bluuebunny/crossref_metadata_2025_split huggingface dataset:
The interplay between subcritical fluctuations and import: understanding COVID-19 epidemiology dynamics
Authors: Stollenwerk Nico , Van-Dierdonck Joseba Bidaurrazaga , Mar Javier , Arrizabalaga Irati Eguiguren , Cusimano Nicole , Knopoff Damián , Anam Vizda , Aguiar Maíra 
Published: December 2020

AbstractThe effective reproduction ratior(t) of an epidemic, defined as the average number of secondary infected cases per infectious case in a population in the current state, including both susceptible and non-susceptible hosts, controls the transition between a subcritical threshold regime (r(t) < 1) and a supercritical threshold regime (r(t) > 1). While in subcritical regimes, an index infected case will cause an outbreak that will die out sooner or later, with large fluctuations observed when approaching the epidemic threshold, the supercritical regimes leads to an exponential growths of infection.The super- or subcritical regime of an outbreak is often not distinguished when close to the epidemic threshold, but its behaviour is of major importance to understand the course of an epidemic and public health management of disease control. In a subcritical parameter regime undetected infection, here called “imported case” or import, i.e. a susceptible individual becoming infected from outside the study area e.g., can either spark recurrent isolated outbreaks or keep the ongoing levels of infection, but cannot cause an exponential growths of infection. However, when the community transmission becomes supercritical, any index case or few “imported cases” will lead the epidemic to an exponential growths of infections, hence being distinguished from the subcritical dynamics by a critical epidemic threshold in which large fluctuations occur in stochastic versions of the considered processes.As a continuation of the COVID-19 Basque Modeling Task Force, we now investigate the role of critical fluctuations and import in basic Susceptible-Infected-Susceptible (SIS) and Susceptible-Infected-Recovered (SIR) epidemiological models on disease spreading dynamics. Without loss of generality, these simple models can be treated analytically and, when considering the mean field approximation of more complex underlying stochastic and eventually spatially extended or generalized network processes, results can be applied to more complex models used to describe the COVID-19 epidemics. In this paper, we explore possible features of the course of an epidemic, showing that the subcritical regime can explain the dynamic behaviour of COVID-19 spreading in the Basque Country, with this theory supported by empirical data data.
A novel fermented Yi traditional medicine efficiently suppresses the replication of SARS-CoV-2 in vitro
Authors: Fang Shisong , Xu Benhong , Song Xiangrong , Liu Wukun , Xie Yongmei , Yang Xifei 
Published: December 2020

AbstractCurrently, the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide epidemic, causing more than 80 million infections and more than 1.7 million deaths. The pandemic has led to the closure of enterprises and schools in many countries, resulting in serious disruption of the global economy and social activities. Remdesivir is currently approved by the FDA for the treatment of COVID-19, but the WHO declared that Remdesivir is almost ineffective against COVID-19. The research and development of vaccines has made great progress, but it will take at least several months for safe and effective vaccines to be widely used clinically. Clinical studies revealed that some Traditional Chinese Medicines, such as Lianhua Qingwen Capsule and Huoxiang Zhengqi Water, exhibited excellent therapeutic effect on COVID-19. However, until now, there is still no cure for COVID-19. Therefore, there is an urgent need to find medicines that can effectively fight against the SARS-CoV-2. In this study, JIE BEN No. 10 (JB10), a fermentation broth produced by Yi traditional medicine fermentation technology, was explored for its anti-coronavirus activity. Thein vitrodata showed that JB10 could significantly suppresses the replication of the SARS-CoV-2 with an EC50of 769.1 times dilution and a selection index of 42.68. Further studies indicated that JB10 had significant anti-inflammatory and antioxidant activities. The analysis of active components suggested that JB10 contained a large amount of superoxide dismutase (SOD), flavones, polyphenols, crude polysaccharide, etc. which may explain the anti-coronavirus activity, anti-inflammatory and antioxidant effects. Our study provides a new potentially therapeutic strategy for COVID-19.
Zinc Dependent Conformational Changes in the Cation Diffusion Facilitator YiiP from S. oneidensis
Authors: Lopez-Redondo Maria , Fan Shujie , Koide Akiko , Koide Shohei , Beckstein Oliver , Stokes David L. 
Published: December 2020

