bluuebunny/crossref_metadata_2025 huggingface dataset:
HB-EGF and zinc activate EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures
Authors: Pastor-Alonso Oier , Durá Irene , Bernardo-Castro Sara , Varea Emilio , Muro-García Teresa , Martín-Suárez Soraya , Encinas-Pérez Juan Manuel , Pineda Jose Ramon
Published: November 2022

Hippocampal seizures mimicking mesial temporal lobe epilepsy (MTLE) cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive-neural stem cells, React-NSCs)) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here we, using a mouse model of MTLE, show that the epidermal growth factor receptor (EGFR) signalization pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signalization pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis.

Significance

In mouse models of MTLE-HS, seizures cause a profound disruption of the hippocampal neurogenic niche and neurogenesis results chronically impaired, in agreement with what occurs in the human MTLE-HS hippocampus. Thus, the normal cognitive functions associated with neurogenesis are altered, but also the endogenous regenerative capacity that could compensate the high rate of neurons in the granule cell layer of the dentate gyrus. We provide here for the first time a molecular mechanism (the EGFR transduction pathway) regulating the induction of React-NSCs.
Overflow of Working Memory from an Easily Accessible Active State
Authors: Ideriha Takuya , Ushiyama Junichi
Published: November 2022

Working memory is a system that realizes short-term memory retention and is essential to everyday activities. Recently, it has been suggested that working memory items can be maintained in both an active state with sustained neural activity and a latent state without any explicit neural activity. However, how easily we can retrieve memories in each state and how much information can be retained in the active state remains unknown. Here, we addressed these questions by adopting a novel experimental paradigm for measuring the reaction time required to recall a letter of the alphabet when presented with a corresponding color, based on memorized color/letter pairs. The results demonstrated that when participants retained only two pairs of items, they could recall both pairs similarly quickly. However, when there were two or more memorized pairs, the most recent or internally attended pairs were recalled more quickly than the other pairs. These results suggest that memories in the “active” state are accessed first and memories that have overflowed into the “latent” state are accessed afterward. Additionally, the capacity of the easily accessible active state is extremely limited (to approximately two chunks of information) compared with the traditionally considered working memory capacity (four to seven chunks). These results provide robust behavioral support for the co-existence of multiple states in working memory and underscore the need for a more detailed classification of the working memory capacity.

SIGNIFICANCE STATEMENT

We sometimes cannot quickly retrieve what we are sure we remember. Regarding working memory retrieval, we observed a phenomenon that the most recently encoded memory was retrieved quickly whereas others were retrieved afterward, showing an “overflow” of memory items from an easily accessible active state. This observation has two critical implications: 1) when maintaining multiple items in working memory, not all items are functionally the same, and there is a dissociation between easily accessible active items and items that have overflowed to a latent state; 2) the number of items that can be maintained in the active state is two, which is remarkably smaller than the traditionally considered working memory capacity of four, necessitating the update of working memory models.
Limiting etioplast gene-expression induces apical hook twisting during skoto-morphogenesis ofArabidopsisseedlings
Authors: Sajib Salek Ahmed , Grübler Björn , Oukacine Cylia , Delannoy Etienne , Courtois Florence , Mauve Caroline , Lurin Claire , Gakière Bertrand , Pfannschmidt Thomas , Merendino Livia
Published: November 2022

When covered by a layer of soil, seedling development follows a dark-specific program (skoto-morphogenesis) consisting of small, non-green cotyledons, a long hypocotyl and an apical hook to protect meristematic cells. We recently highlighted the role played by mitochondria in the high energy-consuming reprogramming ofArabidopsisskoto-morphogenesis. Here, the role played by plastids, another energy supplying organelle, in skoto-morphogenesis is investigated. This study was conducted in dark conditions to exclude light signals so as to better focus on those produced by plastids. It was found that limitation of plastid gene-expression (PGE) induced an exaggerated apical hook bending. Inhibition of PGE was obtained at the level of transcription and translation using the antibiotics rifampicin and spectinomycin, respectively, as well as plastid RPOTP RNA polymerase mutants. Rifampicin-treated seedlings also showed expression induction of marker nuclear genes for mitochondrial stress, perturbation of the mitochondrial metabolism, increase of ROS levels and an augmented capacity of oxygen consumption by mitochondrial alternative oxidases (AOX). AOX enzymes act to prevent over-reduction of the mitochondrial electron transport chain. Previously, we reported that AOX1A, the main AOX isoform, was a key component in the developmental response to mitochondrial respiration deficiency. In this work, we suggest the involvement of AOX1A in the response to PGE dysfunction and propose the importance of signalling between plastids and mitochondria. Finally, it was found that seedling architecture reprogramming in response to rifampicin was independent of canonical organelle retrograde pathways and the ethylene signaling pathway.

