bluuebunny/crossref_metadata_2025 huggingface dataset:
Biopsy of the Parietal Branch of the Superficial Temporal Artery for the Diagnosis of Giant Cell Arteritis
Authors: Elahi Ebby , Afshin Evan E. , Zoltan Susan , Hu Karen Y.
Published: June 2022

Background:

Biopsy of the superficial temporal artery (STA) is central to the diagnosis of giant cell arteritis (GCA), but determining the ideal biopsy site along the course of the STA continues to be a challenge. Traditionally, the frontal branch or preauricular region of the STA is biopsied because of their accessibility, but biopsy at these locations can produce visible cosmetic defects and social disruption that can be distressing to patients, as well as increase the likelihood of adverse events such as injury to the facial nerve. The authors describe a surgical technique of biopsy of the parietal branch of the STA to improve the patient's perioperative and postoperative experience.

Methods:

In this retrospective review, 24 patients with clinical suspicion of GCA who underwent biopsy of the parietal branch of the STA were identified. Patients underwent mapping of the branches of the STA with Doppler ultrasound before the procedure. Biopsy of the parietal branch of the STA was conducted using a CO2 laser.

Results:

Twenty-four patients underwent biopsy of the parietal branch of the STA. Two patients were diagnosed on histopathology with GCA. All patients tolerated the procedure well and without complications.

Conclusion:

Application of preoperative Doppler ultrasound mapping, use of a CO2 laser for incisions and hemostasis, and selection of the parietal branch allowed for improved cosmetic outcomes, no associated adverse events, and improved overall patient experience. The authors advocate biopsy of the parietal branch of the superficial temporal artery for the diagnosis of GCA in the absence of contraindications.
Multi-Platform Proteomic Analysis of Alzheimer’s Disease Cerebrospinal Fluid and Plasma Reveals Network Biomarkers Associated with Proteostasis and the Matrisome
Authors: Dammer Eric B. , Ping Lingyan , Duong Duc M. , Modeste Erica S. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Johnson Erik C.B.
Published: June 2022

Robust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects using three different proteomic platforms—SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry—to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r∼0.7) and plasma (r∼0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-β deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than 7000 protein measurements in CSF and 9500 protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development.
Multimodal single-cell analysis of non-random heteroplasmy distribution in human retinal mitochondrial disease
Authors: Mullin Nathaniel K , Voigt Andrew P , Flamme-Wiese Miles J , Liu Xiuying , Riker Megan J , Varzavand Katayoun , Stone Edwin M , Tucker Budd A , Mullins Robert F
Published: June 2022

Variants within the high copy number mitochondrial genome (mtDNA) can disrupt organelle function and lead to severe multi-system disease. The wide range of manifestations observed in mitochondrial disease patients results from varying fractions of abnormal mtDNA molecules in different cells and tissues, a phenomenon termed heteroplasmy. However, the landscape of heteroplasmy across cell types within tissues and its influence on phenotype expression in affected patients remains largely unexplored. Here, we identify non- random distribution of a pathogenic mtDNA variant across a complex tissue using single-cell RNA sequencing, mitochondrial single-cell ATAC sequencing, and multimodal single-cell sequencing. We profile the transcriptome, chromatin accessibility state, and heteroplasmy in cells from the eyes of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and healthy control donors. Utilizing the retina as a model for complex multi-lineage tissues, we found that the proportion of the pathogenic m.3243A>G allele was neither evenly nor randomly distributed across diverse cell types. All neuroectoderm- derived neural cells exhibited a high percentage of the mutant variant. However, a subset of mesoderm- derived lineage, namely the vasculature of the choroid, was near homoplasmic for the wildtype allele. Gene expression and chromatin accessibility profiles of cell types with high and low proportions of m.3243A>G implicate mTOR signaling in the cellular response to heteroplasmy. We further found by multimodal single-cell sequencing of retinal pigment epithelial cells that a high proportion of the pathogenic mtDNA variant was associated with transcriptionally and morphologically abnormal cells. Together, these findings show the non- random nature of mitochondrial variant partitioning in human mitochondrial disease and underscore its implications for mitochondrial disease pathogenesis and treatment.
Prediction of representative phenotypes using Multi-Attribute Subset Selection
Authors: Herbst Konrad , Wang Taiyao , Forchielli Elena J. , Thommes Meghan , Paschalidis Ioannis Ch. , Segrè Daniel
Published: June 2022

The interpretation of complex biological datasets requires the identification of representative variables that describe the data without critical information loss. This is particularly important in the analysis of large phenotypic datasets (“phenomics”). We introduce Multi-Attribute Subset Selection (MASS), an algorithm which separates a matrix of phenotypes (e.g., yield across microbial species and environmental conditions) into predictor and response sets of conditions. Using mixed integer linear programming, MASS expresses the response conditions as a linear combination of the predictor conditions, while simultaneously searching for the optimally descriptive set of predictors. We applied the algorithm to three microbial datasets and identified environmental conditions that predict phenotypes under other conditions, providing biologically interpretable axes for strain discrimination. MASS could be used to reduce the number of experiments needed to identify species or to map their metabolic capabilities. The generality of the algorithm allows addressing subset selection problems in areas beyond biology.
A new cortical parcellation based on systematic review of primate anatomical tracing studies on corticostriatal projections
Authors: Dinh Tovy , Nerland Stener , Maximov Ivan I. , Barth Claudia , Vernon Anthony C. , Agartz Ingrid , Jørgensen Kjetil Nordbø
Published: June 2022

