bluuebunny/crossref_metadata_2025 huggingface dataset:
CAM5, WRKY53, and TGA5 regulate defense gene expression mediated by the volatile organic compound ethyl vinyl ketone
Authors: Gong Junqing , Guo Zhujuan , Wang Zhaoyuan , Yao Lijuan , Zhao Chuanfang , Lin Sheng , Ma Songling , Shen Yingbai
Published: January 2023

Plants produce ethyl vinyl ketone (evk) in response to biotic stress, but the evk’s identification and downstream defense response remain unclear. In this paper, it is predicted by docking for the first time that evk can be recognized by RBOH protein and assist the electron transfer of RBOHD/RBOHF by binding to its FAD or NADPH binding site. Here, we show that evk treatment increased H2O2and intracellular calcium concentrations inArabidopsis thalianamesophyll cells, as observed by confocal laser scanning microscopy and non-invasive micro-test technology, and that H2O2signaling functioned upstream of Ca2+signaling. Yeast two-hybrid, firefly luciferase complementation imaging, andin vitropull-down assays demonstrated that the ACA8 (AUTOINHIBITED Ca2+-ATPASE, ISOFORM 8)–CML8 (CALMODULIN-LIKE 8) interaction promoted Ca2+efflux to return Ca2+levels to the resting state. Evk treatment led to the antagonism of salicylic acid (SA) and jasmonic acid (JA). CALMODULIN 5 (CAM5) positively regulatesWRKY53expression, and CAM5 and WRKY53 positively regulate SA-related gene expression. These proteins physically interact and form a complex that is unlocked by Ca2+to release WRKY53. An electrophoretic mobility shift assay and dual-luciferase reporter assay demonstrated that WRKY53 and TGA5 cooperate to enhance the expression of the defense genePATHOGENESIS-REALTED 1(PR1) and that WRKY53 enhances the binding of TGA5 to thePR1promoter. This paper proposes a framework that evk, as a RES substance, can achieve plant’s ‘REScue’ through complete defense response.
Sugar restriction and blood ingestion shape divergent immune defense trajectories in the mosquitoAedes aegypti
Authors: Magistrado Dom , El-Dougdoug Noha K. , Short Sarah M.
Published: January 2023

Immune defense is comprised of 1) resistance: the ability to reduce pathogen load, and 2) tolerance: the ability to limit the disease severity induced by a given pathogen load. The study of tolerance in the field of animal immunity is fairly nascent in comparison to resistance. Consequently, studies which examine immune defense comprehensively (i.e., considering both resistance and tolerance in conjunction) are uncommon, despite their exigency in achieving a thorough understanding of immune defense. Furthermore, understanding tolerance in arthropod disease vectors is uniquely relevant, as tolerance is essential to the cyclical transmission of pathogens by arthropods. Here, we tested the effect(s) of dietary sucrose concentration (high or low) and blood meal (present or absent) on resistance and tolerance toEscherichia coliinfection in the yellow fever mosquitoAedes aegypti. Resistance and tolerance were measured concurrently and at multiple timepoints. We found that both blood and sucrose affected resistance. Mosquitoes from the low sugar treatment displayed enhanced resistance at all timepoints post-infection compared to those from the high sugar treatment. Additionally, blood-fed mosquitoes showed enhanced resistance compared to non-blood-fed mosquitoes, but only on day 1 post-infection. Sucrose had no effect on tolerance, but the effect of blood was significant and dynamic across time. Specifically, we show that consuming blood prior to infection ameliorates a temporal decline in tolerance that mosquitoes experience when provided with only sugar meals. Taken together, our findings indicate that different dietary components can have unique and sometimes temporally dynamic impacts on resistance and tolerance. Finally, our findings 1) highlight the value of experimental and analytical frameworks which consider the explicit testing of effects on both resistance and tolerance as separate, but equally important, components of immune defense, and 2) underscore the importance of including a temporal component in studies of immune defense.
Delineating genotypes and phenotypes of individual cells from long-read single cell transcriptomes
Authors: Shiau Cheng-Kai , Lu Lina , Kieser Rachel , Fukumura Kazutaka , Pan Timothy , Lin Hsiao-Yun , Yang Jie , Tong Eric L. , Lee GaHyun , Yan Yuanqing , Huse Jason T. , Gao Ruli
Published: January 2023