Significance statement

In underground germination conditions, seedling development follows a dark-specific program (skoto-morphogenesis) consisting of small and non-green cotyledons, a long hypocotyl and an apical hook to protect meristematic cells. We show that skoto-morphogenesis is reprogrammed when plastid gene expression is perturbed leading to an exaggeration of apical hook bending. We propose the involvement of the cooperation between plastids and mitochondria, the energy-supplying organelles of the cell.
A specific mesh-like organization of human septin octameric complex drives membrane reshaping and curvature sensitivity
Authors: Nakazawa Koyomi , Kumar Gaurav , Chauvin Brieuc , Di Cicco Aurélie , Pellegrino Luca , Trichet Michael , Hajj Bassam , Cabral João , Sain Anirban , Mangenot Stéphanie , Bertin Aurélie
Published: November 2022

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane, we have used a combination of methods to assay their ultrastructural organization, their curvature sensitivity as well as their role in membrane reshaping. In contrast to budding yeast septins, on membranes, human septins systematically organize into a two-layered mesh of orthogonal filaments instead of generating parallel sheets of filaments observed for budding yeast septins. This peculiar mesh organization is curvature sensitive and drives membrane reshaping as well. The observed membrane deformations together with the filamentous organization are recapitulated in a coarsegrained computed simulation to understand their mechanisms. Our results highlight the specificity of animal septins as opposed to fungal proteins.
Differentiation is accompanied by a progressive loss in transcriptional memory
Authors: Fourneaux Camille , Racine Laëtitia , Koering Catherine , Dussurgey Sébastien , Vallin Elodie , Moussy Alice , Parmentier Romuald , Brunard Fanny , Stockholm Daniel , Modolo Laurent , Picard Franck , Gandrillon Olivier , Paldi Andras , Gonin-Giraud Sandrine
Published: November 2022

Cell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to undergo phenotypic change during a differentiation process relies upon a modification in this balance which favors change-inducing gene expression variability. However, there are no experimental data providing insight on how fast the transcriptomes of identical cells would diverge on the scale of the very first two cell divisions during the differentiation process.

In order to quantitatively address this question, we developed different experimental methods to recover the transcriptomes of related cells, after one and two divisions, while preserving the information about their lineage at the scale of a single cell division. We analyzed the transcriptomes of related cells from two differentiation biological systems (human CD34+ cells and T2EC chicken primary erythrocytic progenitors) using two different single-cell transcriptomics technologies (sc-RT-qPCR and scRNA-seq).

We identified that the gene transcription profiles of differentiating sister-cells are more similar to each-other than to those of non related cells of the same type, sharing the same environment and undergoing similar biological processes. More importantly, we observed greater discrepancies between differentiating sister-cells than between self-renewing sister-cells. Furthermore, a continuous increase in this divergence from first generation to second generation was observed when comparing differentiating cousin-cells to self renewing cousin-cells.

Our results are in favor of a continuous and gradual erasure of transcriptional memory during the differentiation process.
Characterization of N distribution in different organs of winter wheat using UAV-based remote sensing
Authors: Wang Falv , Li Wei , Liu Yi , Qin Weilong , Ma Longfei , Zhang Yinghua , Sun Zhencai , Wang Zhimin , Li Fei , Yu Kang
Published: November 2022

Although unmanned aerial vehicle (UAV) remote sensing is widely used for high-throughput crop monitoring, few attempts have been made to assess nitrogen content (NC) at the organ level and its impact on nitrogen use efficiency (NUE). Also, little is known about the performance of UAV-based image texture features in crop nitrogen and NUE monitoring. In this study, eight flying missions were carried out throughout different stages of winter wheat (from the jointing stage to the stage 25 days after flowering) to acquire multispectral images. Forty-three multispectral vegetation indices (VIs) and forty texture features (TFs) were calculated from images and fed into the partial least squares regression (PLSR) and random forest (RF) regression models for predicting nitrogen-related indicators. Our main purposes were to (1) evaluate the potential of UAV-based images to predict NC in different organs of winter wheat and nitrogen agronomic efficiency (NAE); (2) compare the performances of VIs, TFs and the combination of them for nitrogen monitoring. The results showed that the correlation between different features (VIs and TFs) and NC in different organs varied between the vegetative and reproductive phases. Most of VIs were found to be positively correlated with NC, while most of the TFs were negatively correlated with NC. PLSR latent variables extracted from VIs and TFs explained 80% of the variations in NAE. However, no significant differences were found between VIs and TFs in their performance in predicting NC in different organs. This study demonstrated the promise of applying UAV-based imaging to estimate NC and NAE in different organs of winter wheat.
Preservation of thalamocortical circuitry is essential for good recovery in comatose survivors of cardiac arrest
Authors: Tewarie Prejaas K. , Tjepkema-Cloostermans Marleen C. , Abeysuriya Romesh G. , Hofmeijer Jeannette , van Putten Michel J.A.M.
Published: November 2022

