bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth, organic matter release, aggregation and recycling during a diatom bloom: A model-based analysis of a mesocosm experiment
Authors: Kerimoglu Onur , Hintz Nils H. , Lücken Leonhard , Blasius Bernd , Böttcher Lea , Bunse Carina , Dittmar Thorsten , Heyerhoff Benedikt , Mori Corinna , Striebel Maren , Simon Meinhard 
Published: May 2022

AbstractMechanisms terminating phytoplankton blooms are often not well understood. Potentially involved processes such as consumption by grazers, flocculation, and viral lysis each have different post-bloom consequences on the processing of the organic material, therefore it is important to develop a better understanding of the relevance of these processes, and potential interactions between them. In this study, we present a model-based analysis of a spring bloom observed in a mesocosm experiment. The intermediate-complexity (27-state variable) numerical model we extended from an earlier version to this end can resolve C, N, P and Si cycles, and relevant processes like formation of various organic material size classes (low and high molecular weight (hereafter small and large) dissolved organic carbon (DOC), transparent exopolymer particles (TEP), and small/large detritus) and their degradation by two bacterial sub-communities (free-living and particle-attached) and planktonic protists (heterotrophic flagellates and ciliates). The model can explain > 90% of the variation of a rich set of observations consisting of 11 independent variables over the course of 13 days during which a bloom largely dominated by diatoms develops, and disappears almost entirely. Fluxes estimated by the model point to the importance of coagulation (TEP formation) as a sink term for DOC, and a source term for POC. Consequently, aggregation with TEPs constitute an important loss term for phytoplankton. The flocculated phytoplankton, and detrital material, in turn become rapidly degraded by the particle attached bacteria and other protist heterotrophs. Through a scenario analysis, the relevance of nutrient-stress enhanced lysis rates; alterations between small and large DOC in phytoplankton exudates; and coagulation of smaller DOC molecules were investigated. Our results suggest that the former two processes have negligible effects in isolation, but when combined with the latter, they can synergistically cause substantial deviations in TEP formation, hence, in flocculation rates; and consequently in the peak magnitude of the diatom bloom, and in timing of its termination. Our results point to a need for better understanding of processes governing the termination of phytoplankton blooms, their inter-dependencies, and consequences on the global biogeochemical cycles.
Analyses of circRNA expression throughout circadian rhythm reveal a strong link between Cdr1as and light-induced phase shifts in the SCN
Authors: Ivanov Andranik , Mattei Daniele , Radscheit Kathrin , Compagnion Anne-Claire , Pett J. Patrick , Herzel Hanspeter , Paolicelli Rosa Chiara , Piwecka Monika , Meyer Urs , Beule Dieter 
Published: May 2022

SummaryCdr1as is a conserved circular RNA (circRNA) enriched in the CNS and important for maintaining brain homeostasis. The loss of Cdr1as results in aberrant synaptic transmission and deregulation of stress response and circadian clock genes. However, it is not known whether the expression of Cdr1as or circRNAs, in general, follows a circadian pattern in different tissues. Here, using newly generated and public RNA-Seq data, we monitor circRNA expression throughout circadian rhythm in various mouse brain regions. We demonstrate that Cdr1as, despite its stable character, has a highly dynamic expression during the circadian cycle in the mouse suprachiasmatic nucleus (SCN). Cdr1as is one of the highest expressed RNAs in a cluster associated with light-induced synaptic transmission and phase shift in the SCN. Further, we identified that another brain enriched circRNA, mbl, is also substantially deregulated upon light induction in the fly head. Our study highlights the potential impact of abundant and conserved circRNAs on maintaining a healthy circadian cycle across species.
Carbon signaling protein SbtB possesses redox-regulated apyrase activity to facilitate regulation of bicarbonate transporter SbtA
Authors: Selim Khaled A. , Haffner Michael , Albrecht Reinhard , Zhu Hongbo , Forchhammer Karl , Hartmann Marcus D. 
Published: May 2022

