bluuebunny/crossref_metadata_2025 huggingface dataset:
Shifts in carbon partitioning by photosynthetic activity increase terpenoid synthesis in glandular trichomes
Authors: Saadat Nima P. , van Aalst Marvin , Brand Alejandro , Ebenhöh Oliver , Tissier Alain , Matuszyńska Anna B.
Published: October 2022

Several commercially important secondary metabolites are produced and accumulated in high amounts by glandular trichomes, giving the prospect of using them as metabolic cell factories. Due to extremely high metabolic fluxes through glandular trichomes, previous research focused on how such flows are achieved. The question regarding their bioenergetics became even more interesting with the discovery of photosynthetic activity in some glandular trichomes. Despite recent advances, how primary metabolism contributes to the high metabolic fluxes in glandular trichomes is still not fully elucidated. Using computational methods and available multi-omics data, we first developed a quantitative framework to investigate the possible role of photosynthetic energy supply in terpenoid production and next tested experimentally the simulation-driven hypothesis. With this work, we provide the first reconstruction of specialised metabolism in Type-VI photosynthetic glandular trichomes ofSolanum lycopersicum. Our model predicted that increasing light intensities results in a shift of carbon partitioning from catabolic to anabolic reactions driven by the energy availability of the cell. Moreover, we show the benefit of shifting between isoprenoid pathways under different light regimes, leading to a production of different classes of terpenes. Our computational predictions were confirmedin vivo, demonstrating a significant increase in production of monoterpenoids while the sesquiterpenes remained unchanged under higher light intensities. The outcomes of this research provide quantitative measures to assess the beneficial role of chloroplast in glandular trichomes for enhanced production of secondary metabolites and can guide the design of new experiments that aim at modulating terpenoid production.

GRAPHICAL ABSTRACT

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Capsid structure of a metazoan fungal dsRNA megabirnavirus reveals its uniquely acquired structures
Authors: Wang Han , Salaipeth Lakha , Miyazaki Naoyuki , Suzuki Nobuhiro , Okamoto Kenta
Published: October 2022

Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia. necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 Å resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Contrary to the other structurally associated viral capsid proteins, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission, genome packaging, and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus.

Author summary

A fungal plant soil-borne pathogen, Rosellinia necatrix, which can cause devastating disease white root rot in many highly valued fruit trees, is difficult to be controlled with conventional approaches such as fungicide applications. Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a dsRNA virus isolated from the R. necatrix field strain, W779, and this virus can be a viro-control candidate to confer hypovirulence in its host R. necatrix. To make use of RnMBV1 in the white root rot disease control, more molecular and structural investigations will offer us more insights. Here, we have performed cryo-electron microscopy (cryo-EM) single-particle analysis, to obtain the first atomic models of RnMBV1 particles. Based on the atomic structures, we found unique both surface and interior features. In addition, we found a previously unexpected protein on the viral surface. These aforementioned structural features might play important roles in the viral life cycles, and will enable us to apply this fungal virus as a viro-control approach.
Quantitative proteomics identifies tumour matrisome signatures in patients with non-small cell lung cancer
Authors: Titmarsh Helen F. , Kriegsheim Alex von , Wills Jimi C. , O’Connor Richard A. , Dhaliwal Kevin , Frame Margaret C. , Pattle Samuel B. , Dorward David A. , Byron Adam , Akram Ahsan R.
Published: October 2022

The composition and remodelling of the extracellular matrix (ECM) are important factors in the development and progression of cancers, and the ECM is implicated in promoting tumour growth and restricting anti-tumour therapies through multiple mechanisms. The characterisation of differences in ECM composition between normal and diseased tissues may aid in identifying novel diagnostic markers, prognostic indicators and therapeutic targets for drug development. Using tissue from non-small cell lung cancer (NSCLC) patients undergoing curative intent surgery, we characterised quantitative tumour-specific ECM proteome signatures by mass spectrometry, identifying 161 matrisome proteins differentially regulated between tumour tissue and nearby non-malignant lung tissue. We defined a collagen hydroxylation functional protein network that is enriched in the lung tumour microenvironment. We validated two novel putative extracellular markers of NSCLC, the collagen cross-linking enzyme peroxidasin and a disintegrin and metalloproteinase with thrombospondin motifs 16 (ADAMTS16), for discrimination of malignant and non-malignant lung tissue. These proteins were up-regulated in lung tumour samples, and high PXDN and ADAMTS16 gene expression was associated with shorter survival of lung adenocarcinoma and squamous cell carcinoma patients, respectively. These data reveal tumour matrisome signatures in human NSCLC.

