bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallicity gradient of barred galaxies with TYPHOON
Authors: Chen(陈千惠) Qian-Hui , Grasha Kathryn , Battisti Andrew J , Kewley Lisa J , Madore Barry F , Seibert Mark , Rich Jeff A , Beaton Rachael L
Published: December 2022

Bars play an important role in mixing material in the inner regions of galaxies and stimulating radial migration. Previous observations have found evidence for the impact of a bar on metallicity gradients but the effect is still inconclusive. We use the TYPHOON/PrISM survey to investigate the metallicity gradients along and beyond the bar region across the entire star-forming disc of five nearby galaxies. Using emission line diagrams to identify star-forming spaxels, we recover the global metallicity gradients ranging from −0.0162 to −0.073 dex kpc−1 with evidence that the galactic bars act as an agent in affecting in situ star formation as well as the motions of gas and stars. We observe cases with a ‘shallow-steep’ metallicity radial profile, with evidence of the bar flattening the metallicity gradients inside the bar region (NGC 5068 and NGC 1566) and also note instances where the bar appears to drive a steeper metallicity gradient producing ‘steep-shallow’ metallicity profiles (NGC 1365 and NGC 1744). For NGC 2835, a ‘steep-shallow’ metallicity gradient break occurs at a distance ∼4 times the bar radius, which is more likely driven by gas accretion to the outskirt of the galaxy instead of the bar. The variation of metallicity gradients around the bar region traces the fluctuations of star formation rate surface density in NGC 1365, NGC 1566, and NGC 1744. A larger sample combined with hydrodynamical simulations is required to further explore the diversity, and the relative importance of different ISM mixing mechanisms on the gas-phase metallicity gradients in local galaxies.
Detection of Einstein telescope gravitational wave signals from binary black holes using deep learning
Authors: Alhassan Wathela , Bulik T , Suchenek M
Published: December 2022

The expected volume of data from the third-generation gravitational waves (GWs) Einstein Telescope (ET) detector would make traditional GWs search methods such as match filtering impractical. This is due to the large template bank required and the difficulties in waveforms modelling. In contrast, machine learning (ML) algorithms have shown a promising alternative for GWs data analysis, where ML can be used in developing semi-automatic and automatic tools for the detection and parameter estimation of GWs sources. Compared to second generation detectors, ET will have a wider accessible frequency band but also a lower noise. The ET will have a detection rate for Binary Black Holes (BBHs) and Binary Neutron Stars (BNSs) of the order of 105–106 and 7 × 104 yr−1, respectively. We explored the efficiency of using convolutional neural networks (CNNs) for the detection of BBHs’ mergers in synthetic noisy data that was generated according to ET’s parameters. Without performing data whitening or applying bandpass filtering, we trained four CNN networks with the state-of-the-art performance in computer vision, namely VGG, ResNet, and DenseNet. ResNet has significantly better performance, and was able to detect BBHs sources with SNR of 8 or higher with 98.5 per cent accuracy, and with 92.5 per cent, 85 per cent, 60 per cent, and 62 per cent accuracy for sources with SNR range of 7–8, 6–7, 5–6, and 4–5, respectively. ResNet, in qualitative evaluation, was able to detect a BBH’s merger at 60 Gpc with 4.3 SNR. It was also shown that CNN can be used efficiently for near-real time detection of BBHs.
Cystic fibrosis rabbits develop spontaneous hepatobiliary lesions and CF-associated liver disease (CFLD)-like phenotypes
Authors: Wu Qingtian , Liang Xiubin , Hou Xia , Song Zhenfeng , Bouhamdan Mohamad , Qiu Yining , Koike Yui , Rajagopalan Carthic , Wei Hong-Guang , Jiang Hong , Hish Gerry , Zhang Jifeng , Chen Y Eugene , Jin Jian-Ping , Xu Jie , Zhang Kezhong , Sun Fei
Published: December 2022

Cystic fibrosis (CF) is an autosomal recessive genetic disease affecting multiple organs. Approximately 30% CF patients develop CF-related liver disease (CFLD), which is the third most common cause of morbidity and mortality of CF. CFLD is progressive, and many of the severe forms eventually need liver transplantation. The mechanistic studies and therapeutic interventions to CFLD are unfortunately very limited. Utilizing the CRISPR/Cas9 technology, we recently generated CF rabbits by introducing mutations to the rabbit CF transmembrane conductance regulator (CFTR) gene. Here we report the liver phenotypes and mechanistic insights into the liver pathogenesis in these animals. CF rabbits develop spontaneous hepatobiliary lesions and abnormal biliary secretion accompanied with altered bile acid profiles. They exhibit nonalcoholic steatohepatitis (NASH)-like phenotypes, characterized by hepatic inflammation, steatosis, and fibrosis, as well as altered lipid profiles and diminished glycogen storage. Mechanistically, our data reveal that multiple stress-induced metabolic regulators involved in hepatic lipid homeostasis were up-regulated in the livers of CF-rabbits, and that endoplasmic reticulum (ER) stress response mediated through IRE1α-XBP1 axis as well as NF-κB- and JNK-mediated inflammatory responses prevail in CF rabbit livers. These findings show that CF rabbits manifest many CFLD-like phenotypes and suggest targeting hepatic ER stress and inflammatory pathways for potential CFLD treatment.
Three-dimensional coordination of cell-division site positioning in a filamentous cyanobacterium
Authors: Liu Jing , Xing Wei-Yue , Liu Bowen , Zhang Cheng-Cai
Published: December 2022

