Coherent activation of a synthetic mammalian gene network

A quantitative analysis of naturally-occurring regulatory networks, especially those present in mammalian cells, is difficult due to their high complexity. Much simpler gene networks can be engineered in model organisms and analyzed as isolated regulatory modules. Recently, several synthetic networks have been constructed in mammalian systems. However, most of these engineered mammalian networks have been characterized using steady-state population level measurements. Here, we use an integrated experimental-computational approach to analyze the dynamical response of a synthetic positive feedback network in individual mammalian cells. We observe a switch-like activation of the network with variable delay times in individual cells. In agreement with a stochastic model of the network, we find that increasing the strength of the positive feedback results in a decrease in the mean delay time and a more coherent activation of individual cells. Our results are important for gaining insight into biological processes which rely on positive feedback regulation

Using Cash-To-Cash To Benchmark Service Industry Performance

The cash-to-cash (C2C) metric is a measurement tool which may be used to bridge the management of firms and functions in a supply chain.  C2C can be used by management to improve firm liquidity position and overall firm value.  Measuring C2C also offers a consistent measure across time, helps to identify the greatest leverage points and opportunities for improvement, serves as a means to set goals for improvement within the supply chain, and can help to optimize the entire supply chain, instead of sub-optimizing individual portions.  In this study, the authors illustrate the calculation of cash-to-cash, investigate changes in C2C between product and service industries to identify key differences, review and discuss key leverage points of C2C, and provide insights for today’s service industry managers to understand the C2C metric from both accounting and supply chain management perspectives.  Data in this study can also be used for benchmarking purposes

Mosquito Surveillance Program Using Ovitraps Detected Aedes aegypti at the Honolulu International Airport in 2012

mosquito surveillance program using ovitraps at the Honolulu In- ternational Airport (HIA), Hawaii, USA May 2010 to June 2012 revealed that A. albopictus egg counts fluctuated over time during the surveillance program and the highest oviposition was observed from February to May 2011 and the lowest was from September to November 2011. Positive correlations found between a given week’s rainfall and egg counts 1 and 2 weeks later suggested that rainfall triggered the hatching of eggs which were laid before the rainfall, rather than di- rectly stimulating adult oviposition. In January and June 2012, Aedes aegypti was discovered from a small vegetated area located between terminals for out-of-state and within-state flights. This species had not been confirmed present on Oahu at least since 1948. This finding has led us to intensify our surveillance program at the airport, with the hope that we would improve our understanding of the nature of mosquito introductions at this important port of entry for the Hawaiian Islands

Limiting the Persistence of a Chromosome Break Diminishes Its Mutagenic Potential

To characterize the repair pathways of chromosome double-strand breaks (DSBs), one approach involves monitoring the repair of site-specific DSBs generated by rare-cutting endonucleases, such as I-SceI. Using this method, we first describe the roles of Ercc1, Msh2, Nbs1, Xrcc4, and Brca1 in a set of distinct repair events. Subsequently, we considered that the outcome of such assays could be influenced by the persistent nature of I-SceI-induced DSBs, in that end-joining (EJ) products that restore the I-SceI site are prone to repeated cutting. To address this aspect of repair, we modified I-SceI-induced DSBs by co-expressing I-SceI with a non-processive 3′ exonuclease, Trex2, which we predicted would cause partial degradation of I-SceI 3′ overhangs. We find that Trex2 expression facilitates the formation of I-SceI-resistant EJ products, which reduces the potential for repeated cutting by I-SceI and, hence, limits the persistence of I-SceI-induced DSBs. Using this approach, we find that Trex2 expression causes a significant reduction in the frequency of repair pathways that result in substantial deletion mutations: EJ between distal ends of two tandem DSBs, single-strand annealing, and alternative-NHEJ. In contrast, Trex2 expression does not inhibit homology-directed repair. These results indicate that limiting the persistence of a DSB causes a reduction in the frequency of repair pathways that lead to significant genetic loss. Furthermore, we find that individual genetic factors play distinct roles during repair of non-cohesive DSB ends that are generated via co-expression of I-SceI with Trex2

The behavioral ecology of moral dilemmas: childhood unpredictability, but not harshness, predicts less deontological and utilitarian responding

Childhood unpredictability and harshness are associated with patterns of psychology and behavior that enable individuals to make the most of adverse environments. The current research assessed effects of childhood unpredictability and harshness on individual differences in sacrificial moral decision making. Six studies (N = 1,503) supported the hypothesis that childhood unpredictability, but not harshness, would be associated with fewer decisions to reject harm (consistent with deontological ethics) and to maximize overall outcomes (consistent with utilitarian ethics). These associations were not moderated by perceptions of current environmental unpredictability (Studies 3a and 3b) and were robust to potential confounds (religiosity, political conservativism, Big 5 personality traits, and social desirability; Study 5). The associations between childhood unpredictability and lower deontological and utilitarian tendencies were statistically mediated by low levels of empathic concern and poor-quality social relationships (Study 4). Findings are consistent with the possibility that early calibration to ecological unpredictability, but not harshness, undermines other-oriented psychological processes which, in turn, reduce moral concerns about harm and consequences for other people

Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions

Pertambangan di Kawasan Konservasi: Permasalahan Regulasi dan Koordinasi

Informasi dan klaim tentang berlangsungnya kegiatan pertambangan di hutan konservasi dapat dengan mudah kita jumpai. Salah satunya, Komisi Pemberantasan Korupsi (KPK) dalam presentasi tentang koordinasi dan supervisi pengelolaan mineral dan batu bara di 19 provinsi pada akhir 2014, menyatakan bahwa izin pertambangan di kawasan hutan konservasi mencapai 1,37 juta hektar (KPK, 2014)

Monomeric Bistability and the Role of Autoloops in Gene Regulation

Genetic toggle switches are widespread in gene regulatory networks (GRN). Bistability, namely the ability to choose among two different stable states, is an essential feature of switching and memory devices. Cells have many regulatory circuits able to provide bistability that endow a cell with efficient and reliable switching between different physiological modes of operation. It is often assumed that negative feedbacks with cooperative binding (i.e. the formation of dimers or multimers) are a prerequisite for bistability. Here we analyze the relation between bistability in GRN under monomeric regulation and the role of autoloops under a deterministic setting. Using a simple geometric argument, we show analytically that bistability can also emerge without multimeric regulation, provided that at least one regulatory autoloop is present