AbstractYiiP is a secondary transporter that couples Zn2+transport to the proton motive force. Structural studies of YiiP from prokaryotes as well as Znt8 from humans revealed three different Zn2+sites and a conserved homodimeric architecture. These structures define the inward-facing and outward-facing states that characterize the archetypal alternating access mechanism of transport. To study effects of Zn2+binding on the conformational transition, we have used a YiiP/Fab complex for single-particle cryo-EM together with Molecular Dynamics simulation to compare structures of YiiP fromS. oneidensisin presence and absence of Zn2+. Without Zn2+, YiiP exhibits enhanced flexibility and adopts a novel conformation that appears to be an intermediate state. The transition closes a hydrophobic gate and is controlled by the Zn2+site at the cytoplasmic membrane interface. This work enhances our understanding of individual Zn2+binding sites and their role in the conformational dynamics that governs the transport cycle.
Sex reversal and ontogeny under climate change and chemical pollution: are there interactions between the effects of elevated temperature and a xenoestrogen on early development in agile frogs?
Authors: Mikó Zsanett , Nemesházi Edina , Ujhegyi Nikolett , Verebélyi Viktória , Ujszegi János , Kásler Andrea , Bertalan Réka , Vili Nóra , Gál Zoltán , Hoffmann Orsolya I. , Hettyey Attila , Bókony Veronika 
Published: December 2020

AbstractAnthropogenic environmental change poses a special threat to species in which genetic sex determination can be overwritten by the thermal and chemical environment. Endocrine disrupting chemicals as well as extreme temperatures can induce sex reversal in such species, with wide-ranging consequences for fitness, demography, population viability and evolution. Despite accumulating evidence suggesting that chemical and thermal effects may interact in ecological contexts, little is known about their combined effects on sex reversal. Here we assessed the simultaneous effects of high temperature (masculinizing agent) and 17α-ethinylestradiol (EE2), a widespread xenoestrogen (feminizing agent), on sexual development and fitness-related traits in agile frogs (Rana dalmatina). We exposed tadpoles to a six-days heat wave (30 °C) and/or an ecologically relevant concentration of EE2 (30 ng/L) in one of three consecutive larval periods, and diagnosed sex reversals two months after metamorphosis using species-specific markers for genetic sexing. We found that high temperature induced female-to-male sex reversal, decreased survival, delayed metamorphosis, decreased body mass at metamorphosis, and increased the proportion of animals that had no fat bodies, while EE2 had no effect on these traits. Simultaneous exposure to heat and EE2 had non-additive effects on juvenile body mass, which were dependent on treatment timing and further complicated by a negative effect of sex reversal on body mass. These results show that environmentally relevant exposure to EE2 does not diminish the masculinizing effects of high temperature. Instead, our findings on growth suggest that climate change and chemical pollution may have complex consequences for individual fitness and population persistence in species with environment-sensitive sex determination.
Genealogical structure changes as range expansions transition from pushed to pulled
Authors: Birzu Gabriel , Hallatschek Oskar , Korolev Kirill S. 
Published: December 2020

