79 research outputs found

    The dilution effect limits plasmid horizontal transmission in multispecies bacterial communities.

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    By transferring ecologically important traits between species, plasmids drive genomic divergence and evolutionary innovation in their bacterial hosts. Bacterial communities are often diverse and contain multiple coexisting plasmids, but the dynamics of plasmids in multi-species communities are poorly understood. Here, we show, using experimental multi-species communities containing two plasmids, that bacterial diversity limits the horizontal transmission of plasmids due to the 'dilution effect'; this is an epidemiological phenomenon whereby living alongside less proficient host species reduces the expected infection risk for a focal host species. In addition, plasmid horizontal transmission was also affected by plasmid diversity, such that the rate of plasmid conjugation was reduced from co-infected host cells carrying both plasmids. In diverse microbial communities, plasmid spread may be limited by the dilution effect and plasmid-plasmid interactions, reducing the rate of horizontal transmission

    A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

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    Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

    Development of Upper Body Coordination During Sitting in Typically Developing Infants

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    Our goal was to determine how the actions of the thorax and the pelvis are organized and coordinated to achieve independent sitting posture in typically developing infants. The participants were 10 typically developing infants who were evaluated longitudinally from first onset of sitting until sitting independence. Each infant underwent nine testing sessions. The first session included motor evaluation with the Peabody test. The other eight sessions occurred over a period of 4 mo where sitting behavior was evaluated by angular kinematics of the thorax and the pelvis. A physical therapist evaluated sitting behavior in each session and categorized it according to five stages. The phasing relationship of the thorax and the pelvis was calculated and evaluated longitudinally using a one-way analysis of variance. With development, the infants progressed from an in-phase (moving in the same direction) to an out-of-phase (moving in an opposite direction) coordinative relationship between the thorax and the pelvis segments. This change was significant for both sagittal and frontal planes of motion. Clinically, this relationship is important because it provides a method to quantify infant sitting postural development, and can be used to assess efficacy of early interventions for pediatric populations with developmental motor delays

    Characterization of Developmental Pathway of Natural Killer Cells from Embryonic Stem Cells In Vitro

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    In vitro differentiation of embryonic stem (ES) cells is often used to study hematopoiesis. However, the differentiation pathway of lymphocytes, in particular natural killer (NK) cells, from ES cells is still unclear. Here, we used a multi-step in vitro ES cell differentiation system to study lymphocyte development from ES cells, and to characterize NK developmental intermediates. We generated embryoid bodies (EBs) from ES cells, isolated CD34(+) EB cells and cultured them on OP9 stroma with a cocktail of cytokines to generate cells we termed ES-derived hematopoietic progenitors (ES-HPs). EB cell subsets, as well as ES-HPs derived from EBs, were tested for NK, T, B and myeloid lineage potentials using lineage specific cultures. ES-HPs derived from CD34(+) EBs differentiated into NK cells when cultured on OP9 stroma with IL-2 and IL-15, and into T cells on Delta-like 1-transduced OP9 (OP9-DL1) with IL-7 and Flt3-L. Among CD34(+) EB cells, NK and T cell potentials were detected in a CD45(−) subset, whereas CD45(+) EB cells had myeloid but not lymphoid potentials. Limiting dilution analysis of ES-HPs generated from CD34(+)CD45(−) EB cells showed that CD45(+)Mac-1(−)Ter119(−) ES-HPs are highly enriched for NK progenitors, but they also have T, B and myeloid potentials. We concluded that CD45(−)CD34(+) EB cells have lymphoid potential, and they differentiate into more mature CD45(+)Lin(−) hematopoietic progenitors that have lymphoid and myeloid potential. NK progenitors among ES-HPs are CD122(−) and they rapidly acquire CD122 as they differentiate along the NK lineage

    Phagocytic ability of neutrophils and monocytes in neonates

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    <p>Abstract</p> <p>Background</p> <p>Infections by a variety of pathogens are a significant cause of morbidity and mortality during perinatal period. The susceptibility of neonates to bacterial infections has been attributed to immaturity of innate immunity. It is considered that one of the impaired mechanisms is the phagocytic function of neutrophils and monocytes. The purpose of the present study was to investigate the phagocytic ability of neonates at birth.</p> <p>Methods</p> <p>The phagocytic ability of neutrophils and monocytes of 42 neonates was determined using the Phagotest flow cytometry method, that assesses the intake of <it>E. Coli </it>by phagocytes, in cord blood and in peripheral blood 3 days after birth. Fifteen healthy adults were included in the study as controls.</p> <p>Results</p> <p>The phagocytic ability of neutrophils in the cord blood of neonates was significantly reduced compared to adults. The 3<sup>rd </sup>postnatal day the reduction of phagocytic ability of neutrophils was no longer significant compared to adults. The phagocytic ability of monocytes did not show any difference from that of adults either at birth or the 3<sup>rd </sup>postnatal day.</p> <p>Conclusions</p> <p>Our findings indicate that the intake of <it>E. Coli </it>by phagocytes is impaired at birth in both preterm and full term neonates compared to adults. This defect is transient, with the phagocytic ability in neonates reaching that of the adults 3 days after birth.</p

