bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modeling of mpox: a scoping review
Authors: Molla Jeta , Sekkak Idriss , Mundo Ortiz Ariel , Moyles Iain , Nasri Bouchra 
Published: December 2022

AbstractBackgroundMpox (monkeypox), a disease historically endemic to Africa, has seen its largest outbreak in 2022 by spreading to many regions of the world and has become a public health threat. Informed policies aimed at controlling and managing the spread of this disease necessitate the use of adequate mathematical modelling strategies.ObjectiveIn this scoping review, we sought to identify the mathematical models that have been used to study mpox transmission in the literature in order to determine what are the model classes most frequently used, their assumptions, and the modelling gaps that need to be addressed in the context of the epidemiological characteristics of the ongoing mpox outbreak.MethodsThis study employed the methodology of the PRISMA guidelines for scoping reviews to identify the mathematical models available to study mpox transmission dynamics. Three databases (PubMed, Web of Science and MathSciNet) were systematically searched to identify relevant studies.ResultsA total of 5827 papers were screened from the database queries. After screening, 35 studies that met the inclusion criteria were analyzed, and 19 were finally included in the scoping review. Our results show that compartmental, branching process, Monte Carlo (stochastic), agent-based, and network models have been used to study mpox transmission dynamics between humans as well as between humans and animals. Furthermore, compartmental and branching models have been the most commonly used classes.ConclusionsThere is a need to develop modelling strategies for mpox transmission that take into account the conditions of the current outbreak, which has been largely driven by human-to-human transmission in urban settings. In the current scenario, the assumptions and parameters used by most of the studies included in this review (which are largely based on a limited number of studies carried in Africa in the early 80s) may not be applicable, and therefore, can complicate any public health policies that are derived from their estimates. The current mpox outbreak is also an example of how more research into neglected zoonoses is needed in an era where new and re-emerging diseases have become global public health threats.
Whole-Brain Three-Dimensional Imaging of RNAs at Single-Cell Resolution
Authors: Kanatani Shigeaki , Kreutzmann Judith C. , Li Yue , West Zoe , Vougesi Nikou Danai , Lercke Skytte Jacob , Lydolph Larsen Lea , Tanaka Daisuke H. , Kaczynska Dagmara , Fukumoto Keishiro , Uesaka Naofumi , Tanabe Tsutomu , Miyakawa Ayako , Roostalu Urmas , Hecksher-Sørensen Jacob , Uhlén Per 
Published: December 2022

AbstractWhole-brain three-dimensional (3D) imaging is desirable to obtain a comprehensive and unbiased view of architecture and neural circuitry. However, current spatial analytic methods for brain RNAs are limited to thin sections or small samples. Here, we combined multiple new techniques to develop TRIC-DISCO, a new pipeline that allows imaging of RNA spatial distributions in whole adult mouse brains. First, we developed Tris-mediated retention ofin situhybridization signal during clearing (TRIC), which produces highly transparent tissue while maintaining the RNA signal intensities. We then combined TRIC with DISCO clearing (TRIC-DISCO) by controlling temperature during thein situhybridization chain reaction (isHCR) to ensure uniform whole-brain staining. This pipeline eliminates the requirements for both strict RNase-free environments and workflow-compatible RNase inhibitors. Our TRIC-DISCO pipeline enables simple and robust, single-cell, whole-brain, 3D imaging of transcriptional signatures, cell-identity markers, and noncoding RNAs across the entire brain.
To remain modern, the coexistence program requires modern statistical rigor
Authors: Armitage David W. 
Published: December 2022

AbstractA recent study by Van Dyke et al.1paired experimental drought manipulations with demographic models and trait measurements to project major shifts in coexistence among a number of annual plant taxa. However, re-analysis of the data under alternative, more predictive competition models reveals that the authors’ original conclusions are very sensitive to slight variations in model form. Furthermore, propagating model parameter error into coexistence predictions results in relatively weak support for the majority of coexistence shifts predicted by the authors’ original model. These results highlight the need for increased statistical rigor when treating binary predictions of species coexistence as observed experimental outcomes, as is commonly practiced in empirical coexistence studies.
BRCA2 chaperones RAD51 to single molecules of RPA-coated ssDNA
Authors: Bell Jason C. , Dombrowski Christopher C. , Plank Jody L. , Jensen Ryan B. , Kowalczykowski Stephen C. 
Published: December 2022

