The Preference for Potential

When people seek to impress others, they often do so by highlighting individual achievements. Despite the intuitive appeal of this strategy, we demonstrate that people often prefer potential rather than achievement when evaluating others. Indeed, compared with references to achievement (e.g., this person has won an award for his work ), references to potential (e.g., this person could win an award for his work ) appear to stimulate greater interest and processing, which can translate into more favorable reactions. This tendency creates a phenomenon whereby the potential to be good at something can be preferred over actually being good at that very same thing. We document this preference for potential in laboratory and field experiments, using targets ranging from athletes to comedians to graduate school applicants and measures ranging from salary allocations to online ad clicks to admission decisions

Dehalogenases for pollutant degradation: a mini review

Dehalogenases are microbial enzyme catalysed the cleavage of carbon-halogen bond of halogenated organic compounds. It has potential use in the area of biotechnology such as bioremediation and chemical industry. Halogenated organic compounds can be found in a considerable amount in the environment due to utilization in agriculture and industry, such as pesticides and herbicides. The presence of halogenated compound in the environment have been implicated on the health and natural ecosystem. Microbial dehalogenation is a significant method to tackle this problem. This review intends to briefly describe the microbial dehalogenases in relation to the environment where they are isolated. The basic information about dehalogenases in relation to dehalogenation mechanisms, classification, sources and the transportation of these pollutants into bacterial cytoplasm will be described. We also summarised readily available synthetic halogenated organic compound in the environment

Genomic analysis of mesorhizobium loti strain tono reveals dehalogenases for bioremediation

Halogenated compounds are extensively utilized in different industrial applications such as pesticides and herbicides and cause severe environmental problems because of their toxicity and persistence. Degradation of these compounds by the biological method is a significant method to reduce these recalcitrant. Mesorhizobium loti is im-portant for nitrogen fixation in legume roots. Up to now, there is no report to indicate M. loti can produce dehalogenase enzymes. Thus, a total of twenty-five genomes of M. loti strains from the National Center for Biotechnology Information (NCBI) were an-alyzed. These strains notably carry dehalogenase genes and were further investigated. The relative ratio of haloalkane and haloacid dehalogenase type II or L-type from all twenty-five genomes was 26% and 74%, respectively, suggesting type II dehalogen-ase is common. Surprisingly, only M. loti strain TONO carries four dehalogenases and therefore it was further characterized. The chromosome of M. loti strain TONO con-tains four haloacid dehalogenase type II genes namely, dehLt1 (MLTONO_2099), dehLt2 (MLTONO_3660), dehLt3 (MLTONO_4143), and dehLt4 (MLTONO_6945), and their corresponding enzymes were designated as DehLt1, DehLt2, DehLt3, and DehLt4, respectively. The only haloalkane dehalogen-ase gene (MLTONO_4828) was located upstream of the dehLt3 gene and its amino acid share 88% identity with DmlA of Mesorhizobium japonicum MAFF 303099. The putative haloacid permease gene designated as dehrPt (MLTONO_0284) was located downstream of the dehLt1 and its amino acids show 69% identity with haloacid per-mease of Rhizobium sp. RC1. The gene encoding helix-turn-helix (HTH) motif family DNA-binding protein regulator and LysR family transcriptional regulator genes were also identified, possibly for regulatory functions. The genomic studies as such, have good potential to be screened for new type of dehalogenases based on basic molecular structure and functions analysis

Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements

As they proliferate, living cells undergo transitions between specific molecularly and developmentally distinct states. Despite the functional centrality of these transitions in multicellular organisms, it has remained challenging to determine which transitions occur and at what rates without perturbations and cell engineering. Here, we introduce kin correlation analysis (KCA) and show that quantitative cell-state transition dynamics can be inferred, without direct observation, from the clustering of cell states on pedigrees (lineage trees). Combining KCA with pedigrees obtained from time-lapse imaging and endpoint single-molecule RNA-fluorescence in situ hybridization (RNA-FISH) measurements of gene expression, we determined the cell-state transition network of mouse embryonic stem (ES) cells. This analysis revealed that mouse ES cells exhibit stochastic and reversible transitions along a linear chain of states ranging from 2C-like to epiblast-like. Our approach is broadly applicable and may be applied to systems with irreversible transitions and non-stationary dynamics, such as in cancer and development

Dynamic Heterogeneity and DNA Methylation in Embryonic Stem Cells

Cell populations can be strikingly heterogeneous, composed of multiple cellular states, each exhibiting stochastic noise in its gene expression. A major challenge is to disentangle these two types of variability and to understand the dynamic processes and mechanisms that control them. Embryonic stem cells (ESCs) provide an ideal model system to address this issue because they exhibit heterogeneous and dynamic expression of functionally important regulatory factors. We analyzed gene expression in individual ESCs using single-molecule RNA-FISH and quantitative time-lapse movies. These data discriminated stochastic switching between two coherent (correlated) gene expression states and burst-like transcriptional noise. We further showed that the “2i” signaling pathway inhibitors modulate both types of variation. Finally, we found that DNA methylation plays a key role in maintaining these metastable states. Together, these results show how ESC gene expression states and dynamics arise from a combination of intrinsic noise, coherent cellular states, and epigenetic regulation

Environmental assessment of mountain grassland farms with mixed cattle systems: use of bioeconomic simulations