Bacterial cells mostly divide symmetrically. In the filamentous, multicellular cyanobacterium Anabaena, cell-division planes are aligned vertically relative to the long axis of every single cell. This observation suggests that both the placement and the angle of the division planes are controlled in every single cell so that the filament can grow in one single dimension along the long axis. In this study, we showed that inactivation of patU3 encoding a cell-division inhibitor led cells to divide asymmetrically in two dimensions leading to twisted filaments, indicating that PatU3 controls not only the position but also the angle of the division planes. Deletion of the conserved minC and minD genes affected cell division symmetry, but not the angle of the division planes. Remarkably, when both patU3 and minCD were inactivated, cells could divide asymmetrically over 360° angles in three dimensions across different cellular sections, producing not only cells with irregular sizes, but also branching filaments. This study demonstrated the existence of a system operating in a three-dimensional manner for the control of cell division in Anabaena. Such a regulation may have been evolved to accommodate multicellular behaviors, a hallmark in evolution.
The EU as a Global Gender Actor: Tracing Intersectionality in the European Gender Action Plans for External Relations 2010–2025
Authors: Maes Eva Luna , Debusscher Petra
Published: December 2022

In recent years, the European Union has been paying more attention to social categories other than gender in its external policies. The authors’ aim is twofold. First, we trace how the concept of intersectionality has evolved in EU external gender policy since 2010. Second, we analyze to what extent the framing of intersectionality is able to harness intersectionality’s transformative potential. Using a tailored critical frame analysis of EU Gender Action Plans I–III, the study finds a growing and more profound engagement with the concept since 2020, due to the amenability of the policy field and a changed opportunity structure resulting from the 2019 appointment of a new Commission which put (gender) equality back on the agenda. While not yet transformative in the strict sense, the policy shift is an important leverage for equality advocates as it sets out a progressive course for the European Union as a global gender actor.
Mandatory lane-changing decision making and planning in emergency situations
Authors: Liu Yang , Shi Congling
Published: December 2022

By considering mandatory lane-changing as a collision avoidance measure, this paper presented the corresponding lane-change decision making and trajectory planning algorithm under an emergency scenario. Different from the traditional algorithm in which lane-change decision making and trajectory planning are separated, they are here coupled in a proposed algorithm and the related parameters are dynamically adjusted in the whole process. In addition to lane-change collision avoidance feasibility analysis, lane-change time instance and duration time are obtained by solving the constrained convex quadratic optimization programme. By taking lane-change time instance and duration time as inputs, the algorithm then proceeded to propose a kinematic model-based high-order polynomial lane change trajectory. By giving the simulation result compassion with the related algorithm, it is proved that the proposed algorithm has a good robustness and high efficiency.
Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up
Authors: Bramante Carolyn T. , Buse John B. , Liebovitz David , Nicklas Jacinda , Puskarich Michael A. , Cohen Ken , Belani Hrishikesh , Anderson Blake , Huling Jared D. , Tignanelli Christopher , Thompson Jennifer , Pullen Matthew , Siegel Lianne , Proper Jennifer , Odde David J. , Klatt Nichole , Sherwood Nancy , Lindberg Sarah , Wirtz Esteban Lemus , Karger Amy , Beckman Kenny , Erickson Spencer , Fenno Sarah , Hartman Katrina , Rose Michael , Patel Barkha , Griffiths Gwendolyn , Bhat Neeta , Murray Thomas A. , Boulware David R.
Published: December 2022

Background

Long Covid is an emerging chronic illness potentially affecting millions, sometimes preventing the ability to work or participate in normal daily activities. COVID-OUT was an investigator-initiated, multi-site, phase 3, randomized, quadruple-blinded placebo-controlled clinical trial (NCT04510194). The design simultaneously assessed three oral medications (metformin, ivermectin, fluvoxamine) using two by three parallel treatment factorial assignment to efficiently share placebo controls and assessed Long Covid outcomes for 10 months to understand whether early outpatient treatment of SARS-CoV-2 with metformin, ivermectin, or fluvoxamine prevents Long Covid.

Methods

This was a decentralized, remotely delivered trial in the US of 1,125 adults age 30 to 85 with overweight or obesity, fewer than 7 days of symptoms, and enrolled within three days of a documented SARS-CoV-2 infection. Immediate release metformin titrated over 6 days to 1,500mg per day 14 days total; ivermectin 430mcg/kg/day for 3 days; fluvoxamine, 50mg on day one then 50mg twice daily through 14 days. Medical-provider diagnosis of Long Covid, reported by participant by day 300 after randomization was a pre-specified secondary outcome; the primary outcome of the trial was severe Covid by day 14.

