bluuebunny/crossref_metadata_2025_split huggingface dataset:
TandemAligner: a new parameter-free framework for fast sequence alignment
Authors: Bzikadze Andrey V. , Pevzner Pavel A. 
Published: September 2022

AbstractThe recent advances in “complete genomics” revealed the previously inaccessible genomic regions (such as centromeres) and enabled analysis of their associations with diseases. However, analysis of variations in centromeres, immunoglobulin loci, and other extra-long tandem repeats (ETRs) faces an algorithmic bottleneck since there are currently no tools for accurate sequence comparison of ETRs. Counterintuitively, the classical alignment approaches, such as the Smith-Waterman algorithm, that work well for most sequences, fail to construct biologically adequate alignments of ETRs. This limitation was overlooked in previous studies since the ETR sequences across multiple genomes only became available in the last year. We present TandemAligner — the first parameter-free sequence alignment algorithm that introduces a sequence-dependent alignment scoring that automatically changes for any pair of compared sequences. We apply TandemAligner to various human centromeres and primate immunoglobulin loci, arrive at the first accurate estimate of the mutation rates in human centromeres, and quantify the extremely high rate of large insertions/duplications in centromeres. This extremely high rate (that the standard alignment algorithms fail to uncover) suggests that centromeres represent the most rapidly evolving regions of the human genome with respect to their structural organization.
An R-R-type MYB transcription factor promotes nonclimacteric pepper fruit ripening pigmentation
Authors: Yang Ningzuo , Song Jiali , Chen Changming , Sun Binmei , Zhang Shuanglin , Cai Yutong , Zheng Xiongjie , Cao Bihao , Chen Guoju , Jin Dan , Li Bosheng , Bian Jianxin , Lei Jianjun , He Hang , Zhu Zhangsheng 
Published: September 2022

SummaryCarotenoids act as phytohormones and volatile compound precursors that influence plant development and confer characteristic colours, affecting both the aesthetic and nutritional value of fruits. Carotenoid pigmentation in ripening fruits is highly dependent on developmental trajectories. Transcription factors incorporate developmental and phytohormone signalling to regulate the biosynthesis process. In contrast to the well-established pathways regulating ripening-related carotenoid biosynthesis in climacteric fruit, carotenoid regulation in nonclimacteric fruit is poorly understood. Capsanthin is the primary carotenoid of nonclimacteric pepper (Capsicum) fruit; its biosynthesis is tightly associated with fruit ripening, and it confers red pigment to the ripening fruit. In this study, using a weighted gene coexpression network and expression analysis, we identified an R-R-type MYB transcription factor, DIVARICATA1, and demonstrated that it is tightly associated with the levels of carotenoid biosynthetic genes (CBGs) and capsanthin accumulation. DIVARICATA1 encodes a nucleus-localized protein that functions primarily as a transcriptional activator. Functional analyses demonstrated that DIVARICATA1 positively regulates CBG transcript levels and capsanthin contents by directly binding to and activating the CBG promoter transcription. Furthermore, the association analysis revealed a significant positive association between DIVARICATA1 transcription level and capsanthin content. Abscisic acid (ABA) promotes capsanthin biosynthesis in a DIVARICATA1-dependent manner. Comparative transcriptomic analysis of DIVARICATA1 in pepper and its orthologue in a climacteric fruit, tomato, suggests that its function might be subject to divergent evolution among the two species. This study illustrates the transcriptional regulation of capsanthin biosynthesis and offers a novel target for breeding peppers with high red colour intensity.
intSDM: anRpackage for building a reproducible workflow for the field of integrated species distribution models
Authors: Mostert Philip , Bjørkås Ragnhild , Bruls Angeline J.H.M. , Koch Wouter , Martin Ellen C. , Perrin Sam W. 
Published: September 2022