Continuous EEG monitoring contributes to prediction of neurological outcome in comatose cardiac arrest survivors. While the phenomenology of EEG abnormalities in postanoxic encephalopathy is well-known, the pathophysiology, especially the presumed role of selective synaptic failure is less understood. To further this understanding, we estimate biophysical model parameters from the EEG power spectra from individual patients with a good or poor recovery from a postanoxic encephalopathy. This biophysical model includes intracortical, intrathalamic, and corticothalamic synaptic strengths, as well as synaptic time constants and axonal conduction delays. We used continuous EEG measurements from hundred comatose patients recorded during the first 48 hours post-cardiac arrest, fifty with a poor neurological outcome (Cerebral Performance Category (CPC=5)) and fifty with a good neurological outcome (CPC=1). We only included patients that developed (dis-) continuous EEG activity within 48 hours post-cardiac arrest. For patients with a good outcome, we observed an initial relative excitation in the corticothalamic loop and corticothalamic propagation that subsequently evolved towards values observed in healthy controls. For patients with a poor outcome, we observed an initial increase in the cortical excitation-inhibition ratio, increased relative inhibition in the corticothalamic loop, delayed corticothalamic propagation of neuronal activity, and severely prolonged synaptic time constants, that did not return to physiological values. We conclude that the abnormal EEG evolution in patients with a poor neurological recovery after cardiac arrest may result from persistent and selective synaptic failure that includes corticothalamic circuitry, but also delayed corticothalamic propagation.
Contrasting leaf thickness & saturated water content explain diverse structural/physiological properties of arid species
Authors: Lamont Byron B. , Lamont Heather C.
Published: November 2022

Although they account for many thousands of the world’s flowering plants, little is known about the physical/chemical properties of leaf succulents. Eight species in the Namib Desert, South Africa were assessed for leaf area (A) and thickness (z), saturated (Q) and dry mass, relative volume of air (Fa), intrinsic water-us efficiency (δ13C), and N, P and (Na+K) contents. As water-storage capacity is a function ofQvandz, this meansQ/A(=Qv•z) is an ideal index of succulence compared with specific-leaf-area and other indices that highlight mass rather than volume. Specific gravities have a different relationship withFaof sclerophyll-mesophylls: rising succulence infers decreasing air content replaced by water rather than dry matter. The trend among succulent species from Argentina/Spain added to our data was characterized byQ/Aexceeding 1 mg water/mm2leaf whose overall slope was ten times that for co-occurring sclerophyll-mesophyll species. (Na+K), N and P concentrations varied on a dry-matter, but not water-volume, basis.Wirelationships were essentially functions of variations inz(transpiration-resistance) and increased metabolic efficiency. We conclude thatzandQvare keys to the special physiological properties of succulent leaves. Including succulents would force many current monotonic relationships to dichotomize.

Highlight

The key to understanding leaf succulents is their high volumetric water content and thick leaves. These explain their superior water-use-efficiency and contrasting relationships with other variables compared with temperate species.
Modelling surface color discrimination under different lighting environments using image chromatic statistics and convolutional neural networks
Authors: Ponting Samuel , Morimoto Takuma , Smithson Hannah
Published: November 2022

We modeled discrimination thresholds for object colors under different lighting environments [1]. Firstly we built models based on chromatic statistics, testing 60 models in total. Secondly we trained convolutional neural networks (CNNs), using 160,280 images labeled either by the ground-truth or by human responses. No single chromatic statistics model was sufficient to describe human discrimination thresholds across conditions, while human-response-trained CNNs nearly perfectly predicted human thresholds. Guided by region-of-interest analysis of the network, we modified the chromatic statistics models to use only the lower regions of the objects, which substantially improved performance.
Overconfidence undermines global wildlife abundance trends
Authors: Johnson Thomas Frederick , Beckerman Andrew P , Childs Dylan Z , Griffiths Christopher A , Capdevila Pol , Clements Christopher F , Besson Marc , Gregory Richard D. , Delmas Eva , Thomas Gavin , Evans Karl , Webb Tom , Freckleton Rob
Published: November 2022

In the face of rapid global change and an uncertain fate for biodiversity, it is vital to quantify trends in wild populations. These trends are typically estimated from abundance time series for suites of species across large geographic and temporal scales. Such data implicitly contain phylogenetic, spatial, and temporal structure which, if not properly accounted for, may obscure the true magnitude and direction of biodiversity change. Here, using a novel statistical framework to simultaneously account for all three of these structures, we show that the majority of current abundance trends estimates among 10 high-profile datasets, representing millions of abundance observations, are likely unreliable or incorrect. Our new approach suggests that previous models are too simplistic, incorrectly estimating global abundance trends and often dramatically underestimating uncertainty, an aspect that is critical when translating global assessments into policy outcomes. Further, our approach also results in substantial improvements in abundance forecasting accuracy. Whilst our results do not improve the outlook for biodiversity, our framework does allow us to make more robust estimates of global wildlife abundance trends, which is critical for developing policy to protect our biosphere.
Gene model correction for PVRIG in single cell and bulk sequencing data enables accurate detection and study of its functional relevance
Authors: Nemzer Sergey , Sabath Niv , Wool Assaf , Alteber Zoya , Ando Hirofumi , Nickles-Fader Amanda , Wang Tian-Li , Shih Ie-Ming , Pardoll Drew M. , Ganguly Sudipto , Turpaz Yaron , Levine Zurit , Granit Roy Z.
Published: November 2022

