Unrelated toxin-antitoxin systems cooperate to induce persistence.

Persisters are drug-tolerant bacteria that account for the majority of bacterial infections. They are not mutants, rather, they are slow-growing cells in an otherwise normally growing population. It is known that the frequency of persisters in a population is correlated with the number of toxin-antitoxin systems in the organism. Our previous work provided a mechanistic link between the two by showing how multiple toxin-antitoxin systems, which are present in nearly all bacteria, can cooperate to induce bistable toxin concentrations that result in a heterogeneous population of slow- and fast-growing cells. As such, the slow-growing persisters are a bet-hedging subpopulation maintained under normal conditions. For technical reasons, the model assumed that the kinetic parameters of the various toxin-antitoxin systems in the cell are identical, but experimental data indicate that they differ, sometimes dramatically. Thus, a critical question remains: whether toxin-antitoxin systems from the diverse families, often found together in a cell, with significantly different kinetics, can cooperate in a similar manner. Here, we characterize the interaction of toxin-antitoxin systems from many families that are unrelated and kinetically diverse, and identify the essential determinant for their cooperation. The generic architecture of toxin-antitoxin systems provides the potential for bistability, and our results show that even when they do not exhibit bistability alone, unrelated systems can be coupled by the growth rate to create a strongly bistable, hysteretic switch between normal (fast-growing) and persistent (slow-growing) states. Different combinations of kinetic parameters can produce similar toxic switching thresholds, and the proximity of the thresholds is the primary determinant of bistability. Stochastic fluctuations can spontaneously switch all of the toxin-antitoxin systems in a cell at once. The spontaneous switch creates a heterogeneous population of growing and non-growing cells, typical of persisters, that exist under normal conditions, rather than only as an induced response. The frequency of persisters in the population can be tuned for a particular environmental niche by mixing and matching unrelated systems via mutation, horizontal gene transfer and selection

Financing of health services and alternative methods: some suggestions

Presenting Health Care should have priority because of importance of health care for individuals and society. Today, with understanding importance of this point different political ideas and economic ideas put a lot of effort to increase the individual’s productivity and average life expectation and improve investments on humanity. Even so, sometimes statistics on health services can be critter of structure of modern countries. (Average life expectation, percentage of baby death etc.) Providing effective and fair health service which is important as such as life itself limited to cost and question of finding the right sources to cover the cost. Slow economic growth, increasing unemployment, fast growing population are the main factors of increased cost of health services and those factors are appears as actual reasons of financial difficulties on agenda. Financial difficulties of health services will affect to quality and amount of services and also will be the main reason to bring out different methods of practice. But despite those differences, to provide quality health services to the individuals requires strong and continual financial sources. Financial difficulties of health services will affect to the services for individuals so therefore will effect to individuals health. So this essay originated from those important points, aims to explore the financial difficulties throughout historical development and at the same time will look for improvement and alternative managements.Health care services, financing and alternative methods

LAND CHARACTERISTICS TO INCREASE SUGAR CONTENT OF MELON FRUIT (Cucumis melo)

Sugar content is primary importance in determining the quality of melon fruit. Quality melon Nganjuk region, Madiun and Ngawi when glucose levels decreased to below ten (10) Brix, so that does not taste sweet and not durable to be stored. Departing from low sugar levels, which pushed to find reasons for the decrease in sugar content of fruit in terms of land characteristics and environmental characteristics. The purpose of this study is to examine the characteristics of land to do with the chemical characteristics of fruit, especially melons melon fruit sugar content. Materials are. (1) The soil layer 0-20 cm of the soil surface. Soil samples from the center area are Nganjuk melons, Madiun and Ngawi. Each regional center of the melon is represented by six (6) observation point on land characteristics. Observations on land characteristics include. Climate data from the station or the nearest local climatology, physical characteristics, chemical and biological soil, and soil geomorphology. Climate data and geomorphological data useful for determining the level of land suitability for crop melons, while data on land characteristics useful for identification of land quality and soil fertility degree to which the modeling of the relationship with the Chemical characteristics of melonfruit. The results of this study indicate that nearly all regions Region. Ngawi, Madiun and Nganjuk there is a limiting factor content of C-Organic and low potassium. There is a relationship between sugar levels content and land characteristics, especially with potassium content. Key words: land characteristics, sugar content, melo

Co-evolution of Information Systems in Fast-Growing Small Firms

The paper examines the co-evolution of different dimensions of information systems for a sample of fast-growing small firms. The investigation uses primary source longitudinal empirical evidence. The data are taken from a large database on the lifecycle experience of one-hundred-and-fifty new business starts over a four-year period. They were collected by face to face interviews with owner-managers of small entrepreneurial firms. Interviews were conducted using an administered questionnaire that covered the agenda of markets, finance, costs, business strategy, the development of a management information system, human capital, organisation and technical change. This work uses primarily the data on management information systems. The basic approach used is to compare the attributes of the fastest and slowest paced firms, as identified by their growth rates. We then examine the evolution of these firms' management information systems. The measures used to identify changes in systems include: capital investment techniques, such as return on investment, residual income, net present value, internal rate of return and payback period; methods for managing costs, like just-in-time management, activity-based costing, quantitative risk analysis, value analysis, strategic pricing and transfer pricing; and using computer applications for storing information, project appraisal, financial modelling, forecasting and sensitivity analysis. 'Time lines' are graphed to show the points at which various features of information systems are introduced (e.g. data storage, forecasting, sensitivity analysis), and derived techniques (e.g. ROI, ABC) implemented. Firms are dichotomised into highgrowth and low-growth groups. Comparisons are made within firms and across firms in terms of the co-evolution of different aspects of their accounting information systems

Molecular biology techniques as a tool for detection and characterisation of Mycobacterium avium subsp. paratuberculosis

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the causative agent of paratuberculosis, also known as Johne’s disease, a chronic intestinal infection in cattle and other ruminants. Paratuberculosis is characterised by diarrhea and weight loss that occurs after a period of a few months up to several years without any clinical signs. The considerable economic losses to dairy and beef cattle producers are caused by reduced milk production and poor reproduction performance in subclinically infected animals. Early diagnosis of infected cattle is essential to prevent the spread of the disease. Efforts have been made to eradicate paratuberculosis by using a detection and cull strategy, but eradication is hampered by the lack of suitable and sensitive diagnostic methods. This thesis, based on five scientific investigations, describes the development of different DNA amplification strategies for detection and characterisation of M. paratuberculosis. Various ways to pre-treat bacterial cultures, tissue specimens and fecal samples prior to PCR analysis were investigated. Internal positive PCR control molecules were developed and used in PCR analyses to improve the reliability and to facilitate the interpretation of the results. The sensitivity of the ultimate methods was found to be approximate that of culture and allowed detection of low numbers of M. paratuberculosis expected to be found in subclinically infected animals. Genomic DNA of a Swedish mycobacterial isolate, incorrectly identified by PCR as M. paratuberculosis was characterised. The isolate was closely related to M. cookii and harboured one copy of a DNA segment with 94% similarity to IS900, the target sequence used in diagnostic PCR for detection of M. paratuberculosis. This finding highlighted the urgency of developing or evaluating PCR systems based on genes other than IS900. A PCR-based fingerprinting method using primers targeting the enterobacterial intergenic consensus sequence (ERIC) and the IS900 sequence was developed and successfully used to distinguish M. paratuberculosis from closely related mycobacteria, including the above mentioned mycobacterial isolate. In conclusion, the molecular biology techniques developed in these studies have proved useful for accelerating the diagnostic detection and characterisation of M. paratuberculosis