Abstract Figure
Optimal feature selection and software tool development for bacteriocin prediction
Authors: Akhter Suraiya , Miller John
Published: October 2022

Antibiotic resistance is a major public health concern around the globe. As a result, researchers always look for new compounds to develop new antibiotic drugs for combating antibiotic-resistant bacteria. Bacteriocin becomes a promising antimicrobial agent to fight against antibiotic resistance, due to its narrow killing spectrum. Sequence matching methods are widely used to identify bacteriocins by comparing them with the known bacteriocin sequences; however, these methods often fail to detect new bacteriocin sequences due to sequences’ high diversity. The ability to use a machine learning approach can help find new highly dissimilar bacteriocins for developing highly effective antibiotic drugs. The aim of this work is to identify optimal sets of features and develop a machine learning-based software tool for predicting bacteriocin protein sequences with high accuracy. We extracted potential features from known bacteriocin and non-bacteriocin sequences by considering the physicochemical and structural properties of the protein sequences. Then we reduced the feature set using statistical justifications and recursive feature elimination technique. Finally, we built support vector machine (SVM) and random forest (RF) models using the selected features and our models can achieve accuracy up to 95.54%. We compared the performance of our method with a popular sequence matching-based approach and a deep learning-based method. We also developed a software tool called Bacteriocin Prediction (BacPred) that implements the prediction model using the optimal set of features obtained from this study. The software package and its user manual are available at https://github.com/suraiya14/ML_bacteriocins/BacPred.
Asymmetric distribution of centromere proteins between germline stem and daughter cells maintains a balanced niche in Drosophila males
Authors: Kochendoerfer Antje M , Dunleavy Elaine M
Published: October 2022

In the germline, stem cells undergo asymmetric cell division (ACD) to give rise to one new stem cell as well as one daughter cell that differentiates and eventually gives rise to the gamete (egg or sperm). The silent sister hypothesis proposes the selective inheritance of one set of sister chromatids carrying specific epigenetic marks to explain how genetically identical stem and daughter cells can adopt different fates. It also proposes that centromeres of sister chromatids might differ epigenetically. In Drosophila germline stem cells (GSCs), the centromeric histone CENP-A - CID in flies - is asymmetrically distributed between sister chromatids such that chromosomes that end up in the GSC harbour more CID at centromeres. In this system, a model of ‘mitotic drive’ has been proposed. According to this model, stronger and earlier centromere and kinetochore interactions with microtubules bias sister chromatid segregation during ACD. Here we show that in Drosophila males, CID, CENP-C and CAL1 are asymmetrically distributed between newly divided GSCs and daughter cells that have entered S-phase of the next cell cycle. We find that overexpression of CID, overexpression of CID together with CAL1 or CENP-C depletion disrupts CID asymmetry, with an increased pool of GSCs relative to daughter cells detectable in the niche. This result suggests a shift toward GSC self-renewal rather than differentiation, which is important to maintain tissue homeostasis. Over-expression of CAL1 does not disrupt asymmetry, nor does it affect the GSC and daughter cell balance, but instead drives germ cell proliferation in the niche. Our results in male GSCs are closely aligned with previous observations in female GSCs, indicating that despite differences in signaling, organisation and niche composition, centromere asymmetry and its effects on GSC maintenance are conserved between the sexes.
Voxel-Wise Brain Graphs from Diffusion MRI: Intrinsic Eigenspace Dimensionality and Application to Functional MRI
Authors: Behjat Hamid , Tarun Anjali , Abramian David , Larsson Martin , Van De Ville Dimitri
Published: October 2022

Structural brain graphs are conventionally limited to defining nodes as gray matter regions from an atlas, with edges reflecting the density of axonal projections between pairs of nodes. Here we explicitly model the entire set of voxels within a brain mask as nodes of high-resolution, subject-specific graphs. We define the strength of local voxel-to-voxel connections using diffusion tensors and orientation distribution functions derived from diffusion MRI data. We study the graphs’ Laplacian spectral properties on data from the Human Connectome Project. We then assess the extent of inter-subject variability of the Laplacian eigenmodes via a procrustes validation scheme. Finally, we demonstrate the extent to which functional MRI data are shaped by the underlying anatomical structure via graph signal processing. The graph Laplacian eigen-modes manifest highly resolved spatial profiles, reflecting distributed patterns that correspond to major white matter pathways. We show that the intrinsic dimensionality of the eigenspace of such high-resolution graphs is only a mere fraction of the graph dimensions. By projecting task and resting-state data on low-frequency graph Laplacian eigenmodes, we show that brain activity can be well approximated by a small subset of low-frequency components. The proposed graphs open new avenues in studying the brain, be it, by exploring their organisational properties via graph or spectral graph theory, or by treating them as the scaffold on which brain function is observed at the individual level.
Fluctuations in chromatin state at regulatory loci occur spontaneously under relaxed selection and are associated with epigenetically inherited variation in C. elegans gene expression
Authors: Wilson Rachel , Bourgeois Maxime Le , Perez Marcos , Sarkies Peter
Published: October 2022