Single cell RNA sequencing (scRNA-seq) has gained increased popularity in recent years and has revolutionized the study of cell populations; however, this technology presents several caveats regarding specific gene expression measurement. Here we examine the expression levels of several immune checkpoint genes, which are currently assessed in clinical studies. We find that unlike in most bulk sequencing studies, PVRIG, a novel immune-modulatory receptor in the DNAM-1 axis, suffers from poor detection in 10x Chromium scRNA-seq and other types of assays that utilize the GENCODE transcriptomic reference (gene model). We show that the default GENCODE gene model, typically used in the analysis of such data, is incorrect in the PVRIG genomic region and demonstrate that fixing the gene model recovers genuine PVRIG expression levels. We explore computational strategies for resolving multi-gene mapped reads, such as those implemented in RSEM and STARsolo and find that they provide a partial solution to the problem. Our study provides means to better interrogate the expression of PVRIG in scRNA-seq and emphasizes the importance of optimizing gene models and alignment algorithms to enable accurate gene expression measurement in scRNA-seq and bulk sequencing. The methodology applied here for PVRIG can be applied to other genes with similar issues.
An inhibitory plasticity mechanism for world structure inference by hippocampal replay
Authors: Liao Zhenrui , Hadjiabadi Darian , Terada Satoshi , Soltesz Ivan , Losonczy Attila
Published: November 2022

Memory consolidation assimilates recent experiences into long-term memory. This process requires the replay of learned sequences, though the content of these sequences remains controversial. Recent work has shown that the statistics of replay deviate from those of experience: stimuli which are experientially salient may be either selected or suppressed. We find that this phenomenon can be explained parsimoniously and biologically plausibly by a Hebbian spike time-dependent plasticity rule at inhibitory synapses. Using spiking networks at three levels of abstraction–leaky integrate-and-fire, biophysically detailed, and abstract binary–we show that this rule enables efficient inference of a model of the structure of the world. We present analytical results that these replayed sequences converge to ground truth under a mathematical model of replay. Finally, we make specific predictions about the consequences of intact and perturbed inhibitory dynamics for network dynamics and cognition. Our work outlines a potential direct link between the synaptic and cognitive levels of memory consolidation, with implications for both normal learning and neurological disease.
Mechanisms of vascular maturation and maintenance captured by longitudinal imaging of live mouse skin
Authors: Kam Chen Yuan , Singh Ishani D. , Matte-Martone Catherine , Gonzalez David G. , Solá Paloma , Solanas Guiomar , Bonjoch Júlia , Marsh Edward D. , Hirschi Karen K. , Greco Valentina
Published: November 2022

A functional network of blood vessels is essential for organ growth and homeostasis. Yet, how the vasculature matures and maintains adult homeostasis remains elusive in live mice. By longitudinally tracking the same neonatal endothelial cells (ECs) over days to weeks, we found that capillary plexus expansion is driven by network-wide vessel regression and transient angiogenesis. A fixed number of neonatal ECs rearrange their positions to evenly distribute throughout the developing plexus and become positionally stable in adulthood. Upon injury, while neonatal ECs are predisposed to die, adult ECs survive through a plasmalemmal self-repair response. Furthermore, adult neighboring ECs reactivate migration to assist vessel repair. Lastly, neonatal vessel regression and adult vascular maintenance are orchestrated by temporally restricted VEGFR2 dependent signaling. Our work sheds light on fundamental cellular mechanisms that underlie both vascular maturation and adult homeostasisin vivo.
transmorph: a unifying computational framework for single-cell data integration
Authors: Fouché Aziz , Chadoutaud Loïc , Delattre Olivier , Zinovyev Andrei
Published: November 2022

Data integration of single-cell data describes the task of embedding datasets obtained from different sources into a common space, so that cells with similar cell type or state end up close from one another in this representation independently from their dataset of origin. Data integration is a crucial early step in most data analysis pipelines involving multiple batches and allows informative data visualization, batch effect reduction, high resolution clustering, accurate label transfer and cell type inference. Many tools have been proposed over the last decade to tackle data integration, and some of them are routinely used today within data analysis workflows. Despite constant endeavors to conduct exhaustive benchmarking studies, a recent surge in the number of these methods has made it difficult to choose one objectively for a given use case. Furthermore, these tools are generally provided as rigid pieces of software allowing little to no user agency on their internal parameters and algorithms, which makes it hard to adapt them to a variety of use cases. In an attempt to address both of these issues at once we introducetransmorph, an ambitious unifying framework for data integration. It allows building complex data integration pipelines by combining existing and original algorithmic modules, and is supported by a rich software ecosystem to easily benchmark modules, analyze and report results. We demonstratetransmorphcapabilities and the value of its expressiveness by solving a variety of practical single-cell applications including supervised and unsupervised joint datasets embedding, RNA-seq integration in gene space and label transfer of cell cycle phase within cell cycle genes space. We providetransmorphas a free, open source and computationally efficient python library, with a particular effort to make it compatible with the other state-of-the-art tools and workflows.
The Sponges of the Carmel Pinnacles Marine Protected Area
Authors: Turner Thomas L. , Lonhart Steve
Published: November 2022