Management practices of cattle farming systems must be improved, particularly to increase the systems’ feed self-sufficiency, food production and environmental performances. In mountain areas of the Massif Central (central France), mixed dairy/suckler cattle systems enable farmers to use grassland resources better and cope with economic fluctuations. Our objective was to estimate levels of ecosystem services provided by mixed dairy/suckler cattle systems as a function of the degree of mixing, along with their greenhouse gas emissions and energy use when their operation is optimized on an economic basis. The hypothesis was that mixed dairy/suckler cattle systems allow for controlled use of biomass, with better environmental performances than specialized systems (pure dairy or suckler herd) by maintaining grassland ecosystem services. Five herd-distribution scenarios were simulated using the Orfee bioeconomic optimization model. Environmental performances of the five systems were assessed according to three functional units (i.e., per farm, ha and kg protein produced). Mixed dairy/suckler cattle systems, which enabled larger herds, had higher greenhouse gas emissions per ha than specialized systems. However, because dairy cows produce more protein (milk and beef) than suckler cows, specialized dairy systems had the lowest greenhouse gas emissions and energy use per kg of protein. Specialized dairy systems had less advantage when dairy cows had less access to grassland. For the production of both milk and beef, mixed dairy/suckler cattle systems favour more sustainable use of biomass and tend to maintain a better combination of levels of ecosystem services for livestock production than specialized cattle farming systems

Dasatinib inhibits the growth of molecularly heterogeneous myeloid leukemias.

PURPOSE: Dasatinib is a dual Src/Abl inhibitor recently approved for Bcr-Abl+ leukemias with resistance or intolerance to prior therapy. Because Src kinases contribute to multiple blood cell functions by triggering a variety of signaling pathways, we hypothesized that their molecular targeting might lead to growth inhibition in acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: We studied growth factor-dependent and growth factor-independent leukemic cell lines, including three cell lines expressing mutants of receptor tyrosine kinases (Flt3 or c-Kit) as well as primary AML blasts for responsiveness to dasatinib. RESULTS: Dasatinib resulted in the inhibition of Src family kinases in all cell lines and blast cells at approximately 1 x 10(-9) mol/L. It also inhibited mutant Flt3 or Kit tyrosine phosphorylation at approximately 1 x 10(-6) mol/L. Mo7e cells expressing the activating mutation (codon 816) of c-Kit were most sensitive to growth inhibition with a GI(50) of 5 x 10(-9) mol/L. Primary AML blast cells exhibited a growth inhibition of \u3c1 x\u3e10(-6) mol/L. Cell lines that showed growth inhibition at approximately 1 x 10(-6) mol/L showed a G(1) cell cycle arrest and correlated with accumulation of p21 and p27 protein. The addition of rapamycin or cytotoxic agents enhanced growth inhibition. Dasatinib also caused the apoptosis of Mo7e cells expressing oncogenic Kit. CONCLUSIONS: Although all of the precise targets for dasatinib are not known, this multikinase inhibitor causes either growth arrest or apoptosis in molecularly heterogeneous AML. The addition of cytotoxic or targeted agents can enhance its effects

Single-Cell Transcriptome Analysis Reveals Dynamic Changes in lncRNA Expression during Reprogramming

Cellular reprogramming highlights the epigenetic plasticity of the somatic cell state. Long noncoding RNAs (lncRNAs) have emerging roles in epigenetic regulation, but their potential functions in reprogramming cell fate have been largely unexplored. We used single-cell RNA sequencing to characterize the expression patterns of over 16,000 genes, including 437 lncRNAs, during defined stages of reprogramming to pluripotency. Self-organizing maps (SOMs) were used as an intuitive way to structure and interrogate transcriptome data at the single-cell level. Early molecular events during reprogramming involved the activation of Ras signaling pathways, along with hundreds of lncRNAs. Loss-of-function studies showed that activated lncRNAs can repress lineage-specific genes, while lncRNAs activated in multiple reprogramming cell types can regulate metabolic gene expression. Our findings demonstrate that reprogramming cells activate defined sets of functionally relevant lncRNAs and provide a resource to further investigate how dynamic changes in the transcriptome reprogram cell state

Synthetic recording and in situ readout of lineage information in single cells

Reconstructing the lineage relationships and dynamic event histories of individual cells within their native spatial context is a long-standing challenge in biology. Many biological processes of interest occur in optically opaque or physically inaccessible contexts, necessitating approaches other than direct imaging. Here, we describe a new synthetic system that enables cells to record lineage information and event histories in the genome in a format that can be subsequently read out in single cells in situ. This system, termed Memory by Engineered Mutagenesis with Optical In situ Readout (MEMOIR), is based on a set of barcoded recording elements termed scratchpads. The state of a given scratchpad can be irreversibly altered by Cas9-based targeted mutagenesis, and read out in single cells through multiplexed single-molecule RNA fluorescence hybridization (smFISH). To demonstrate a proof of principle of MEMOIR, we engineered mouse embryonic stem (ES) cells to contain multiple scratchpads and other recording components. In these cells, scratchpads were altered in a progressive and stochastic fashion as cells proliferated. Analysis of the final states of scratchpads in single cells in situ enabled reconstruction of the lineage trees of cell colonies. Combining analysis of endogenous gene expression with lineage reconstruction in the same cells further allowed inference of the dynamic rates at which ES cells switch between two gene expression states. Finally, using simulations, we showed how parallel MEMOIR systems operating in the same cell can enable recording and readout of dynamic cellular event histories. MEMOIR thus provides a versatile platform for information recording and in situ, single cell readout across diverse biological systems