Biology subjects

Rodriguez, R.

Publications and source records attributed to Rodriguez, R..

36 records · Page 2Linked to original sources

bioRxiv2024

Presence of Triatoma breyeri (Reduviidae, Triatominae) in Bolivia

The study focuses on identifying and understanding the ecological dynamics of Triatoma breyeri in Bolivia. Morphological identification and molecular analysis using gene fragments (COI, CytB and 16S) confirms T. breyeris presence and its relation to other species. The species has been consistently found in the Estancia-Mataral - La Palma region since 2010 but has not spread to other regions in Bolivia. The region of occurrence is a small characteristic dry inter-Andean valley. A MaxEnt model suggests part of the Bolivian Montane Dry Forest ecoregion serves as a unique habitat within its range. The infrequent presence in Bolivia and the distance from its main range in Argentina suggest recent accidental introduction, possibly through human transport. Further research is needed to comprehend its persistence in this small area of Bolivia.

ecology↗

bioRxiv2024

SMORES: A Simple Microfluidic Operating Room for the Examination and Surgery of Stentor coeruleus

Ciliates are powerful unicellular model organisms that have been used to elucidate fundamental biological processes. However, the high motility of ciliates presents a major challenge in studies using live-cell microscopy and microsurgery. While various immobilization methods have been developed, they are physiologically disruptive to the cell and incompatible with microscopy and/or microsurgery. Here, we describe a Simple Microfluidic Operating Room for the Examination and Surgery of Stentor coeruleus (SMORES). SMORES uses Quake valve-based microfluidics to trap, compress, and perform surgery on Stentor as our model ciliate. Compared with previous methods, immobilization by physical compression in SMORES is more effective and uniform. The mean velocity of compressed cells is 24 times less than that of uncompressed cells. The compression is minimally disruptive to the cell and is easily applied or removed using a 3D-printed pressure rig. We demonstrate cell immobilization for up to 2 hours without sacrificing cell viability. SMORES is compatible with confocal microscopy and is capable of media exchange for pharmacokinetic studies. Finally, the modular design of SMORES allows laser ablation or mechanical dissection of a cell into many cell fragments at once. These capabilities are expected to enable biological studies previously impossible in ciliates and other motile species.

bioengineering↗

bioRxiv2023

A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma

BackgroundSarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. Among sarcomas, the clinical management of chondrosarcomas remains a complex challenge, as high-grade tumors do not respond to current therapies. Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are among the most common mutations detected in chondrosarcomas and may represent a therapeutic opportunity. The presence of mutated IDH (mIDH) enzymes results in the accumulation of the oncometabolite 2-HG leading to molecular alterations that contribute to drive tumor growth. MethodsWe developed a personalized medicine strategy based on the targeted NGS/Sanger sequencing of sarcoma samples (n=6) and the use of matched patient-derived cell lines as a drug-testing platform. The anti-tumor potential of IDH mutations found in two chondrosarcoma cases was analyzed in vitro, in vivo and molecularly (transcriptomic and DNA methylation analyses). FindingsWe treated several chondrosarcoma models with specific mIDH1/2 inhibitors. Among these treatments, only the mIDH2 inhibitor enasidenib was able to decrease 2-HG levels and efficiently reduce the viability of mIDH2 chondrosarcoma cells. Importantly, oral administration of enasidenib in xenografted mice resulted in a complete abrogation of tumor growth. Enasidenib induced a profound remodeling of the transcriptomic landscape not associated to changes in the 5mC methylation levels and its anti-tumor effects were associated with the repression of proliferative pathways such as those controlled by E2F factors. InterpretationOverall, this work provides the first preclinical evidence for the use of enasidenib to treat mIDH2 chondrosarcomas. FundingSpanish Research Agency (grants PID2019-106666RB-I00; PI20CIII/00020; DTS18CIII/00005; CB16/12/00390; CB06/07/1009; CB19/07/00057). RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSSarcomas represent an extensive group of malignant diseases affecting mesodermal tissues. The genomic nature of most sarcoma subtypes, displaying high inter- and intra-tumor heterogeneity with few recurrent driver mutations in a small portion of patients, makes these tumors especially indicated for personalized treatment approaches. For optimal development of these personalized protocols and a more efficient translation to the clinic, it is necessary to create patient-derived models suitable for testing the efficiency of candidate therapies. These strategies might be especially indicated for chondrosarcomas, a subtype of bone sarcoma that is inherently resistant to current therapies. Added value of this studyTo develop a personalized medicine strategy for sarcomas we have applied targeted sequencing protocols to detect druggable mutations in a collection of sarcomas cases with available patient-derived models. Among those potential druggable alterations detected in patient samples and avatar cell lines, we found IDH mutations in two chondrosarcomas. The presence of mutated IDH enzymes results in the accumulation of the oncometabolite 2-HG which contributes to driving tumor growth. In vitro and in vivo experiments evidenced the anti-tumor potential of the IDH mutant inhibitor enasidenib for the treatment of IDH2 mutant chondrosarcomas. Our transcriptomic and epigenomic analyses show that the mechanism of action of this drug is associated with the repression of proliferative pathways rather than with the promotion of tumor differentiation. Implications of all the available evidenceThis study suggests that enasidenib may represent an efficient therapeutic alternative for mutant IDH2 chondrosarcomas. This anti-proliferative mechanism of action of this drug may be especially relevant in dedifferentiated chondrosarcomas where reversal of this phenotype is not possible. In addition, this work provides support for the use of sarcoma patient-derived lines as avatar models capable of predicting (pre)-clinical responses in personalized medicine strategies.