Result

The median age was 45 years (IQR 37 to 54), 56% female of whom 7% were pregnant. Two percent identified as Native American; 3.7% as Asian; 7.4% as Black/African American; 82.8% as white; and 12.7% as Hispanic/Latino. The median BMI was 29.8 kg/m2(IQR 27 to 34); 51% had a BMI >30kg/m2. Overall, 8.4% reported having received a diagnosis of Long Covid from a medical provider: 6.3% in the metformin group and 10.6% in the metformin control; 8.0% in the ivermectin group and 8.1% in the ivermectin control; and 10.1% in the fluvoxamine group and 7.5% in the fluvoxamine control. The Hazard Ratio (HR) for Long Covid in the metformin group versus control was 0.58 (95% CI 0.38 to 0.88); 0.99 (95% CI 0.592 to 1.643) in the ivermectin group; and 1.36 in the fluvoxamine group (95% CI 0.785 to 2.385).

Conclusions

There was a 42% relative decrease in the incidence of Long Covid in the metformin group compared to its blinded control in a secondary outcome of this randomized phase 3 trial.

Trial registration

NCT04510194.

IND

152439
High-Intensity Interval Training Reduces Transcriptomic Age: A Randomized Controlled Trial
Authors: Lohman Trevor , Bains Gurinder , Cole Steve , Gharibvand Lida , Berk Lee , Lohman Everett
Published: December 2022

Background

The relationship between exercise and lifespan is well documented, but little is known about the effects of specific exercise protocols on modern measures of biological age. Transcriptomic age predictors provide an opportunity to test the effects of high intensity interval training (HIIT) on biological age utilizing whole-genome expression data.

Methods

A single-site, single-blinded, randomized controlled clinical trial design was utilized. Thirty sedentary participants (aged 40 to 65) were assigned to either a HIIT group or a no-exercise control group. After collecting baseline measures, HIIT participants performed three 10×1 HIIT sessions per week for 4 weeks. Each session lasted 23 minutes, and total exercise duration was 276 minutes over the course of the 1-month exercise protocol. Transcriptomic age, PSS-10 score, PSQI score, PHQ-9 score, and various measures of body composition were all measured at baseline and again following the conclusion of exercise/control protocols.

Results

Transcriptomic age reduction of 3.59 years was observed in the exercise group while a 3.28-year increase was observed in the control group. PHQ-9, PSQI, BMI, body fat mass, and visceral fat measures were all improved in the exercise group. A hypothesis-generation gene expression analysis suggested exercise may modify autophagy, mTOR, AMPK, IP3K, neurotrophin signaling, insulin signaling, and other age-related pathways.

Conclusion

A low dose of HIIT can reduce an RNA-based measure of biological age in sedentary males and females between the ages of 40 and 65. Other changes to gene expression were relatively modest, which may indicate a focal effect of exercise on age-related biological processes.
Decrypting the microbiota on the black soldier fly’s (Hermetia illucensL., Diptera: Stratiomyidae) egg surface and their origin during development
Authors: Heussler Carina D. , Klammsteiner Thomas , Stonig Katharina T. , Insam Heribert , Schlick-Steiner Birgit C. , Steiner Florian M.
Published: December 2022

The increasing global population leads to a soaring demand for protein for food and feed, and also challenges in organic waste management are growing. All this leads to environmental stress, causing biodiversity loss and an increase in greenhouse gas emissions. Alternative and sustainable animal protein sources are needed to reduce the negative environmental impact of food production. In the last years, the black soldier fly (BSF) has been proposed to substitute animal protein, since BSF may consume and reduce a variety of waste organic matter. Successful industrial rearing of BSF depends on a flourishing reproduction of adults, which is influenced not only by environmental but also by physiological factors. The BSF female oviposits single eggs into clutches close to decomposing organic matter and conspecific eggs. Studies have shown that microbes play a significant role in the oviposition of BSF eggs. In this study, we focus on the surface microbiota of the egg and its origin. We investigated if the microbiota is inoculated before, during, or actively after oviposition. For this purpose, we analysed the microbiota in the larval haemolymph and the gut of larvae raised on sterilized and non-sterilized feed, the pupal cell pulp, the wash of the egg-laying apparatus and the eggs directly collected after oviposition, the ovarian eggs and the empty female abdomen, the eggs with contact to adult BSF, and sterilized eggs. The bacterial communities were identified through 16S rRNA gene sequencing to assess the stage in BSF development during which the microbial colonization of the egg surface occurs. We demonstrated that bacteria differ among life stages resulting in a shift during BSF development from dominance ofEnterobacteriaceaeduring the larval stage to dominance ofBurkholderiaceae spp. in all analysed eggs. A predominant microbiota is present before oviposition and persists through all life stages, however, the overall population’s structure successively shifts during development. A better understanding of egg surface microbiota and oviposition attractants could significantly increase egg production and facilitate the mass harvesting of BSF larvae.

Graphical abstract.