AbstractMutations in the breast cancer susceptibility gene, BRCA2, greatly increase an individual’s lifetime risk of developing breast and ovarian cancers. BRCA2 suppresses tumor formation by potentiating DNA repair via homologous recombination. Central to recombination is the assembly of a RAD51 nucleoprotein filament, which forms on single-stranded DNA (ssDNA) generated at or near the site of chromosomal damage. However, Replication Protein-A (RPA) rapidly binds to and continuously sequesters this ssDNA, imposing a kinetic barrier to RAD51 filament assembly that suppresses unregulated recombination. Recombination mediator proteins––of which BRCA2 is the defining member in humans ––alleviate this kinetic barrier to catalyze RAD51 filament formation. We combined microfluidics, microscopy, and micromanipulation to directly measure both the binding of full-length BRCA2 to––and the assembly of RAD51 filaments on––a region of RPA-coated ssDNA within individual DNA molecules designed to mimic a resected DNA lesion common in replication-coupled recombinational repair. We demonstrate that a dimer of RAD51 is minimally required for spontaneous nucleation; however, growth self-terminates below the diffraction limit. BRCA2 accelerates nucleation of RAD51 to a rate that approaches the rapid association of RAD51 to naked ssDNA, thereby overcoming the kinetic block imposed by RPA. Furthermore, BRCA2 eliminates the need for the rate-limiting nucleation of RAD51 by chaperoning a short pre-assembled RAD51 filament onto the ssDNA complexed with RPA. Therefore, BRCA2 regulates recombination by initiating RAD51 filament formation.SignificanceDespite decades of genetic and cell biological studies, mechanistic biochemical analyses of human BRCA2 function in recombinational DNA repair have only been possible since the purification of full-length BRCA2. These mechanistic studies crucially inform with respect to the molecular function of BRCA2 in genome maintenance. Here, we use single-molecule methods to visualize the assembly of RAD51 on individual RPA-coated ssDNA molecules and to see how this process is regulated by the tumor suppressor protein, BRCA2. We show that BRCA2 serves as a chaperone to nucleate RAD51 and deliver it to RPA-coated ssDNA. This work advances understanding of the molecular functions of BRCA2 and, consequently, the molecular etiology of breast cancer in an important way.
On-line reoptimization of mammalian fed-batch culture using a nonlinear model predictive controller
Authors: Ohkubo Tomoki , Sakumura Yuichi , Kunida Katsuyuki 
Published: December 2022

AbstractFed-batch culture enables high productivity by maintaining low substrate concentrations in the early stage of the culture to suppress the accumulation of by-products that are harmful to cell growth. Therefore, they are widely used in the production of biopharmaceuticals by mammalian cells. However, there exists a trade-off in the design of the fed-batch process: early feeding results in the accumulation of harmful by-products, whereas late feeding results in a shortage of substrates needed for cell growth and synthesis of the desired product. To manage this trade-off and maximize the product yield, model-based optimization of the feeding trajectory has been reported in several studies. A significant drawback of this off-line optimization approach is the mismatch between the predictions made using the model and the actual process states, called the process-model mismatch (PMM). If the PMM is large, the off-line optimized feeding trajectory is no longer optimal for the actual process, resulting in lower product yields. Mammalian cell culture models typically contain dozens of unknown parameters that must be estimated prior to optimization. Sufficient parameter estimation is often unachievable owing to the nonlinear nature of these models. We believe that reoptimizing the feeding trajectory in real time using a nonlinear model predictive controller (NLMPC) is an effective solution to this PMM. Although NLMPC is a model-based feedback controller widely utilised in mammalian fed-batch culture, only a few studies have applied it to on-line reoptimization, and it remains unclear whether NLMPC with a standard kinetic model can effectively compensate for a large PMM. In this study, we demonstrated the reoptimization of the feeding trajectory with a NLMPC using two previously reported standard monoclonal antibody (mAb) production models. In both models, NLMPC successfully suppressed the reduction in mAb yield caused by the intentional introduction of PMM.
Temperature moderates eDNA-biomass relationships in northern pike
Authors: Ogonowski M. , Karlsson E. , Vasemägi A. , Sundin J. , Bohman P. , Sundblad G. 
Published: December 2022