Single-cell nanopore sequencing of full-length mRNAs (scNanoRNAseq) is transforming singlecell multi-omics studies. However, challenges include computational complexity and dependence on short-read curation. To address this, we developed a comprehensive toolkit, scNanoGPS to calculate same-cell genotypes-phenotypes without short-read guidance. We applied scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell lines. Standalone, scNanoGPS accurately deconvoluted error-prone long-reads into single-cells and single-molecules. Further, scNanoGPS simultaneously accessed both phenotypes (expressions/isoforms) and genotypes (mutations) of individual cells. Our analyses revealed that tumor and stroma/immune cells often expressed significantly distinct combinations of isoforms (DCIs). In a kidney tumor, we identified 924 genes with DCIs involved in cell-type-specific functions such asPDE10Ain tumor cells andCCL3in lymphocytes. Moreover, transcriptome-wide mutation analyses identified many cell-type-specific mutations includingVEGFAmutations in tumor cells andHLA-Amutations in immune cells, highlighting critical roles of different populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing.
A fundamental law underlying predictive remapping
Authors: Adeyefa-Olasupo Ifedayo-EmmanuEL
Published: January 2023

Predictive remapping (R) — the ability of cells in retinotopic brain structures to transiently exhibit spatiotemporal shifts beyond the spatial extent of their classical anatomical receptive fields — has been proposed as a primary mechanism that stabilizes an organism’s percept of the visual world around the time of a saccadic eye movement. Despite the well-documented effects ofR, a biologically plausible mathematical abstraction that specifies a fundamental law and the functional architecture that actively mediates this ubiquitous phenomenon does not exist. I introduce the Newtonian model ofR, where each modular component ofRmanifests as three temporally overlapping forces - a centripetal, convergentand translational force, that perturb retinotopic cells from their equilibrium extent. The resultant and transient influences of these forcesgives rise to a neuronal force field that governs the spatiotemporal dynamics ofR. This neuronal force field fundamentally obeys an inverse-distance law, akin to Newton’s law of universal gravitation [1] and activates retinotopic elastic fields (elφs). I posit that elφs are transient functional structures that are self-generated by a visual system during active vision and approximate the sloppiness (or degrees of spatial freedom) within which receptive fields are allowed to shift while ensuring that retinotopic organization does not collapse. The predictions of the proposed general model are borne out by the spatiotemporal changes in sensitivity to probe stimuli in human subjects around the time of a saccadic eye movement and qualitatively match neural signatures associated with predictive shifts in the receptive fields of cells in premotor and higher-order retinotopic brain structures.
A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity
Authors: Dedhia Priya H. , Sivakumar Hemamylammal , Rodriguez Marco A. , Nairon Kylie G. , Zent Joshua M. , Zheng Xuguang , Jones Katie , Popova Liudmila , Leight Jennifer L. , Skardal Aleksander
Published: January 2023

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3Din vitromodels of tissues or tumors can model certain complexities of humanin vivobiology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

Significance

The paucity of preclinical research models has contributed to lack of progress in treatment of adrenocortical carcinoma (ACC). Three-dimensional modeling of ACC may provide novel insights for preclinical studies and advance ACC research.
Learning accelerates the evolution of slow aging but obstructs negligible senescence
Authors: Lenart Peter , Psalmon Sacha , Towbin Benjamin D.
Published: January 2023

The risk of dying tends to increase with age, but this trend is far from universal. For humans, mortality is high during infancy, declines during juvenile development, and increases during adulthood. For other species, mortality never increases, or even continuously declines with age, which has been interpreted as absent- or reverse-aging. We developed a mathematical model that suggests an alternative interpretation. The model describes the age-dependence of mortality as the sum of two opposite processes. The mortality risk due to physiological decline increases monotonously with age. But old individuals gain survival benefits through processes like growth and learning. This simple model fits mortality dynamics for all human age classes and for species across the tree of life. Simulations revealed an unexpected complexity by which learning impacts the evolution of aging. An ability to learn initially accelerated the evolution of slower aging but constrained the slowest possible rate of aging that can evolve. This constraint occurs when learning reduces mortality during the reproductive period to near negligible levels and thereby eliminates selection for a further slow-down of aging. In conclusion, learning accelerates the evolution of slower aging, but obstructs the evolution of negligible senescence for species with strong learning-associated survival benefits.
GABAergic signaling shapes multiple aspects ofDrosophilacourtship motor behavior
Authors: Amin Hoger , Nolte Stella S. , Swain Bijayalaxmi , von Philipsborn Anne C.
Published: January 2023

Inhibitory neurons are essential for nervous system function. GABA is the most important neurotransmitter for fast neuronal inhibition in vertebrates and invertebrates. GABAergic signaling in sex specific,fruitlessexpressing neuronal circuits ofDrosophilais required for multiple aspects of male courtship behavior. RNAi mediated knockdown of the GABA producing enzyme Gad1 and the ionotropic receptor Rdl in the ventral nerve cord causes uncoordinated and futile copulation attempts, defects in wing extension choice and severe alterations of courtship song. Altered song of GABA depleted males fails to stimulate female receptivity, but rescue of song patterning alone is not sufficient to rescue male mating success. Knockdown of Gad1 and Rdl in brain circuits abolishes courtship conditioning. We characterize the around 220 neurons coexpressing Gad1 and Fruitless in theDrosophilamale nervous system and propose inhibitory circuit motifs underlying key features of courtship behavior based on the observed phenotypes.
Bacillus subtilisRadA/Sms-mediated nascent lagging-strand unwinding at stalled or reversed forks is a two-step process: RadA/Sms assists RecA nucleation, and RecA loads RadA/Sms
Authors: Torres Rubén , Carrasco Begoña , Alonso Juan C.
Published: January 2023