Corticostriatal projections form the input level of a circuitry that connects the cerebral cortex, basal ganglia, and thalamus. Three distinct, functional subcircuits exist according to the tripartite model: Sensorimotor cortices projecting mainly to the dorsolateral striatum; associative cortices projecting to the dorsomedial striatum and limbic cortices projecting to the ventral striatum. However, there is to date no atlas that allows researchers to label cortical projection areas belonging to each of these subcircuits separately.

To address this research gap, the aim of this study was threefold: First, to systematically review anatomical tracing studies that focused on corticostriatal projections in non-human primates, and to classify their findings according to the tripartite model. Second, to develop an atlas of the human cerebral cortex based on this classification. Third, to test the hypothesis that labels in this atlas show structural connectivity with specific striatal subregions in humans using diffusion-based tractography in a sample of 24 healthy participants.

In total, 98 studies met the inclusion criteria for our systematic review. Information about projections from the cortex to the striatum was systematically extracted by Brodmann area, and cortical areas were classified by their dominant efferent projections. Taking known homological and functional similarities and differences between non-human primate and human cortical regions into account, a new human corticostriatal projection (CSP) atlas was developed. Using human diffusion-based tractography analyses, we found that the limbic and sensorimotor atlas labels showed preferential structural connectivity with the ventral and dorsolateral striatum, respectively. However, the pattern of structural connectivity for the associative label showed the greatest degree of overlap with other labels.

We provide this new atlas as a freely available tool for neuroimaging studies, where it allows for the first-time delineation of anatomically informed regions-of-interest to study functional subcircuits within the corticostriatal circuitry. This tool will enable specific investigations of subcircuits involved in the pathogenesis of neuropsychiatric illness such as schizophrenia and bipolar disorders.

Highlights

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Systematic review of anatomical projections from the cerebral cortex to the striatum in non-human primates.

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Development of a novel cortical atlas for use in neuroimaging studies focusing on the corticostriatal brain circuitry.

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Tractography in human diffusion-weighted imaging data to test if associative, limbic, and sensorimotor cortical atlas labels show preferential connectivity to regions within the striatum.
Covariations of cerebral blood volume and single neurons discharge during resting state and behavioral visual cognitive tasks in non-human primates
Authors: Claron Julien , Provansal Matthieu , Salardaine Quentin , Tissier Pierre , Dizeux Alexandre , Deffieux Thomas , Picaud Serge , Tanter Mickael , Arcizet Fabrice , Pouget Pierre
Published: June 2022

To better understand how the brain allows primates to perform various set of tasks, the ability to simultaneously record the activity of the brain at multiple temporal and spatial scales is challenging but necessary. In non-human primates, combined fMRI and electrophysiological recordings have not disentangle the contributions of spiking activity to the neurovascular response. Here, we combined functional ultrasound imaging (fUS) of cerebral blood volume (CBV) and recording of single-unit activities (SUA) in visual and fronto-medial cortices of behaving macaques. We computed task-induced and SUA-induced CBV activation maps. We demonstrate that SUA provides a significant estimate of the neurovascular response below the typical fMRI voxel spatial resolution of 2mm3. Furthermore, our results also show that single unit and CBV activities are statistically uncorrelated during the resting states but correlate during behaving tasks. Conversely, during the resting states, CBV activities across known connected brain areas are correlated but decorrelate at the onset of the tasks as expected if participating in the default mode network (DMN). These results have important implications for interpreting functional imaging findings collected with fMRI or fUS while one constructs inferences of spiking activities during resting-state or while primates perform tasks.
Social isolation produces a brain-region specific expansion of microglia structure and reorganization of neural activity
Authors: Vu Alex P. , Lam David , Denney Cayla , Lee Kelly V. , Plemel Jason R. , Jackson Jesse
Published: June 2022

