J Immunol. 2021 Feb 19:ji2001355. doi: 10.4049/jimmunol.2001355. Online ahead of print.

ABSTRACT

Follicular dendritic cells (FDCs) retain immune complexes (ICs) for prolonged time periods and are important for germinal center (GC) reactions. ICs undergo periodic cycling in FDCs, a mechanism supporting an extended half-life of Ag. Based on experimental data, we estimated that the average residence time of PE-ICs on FDC surface and interior were 21 and 36 min, respectively. GC simulations show that Ag cycling might impact GC dynamics because of redistribution of Ag on the FDC surface and by protecting Ag from degradation. Ag protection and influence on GC dynamics varied with Ag cycling time and total Ag concentration. Simulations predict that blocking Ag cycling terminates the GC reaction and decreases plasma cell production. Considering that cycling of Ag could be a target for the modulation of GC reactions, our findings highlight the importance of understanding the mechanism and regulation of IC cycling in FDCs.

PMID:33608455 | DOI:10.4049/jimmunol.2001355

Mol Cancer. 2021 Feb 19;20(1):36. doi: 10.1186/s12943-021-01330-w.

ABSTRACT

Early detection is crucial to improve breast cancer (BC) patients' outcomes and survival. Mammogram and ultrasound adopting the Breast Imaging Reporting and Data System (BI-RADS) categorization are widely used for BC early detection, while suffering high false-positive rate leading to unnecessary biopsy, especially in BI-RADS category-4 patients. Plasma cell-free DNA (cfDNA) carrying on DNA methylation information has emerged as a non-invasive approach for cancer detection. Here we present a prospective multi-center study with whole-genome bisulfite sequencing data to address the clinical utility of cfDNA methylation markers from 203 female patients with breast lesions suspected for malignancy. The cfDNA is enriched with hypo-methylated genomic regions. A practical computational framework was devised to excavate optimal cfDNA-rich DNA methylation markers, which significantly improved the early diagnosis of BI-RADS category-4 patients (AUC from 0.78-0.79 to 0.93-0.94). As a proof-of-concept study, we performed the first blood-based whole-genome DNA methylation study for detecting early-stage breast cancer from benign tumors at single-base resolution, which suggests that combining the liquid biopsy with the traditional diagnostic imaging can improve the current clinical practice, by reducing the false-positive rate and avoiding unnecessary harms.

PMID:33608029 | PMC:PMC7893735 | DOI:10.1186/s12943-021-01330-w

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2021/02/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Front Public Health. 2021 Feb 2;8:590096. doi: 10.3389/fpubh.2020.590096. eCollection 2020.

ABSTRACT

Following the outbreak of COVID-19, multidisciplinary research focusing on the long-term effects of the COVID-19 infection and the complete recovery is still scarce. With regards to long-term consequences, biomarkers of physiological effects as well as the psychological experiences are of significant importance for comprehensively understanding the complete COVID-19 recovery. The present research surveys the IgG antibody titers and the impact of COVID-19 as a traumatic experience in the aftermath of the active infection period, around 2 months after diagnosis, in a subset of COVID-19 patients from the first wave (March-April 2020) of the outbreak in Northern Cyprus. Associations of antibody titers and psychological survey measures with baseline characteristics and disease severity were explored, and correlations among various measures were evaluated. Of the 47 serology tests conducted for presence of IgG antibodies, 39 (83%) were positive. We identified trends demonstrating individuals experiencing severe or critical COVID-19 disease and/or those with comorbidities are more heavily impacted both physiologically and mentally, with higher IgG titers and negative psychological experience compared to those with milder disease and without comorbidities. We also observed that more than half of the COVID-19 cases had negative psychological experiences, being subjected to discrimination and verbal harassment/insult, by family/friends. In summary, as the first study co-evaluating immune response together with mental status in COVID-19, our findings suggest that further multidisciplinary research in larger sample populations as well as community intervention plans are needed to holistically address the physiological and psychological effects of COVID-19 among the cases.

PMID:33604323 | PMC:PMC7884822 | DOI:10.3389/fpubh.2020.590096

Blood Cancer Discov. 2021 Jan;2(1):54-69. doi: 10.1158/2643-3230.BCD-19-0058. Epub 2020 Dec 3.