Replication fork rescue requiresBacillus subtilisRecA, its negative (SsbA) and positive (RecO) mediators, and fork-processing (RadA/Sms). To understand how they work to promote fork remodeling, reconstituted branched replication intermediates were used. We show that RadA/Sms (or its variant RadA/Sms C13A) binds to the 5′-tail of a reversed fork with longer nascent lagging-strand and unwinds it in the 5′→3′ direction, but RecA and its mediators limit unwinding. RadA/Sms cannot unwind a reversed fork with a longer nascent leading-strand, or a gapped stalled fork, but RecA interacts with and activates unwinding. Here, the molecular mechanism by which RadA/Sms, in concert with RecA, in a two-step reaction, unwinds the nascent lagging-strand of reversed or stalled forks is unveiled. First, RadA/Sms, as amediator, contributes to SsbA displacement from the forks, and nucleates RecA onto single-stranded DNA. Then, RecA, as aloader, interacts with and recruits RadA/Sms onto the nascent lagging strand of these DNA substrates to unwind them. Within this process, RecA limits RadA/Sms self-assembly to control fork processing, and RadA/Sms prevents RecA from provoking unnecessary recombination.
TSD: Transformers for Seizure Detection
Authors: Ma Yongpei , Liu Chunyu , Ma Maria Sabrina , Yang Yikai , Truong Nhan Duy , Kothur Kavitha , Nikpour Armin , Kavehei Omid
Published: January 2023

Epilepsy is a common neurological disorder that sub-stantially deteriorates patients’ safety and quality of life. Electroencephalogram (EEG) has been the golden-standard technique for diagnosing this brain disorder and has played an essential role in epilepsy monitoring and disease management. It is extremely laborious and challenging, if not practical, for physicians and expert humans to annotate all recorded signals, particularly in long-term monitoring. The annotation process often involves identifying signal segments with suspected epileptic seizure features or other abnormalities and/or known healthy features. Therefore, automated epilepsy detection becomes a key clinical need because it can greatly improve clinical practice’s efficiency and free up human expert time to attend to other important tasks. Current automated seizure detection algorithms generally face two challenges: (1) models trained for specific patients, but such models are patient-specific, hence fail to generalize to other patients and real-world situations; (2) seizure detection models trained on large EEG datasets have low sensitivity and/or high false positive rates, often with an area under the receiver operating characteristic (AUROC) that is not high enough for potential clinical applicability.

This paper proposes Transformers for Seizure Detection, which we refer to as TSD in this manuscript. A Transformer is a deep learning architecture based on an encoder-decoder structure and on attention mechanisms, which we apply to recorded brain signals. The AUROC of our proposed model has achieved 92.1%, tested with Temple University’s publically available electroencephalogram (EEG) seizure corpus dataset (TUH). Additionally, we highlight the impact of input domains on the model’s performance. Specifically, TSD performs best in identifying epileptic seizures when the input domain is a time-frequency. Finally, our proposed model for seizure detection in inference-only mode with EEG recordings shows outstanding performance in classifying seizure types and superior model initialization.
Molecular portraits of colorectal cancer morphological regions
Authors: Budinská Eva , Hrivňáková Martina , Ivkovic Tina Catela , Madrzyk Marie , Nenutil Rudolf , Bencsiková Beatrix , Tukmachi Dagmar Al , Ručková Michaela , Dubská Lenka Zdražilová , Slabý Ondřej , Feit Josef , Dragomir Mihnea-Paul , Linhartova Petra Borilova , Tejpar Sabine , Popovici Vlad
Published: January 2023

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole- tumor molecular descriptors depend on the morphological heterogeneity with significant impact on current molecular predictors.

We investigated intra-tumor heterogeneity by morphology-guided transcriptomics to better understand the links between gene expression and tumor morphology represented by six morphological patterns (morphotypes): complex tubular, desmoplastic, mucinous, papillary, serrated, and solid/trabecular. Whole-transcriptome profiling by microarrays of 202 tumor regions (morphotypes, tumor-adjacent normal tissue, supportive stroma, and matched whole tumors) from 111 stage II-IV CRCs identified morphotype-specific gene expression profiles and molecular programs and differences in their cellular buildup. The proportion of cell types (fibroblasts, epithelial and immune cells) and differentiation of epithelial cells were the main drivers of the observed disparities with activation of EMT and TNF-α signaling in contrast to MYC and E2F targets signaling, defining major gradients of changes at molecular level. Several gene expression-based (including single-cell) classifiers, prognostic and predictive signatures were examined to study their behavior across morphotypes. Most exhibited important morphotype-dependent variability within same tumor sections, with regional predictions often contradicting the whole-tumor classification.