Some epigenetic information can be transmitted between generations without changes in the underlying DNA sequence. Changes in epigenetic regulation, termed epimutations, can occur spontaneously and be propagated in populations in a manner reminiscent of DNA mutations. Epimutations mediated by small non-coding RNAs occur in C. elegans and persist for around 3-5 generations on average. Here, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational epigenetic inheritance. We compared the chromatin and gene expression profiles at matched time points from three independent lineages of C. elegans propagated at minimal population size. Spontaneous changes in chromatin occurred in around 1% of regulatory regions each generation. Some were heritable epimutations and were significantly enriched for heritable changes in expression of nearby protein-coding genes. Most chromatin-mediated epimutations were short-lived but a subset had longer duration. Genes subject to long-lived epimutations were enriched for multiple components of xenobiotic response pathways. This points to a possible role for epimutations in adaptation to environmental stressors.
Rapid evolutionary diversification of theflamencolocus across simulans cladeDrosophilaspecies
Authors: Signor Sarah , Vedanayagam Jeffrey , Kim Bernard Y. , Wierzbicki Filip , Kofler Robert , Lai Eric C.
Published: October 2022

Effective suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. InD. melanogaster,flamencois a master suppressor of TEs, preventing their movement from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, that is metabolized into Piwi-interacting RNAs (piRNAs) that target active TEs via antisense complementarity.flamencois thought to operate as a trap, owing to its high content of recent horizontally transferred TEs that are enriched in antisense orientation. Using newly-generated long read genome data, which is critical for accurate assembly of repetitive sequences, we find thatflamencohas undergone radical transformations in sequence content and even copy number acrosssimulansclade Drosophilid species.D. simulans flamencohas duplicated and diverged, and neither copy exhibits synteny withD. melanogasterbeyond the core promoter. Moreover,flamencoorganization is highly variable acrossD. simulansindividuals. Next, we find thatD. simulansandD. mauritiana flamencodisplay signatures of a dual-stranded cluster, with ping-pong signals in the testis and/or embryo. This is accompanied by increased copy numbers of germline TEs, consistent with these regions operating as functional dual stranded clusters. Overall, the physical and functional diversity offlamencoorthologs is testament to the extremely dynamic consequences of TE arms races on genome organization, not only amongst highly related species, but even amongst individuals.
Discovery of E6AP AZUL binding to UBQLN1/2 in cells, phase-separated droplets, and an AlphaFold-NMR integrated structure
Authors: Buel Gwen R. , Chen Xiang , Myint Wazo , Kayode Olumide , Folimonova Varvara , Cruz Anthony , Skorupka Katarzyna A , Matsuo Hiroshi , Walters Kylie J.
Published: October 2022

The E3 ligase E6AP/UBE3A has a dedicated binding site in the 26S proteasome provided by the RAZUL domain of substrate receptor hRpn10/S5a/PSMD4. Guided by RAZUL sequence similarity, we test and demonstrate here that the E6AP AZUL binds transiently to the UBA of proteasomal shuttle factor UBQLN1/2. Despite a weak binding affinity, E6AP AZUL is recruited to UBQLN2 phase-separated droplets and E6AP interacts with UBQLN1/2 in cells. Steady-state and transfer NOE experiments indicate direct interaction of AZUL with the UBQLN1 UBA domain. Intermolecular contacts identified by NOESY data were combined with AlphaFold2-Multimer predictions to yield an AZUL:UBA model structure. We also identify a concentration-dependent oligomerization domain directly adjacent to UBQLN1/2 UBA (UBA-adjacent, UBAA) that is α-helical and allosterically reconfigured by AZUL binding to UBA. These data lead to a model of E6AP recruitment to UBQLN1/2 by AZUL:UBA interaction and provide fundamental information on binding requirements for interactions in droplets and cells.
Proteomic Mapping of Intercellular Synaptic Environments via Flavin-Dependent Photoredox Catalysis
Authors: Bechtel Tyler J. , Bertoch Jayde M. , Olow Aleksandra K. , Duich Margaret , White Cory H. , Reyes-Robles Tamara , Fadeyi Olugbeminiyi O. , Oslund Rob C.
Published: October 2022

Receptor-ligand interactions play essential signaling roles within intercellular contact regions. This is particularly important within the context of the immune synapse where protein communication at the surface of physically interacting T cells and antigen-presenting cells regulate downstream immune signaling responses. To identify protein microenvironments within immunological synapses, we combined a flavin-dependent photocatalytic labeling strategy with quantitative mass spectrometry-based proteomics. Using α-PD-L1 or α-PD-1 single-domain antibody (VHH)-based photocatalyst targeting modalities, we profiled protein microenvironments within the intercellular region of an immune synapse-forming co-culture system. In addition to enrichment of both PD-L1 and PD-1 with either targeting modality, we also observed enrichment of both known immune synapse residing receptor-ligand pairs and surface proteins, as well as previously unknown synapse residing proteins.
Detecting and dissecting signaling crosstalk via the multilayer network integration of signaling and regulatory interactions
Authors: Halu Arda , Baek Seung Han , Lo Ian , Martini Leonardo , Silverman Edwin K. , Weiss Scott T. , Glass Kimberly R.
Published: October 2022

