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1.

Background

Multiscale approaches for integrating submodels of various levels of biological organization into a single model became the major tool of systems biology. In this paper, we have constructed and simulated a set of multiscale models of spatially distributed microbial communities and study an influence of unevenly distributed environmental factors on the genetic diversity and evolution of the community members.

Results

Haploid Evolutionary Constructor software http://evol-constructor.bionet.nsc.ru/ was expanded by adding the tool for the spatial modeling of a microbial community (1D, 2D and 3D versions). A set of the models of spatially distributed communities was built to demonstrate that the spatial distribution of cells affects both intensity of selection and evolution rate.

Conclusion

In spatially heterogeneous communities, the change in the direction of the environmental flow might be reflected in local irregular population dynamics, while the genetic structure of populations (frequencies of the alleles) remains stable. Furthermore, in spatially heterogeneous communities, the chemotaxis might dramatically affect the evolution of community members.
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2.

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.
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3.

Background and Aims

Phosphorus (P) is an essential nutrient for plants but its low availability often necessitates amendments for agronomical issues. Objectives were to determine P spatial distribution and speciation that remain poorly understood in cultivated soils.

Methods

Aquic Argiudoll soil samples developed on a calcareous loam glacial till were collected from experimental plots submitted to contrasting crop rotations and amendments. Micro-X-ray fluorescence (μ-XRF) maps were collected on undisturbed samples. X-ray absorption near edge structure (XANES) spectra were collected on bulk samples and on fractions thereof, and on points of interests selected from μ-XRF maps. Results were compared with chemical analyses and extraction techniques results.

Results

Chemical analyses show variations in total and exchangeable P contents depending on the samples but no significant difference is observed in terms of P distribution and speciation. P distribution is dominated by a low-concentration diffuse background with a minor contribution from minute hot spots. P speciation is dominated by phosphate groups bound to clay-humic complexes. No modification of P distribution and speciation is observed close to roots.

Conclusions

This study evidenced minor effect of cropping and fertilizing practices on P speciation in cultivated soils. Despite analytical challenges, the combined use of μ-XRF and XANES provides relevant information on P speciation in heterogeneous soil media.
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4.

Objective

To investigate the roles of miR-145 in lung adenocarcinoma (LAC) and to clarify the regulation of N-cadherin by miR-145.

Results

In 57 paired clinical LAC tissues, diminished miR-145 was significantly correlated with the lymph node metastasis and was negatively correlated with N-cadherin mRNA level expression. Wound healing and transwell assays revealed a reduced capability of tumor metastasis induced by miR-145 in LAC. miR-145 negatively regulated the invasion of cell lines through targeting N-cadherin by directly binding to its 3′-untranslated region. Silencing of N-cadherin inhibited invasion and migration of LAC cell lines similar to miR-145 overexpression.

Conclusions

MiR-145 could inhibit invasion and migration of lung adenocarcinoma cell lines by directly targeting N-cadherin.
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5.

Background and aims

Carpobrotus spp. are amongst the most impactful and widespread plant invaders of Mediterranean habitats. Despite the negative ecological impacts on soil and vegetation that have been documented, information is still limited about the effect by Carpobrotus on soil microbial communities. We aimed to assess the changes in the floristic, soil and microbial parameters following the invasion by Carpobrotus cfr. acinaciformis within an insular Mediterranean ecosystem.

Methods

Within three study areas a paired-site approach, comparing an invaded vs. a non-invaded plot, was established. Within each plot biodiversity indexes, C and N soil content, pH and microbial biomass and structure (bacterial and fungal) were assessed.

Results

Invaded plots showed a decrease of α-species richness and diversity. The least represented plant species in invaded plots were those related to grassland habitats. In all invaded soils, a significant increase of carbon and nitrogen content and a significant decrease of pH were registered. Carpobrotus significantly increased bacterial and fungal biomass and altered soil microbial structure, particularly favoring fungal growth.

Conclusions

Carpobrotus may deeply impact edaphic properties and microbial communities and, in turn, these strong modifications probably increase its invasive potential and its ability to overcome native species, by preventing their natural regeneration.
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6.

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.
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7.

Objectives

Identification of novel microbial factors contributing to plant protection against abiotic stress.

Results

The genome of plant growth-promoting bacterium Pseudomonas fluorescens FR1 contains a short mobile element encoding a novel type of extracellular polyhydroxybutyrate (PHB) polymerase (PhbC) associated with a type I secretion system. Genetic analysis using a phbC mutant strain and plants showed that this novel extracellular enzyme is related to the PHB production in planta and suggests that PHB could be a beneficial microbial compound synthesized during plant adaptation to cold stress.

Conclusion

Extracellular PhbC can be used as a new tool for improve crop production under abiotic stress.
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8.

Objectives

To investigate whether miR-1260b can regulate migration and invasion of hepatocellular carcinoma (HCC) by targeting RGS22.