The results show that morphotype-based tumor sampling allows the detection of molecular features that would otherwise be distilled in whole tumor profile, while maintaining histopathology context for their interpretation. This represents a practical approach at improving the reproducibility of expression profiling and, by consequence, of gene-based classifiers.
A Comprehensive Atlas of Perineuronal Net Distribution and Colocalization with Parvalbumin in the Adult Mouse Brain
Authors: Lupori Leonardo , Totaro Valentino , Cornuti Sara , Ciampi Luca , Carrara Fabio , Grilli Edda , Viglione Aurelia , Tozzi Francesca , Putignano Elena , Mazziotti Raffaele , Amato Giuseppe , Gennaro Claudio , Tognini Paola , Pizzorusso Tommaso
Published: January 2023

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present the first comprehensive atlas of PNN distribution (in Allen Brain Atlas coordinates) and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain. Data analysis showed that PV expression is a good predictor of PNN aggregation. In the cortex, PNNs are dramatically enriched in layer 4 of all primary sensory areas in correlation with thalamocortical input density, and their distribution mirrors intracortical connectivity patterns. Gene expression analysis identified many PNN correlated genes. Strikingly, PNN anticorrelated transcripts were enriched in synaptic plasticity genes, generalizing PNN role as circuit stability factors. Overall, this atlas offers novel resources for understanding the organizational principles of the brain extracellular matrix.
Redox-mediated activation of ATG3 promotes ATG8 lipidation and autophagy progression in Chlamydomonas
Authors: Mallén-Ponce Manuel J. , Pérez-Pérez María Esther
Published: January 2023

Autophagy is one of the main degradative pathways used by eukaryotic organisms to eliminate useless or damaged intracellular material in order to maintain cellular homeostasis under stress conditions. Mounting evidence indicates a strong interplay between the generation of ROS and the activation of autophagy. Although a tight redox regulation of autophagy has been shown in several organisms including microalgae, the molecular mechanisms underlying this control remain poorly understood. In this study, we have performed an in-depthin vitroandin vivoredox characterization of ATG3, an E2-activating enzyme involved in ATG8 lipidation and autophagosome formation, from two evolutionary distant unicellular model organisms: the green microalgaChlamydomonas reinhardtiiand the budding yeastSaccharomyces cerevisiae. Our results indicated that ATG3 activity from both organisms is subjected to redox regulation since these proteins require reducing equivalents to transfer ATG8 to the phospholipid phosphatidylethanolamine. We established the catalytic Cys of ATG3 as redox target in algal and yeast proteins, and showed that the oxidoreductase thioredoxin efficiently reduces ATG3. Moreover,in vivostudies revealed that the redox state of ATG3 fromChlamydomonas reinhardtiiundergoes profound changes in the absence of photoprotective carotenoids, a stress condition that activates autophagy in algae.
IRF1 regulates self-renewal and stress-responsiveness to support hematopoietic stem cell maintenance
Authors: Rundberg Nilsson Alexandra , Xian Hongxu , Shalapour Shabnam , Cammenga Jörg , Karin Michael
Published: January 2023

Inflammatory mediators induce emergency myelopoiesis and cycling of adult hematopoietic stem cells (HSCs) through incompletely understood mechanisms. To suppress the unwanted effects of inflammation and preserve its beneficial outcomes, the mechanisms by which inflammation affects hematopoiesis need to be fully elucidated. Rather than focusing on specific inflammatory stimuli, we here investigated the role of transcription factor Interferon (IFN) regulatory factor 1 (IRF1), which receives input from several inflammatory signaling pathways. We identify IRF1 as a master HSC regulator. IRF1 loss impairs HSC self-renewal, increases stress-induced cell cycle activation, and confers apoptosis resistance. Transcriptomic analysis revealed an aged, inflammatory signature devoid of IFN signaling with reduced megakaryocytic/erythroid priming and antigen presentation in IRF1-deficient HSCs. Finally, we conducted IRF1-based AML patient stratification to identify groups with distinct proliferative, survival and differentiation features, overlapping with our murine HSC results. Our findings position IRF1 as a pivotal regulator of HSC preservation and stress-induced responses.
Gradual change of cortical representations with growing visual expertise for synthetic shapes
Authors: Kakaei Ehsan , Braun Jochen
Published: January 2023

Visual expertise for particular categories of objects (e.g., birds, mushrooms, minerals, and so on) is known to enhance cortical responses in parts of the ventral occipitotemporal cortex. How is such additional expertise integrated into the prior cortical representation of life-long cumulative visual experience? To address this question, we record multivariate BOLD responses to synthetic visual objects and track changes in pairwise distance as initially unfamiliar objects gradually become familiar (‘representational similarity analysis’, RSA).