The versatility of cellular response arises from the communication, or crosstalk, of signaling pathways in a complex network of signaling and transcriptional regulatory interactions. Understanding the various mechanisms underlying crosstalk on a global scale requires untargeted computational approaches. We present a network-based statistical approach, MuXTalk, that uses high-dimensional edges called multilinks to model the unique ways in which signaling and regulatory interactions can interface. We demonstrate that the signaling-regulatory interface is located primarily in the intermediary region between signaling pathways where crosstalk occurs, and that multilinks can differentiate between distinct signaling-transcriptional mechanisms. Using statistically over-represented multilinks as proxies of crosstalk, we predict crosstalk among 60 signaling pathways, expanding currently available crosstalk databases by more than five-fold. MuXTalk surpasses existing methods in terms of prediction performance, identifies additions to manual curation efforts, and pinpoints potential mediators of crosstalk for each prediction. Moreover, it accommodates the inherent context-dependence of crosstalk, allowing future applications to cell type- and disease-specific crosstalk.
Targeting Fusobacterium nucleatum through Chemical Modifications of Host-Derived Transfer RNA Fragments
Authors: Yang Mengdi , Dong Pu-Ting , Cen Lujia , Shi Wenyuan , He Xuesong , Li Jiahe
Published: October 2022

Host mucosal barriers possess an arsenal of defense molecules to maintain mucosal health. In addition to well-established defense molecules such as antimicrobial peptides and immunoglobulins, a subset of extracellular host-derived small RNAs (sRNAs) also exhibits antimicrobial functions in a cross-kingdom fashion. We recently uncovered the sRNA-mediated crosstalk between human normal oral keratinocytes and Fusobacterium nucleatum (Fn), an opportunistic oral pathobiont with increasing implications in extra-oral diseases. Notably, when challenged with Fn, oral keratinocytes released Fn-targeting tRNA-derived sRNAs (tsRNAs), an emerging class of noncoding sRNAs with diverse functions in gene regulation. Additionally, synthetic mimics of the Fn-targeting tsRNAs exhibited highly selective antimicrobial activity against Fn. However, excess synthetic tsRNAs (in the micromolar range) were required to achieve growth inhibition, which limits their potential as antimicrobials. Here, we chemically modify nucleotides of the anti-Fn tsRNAs, termed MOD-tsRNAs, and demonstrate their species- and sequence-specific inhibition in the nanomolar range in various Fn type strains and clinical tumor isolates. In contrast, the same MOD-tsRNAs do not inhibit two representative oral bacteria, Porphoromonas gingivalis (Pg) and Streptococcus mitis (Sm). Additionally, MOD-tsRNAs are internalized by different Fn strains while exhibiting minimal uptake by Pg and Sm. Further RNA sequencing and affinity pull-down assays implicate MOD-tsRNAs as potential ribosome-targeting antimicrobials against Fn. Taken together, our work provides a framework to target opportunistic pathobionts through co-opting host-derived extracellular tsRNAs, whose potential applications may have been limited by their intrinsic instability as well as our limited understanding of the inhibition mechanism.
Attentional inhibition ability predicts neural representation during challenging auditory streaming
Authors: Belo Joan , Clerc Maureen , Schön Daniele
Published: October 2022

Focusing on a single source within a complex auditory scene is challenging. M/EEG-based auditory attention detection allows to detect which stream, within a set of multiple concurrent streams, an individual is attending to. The high inter-individual variability in the AAD performance is most often attributed to physiological factors and signal to noise ratio of neural data. Here we address the hypothesis that cognitive factors and in particular sustained attention, WM and attentional inhibition, may also partly explain the variability in AAD performance, because they support the cognitive processes required when listening to complex auditory scenes. Here, we chose a particularly challenging auditory scene, by presenting dichotically polyphonic classical piano excerpts lasting one minute each. Two different excerpts were presented simultaneously in each ear. Forty-one participants, with different degrees of musical expertise, listened to these complex auditory scenes focussing on one ear while we recorded the EEG. Participants also completed several tasks assessing executive functions. As expected, attended stimuli were better decoded than unattended stimuli. Importantly, attentional inhibition ability did explain around 10% of the reconstruction accuracy and around 8% of the classification accuracy. No other cognitive function was a significant predictor of reconstruction or of classification accuracies. No clear effect of musical expertise was found on reconstruction and classification performances. In conclusion, cognitive factors seem to impact the robustness of the auditory representation and hence the performance of neural based decoding approaches. Taking advantage of this relation could be useful to improve next-generation hearing aids.
Butyrate decreases Campylobacter jejuni motility and attachment partially through influence on LysR expression
Authors: Gunther Nereus W. , Nunez Alberto , Bagi Lori , Abdul-Wakeel Aisha , Ream Amy , Liu Yanhong , Uhlich Gaylen
Published: October 2022

The food pathogen Campylobacter jejuni both colonizes the lower intestines of poultry and infects the lower intestines of humans. The lower intestines of both poultry and humans are also home to a wide range of commensal organisms which compete with an organism like C. jejuni for space and resources. The commensal organisms are believed to protect humans against infection by pathogens of the digestive tract like C. jejuni. The short chain fatty acid (SCFA) butyrate is a metabolite commonly produced by commensal organisms within both the poultry and human digestive tract. We investigated the affect that physiologically relevant concentrations of butyrate have on C. jejnui. Butyrate at concentrations of 5 and 20 mM negatively impacted C. jejuni motility and attachment. These two traits are believed important for C. jejuni’s ability to infect the lower intestines of humans. Additionally, 20 mM butyrate concentrations were observed to influence the expression of a range of different Campylobacter proteins. Constitutive expression of one of these proteins, LysR, within a C. jejuni strain partially lessened the negative influence butyrate had on the bacteria’s motility.