Social isolation is a profound form of psychological stress that impacts the mental health of a large proportion of society. Other experimental models of stress and injury have demonstrated microglia activation and alterations in neural activity. Microglia and neural activity undergo coordinated changes under physiological and pathological states. However, the effect of social isolation on microglia and neural activity has not been thoroughly investigated. Here we show that the dorsal medial hypothalamus and hippocampal CA2 region of male mice undergo an increased microglia volume and branching following social isolation, whereas females exhibit this increase in the hypothalamus only. The prefrontal cortex, central amygdala, nucleus accumbens shell, and visual cortex did not exhibit changes in microglia structure in either male or female mice. The home cage resting level of neural activity, as measured by the immediate early gene c-fos, was reduced in CA2 and the prefrontal cortex of female but not male mice following isolation. However, the co-variation in neural activity across brain regions was abolished in male but not female isolated mice. These data show that different brain regions undergo independent and dissociable changes in microglia structure and network activity following social isolation which may account for changes in cognition and behavior associated with this form of psychological stress.
Surface Acoustic Wave Integrated Microfluidics for Repetitive and Reversible Temporary Immobilization of C. elegans
Authors: Sridhar Nakul , Fajrial Apresio Kefin , Doser Rachel , Hoerndli Frederic , Ding Xiaoyun
Published: June 2022

Caenorhabditis elegans is an important genetic model for neuroscience studies due to its unique combination of genetics, transparency, complete synaptic connectome, and well-characterized behaviors. These factors, in turn, enable analyses of how genes control connectivity, neuronal function, and behavior. To date, however, most studies of neuronal function in C. elegans are incapable of performing microscopy imaging with subcellular resolution and behavior analysis in the same set of animals. This constraint stems from the immobilization requirement for high-resolution imaging that is incompatible with behavioral analysis. In particular, conventional immobilization methods often lead to either irreversible, partial, or slowly reversible immobilization of animals preventing a multiplexed approach. Here, we present a novel microfluidic device that uses surface acoustic waves (SAW) as a non-contact method to temporarily immobilize worms for a short period (40 seconds). This device allows non-invasive analysis of swimming behavior and high-resolution synaptic imaging in the same animal. In addition, because of the low impact of this SAW approach, the device enables fast, repeated imaging of single neurons and behavior in the same animals for three to four days. We anticipate that this device will enable longitudinal analysis of animal motility and subcellular morphological changes during development and ageing in C. elegans.
DeepAction: A MATLAB toolbox for automated classification of animal behavior in video
Authors: Harris Carl , Finn Kelly R. , Tse Peter U.
Published: June 2022

The identification of behavior in video is a critical but time-consuming component in many areas of animal behavior research. Here, we introduce DeepAction, a deep learning-based toolbox for automatically annotating animal behavior in video. Our approach uses features extracted from raw video frames by a pretrained convolutional neural network to train a recurrent neural network classifier. We evaluate the classifier on two benchmark rodent datasets and show that it achieves high accuracy, requires little training data, and surpasses both human agreement and similar existing methods. We also create a confidence score for classifier output, and show our method provides an accurate estimate of classifier performance and reduces the time required by human annotators to review and correct automatically-produced annotations. We release our system and accompanying annotation interface as an adaptable, non-technical, and open-source MATLAB toolbox.
A novel MRI-based three-dimensional model of stomach volume, surface area and geometry in response to gastric filling and emptying
Authors: Bertoli D , Mark EB , Liao D , Brock C , Frøkjær JB , Drewes AM
Published: June 2022

Background

Gastric motility and accommodation have a critical role in maintaining normal gastrointestinal homeostasis. Different modalities can be adopted to quantify those processes, i.e., scintigraphy to measure emptying time and intragastric Barostat for accommodation assessment. However, magnetic resonance imaging (MRI) can assess the same parameters non-invasively without ionizing radiation. Our study aimed to develop a detailed three-dimensional (3D) MRI model of the stomach to describe gastric volumes, surface areas, wall tension distribution, and inter-observer agreement.

Methods

Twelve healthy volunteers underwent an MRI protocol of six axial T2-weighted acquisitions. Each dataset was used to construct a 3D model of the stomach: Firstly, the volumes of the whole stomach, gastric liquid, and air were segmented. After landmark placing, a raw 3D model was generated from segmentation data. Subsequently, irregularities were removed, and the model was divided into compartments. Finally, surface area and 3D geometry parameters (inverse curvatures) were extracted. The inverse curvatures were used to as a proxy for wall tension distribution without measuring the intragastric pressure.

Key Results

The model was able to describe changes in volume and surface geometry for each compartment with a distinct pattern in response to filling and emptying. The surface tension was distributed non-homogeneously between compartments and showed dynamical changes at various time points.

Conclusion & Inferences

The presented model offers a detailed tool for evaluating gastric volumes, surface geometry, and wall tension in response to filling and emptying and will provide insights into gastric emptying and accommodation in diseases such as diabetic gastroparesis.

KEY POINTS

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While MRI and ultrasound are getting progressively accepted as methods for evaluating gastric emptying and accommodation, they still do not provide essential insights into those processes.

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This study presents a three-dimensional stomach model able to report volume and surface data, and to describe the distribution of the gastric wall tension of gastric compartments by applying the Young-Laplace law.

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We observed that volumes and surface geometry showed distinct emptying patterns in each compartment and that the wall geometry distributed non-homogeneously in the stomach, showing different dynamical changes during the emptying phase. Our observations indicate the fundus as essential in the first phase of digestion, confirming its role as reservoir.