California’s network of marine protected areas was created to protect the diversity and abundance of native marine life, but the status of some taxa is very poorly known. Here we describe the sponges (phylum Porifera) from the Carmel Pinnacles State Marine Reserve, as assessed by a SCUBA-based survey in shallow waters. Of the 29 sponge species documented, 12 (41%) of them were previously unknown. Using a combination of underwater photography, DNA sequencing, and morphological taxonomy, we greatly improve our understanding of the status and distribution of previously described species and formally describe the new species asHymedesmia prominasp. nov., Phorbas nebulosussp. nov., Clathria unoriginalissp. nov.,Clathria rumsenasp. nov., Megaciella sanctuariumsp. nov., Mycale lobossp. nov., Xestospongia ursasp. nov., Haliclona melissaesp. nov., Halichondria lomasp. nov., Hymeniacidon fusiformissp. nov., Scopalina carmelasp. nov., andObruta collectorgen. nov., sp. nov. An additional species,Lissodendoryx topsenti(de Laubenfels 1930), is moved toHemimycale,andH. polyboletuscomb. nov., nom. nov. is created due to preoccupation byH. topsenti(Burton, 1929). Several of the new species appear to be rare and/or have very restricted distributions, as they were not found at comparative survey sites outside of Carmel Bay. These results illustrate the potential of qualitative presence/absence systematic surveys of understudied taxa to discover and document substantial novel diversity.
Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches
Authors: Sosa-Carrillo Sebastián , Galez Henri , Napolitano Sara , Bertaux François , Batt Gregory
Published: November 2022

The production of recombinant proteins is a problem of major industrial and pharmaceutical importance. Secretion of the protein by the host cell considerably simplifies downstream purification processes. However, it is also the limiting production step for many hard-to-secrete proteins. Current solutions involve extensive chassis engineering to favor trafficking and limit protein degradation triggered by excessive secretion-associated stress. Here, we propose instead a regulation-based strategy in which induction is dynamically adjusted based on the current stress level of the cells. Using a small collection of hard-to-secrete proteins and a bioreactor-based platform with automated cytometry measurements, we demonstrate that the regulation sweet spot is indicated by the appearance of a bimodal distribution of internal protein and of secretory stress levels, when a fraction of the cell population accumulates high amounts of proteins, decreases growth, and faces significant stress, that is, experiences a secretion burn-out. In these cells, adaptations capabilities are overwhelmed by a too strong production. With these notions, we define an optimal stress level based on physiological readouts. Then, using real-time control, we demonstrate that a strategy that keeps the stress at optimal levels increases production of a single-chain antibody by 70%.
Malassezia sympodialisMala s 1 allergen is a potential KELCH protein that cross reacts with human skin
Authors: Corzo Leon Dora E. , Scheynius Annika , MacCallum Donna M. , Munro Carol A.
Published: November 2022

Malasseziayeast species are the dominant commensal fungal species of the human skin microbiota, but are also associated with inflammatory skin diseases, such as seborrheic dermatitis and atopic eczema (AE). Mala s 1, a β-propeller protein, is an allergen identified inMalassezia sympodialisinducing both IgE and T-cell reactivity in the majority of patients with AE. In this study, we aimed to elucidate the role of Mala s 1 allergen in skin disease. An anti-Mala s 1 antibody was used to investigate the cellular localisation of Mala s 1, the potential of Mala s 1 as a therapeutic target and examine cross-reactivity of the anti-Mala s 1 antibody with human skin. We demonstrate by high pressure freezing electron microscopy and immune-staining that Mala s 1 is located in the cell wall ofM. sympodialisyeast cells. Despite the ability of the anti-Mala s 1 antibody to bind to yeast cells, it did not inhibitM. sympodialisgrowth suggesting Mala s 1 may not be an attractive antifungal target. The Mala s 1 predicted protein sequence was analysedin silicoand was found to contain a motif indicative of a KELCH protein, a group of β-propeller proteins. Humans express a large number of KELCH proteins including some that are localised in the skin. To test the hypothesis that antibodies against Mala s 1 cross react with human skin proteins we examined the binding of anti-Mala s 1 antibody to human skin explant samples. Reactivity with the antibody was visualised in the epidermal layer of skin. To further characterise putative human targets recognised by the anti-Mala s 1 antibody, proteins were extracted from immunoblot gel bands and proteomic analysis performed. Several candidate human proteins were identified. To conclude, we propose that Mala s 1 is a KELCH-like β-propeller protein with similarity to human skin proteins and Mala s 1 recognition may trigger the production of cross-reactive responses that contribute to skin diseases associated withM. sympodialis.
Parabolic avalanche scaling in the synchronization of cortical cell assemblies
Authors: Capek Elliott , Ribeiro Tiago L. , Kells Patrick , Srinivasan Keshav , Miller Stephanie R. , Geist Elias , Victor Mitchell , Vakili Ali , Pajevic Sinisa , Chialvo Dante R. , Plenz Dietmar
Published: November 2022

Neurons in cortex synchronize their spiking in response to local and distant inputs. These synchronized assemblies are fundamental to cortex function, yet basic dynamical aspects about their size and duration are largely unknown. Using 2-photon imaging of neurons in superficial cortex of awake mice, we show that synchronized assemblies organize as scale-invariant avalanches that quadratically grow with duration. This quadratic expansion was found only for correlated neurons and required temporal coarse graining to compensate for spatial subsampling when network dynamics are critical, as demonstrated in simulations. The corresponding time course of an inverted parabola with exponent of χ = 2 described avalanches of up to 5 s duration and maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches.