Importance

Research studies on the short chain fatty acid, butyrate, have produced evidence for it both negatively and positively impacting Campylobacter jejuni’s colonization of poultry or infection of the human intestinal tract. There is significant value in clarifying if butyrate has potential as an intervention agent capable of interfering in the virulence process of C. jejuni. The results presented, show that butyrate, at physiological levels, negatively impacts C. jejuni motility and attachment, two important factors in the virulence process. Additionally, a proteomic analysis of butyrate’s influence on C. jejuni, identified that the expression of the transcriptional factor, LysR, was repressed in the presence of butyrate. Overexpression of the lysR gene restored some motility in the presence of butyrate suggesting this factor had a positive influence on the flagella necessary for C. jejuni’s movement.
Biomass generation and heterologous isoprenoid milking from engineered microalgae grown in anaerobic membrane bioreactor effluent
Authors: de Freitas Bárbara Bastos , Overmans Sebastian , Medina Julie Sanchez , Hong Pei-Ying , Lauersen Kyle J.
Published: October 2022

1.

Wastewater (WW) treatment in anaerobic membrane bioreactors (AnMBR) is considered more sustainable than in their aerobic counterparts. However, outputs from AnMBR are mixed methane and carbon dioxide gas streams as well as ammonium- (N) and phosphate- (P) containing waters. Using AnMBR outputs as inputs for photoautotrophic algal cultivation can strip the CO2 and remove N and P from effluent which feed algal biomass generation. Recent advances in algal engineering have generated strains for concomitant high-value side product generation in addition to biomass, although only shown in heavily domesticated, lab-adapted strains. Here, investigated whether such a strain of Chlamydomonas reinhardtii could be grown directly in AnMBR effluent with CO2 at concentrations found in its off-gas. The domesticated strain was found to proliferate over bacteria in the non-sterile effluent, consume N and P to levels that meet general discharge or reuse limits, and tolerate cultivation in modelled (extreme) outdoor environmental conditions prevalent along the central Red Sea coast. High-value co-product milking was then demonstrated, up to 837 μg L−1 culture in 96 h, in addition to algal biomass production, ∼2.4 g CDW L−1 in 96 h, directly in effluents. This is the first demonstration of a combined bio-process that employs a heavily engineered algal strain to enhance the product generation potentials from AnMBR effluent treatment. This study shows it is possible to convert waste into value through use of engineered algae while also improve wastewater treatment economics through co-product generation.

Abstract Figure
Molecular view of ER membrane remodeling by the Sec61/TRAP translocon
Authors: Karki Sudeep , Javanainen Matti , Tranter Dale , Rehan Shahid , Huiskonen Juha T. , Happonen Lotta , Paavilainen Ville O.
Published: October 2022

Protein translocation across the endoplasmic reticulum (ER) membrane is an essential initial step in protein entry into the secretory pathway. The conserved Sec61 protein translocon facilitates polypeptide translocation and coordinates cotranslational polypeptide processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation or cotranslational modifications such as N-glycosylation remains unknown. Here, we demonstrate the structure of the core Sec61/TRAP complex bound to a mammalian ribosome by Cryo-EM. The interactions with ribosome anchor the Sec61/TRAP complex in a conformation that renders the ER membrane locally thinner by significantly curving its the lumenal leaflet. We propose a model for how TRAP stabilizes the ribosome exit tunnel to assist nascent polypeptide insertion through Sec61 and provides a ratcheting mechanism into the ER lumen by direct polypeptide interactions.
Interpretable brain decoding from sensations to cognition to action: graph neural networks reveal the representational hierarchy of human cognition
Authors: Zhang Yu , Fan Lingzhong , Jiang Tianzi , Dagher Alain , Bellec Pierre
Published: October 2022

Inter-subject modeling of cognitive processes has been a challenging task due to large individual variability in brain structure and function. Graph neural networks (GNNs) provide a potential way to project subject-specific neural responses onto a common representational space by effectively combining local and distributed brain activity through connectome-based constraints. Here we provide in-depth interpretations of biologically-constrained GNNs (BGNNs) that reach state-of-the-art performance in several decoding tasks and reveal inter-subject aligned neural representations underpinning cognitive processes. Specifically, the model not only segregates brain responses at different stages of cognitive tasks, e.g. motor preparation and motor execution, but also uncovers functional gradients in neural representations, e.g. a gradual progression of visual working memory (VWM) from sensory processing to cognitive control and towards behavioral abstraction. Moreover, the multilevel representations of VWM exhibit better inter-subject alignment in brain responses, higher decoding of cognitive states, and strong phenotypic and genetic correlations with individual behavioral performance. Our work demonstrates that biologically constrained deep-learning models have the potential towards both cognitive and biological fidelity in cognitive modeling, and open new avenues to interpretable functional gradients of brain cognition in a wide range of cognitive neuroscience questions.