AbstractRange expansions accelerate evolution through multiple mechanisms including gene surfing and genetic drift. The inference and control of these evolutionary processes ultimately relies on the information contained in genealogical trees. Currently, there are two opposing views on how range expansions shape genealogies. In invasion biology, expansions are typically approximated by a series of population bottlenecks producing genealogies with only pairwise mergers between lineages—a process known as the Kingman coalescent. Conversely, traveling-wave models predict a coalescent with multiple mergers, known as the Bolthausen–Sznitman coalescent. Here, we unify these two approaches and show that expansions can generate an entire spectrum of coalescent topologies. Specifically, we show that tree topology is controlled by growth dynamics at the front and exhibits large differences between pulled and pushed expansions. These differences are explained by the fluctuations in the total number of descendants left by the early founders. High growth cooperativity leads to a narrow distribution of reproductive values and the Kingman coalescent. Conversely, low growth cooperativity results in a broad distribution, whose exponent controls the merger sizes in the genealogies. These broad distribution and non-Kingman tree topologies emerge due to the fluctuations in the front shape and position and do not occur in quasi-deterministic simulations. Overall, our results show that range expansions provide a robust mechanism for generating different types of multiple mergers, which could be similar those observed in populations with strong selection or high fecundity. Thus, caution should be exercised in making inferences about the origin of non-Kingman genealogies.Significance statementSpatial dynamics are important for understanding genetic diversity in many contexts, such as cancer and infectious diseases. Coalescent theory offers a powerful framework for interpreting and predicting patters of genetic diversity in populations, but incorporating spatial structure into the theory has proven difficult. Here, we address this long-standing problem by studying the coalescent in a spatially expanding population. We find the topology of the coalescent changes depending on the growth dynamics at the front. Using analytical arguments, we show that the transition between coalescent topologies is universal and is controlled by a parameter related to the expansion velocity. Our theory makes precise predictions about the effects of population dynamics on genetic diversity at the expansion front, which we confirm in simulations.
Preventing cancer by long-term partial Myc suppression
Authors: Sodir Nicole M. , Pellegrinet Luca , Kortlever Roderik M. , Kwon Yong-Won , Kim Shinseog , Garcia Daniel , Perfetto Alessandra , Anastasiou Panayiotis , Swigart Lamorna Brown , Littlewood Trevor D. , Evan Gerard I. 
Published: December 2020

AbstractMyc+/−haploinsufficient mice and mice with deletedMycenhancers express reduced levels of the pleiotropic transcription factor Myc. Such mice are viable, with relatively mild pathologies, but show delay in onset of certain cancers. However, many phenotypes arising from germline gene perturbation are indirect consequences of adaptive developmental compensation and so do not translate to equivalent phenotypes when applied to adults. To ascertain whether systemic Myc hypomorphism also conferred cancer protection when acutely imposed in adults, and what the side-effects of this might be, we constructed a genetically engineered mouse model in which Myc expression may be systemically and reversibly hypomorphed at will. Acute imposition of Myc hypomorphism in adult mice conferred potent protection against both KRasG12D-driven lung and pancreatic cancers yet elicited only mild haematopoietic side effects. These side effects were completely suppressed by imposing Myc hypomorphism metronomically – a regimen that nonetheless retained potent cancer prophylaxis. Our data identify a key bottleneck at the transition from pre-malignant hyperplasia to overt tumour that is peculiarly reliant on levels of Myc that are higher than those required for most adult physiology, offering a possible window of opportunity for Myc inhibition in cancer prophylaxis.
Search behavior of individual foragers involves neurotransmitter systems characteristic for social scouting
Authors: Chatterjee Arumoy , Bais Deepika , Brockmann Axel , Ramesh Divya 
Published: December 2020

AbstractIn honey bees search behavior occurs as social and solitary behavior. In the context of foraging, searching for food sources is performed by behavioral specialized foragers, the scouts. When the scouts have found a new food source, they recruit other foragers (recruits). These recruits never search for a new food source on their own. However, when the food source is experimentally removed, they start searching for that food source. Our study provides a detailed description of this solitary search behavior and the variation of this behavior among individual foragers. Furthermore, mass spectrometric measurement showed that the initiation and performance of this solitary search behavior is associated with changes in glutamate, GABA, histamine, aspartate and the catecholaminergic system in the optic lobes and central brain area. These findings strikingly correspond with the results of an earlier study that showed that scouts and recruits differ in the expression of glutamate and GABA receptors. Together, the results of both studies provide first clear support for the hypothesis that behavioral specialization in honey bees is based on adjusting modulatory systems involved in solitary behavior to increase the probability or frequency of that behavior.
CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm
Authors: Kim Eun Na , Yu Jiyoung , Lim Joon Seo , Jeong Hwangkyo , Kim Chong Jai , Choi Jae-Sung , Kim So Ra , Ahn Hee-Sung , Kim Kyunggon , Oh Se Jin 
Published: December 2020