We find view-independent responses to synthetic shapes (i.e., an invariant representation) in large parts of the ventral occipitotemporal cortex, including the primary visual cortex. Surprisingly, the quality of representation is already high even when shapes are still unfamiliar. As shapes become familiar with repeated viewing, this quality remains high, but representational geometry shifts with more experience. For visually similar shapes that are not repeated and therefore remain unfamiliar, the representation degrades and becomes progressively marginalized.

We conclude that, at least for highly dissimilar synthetic shapes, functional imaging responses can reveal detailed representational geometry at the level of exemplars, as well as gradual changes in this geometry due to experience and learning.
Nature Forest Reserves in Tanzania and their importance for conservation
Authors: Ract Claire , Burgess Neil D. , Dinesen Lars , Sumbi Peter , Malugu Isaac , Latham Julia , Anderson Lucy , Gereau Roy E. , de Lima Marcelo Gonçalves , Akida Amina , Nashanda Evarist , Lyatuu Gertrude , Platts Phil , Rovero Francesco
Published: January 2023

Since 1997 Tanzania has undertaken a process to identify and declare a network of Nature Forest Reserves (NFRs) with high biodiversity values, mainly from within its existing portfolio of national Forest Reserves, but with some new extensions. In recent years this expansion has accelerated, with ten NFRs declared since 2015. The current network of 19 existing NFRs covered 918,212 hectares by the end of 2020 (with an additional three reserves covering 34,862 hectares in the process of being declared). The coverage by NFRs of Tanzanian habitat types has increased to include the main forest types, wet, seasonal, and dry, and includes wetlands and grasslands. This has led to more than a doubling of the coverage of species ranges of vertebrates by the NFR network. Declared and proposed reserves now contain at least 178 of Tanzania’s 242 endemic vertebrate species, of which over 50% are threatened with extinction, and 553 Tanzanian endemic plant taxa (species, subspecies, and varieties), of which 61.3% are threatened. NFRs also support 41 single site endemic vertebrate species and 76 single site endemic plant taxa. Time series data show that NFR management effectiveness is increasing, especially where donor funds are available. Tourism, diversified revenue generation and investment schemes are required to create a network of economically self-sustaining NFRs able to conserve critical biodiversity values. Improved management and investment have reduced some threats in recent years, but ongoing challenges include illegal logging, charcoal production, firewood, pole cutting, hunting, fire, wildlife trade, and the unpredictable impacts of climate change.
Enhancing additive series relay intercropping of grass pea (Lathyrus sativus L.) with low land rice (Oryza sativa L.) in North-Western Ethiopia: A farmer’s indigenous knowledge
Authors: Assefa Endeshew , Bitew Yayeh
Published: January 2023

In Ethiopia the facts of farmer’s indigenous knowledge based cropping system has been rarely investigated through research. A field experiment was conducted during 2021/2022 main cropping season at Fogera plain with the objective of examining the effect of additive series relay intercropping of grass pea with lowland rice on the grain yield of the component crops and production efficiency of the cropping system. The experiment consisted of a factorial combination of four seed proportion of grass pea (SPGP) (25%, 50%, 75% and 100% of the recommended seed rate of sole grass pea) relay intercropped with full seed rate of rice in four Rice: Grass pea spatial arrangements (SA) (1:1, 2:1, 3:1 and their mixed relay intercropping system). The treatments were arranged in Randomized Complete Block Design with three replications. Data on grain yield of the component crops were collected and analyzed using SAS-JMP-16 software. Results revealed that SPGP and SA had no significant effect on rice. The highest grain yield of grass pea was obtained when 25% SPGP was relay intercropped with rice in 1:3 SA (5.10 t ha-1). Maximum production efficiency in terms of total land output yield (9. 89 t ha-1) and land use efficiency (ATER =1.33), net benefit (33, 5176.79 Birr ha-1), marginal rate of return (21,428%) and positive monetary advantage index with lower competitive ratio was obtained when 50% SPGP was relay intercropped with rice in 1:3 SA. Thus, this mixture seems contributing in the development of sustainable crop production with a limited use of external inputs. Rice intercropping with other staple legume crops under residual soil moisture needs to be tested across locations and years to intensify the production efficiency and profitability of the cropping system.
Two avianPlasmodiumspecies trigger different transcriptional responses on their vectorCulex pipiens
Authors: Garrigós M , Ylla G , Martínez-de la Puente J , Figuerola J , Ruiz-López MJ
Published: January 2023