Highlights

BGNN improves inter-subject alignment in task-evoked responses and promotes brain decoding

BGNN captures functional gradients of brain cognition, transforming from sensory processing to cognition to representational abstraction.

BGNNs with diffusion or functional connectome constraints better predict human behaviors compared to other graph architectures

Graphic Abstract

Multilevel representational learning of cognitive processes using BGNN
Neural representations of the content and production of human vocalization
Authors: Voigtlaender Vera A. , Sandhaeger Florian , Hawellek David J. , Hage Steffen R. , Siegel Markus
Published: October 2022

Speech, as the spoken form of language, is fundamental for human communication. The phenomenon of covert inner speech implies a functional independence of speech content and motor production. However, it remains unclear how a flexible mapping between speech content and production is achieved on the neural level. To address this, we recorded magnetoencephalography (MEG) in humans performing a rule-based vocalization task. On each trial, vocalization content (one of two vowels) and production form (overt or covert) were instructed independently. Using multivariate pattern analysis, we found robust neural information about vocalization content and production, mostly originating from speech areas of the left hemisphere. Production signals dynamically transformed upon presentation of the content cue, whereas content signals remained largely stable throughout the trial. In sum, our results show dissociable neural representations of vocalization content and production in the human brain and provide new insights into the neural dynamics underlying human vocalization.
Transcriptionally active nitrogen fixation and biosynthesis of diverse secondary metabolites by Dolichospermum and Aphanizominom-like Cyanobacteria in western Lake Erie Microcystis blooms
Authors: Yancey Colleen E. , Mathiesen Olivia , Dick Gregory J.
Published: October 2022

Cyanobacterial harmful algal blooms (cyanoHABs) in the western basin of Lake Erie are dominated by microcystin producing Microcystis spp., but other cyanobacterial taxa that coexist in these communities may play important roles in production of toxins and shaping bloom dynamics and community function. In this study, we used metagenomic and metatranscriptomic data from the 2014 western Lake Erie cyanoHAB to explore the genetic diversity and biosynthetic potential of cyanobacteria belonging to the Anabaena, Dolichospermum, Aphanizomenon (ADA) clade. We reconstructed two near-complete metagenome-assembled genomes from two distinct ADA clade species, each containing biosynthetic gene clusters that encode novel and known secondary metabolites that were transcriptionally active. These taxa also appear to have varying nutrient acquisition strategies, and their ability to fix N may be important for synthesizing N rich metabolites as well as supporting bloom persistence. Although not the dominant organism in this system, these results suggest that ADA may be important community members in western Lake Erie cyanoHABs that have the potential to produce unmonitored toxins.

Highlights

Through metagenomic approaches, we generated two near-complete metagenome assembled genomes from two distinct species that are dispersed across the ADA clade of cyanobacteria.

These ADA cyanobacteria have the potential to produce a variety of known and novel secondary metabolites, and use different nitrogen fixation strategies as observed through differential transcript abundance

This works highlights the diversity of cyanobacteria in western Lake Erie blooms despite their continued dominance by Microcystis, and that these less abundant cyanobacteria may produce unmonitored toxins and shape bloom dynamics through N-fixation.
Posttranscriptional regulation of cell wall integrity in budding yeast
Authors: Bresson Stefan , Shchepachev Vadim , Tollervey David
Published: October 2022

The fungal cell wall provides protection and structure, and is an important target for antifungal compounds. A MAP kinase cascade termed the cell wall integrity (CWI) pathway regulates transcriptional responses to cell wall damage. Here we describe a posttranscriptional pathway that plays an important complementary role. We discovered that the RNA-binding proteins (RBPs) Mrn1 and Nab6 specifically target the 3’ UTRs of a largely overlapping set of cell wall-related mRNAs. These mRNAs are downregulated in the absence of Nab6, indicating a function in target mRNA stabilization. Nab6 acts in parallel to CWI signaling to maintain appropriate expression of cell wall genes during stress. Cells lacking both pathways are hypersensitive to antifungal compounds targeting the cell wall. Deletion of MRN1 partially alleviates growth defects associated with Δnab6 and Mrn1 has an opposing function in mRNA destabilization. Our results uncover a novel posttranscriptional pathway which mediates cellular resistance to antifungal compounds.
Telomere Position Effect Over Long Distance acts as a genome-wide epigenetic regulator through a commoncis- element
Authors: Chevalier Raphaël , Pienkwoski Victor Murcia , Jullien Nicolas , Caron Leslie , Magdinier Frédérique , Robin Jérôme D.
Published: October 2022

