bluuebunny/crossref_metadata_2025_split huggingface dataset:
SMITH: Spatially Constrained Stochastic Model for Simulation of Intra-Tumour Heterogeneity
Authors: Streck Adam , Kaufmann Tom , Schwarz Roland F. 
Published: July 2022

AbstractMotivationSimulations of cancer evolution and cellular growth have proven highly useful to study, in detail, the various aspects of intra-tumour heterogeneity, including the effect of selection, mutation rates, and spatial constraints. However, most methods are computationally expensive lattice-embedded models which cannot simulate tumours with a realistic number of cells and rely on various simplifications. Alternatively, well-mixed stochastic models, while efficient and scalable, do not typically include spatial constraints and cannot reproduce the rich clonal dynamics observed in real-world tumours.ResultsWe present SMITH, a simple, efficient, and explainable model of cancer evolution that combines the advantages of well-mixed stochastic models with a new confinement mechanism which limits the growth of clones based on the overall tumour size. We demonstrate that this confinement mechanism is sufficient to induce the rich clonal dynamics observed in spatial models, while allowing for a clear geometric interpretation and efficient simulation of one billion cells within a few minutes on a desktop PC. We explore the extent of stochasticity and rigorously assess the effects of cell turnover, mutation rate, fitness effects and confinement on the resulting clonal structures.Availability and ImplementationSMITH is implemented in C# and freely available at bitbucket.org/schwarzlab/smith together with binaries for all major platforms. For rich visualisations of the simulated clonal dynamics we provide an accompanying Python package PyFish at bitbucket.org/schwarzlab/pyfish.Supplementary informationAll supplementary figures are in the supplementary document.
FunFun: ITS-based functional annotator of fungal communities
Authors: Krivonos Danil V. , Konanov Dmitry N. , Ilina Elena N. 
Published: July 2022

AbstractFungi are inseparable companions of human life, they can be found in both the environment and human organs including skin, respiratory tract and gut. Studies of fungal communities are of great interest to modern biology, partially due to their specific way of life and the presence of unique biochemical pathways they have. Fungi have been shown to be both producers of useful compounds, such as antibiotics and organic acids, and pathogens of various diseases. When considering the selected fungal community, in a number of cases it is rather difficult to evaluate its functional capabilities, which is partially caused by some technical difficulties in the analysis and annotation of whole eukaryotic genomes. In practice, the taxonomic composition of fungal communities is determined using short marker sequences. The most popular fungal taxonomy markers are ITS (internal transcribed spacer) sequences. Here, we present FunFun, the instrument that allows to evaluate the functional content of an individual fungus or mycobiome based on ITS sequencing data.
Wireless Neuromodulation at Submillimeter Precision via a Microwave Split-Ring Resonator
Authors: Marar Carolyn , Jiang Ying , Li Yueming , Lan Lu , Zheng Nan , Yang Chen , Cheng Ji-Xin 
Published: July 2022

AbstractMicrowaves, with wavelengths on the order of millimeters, have centimeter-scale penetration depth and have been shown to reversibly inhibit neuronal activity. Yet, microwaves alone do not provide sufficient spatial precision to modulate target neurons without affecting surrounding tissues. Here, we report an implantable split-ring resonator (SRR) that generates a localized and enhanced microwave field at the gap site with submillimeter spatial precision. The SRR breaks the microwave diffraction limit and greatly enhances the efficiency of microwave inhibition. With the SRR, microwaves at dosages below the safe exposure limit are shown to inhibit neurons within 1 mm from the gap site. Application of the microwave SRR to suppress seizures in an in vivo model of epilepsy is demonstrated.
Transcriptome profiling implicates a role for Wnt signaling during epileptogenesis in a mouse model of temporal lobe epilepsy
Authors: Mardones Muriel D , Gupta Kunal 
Published: July 2022