cancer biology↗

bioRxiv2023

Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constraints symbiont populations. We parameterized metabolic theory equations to predict how bird species body size and the body size of their feather mites relate to mite abundance according to four potential energy (microbial abundance, uropygial gland size) and space constraints (wing area, number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance from 26,604 birds of 106 passerine species, using phylogenetic modelling and quantile regression. Feather mite populations were strongly constrained by host space (number of feather barbs) and not energy. Moreover, feather mite species body size was unrelated to their abundance or to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

ecology↗

bioRxiv2022

MarR-Dependent Transcriptional Regulation of mmpSL5 Induces Ethionamide Resistance in Mycobacterium abscessus

Mycobacterium abscessus (Mabs) is an emerging non-tuberculosis mycobacterial (NTM) pathogen responsible for a wide variety of respiratory and cutaneous infections that are difficult to treat with standard antibacterial therapy. Mabs has a high degree of both innate and acquired antibiotic resistance to most clinically relevant drugs, including standard anti-mycobacterial agents. Ethionamide (ETH), an inhibitor of mycolic acid biosynthesis is currently utilized as a second-line agent for treating multidrug resistant tuberculosis (MDR-TB) infections. Here, we show that ETH has activity against clinical strains of Mabs in vitro at concentrations that are therapeutically achievable. Using transposon mutagenesis and whole genome sequencing of spontaneous drug-resistant mutants, we identified marR (MAB_2648c) as a genetic determinant of ETH sensitivity in Mabs. The gene marR encodes a transcriptional regulator of the TetR family of regulators. We show that MarR represses expression of MAB_2649 (mmpS5) and MAB_2650 (mmpL5). Further, we show that de-repression of these genes in marR mutants confers resistance to ETH, but not other antibiotics. To identify determinants of resistance that may be shared across antibiotics, we also performed Tn-Seq during treatment with amikacin and clarithromycin, drugs currently used clinically to treat Mabs. We found very little overlap in genes that modulate the sensitivity of Mabs to all three antibiotics, suggesting a high degree of specificity for resistance mechanisms in this emerging pathogen. ImportanceAntibiotic resistant infections caused by Mycobacterium abscessus (Mabs) have been increasing in prevalence and treatment is often unsuccessful. Success rates range from 30-50%, primarily due to the high intrinsic resistance of Mabs to most clinically useful antibiotics. New therapeutic strategies, including repurposing of existing antibiotics, are urgently needed to improve treatment success rates. Here, we show that the anti-TB antibiotic ethionamide (ETH) has repurposing potential against Mabs, displaying bacteriostatic activity and delaying emergence of drug resistance when combined with clinically relevant antibiotics currently used against Mabs in vitro. We identified genes that modulated susceptibility of Mabs to ETH. marR encodes a transcriptional regulator that when deleted, confers ETH resistance. Our collective findings can be used to further explore the function of other genes that contribute to ETH susceptibility and help design the next generation of antibacterial regimens against Mabs that may potentially include ETH.