Significance Statement

The synchronization of cell assemblies is fundamental to many brain theories. Here we show such synchronization to grow according to an inverted parabola that maximizes temporal complexity. This quadratic scaling found for cell assemblies of highly diverse size and duration is in line with prediction for neuronal avalanches and the cortex being in a critical state.
Characterisation of acetogen formatotrophic potential usingE. limosum
Authors: Wood Jamin C. , Gonzalez-Garcia R. Axayacatl , Daygon Dara , Talbo Gert , Plan Manuel R. , Marcellin Esteban , Virdis Bernardino
Published: November 2022

Formate is a promising energy carrier that could be used to transport renewable electricity. Some acetogenic bacteria, such asEubacterium limosum, have the native ability to utilise formate as a sole substrate for growth, which has sparked interest in the biotechnology industry. However, formatotrophic metabolism in acetogens is poorly understood, and a systems-level characterization in continuous cultures is yet to be reported. Here we present the first steady-state dataset forE. limosumformatotrophic growth. At a defined dilution rate of 0.4 d-1, there was a high specific uptake rate of formate (280±56 mmol/gDCW/d), however, most carbon went to CO2(150±11 mmol/gDCW/d). Compared to methylotrophic growth, protein differential expression data and intracellular metabolomics revealed several key features of formate metabolism. Upregulation of pta appears to be a futile attempt of cells to produce acetate as the major product. Instead, a cellular energy limitation resulted in the accumulation of intracellular pyruvate and upregulation of Pfl to convert formate to pyruvate. Therefore, metabolism is controlled, at least partially, at the protein expression level, an unusual feature for an acetogen. We anticipate that formate could be an important one-carbon substrate for acetogens to produce chemicals rich in pyruvate, a metabolite generally in low abundance during syngas growth.
Low-frequency motor cortex EEG predicts four levels of rate of change of force during ankle dorsiflexion
Authors: O’Keeffe Rory , Shirazi Seyed Yahya , Del Vecchio Alessandro , Ibáñez Jaime , Mrachacz-Kersting Natalie , Bighamian Ramin , Rizzo JohnRoss , Farina Dario , Atashzar S. Farokh
Published: November 2022

The movement-related cortical potential (MRCP) is a low-frequency component of the electroencephalography (EEG) signal recorded from the motor cortex and its neighboring cortical areas. Since the MRCP encodes motor intention and execution, it may be utilized as an interface between patients and neurorehabilitation technologies. This study investigates the EEG signal recorded from the Cz electrode to discriminate between four levels of rate of force development (RFD) of the tibialis anterior muscle. For classification, three feature sets were evaluated to describe the EEG traces. These were (i)MRCP morphological characteristicsin theδ-band such as amplitude and timing, (ii)MRCP statistical characteristicsin theδ-band such as mean, standard deviation, and kurtosis, and (iii)wideband time-frequency featuresin the 0.5-90 Hz range. Using a support vector machine for classification, the four levels of RFD were classified with a mean (SD) accuracy of 82% (7%) accuracy when using the time-frequency feature space, and with an accuracy of 75% (12%) when using the MRCP statistical characteristics. It was also observed that some of the key features from the statistical and morphological sets responded monotonically to the intensity of the RFD. Examples are slope and standard deviation in the (0, 1)s window for the statistical, andmin1andminnfor the morphological sets. This monotonical response of features explains the observed performance of theδ-band MRCP and corresponding high discriminative power. Results from temporal analysis considering the pre-movement phase ((-3, 0)s) and three windows of the post-movement phase ((0, 1)s, (1, 2)s, and (2, 3)s)) suggest that the complete MRCP waveform represents high information content regarding the planning, execution, duration, and ending of the isometric dorsiflexion task using the tibialis anterior muscle. Results shed light on the role ofδ-band in translating to motor command, with potential applications in neural engineering systems.
IPLS-LDA: An Improved Partial Least Square Discriminant Analysis for Heterogeneous Transcriptomics and Metabolomics Data Analysis
Authors: Sarkar Snigdha , Shahjaman Md. , Das Sukanta
Published: November 2022