ABSTRACT

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.

PMID:33604581 | PMC:PMC7888194 | DOI:10.1158/2643-3230.BCD-19-0058

Sci Total Environ. 2021 Feb 6;774:145114. doi: 10.1016/j.scitotenv.2021.145114. Online ahead of print.

ABSTRACT

Securing adequate supply of high-quality water is of increasing global importance and relies in large part on ecosystem services provided by freshwater biota. Unionid mussels are important keystone species and habitat engineers that shape freshwater ecosystems through water filtration, nutrient cycling and provision of habitats; their rapid global declines result in dramatic losses of ecosystem functions. Maintenance and enhancement of the services they provide depend on the identification of their crucial habitats. Following theoretical assumptions, this study analyses the importance of lake-stream transition zones for unionid mussels, based on data collected in 1984 and 2019 from an undisturbed stream flowing through five consecutive lakes. Mussel distribution matched the distribution of host fish and was strongly influenced by lakes: densities were highest near lake outlets, reaching 290 ind. m-2 (14.7 kg m-2) in 2019, and declined with downstream distance following a negative power function. This pattern was spatially consistent and sustained over time. All six unionid species native to north-central Europe were present, but common species (Anodonta anatina, Unio pictorum, U. tumidus) contributed about 80% of individuals and were responsible for most of the ecosystem services provided by unionid mussels. Estimated 1.9 × 106 mussel individuals inhabiting 3.2 km of stream length filtered a water volume equivalent to the total stream discharge approximately 2.5 times daily. Aggregations of spent shells, up to 17 kg m-2, accumulated downstream of lakes, forming extensive shell and mussel beds, providing habitats and contributing shell hash that improved stream-bed conditions. Globally invasive Dreissena polymorpha was present at low densities and did not spread or increase in abundance, indicating a long-term biotic resistance of the natural native community. Our study underscores the importance of undisturbed lake outlets, longitudinal connectivity of riverine ecosystems, and of common mussel species in maintaining freshwater ecosystem functionality and provision of vital services.

PMID:33607437 | DOI:10.1016/j.scitotenv.2021.145114

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2021/02/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Front Cell Dev Biol. 2021 Feb 1;9:634708. doi: 10.3389/fcell.2021.634708. eCollection 2021.

ABSTRACT

The Arp2/3 complex generates branched actin filament networks operating in cell edge protrusion and vesicle trafficking. Here we employ a conditional knockout mouse model permitting tissue- or cell-type specific deletion of the murine Actr3 gene (encoding Arp3). A functional Actr3 gene appeared essential for fibroblast viability and growth. Thus, we developed cell lines for exploring the consequences of acute, tamoxifen-induced Actr3 deletion causing near-complete loss of functional Arp2/3 complex expression as well as abolished lamellipodia formation and membrane ruffling, as expected. Interestingly, Arp3-depleted cells displayed enhanced rather than reduced cell spreading, employing numerous filopodia, and showed little defects in the rates of random cell migration. However, both exploration of new space by individual cells and collective migration were clearly compromised by the incapability to efficiently maintain directionality of migration, while the principal ability to chemotax was only moderately affected. Examination of actin remodeling at the cell periphery revealed reduced actin turnover rates in Arp2/3-deficient cells, clearly deviating from previous sequestration approaches. Most surprisingly, induced removal of Arp2/3 complexes reproducibly increased FMNL formin expression, which correlated with the explosive induction of filopodia formation. Our results thus highlight both direct and indirect effects of acute Arp2/3 complex removal on actin cytoskeleton regulation.

PMID:33598464 | PMC:PMC7882613 | DOI:10.3389/fcell.2021.634708

63 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2021/02/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

62 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2021/02/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

medRxiv. 2021 Feb 12:2020.10.14.20212803. doi: 10.1101/2020.10.14.20212803. Preprint.