1AbstractThere has been an exponential increase in quantity and type of biodiversity data in recent years, including presence-absence, counts, and presence-only citizen science data. Species Distribution Models (SDMs) have typically been used in ecology to estimate current and future ranges of species, and are a common tool used when making conservation prioritisation decisions. However integration of these data in a model-based framework is needed to address many of the current large-scale threats to biodiversity.Current SDM practice typically underutilizes the large amount of publicly available biodi-versity data and does not follow a set of standard best practices. Integrating different data types with open-source tools and reproducible workflows saves time, increases collaboration opportunities, and increases the power of data inference in SDMs.We aim to address this issue by (1) proposing methods and (2) generating a reproducible workflow to integrate different available data types to increase the power of SDMs. We provide theRpackageintSDM, as well as guidance on how to accommodate users’ diverse needs and ecological questions with different data types available on the Global Biodiversity Information Facility (GBIF), the largest biodiversity data aggregator in the world.Finally, we provide a case study of the application of our proposed reproducible workflow by creating SDMs for vascular plants in Norway, integrating presence-only and presence-absence species occurrence data and climate data.
Circadian rhythms in the gut microbiota shape sex differences in host gene expression and metabolism
Authors: Munyoki Sarah K. , Goff Julie P. , Kolobaric Antonija , Long Armari , Mullett Steven J. , Burns Jennifer K. , Jenkins Aaron K. , DePoy Lauren , Wendell Stacy G. , McClung Colleen A. , Morrison Kathleen E. , Jašarević Eldin 
Published: September 2022

SUMMARYCircadian rhythms dynamically regulate sex differences in metabolism and immunity, and circadian disruption increases the risk of metabolic disorders. We investigated the role of sex-specific microbial circadian rhythms in host metabolism using germ-free and conventionalized female and male mice, dietary manipulations, coupled with a systems biology approach. Sex differences in circadian rhythms of genes involved in immunity and metabolism are dependent on oscillations in the microbiota, microbial metabolic functions, and microbial metabolites. Further, dietary factors modify the magnitude of sex differences in host-microbe circadian dynamics. We show that consuming an obesogenic high-fat, low-fiber diet produced sex-specific changes in circadian rhythms in microbiota, metabolites, and host gene expression, which were linked to sex differences in the severity of metabolic dysfunction. These results reveal that microbial circadian rhythms contribute to sex differences in metabolism, emphasizing the need to consider sex as a biological variable in research on microbial contributions to metabolic dysfunction.HIGHLIGHTSMicrobial circadian rhythms differ by sex.Sex-specific rhythms in host transcriptional networks are microbiome-dependent.Diet-induced obesity entrains new sex-specific rhythms in microbiome and host genes.Timing of data collection influences magnitude of sex differences.
Parvalbumin protein controls inhibitory tone in the spinal cord
Authors: Qiu Haoyi , Miraucourt Lois , Petitjean Hugues , Davidova Albena , Levesque-Damphousse Philipa , Estall Jennifer L. , Sharif-Naeini Reza 
Published: September 2022

AbstractThe nervous system processes sensory information by relying on the precise coordination of neuronal networks and their specific synaptic firing patterns. In the spinal cord, disturbances to the firing pattern of the tonic firing parvalbumin (PV)-expressing inhibitory interneuron (PV neurons) disrupt the ability of the dorsal horn to integrate touch information and may result in pathological phenotypes. The parvalbumin protein (PVp) is a calcium (Ca2+)-binding protein that buffers the accumulation of Ca2+ following a train of action potential to allow for tonic firing. Here, we find that peripheral nerve injury causes a decrease in PVp expression in PV neurons and makes them transition from tonic to adaptive firing. We also show that reducing the expression of PVp causes otherwise healthy adult mice to develop mechanical allodynia and causes their PV neurons to lose their high frequency firing pattern. We show that this frequency adaptation is mediated by activation of SK channels on PV neurons. Further, we show their tonic firing can be partially restored after nerve injury by selectively inhibiting the SK2 channels of PV neurons. We also reveal that a decrease in the transcriptional coactivator, PGC-1α, causes decrease PVp expression and the development of mechanical allodynia. By preventing the decrease in PVp expression before nerve injury, we were able to protect mice from developing mechanical allodynia. Our results indicate an essential role for PVp-mediated calcium buffering in PV neuron firing activity and the development of mechanical allodynia after nerve injury.
Insights into the molecular mechanism of translation inhibition by the ribosome-targeting antibiotic thermorubin
Authors: Paranjpe Madhura N. , Marina Valeria I. , Grachev Aleksandr A. , Maviza Tinashe P. , Tolicheva Olga A. , Paleskava Alena , Osterman Ilya A. , Sergiev Petr V. , Konevega Andrey L. , Polikanov Yury S. , Gagnon Matthieu G. 
Published: September 2022

ABSTRACTThermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It is known to bind to the 70S ribosome at the intersubunit bridge B2a and was thought to inhibit factor-dependent initiation of translation and obstruct the accommodation of tRNAs into the A site. Here, we show that thermorubin causes ribosomes to stall in vivo and in vitro at internal and termination codons, thereby allowing the ribosome to initiate protein synthesis and translate at least a few codons before stalling. Our biochemical data show that THR affects multiple steps of translation elongation with a significant impact on the binding stability of the tRNA in the A site, explaining premature cessation of translation. Our high-resolution crystal and cryo-EM structures of the 70S-THR complex show that THR can co-exist with P- and A-site tRNAs, explaining how ribosomes can elongate in the presence of the drug. Remarkable is the ability of THR to arrest ribosomes at the stop codons. Our data suggest that by causing structural re-arrangements in the decoding center, THR interferes with the accommodation of tRNAs or release factors into the ribosomal A site.HIGHLIGHTSThermorubin is a potent inhibitor of protein synthesis both in vivo and in vitro;Thermorubin does not prevent the binding of P- and A-site tRNAs;Thermorubin affects multiple steps of translation elongation with a major impact on binding stability of the A-site tRNA;Thermorubin can act as an inhibitor of translation termination on some ORFs.
Geological drivers of diversification in Papuan microhylid frogs
Authors: Hill Ethan C. , Gao Diana F. , Polhemus Dan A. , Fraser Claire J. , Iova Bulisa , Allison Allen , Butler Marguerite A. 
Published: September 2022

AbstractStudies of the Papuan region have provided fundamental insights into both the evolutionary processes generating its exceptional biodiversity, as well support for alternative hypotheses of geological history. Lying at the junction of five tectonic plates, this region has experienced a turbulent geological history that has not only produced towering mountains allowing elevational specialization, and island archipelagos of varying distance promoting vicariance, but also active margins where land masses have collided and been subsequently rifted apart creating a mosaic of intermixed terranes with vastly different geological histories which may influence the evolutionary history of its biota. Asterophryine frogs are a hyperdiverse clade representing half the world’s microhylid diversity (over 360 species) centered on New Guinea and its satellite islands. We show that vicariance facilitated by geological history, and not elevational specialization best explain this far and wide distribution of a clade that should have poor dispersal abilities. Thus, some of the predictions of island biogeography theory are supported if informed by geological history. We recovered a mainland tectonic unit, the East Papua Composite Terrane (EPCT), as the center of origin for Asterophryinae and no fewer than 71 instances of what appear to be long-distance dispersal events, 29 of which are between mainland regions, with 42 from the mainland to the islands, some presently as far as 200 km away from source populations over open ocean. Furthermore, we find strong support for a “Slow and Steady” hypothesis for the formation of the northern margin of New Guinea by many separate accretion events during the Miocene, over other major geological alternatives, consistent with the 20 M year age of the clade and arrival via the EPCT. In addition, the historical biogeography of our frogs strongly support an affiliation of the Louisiade Archipelago and Woodlark Island with the Owen Stanley Mountain range on the EPCT, and the recent proximity of the large New Britain island. Our results show that Asterophryinae did not have to repeatedly and independently disperse across and large ocean barriers to the offshore islands, but that the current distribution can be explained through vicariance and short-distance oceanic dispersal as historical land connections disappeared and islands slowly became separated from each other. We show that islands have a life history, undergoing changes in area through island-building and erosion, but also change in distance from other land masses, with consequent opportunities for dispersal, isolation, and cladogenesis of their biotas. More broadly, we can begin to see how the geological history of the Papuan region can result in the rapid accumulation and staggering number of extant species.
Glucocorticoids negatively relate to body mass on the short-term in a free-ranging ungulate
Authors: Lalande Lucas D. , Gilot-Fromont Emmanuelle , Carbillet Jeffrey , Débias François , Duhayer Jeanne , Gaillard Jean-Michel , Lemaître Jean-François , Palme Rupert , Pardonnet Sylvia , Pellerin Maryline , Rey Benjamin , Vuarin Pauline 
Published: September 2022