AbstractThe PII superfamily consists of widespread signal transduction proteins found in all domains of life. In addition to canonical PII proteins involved in C/N sensing, structurally similar PII-like proteins evolved to fulfill diverse, yet poorly understood cellular functions. In cyanobacteria, the bicarbonate transporter SbtA is expressed with the conserved PII-like protein, SbtB, to augment intracellular Ci levels for efficient CO2-fixation. We identified SbtB as a sensor of various adenine nucleotides including the second messenger nucleotides cAMP, known as carbon-status indicator, and c-di-AMP, involved in global cellular homeostasis. Moreover, many SbtB proteins possess a C-terminal extension with a disulfide bridge. We previously implied a redox-regulatory function of this extension, which we now call R-loop. Here, we reveal an unusual ATP/ADP apyrase (diphosphohydrolase) activity of SbtB that is controlled by the R-loop. We followed the sequence of the hydrolysis reactions from ATP over ADP to AMP in crystal-lographic snapshots and reveal the structural mechanism by which changes of the R-loop redox state modulate apyrase activity. We further gathered evidence that this redox state is controlled by thioredoxin TrxA, suggesting that it is generally linked to cellular metabolism. Finally, we present a refined model of how SbtB regulates SbtA activity, in which both the apyrase activity and its redox regulation play a central role. This highlights SbtB as a central switch-point in cyanobacterial cell physiology, integrating not only signals from the energy state (adenyl-nucleotide binding) and the carbon supply via cAMP binding, but also from the day/night status reported by the C-terminal redox-switch.
SARS-CoV-2 Subunit Virus-Like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study
Authors: Vakhrusheva A.V. , Kudriavtsev A.V. , Kryuchkov N.A. , Deev R.V. , Frolova M.E. , Blagodatskikh K.A. , Djonovic M. , Nedorubov A.A. , Odintsova E. , Ivanov A.V. , Romanovskaya-Romanko E.A. , Stukova M.A. , Isaev A.A. , Krasilnikov I.V. 
Published: May 2022

AbstractPublic health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of “Betuvax-CoV-2”, a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based spherical virus-like nanoparticles as an adjuvant (“Betuspheres”). The aim of the study was to demonstrate vaccine safety in mice, rats, and Chinchilla rabbits through acute, subchronic, and reproductive toxicity studies. Along with safety, the vaccine demonstrated protective efficacy through SARS-CoV-2-neutralizing antibody production in mice, rats, hamsters, rabbits, and primates (rhesus macaque), and lung damage and infection protection in hamsters and rhesus macaque model. Eventually, “Betuvax-CoV-2” was proved to confer superior efficacy and protection against the SARS-CoV-2 in preclinical studies. Based on the above results, the vaccine was enabled to enter clinical trials that are currently underway.
Chromosome folding and prophage activation reveal gut-specific genome dynamics of bacteria in the OMM12consortium
Authors: Lamy-Besnier Quentin , Bignaud Amaury , Garneau Julian R. , Titecat Marie , Conti Devon , Von Strempel Alexandra , Monot Marc , Stecher Bärbel , Koszul Romain , Debarbieux Laurent , Marbouty Martial 
Published: May 2022

AbstractBacteria and their viruses, bacteriophages, are the most abundant entities of the gut microbiota, a complex community of microorganisms associated with human health and disease. In this ecosystem the interactions between these two key components are still largely unknown. In particular, the impact of the gut environment on bacteria and their associated prophages is yet to be deciphered. To gain insight into the activity of lysogenic phages within the context of their host genomes, we performed Hi-C on the 12 strains of the OMM12synthetic bacterial community stably associated within mice gut (gnotobiotic mouse line OMM12) in bothin vitroandin vivoconditions. High-resolution contact maps of the chromosome 3D organization of the bacterial genomes revealed a wide diversity of architectures, differences between environments and an overall stability over time in the gut of mice. The DNA contacts also pointed at 3D signatures of prophages leading to predict 16 of them as functional. We identified circularization signals and observed different 3D patterns depending on the condition. Concurrent virome analysis showed that 11 of these prophages produced viral particlesin vivoand/orin vitro, and that OMM12mice do not carry other intestinal viruses. By predicting functional prophages, the Hi-C approach unlocks the study of phage-bacteria interaction dynamics.
Cross regulation between the molecular clock and kidney inflammatory, metabolic and fibrotic responses
Authors: Rey-Serra Carlos , Tituaña Jessica , Lin Terry , Herrero J. Ignacio , Miguel Verónica , Barbas Coral , Meseguer Anna , Ramos Ricardo , Firsov Dmitri , Chaix Amandine , Panda Satchidananda , Lamas Santiago 
Published: May 2022