Illustration of the sampling procedure to assess egg surface microbiome of black soldier fly and its origin: Larval fed with unsterile (GU) and sterile (GS) feed and the larval haemolymph of GS (LH), the pupal cell pulp (CP), and from the female adults after mating, a wash of the egg-laying apparatus (WS) and the afterwards placed eggs of the egg-laying apparatus (EA), eggs collected from the ovary (EO) and the empty female abdomen (FA), eggs collected from a fly cage after forced exposure to adults (EC) and sterilized (ES).
Distinct function of SPL genes in age-related resistance inArabidopsis
Authors: Hu Lanxi , Qi Peng , Peper Alan , Kong Feng , Yao Yao , Yang Li
Published: December 2022

In plants, age-related resistance (ARR) refers to a gain of disease resistance during shoot or organ maturation. ARR associated with vegetative phase change, a transition from juvenile to adult stage, is a widespread agronomic trait affecting resistance against multiple pathogens. How innate immunity in a plant is differentially regulated during successive stages of shoot maturation is unclear. In this work, we found thatArabidopsis thalianashowed ARR against its bacterial pathogenPseudomonas syringae pv. tomatoDC3000 during vegetative phase change. The timing of the ARR activation was associated with a temporal drop of miR156 level. A systematic inspection of the loss- and gain-of-function mutants of 11SPLgenes revealed that a subset ofSPLgenes, notablySPL2, SPL10, andSPL11, activated ARR in adult stage. The immune function of SPL10 was independent of its role in morphogenesis. Furthermore, the SPL10 mediated an age-dependent augmentation of the salicylic acid (SA) pathway partially by direct activation ofPAD4. Disrupting SA biosynthesis or signaling abolished the ARR againstPtoDC3000. Our work demonstrated that the miR156-SPL10 module inArabidopsisis deployed to operate immune outputs over developmental timing.

Significance

Age-associated change of immunity is a widespread phenomenon in animals and plants. How organisms integrate immune maturation into a developmental clock is a fundamental question. Heterochronic microRNAs are key regulators of developmental timing. We found that a conserved heterochronic microRNA (miRNA) inArabidopsis, microRNA156, regulates the timing of age-related resistance associated with a transition from the juvenile to the adult vegetative phase. The coordination between developmental maturation and gain of disease resistance is achieved through miR156-controlled SPL transcription factors with distinct functions. A subset of SPL transcription factors promoted resistance by directly activating key genes in defense signaling. This work bridges the knowledge gap between vegetative development and age-related resistance. Pinpointing mechanisms of the developmental regulation on immunity may pave a way for unlocking the age limit on plant immunity and lay a foundation to applications in the precision agriculture.
Using the DNA methylation profile of the stress driver geneFKBP5for chronic pain diagnosis
Authors: Maiarù Maria , Acton Richard J. , Woźniak Eva L. , Mein Charles A. , Bell Christopher G. , Géranton Sandrine M.
Published: December 2022

Epigenetic changes can bring insight into gene regulatory mechanisms associated with disease pathogenicity, including chronicity and increased vulnerability. To date, we are yet to identify genes sensitive to epigenetic regulation that contribute to the maintenance of chronic pain and with an epigenetic landscape indicative of the susceptibility to persistent pain. Such genes would provide a novel opportunity for better pain management, as their epigenetic profile could be targeted for the treatment of chronic pain or used as an indication of vulnerability for prevention strategies. Here, we investigated the epigenetic profile of the geneFKBP5for this potential, using targeted bisulphite sequencing in rodent pre-clinical models of chronic and latent hypersensitive states. TheFKBP5promoter DNA methylation (DNAm) signature in the CNS was significantly different between models of persistent pain and there was a significant correlation between CNS and peripheral bloodFKBP5DNAm, indicating that further exploration ofFKBP5promoter DNAm as a biomarker of chronic pain pathogenic origin is warranted. We also found that maternal separation, which promotes the persistency of inflammatory pain in adulthood, was accompanied by long-lasting reduction inFKBP5DNAm, suggesting thatFKPB5DNAm profile may indicate the increased vulnerability to chronic pain in individuals exposed to trauma in early life. Overall, our data demonstrate that theFKBP5promoter DNAm landscape brings novel insight into the differing pathogenic origins of chronic pain, may be able to diagnose and stratify patients, and predict the susceptibility to chronic pain.
Leveraging the resting brain to predict memory decline after temporal lobectomy
Authors: Audrain Sam , Barnett Alexander , McAndrews Mary Pat
Published: December 2022

Objectives

Anterior temporal lobectomy as a treatment for temporal lobe epilepsy is associated with a variable degree of postoperative memory decline, and estimating this decline for individual patients is a critical step of preoperative planning. Presently, predicting memory morbidity relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly understood as a network disorder, and memory a network phenomenon. We aimed to assess the utility of functional network measures to predict postoperative memory changes.

Methods

Patients with left and right temporal lobe epilepsy (TLE) were recruited from an epilepsy clinic. Patients underwent preoperative resting-state fMRI (rs-fMRI) and pre- and postoperative neuropsychological assessment approximately one year after surgery. We compared functional connectivity throughout the memory network of each patient to a healthy control template based on 19 individuals to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical and demographic variables as predictors of memory change after surgery.