Among epigenetic modifiers, telomeres, represent attractive modulators of the genome in part through position effects. Telomere Position Effect – Over Long Distances (TPE-OLD) modulates genes expression by changes in telomere-dependent long-distance loops, with a reach of 10Mb from a telomere. However, TPE-OLD remains poorly defined. To gain further insights into the genome-wide impact of telomere length on genomic and epigenomic regulation through TPE-OLD, we used cells with controlled telomere length combined to a genome wide transcriptome and methylome analysis. By integrating omics data, we identified a commoncis-acting motif that behaves as an insulator or enhancer. Using reporter assays integrating this element, we uncovered thetranspartners regulating this activity. Further exploiting our cellular model, we observed the depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. We concluded that, at the genome-wide level, TPE-OLD is relayed by RBPJ binding Alu-like elements to telomeres that acts as enhancers. In response to external stimuli (i.e., Aging), TPE-OLD might act by coordinating telomere length to the action of Alu newly evolved enhancers in association with RBPJ.
Distinct RPA functions promote eukaryotic DNA replication initiation and elongation
Authors: Pike Alexandra M. , Friend Caitlin M. , Bell Stephen P.
Published: October 2022

Single-stranded DNA binding proteins (SSBs) are essential for DNA replication across all domains of life, but vary significantly in their structure and subunit composition. The eukaryotic SSB, Replication Protein A (RPA), serves critical functions in DNA replication, the DNA damage response, and DNA repair. We sought to determine the requirements for RPA during eukaryotic DNA replication initiation and elongation. To determine whether the ssDNA-binding activity is sufficient, we tested SSBs from different domains of life in reconstituted S. cerevisiae origin unwinding and DNA replication reactions. Interestingly, E. coli SSB, but not T4 bacteriophage Gp32, fully substitutes for RPA in promoting origin DNA unwinding. Using RPA mutants, we found that only large, multimeric complexes with multiple DNA-binding domains support origin unwinding. In contrast, our studies demonstrated that eukaryotic replication fork function requires specific RPA domains for normal leading- and lagging-strand DNA synthesis. Together, these results reveal new requirements for ssDNA-binding proteins in eukaryotic replication origin unwinding and uncover RPA domains that are critical for faithful replication fork function.
Estrogens dynamically regulate neurogenesis in the dentate gyrus of adult female rats
Authors: Yagi Shunya , Wen Yanhua , Burrowes Ariel A Batallán , Blankers Samantha A , Galea Liisa AM
Published: October 2022

Estrone and estradiol differentially modulate neuroplasticity and cognition, but how they influence maturation pathways of new neurons in the adult hippocampus is not known. The present study assessed the effects of estrone and estradiol on various aspects of neurogenesis in the dentate gyrus (DG) of ovariectomized young adult Sprague-Dawley rats using daily subcutaneous injections of 17β-estradiol or estrone. Rats were injected with a DNA synthesis marker, 5-bromo-2-deoxyuridine (BrdU), and were perfused one, two, or three weeks after BrdU injection and treatment. Immunofluorescent labelling for GFAP/Sox2 was used to examine the density of neural stem/progenitor cells and Ki67 for cell proliferation. Double-immunofluorescent labelling of BrdU with doublecortin (DCX) or NeuN was used to examine the attrition and maturation of adult-born neurons over time. Length of time post ovariectomy was associated with a reduction in neural stem/progenitor cells in the DG. Estrogens had effects on different components of neurogenesis after one week of exposure but not after prolonged treatment. Estradiol enhanced, whereas estrone reduced, cell proliferation after one week but not after longer exposure to hormones. Both estrogens increased the density of BrdU/DCX-ir cells after one week of exposure but showed greater attrition of new neurons between one and two weeks after exposure, suggesting that the effects of estrogens on neurogenesis were not sustained. These results demonstrate that estrogens modulate several aspects of adult hippocampal neurogenesis differently in the short term, but may lose their ability to influence neurogenesis after long-term exposure.
“Helicase” Activity Promoted Through Dynamic Interactions Between a ssDNA Translocase and a Diffusing SSB Protein
Authors: Mersch Kacey , Sokoloski Joshua E. , Nguyen Binh , Galletto Roberto , Lohman Timothy M.
Published: October 2022

Replication protein A (RPA) is a eukaryotic single stranded (ss) DNA binding (SSB) protein that is essential for all aspects of genome maintenance. RPA binds ssDNA with high affinity but can also diffuse along ssDNA. By itself, RPA is capable of transiently disrupting short regions of duplex DNA by diffusing from a ssDNA that flanks the duplex DNA. Using single molecule total internal reflection fluorescence and optical trapping combined with fluorescence approaches we show that S. cerevisiae Pif1 can use its ATP-dependent 5’ to 3’ translocase activity to chemo-mechanically push a single human RPA (hRPA) directionally along ssDNA at rates comparable to those of Pif1 translocation alone. We further show that using its translocation activity Pif1 can push hRPA from a ssDNA loading site into a duplex DNA causing stable disruption of at least 9 bp of duplex DNA. These results highlight the dynamic nature of hRPA enabling it to be readily reorganized even when bound tightly to ssDNA and demonstrate a new mechanism by which directional DNA unwinding can be achieved through the combined action of a ssDNA translocase that pushes an SSB protein.
An Integrated Physiological, Cytology and Proteomics Reveals Network of Sugarcane Protoplasts Responses to Enzymolysis
Authors: Zhang Demei , Wang Rui , xiao Jiming , Zhu Shuifang , Li Xinzhu , Han Shijian , Li Zhigang , Zhao Yang , Islam Shohag Md. Jahidul , He Zhenli , Li Suli
Published: October 2022