ABSTRACT

Background Data on the characteristics of COVID-19 patients disaggregated by race/ethnicity remain limited. We evaluated the sociodemographic and clinical characteristics of patients across racial/ethnic groups and assessed their associations with COVID-19 outcomes. Methods This retrospective cohort study examined 629,953 patients tested for SARS-CoV-2 in a large health system spanning California, Oregon, and Washington between March 1 and December 31, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression. Results 570,298 patients with known race/ethnicity were tested for SARS-CoV-2, of whom 27.8% were non-White minorities. 54,645 individuals tested positive, with minorities representing 50.1%. Hispanics represented 34.3% of infections but only 13.4% of tests. While generally younger than White patients, Hispanics had higher rates of diabetes but fewer other comorbidities. 8,536 patients were hospitalized and 1,246 died, of whom 56.1% and 54.4% were non-White, respectively. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increased odds of testing positive and hospitalization were associated with all minority races/ethnicities. Hispanic patients also exhibited increased morbidity, and Hispanic race/ethnicity was associated with in-hospital mortality (OR: 1.39 [95% CI: 1.14-1.70]). Conclusion Major healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, required excess hospitalization and mechanical ventilation, and had higher odds of in-hospital mortality despite younger age. Targeted, culturally-responsive interventions and equitable vaccine development and distribution are needed to address the increased risk of poorer COVID-19 outcomes among minority populations. .

PMID:33594379 | PMC:PMC7885938 | DOI:10.1101/2020.10.14.20212803

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2021/02/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Physical mechanisms of chromatin spatial organization.

FEBS J. 2021 Feb 14;:

Authors: Chiariello AM, Bianco S, Esposito A, Fiorillo L, Conte M, Irani E, Musella F, Abraham A, Prisco A, Nicodemi M

Abstract
In higher eukaryotes, chromosomes have a complex three-dimensional (3D) conformation in the cell nucleus serving vital functional purposes, yet their folding principles remain poorly understood at the single-molecule level. Here, we summarize recent approaches from polymer physics to comprehend the physical mechanisms underlying chromatin architecture. In particular, we focus on two models that have been supported by recent, growing experimental evidence, the Loop-Extrusion model and the Strings&Binders phase separation model. We discuss their key ingredients, how they compare to experimental data and some insight they provide on chromatin architecture and gene regulation. Progresses in that research field are opening the possibility to predict how genomic mutations alter the network of contacts between genes and their regulators and how that is linked to genetic diseases, such as congenital disorders and cancer.

PMID: 33583147 [PubMed - as supplied by publisher]

Pharmacology of TAS1R2/TAS1R3 Receptors and Sweet Taste.

Handb Exp Pharmacol. 2021 Feb 14;:

Authors: Behrens M

Abstract
The detection of energy-rich sweet food items has been important for our survival during evolution, however, in light of the changing lifestyles in industrialized and developing countries our natural sweet preference is causing considerable problems. Hence, it is even more important to understand how our sense of sweetness works, and perhaps even, how we may deceive it for our own benefit. This chapter summarizes current knowledge about sweet tastants and sweet taste modulators on the compound side as well as insights into the structure and function of the sweet taste receptor and the transduction of sweet signals. Moreover, methods to assess the activity of sweet substances in vivo and in vitro are compared and discussed.

PMID: 33582884 [PubMed - as supplied by publisher]

Approaches for characterizing and tracking hospital-associated multidrug-resistant bacteria.

Cell Mol Life Sci. 2021 Feb 13;:

Authors: Blake KS, Choi J, Dantas G

Abstract
Hospital-associated infections are a major concern for global public health. Infections with antibiotic-resistant pathogens can cause empiric treatment failure, and for infections with multidrug-resistant bacteria which can overcome antibiotics of "last resort" there exists no alternative treatments. Despite extensive sanitization protocols, the hospital environment is a potent reservoir and vector of antibiotic-resistant organisms. Pathogens can persist on hospital surfaces and plumbing for months to years, acquire new antibiotic resistance genes by horizontal gene transfer, and initiate outbreaks of hospital-associated infections by spreading to patients via healthcare workers and visitors. Advancements in next-generation sequencing of bacterial genomes and metagenomes have expanded our ability to (1) identify species and track distinct strains, (2) comprehensively profile antibiotic resistance genes, and (3) resolve the mobile elements that facilitate intra- and intercellular gene transfer. This information can, in turn, be used to characterize the population dynamics of hospital-associated microbiota, track outbreaks to their environmental reservoirs, and inform future interventions. This review provides a detailed overview of the approaches and bioinformatic tools available to study isolates and metagenomes of hospital-associated bacteria, and their multi-layered networks of transmission.