Results

Seventy-two adults with TLE were included in this study (37 left/35 right). Left TLE patients with more abnormal memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change (F(2,31)=12.01, p=0.0001), outperforming standard clinical and demographic variables. None of the variables examined in this study were associated with visuospatial memory change in patients with right TLE.

Conclusion

Resting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue as well as functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE.
Down regulation of the liver lipid metabolism induced by hypothyroidism in mice: metabolic flexibility favors compensatory mechanisms in white adipose tissue
Authors: Chamas Lamis , Seugnet Isabelle , Tanvé Odessa , Enderlin Valérie , Clerget-Froidevaux Marie-Stéphanie
Published: December 2022

In mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (TH), among their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, leading to a reduction in energy expenditure, as well as in lipid and glucose metabolism, and to insulin resistance. Our objective was to evaluate whether metabolic deregulations induced by hypothyroidism could be avoid by regulatory mechanisms involved in metabolic flexibility. To this aim, we compared the response to hypothyroidism in two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and the C57BL/6J mice, prone to DIO. Adult mice were fed with a low-iodine diet supplemented with 6-n-propyl-2-thiouracyl (PTU) for 7 weeks to induce hypothyroidism. Our results show that hypothyroidism, characterized by a decrease in serum T4 levels, led to metabolic deregulations, as an alteration of lipid metabolism in the liver of both strains. However, the decrease in hepatic lipid synthesis was compensated in WSB/EiJ mice by a mobilization of lipid reserves from white adipose tissue, but not in the C57BL/6J mice. No peripheral or hypothalamic inflammatory response to hypothyroidism was observed in both strains. Moreover, gene expression analysis showed that hypothyroidism stimulates the hypothalamic orexigenic circuit in both strains, but unchanged Mc4r and LepR expression in hypothyroid WSB/EiJ mice strain, which reflect their adaptability to maintain their body weight, contrary to C57BL/6J mice. Our results show that WSB/EiJ mice displayed a phenotype of resistance to metabolic dysregulations induced by hypothyroidism, by compensatory mechanisms. This response as well as their resistance to HFD-induced obesity highlights their adaptive capacities to maintain metabolic homeostasis, namely, their high metabolic flexibility, despite serum hypothyroidism. This model sheds light on the importance of local thyroid homeostasis to maintain lipid metabolism and metabolic homeostasis.
Vessel Metrics: A python based software tool for automated analysis of vascular structure in confocal imaging
Authors: McGarry Sean D. , Adjekukor Cynthia , Ahuja Suchit , Greysson-Wong Jasper , Vien Idy , Rinker Kristina D. , Childs Sarah.J.
Published: December 2022

Images contain a wealth of information that is often under analyzed in biological studies. Developmental models of vascular disease are a powerful way to quantify developmentally regulated vessel phenotypes to identify the roots of the disease process. We present vessel Metrics, a software tool specifically designed to analyze developmental vascular microscopy images that will expedite the analysis of vascular images and provide consistency between research groups.

We developed a segmentation algorithm that robustly quantifies different image types, developmental stages, organisms, and disease models at a similar accuracy level to a human observer. We validate the algorithm on confocal, lightsheet, and two photon microscopy data in zebrafish. The tool accurately segments data taken by multiple scientists on varying microscopes. We validate vascular parameters such as vessel density, network length, and diameter, across developmental stages, genetic mutations, and drug treatments, and show a favorable comparison to other freely available software tools. Vessel Metrics reduces the time to analyze experimental results, improves repeatability within and between institutions, and expands the percentage of a given vascular network analyzable in experiments.

Summary statement

Vessel Metrics is an automated software tool designed to standardize and streamline the analysis of vascular microscopy images.
Development and characterization of a recombinant silk network for 3D culture of immortalized and fresh tumor-derived breast cancer cells
Authors: Collodet Caterina , Blust Kelly , Gkouma Savvini , Ståhl Emmy , Chen Xinsong , Hartman Johan , Hedhammar My
Published: December 2022

Traditional cancer models rely on 2D cell cultures or 3D spheroids, which fail to recapitulate cell-extracellular matrix (ECM) interactions, a key element of tumor development. Existing hydrogel-based 3D alternatives lack mechanical support for cell growth and often suffer from low reproducibility. Here we report a novel strategy to make 3D models of breast cancer using a tissue-like, well-defined network environment based on recombinant spider silk, functionalized with a cell adhesion motif from fibronectin (FN-silk). With this approach, the canonical cancer cells SK-BR-3, MCF-7, and MDA-MB-231, maintain their characteristic expression of markers (i.e., ERα, HER2, and PGR) while developing distinct morphology. Transcriptomic analyses demonstrate how culture in the FN-silk networks modulates the biological processes of cell adhesion and migration while affecting physiological events involved in malignancy, such as inflammation, remodeling of the ECM, and resistance to anticancer drugs. Finally, we show that integration in FN-silk networks promotes the viability of cells obtained from the superficial scraping of patients’ breast tumors.
An annotated chromosome-scale reference genome for Eastern Black-eared Wheatear (Oenanthe melanoleuca)
Authors: Peona Valentina , Palacios-Gimenez Octavio Manuel , Lutgen Dave , Olsen Remi André , Kakhki Niloofar Alaei , Andriopoulos Pavlos , Bontzorlos Vasileios , Schweizer Manuel , Suh Alexander , Burri Reto
Published: December 2022