microbiology↗

bioRxiv2022

The evolution of two transmissible leukaemias colonizing the coasts of Europe

Transmissible cancers are malignant cell clones that spread among individuals through transfer of living cancer cells. Several such cancers, collectively known as bivalve transmissible neoplasia (BTN), are known to infect and cause leukaemia in marine bivalve molluscs. This is the case of BTN clones affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and north-west Africa. To investigate the origin and evolution of contagious cancers in common cockles, we collected 6,854 C. edule specimens and diagnosed 390 cases of BTN. We then generated a reference genome for the species and assessed genomic variation in the genomes of 61 BTN tumours. Analysis of tumour-specific variants confirmed the existence of two cockle BTN lineages with independent clonal origins, and gene expression patterns supported their status as haemocyte-derived marine leukaemias. Examination of mitochondrial DNA sequences revealed several mitochondrial capture events in BTN, as well as co-infection of cockles by different tumour lineages. Mutational analyses identified two lineage-specific mutational signatures, one of which resembles a signature associated with DNA alkylation. Karyotypic and copy number analyses uncovered genomes marked by pervasive instability and polyploidy. Whole-genome duplication, amplification of oncogenes CCND3 and MDM2, and deletion of the DNA alkylation repair gene MGMT, are likely drivers of BTN evolution. Characterization of satellite DNA identified elements with vast expansions in the cockle germ line, yet absent from BTN tumours, suggesting ancient clonal origins. Our study illuminates the evolution of contagious cancers under the sea, and reveals long-term tolerance of extreme instability in neoplastic genomes.

evolutionary biology↗

bioRxiv2022

Nervous system reduction in branched-chain amino acid metabolism disrupts hippocampal neurogenesis and memory

A role for macronutrient metabolism in learning and memory is supported by numerous epidemiological studies. The Ppm1k gene encodes the branched-chain keto acid dehydrogenase (BCKDH) phosphatase that promotes the metabolism of branched-chain amino acids (BCAA). Here we show that nervous system deletion of Ppm1k in mice increases BCAA levels in brain tissue but not in plasma. These mice have significant impairments in working memory accompanied by a robust accumulation of DCX+/NeuroD1+ immature neurons within the dentate gyrus granule cell layer. Through single cell RNA sequencing and pathway analysis we identified substantial increases in transit-amplifying cells and immature neurons along with activated hedgehog signaling in Ppm1k deficient primary neural stem cells (NSCs). Inhibition of mTOR signaling reversed the effects of Ppm1k deletion on neuronal progenitor gene activation in primary NSCs. Together our findings uncover a new molecular link between BCAA metabolism, hippocampal neurogenesis, and cognitive performance.

neuroscience↗

bioRxiv2022

Discovery of a druggable copper-signaling pathway that drives cell plasticity and inflammation

Inflammation is a complex physiological process triggered in response to harmful stimuli. It involves specialized cells of the immune system able to clear sources of cell injury and damaged tissues to promote repair. Excessive inflammation can occur as a result of infections and is a hallmark of several diseases. The molecular basis underlying inflammatory responses are not fully understood. Here, we show that the cell surface marker CD44, which characterizes activated immune cells, acts as a metal transporter that promotes copper uptake. We identified a chemically reactive pool of copper(II) in mitochondria of inflammatory macrophages that catalyzes NAD(H) redox cycling by activating hydrogen peroxide. Maintenance of NAD+ enables metabolic and epigenetic programming towards the inflammatory state. Targeting mitochondrial copper(II) with a rationally-designed dimer of metformin triggers distinct metabolic and epigenetic states that oppose macrophage activation. This drug reduces inflammation in mouse models of bacterial and viral (SARS-CoV-2) infections, improves well-being and increases survival. Identifying mechanisms that regulate the plasticity of immune cells provides the means to develop next-generation medicine. Our work illuminates the central role of copper as a regulator of cell plasticity and unveils a new therapeutic strategy based on metabolic reprogramming and the control of epigenetic cell states.