PMID: 33582841 [PubMed - as supplied by publisher]

Genome-wide analysis in response to nitrogen and carbon identifies regulators for root AtNRT2 transporters.

Plant Physiol. 2021 Feb 05;:

Authors: Ruffel S, Chaput V, Przybyla-Toscano J, Fayos I, Ibarra C, Moyano T, Fizames C, Tillard P, O'Brien JA, Gutiérrez RA, Gojon A, Lejay L

Abstract
In Arabidopsis (Arabidopsis thaliana), the High-Affinity Transport System (HATS) for root nitrate (NO3-) uptake depends mainly on four NRT2 NO3- transporters, namely NRT2.1, NRT2.2, NRT2.4, and NRT2.5. The HATS is the target of many regulations to coordinate nitrogen (N) acquisition with the N status of the plant and with carbon (C) assimilation through photosynthesis. At the molecular level, C and N signaling pathways control gene expression of the NRT2 transporters. Although several regulators of these transporters have been identified in response to either N or C signals, the response of NRT2 gene expression to the interaction of these signals has never been specifically investigated, and the underlying molecular mechanisms remain largely unknown. To address this question we used an original systems biology approach to model a regulatory gene network targeting NRT2.1, NRT2.2, NRT2.4, and NRT2.5 in response to N/C signals. Our systems analysis of the data identified three transcription factors, TGA3, MYC1, and bHLH093. Functional analysis of mutants combined with yeast one-hybrid experiments confirmed that all three transcription factors are regulators of NRT2.4 or NRT2.5 in response to N or C signals. These results reveal a role for TGA3, MYC1, and bHLH093 in controlling the expression of root NRT2 transporter genes.

PMID: 33582801 [PubMed - as supplied by publisher]

Tissue-specific transcriptome profiling of the Arabidopsis inflorescence stem reveals local cellular signatures.

Plant Cell. 2020 Dec 02;:

Authors: Shi D, Jouannet V, Agustí J, Kaul V, Levitsky V, Sanchez P, Mironova VV, Greb T

Abstract
Genome-wide gene expression maps with a high spatial resolution have substantially accelerated plant molecular science. However, the number of characterized tissues and growth stages is still small due to the limited accessibility of most tissues for protoplast isolation. Here, we provide gene expression profiles of the mature inflorescence stem of Arabidopsis thaliana covering a comprehensive set of distinct tissues. By combining fluorescence-activated nucleus sorting and laser-capture microdissection with next-generation RNA sequencing, we characterized the transcriptomes of xylem vessels, fibers, the proximal and distal cambium, phloem, phloem cap, pith, starch sheath, and epidermis cells. Our analyses classified more than 15,000 genes as being differentially expressed among different stem tissues and revealed known and novel tissue-specific cellular signatures. By determining overrepresented transcription factor binding regions in the promoters of differentially expressed genes, we identified candidate tissue-specific transcriptional regulators. Our datasets predict the expression profiles of an exceptional number of genes and allow hypotheses to be generated about the spatial organization of physiological processes. Moreover, we demonstrate that information about gene expression in a broad range of mature plant tissues can be established at high spatial resolution by nuclear mRNA profiling. Tissue-specific gene expression values can be accessed online at https://arabidopsis-stem.cos.uni-heidelberg.de/.

PMID: 33582756 [PubMed - as supplied by publisher]

Assessment bioaccumulation factor (BAF) of methyl siloxanes in crucian carp (Carassius auratus) around a siloxane production factory.