Pervasive convergent evolution and in part high incidences of hybridization distinguish wheatears (songbirds of the genusOenanthe) as a versatile system to address questions at the forefront of research on the molecular bases of phenotypic and species diversification. To prepare the genomic resources for this venture, we here generated and annotated a chromosome-scale assembly of the Eastern Black-eared Wheatear (O. melanoleuca). This species is part of theO. hispanica-complex that is characterized by convergent evolution of plumage coloration and high rates of hybridization. The long-read-based male nuclear genome assembly comprises 1.04 Gb in 32 autosomes, the Z chromosome, and the mitogenome. The assembly is highly contiguous (contig N50: 12.6 Mb; scaffold N50: 70 Mb), with 96% of the genome assembled at chromosome level and 96% BUSCO completeness. The nuclear genome was annotated with 18’160 protein-coding genes and 30’730 mRNAs, and about 10% of the genome consists of repetitive DNA. The annotated chromosome-scale reference genome of Eastern Black-eared Wheatear provides a crucial resource for research into the genomics of adaptation and speciation in an intriguing group of passerines.
Evidence for intraflagellar transport in butterfly spermatocyte cilia
Authors: Gottardo Marco , Riparbelli Maria Giovanna , Callaini Giuliano , Megraw Timothy L.
Published: December 2022

In the model organism insectDrosophila melanogastershort cilia assemble on spermatocytes that elaborate into 1.8 mm long flagella during spermatid differentiation. A unique feature of these cilia/flagella is their lack of dependence on intraflagellar transport (IFT) for their assembly. Here we show that in the common butterflyPieris brassicaethe spermatocyte cilia are exceptionally long: about 40 µm compared to less than 1 µm in Drosophila. By transmission electron microscopy we show thatP. brassicaespermatocytes display several features not found in melanogaster, including compelling evidence of IFT structures and features of motile cilia.

Summary statement

This work shows ultrastructural definition of the exceptionally long cilia that persist on butterfly (P. brassicae) spermatocytes, including evidence of intraflagellar transport, during meiotic division.
Recursive splicing discovery using lariats in total RNA sequencing
Authors: Hoppe Emma R. , Udy Dylan B. , Bradley Robert K.
Published: December 2022

Recursive splicing is a noncanonical splicing mechanism in which an intron is removed in segments via multiple splicing reactions. Relatively few recursive splice sites have been identified with high confidence in human introns, and more comprehensive analyses are needed to better characterize where recursive splicing happens and whether or not it has a regulatory function. In this study, we use an unbiased approach utilizing intron lariats to search for recursive splice sites in constitutive introns and alternative exons in the human transcriptome. We find evidence for recursive splicing in a broader range of intron sizes than previously reported and detail a new location for recursive splicing at the distal ends of cassette exons. Additionally, we identify evidence for the conservation of these recursive splice sites among higher vertebrates and the use of these sites to influence alternative exon exclusion. Together, our data demonstrate the prevalence of recursive splicing and its potential influence on gene expression through alternatively spliced isoforms.
High Estradiol reduces adult neurogenesis but strengthens functional connectivity within the hippocampus during spatial pattern separation in adult female rats
Authors: Yagi Shunya , Lieblich Stephanie E. , Galea Liisa A.M.
Published: December 2022

Adult neurogenesis in the dentate gyrus plays an important role for pattern separation, the process of separating similar inputs and forming distinct neural representations. Estradiol modulates neurogenesis and hippocampus function, but to date no examination of estradiol’s effects on pattern separation have been conducted. Here, we examined estrogenic regulation of adult neurogenesis and functional connectivity in the hippocampus after the spatial pattern separation task in female rats. Ovariectomized Sprague-Dawley rats received daily injections of vehicle, 0.32µg (Low) or 5 µg (High) of estradiol benzoate until the end of experiment. A single bromodeoxyuridine (BrdU) was injected one day after initiation of hormone or vehicle treatment and rats were tested in the delayed nonmatching to position spatial pattern separation task in the 8-arm radial maze for 14 days beginning two weeks after BrdU injection. Rats were perfused 90 minutes after the final trial and brain sections were immunohistochemically stained for BrdU/neuronal nuclei (NeuN) (new neurons), Ki67 (cell proliferation), and the immediate early gene, zif268 (activation). Results showed that only high estradiol reduced the density of BrdU/NeuN-ir cells and had significant inter-regional correlations of zif268-ir cell density in the hippocampus following pattern separation. Estradiol treatment did not influence pattern separation performance or strategy use. These results show that higher doses of estradiol can reduce neurogenesis but at the same time increases correlations of activity of neurons within the hippocampus during spatial pattern separation.
Biogenesis of specialized lysosomes in differentiated keratinocytes relies on close apposition with the Golgi apparatus
Authors: Mahanty Sarmistha , Bergam Ptissam , Belapurkar Vivek , Eluvathingal Litralson , Gupta Nikita , Goud Bruno , Nair Deepak , Raposo Graca , Gangi Setty Subba Rao
Published: December 2022