AbstractMesial Temporal lobe epilepsy (mTLE) is a life-threatening condition characterized by recurrent epileptic seizures initiating in the hippocampus. mTLE can develop after exposure to risk factors such as seizure, trauma, and infection. Within the latent period between exposure and onset of recurrent seizures, pathological remodeling events occur which are believed to contribute to epileptogenesis. The molecular mechanisms responsible for epileptogenesis in the seizure network are currently unclear. We used the mouse intrahippocampal kainate model of mTLE to investigate transcriptional dysregulation in the ipsilateral-injected epileptogenic zone (EZ), and contralateral peri-ictal zone (PIZ) in the dentate gyrus (DG) of the hippocampus during the first 14-days after induction of status epilepticus (SE). DG were micro-dissected 3, 7 and 14-days after SE for high-throughput RNA-sequencing. In the EZ, dynamic transcriptional dysregulation was evident over 2-weeks with early expression of genes representing cell signaling, migration and proliferation. In the PIZ, gene dysregulation was most prominent at 3-days in similar domains. Inflammatory gene groups were also prominent over the 2-week epileptogenic period in the EZ and PIZ. We uncovered that the Wnt signaling pathway was dysregulated in the EZ and PIZ at 3-days and we validated these changes via immunohistochemistry. This suggests that critical gene changes occur early after neurological insult and that canonical Wnt signaling may play a role within this latent period. These findings offer new insights into gene expression changes that occur in the hippocampal DG early after SE and may help to identify novel therapeutic targets that could prevent epileptogenesis.Significance statementMesial temporal lobe epilepsy (mTLE) is a severe life-threatening condition that is often medically refractory. While risk factors for the delayed development of mTLE are well-known, there are currently no therapeutic interventions that prevent epileptogenesis. Knowledge of the gene dysregulation events that occur during the latent period between exposure and epilepsy is critical to understanding epileptogenesis and developing new therapies. We utilized a mouse model of adult focal mTLE, the most common form of adult clinical epilepsy, and investigated transcriptional changes in the dentate gyrus during the first 2-weeks after status epilepticus. These data provide new insights into specific gene changes and pathways within different regions of the seizure network that could be targeted to prevent the development of epilepsy.
Body-plan reorganization in a sponge correlates with microbiome change
Authors: Vargas Sergio , Leiva Laura , Eitel Michael , Curdt Franziska , Rohde Sven , Arnold Christopher , Nickel Michael , Schupp Peter , Orsi William D. , Adamska Maja , Wörheide Gert 
Published: July 2022

AbstractMounting evidence suggests that animals and their associated bacteria interact via intricate molecular mechanisms, and it is hypothesized that disturbances to the microbiome can influence animal development. Sponges diverged from other animals more than 750 MYA and represent one of the earliest branching animal phyla that exhibit symbiotic relationships with diverse bacteria. Over 41 microbial phyla have been found in association with sponges, forming a holobiont that is integral to aquatic ecosystems worldwide. Sponge-associated microbes contain an enriched set of proteins bearing eukaryotic-like domains, and their metabolism supports the host with nutrients. This indicates strong physiological interconnections in the holobiont, which are thought to be modulated by sponge immunity and pattern-recognition proteins. Despite the hypothesized tight physiological integration and ancient origin of the sponge holobiont, the effect of changes in the symbiotic community on the sponge metabolism and morphogenesis remains poorly understood. Here, we show that the loss of a key microbial sponge symbiont correlates with a stark body plan reorganization of the sponge host. This reorganization is coupled with broad transcriptomic changes and includes the modulation of signaling pathways known to be involved in morphogenesis and innate immune response in sponges and other animals. This study provides a combined genetic, physiological, and morphological assessment of the effect of changes in the microbiome on sponge post-embryonic development and homeostasis. The drastic microbiome reorganization and the correlated response observed in the sponge host provide evidence for a coupling between sponge transcriptomic state and the state of its microbiome. Our results suggest that sponges use molecular mechanisms to respond to changes in their microbiome and that the ability to sense and respond to microbiome perturbations has deep evolutionary origins among animals.
Disaggregation as an interaction mechanism among intestinal bacteria
Authors: Sundarraman Deepika , Smith T. Jarrod , Kast Jade V. Z. , Guillemin Karen , Parthasarathy Raghuveer 
Published: July 2022