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The non-invasive model has the potential to give detailed information about the gastric volumes and surface geometry in response to filling and emptying, with the potential to understand the pathophysiology and improve treatment in patients with gastroparesis.

GRAPHICAL ABSTRACT
The unfolded protein response transcription factor XBP1s ameliorates Alzheimer’s disease by improving synaptic function and proteostasis
Authors: Duran-Aniotz Claudia , Rivera-Krstulovic Catalina , Poblete Natalia , Ardiles Álvaro O. , Li Díaz Mei , Sabusap Carleen Mae P. , Gerakis Yannis , Miranda Felipe Cabral , Diaz Javier , Fuentealba Matias , Muñoz Ernesto , Espinoza Sandra , Martinez Gabriela , Quiroz Gabriel , Tamburini Giovanni , Medinas Danilo B. , Contreras Darwin , Piña Ricardo , Lourenco Mychael V. , Ribeiro Felipe C. , Ferreira Sergio T. , Rozas Carlos , Morales Bernardo , Plate Lars , Gonzalez-Billault Christian , Palacios Adrian G. , Hetz Claudio
Published: June 2022

Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer’s disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol requiring enzyme-1 (IRE1) is an ER-located kinase and endoribonuclease that operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-Box binding protein 1 (XBP1). A polymorphism in the XBP1 promoter has been suggested as a risk factor for AD. To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in neurons using preclinical models. Overexpression of an active form of XBP1 in the nervous system using transgenic mice significantly reduced the load of amyloid deposits in the cerebral cortex and hippocampus and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an AD mice using adeno-associated vectors improved long-term potentiation, memory performance, and dendritic spine density. Quantitative proteomics of the hippocampus revealed that XBP1 expression corrects a large proportion of the alterations observed in the 5xFAD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.
Ancient electrogenic survival metabolism of β -proteobacterial ammonia oxidizers for oxygen deficiency
Authors: Gülay Arda , Fournier Greg , Smets Barth F. , Girguis Peter R.
Published: June 2022

Oxygen availability is critical for microbes as some are obligatorily dependent on oxygen for energy conservation. However, aerobic microbes that live in environments with varying oxygen concentrations experience pressures over evolutionary time, selecting alternative energy metabolisms that relax the dependence on oxygen. One such capacity is extracellular electron transfer (or EET), which is the ability to transfer electrons from central metabolism to extracellular oxidants such as iron and manganese oxides. We posit that the β-proteobacterial ammonia-oxidizing bacteria, highly specialized lineages heretofore recognized as strict aerobes, can be capable of EET as they have been constantly observed in oxygen-limiting and depleted environments. Here, we show that a strictly aerobic ammonia-oxidizer, Nitrosomonas communis, utilized a poised electrode to maintain metabolic activity in anoxic conditions. The presence and activity of multi-heme cytochromes suggested that direct electron transfer is the mechanism underlying EET. Molecular clock models suggest that the ancestors of β-proteobacterial ammonia oxidizers appeared after the oxygenation of Earth when the oxygen levels were >10-4pO2 (PAL), suggesting their aerobic origins. Phylogenetic reconciliations of gene and species trees show that the multi-heme c-type EET proteins in Nitrosomonas and Nitrosospira were acquired by gene transfer from β-proteobacteria during oxygen scarcity. The preservation of EET metabolism over billions of years under fluctuating oxygen levels and aspects of EET physiology in β-proteobacterial ammonia oxidizers might explain how they have been coped with oxygen stress and survived under oxygen deprivation.

SIGNIFICANCE

Metabolic versatility can permit typically aerobic microbes to survive in anaerobic conditions when oxygen is deficient as a terminal electron acceptor. This article demonstrates a previously unidentified anaerobic extracellular electron transfer metabolism that operates in aerobic β–proteobacterial ammonia oxidizers and reconstructs the evolutionary history of this metabolism, linking it to the early history of Earth’s oxygenation. Our approach contributes to the understanding of metabolisms in the N-cycle and their evolution on Earth, as well as how aerobic microbes manage to retain energy generation under oxygen-limiting or depleted conditions.

AUTHOR CONTRIBUTIONS

AG designed the physiological research with PRG and the phylogenetic research with GF; AG performed the research, AG analyzed the data with PRG and GF. AG wrote the paper, and all authors edited and approved the manuscript.
Trajectories for the evolution of bacterial CO2-concentrating mechanisms
Authors: Flamholz Avi I. , Dugan Eli , Panich Justin , Desmarais John J. , Oltrogge Luke M. , Fischer Woodward W. , Singer Steven W. , Savage David F.
Published: June 2022