Results

miR-1260b was up-regulated in HCC tissues compared with their corresponding non-cancerous tissues. Over-expression of miR-1260b increased migration and invasion of HepG2 and SMMC-7721 cells associated with HCC. Regulator of G-protein signaling 22 (RGS22) was identified as a directly target of miR-1260b and was inhibited by miR-1260b. Knockdown of RGS22 increased proliferation of HCC cells.

Conclusions

The new identified miR-1260b/RGS22 axis provides useful therapeutic methods for treatment of HCC deepening on our understanding of underlying mechanisms of HCC tumorigenesis.
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9.
Background

Bacteriophages are known to be one of the driving forces of bacterial evolution. Besides promoting horizontal transfer of genes between cells, they may induce directional selection of cells (for instance, according to more or less resistance to phage infection). Switching between lysogenic and lytic pathways results in various types of (co)evolution in host-phage systems. Spatial (more generally, ecological) organization of the living environment is another factor affecting evolution. In this study, we have simulated and analyzed a series of computer models of microbial communities evolving in spatially distributed environments under the pressure of phage infection.

Results

We modeled evolving microbial communities living in spatially distributed flowing environments. Non-specific nutrient supplied in the only spatial direction, resulting in its non-uniform distribution in environment. We varied the time and the location of initial phage infestation of cells as well as switched chemotaxis on and off. Simulations were performed with the Haploid evolutionary constructor software (http://evol-constructor.bionet.nsc.ru/).

Conclusion

Simulations have shown that the spatial location of initial phage invasion may lead to different evolutionary scenarios. Phage infection decreases the speciation rate by more than one order as far as intensified selection blocks the origin of novel viable populations/species, which could carve out potential ecological niches. The dependence of speciation rate on the invasion node location varied on the time of invasion. Speciation rate was found to be lower when the phage invaded fully formed community of sedentary cells (at middle and late times) at the species-rich regions. This is especially noticeable in the case of late-time invasion.

Our simulation study has shown that phage infection affects evolution of microbial community slowing down speciation and stabilizing the system as a whole. This influencing varied in its efficiency depending on spatially-ecological factors as well as community state at the moment of phage invasion.

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10.

Background

Paracoccidioidomycosis is a neglected tropical fungal infection with great predilection for adult men, indicating the participation of female hormone estrogen in preventing paracoccidioidomycosis development in women. Estrogen has an immunologic effect leading to polarization toward the Th2 immune response, which favors the disease evolution.

Objectives

To evaluate estrogen and progesterone receptors in oral paracoccidioidomycosis lesions and to verify any association with tissue fungi counting in women and men.

Methods

Thirty-two cases of chronic oral paracoccidioidomycosis were included. Immunohistochemical analyses for anti-estrogen receptor-α, anti-progesterone receptor and anti-Paracoccidioides brasiliensis antibodies were performed. The differences between women and men and the relations among the immunomarkers for each gender were also evaluated.

Results

A significant positive correlation was observed between estrogen receptor-α and the amount of fungi in women. In addition, estrogen receptor-α was mildly expressed in the inflammatory cells of female patients, while progesterone receptor was expressed in both genders, with similar expression between women and men. Moreover, fungi counting revealed no differences between genders.

Conclusions

Estrogen receptor-α was expressed only in women and showed a positive correlation with the amount of fungi in oral paracoccidioidomycosis, while progesterone receptor was observed in both genders and exhibited no correlation with estrogen receptor-α or fungi counting.
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11.

Objective

To isolate specific nanobodies to porcine reproductive and respiratory syndrome virus (PRRSV) non-structural protein 4 (Nsp4) and investigate their potential antiviral activities.

Results

Three PRRSV Nsp4-specific nanobodies were isolated from a phage display library of the variable domains of camelid heavy chain-only antibodies. Nanobody genes were introduced into MARC-145 cells using lentivirus vectors to establish cell lines stably expressing nanobodies. These intracellularly expressed nanobodies were tested for interaction with PRRSV-encoded Nsp4 within PRRSV-infected MARC-145 cells. Nb41 and Nb43 intrabodies each potently inhibited PRRSV replication, protected MARC-145 cells from PRRSV-induced cytopathic effect and fully blocked PRRSV replication at an MOI of 0.001 or lower.

Conclusion

Intracellularly expressed Nb41 and Nb43 potently suppressed PRRSV replication in MARC-145 cells. Nanobodies hold great potential for development as novel antiviral treatments for PRRSV infection.
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12.

Aims

Most plants produce a root tip extracellular matrix that includes viable border cell populations programmed to disperse into soil. Like neutrophils, border cells export structures that trap pathogens and prevent root tip infection. Border cells also trap metals. The goal of this study was to determine if border cells trap Pb.