    Posterior Decompression and Fusion: Whole-Spine Functional and Clinical Outcomes

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    The mobility of the spine and the change in the angle of the curvatures are directly related to spinal pain and spinal stenosis. The aim of the study was the evaluation of morphology and mobility of the spine in patients who were subjected to decompression and posterior fusion with pedicle screws. The treatment group consisted of 20 patients who underwent posterior fixation of lumbar spine (one and two level fusion). The control group consisted of 39 healthy subjects. Mobility and curvatures of the spine were measured with a non-invasive device, the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of the functional disability and the quality of life, respectively. The measurements were recorded preoperatively and at 3, 6 and 12 months postoperatively. The mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12 months compared to the measurements at 3 months. The mobility of the thoracic spine in the frontal plane increased (p = 0.009) at 12 months compared to the preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved significantly (p<0.001). The levels of fusion exhibited a strong linear correlation (r = 0.651, p = 0.002) with the total trunk inclination in the upright position. Although pain, quality of life and spinal mobility in the sagittal and frontal planes significantly improved in the treatment group, these patients still had limited mobility and decreased curves/angles values compared to control group

    A role for the cell-wall protein silacidin in cell size of the diatom Thalassiosira pseudonana

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    Diatoms contribute 20% of global primary production and form the basis of many marine food webs. Although their species diversity correlates with broad diversity in cell size, there is also an intraspecific cell-size plasticity due to sexual reproduction and varying environmental conditions. However, despite the ecological significance of the diatom cell size for food-web structure and global biogeochemical cycles, our knowledge about genes underpinning the size of diatom cells remains elusive. Here, a combination of reverse genetics, experimental evolution and comparative RNA8 sequencing analyses enabled us to identify a previously unknown genetic control of cell size in the diatom Thalassiosira pseudonana. In particular, the targeted deregulation of the expression of the cell-wall protein silacidin caused a significant increase in valve diameter. Remarkably, the natural downregulation of the silacidin gene transcript due to experimental evolution under low temperature also correlated with cell-size increase. Our data give first evidence for a genetically controlled regulation of cell size in Thalassiosira pseudonana and possibly other centric diatoms as they also encode the silacidin gene in their genomes

    Climatic risks and impacts in South Asia: extremes of water scarcity and excess

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    This paper reviews the current knowledge of climatic risks and impacts in South Asia associated with anthropogenic warming levels of 1.5°C to 4°C above pre-industrial values in the 21st century. It is based on the World Bank Report “Turn Down the Heat, Climate Extremes, Regional Impacts and the Case for Resilience” (2013). Many of the climate change impacts in the region, which appear quite severe even with relatively modest warming of 1.5–2°C, pose significant hazards to development. For example, increased monsoon variability and loss or glacial meltwater will likely confront populations with ongoing and multiple challenges. The result is a significant risk to stable and reliable water resources for the region, with increases in peak flows potentially causing floods and dry season flow reductions threatening agriculture. Irrespective of the anticipated economic development and growth, climate projections indicate that large parts of South Asia’s growing population and especially the poor are likely to remain highly vulnerable to climate change

    ETS Transcription Factors Control Transcription of EZH2 and Epigenetic Silencing of the Tumor Suppressor Gene Nkx3.1 in Prostate Cancer

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    ETS transcription factors regulate important signaling pathways involved in cell differentiation and development in many tissues and have emerged as important players in prostate cancer. However, the biological impact of ETS factors in prostate tumorigenesis is still debated.We performed an analysis of the ETS gene family using microarray data and real-time PCR in normal and tumor tissues along with functional studies in normal and cancer cell lines to understand the impact in prostate tumorigenesis and identify key targets of these transcription factors. We found frequent dysregulation of ETS genes with oncogenic (i.e., ERG and ESE1) and tumor suppressor (i.e., ESE3) properties in prostate tumors compared to normal prostate. Tumor subgroups (i.e., ERG(high), ESE1(high), ESE3(low) and NoETS tumors) were identified on the basis of their ETS expression status and showed distinct transcriptional and biological features. ERG(high) and ESE3(low) tumors had the most robust gene signatures with both distinct and overlapping features. Integrating genomic data with functional studies in multiple cell lines, we demonstrated that ERG and ESE3 controlled in opposite direction transcription of the Polycomb Group protein EZH2, a key gene in development, differentiation, stem cell biology and tumorigenesis. We further demonstrated that the prostate-specific tumor suppressor gene Nkx3.1 was controlled by ERG and ESE3 both directly and through induction of EZH2.These findings provide new insights into the role of the ETS transcriptional network in prostate tumorigenesis and uncover previously unrecognized links between aberrant expression of ETS factors, deregulation of epigenetic effectors and silencing of tumor suppressor genes. The link between aberrant ETS activity and epigenetic gene silencing may be relevant for the clinical management of prostate cancer and design of new therapeutic strategies

    Predicting species dominance shifts across elevation gradients in mountain forests in Greece under a warmer and drier climate

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    The Mediterranean Basin is expected to face warmer and drier conditions in the future, following projected increases in temperature and declines in precipitation. The aim of this study is to explore how forests dominated by Abies borisii-regis, Abies cephalonica, Fagus sylvatica, Pinus nigra and Quercus frainetto will respond under such conditions. We combined an individual-based model (GREFOS), with a novel tree ring data set in order to constrain tree diameter growth and to account for inter- and intraspecific growth variability. We used wood density data to infer tree longevity, taking into account inter- and intraspecific variability. The model was applied at three 500-m-wide elevation gradients at Taygetos in Peloponnese, at Agrafa on Southern Pindos and at Valia Kalda on Northern Pindos in Greece. Simulations adequately represented species distribution and abundance across the elevation gradients under current climate. We subsequently used the model to estimate species and functional trait shifts under warmer and drier future conditions based on the IPCC A1B scenario. In all three sites, a retreat of less drought-tolerant species and an upward shift of more drought-tolerant species were simulated. These shifts were also associated with changes in two key functional traits, in particular maximum radial growth rate and wood density. Drought-tolerant species presented an increase in their average maximal growth and decrease in their average wood density, in contrast to less drought-tolerant species
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