Cyanobacteria rely on CO2 concentrating mechanisms (CCMs) that depend on ≈15 genes to produce two protein complexes: an inorganic carbon (Ci) transporter and a 100+ nm carboxysome compartment that encapsulates rubisco with a carbonic anhydrase (CA) enzyme. Mutations disrupting CCM components prohibit growth in today’s atmosphere (0.04% CO2), indicating that CCMs evolved to cope with declining environmental CO2. Indeed, geochemical data and models indicate that atmospheric CO2 has been generally decreasing from high concentrations over the last ≈3.5 billion years. We used a synthetic reconstitution of a bacterial CCM in E. coli to study the co-evolution of CCMs with atmospheric CO2. We constructed strains expressing putative ancestors of modern CCMs — strains lacking one or more CCM components — and evaluated their growth in a variety of CO2 concentrations. Partial forms expressing CA or Ci uptake genes grew better than controls in intermediate CO2 levels (≈1%); we observed similar phenotypes in genetic studies of two autotrophic bacteria, H. neapolitanus and C. necator. To explain how partial CCMs improve growth, we advance a model of co-limitation of autotrophic growth by CO2 and HCO3-, as both are required to produce biomass. Our model and results delineated a viable trajectory for bacterial CCM evolution where decreasing atmospheric CO2 induces an HCO3- deficiency that is alleviated by acquisition of CAs or Ci uptake genes, thereby enabling the emergence of a modern CCM. This work underscores the importance of considering physiology and environmental context when studying the evolution of biological complexity.

Significance

The greenhouse gas content of the ancient atmosphere is estimated using models and measurements of geochemical proxies. Some inferred high ancient CO2 levels using models of biological CO2 fixation to interpret the C isotopes found in preserved organic matter. Others argued that elevated CO2 could reconcile a faint young Sun with evidence for liquid water on Earth. We took a complementary “synthetic biological” approach to understanding the composition of the ancient atmosphere by studying present-day bacteria engineered to resemble ancient autotrophs. By showing that it is simpler to rationalize the emergence of modern bacterial autotrophs if CO2 was once high, these investigations provided independent evidence for the view that CO2 concentrations were significantly elevated in the atmosphere of early Earth.
Response of sugarcane rhizosphere soil fungal communities on a temporal gradient to changes in critical growth periods
Authors: Yuan Zhaonian , Liu Qiang , Pang Ziqin , Liu Yueming , Nyumah Fallah , Hu Chaohua , Lin Wenxiong
Published: June 2022

Understanding the normal variation of the sugarcane rhizosphere fungal microbiota throughout its life cycle is essential for the development of agricultural practices for fungal diseases (e.g., sugarcane tip rot, sugarcane red rot, and sugarcane smut) and ecological health associated with the microbiota. Therefore, we performed high-throughput sequencing of 18S rDNA of soil samples using the Illumina sequencing platform for correlation analysis of sugarcane rhizosphere microbiota time series, covering information from 84 samples in four growth periods. The results revealed that the sugarcane rhizosphere fungi possessed the maximum fungal richness in July (Tillering). Rhizosphere fungi are closely associated with sugarcane growth, including Ascomycota, Basidiomycota, and Ochrophyta showed high abundance in a stage-specific manner. Through the Manhattan plots, 11 fungal genera were found to show a decreasing trend throughout the sugarcane growth period, and two fungal genera were significantly enriched at three stages of sugarcane growth (p < 0.05) including Pseudallescheria and Nectriaceae. In addition, soil pH, soil temperature (Tem), total nitrogen (TN) and total potassium (TP) were important drivers of fungal community structure at different stages of sugarcane growth. Using structural equation modeling (SEM) found that sugarcane disease status showed a significant and strong negative effect with selected soil properties, suggesting that poor soil may increase the likelihood of sugarcane disease. In addition changes in sugarcane rhizosphere community structure over time were mainly influenced by stochastic factors, but the contribution decreased to the lowest value after the sugarcane root adaptation system was stabilized (Maturity).

IMPORTANCE

Rhizosphere microbes are closely related to plant growth, and more studies have shown that the rhizosphere fungal microbial community has an important influence on plant health and growth status. However, little is known about the response of the rhizosphere fungal community to plant growth during the critical plant reproductive period. In this study, we analyzed the important response of the rhizosphere fungal community of sugarcane through the pattern of abundance changes in its critical growth nodes by various methods to investigate the subtle changes in the assembly of the rhizosphere fungal community with the growth of sugarcane. Our work provides innovative ideas for the prevention of soil-borne diseases in plants and also provides a solid basis for the development of microbial models of crops rhizosphere soil.
Ratchet, swivel, tilt and roll: A complete description of subunit rotation in the ribosome
Authors: Hassan Asem , Byju Sandra , Freitas Frederico Campos , Roc Claude , Pender Nisaa , Nguyen Kien , Kimbrough Evelyn M. , Mattingly Jacob , Gonzalez Ruben L. , de Oliveira Ronaldo Junio , Dunham Christine M. , Whitford Paul C.
Published: June 2022