Malaria is a mosquito-borne disease caused by protozoans of the genusPlasmodiumthat affects both humans and wildlife. The fitness consequences of infections by avian malaria are well known in birds, however, little information exists on its impact on mosquitoes. Here we study howCulex pipiensmosquitoes transcriptionally respond to infection by two differentPlasmodiumspecies,P. relictumandP. cathemerium, differing in their virulence (mortality rate) and transmissibility (parasite presence in exposed mosquitoes’ saliva). We study the mosquito response to the infection at three critical stages of parasite development: formation of ookinetes at 24 hours post-infection (hpi), the release of sporozoites into the hemocoel at 10 days post-infection (dpi), and storage of sporozoites in the salivary glands at 21dpi. For each time point, we characterized the gene expression of mosquitoes infected with eachP. relictumandP. cathemeriumand mosquitoes fed on an uninfected bird and, subsequently, compared their transcriptomic responses. Differential gene expression analysis showed most of the transcriptomic changes occurred during the early infection stage (24 hpi), especially when comparingP. relictumandP. cathemeriuminfected mosquitoes. Differentially expressed genes in mosquitoes infected with each species were related mainly to the immune response, trypsin, and other serine-proteases metabolism. We conclude that these differences in response may partly play a role in the differential virulence and transmissibility previously observed inP. relictumandP. cathemeriuminCx. pipiens.
Quantitative comparison between aMRI and DENSE for the assessment of brain tissue motion
Authors: Adams Ayodeji L. , Terem Itamar , Champagne Allen , Holdsworth Samantha J. , Zwanenburg Jaco J. M.
Published: January 2023

Purpose

Amplified MRI (aMRI) holds potential for assessing brain tissue motion and strain, using images acquired from readily-available sequences. However, image registration is necessary to extract displacements from the motion-amplified images, which may limit its accuracy. We aimed to separately assess the errors from imperfections in the aMRI amplification, and errors from the registration algorithm, using a semi-synthetic approach.

Methods

Ground truth brain tissue motion was derived from smoothed Displacement Encoding with Stimulated Echoes (DENSE) measurements acquired at 7T (8 subjects). Those were then applied to a still sagittal anatomical balanced-SSFP image to obtain a DENSE-animated MRI series to which aMRI (amplification factor 10) was applied. DENSE-amplified MRI series served as a reference (Damp-MRI; amplification factor, 10). Amplified displacements were extracted from aMRI and Damp-MRI using a common registration algorithm. Linear regression was used to estimate the amplification and r2agreement of the amplified displacements relative to the ground truth.

Results

The estimated amplification was consistently lower for aMRI-derived displacements (range: [4.9±0.3 5.7±0.3]) than for Damp-MRI measurements (range: [6.7±0.5 7.7±0.5]). Nevertheless, the spatial, temporal and average characteristics of brain tissue motion derived from aMRI were comparable to the ground truth for Anterior-Posterior and Feet-Head displacements: (group averaged r2≥0.84), as were the Damp-MRI derived displacements (r2≥0.88). When aMRI was applied to in-vivo cine-bSSFP images and compared to the ground truth, the results were less favorable, highlighting the need for artefact-free images.

Conclusion

These results strengthen the potential of aMRI as a tool for semi-quantitative assessment of brain tissue motion in disease.
Static and dynamic functional connectomes represent largely similar information
Authors: Matkovič Andraž , Anticevic Alan , Murray John D. , Repovš Grega
Published: January 2023

Functional connectivity (FC) of blood-oxygen-level-dependent (BOLD) fMRI time series can be estimated using methods that differ in sensitivity to the temporal order of time points (static vs. dynamic) and the number of regions considered in estimating a single edge (bivariate vs. multivariate). Previous research suggests that dynamic FC explains variability in FC fluctuations and behavior beyond static FC. Our aim was to systematically compare methods on both dimensions. We compared five FC methods: Pearson’s/full correlation (static, bivariate), lagged correlation (dynamic, bivariate), partial correlation (static, multivariate) and multivariate AR model with and without self-connections (dynamic, multivariate). We compared these methods by (i) assessing similarities between FC matrices, (ii) by comparing node centrality measures, and (iii) by comparing the patterns of brain-behavior associations. Although FC estimates did not differ as a function of sensitivity to temporal order, we observed differences between the multivariate and bivariate FC methods. The dynamic FC estimates were highly correlated with the static FC estimates, especially when comparing group-level FC matrices. Similarly, there were high correlations between the patterns of brain-behavior associations obtained using the dynamic and static FC methods. We conclude that the dynamic FC estimates represent information largely similar to that of the static FC.
The possible role of lipid bilayer properties in the evolutionary disappearance of betaine lipids in seed plants
Authors: Bolik Stéphanie , Schlaich Alexander , Mukhina Tetiana , Amato Alberto , Bastien Olivier , Schneck Emanuel , Demé Bruno , Jouhet Juliette
Published: January 2023