Ecotoxicol Environ Saf. 2021 Feb 11;213:111983

Authors: Guo W, Dai Y, Chu X, Cui S, Sun Y, Li YF, Jia H

Abstract
Methyl siloxanes are identified as emerging persistent toxic compounds and the ecological environment risks of these compounds have been caused of great concern worldwide. In this study, the concentrations of methyl siloxanes were reported in dissolved water and crucian carp around a methyl siloxane production factory located in Liaoning Province, Northeast China. D4, D5, D6, D7, L4, L5 and L6 were detectable both in dissolved water and crucian carp. The total concentrations of 7 methyl siloxanes (Σ7MS) were 14 ± 6.3 ng/L in dissolved water and 43 ± 22 ng/g ww in crucian carp, respectively. D5 has the highest concentration both in dissolved water (5.5 ± 3.5 ng/L) and crucian carp (17 ± 11 ng/g ww). Based on the monitoring values, bioaccumulation factor (BAF) of these compounds were calculated. Significant bioaccumulation potential was observed for D4 (BAF = 5900 ± 3500 L/kg) based on the bioaccumulation criteria suggested by USEPA and EU (BAF > 5000 L/kg). To our understanding, this is the first report of BAF values of methyl siloxane in field study, which will provide important support for further assessment of bioaccumulation of these compounds.

PMID: 33582413 [PubMed - as supplied by publisher]

Protein phosphorylation in depolarized synaptosomes: Dissecting primary effects of calcium from synaptic vesicle cycling.

Mol Cell Proteomics. 2021 Feb 11;:100061

Authors: Silbern I, Pan KT, Fiosins M, Bonn S, Rizzoli SO, Fornasiero EF, Urlaub H, Jahn R

Abstract
Synaptic transmission is mediated by the regulated exocytosis of synaptic vesicles. When the presynaptic membrane is depolarized by an incoming action potential, voltage-gated calcium channels open, resulting in the influx of calcium ions that triggers the fusion of synaptic vesicles (SV) with the plasma membrane. SV are recycled by endocytosis. Phosphorylation of synaptic proteins plays a major role in these processes, and several studies have shown that the synaptic phosphoproteome changes rapidly in response to depolarization. However, it is unclear which of these changes are directly linked to SV-cycling and which might regulate other presynaptic functions that are also controlled by calcium-dependent kinases and phosphatases. To address this question, we analyzed changes in the phosphoproteome using rat synaptosomes in which exocytosis was blocked with botulinum neurotoxins (BoNTs) while depolarization-induced calcium influx remained unchanged. BoNT-treatment significantly alters the response of the synaptic phoshoproteome to depolarization and results in reduced phosphorylation levels when compared to stimulation of synaptosomes by depolarization with KCl alone. We dissect the primary Ca2+-dependent phosphorylation from SV-cycling dependent phosphorylation and confirm an effect of such SV-cycling-dependent phosphorylation events on syntaxin-1a-T21/T23, Vamp2-S75, and cannabinoid receptor-1-S314/T322 on exo- and endocytosis in cultured hippocampal neurons.

PMID: 33582301 [PubMed - as supplied by publisher]

New proteomic signatures to distinguish between Zika and dengue infections.

Mol Cell Proteomics. 2021 Feb 11;:100052

Authors: Allgoewer K, Maity S, Zhao A, Lashua L, Ramgopal M, Balkaran BN, Liu L, Purushwani S, Arévalo MT, Ross TM, Choi H, Ghedin E, Vogel C

Abstract
Distinguishing between Zika and dengue virus infections is critical for accurate treatment, but we still lack detailed understanding of their impact on their host. To identify new protein signatures of the two infections, we used next-generation proteomics to profile 122 serum samples from 62 Zika and dengue patients. We quantified >500 proteins and identified 13 proteins that were significantly differentially expressed (adjusted p-value < 0.05). These proteins typically function in infection and wound healing, with several also linked to pregnancy and brain function. We successfully validated expression differences with Carbonic Anhydrase 2 in both the original and an independent sample set. Three of the differentially expressed proteins, i.e. Fibrinogen Alpha, Platelet Factor 4 Variant 1, and Pro-Platelet Basic Protein, predicted Zika virus infection at a ∼70% true positive and 6% false positive rate. Further, we showed that intra-individual temporal changes in protein signatures can disambiguate diagnoses and serve as indicators for past infections. Taken together, we demonstrate that serum proteomics can provide new resources that serve to distinguish between different viral infections.

PMID: 33582300 [PubMed - as supplied by publisher]