Protein synthesis by the ribosome involves large-scale rearrangements of the “small” subunit (SSU; ∼1 MDa), which include inter- and intra-subunit rotational motions. With more than 1000 structures of ribosomes and ribosomal subunits now publicly available, it is becoming increasingly difficult to design precise experiments that are based on a comprehensive analysis of all known rotation states. To overcome this limitation, we present the Ribosome Angle Decomposition (RAD) method, where the orientation of each small subunit head and body is described in terms of three angular coordinates (rotation, tilt and tilt direction) and a single translation. To demonstrate the utility of the accompanying software (RADtool) we applied it to all published ribosome and mitoribosome structures. This identified and analyzed 1077 fully-assembled ribosome complexes, as well as 280 isolated small subunits from 48 organisms. The RAD approach quantitatively distinguishes between previously described qualitative rotational features, determines when rotation-only descriptions are insufficient, and shows that tilt-like rearrangements of the SSU head and body are pervasive in both prokaryotic and eukaryotic ribosomes. Together, the presented database and technique provide a robust platform for systematically analyzing, visualizing, and comparing subunit orientations of ribosomes from all kingdoms of life. Accordingly, the RAD resource establishes a common foundation with which structural, simulation, single-molecule and biochemical efforts can precisely interrogate the dynamics of this prototypical molecular machine.
Navigation task and action space drive the emergence of egocentric and allocentric spatial representations
Authors: Vijayabaskaran Sandhiya , Cheng Sen
Published: June 2022

In general, strategies for spatial navigation could employ one of two spatial reference frames: egocentric or allocentric. Notwithstanding intuitive explanations, it remains unclear however under what circumstances one strategy is chosen over another, and how neural representations should be related to the chosen strategy. Here, we first use a deep reinforcement learning model to investigate whether a particular type of navigation strategy arises spontaneously during spatial learning without imposing a bias onto the model. We then examine the spatial representations that emerge in the network to support navigation. To this end, we study two tasks that are ethologically valid for mammals – guidance, where the agent has to navigate to a goal location fixed in allocentric space, and aiming, where the agent navigates to a visible cue. We find that when both navigation strategies are available to the agent, the solutions it develops for guidance and aiming are heavily biased towards the allocentric or the egocentric strategy, respectively, as one might expect. Nevertheless, the agent can learn both tasks using either type of strategy. Furthermore, we find that place-cell-like allocentric representations emerge preferentially in guidance when using an allocentric strategy, whereas egocentric vector representations emerge when using an egocentric strategy in aiming. We thus find that alongside the type of navigational strategy, the nature of the task plays a pivotal role in the type of spatial representations that emerge.
Rotations improve the diversity of rhizosphere soil bacterial communities, enzyme activities and tomato yield
Authors: Feng Cui , Yi Zhengwei , Qian Wei , Liu Huiying , Jiang Xiaosan
Published: June 2022

The use of rotations is an effective strategy to control crop diseases and improve plant health. The soil bacterial communities in the rhizosphere are highly important for maintaining soil productivity. However, the composition and structure of soil bacterial communities in the rotations of vegetable crops remain unclear. In this study, we explored the bacterial diversity and community structure of the tomato rhizosphere, including enzyme activities, yield, and fruit quality, under three different cropping systems: tomato-tomato continuous cropping (TY1), eggplant-tomato (S. melongena) rotation (TY2) and arrowhead-tomato (Sagittaria trifolia-Solanum lycopersicum) rotation (TY3). The composition and diversity of the rhizosphere bacterial communities differed significantly. The diversity was more in the TY2 and TY3 treatments than those in the TY1 treatment. Chujaibacter and Rhodanobacter were two predominant and unique strains detected only in TY1, while the relative abundances of Curvibacter and Luteimonas were the highest in TY2 and TY3, respectively. Moreover, Lysobacterium was a relatively abundant type of biocontrol bacterium found only in the TY3 treatment, which could contribute to alleviating the obstacle of tomato continuous cropping. Compared with the TY1 treatment, the activities of catalase were significantly higher in the TY2 and TY3 treatments. In addition, compared with TY1, the TY2 and TY3 plots increased the following parameters: tomato yields by 24–46%, total soluble solids by 37-93%, total organic acid by 10-15.7% and soluble protein by 10-21%, while the content of nitrate was significantly reduced by 23%. Altogether, compared with the tomato monoculture, the rotations of tomato with eggplant and arrowhead shifted the rhizosphere bacterial communities and improved the yield and quality of the vegetables. Moreover, a tomato rotation, particularly with arrowhead, was an effective way to alleviate the obstacles of continuous cropping.
Identification of Circular Dorsal Ruffles as Signal Platforms for the AKT pathways in Glomerular Podocytes
Authors: Hua Rui , Torres Mauricio , Wei Jinzi , Sun Xiaowei , Wang Li , Inoki Ken , Yoshida Sei
Published: June 2022