Phosphate is vital for plant and algae growth, yield, and survival, but in most environments, it is poorly available. To cope with phosphate starvation, photosynthetic organisms used their phospholipids as a phosphate reserve. In microalgae, betaine lipids replace phospholipids whereas, in higher plants, betaine lipid synthesis is lost, driving plants to other strategies. The aim of this work was to evaluate to what extent betaine lipids and PC lipids share physicochemical properties and could thus substitute each other. Using neutron diffraction and molecular dynamics simulations of two synthetic lipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoyl-diacylglyceryl-N,N,N-trimethylhomoserine (DP-DGTS), we show that DP-DGTS bilayers are thicker, more rigid, and mutually more repulsive than DPPC bilayers. The different properties and hydration response of PC and DGTS provide an explanation for the diversity of betaine lipids observed in marine organisms and for their disappearance in seed plants.
A conserved family of immune effectors cleaves cellular ATP upon viral infection
Authors: Rousset Francois , Yirmiya Erez , Nesher Shahar , Brandis Alexander , Mehlman Tevie , Itkin Maxim , Malitsky Sergey , Millman Adi , Melamed Sarah , Sorek Rotem
Published: January 2023

During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. In this study, we report a family of immune effectors in bacteria which, in response to phage infection, degrade cellular ATP and dATP by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems including CBASS, prokaryotic argonautes and NLR-like proteins, and we show that degradation of (d)ATP during infection halts phage propagation and aborts infection. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a new family of bacterial defense systems with a two-component phosphotransfer signaling architecture. The immune ATP nucleosidase domain is also encoded within a diverse set of eukaryotic proteins that have immune-like architectures, and we show biochemically that these eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.
Intraspecific competition for a nest and its implication for the fitness of relocating ant colonies
Authors: Halder Eshika , Annagiri Sumana
Published: January 2023

Competitive interaction is important in structuring species composition of a habitat. Several studies have been conducted on intraspecific competition but little is known in the context of the goal-oriented task of colony relocation. Current study examines how relocating colonies respond when the new nest is a limiting resource. Examining this competition across equal sized colonies (n=17) and unequal sized colonies (n=14), we found that most trails had a clear outcome with one of the colony’s occupying the new nest, while 25% of colonies merged. Larger colonies had a significantly higher chance of occupying the new nest and outcompeted the smaller colonies in most of the cases. Colonies that had lower latency to discover and more explorers had a significantly higher chance of gaining control of the new nest and interesting the level of aggression shown by both the competing colonies was comparable. Spatio-temporal analysis of the aggression revealed that the area surrounding the old, new nest and the time at which transportation occurs has higher levels of aggression. While both the competing colonies stole pupa from each other, the mean number of successful stealing by the larger colonies was 8 times larger than smaller colonies while stealing was comparable between similar sized colonies. Relocating colonies experienced significantly more mortality as compared to controls and competition for the new nest imposed additional mortality on losing colonies over the short time. Due to the potential merging of colonies, incorporation of stolen brood and increased mortality, the overall fitness of the colonies is likely to be negatively impacted due to intraspecific competition for a new nest.
Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations
Authors: Brown Jessica , Camporesi Elena , Lantero-Rodriguez Juan , Olsson Maria , Wang Alice , Medem Blanca , Zetterberg Henrik , Blennow Kaj , Karikari Thomas K. , Wall Mark , Hill Emily
Published: January 2023

Alzheimer’s disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, including the aggregated forms, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input-output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.

Graphic Abstract
Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2
Authors: Colozza Gabriele , Lee Heetak , Merenda Alessandra , Wu Szu-Hsien Sam , Català-Bordes Andrea , Radaszkiewicz Tomasz W. , Jordens Ingrid , Lee Ji-Hyun , Bamford Aileen-Diane , Farnhammer Fiona , Low Teck Yew , Maurice Madelon M. , Bryja Vítězslav , Kim Jihoon , Koo Bon-Kyoung
Published: January 2023