The protoplast experimental system has been becoming a powerful tool for functional genomics and cell fusion breeding. However, the physiology and molecular mechanism during enzymolysis is not completely understood and has become a major obstacle to protoplast regeneration. Our study used physiological, cytology, iTRAQ (Isobaric Tags for Relative and Absolute Quantification) -based proteomic and RT-PCR analyses to compare the young leaves of sugarcane (ROC22) and protoplasts of more than 90% viability. We found that oxidation product MDA content increased in the protoplasts after enzymolysis and several antioxidant enzymes such as POD, CAT, APX, and O2- content significantly decreased. The cytology results showed that after enzymolysis, the cell membranes were perforated to different degrees, the nuclear activity was weakened, the nucleolus structure was not obvious, and the microtubules depolymerized and formed many short rod-like structures in protoplasts. The proteomic results showed that 1,477 differential proteins were down-regulated and 810 were up-regulated after enzymolysis of sugarcane young leaves. The GO terms, KEGG and KOG enrichment analysis revealed that differentially abundant proteins were mainly involved in bioenergetic metabolism, cellular processes, osmotic stress, and redox homeostasis of protoplasts, which would allow protein biosynthesis or / degradation. The RT-PCR analysis revealed the expression of osmotic stress resistance genes such as DREB, WRKY, MAPK4, and NAC were up-regulated. Meanwhile, the expression of key regeneration genes such as CyclinD3, CyclinA, CyclinB, Cdc2, PSK, CESA and GAUT were significantly down-regulated in the protoplasts. Hierarchical clustering, identification of redox proteins and oxidation products showed that these proteins were involved in dynamic networks in response to oxidative stress after enzymolysis. We used a variety of methods to figure out how young sugarcane leaves react to enzymes.
A complex containing RhoBTB3-SHIP164-Vps26B promotes the biogenesis of early endosome buds at Golgi-endosome contacts
Authors: Wang Jingru , Chu Qingzhu , Chang Weiping , Deng Lin , Ji Wei-Ke
Published: October 2022

Early endosomes (EEs) are central hubs for cargo sorting in vesicular trafficking. Cargoes destined for degradation retain in EEs that are eventually delivered to lysosomes, while recycled cargo destined for the plasma membrane (PM) or to the Golgi are segregated into EE buds, a specialized membrane structure transiently generated on EEs during cargo sorting. Until now, the molecular basis of the membrane expansion during the biogenesis of EE buds is completely elusive. Here, we identify a protein complex containing a Vps13 domain-containing lipid transporter SHIP164, ATPase RhoBTB3 and retromer component Vps26B, promotes the membrane expansion in the biogenesis of EE buds at Golgi-EE contacts. SHIP164 depletion specifically reduces the size and number of EE buds marked by Vps26B and actin, and results in less but enlarged EEs, which can be substantially rescued by wild type SHIP164 other than lipid transfer-defective mutants, suggesting a role of lipid transfer of SHIP164 in the process. SHIP164 and RhoBTB3 interact with enzymes for phospholipid synthesis on motile Golgi vesicles, that frequently contact EEs. Functionally, SHIP164 depletion substantially reduces the trafficking of sphingomyelin to the PM, and impairs cell growth. Together, we propose a lipid transport-dependent route from the Golgi to EEs at the contacts required for EE bud biogenesis.
Making do: Anthropology and economy
Authors: Gudeman Stephen
Published: October 2022

Anthropologists explore how people create connections among themselves and to the larger world. Economists use deductive reasoning to explain much the same. Anthropologists expect serendipity; economists draw on calculation and design. Positioned between the two, economic anthropology can build on the idea of making do or using what is at hand to get something done, from raising crops, cooking a meal or repairing a home to producing a commodity or constructing a myth. Making do captures much of economic, social and conceptual life, as well as fieldwork practice.
Towards an anthropology of misinformation
Authors: Polleri Maxime
Published: October 2022

This article stresses the importance of further developing an anthropological approach to misinformation studies. It argues that misinformation studies should outgrow their dichotomy between truth and falsity to instead study misinformation as signals that reveal a range of narratives and experiences within specific issues, such as the causes of mistrust in experts’ organizations. Drawing on case studies surrounding Covid‐19, police brutality and geopolitical tensions, this article provides three ways of anthropologically studying misinformation: (1) analysing misinformation within its context of production, rather than as isolated pieces of information; (2) analysing misinformation as a signal of trust towards the Other; and (3) analysing the unique characteristics of the network that allow misinformation to proliferate in digital social media. By theorizing misinformation beyond the duality of truth and falsity and highlighting methodological ways to research it pragmatically, the article encourages further education on the many forms that misinformation embodies.