Circular dorsal ruffles (CDRs) are rounded membrane ruffles induced by growth factors to function as precursors of the large-scale endocytosis called macropinocytosis. In cell line systems, CDR/macropinocytosis regulate the AKT-mTORC1 pathway, a canonical growth factor signaling. However, it is not known if this mechanism occurs in tissues. Here, utilizing ultra-high-resolution scanning electron microscopy, we report that CDRs are expressed in glomerular podocytes ex vivo and in vivo. Biochemical and imaging analysis revealed that AKT phosphorylation is localized to CDRs upstream of mTORC1 activation in podocyte cell line and isolated glomeruli, indicating that CDRs function as signal platforms for AKT-mTORC1 pathway in podocytes to maintain the kidney function. Because mTORC1 has critical roles in the podocyte metabolism and the aberrant activation of mTORC1 triggers podocytopathies, these results suggest that targeting CDR formation would be a potential therapeutic approach for the diseases.
ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia
Authors: Kreider-Letterman Gabriel , Castillo Abel , Mahlandt Eike K. , Goedhart Joachim , Rabino Agustin , Goicoechea Silvia , Garcia-Mata Rafael
Published: June 2022

Invadopodia formation is regulated by Rho GTPases. However, the molecular mechanisms that control Rho GTPase signaling at invadopodia remain poorly understood. Here, we have identified ARHGAP17, a Cdc42-specific RhoGAP, as a key regulator of invadopodia in breast cancer cells and by RhoGAPs characterized a novel ARHGAP17-mediated signaling pathway that controls the spatiotemporal activity of Cdc42 during invadopodia turnover. Our results show that during invadopodia assembly, ARHGAP17 localizes to the invadopodia ring and restricts the activity of Cdc42 to the invadopodia core, where it promotes invadopodia growth. Invadopodia disassembly starts when ARHGAP17 translocates from the invadopodia ring to the core, in a process that is mediated by its interaction with the Cdc42 effector CIP4. Once at the core, ARHGAP17 inactivates Cdc42 to promote invadopodia disassembly. Our results in invadopodia provide new insights on the coordinated transition between the activation and inactivation of Rho GTPases.
Genetic risk factors associated with SARS-CoV-2 susceptibility in multiethnic populations
Authors: Sriram Aditya Dandapani
Published: June 2022

Susceptibility to infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes the disease COVID-19, may be understood more clearly by looking at genetic variants and their associations to susceptibility phenotype. I conducted a genome-wide association study of SARS-CoV-2 susceptibility in a multiethnic set of three populations (European, African, and South Asian) from a UK BioBank clinical and genomic dataset. I estimated associations between susceptibility phenotype and genotyped or imputed SNPs, adjusting for age at enrollment, sex, and the ten top principal components of ancestry. Three genome-wide significant loci and their top associated SNPs were discovered in the European ancestry population: SLC6A20 in the chr3p21.31 locus (rs73062389-A; P = 2.315 × 10-12), ABO on chromosome 9 (rs9411378-A; P = 2.436 × 10-11) and LZTFL1 on chromosome 3 (rs73062394; P = 4.4 × 10-11); these SNPs were not found to be significant in the African and South Asian populations. A multiethnic GWAS may help elucidate further insights into SARS-CoV-2 susceptibility.
Cell and chromatin transitions in intestinal stem cell regeneration
Authors: Singh Pratik N.P. , Madha Shariq , Leiter Andrew B. , Shivdasani Ramesh A.
Published: June 2022

The progeny of intestinal stem cells (ISCs) dedifferentiate in response to ISC attrition. The precise cell sources, transitional states, and chromatin remodeling behind this activity remain unclear. In the skin, stem cell recovery after injury preserves an epigenetic memory of the damage response; whether similar memories arise and persist in regenerated ISCs is not known. We addressed these questions by examining gene activity and open chromatin at the resolution of single Neurog3-labeled mouse intestinal crypt cells, hence deconstructing forward and reverse differentiation of the intestinal secretory (Sec) lineage. We show that goblet, Paneth, and enteroendocrine cells arise by multilineage priming in common precursors, followed by selective access at thousands of cell-restricted cis-elements. Selective ablation of the ISC compartment elicits speedy reversal of chromatin and transcriptional features in large fractions of precursor and mature crypt Sec cells without obligate cell cycle re-entry. ISC programs decay and reappear along a cellular continuum lacking discernible discrete interim states. In the absence of gross tissue damage, Sec cells simply reverse their forward trajectories, without invoking developmental or other extrinsic programs, and starting chromatin identities are effectively erased. These findings identify strikingly plastic molecular frameworks in assembly and regeneration of a self-renewing tissue.
Histone methyltransferase DOT1L is essential for self-renewal of germline stem cells
Authors: Lin Huijuan , Cheng Keren , Kubota Hiroshi , Lan Yemin , Riedel Simone S. , Kakiuchi Kazue , Sasaki Kotaro , Bernt Kathrin M. , Bartolomei Marisa S. , Luo Mengcheng , Wang P. Jeremy
Published: June 2022