The mammalian intestine is one of the most rapidly self-renewing tissues, driven by actively cycling stem cells residing at the crypt bottom1,2. Together with stromal cells, Paneth cells form a major element of the niche microenvironment that provides various growth factors to orchestrate intestinal stem cell homeostasis, such as Wnt33. With 19 family members, different Wnt ligands can selectively activate β-catenin dependent (canonical) or independent (non-canonical) signaling4,5. Here, we report that Dishevelled-associated activator of morphogenesis 1 (Daam1) and its paralogue Daam2 asymmetrically regulate canonical and non-canonical Wnt (Wnt/PCP) signaling, and their function is required for Paneth cell progenitor differentiation. We found that Daam1/2 interacts with the Wnt antagonist Rnf43, and Daam1/2 double knockout stimulates canonical Wnt signaling by preventing Rnf43-dependent endo-lysosomal degradation of the ubiquitinated Wnt receptor, Frizzled (Fzd). Moreover, single-cell RNA sequencing analysis revealed that Paneth cell differentiation is impaired by Daam1/2 depletion, as a result of defective Wnt/PCP signaling. Taken together, we identified Daam1/2 as an unexpected hub molecule coordinating both canonical and non-canonical Wnt signaling, the regulation of which is fundamental for specifying an adequate number of Paneth cells while maintaining intestinal stem cell homeostasis.
Maternal and intrauterine influences on feto-placental growth are accompanied by sexually dimorphic changes in placental mitochondrial respiration, and metabolic signalling pathways
Authors: Salazar-Petres Esteban , Pereira-Carvalho Daniela , Lopez-Tello Jorge , Sferruzzi-Perri Amanda Nancy
Published: January 2023

Adverse maternal environments such as small size, malnutrition and metabolic conditions are known to influence fetal growth outcomes. Similarly, fetal growth and metabolic alterations may alter the intrauterine environment and affect all fetuses in multiple gestations/litter bearing species. The placenta is the site of convergence between signals derived from the mother and the developing fetus/es. Its functions are fuelled by energy generated by mitochondrial oxidative phosphorylation (OXPHOS). The aim of this study was to delineate the role of an altered maternal and/or fetal/intrauterine environment in feto-placental growth and placental mitochondrial energetic capacity. To address this, in mice we used disruptions of the gene encoding phosphoinositol 3-kinase (PI3K) p110α, a growth and metabolic regulator to perturb the maternal and/or fetal/intrauterine environment and study the impact on wildtype conceptuses. We found that feto-placental growth was modified by a perturbed maternal and intrauterine environment, and effects were most evident for wildtype males compared to females. However, placental mitochondrial complex I+II OXPHOS and total electron transport system (ETS) capacity were similarly reduced for both fetal sexes, yet reserve capacity was additionally decreased in males in response to the maternal and intrauterine perturbations. These were also sex-dependant differences in the placental abundance of mitochondrial-related proteins (e.g. citrate synthase, ETS complexes), and activity of growth/metabolic signalling pathways (AKT and MAPK) with maternal and intrauterine alterations. Our findings thus identify that the mother and intrauterine environment provided by littermates, modulate feto-placental growth, and placental bioenergetics and metabolic signalling in a manner dependent on fetal sex. This may have relevance for understanding the pathways leading to reduced fetal growth, particularly in the context of suboptimal maternal environments and multiple gestations/litter bearing species.
Spatiotemporal Dynamics of Vcam1 Regulates Cholangiocarcinoma Mass Expansion and Tumor Dissemination under Growth-suppressive Peritumoral Myofibroblasts
Authors: Tian Cheng , Li Liyuan , Pan Qingfei , Xu Beisi , Li Yizhen , Fan Li , Brown Anthony , Morrison Michelle , Dey Kaushik , Yang Jun J. , Yu Jiyang , Glazer Evan S , Zhu Liqin
Published: January 2023

Intrahepatic cholangiocarcinoma (iCCA) is characterized by its highly desmoplastic stroma. Myofibroblasts (MFs) are present both within the tumor mass (intratumoral MFs, iMFs) and at the tumor border (peritumoral MFs, pMFs). Using a spheroid-based coculture system, we show that the initial iCCA-pMF contact is growth suppressive to the tumor cells. However, prolonged iCCA-pMF interaction elicits significant tumor cell invasion and dissemination. We find that vascular cell adhesion molecule-1 (Vcam1) level is elevated in tumor cells in contact with pMFs but low in disseminated tumor cells both in vitro and in vivo. A gene regulatory network analysis of mouse and patient iCCA tumors andVcam1knockout (Vcam1KO) demonstrate a heavy involvement of Vcam1 in epithelial-to-mesenchymal transition. WhileVcam1KOhas only a limited impact on tumor cell growth in their monoculture,Vcam1KOspheroids exhibit instant dissemination and a severe growth defect when cocultured with pMFs. When transplanted into the liver,Vcam1KOiCCA cells show a similar increase in dissemination but a significant defect in establishing primary and metastatic tumors. Incomplete blocking of Vcam1 in vivo reduces the size but increase the number of metastatic lesions. Overall, our study shows a spatiotemporal regulation of iCCA growth and dissemination by pMFs in a Vcam1-dependent manner.