AbstractThe gut microbiome contains hundreds of interacting species that together influence host health and development. The mechanisms by which intestinal microbes can interact, however, remain poorly mapped and are often modeled as spatially unstructured competitions for chemical resources. Recent imaging studies examining the zebrafish gut have shown that patterns of aggregation are central to bacterial population dynamics. In this study, we focus on bacterial species of genera Aeromonas and Enterobacter. Two zebrafish gut derived isolates, Aeromonas ZOR0001 (AE) and Enterobacter ZOR0014 (EN), when mono-associated with the host, are highly aggregated and located primarily in the intestinal midgut. An Aeromonas isolate derived from the commensal strain, Aeromonas-MB4 (AE-MB4), differs from the parental strain in that it is composed mostly of planktonic cells localized to the anterior gut. When challenged by AE-MB4, clusters of EN rapidly fragment into non-motile, slow-growing, dispersed individual cells with overall abundance two orders of magnitude lower than the mono-association value. In the presence of a certain set of additional gut bacterial species, these effects on EN are dampened. In particular, if AE-MB4 invades an already established multi-species community, EN persists in the form of large aggregates. These observations reveal an unanticipated competition mechanism based on manipulation of bacterial spatial organization, namely dissolution of aggregates, and provide evidence that multi-species communities may facilitate stable intestinal co-existence.SignificanceThe diverse microbial communities inhabiting vertebrate intestines influence many aspects of their hosts’ health and development. The rules governing community assembly and even the types of interactions that are possible among gut microbes remain poorly understood, however, with the role of spatial aggregation in interspecies dynamics being especially unclear. To address this, we performed live imaging studies of the larval zebrafish gut, focusing on two spatially distinct bacterial species that exhibit strong competition, discovering that the latter can induce a striking, rapid disintegration of aggregates of the former. This competition is attenuated in the presence of a particular set of additional bacterial species. Our findings reveal an unanticipated interaction mechanism and highlight that diverse communities may stabilize the gut microbiome.
Metabolic functional redundancy of the CYP9A subfamily members leads to P450-mediated lambda-cyhalothrin resistance in Cydia pomonella
Authors: Li Pei-Rong , Shi Yu , Liu Yu-Xi , Wang Wei , Ju Di , He Ying-Shi , Zhang Yu-Yun , Yang Xue-Qing 
Published: July 2022

ABSTRACTBACKGROUNDThe evolution of insect resistance to pesticides poses a continuing threat to sustainable pest management. While much is known about the molecular mechanisms that confer resistance in model insects and few agricultural pests, far less is known about fruit pests.RESULTSHere we found that functional redundancy and preference of metabolism by cytochrome P450 monooxygenases (P450s) genes in the CYP9A subfamily confer resistance to lambda-cyhalothrin in Cydia pomonella, a major invasive pest of pome fruit. A total of four CYP9A genes, including CYP9A61, CYP9A120, CYP9A121, and CYP9A122, were identified from C. pomonella. Among these, CYP9A120, CYP9A121, and CYP9A122 were predominantly expressed in the midgut of larvae. The expression levels of these P450 genes were significantly induced by LD10 of lambda-cyhalothrin and were overexpressed in a field-evolved lambda-cyhalothrin resistant population. Knockdown of CYP9A120 and CYP9A121 by RNA-mediated interference (RNAi) increased the susceptibility of larvae to lambda-cyhalothrin. In vitro assays demonstrated that recombinant P450s expressed in Sf9 cells can metabolize lambda-cyhalothrin, but with functional redundancy and divergence through regioselectivity of metabolism. CYP9A121 preferred to convert lambda-cyhalothrin to 2′-hydroxy-lambda-cyhalothrin, whereas CYP9A122 only generated 4′-hydroxy metabolite of lambda-cyhalothrin. Although possesses a relatively low metabolic capability, CYP9A120 balanced catalytic competence to generate both 2′- and 4′-metabolites.CONCLUSIONCollectively, these results reveal that metabolic functional redundancy of three members of the CYP9A subfamily leads to P450-mediated lambda-cyhalothrin resistance in C. pomonella, thus representing a potential adaptive evolutionary strategy during its worldwide expansion.
Deleterious Mechanical Deformation Selects Mechanoresilient Cancer Cells with Enhanced Proliferation and Chemoresistance
Authors: Jiang Kuan , Lim Su Bin , Xiao Jingwei , Jokhun Doorgesh Sharma , Shang Menglin , Song Xiao , Zhang Pan , Liang Lanfeng , Low Boon Chuan , Shivashankar G.V. , Lim Chwee Teck 
Published: July 2022