AbstractChronic kidney disease is a highly prevalent condition that remains a major clinical and biomedical challenge. Tubulo-interstitial fibrosis is the common pathological substrate for many causes that lead to chronic kidney disease. It is characterized by profound derangements in metabolic and inflammatory responses, whereby functional tissue is replaced with extracellular matrix, leading to the suppression of renal function. Perturbations in the circadian rhythm have been associated with many human pathologies, including renal disease. However, the role of the molecular clock in the instauration of fibrosis remains incompletely understood. We investigated the relationship between the molecular clock and renal damage in experimental models of injury and fibrosis (UUO, FAN and adenine toxicity), employing genetically-modified mice with selective deficiencies of the clock components Bmal1, Clock and Cry. We found that UUO induced a marked increase in the expression of Bmal1. In human tubular epithelial cells, the pro-fibrotic mediator, TGF-β, significantly altered the expression of core clock components. We further observed that the absence of Cry drastically aggravated kidney fibrosis, while both Cry and Clock played a role in the neutrophil and macrophage mediated inflammatory response, respectively. Suppression of Cry1/2 was associated with a major shift in the expression of metabolism-related genes, underscoring the importance of metabolic dysfunction in fibrosis. These results support a reciprocal interaction between the circadian clock and the response to kidney injury.Translational statementChronic kidney disease (CKD) is a highly prevalent clinical syndrome that still poses major clinical challenges. Kidney fibrosis underlies many cases of CKD and therapies against it are of very limited efficacy. Alterations in circadian rhythms (CR) are relevant in patients with CKD, but very little is known about the relationship between CKD and CR. Our study shows that disruption of the molecular clock can impact kidney inflammation and fibrosis and that, reciprocally, kidney fibrosis can alter the expression of clock components. A better understanding of this crosstalk could open new therapeutic avenues for the prevention and treatment of CR-related CKD.
Zmiz1 is required for mature β-cell function and mass expansion upon high fat feeding
Authors: Alghamdi Tamadher A. , Krentz Nicole A. J. , Smith Nancy , Spigelman Aliya F. , Rajesh Varsha , Jha Alok , Ferdaoussi Mourad , Manning Fox Jocelyn E , Sun Han , Sun Zijie , Gloyn Anna L. , MacDonald Patrick E. 
Published: May 2022

ABSTRACTGenome-wide association studies have identified hundreds of signals for type 2 diabetes (T2D), most of which confer risk through effects on gene expression. We previously identified the transcription factor ZMIZ1 as a probable effector transcript in human islets, but how altered ZMIZ1 expression impacts T2D risk is unknown. We now show that islets from carriers of the T2D-risk alleles have reduced islet insulin content and glucose-stimulated insulin secretion. To elucidate the mechanism for islet-cell dysfunction, we generated β-cell-specific Zmiz1 knockout (Zmiz1βKO) mice. Male and female Zmiz1βKO mice were glucose intolerant with impaired insulin secretion, compared with control littermates. Transcriptomic profiling of Zmiz1βKO islets identified over 500 differentially expressed genes including those involved in β-cell function and maturity which we confirmed at the protein level. After high fat feeding, Zmiz1βKO mice fail to expand β-cell mass and become severely diabetic. Thus, Zmiz1 is required for normal glucose homeostasis and may contribute to T2D risk by maintaining a mature β-cell state and allowing islet mass expansion upon metabolic stress.
ABHD6 selectively controls metabotropic-dependent increases in 2-AG production
Authors: Singh Simar , Sarroza Dennis , English Anthony , Whittington Dale , Dong Ao , van der Stelt Mario , Li Yulong , Zweifel Larry , Bruchas Michael R. , Land Benjamin B. , Stella Nephi 
Published: May 2022