Supervised machine learning (SML) is an approach that learns from training data with known category membership to predict the unlabeled test data. There are many SML approaches in the literature and most of them use a linear score to learn its classifier. However, these approaches fail to elucidate biodiversity from heterogeneous biomedical data. Therefore, their prediction accuracies become low. Partial Least Square Linear Discriminant Analysis (PLS-LDA) is widely used in gene expression (GE) and metabolomics datasets for predicting unlabelled test data. Nevertheless, it also does not consider the non-linearity and heterogeneity pattern of the datasets. Hence, in this study, an improved PLS-LDA (IPLS-LDA) was developed by capturing the heterogeneity of datasets through an unsupervised hierarchical clustering approach. In our approach a non-linear score was calculated by combining all the linear scores obtained from the clustering method. The performance of IPLS-LDA was investigated in a comparison with six frequently used SML methods (SVM, LDA, KNN, Naïve Bayes, RF, PLS-LDA) using one simulation data, one colon cancer gene expression data (GED) and one lung cancer metabolomics datasets. The resultant IPLS-LDA predictor achieved accuracy 0.841 using 10-fold cross validation in colon cancer data and accuracy 0.727 from two independent metabolomics data analysis. In both the cases IPLS-LDA outperformed other SML predictors. The proposed algorithm has been implemented in an R package, Uplsda was given in thehttps://github.com/snotjanu/UplsLda.
Single-cell assessment of trophoblast stem cell-based organoids as human placenta-modeling platforms
Authors: Shannon Matthew J. , McNeill Gina L. , Koksal Burak , Baltayeva Jennet , Wächter Jasmin , Castellana Barbara , Peñaherrera Maria S. , Robinson Wendy P. , Leung Peter C. K. , Beristain Alexander G.
Published: November 2022

The recent discovery of human trophoblast stem cells (hTSC) and techniques allowing for trophoblast organoid (TOrg) culture have established promising approaches for studying human trophoblast development. To validate the accuracy of these models at single-cell resolution, we directly comparedin vitroTOrg cultures derived from primary progenitor cytotrophoblasts (CTB) or commercially available hTSC lines toin vivohuman trophoblasts using a scRNA-seq approach. While patient-derived (PD)- and hTSC-derived TOrgs overall reflect cell differentiation trajectories with accuracy, specific features related to trophoblast state make-up, distinct sub-paths of differentiation, and predicted transcriptional drivers regulating stem cell maintenance were shown to be misaligned in thein vitroplatforms. This is best exemplified by the identification of a distinct progenitor state in hTSC-derived TOrgs that showed characteristics of CTB- and extravillous-like cell states. Together, this work provides a comprehensive resource that identifies underlying strengths and limitations of current TOrg platforms.

Summary Statement

Single-cell transcriptomics provides comprehensive comparison between trophoblast organoids derived from commercially available trophoblast stem cells and first-trimester primary human cytotrophoblasts.

HIGHLIGHTS

An integrated single cell transcriptomic atlas of placental and organoid trophoblasts establishes a comprehensive and public web-based resource

Direct comparison of trophoblasts from placental/decidual tissue to trophoblasts extracted from two distinct organoid platforms highlights both conserved and divergent features

Computational modeling describes novel trophoblast states and routes of cell differentiation in human trophoblast organoids

IN BRIEF

While the merits and utility of current trophoblast organoid cultures have been established, high-resolution assessment and comparison of conserved and divergent features of these systems to cell states and differentiation trajectories of trophoblastsin situorin vitrohas not been performed. Here, Shannon et al. generate a single-cell transcriptomic atlas of two trophoblast organoids that comprehensively define the similarities and discrepancies in relation to trophoblasts from the placental-maternal interface.
The conserved protein WhiA influences branched-chain fatty acid precursors inBacillus subtilis
Authors: Bohorquez Laura C. , de Sousa Joana , Garcia-Garcia Transito , Dugar Gaurav , Wang Biwen , Jonker Martijs J. , Noirot-Gros Marie-Françoise , Lalk Michael , Hamoen Leendert W.
Published: November 2022

The conserved WhiA protein family is present in most Gram-positive bacteria and plays a role in cell division. WhiA contains a DNA-binding motive and has been identified as a transcription factor in actinomycetes. InBacillus subtilis, the absence of WhiA influences cell division and chromosome segregation, however, it is still unclear how WhiA influences these processes, but the protein does not seem to function as transcription factor in this organism. To further investigate the function of WhiA inB. subtilis, we performed a yeast two-hybrid screen to find interaction partners, and a Hi-C experiment to reveal possible changes in chromosome conformation. The latter experiment indicated a reduction in short range chromosome interactions, but how this would affect either cell division or chromosome segregation is unclear. Based on adjacent genes, a role in carbon metabolism was put forward. To study this, we measured exometabolome fluxes during growth on different carbon sources. This revealed that in ΔwhiAcells the pool of branched-chain fatty acid precursors is lower. However, the effect on the membrane fatty acid composition was minimal. Transcriptome data could not link the metabolome effects to gene regulatory differences.