AbstractSupport for eDNA as a quantitative monitoring tool is growing worldwide. Despite advances there are still uncertainties regarding the representability of the eDNA signal over varying spatiotemporal scales, influence of abiotic forcing and phenological changes affecting behavior of the study organism, particularly in open environments. To assess the spatiotemporal variability and predictive power of quantitative eDNA analysis, we applied species-specific real-time quantitative PCR on water filtrates during two visits to 22 coastal bays in the Baltic Sea. Within bays, we collected water along four transects across each bay and compared the pooled eDNA concentration to temporally matched catches from standardized angling targeting the northern pike (Esox lucius) a species for which reliable monitoring data is lacking. We found the variability in eDNA concentrations between transects to be moderate (21%) but still considerably lower than across bays and visits (52%), suggesting small scale spatial differences are of less importance during spring when pike spawn. Standardized angling catches, bay area, and water temperature together explained 48% of the variance in eDNA concentrations. DNA concentrations decreased with increasing bay area, likely indicating a dilution effect. Notably, the relationship between eDNA and standardized catches was positive but varied with temperature and the eDNA-abundance relationship was only significant at higher temperatures, which also coincided with a higher proportion of spawning/spent fish. We conclude that temperature is a key moderating factor driving changes in pike behaviour and spring DNA-dynamics. We recommend that future surveys focus on larger spatiotemporal scales during times when the influence of changing temperatures is minimized.
Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit cytopathic effect, Papain-like Protease and MPROof SARS-CoV-2
Authors: Bello Shaibu Oricha , Imam Mustapha Umar , Bello Muhammad Bashir , Yunusa Abdulmajeed , Adamu Adamu Ahmed , Shuaibu Abdulmalik , Igumbor Ehimario Uche , Habib Zaiyad Garba , Popoola Mustapha Ayodele , Ochu Chinwe Lucia , Bello Aishatu Yahaya , Deeni Yusuf Yahaya , Okoye Ifeoma 
Published: December 2022

AbstractWe previously showed that Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin inhibit SARS-COV-2 induced cytopathic effect (CPE) in Vero cells. In this study and using validated quantitative neutral red assay, we show that the inhibition of CPE is concentration dependent with Inhibitory Concentration-50(IC50) of 3.27 μM, 4.23 μM, 9.29 μM, 3.19 μM and 84.31 μM respectively. Furthermore, Erythromycin, Retapamulin, Pyridoxine, Folic acid and Ivermectin dose dependently inhibit SARS-CoV-2 Papain-like Protease with IC50of 0.94 μM, 0.88 μM, 1.14 μM, 1.07 μM, 1.51 μM respectively and the main protease(MPRO) with IC50of 1.35 μM, 1.25 μM, 7.36 μM, 1.15 μM and 2.44 μM respectively. The IC50for all the drugs, except ivermectin, are at the clinically achievable plasma concentration in human, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by Ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.
Selective transduction and photoinhibition of pre-Botzinger neurons that project to the facial nucleus in rats affect the nasofacial activity
Authors: Melo MR , Wykes A , Connelly AA , Bassi JK , Cheung SD , McDougall S , Menuet C , Bathgate RAD , Allen AM 
Published: December 2022

ABSTRACTThe preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.
Fraction of copy-number alterations significantly predicts survival following immunotherapy in a few cancers
Authors: Chang Tiangen , Cao Yingying , Shulman Eldad D. , Schäffer Alejandro A. , Ruppin Eytan 
Published: December 2022

SUMMARYVarious studies have shown that high tumor mutation burden (TMB) may predict response to immune checkpoint therapy, at least in some cancer types1,2. However, identifying patients with low TMB that are still likely to respond to cancer immunotherapy is an important open challenge. Recently, Spurr et al.3reported that the tumoraneuploidy score(AS), defined as the fraction of chromosome arms with arm-level copy number alterations in a sample, is predictive of survival following immunotherapy in low-TMB patients across multiple cancers. By re-analyzing the same data set by performing survival analysis in individual cancer types separately, we find that AS only significantly predicts survival in one single cancer indication. We further find that another metric conceptually related to the AS,the fraction of genome encompassed by copy number alterations (FGA), if called with a conventional copy number calling cutoff, has stronger predictive power than the AS proposed in3, and that this observation holds even if the FGA and AS thresholds for presence/absence of copy number events are set comparably. However, with the current available data, even FGA can predict survival following immunotherapy in only a few cancer indications.
Phylogenetic endemism of the world’s seed plants
Authors: Cai Lirong , Kreft Holger , Taylor Amanda , Schrader Julian , Dawson Wayne , Essl Franz , van Kleunen Mark , Pergl Jan , Pyšek Petr , Winter Marten , Weigelt Patrick 
Published: December 2022