Intracellular organelles support cellular physiology in diverse conditions. In the skin, epidermal keratinocytes undergo differentiation with gradual changes in cellular physiology, accompanying remodeling in lysosomes and the Golgi apparatus. However, the functional significance and the molecular link between lysosome and Golgi remodeling were unknown. Here, we show that in differentiated keratinocytes, the Golgi apparatus redistributes as ministacks leading to a significant increase in total protein secretion. The Golgi ministacks establish contact with lysosomes facilitated by Golgi tethering protein GRASP65, the depletion of which is associated with the loss of Golgi-lysosome contact and malformation of lysosomes defined by their aberrant morphology, size, and function. Strikingly, these lysosomes receive secretory Golgi cargoes, contribute to the protein secretion from the Golgi, and are critically maintained by the secretory function of the Golgi apparatus. We uncovered a novel mechanism of lysosome specialization through unique Golgi-lysosome contact that likely supports high secretion from differentiated keratinocytes.

Key points

Calcium induced differentiation of human keratinocytes accompanies the dispersal of functional Golgi stacks and lysosomes.

Dispersed Golgi stacks establish contact/physical apposition with the lysosomes.

Golgi tether GRASP65 surrounds keratinocyte lysosomes and facilitates Golgi-lysosome apposition.

GRASP65 depletion abolishes Golgi-lysosome apposition and accumulates morphologically altered non-degradative lysosomes.

Lysosomes of differentiated keratinocytes receive secretory Golgi cargo and contribute to the protein secretion from the Golgi.

Specialized lysosomes are maintained by the secretory function of the Golgi apparatus.
Yeasts have evolved divergent enzyme strategies to deconstruct and metabolize xylan
Authors: Ravn Jonas L. , Ristinmaa Amanda Sörensen , Coleman Tom , Larsbrink Johan , Geijer Cecilia
Published: December 2022

Together with bacteria and fungi, yeasts actively take part in the global carbon cycle. Over a hundred yeast species have been shown to grow on the major plant polysaccharide xylan, which requires an arsenal of carbohydrate active enzymes. However, which enzymatic strategies yeasts use to deconstruct xylan and what specific biological roles they play in its conversion remain unclear. In fact, genome analyses reveal that many xylan-metabolizing yeasts lack expected xylanolytic enzymes. Guided by bioinformatics, we have here selected three xylan-metabolizing ascomycetous yeasts for in-depth characterization of growth behavior and xylanolytic enzymes. The savanna soil yeastBlastobotrys mokoenaiidisplays superior growth on xylan thanks to an efficient secreted glycoside hydrolase family 11 (GH11) xylanase; solving its crystal structure revealed a high similarity to xylanases from filamentous fungi. The termite gut-associatedScheffersomyces lignosusin contrast grows more slowly and its xylanase activity was found to be mainly cell surface-associated. The wood-isolatedWickerhamomyces canadensissurprisingly could not utilize xylan as the sole carbon source without adding xylooligosaccharides, exogenous xylanases or even by co-culturing withB. mokoenaii, suggesting thatW. canadensisrelies on initial xylan hydrolysis by neighboring cells. Furthermore, our characterization of a novelW. canadensisGH5 subfamily 49 (GH5_49) xylanase represents the first demonstrated activity in this subfamily. Our collective results provide new information on the variable xylanolytic systems evolved by yeasts and their potential roles in natural carbohydrate conversion.

Importance

Microbes that take part in the degradation of the polysaccharide xylan, the major hemicellulose component in plant biomass, are equipped with specialized enzyme machineries to hydrolyze the polymer into monosaccharides for further metabolism. However, despite being found in virtually every habitat, little is known of how yeasts break down and metabolize xylan and what biological role they may play in its turnover in nature. Here, we have explored the enzymatic xylan deconstruction strategies of three underexplored yeasts from diverse environments:Blastobotrys mokoenaiifrom soil,Scheffersomyces lignosusfrom insect guts andWickerhamomyces canadensisfrom trees, and show that each species has a distinct behavior regarding xylan conversion. These findings may be of high relevance for future design and development of microbial cell factories and biorefineries utilizing renewable plant biomass.
plastiC: A pipeline for recovery and characterization of plastid genomes from metagenomic datasets
Authors: Cameron Ellen S. , Blaxter Mark L. , Finn Robert D.
Published: December 2022