AbstractObjectiveThe molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited in AAA and examined the associated pathogenic signaling pathways.MethodsTwenty-four cases of AAA were analyzed and their histological features were compared according to the level of serum CRP and the degree of mCRP deposition. Proteomic analysis was performed in AAA cases with strong and diffuse CRP immunopositivity (n=7) and those with weak, focal, and junctional CRP immunopositivity (n=3).ResultsmCRP was deposited in the aortic specimens of AAA in a characteristic pattern that coincided with the lesion of the diminished elastic layer of the aortic wall. High serum CRP level was associated with stronger mCRP immunopositivity and a larger maximal diameter of aortic aneurysm. Proteomic analysis in AAA showed that multiple proteins were differentially expressed according to mCRP immunopositivity. Also, ingenuity pathway analysis showed that pathways associated with atherosclerosis, acute phase response, complement system, immune system, and coagulation were enriched in AAA cases with high mCRP immunopositivity.ConclusionsAAA showed a characteristic deposition of mCRP, and multiple potentially pathologic signaling pathways were upregulated in AAA cases with strong CRP immunopositivity. mCRP and the aforementioned pathological pathways may serve as targets for managing the progression of AAA.
Bab2 activates JNK signaling to reprogramDrosophilawing disc development
Authors: Zhao Yunpo , Duan Jianli , Dziedziech Alexis , Büttner Sabrina , Engström Ylva 
Published: December 2020

AbstractIn response to cellular stress and damage, certain tissues are able to regenerate and to restore tissue homeostasis. InDrosophilaimaginal wing discs, dying cells express mitogens that induce compensatory proliferation in the surrounding tissue. Here we report that high levels of the BTB/POZ transcription factor Bab2 in the posterior compartment of wing discs activates c-Jun N-terminal kinase (JNK) signaling and local, cell-autonomous apoptotic cell death. This in turn triggered the upregulation of the Dpp mitogen and cellular proliferation in the anterior compartment in a JNK-dependent manner. In the posterior compartment, however,dppexpression was suppressed, most likely by direct transcriptional repression by Bab2. This dual-mode of JNK-signaling, autocrine pro-apoptotic signaling and paracrine pro-proliferative signaling, led to opposite effects in the two compartments and reprogramming of the adult wing structure. We establish Bab2 as a regulator of wing disc development, with the capacity to reprogram development via JNK activation in a cell-autonomous and non-cell-autonomous manner.Summary statementZhao et al. shows that the BTB/POZ transcription factor Bab2 is a potent activator of JNK signaling, apoptosis and compensatory proliferation, thereby driving both pro-tumorigenic and anti-tumorigenic processes.
ARHGEF26 enhancesSalmonellainvasion and inflammation in cells and mice
Authors: Bourgeois Jeffrey S. , Wang Liuyang , Alvarez Monica I. , Everitt Jeffrey , Awadia Sahezeel , Wittchen Erika S. , Garcia-Mata Rafael , Ko Dennis C. 
Published: December 2020