Methods

Border cell responses to Pb were observed microscopically. Border cell impact on Pb-induced injury to roots was assessed using root growth assays. Pb removal from solution was measured using inductively coupled plasma mass spectrometry (ICP-MS). Speciation of Pb associated with border cells was evaluated by synchrotron X-ray absorption spectroscopy (XAS).

Results

Increased border cell trap size and number occurred within minutes in response to Pb but not silicon (Si). Transient immersion of root tips into Pb after border cells were removed resulted in growth inhibition. Immersion of root tips and border cells into Pb solution resulted in significant removal of Pb. Si levels in the presence of root tips remained unchanged. The Pb speciation, measured with Pb LIII XAS, altered when reacted with border cells, indicating that direct binding by extracellular traps occurred.

Conclusions

Border cells can trap Pb and prevent damage to the root tip.
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13.

Objectives

To screen and identify the probe markers specifically binding to human cervical cancer, a phage-displayed 12-mer peptide library was used for biopanning of SiHa cells.

Results

After four rounds of whole-cell subtraction biopanning, the phage recovery was 21-fold higher (from 3.9 × 10?5 to 8.3 × 10?4) than that of the first round, and specific phage clones were significantly enriched. 57 randomly selected phage clones were tested by ELISA, and 36 phage clones were identified as positive clones. After sequencing of positive clones, six different peptide sequences were obtained and CSP3 showed best affinity and specificity to SiHa cells via immunofluorescence assay.

Conclusions

Peptide, CSP3, bound to SiHa cells specifically and sensitively. It may be a potential candidate for molecular imaging detection and targeting therapy of cervical cancer.
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14.

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.
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15.

Background and aims

Drought events, agricultural practices and plant communities influence microbial and soil abiotic parameters which can feedback to fodder production. This study aimed to determine which soil legacies influence plant biomass production and nutritional quality, and its resistance and recovery to extreme weather events.

Methods

In a greenhouse experiment, soil legacy effects on Lolium perenne were examined, first under optimal conditions, and subsequently during and after drought. We used subalpine grassland soils previously cultivated for two years with grass communities of distinct functional composition, and subjected to combinations of climatic stress and simulated management.

Results

The soil legacy of climatic stress increased biomass production of Lolium perenne and its resistance and recovery to a new drought. This beneficial effect resulted from higher nutrient availability in soils previously exposed to climatic stresses due to lower competitive abilities and resistance of microbial communities to a new drought. This negative effect on microbial communities was strongest in soils from previously cut and fertilized grasslands or dominated by conservative grasses.

Conclusion

In subalpine grasslands more frequent climatic stresses could benefit fodder production in the short term, but threaten ecosystem functioning and the maintenance of traditional agricultural practices in the long term.
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16.

Introduction

Microbial cells secrete many metabolites during growth, including important intermediates of the central carbon metabolism. This has not been taken into account by researchers when modeling microbial metabolism for metabolic engineering and systems biology studies.

Materials and Methods

The uptake of metabolites by microorganisms is well studied, but our knowledge of how and why they secrete different intracellular compounds is poor. The secretion of metabolites by microbial cells has traditionally been regarded as a consequence of intracellular metabolic overflow.

Conclusions

Here, we provide evidence based on time-series metabolomics data that microbial cells eliminate some metabolites in response to environmental cues, independent of metabolic overflow. Moreover, we review the different mechanisms of metabolite secretion and explore how this knowledge can benefit metabolic modeling and engineering.
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17.

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.
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18.

Background

The recently discovered small-molecule BI-2 potently blocks HIV-1 infection. BI-2 binds to the N-terminal domain of HIV-1 capsid. BI-2 utilizes the same capsid pocket used by the small molecule PF74. Although both drugs bind to the same pocket, it has been proposed that BI-2 uses a different mechanism to block HIV-1 infection when compared to PF74.

Findings

This work demonstrates that BI-2 destabilizes the HIV-1 core during infection, and prevents the binding of the cellular factor CPSF6 to the HIV-1 core.

Conclusions

Overall this short-form paper suggests that BI-2 is using a similar mechanism to the one used by PF74 to block HIV-1 infection.
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19.

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.
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20.

Objective

To improve the diagnosis and treatment of Penicilliosis marneffei without human immunodeficiency virus infection.

Methods

Analyze and review the clinical features, diagnosis and treatment of six cases of P. marneffei without human immunodeficiency virus infection at The First Affiliated Hospital of Fujian Medical University.

Results

Two cases were diagnosed in the ENT Department, three cases in the respiratory department and one case in the dermatological department. Penicillium marneffei infection was confirmed by sputum culture, blood culture and tissue biopsy. After definite diagnosis, one refused further treatment, and others showed significant improvement.

Conclusion

Penicilliosis marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve early diagnosis and appropriate treatment, doubtful cases should be alerted for the diagnoses as P. marneffei.
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