cell biology↗

bioRxiv2021

Nanoscopic resolution within a single imaging frame

Mean-Shift Super Resolution (MSSR) is a principle based on the Mean Shift theory that extends spatial resolution in fluorescence images, beyond the diffraction limit. MSSR works on low- and high-density fluorophore images, is not limited by the architecture of the detector (EM-CCD, sCMOS, or photomultiplier-based laser scanning systems) and is applicable to single images as well as temporal series. The theoretical limit of spatial resolution, based on optimized real-world imaging conditions and analysis of temporal image series, has been measured to be 40 nm. Furthermore, MSSR has denoising capabilities that outperform other analytical super resolution image approaches. Altogether, MSSR is a powerful, flexible, and generic tool for multidimensional and live cell imaging applications.

bioinformatics↗

bioRxiv2021

Persistence of SARS CoV-2 S1 Protein in CD16+ Monocytes in Post-Acute Sequelae of COVID-19 (PASC) Up to 15 Months Post-Infection

The recent COVID-19 pandemic is a treatment challenge in the acute infection stage but the recognition of chronic COVID-19 symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC) may affect up to 30% of all infected individuals. The underlying mechanism and source of this distinct immunologic condition three months or more after initial infection remains elusive. Here, we investigated the presence of SARS-CoV-2 S1 protein in 46 individuals. We analyzed T-cell, B-cell, and monocytic subsets in both severe COVID-19 patients and in patients with post-acute sequelae of COVID-19 (PASC). The levels of both intermediate (CD14+, CD16+) and non-classical monocyte (CD14Lo, CD16+) were significantly elevated in PASC patients up to 15 months post-acute infection compared to healthy controls (P=0.002 and P=0.01, respectively). A statistically significant number of non-classical monocytes contained SARS-CoV-2 S1 protein in both severe (P=0.004) and PASC patients (P=0.02) out to 15 months post-infection. Non-classical monocytes were sorted from PASC patients using flow cytometric sorting and the SARS-CoV-2 S1 protein was confirmed by mass spectrometry. Cells from 4 out of 11 severe COVID-19 patients and 1 out of 26 PASC patients contained ddPCR+ peripheral blood mononuclear cells, however, only fragmented SARS-CoV-2 RNA was found in PASC patients. No full length sequences were identified, and no sequences that could account for the observed S1 protein were identified in any patient. Non-classical monocytes are capable of causing inflammation throughout the body in response to fractalkine/CX3CL1 and RANTES/CCR5.

immunology↗

bioRxiv2021

Mitochondrial genome sequencing of marine leukemias reveals cancer contagion between clam species in the Seas of Southern Europe

Clonally transmissible cancers are tumour lineages that are transmitted between individuals via the transfer of living cancer cells. In marine bivalves, leukemia-like transmissible cancers, called hemic neoplasia, have demonstrated the ability to infect individuals from different species. We performed whole-genome sequencing in eight warty venus clams that were diagnosed with hemic neoplasia, from two sampling points located more than 1,000 nautical miles away in the Atlantic Ocean and the Mediterranean Sea Coasts of Spain. Mitochondrial genome sequencing analysis in tumour tissues from neoplastic animals revealed the coexistence of haplotypes from two different clam species. Phylogenies estimated from mitochondrial and nuclear markers confirmed this leukemia originated in striped venus clams and later transmitted to clams of the species warty venus, in which it survives as a contagious cancer. The analysis of mitochondrial and nuclear gene sequences supports all studied tumours belong to a single neoplastic lineage that spreads in the Seas of Southern Europe.

genomics↗

bioRxiv2021

The dilemma of infection versus colonization at mucosal tissues: immunological and bacteriological features of obstructive tonsillar hypertrophy