AbstractSalmonellahijack host machinery in order to invade cells and establish infection. While considerable work has described the role of host proteins in invasion, much less is known regarding how natural variation in these invasion-associated host proteins affectsSalmonellapathogenesis. Here we leveraged a candidate cellular GWAS screen to identify natural genetic variation in theARHGEF26 (Rho Guanine Nucleotide Exchange Factor 26) gene that renders lymphoblastoid cells susceptible toSalmonellaTyphi and Typhimurium invasion. Experimental follow-up redefined ARHGEF26’s role inSalmonellaepithelial cell invasion, identified serovar specific interactions, implicated ARHGEF26 in SopE-mediated invasion, and revealed that the ARHGEF26-associated proteins DLG1 and SCRIB facilitateS. Typhi uptake. Importantly, we show that ARHGEF26 plays a critical role inS. Typhimurium pathogenesis by contributing to bacterial burden in the enteric fever murine model, as well as inflammation in the gastroenteritis infection model. The impact ofARHGEF26on inflammation was also seen in cells, as knockdown reduced IL-8 production in HeLa cells. Together, these data reveal pleiotropic roles for ARHGEF26 function during infection and highlight that many of the interactions that occur during infection that are thought to be well understood likely have underappreciated complexity.Author SummaryDuring infection,Salmonellamanipulates host cells into engulfing the bacteria and establishing an intracellular niche. While many studies have identified genes involved in different stages of thisSalmonellainvasion process, few studies have examined how differences between human hosts contribute to infection susceptibility. Here we leveraged a candidate genetic screen to identify natural genetic variation in the human ARHGEF26 gene that correlates withSalmonellainvasion. Springboarding from this result, we experimentally tested and revised existing models of ARHGEF26’s role inSalmonellainvasion, discovered an additional new role for ARHGEF26 duringSalmonelladisease, and confirmed our findings in mouse models. Building on how ARHGEF26 functions in other contexts, we implicated two ARHGEF26-interacting host proteins as contributors toSalmonellapathobiology. Collectively, these results identify a potential source of inter-person diversity in susceptibility to Salmonella disease, expand our molecular understanding of Salmonella infection to include a multifaceted role for ARHGEF26, and identify several important future directions that will be important to understand howSalmonellarecruit and manipulate ARHGEF26 as well as how ARHGEF26 is able to driveSalmonella-beneficial processes.
The effect of prior long-term recellularization with keratocytes of decellularized porcine corneas implanted in a rabbit anterior lamellar keratoplasty model
Authors: Fernández-Pérez Julia , Madden Peter W. , Brady Robert Thomas , Nowlan Peter F. , Ahearne Mark 
Published: December 2020

AbstractDecellularized porcine corneal scaffolds are a potential alternative to human cornea for keratoplasty. Although clinical trials have reported promising results, there can be corneal haze or scar tissue. Here, we examined if recellularizing the scaffolds with human keratocytes would result in a better outcome. Scaffolds were prepared that retained little DNA (14.89 ± 5.56 ng/mg) and demonstrated a lack of cytotoxicity byin vitro. The scaffolds were recellularized using human corneal stromal cells and cultured for between 14 in serum-supplemented media followed by a further 14 days in either serum free or serum-supplemented media. All groups showed full-depth cell penetration after 14 days. When serum was present, staining for ALDH3A1 remained weak but after serum-free culture, staining was brighter and the keratocytes adopted a native dendritic morphology with an increase (p < 0.05) of keratocan, decorin, lumican and CD34 gene expression. A rabbit anterior lamellar keratoplasty model was used to compare implanting a 250 µm thick decellularized lenticule against one that had been recellularized with human stromal cells. In both groups, host rabbit epithelium covered the implants, but transparency was not restored after 3 months. Post-mortem histology showed under the epithelium, a less-compact collagen layer, which appeared to be a regenerating zone with some α-SMA staining, indicating fibrotic cells. In the posterior scaffold, ALDH1A1 staining was present in all the acellular scaffold, but in only one of the recellularized lenticules. We conclude that recellularization with keratocytes alone may not be sufficiently beneficial to justify introducing allogeneic cells without concurrent treatment to further manage keratocyte phenotype.