Self-renewal of spermatogonial stem cells is vital to lifelong production of male gametes and thus fertility. However, the underlying mechanisms remain enigmatic. Here, we show that DOT1L, the sole H3K79 methyltransferase, is required for spermatogonial stem cell self-renewal. Mice lacking DOT1L fail to maintain spermatogonial stem cells, characterized by a sequential loss of germ cells from spermatogonia to spermatids and ultimately a Sertoli cell only syndrome. Inhibition of DOT1L reduces the stem cell activity after transplantation. DOT1L promotes expression of the fate-determining HoxC transcription factors in spermatogonial stem cells. Furthermore, H3K79me2 accumulates at HoxC9 and HoxC10 genes. Our findings identify an essential function for DOT1L in adult stem cells and provide an epigenetic paradigm for regulation of spermatogonial stem cells.
Optimizing experimental design in neutron reflectometry
Authors: Durant James H. , Wilkins Lucas , Cooper Joshaniel F. K.
Published: June 2022

Using the Fisher information (FI), the design of neutron reflectometry experiments can be optimized, leading to greater confidence in parameters of interest and better use of experimental time [Durant, Wilkins, Butler & Cooper (2021). J. Appl. Cryst.
54, 1100–1110]. In this work, the FI is utilized in optimizing the design of a wide range of reflectometry experiments. Two lipid bilayer systems are investigated to determine the optimal choice of measurement angles and liquid contrasts, in addition to the ratio of the total counting time that should be spent measuring each condition. The reduction in parameter uncertainties with the addition of underlayers to these systems is then quantified, using the FI, and validated through the use of experiment simulation and Bayesian sampling methods. For a `one-shot' measurement of a degrading lipid monolayer, it is shown that the common practice of measuring null-reflecting water is indeed optimal, but that the optimal measurement angle is dependent on the deuteration state of the monolayer. Finally, the framework is used to demonstrate the feasibility of measuring magnetic signals as small as 0.01 μB per atom in layers only 20 Å thick, given the appropriate experimental design, and that the time to reach a given level of confidence in the small magnetic moment is quantifiable.
MoloVol: an easy-to-use program for analyzing cavities, volumes and surface areas of chemical structures
Authors: Maglic Jasmin B. , Lavendomme Roy
Published: June 2022

Cavities are a ubiquitous feature of chemical structures encountered in various fields ranging from supramolecular chemistry to molecular biology. They are involved in the encapsulation, transport and transformation of guest molecules, thus necessitating a precise and accessible tool for estimating and visualizing their size and shape. MoloVol, a free user-parametrizable open-source software, developed for calculating a range of geometric features for both unit-cell and isolated structures, is presented here. MoloVol utilizes up to two spherical probes to define cavities, surfaces and volumes. The program was optimized by combining an octree data structure with voxel-partitioned space, allowing for even high-resolution protein structure calculations on reasonable timescales. MoloVol comes with a user-friendly graphic interface along with a command-line interface for high-throughput calculations. It was written in C++ and is available on Windows, macOS and Linux distributions.
Innovative pressure environment combining hydrostatic pressure gradient and mechanical compression for structural investigations of nanoporous soft films
Authors: Wolanin Julie , Giraud Jérôme , Morfin Isabelle , Rollet Anne-Laure , Michot Laurent , Plazanet Marie
Published: June 2022

The development of a new sample environment enabling X-ray scattering measurements at small and large angles under mechanical compression and hydraulic flow is presented. The cell, which is adapted for moderate pressures, includes beryllium windows, and allows applying simultaneously a compressive pressure up to 2.5 kbar in the perpendicular direction to the flow and either a hydrostatic pressure up to 300 bar or a pressure gradient of the same amplitude. The development of high-pressure devices for synchrotron experiments is relevant for many scientific fields in order to unveil details of a material's structure under relevant conditions of stresses. In particular, mechanical constraints coupled to hydrostatic pressure or flow, leading to complex stress tensor and mechanical response, and therefore unexpected deformations (swelling and pore deformation), are poorly addressed. Here, first the design of the environment is described, and then its performance with measurements carried out on a regenerated cellulose membrane is demonstrated.
Development and magnetic field measurement of a 0.5-m-long superconducting undulator at IHEP
Authors: Wei Junhao , Li Yuhui , Yang Xiangchen , Chen Zilin , Zhang Xiangzhen , Bian Xiaojuan
Published: June 2022

Undulators are important devices for accelerator-based light sources whose magnetic field quality determines the photon beam performance. Superconducting-type undulators have been developing rapidly in recent years around the world. The insertion device group at the Institute of High Energy Physics (IHEP) in China started an R&D project to develop prototypes of superconducting undulators (SCUs). A half-meter-long planar SCU has been produced recently. The SCU was designed based on the simulation program OPERA-3D giving a period length of 15 mm and a gap of 7 mm. This prototype was manufactured and fabricated precisely, and was then tested by vertically submerging in liquid helium in a Dewar. After quench training several times, the maximum current in the main coils reached 480 A. The magnetic field was measured by Hall probes mounted on a sledge in the middle of the undulator gap. The peak magnetic field reached 1 T. The measurement results indicate that correction coils with suitable current can not only optimize the magnetic first and second integrals but also reduce the phase error, which is expected by design.