AbstractEnvironmental fluctuations force animals to adjust glucocorticoids (GCs) secretion and release to current conditions. GCs are a widely used proxy of an individual stress level. While short-term elevation in GCs is arguably beneficial for fitness components, previous studies have documented that the relationship between long-term baseline GCs elevation and fitness components can vary according to ecological and individual factors and according to the life-history of the species studied. Using longitudinal data on roe deer (Capreolus capreolus) from two populations facing markedly different environmental contexts, we tested whether baseline GC levels negatively correlate with body mass – a trait positively associated with demographic individual performance – on the short- to long-term. In support, higher baseline GC concentrations were associated to lighter body mass, both measured during the same capture event, in adults of both populations. Overall, we showed that despite the marked environmental and demographic differences between populations and despite the between-sex differences in life history (i.e. reproductive tactics), the relationship between body mass and GCs is consistent across environmental contexts, but might differ according to the life history stage of an individual. This work opens promising perspectives to further explore the relationship between GC and fitness-related traits according to life history stages in free-ranging mammals across seasonal and environmental contexts. The timing and context-dependence of GC levels highlight the complexity of studying stress responses in the wild.
MEF2A suppresses replicative stress responses that trigger DDX41-dependent IFN production
Authors: Smith Julian R. , Dowling Jack W. , Karp Andrew , Schwerk Johannes , Savan Ram , Forero Adriana 
Published: September 2022

ABSTRACTInterferons (IFN) are induced by sensing of self- and non-self DNA or genomic lesions by pathogen recognition receptors (PRR) that activate STING. These pathways must be kept in check by negative regulators to prevent unscheduled activation of IFN, which contributes to autoinflammation. Here we show that MEF2A as a novel negative regulator of inflammation that suppresses homeostatic induction of IFNs. Indeed, MEF2A deficiency results in the spontaneous production of type I IFN and robust downstream IFN-stimulated gene expression that coincided with a robust cellular antiviral state. Mechanistically, MEF2A depletion promoted the accumulation of R-loops that activate the DDX41/STING pathway. This pro-inflammatory pathway was dependent on ATR kinase activity, hallmark of the replicative stress response, was necessary for the activation of STING upon loss of MEF2A expression. Thus, our study connects MEF2A with protection from maladaptive type I IFN responses triggered by R-loop accumulation and links the DDX41-dependent activation of STING to the DNA damage response.
Can root systems redistribute soil water to mitigate the effects of drought?
Authors: Mair Andrew , Dupuy Lionel X , Ptashnyk Mariya 
Published: September 2022

SummaryPlants adapt both morphologically and physiologically in response to drought. This work considers another potential mechanism of plant drought resistance. Namely, the capacity of root systems to modify the hydraulic properties of surrounding soil, and extend the post-precipitation lifetime of water in the rooted zone.In studies of plant drought resistance, the effect of root-oriented preferential soil water transport is seldom considered, despite experimental evidence that it occurs. We developed a model for water transport through soil that incorporates preferential flow induced by a root system. Bayesian optimisation was employed to calibrate the model against experimental data, and the finite element method was used to obtain model simulations for the influence of different root architectures on post-precipitation water lifetime.When increasing preferential flow strength, simulations indicated a trade-off between evaporation and deep percolation losses. It was also observed that the soil surrounding root systems with a reduced gravitropic response, retained the most water following precipitation.This work provides new insight into the role of root system traits in plant drought resistance, and identifies potential crop phenotypes for improved water use efficiency.
Cell-type-specific roles of inhibitory interneurons in the rehabilitation of auditory cortex after peripheral damage
Authors: Kumar Manoj , Handy Gregory , Kouvaros Stylianos , Ljungqvist Brinson Lovisa , Bizup Brandon , Doiron Brent , Tzounopoulos Thanos 
Published: September 2022