AbstractAssessing phylogenetic endemism, i.e., the distribution of geographically restricted and evolutionarily unique species, is key to understanding biogeographic patterns and processes and critical for global conservation planning. Here, we quantified the geographic distribution and drivers of phylogenetic endemism for ~320,000 seed plants worldwide and identified centers and drivers of evolutionarily young (neoendemism) and evolutionarily old endemism (paleoendemism). Tropical and subtropical islands of the Southern Hemisphere as well as tropical mountainous regions displayed the world’s highest phylogenetic endemism. Tropical moist forests (e.g. Amazonia) and continental islands in south-east Asia emerged as centers of paleoendemism, while both high neo- and paleoendemism were found on ancient continental fragment islands (e.g. Madagascar) and in Mediterranean-climate regions. Global variation in phylogenetic endemism was best explained by a combination of past and present environmental factors (80.3% – 88.1% of variance explained). Geographic isolation and environmental heterogeneity emerged as primary drivers promoting high phylogenetic endemism. Also, warm and wet climates with long-term climatic stability showed a significant positive effect. However, environmental effects on phylogenetic endemism varied with geographic isolation, reflecting the unique evolutionary and biogeographic dynamics on oceanic islands. Long-term climatic stability promoted the persistence of paleoendemics, while isolation promoted higher neoendemism leading to oceanic islands and tropical mountainous regions being centers of both neo- and paleoendemism. Our study provides new insights into the evolutionary underpinnings of biogeographic patterns in seed plants, and by identifying areas of high evolutionary and biogeographic uniqueness, it may serve as a key resource for setting global conservation priorities.
Insights into mammalian TE diversity via the curation of 248 mammalian genome assemblies
Authors: Osmanski Austin B. , Paulat Nicole S. , Korstian Jenny , Grimshaw Jenna R. , Halsey Michaela , Sullivan Kevin A.M. , Moreno-Santillán Diana D. , Crookshanks Claudia , Roberts Jacquelyn , Garcia Carlos , Johnson Matthew G. , Densmore Llewellyn D. , Stevens Richard D. ,   Zoonomia Consortium, Rosen Jeb , Storer Jessica M. , Hubley Robert , Smit Arian F.A. , Dávalos Liliana M. , Lindblad-Toh Kerstin , Karlsson Elinor K. , Ray David A. 
Published: December 2022

AbstractWe examined transposable element (TE) content of 248 placental mammal genome assemblies, the largestde novoTE curation effort in eukaryotes to date. We find that while mammals resemble one another in total TE content and diversity, they show substantial differences with regard to recent TE accumulation. This includes multiple recent expansion and quiescence events across the mammalian tree. Young TEs, particularly LINEs, drive increases in genome size while DNA transposons are associated with smaller genomes. Mammals tend to accumulate only a few types of TE at any given time, with one TE type dominating. We also found association between dietary habit and the presence of DNA transposon invasions. These detailed annotations will serve as a benchmark for future comparative TE analyses among placental mammals.One-Sentence SummaryAde novoassessment of TE content in 248 mammals finds informative trends in mammalian genome evolution.
Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein
Authors: Korn Sophie M. , von Ehr Julian , Dhamotharan Karthikeyan , Tants Jan-Niklas , Abele Rupert , Schlundt Andreas 
Published: December 2022

AbstractThe family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing, and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately-100-kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA- and RNA-binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerise, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.
Spi-C and PU.1 counterregulateRag1andIgκ transcription to effect immunoglobulin kappa recombination in small pre-B cells
Authors: Xu Li S. , Zhu Jiayu T. , Raczkowski Hannah L. , Batista Carolina R. , DeKoter Rodney P. 
Published: December 2022

AbstractB cell development requires the ordered rearrangement ofIggenes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags.Igκ rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26-transformation-specific (ETS) transcription factor Spi-C is activated in response to double-stranded DNA breaks (DSBs) in small pre-B cells to negatively regulate pre-BCR signaling andIgκ rearrangement. However, it is not clear if Spi-C regulatesIgκ rearrangement through transcription or by controlling RAG expression. In this study, we investigated the mechanism of Spi-C negative regulation ofIgκ light chain rearrangement. Using an inducible expression system in a pre-B cell line, we found that Spi-C negatively regulatedIgκ rearrangement,Igκ transcript levels, andRag1transcript levels. We found thatIgκ andRag1transcript levels were increased in small pre-B cells fromSpic-/-mice. In contrast,Igκ andRag1transcript levels were activated by PU.1 and were decreased in small pre-B cells from PU.1-deficient mice. Using chromatin immunoprecipitation analysis, we identified an interaction site for PU.1 and Spi-C located in theRag1promoter region. These results suggest that Spi-C and PU.1 counterregulateIgκ transcription andRag1transcription to effectIgκ recombination in small pre-B cells.