AbstractThe most abundant endocannabinoid (eCB) in the brain, 2-arachidonoyl glycerol (2-AG), is hydrolyzed by α/β-hydrolase domain containing 6 (ABHD6); yet how ABHD6 controls stimuli-dependent increases in 2-AG production is unknown. To explore this question, we leveraged the recently developed 2-AG sensor, GRABeCB2.0, and found that stimulation of Neuro2a cells in culture with bradykinin (BK) acting at metabotropic B2K receptors and ATP acting at ionotropic P2X7 receptors led to differential increases in 2-AG levels. B2K triggered increases in 2-AG levels via diacylglycerol lipase (DAGL), and this mechanism was potentiated by increases in intracellular calcium and ABHD6 inhibition. By contrast, P2X7-triggered increases in 2-AG levels were dependent on DAGL and extracellular calcium but unaffected by ABHD6 inhibition. Thus, ABHD6 preferentially regulates metabotropic-dependent increases in 2-AG levels over ionotropic-dependent increases in 2-AG levels. Our study indicates that ABHD6 selectively controls stimuli-dependent increases in 2-AG production and emphasizes its specific role in eCB signaling.
Characterizing transition cells in developmental processes from scRNA-seq data
Authors: Wang Yuanxin , Mohanty Vakul , Dou Jinzhuang , Liang Shaoheng , Liang Qingnan , Tan Yukun , Li Jin , Li Ziyi , Chen Rui , Chen Ken 
Published: May 2022

AbstractMulti-cellular organism development involves orchestrated gene regulations of different cell types and cell states. Single-cell RNA-Seq, enable simultaneous observation of cells in various states, making it possible to study the underlying molecular mechanisms. However, most of the analytical methods do not make full use of the dynamics captured. Here, we model single-cell RNA-seq data obtained from a developmental process as a function of gene regulatory network using stochastic differential equations (SDEs). Based on dynamical systems theory, we showed that pair-wise gene expression correlation coefficients can accurately infer cell state transitions and validated it using mouse muscle cell regeneration scRNA-seq data. We then applied our analytical framework to the PDAC (Pancreatic ductal adenocarcinoma) mouse model scRNA-seq data. Through transition cells found in the pancreatic preinvasive lesions scRNA-seq data, we can better explain the heterogeneity and predict distinct cell fate even at early tumorigenesis stage. This suggests that the biomarkers identified by transition cells can be potentially used for diagnosis, prognosis and therapeutics of diseases.
Delayed benefits for fallow bucks: more fights decrease same day mating success, but may increase matings the next day
Authors: Bateman-Neubert Alessandra , Briefer Elodie F. , McElligott Alan G. 
Published: May 2022

ABSTRACTDominance hierarchies help to reduce unnecessary fights and associated costs during the mating season. Fallow deer (Dama dama) typically have high levels of male-male competition and strong reproductive skew. Nevertheless, how male dominance and daily fight rates affect mating success remains unknown. We used a two-year dataset from a large population of tagged fallow deer (620-689 individuals), to calculate male dominance ranks based on their agonistic interactions prior to the mating season (‘prerut’), in order to then examine how rank is related to fight rates and mating success during the mating season (‘rut’). Overall, higher-ranked males fought at least twice a day on a higher proportion of days during the rut and secured more matings. Males engaging in more than 10 fights per day were less likely to secure a mating that same day, and those males exceeding 15 fights per day secured no matings at all. Nevertheless, males with the highest numbers of fights (i.e. 15-21 fights per day) on a given day had higher mating success on subsequent days. Although higher-ranked males secured most matings during the rut, their fight rates decreased towards the end. We propose that engaging in more fights negatively affects daily individual mating success, but may benefit mating success on subsequent days, and potentially increase long-term fitness benefits. Additionally, engaging in more fights as the rut progresses probably allows lower-ranked males to secure some matings before the availability of oestrous females ends for almost a year.SIGNIFICANCE STATEMENTFighting carries a risk of injury and high energetic costs. Male fallow deer establish dominance hierarchies, that help reduce unnecessary fights among individuals of different competitive abilities. However, whether high-ranked males fight more or less is yet unknown. By calculating social ranks of fallow bucks before the start of their mating period, we show that males of higher social status do fight and mate more during the mating season (rut). Furthermore, by investigating how investment in fights affects individual mating success that same day and the next day, we find that males that fight more cause a decrease in their immediate daily mating success, but can potentially increase their chances of mating in subsequent days. Thus, to fight more may allow males to climb the hierarchical social ladder, hence increasing longer-term fitness benefits associated to higher ranks.
Pangenomic genotyping with the marker array
Authors: Mun Taher , Vaddadi Naga Sai Kavya , Langmead Ben 
Published: May 2022