AbstractCancer cells derived from secondary tumors can form new distant metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, it is unclear how cancer cells may acquire such metastatic competency after overcoming deleterious mechanical stresses. Here, by forcing cancer cells to flow through small capillary-sized constrictions, we demonstrate that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing-induced cell death. Transcriptomic profiling reveals up-regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy-resistant phenotype. Our results highlight a potential link between the microenvironmental physical barriers and the enhanced malignancy of metastasizing cancer cells which may potentially be utilized for novel therapeutic strategies in preventing the metastatic spread of cancer cells.
Viability Discrimination of Bacterial Microbiomes in Home Kitchen Dish Sponges via Propidium Monoazide Treatment
Authors: Carstens Christina K. , Salazar Joelle K. , Sharma Shreela , Chan Wenyaw , Darkoh Charles 
Published: July 2022

AbstractDish sponges are known to support the survival and growth of human bacterial pathogens yet are commonly used by consumers to wash dishes and clean kitchen surfaces. Exposure to foodborne pathogens via sponge use may lead to foodborne illness, which is of particular concern among susceptible populations. Limitations associated with culture-independent or - dependent methods for bacterial community characterization have challenged the complete assessment of foodborne pathogen exposure risk presented by sponges. In this study, the bacterial microbiomes of five dish sponges were characterized to evaluate the presence of viable bacterial foodborne pathogens using propidium monoazide treatment, which is a novel approach in this medium. Total and viable sponge microbiomes were subsequently metataxonomically evaluated via targeted 16S rRNA sequencing. Select pathogen viability was confirmed using targeted selective enrichment. The comparison of total and viable sponge microbiome beta diversity indicated that sponge taxonomic abundance profiles did not vary significantly according to PMA treatment. The numbers of unique bacterial species (p-value = 0.0465) and unique bacterial foodborne pathogens (p-value = 0.0102) identified were significantly lower after PMA-treatment. A total of 20 unique bacterial foodborne pathogens were detected among sponge microbiomes regardless of PMA treatment. Three to six unique viable foodborne pathogens were identified in each sponge.Escherichia coliandStaphylococcus aureuswere identified in all five viable sponge microbiomes evaluated. ViableE. coliwere recovered from two of five sponges via targeted selective enrichment. These findings suggest that most sponge-associated bacterial communities may be viable and contain multiple viable bacterial foodborne pathogens.ImportanceBacterial pathogens may exist in the domestic kitchen environment, threatening both sanitation levels and the health of residents. Dish sponges are commonly used kitchen tools that can harbor foodborne pathogens as they present adequate conditions for the survival and growth of bacteria. Using a contaminated sponge may lead to foodborne illness through direct contact with pathogens or via cross-contamination with food or other surfaces. Although bacterial foodborne pathogens have been identified in sponges, previous limitations in methodology have prevented the complete understanding of sponge microbiomes. This study used a novel application of a chemical reagent coupled with targeted amplicon sequencing to identify sponge communities and differentiate between viable and non-viable bacteria. Insights into dish sponge microbiomes and potential risks of bacterial foodborne pathogen exposure can inform food safety education programs to aid in the prevention of home-acquired foodborne illness and cross-contamination events.
Evaluation of Seropositivity after Standard Doses of Vaccination against SARS-CoV-2 in Early Breast Cancer Patients Receiving Adjuvant Treatment
Authors: Kim Jinyong , Chang Euijin , Park Song Yi , Lee Dae-Won , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Oh Myoung-don , Park Wan Beom , Lee Kyung-Hun , Im Seock-Ah 
Published: July 2022