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We uncovered a crucial role of pro-inflammatory tonsillar B and T cells in sustaining hypertrophy and hyperplasia by producing TNF and IL17, respectively. We detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. By combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work shed light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization.

immunology↗

bioRxiv2020

A Low-Cost Mass Spectrometry-Based Approach for Quantifying Purines in Placental Extracts

Hyperhomocysteinemia is a medical condition characterized by an abnormally high level of homocysteine in the blood associated with multiple human pathologies including preeclampsia - the most feared complication of pregnancy, with placenta playing the central role in the pathogenesis of preeclampsia. The developing placenta is highly sensitive to different adverse factors but its response to hyperhomocysteinemia is not fully clear. Previously we have demonstrated the activation of reactions of methionine cycle and the transsulfuration pathway in placental explants cultivated with homocysteine. The reactions of the methionine cycle are tightly connected with reactions of the folate cycle, encompassing reactions of de novo purine biosynthesis, which are crucial for the developing placenta, as they support rapid ATP generation to maintain energy status and increased biosynthesis of macromolecules. The sensitivity of de novo purine biosynthesis to hyperhomocysteinemia is not known. The aim of this study was to evaluate the impact of homocysteine on placental de novo purine biosynthesis. MethodsWe developed a simplified method to measure the level of all and newly formed purines by HPLC/ESI-MS, using a stable isotope glycine to label newly synthesized purines. The developed method proved to be highly sensitive, interday repeatable and intraday reproducible. We applied a method for placental explants from the first and third trimesters of gestation and MCF7 cells cultivated with 20 M and 40 M homocysteine corresponding to its concentrations at mild and intermediate hyperhomocysteinemia. ResultsThe developed method proved to be highly sensitive, interday repeatable and intraday reproducible. The content of total purines in placental explants from the first trimester of gestation was around 9.0 mol/g wet tissues at specified conditions of cultivation. The newly formed purines comprised around 1 % of total purines, decreased steadily in explants cultivated with 20 M and 40 M homocysteine, and reached the values characteristic for explants from third trimester cultivated without homocysteine, 4.0 mol/g wet tissues. The effect of homocysteine reproduced with MCF7 cells. ConclusionHomocysteine in concentrations characteristic of mild and intermediate hyperhomocysteinemia induces the down regulation of de novo purine biosynthesis in placental explants, and implies the shift of metabolic pathway to homocysteine remethylation and transsulfuration at the expense of de novo purine biosynthesis.

molecular biology↗

bioRxiv2019

Estrogen Drives Melanocortin Neurons To Reduce Sedentary Behavior

Estrogen depletion in rodents and humans leads to inactivity, unhealthy fat accumulation, and diabetes1,2, underscoring the conserved metabolic benefits of estrogen that inevitably decline with aging. In rodents, the preovulatory surge in 17{beta}-estradiol (E2) temporarily allows energy expenditure to outpace energy intake, thus coordinating increased physical activity with peak sexual receptivity. To investigate how estrogen rebalances energy allocation in females, we examine estrogen receptor alpha (ER) signaling in the ventrolateral ventromedial hypothalamic nucleus (VMHvl)3-7. We uncover a small population of VMHvlER neurons expressing the melanocortin-4 receptor (MC4R) that integrates estrogen and melanocortin signals and projects to arousal centers in the hippocampus and hindbrain, enabling bursts of physical activity. ER recruitment to the Mc4r gene promotes upregulation of Mc4r in VMHvl neurons during the preovulatory surge or following E2 treatment. We leveraged three models to stimulate VMHvlMC4R neurons, restore MC4R signaling in the VMHvl of hyperphagic MC4R null females, or increase Mc4r levels in the VMHvl by CRISPR-mediated activation. All models increase spontaneous activity, whereas silencing VMHvlMC4R neurons blunts normal activity. Direct activation of the VMHvlMC4R node overrides the inactivity and hypometabolism following hormone depletion. These data extend the impact of MC4R signaling - the most common cause of monogenic human obesity8 - beyond the regulation of food intake. Our findings also rationalize reported sex differences in melanocortin signaling, including the greater disease severity of MC4R insufficiency in women9. The hormone-dependent node identified here illuminates the power of estrogen in motivating behavior during the female reproductive cycle and for maintaining an active lifestyle.

