and development staff can develop specific programs based on the 3PL senior management skill sets especially on relational and behavioural skills, which are needed for future managers as well as up-skill senior managers' skills which are deemed to be most important in the current 3PL market.Originality/valueThis paper contributes to the supply chain skills discussion and reports subject relevant challenges for today’s senior management in the 3PL industry. The findings have generated preliminary discussions on whether senior management skills are changing with the broadening scope of supply chains.