AbstractBackgroundCoronavirus disease 2019 (COVID-19) pandemic affected millions of individuals and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data is available on their efficacy in patients under active anti-cancer therapies.Materials and MethodsIn this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination in early breast cancer patients with concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments.ResultsStandard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy.ConclusionOur study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.Implications for PracticeIn this article, we present rare data on the homogeneous population of patients with early breast cancer under active anti-cancer treatments. The patients showed adequate serologic responses against SARS-CoV-2 virus after standard doses of vaccination without serious adverse events in concurrence with active adjuvant anti-cancer therapy. The patients receiving concurrent cytotoxic chemotherapy, however, have significantly lower serum anti-spike antibody titers than those under non-cytotoxic anti-cancer treatments or without treatments. Selection of the COVID-19 vaccines should be based on personalized risk stratification considering the use of concurrent cytotoxic chemotherapy and the patient’s medical circumstances. Booster doses of vaccination could be considered for the vulnerable population, such as elderly with comorbidities and the single standard dose of vaccination.
SGLT2 inhibition mitigates perturbations in nephron segment-specific metabolic transcripts and mTOR pathway activity in kidneys of young persons with type 2 diabetes
Authors: Schaub Jennifer A. , AlAkwaa Fadhl M. , McCown Phillip J. , Naik Abhijit S. , Nair Viji , Eddy Sean , Menon Rajasree , Otto Edgar A. , Hartman John , Fermin Damian , O’Connor Christopher , Bitzer Markus , Harned Roger , Ladd Patricia , Pyle Laura , Hodgin Jeffrey B. , Brosius Frank C. , Nelson Robert G. , Kretzler Matthias , Bjornstad Petter 
Published: July 2022

AbstractThe molecular mechanisms of SGLT2 inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometrics data were collected from research kidney biopsies donated by participants with youth onset type 2 diabetes (T2D), aged 12-21 years of age, and healthy controls (HC) to study the effects of SGLT2i on kidney transcriptomics. Participants with T2D were more obese, had higher glomerular filtration rate, mesangial and glomerular volumes than HC. There were no clinically significant differences between participants prescribed SGLT2i (T2Di(+), n=10) and other T2D (T2Di(-), n=6). Transcriptional profiles showed SGLT2 expression exclusively in the proximal tubular (PT) cluster. Transcriptional alterations in T2Di(+) compared to T2Di(-) were seen across most nephron segments, most prominently in the distal nephron. SGLT2i treatment was associated with suppression of genes in the glycolysis, gluconeogenesis, tricarboxylic acid cycle pathways in PT, but enhanced expression in thick ascending limb. The energy sensitive mTOR signaling pathway transcripts were suppressed towards HC level in all nephron segments in T2Di(+). These transcriptional changes were confirmed in a diabetes mouse model treated with SGLT2i. Therefore, the beneficial effects of SGLT2i treatment to the kidneys might be from mitigating diabetes-induced metabolic perturbations via suppression of mTORC1 signaling across nephron segments, including those not expressing SGLT2.
Vaccination strategies impact the probability of outbreak extinction: a case study of COVID-19 transmission
Authors: Jitsuk Natcha C. , Chadsuthi Sudarat , Modchang Charin 
Published: July 2022

AbstractMass vaccination has been one of the effective control measures for mitigating infectious disease transmission. Several vaccination strategies have been introduced throughout history to control infections and terminate the outbreak. Here, we employed the coronavirus disease 2019 (COVID-19) transmission as a case study and constructed a stochastic age-structured compartmental model to investigate the effectiveness of different vaccination strategies. We estimated the outbreak extinction probability under different vaccination scenarios in homogeneous and heterogeneous populations. We found that population heterogeneity could enhance the likelihood of outbreak extinction at various vaccine coverage. In addition, prioritizing vaccines for people with higher infection risk could maximize the outbreak extinction probability and reduce more infections. In contrast, allocating vaccines to individuals with higher mortality risk provides better results in reducing deaths. We also found that as the vaccine effectiveness wane over time, a booster dose of vaccine could significantly enhance the extinction probability and mitigate disease transmission.