IMPORTANCE

WhiA is a conserved DNA binding protein that influences cell division and chromosome segregation in the Gram-positive model bacteriumB. subtilis. The molecular function of WhiA is still unclear, but a previous study has suggested that the protein does not function as a transcription factor. In this study, we used yeast two-hybrid screening, chromosome conformation capture analysis, metabolomics, transcriptomics and fatty acid analysis to obtain more information about the workings of this enigmatic protein.
Cell-density regulated adhesins contribute to early disease development and adhesion inRalstonia solanacearum
Authors: Carter Mariama D. , Khokhani Devanshi , Allen Caitilyn
Published: November 2022

Adhesins (adhesive proteins) help bacteria stick to and colonize diverse surfaces and often contribute to virulence. The genome of the bacterial wilt pathogenRalstonia solanacearum(Rs) encodes dozens of putative adhesins, some of which are upregulated during plant pathogenesis. Little is known about the role of these proteins in bacterial wilt disease. During tomato colonization, three putativeRsadhesin genes were upregulated in a ΔphcAquorum sensing mutant that cannot respond to high cell densities:radA(Ralstoniaadhesin),rcpA(Ralstoniacollagen-likeprotein), andrcpB. Based on this differential gene expression, we hypothesized that adhesins repressed by PhcA contribute to early disease stages whenRsexperiences a low cell density. During root colonizationRsupregulatedrcpAandrcpB, but notradA, relative to bacteria in the stem at mid-disease. Root attachment assays and confocal microscopy with ΔrcpA/Band ΔradArevealed that all three adhesins helpRsattach to tomato seedling roots. Biofilm assays on abiotic surfaces found thatRsdoes not require RadA, RcpA, or RcpB for interbacterial attachment (cohesion), but these proteins are essential for anchoring aggregates to a surface (adhesion). However,Rsdid not require the adhesins for later disease stagesin planta, including colonization of the root endosphere and stems. Interestingly, all three adhesins were essential for full competitive fitnessin planta. Together, these infection stage-specific assays identified three proteins that contribute to adhesion and the critical first host-pathogen interaction in bacterial wilt disease.

Importance

Every microbe must balance its need to attach to surfaces with the biological imperative to move and spread. The high-impact plant pathogenic bacteriumRalstonia solanacearumcan stick to biotic and abiotic substrates, presumably using some of the dozens of putative adhesins encoded in its genome. We confirmed the functions and identified the biological roles of several afimbrial adhesins. By assaying the competitive fitness and the success of adhesin mutants in three individual plant compartments, we identified the specific disease stages and host tissues where three previously cryptic adhesins contribute to bacterial success. Combined with tissue-specific regulatory data, this work indicates thatR. solanacearumdeploys distinct adhesins that help it succeed at different stages of plant pathogenesis.

Research Areas

Plant Microbiology, Host-Microbial Interactions, Microbial Pathogenesis
Identification of NAD-RNAs and ADPR-RNA decapping in the archaeal model organismsSulfolobus acidocaldariusandHaloferax volcanii
Authors: Gomes-Filho José Vicente , Breuer Ruth , Morales-Filloy Hector Gabriel , Pozhydaieva Nadiia , Borst Andreas , Paczia Nicole , Soppa Jörg , Höfer Katharina , Jäschke Andres , Randau Lennart
Published: November 2022

NAD is a coenzyme central to metabolism that was also found to serve as a 5’-terminal cap of bacterial and eukaryotic RNA species. The presence and functionality of NAD-capped RNAs (NAD-RNAs) in the archaeal domain remain to be characterized in detail. Here, by combining LC-MS and NAD captureSeq methodology, we quantified the total levels of NAD-RNAs and determined the identity of NAD-RNAs in the two model archaea,Sulfolobus acidocaldariusandHaloferax volcanii. A complementary differential RNA-Seq (dRNA-Seq) analysis revealed that NAD transcription start sites (NAD-TSS) correlate with well-defined promoter regions and often overlap with primary transcription start sites (pTSS). The population of NAD-RNAs in the two archaeal organisms shows clear differences, withS. acidocaldariuspossessing more capped small non-coding RNAs (sncRNAs) and leader sequences. The NAD-cap did not prevent 5’→3’ exonucleolytic activity by the RNase Saci-aCPSF2. To investigate enzymes that facilitate the removal of the NAD-cap, four Nudix proteins ofS. acidocaldariuswere screened. None of the recombinant proteins showed NAD decapping activity. Instead, the Nudix protein Saci_NudT5 showed activity after incubating NAD-RNAs at elevated temperatures. Hyperthermophilic environments promote the thermal degradation of NAD into the toxic product ADPR. Incorporating NAD into RNAs and the regulation of ADPR-RNA decapping by Saci_NudT5 is proposed to provide additional layers of maintaining stable NAD levels in archaeal cells.

Importance

This study reports the first characterization of 5’-terminally modified RNA molecules in Archaea and establishes that NAD-RNA modifications, previously only identified in the other two domains of life, are also prevalent in the archaeal model organismsSulfolobus acidocaldariusandHaloferax volcanii. We screened for NUDIX hydrolases that could remove the NAD-RNA cap and showed that none of these enzymes removed NAD modifications, but we discovered an enzyme that hydrolyzes ADPR-RNA. We propose that these activities influence the stabilization of NAD and its thermal degradation to potentially toxic ADPR products at elevated growth temperatures.