neuroscience↗

bioRxiv2019

VARIATIONS IN THE COVERAGE OF BIOLOGICAL SOIL CRUSTS ALONG A GRADIENT OF ARIDITY IN THE CENTER-WEST OF ARGENTINA

The biological soil crusts (biocrust) play a fundamental role in the arid and semiarid areas of South America. However, little attention has been paid to the distribution and coverage of them. In Argentina, studies about biocrust are still scarce. The goal of this contribution is to analyze the coverage of the biocrust and each of the functional component along a gradient of aridity in the center-west of Argentina. The gradient included three differentiated sites: semiarid, arid, and hyperarid sites. The coverage was recorded using the Point-quadrat method on 30 transects through a gradient consisting of three sites: semiarid, arid, and hyper-arid sites. The arid site was the system with the highest coverage of biocrust followed by the hyper-arid site. The semiarid site had the lowest values of coverage and showed significant differences among the three systems were found. Cyanobacterias dominate in the hyper-arid site. On the other hand, cyanobacteria and lichens were dominant in the arid site. The coverage of studied organisms showed variations in the semiarid site. These results support the idea that the coverage has a strong relationship with the features of the studied ecosystem and the environmental factors both at a mesoscale and a microscale in a determined community.

ecology↗

bioRxiv2019

CD44 regulates epigenetic plasticity by mediating iron endocytosis

CD44 is a transmembrane glycoprotein that is linked to various biological processes reliant on the epigenetic plasticity of cells, including development, inflammation, immune responses, wound healing and cancer progression. While thoroughly studied, functional regulatory roles of this so-called cell surface marker remain elusive. Here, we report the discovery that CD44 mediates endocytosis of iron interacting with hyaluronates in tumorigenic cell lines and primary cancer cells. We found that this glycan-mediated iron endocytosis mechanism is enhanced during epithelial-mesenchymal transition, unlike the canonical transferrin-dependent pathway. This transition is further characterized by molecular changes required for iron-catalyzed oxidative demethylation of the repressive histone mark H3K9me2 that governs the expression of mesenchymal genes. CD44 itself is transcriptionally regulated by nuclear iron, demonstrating a positive feedback loop, which is in contrast to the negative regulation of transferrin receptor by excess iron. Finally, we show that epigenetic plasticity can be altered by interfering with iron homeostasis using small molecules. This comprehensive study reveals an alternative iron uptake mechanism that prevails in the mesenchymal state of mammalian cells, illuminating a central role of iron as a rate-limiting regulator of epigenetic plasticity.

cell biology↗

bioRxiv2019

Establishment of primary transgenic human airway epithelial cell cultures to study respiratory virus-host interactions

Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for FACS-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly(I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (RSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures thereby unlocking a unique potential for detailed molecular characterization of virus - host interactions in human respiratory epithelium.

microbiology↗

bioRxiv2019

CytoGPS: A Web-Enabled Karyotype Analysis Tool for Cytogenetics

Karyotype data are the most common form of genetic data that is regularly used clinically. They are collected as part of the standard of care in many diseases, particularly in pediatric and cancer medicine contexts. Karyotypes are represented in a unique text-based format, with a syntax defined by the International System for human Cytogenetic Nomenclature (ISCN). While human-readable, ISCN is not intrinsically machine-readable. This limitation has prevented the full use of complex karyotype data in discovery science use cases. To enhance the utility and value of karyotype data, we developed a tool named CytoGPS. CytoGPS first parses ISCN karyotypes into a machine-readable format. It then converts the ISCN karyotype into a binary Loss-Gain-Fusion (LGF) model, which represents all cytogenetic abnormalities as combinations of loss, gain, or fusion events, in a format that is analyzable using modern computational methods. Such data is then made available for comprehensive \"downstream\" analyses that previously were not feasible.\n\nAvailability and ImplementationFreely available at https://cytogps.org\n\nContactprpayne@wustl.edu\n\nSupplementary informationNot applicable

bioinformatics↗