AbstractWe present a new method and software tool called rowbowt that applies a pangenome index to the problem of inferring genotypes from short-read sequencing data. The method uses a novel indexing structure called the marker array. Using the marker array, we can genotype variants with respect from large panels like the 1000 Genomes Project while avoiding the reference bias that results when aligning to a single linear reference. rowbowt can infer accurate genotypes in less time and memory compared to existing graph-based methods. The method is implemented in the open source software tool rowbowt available at https://github.com/alshai/rowbowt.
Spatial and temporal diversity of positive selection on shared haplotypes at thePSCAlocus among worldwide human populations
Authors: Iwasaki Risa L. , Satta Yoko 
Published: May 2022

AbstractSelection on standing genetic variation is important for rapid local genetic adaptation when the environment changes. We report that, for the prostate stem cell antigen (PSCA) gene, different populations have different target haplotypes, even though haplotypes are not unique to specific populations. The C-C-A haplotype, whereby the first C is located at rs2294008 ofPSCAand is a low risk allele for gastric cancer, has become a target of positive selection mainly in Asian populations. Conversely, the C-A-G haplotype carrying the same C allele has become a selection target in African populations. However, Asian and African populations share both haplotypes, consistent with the haplotype divergence time (170 kya) prior to out-of-Africa. The frequency of C-C-A/C-A-G is 0.344/0.278 in Asia and 0.209/0.416 in Africa. 2D-SFS analysis revealed that the extent of intra-allelic variability of the target haplotype is extremely small in each local population, suggesting that C-C-A or C-A-G is under ongoing hard sweeps in local populations. From the TMRCA of selected haplotypes, the estimated onset times of positive selection were recent (3-55 kya), concurrently with population subdivision from a common ancestor. Additionally, estimated selection coefficients from ABC analysis were up to ∼3%, similar to those at other loci under recent positive selection on standing genetic variation. Phylogeny of local populations and TMRCA of selected haplotypes revealed that spatial and temporal switching of positive selection targets is a unique and novel feature of ongoing positive selection atPSCA. This switching may reflect potential of rapid adaptability to distinct environments.
Space-time home range estimates and resource selection for the Critically Endangered Philippine Eagle on Mindanao
Authors: Sutton Luke J. , Ibañez Jayson C. , Salvador Dennis I. , Taraya Rowell L. , Opiso Guiller S. , Senarillos Tristan Luap P. , McClure Christopher J.W. 
Published: May 2022

AbstractQuantifying home range size and habitat resource selection are important elements in wildlife ecology and are useful for informing conservation action. Many home range estimators and resource selection functions are currently in use. However, both methods are fraught with analytical issues inherent within autocorrelated movement data from irregular sampling and interpretation of resource selection model parameters to inform conservation management. Here, we apply satellite telemetry and remote sensing technologies to provide first estimates of home range size and resource selection for six adult Philippine Eagles (Pithecophaga jefferyi), using five home range estimators and non-parametric resource selection functions. From all home range estimators, the median 95 % home range size was between 39-68 km2 (range: 22-161 km2), with the 50 % core range size between 6-13 km2 (range: 5-33 km2). The space-time autocorrelated kernel density estimate (AKDE) had the largest median 95 % home range size = 68 km2 and a 50 % core range = 13 km2. Local convex hulls (LoCoH) estimated the smallest median 95 % home range = 39 km2 and a 50 % core range = 6 km2. From the resource selection functions, all adults used areas high in photosynthetic leaf and canopy structure but avoided areas of old growth biomass and denser areas of vegetation, possibly due to foraging forays into fragmented areas away from nesting sites. For the first time, we determine two important spatial processes for this Critically Endangered raptor that can help in directing conservation management. Rather than employing a single home range estimator, we recommend that analysts consider multiple approaches to animal movement data to fully explore space-time and resource use.