The use of culture independent molecular methods, often referred to as metagenomics, have revolutionized the ability to explore and characterize microbial communities from diverse environmental sources. Most metagenomic workflows have been developed for identification of prokaryotic and eukaryotic community constituents, but tools for identification of plastid genomes are lacking. The endosymbiotic origin of plastids also poses challenges where plastid metagenomic assembled genomes (MAGs) may be misidentified as low-quality bacterial MAGs. Current tools are limited to classification of contigs as plastid and do not provide further assessment or characterization of plastid MAGs.plastiCis a workflow that allows users to identify plastid genomes in metagenome assemblies, assess completeness, and predict taxonomic association from diverse environmental sources.plastiCis a Snakemake workflow available athttps://github.com/Finn-Lab/plastiC. We demonstrate the utility of this workflow with the successful recover of algal plastid MAGs from publicly available lichen metagenomes.
New mitochondrial genomes of leptosporangiate ferns allow modeling the mitogenomic inflation syndrome across all land plant lineages
Authors: Feng Yanlei , Wicke Susann
Published: December 2022

Plants’ mitochondrial genomes (mitogenome) evolve in a hard-to-predict fashion. To reconstruct the evolutionary trajectories of land plant mitogenomes, we, here, filled the last major mitogenomic gap within land plants by assembling the mitogenomes of the leptosporangiate fernsAzolla filiculoidesandPteridium revolutumand, secondly, analyzed the mitogenomic evolutionary regime shifts across land plants. By testing various Ornstein-Uhlenbeck stabilizing selection models in an a priori-free analysis of five selected mitogenomic traits, we observed 71 evolutionary regime shifts across 218 land plant species. These shifts can lead to genomic convergence, in which certain traits such as size, GC content, and the proportion of non-coding DNA converge, or non-converging regimes, which are characterized by exceptional paths of genomic evolution such as extreme GC content or size. We also found that non-seed plants have a slightly, but significantly, higher rate of synonymous substitutions across all gene classes than seed plants, and that ferns differ significantly in the number of nonsynonymous and synonymous changes compared with other non-seed and seed plants. This pattern matches an outstandingly high rate of RNA editing in the small but repeat-rich mitogenomes of leptosporangiate ferns. In sum, our study highlights the considerable changes in mito-chromosomal architecture that occur during land plant evolution and suggests that these changes may be related to increases in error-prone repair mechanisms. Further study of underrepresented plant groups such as ferns and lycophytes is needed to understand the mechanisms and dominating forces behind the evolutionary dynamics and the mitogenomic inflation syndrome.

Significance Statement

Our study provides new insights into the complexity and diversity of land plant mitogenome evolution and reveals that they take many turns of molecular evolutionary directions across 218 land plant species. Our results have the potential to inform future research in this area and to advance our understanding of the mitogenomic inflation syndrome during plant evolution.
Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data
Authors: Bornhofen Elesandro , Fè Dario , Nagy Istvan , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian Sig , Asp Torben , Janss Luc
Published: December 2022

Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce. Therefore, this study aimed to combine multi-omics from grass hybrids by prioritizing omic features based on the reconstruction of interacting networks and assessing their relevance in explaining economically important phenotypes. Transcriptomic and NMR-based metabolomic data were used for sparse estimation via the fused graphical lasso, followed by modularity-based gene expression and metabolite-metabolite network reconstruction, node hub identification, omic-phenotype association via pairwise fitting of a multivariate genomic model, and machine learning-based prediction study. Analyses were jointly performed across two data sets composed of family pools of hybrid ryegrass (Lolium perenne×L. multiflorum) andFestulolium loliaceum(L. perenne×Festuca pratensis), whose phenotypes were recorded for eight traits in field trials across two European countries in 2020/21. Our results suggest substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizingL. perennewith another species within the genus relative to across genera. However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled. The use of the graphical lasso method for network reconstruction and identification of biological targets is discussed with an emphasis on forage grass breeding.
Cycad phylogeny predicts host plant use ofEumaeusbutterflies
Authors: Sierra-Botero Laura , Calonje Michael , Robbins Robert K. , Rosser Neil , Pierce Naomi E. , López-Gallego Cristina , Valencia-Montoya Wendy A.
Published: December 2022

Eumaeusbutterflies are obligate herbivores ofZamia, the most diverse neotropical genus of cycads.Eumaeus-Zamiainteractions have been mainly characterized for species distributed in North and Central America. However, host plant use by the southernEumaeusclade remains largely unknown, precluding a comprehensive study of co-evolution between the genera. Here, we combine fieldwork with museum and literature surveys to expand herbivory records forEumaeusfrom 21 to 38Zamiaspecies. We inferred a time-calibrated phylogeny ofEumaeusto test for distinct macroevolutionary scenarios of host plant conservatism and co-evolution. We found remarkable coincidence betweenEumaeusandZamiadiversification, with the butterfly stem group diverging at the same time as the most recent radiation ofZamiain the Miocene. Cophylogenetic reconciliation analyses show a strong cophylogenetic signal between cycads and their butterfly herbivores. Bipartite model-based approaches indicate that this is because closely relatedZamiaspecies are used by the sameEumaeusspecies, suggesting host plant resource tracking by the butterfly herbivores. Our results highlight a case of tight evolution betweenEumaeusbutterflies and cycads, pointing to the generality of correlated evolution and phylogenetic tracking in plant-herbivore interactions across seed plants.