AbstractPeripheral sensory organ damage leads to compensatory cortical plasticity that supports a remarkable recovery of perceptual capabilities. A major knowledge gap is the lack of precise mechanisms that explain how this plasticity is implemented and distributed over a diverse collection of excitatory and inhibitory cortical neurons. Here, we explored these mechanisms in mouse A1. After peripheral damage, we found recovered sound-evoked activity of excitatory principal neurons (PNs) and parvalbumin (PVs) interneurons (INs), reduced activity in somatostatin-INs (SOMs), and recovered activity in vasoactive intestinal peptide-INs (VIPs). Given the sequentially organized cortical network where VIPs inhibit INs, SOMs inhibit PVs and PNs, and PVs inhibit PNs, our results suggest that PVs contribute to PN stability, SOMs allow for increased PN and PV activity, and VIPs enable the PN and PV recovery by inhibiting SOMs. These results highlight a strategic, cooperative, and cell-type-specific plasticity program that restores cortical sound processing after peripheral damage.
Translating DNA origami Nanotechnology to Middle School, High School, and Undergraduate Laboratories
Authors: Beshay P. E. , Kucinic A. , Wile N. , Halley P. , Des Rosiers L. , Chowdhury A. , Hall J. L. , Castro C. E. , Hudoba M. W. 
Published: September 2022

ABSTRACTDNA origami is a rapidly emerging nanotechnology that enables researchers to create nanostructures with unprecedented geometric precision that have tremendous potential to advance a variety of fields including molecular sensing, robotics, and nanomedicine. Hence, many students could benefit from exposure to basic knowledge of DNA origami nanotechnology. However, due to the complexity of design, cost of materials, and cost of equipment, experiments with DNA origami have been limited mainly to research institutions in graduate level laboratories with significant prior expertise and well- equipped laboratories. This work focuses on overcoming critical barriers to translating DNA origami methods to educational laboratory settings. In particular, we present a streamlined protocol for fabrication and analysis of DNA origami nanostructures that can be carried out within a 2-hour laboratory course using low-cost equipment, much of which is readily available in educational laboratories and science classrooms. We focus this educational experiment module on a DNA origami nanorod structure that was previously developed for drug delivery applications. In addition to fabricating nanostructures, we demonstrate a protocol for students to analyze structures via gel electrophoresis using classroom-ready gel equipment. These results establish a basis to expose students to DNA origami nanotechnology and can enable or reinforce valuable learning milestones in fields such as biomaterials, biological engineering, and nanomedicine. Furthermore, introducing students to DNA nanotechnology and related fields can also have the potential to increase interest and future involvement by young students.GRAPHICAL ABSTRACT
Visual-motor integration deficits in 3q29 deletion syndrome
Authors: Pollak Rebecca M , Burrell T Lindsey , Cubells Joseph F , Klaiman Cheryl , Murphy Melissa M , Saulnier Celine A , Walker Elaine F , White Stormi Pulver , Mulle Jennifer G 
Published: September 2022

AbstractPurpose3q29 deletion syndrome (3q29del) is associated with neuropsychiatric and neurodevelopmental phenotypes. We previously reported that graphomotor weakness is present in up to 78% of individuals with 3q29del. We have now explored nuances of the graphomotor phenotype and its association with other comorbidities in this population.MethodsParticipants were recruited from the online 3q29 registry (3q29deletion.org) for two days of deep phenotyping. 32 individuals with 3q29del (62.5% male) were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) to assess visual-motor integration. Participants were also evaluated with measures of cognitive ability, executive function, adaptive behavior, and school function.ResultsMales with 3q29del performed significantly worse than females on the VMI and Motor Coordination subtest. VMI performance was significantly associated with ADHD diagnosis and cognitive ability. Compared to published data from individuals with 22q11.2 deletion syndrome, individuals with 3q29del showed significantly more impairment.ConclusionThe 3q29 deletion is associated with substantial deficits in visual-motor integration, Visual Perception, and Motor Coordination. Our data suggests that 3q29del may qualify as a nonverbal learning disability, and that all individuals with 3q29del may benefit from early interventions, including occupational therapy.