Use of Ecologically-and Evolutionary Relevant Transcriptomic Data to Infer Functions of Fungal Pathogen Gene Orthologs Important for Limiting Fungal Stresses Caused by Interacting Host Plants and Bacteria

We identified key genes needed for maintenance and growth and homed in on genes where there could be a competition between maintenance requirements (stress) and growth requirements. Such processes are synthesis of arginine, synthesis of DNA-bases, nitric oxide synthesis needing arginine, autophagy, DNA synthesis and DNA repair. Using procedures previously developed for the use of sets of downloaded transcriptomic data to test hypotheses concerning at what time under the course of infection of plants genes are expressed for the two pathogens Fusarium graminearum and Magnaporthe oryzae, we constructed a simplified regulatory network for these genes for both organisms. Our analysis shows that the transcription effort (cost) to maintain the fungal cells (maintenance) are high before infection and in early infection. During the following biotrophic phase maintenance cost drops for later in the transition to the necrotrophic phase increase dramatically. Finally, in the necrotrophic phase, maintenance is lower again despite the high growth rate that can also cause stress. The expressions of all identified genes behaved almost similar for both fungi except the DNA repair genes PARP/PARG that was not responding or absent in the mainly clonal M. oryzae which might indicate this species is more subject to evolution by point mutations than F. graminearum where sexual reproduction is frequent. The potential consequences of these different roles for PARP/PARG in the development and the accelerated breakage of host species resistance in a Red Queen dynamics scenario is discussed. Our analysis demonstrates the possibility to use large transcriptome datasets and co-regulations between key genes to test hypotheses and discusses the advantages with this technique as complement to molecular techniques employing knockouts and over-expression of target genes to suggest gene roles.

Designing a Visual Novel Game in Nusantara Folklore 'The Origin of Lake Toba' using Renpy Visual Novel Engine

<p align="justify">Public knows about the folklore of the archipelago in Indonesia through stories told directly by parents and their families, passed down orally from parents to children and their ancestors to future generations. Likewise, the folklore of the origin of Lake Toba. The folklore of the archipelago seems to be slowly disappearing because it is only passed down orally and is less desirable and does not rule out being forgotten and extinct. This is what makes the writer decide to conduct research on the folklore of the archipelago through the media of games, namely visual novels with the story of the origin of Lake Toba as the object. The researcher wants to make an application in the form of animation with the help of a program that wants to be enjoyed by many people and can also be used as a learning medium.The game application that will be produced will later be made using the Ren'Py Novel Visual Engine application and the research method that the author will use is an extreme programming as a management system with the following stages: Exploration Phase, Planning Phase, Iteration Phase, Production Phase, Maintenance Phase and Final Publication Stage ( Death Phase), with the existing tools can make the application of the story of the origin of Lake Toba well, then for future research to make it in a 3-dimension version</p>

0478 A Multicenter Pilot Study to Evaluate Next-Dose Transition from Zolpidem to Lemborexant for the Treatment of Insomnia

Introduction Switching of medications for insomnia occurs often in clinical practice based on a variety of reasons. However, few clinical studies have examined methods for transitioning patients between different insomnia medications. This is especially important to consider when the classes of drugs are different (e.g., GABA-ergic agonism vs orexin receptor antagonism); thus, clinical guidance would be valuable. The safety and efficacy of the dual orexin receptor antagonist lemborexant (LEM) for the treatment of insomnia was confirmed in two Phase 3 studies, SUNRISE-1 (NCT02783729, E2006-G000-304) and SUNRISE-2 (NCT02952820, E2006-G000-303). This pilot study (NCT04009577, E2006-A001-312) was designed to assess pre-specified dosing approaches for directly transitioning from the sedative-hypnotic zolpidem (ZOL), a commonly prescribed sleep aid, to LEM. Methods This multicenter pilot study has enrolled subjects age ≥18 years with an insomnia diagnosis (DSM-5 criteria), who used ZOL (intermittently or frequently) as their only insomnia treatment. Following a 3-week Screening period, eligible subjects enter the Treatment Phase (2-week titration period: assigned to 1 of 3 treatment arms based on ZOL use during Screening), and then the Extension Phase (maintenance period up to 12 weeks). During both the Treatment and Extension Phases, the dose of LEM is flexible between 5 and 10 mg, depending on efficacy and tolerability. The primary endpoint is to evaluate the proportion of subjects taking ZOL who successfully transition to LEM (lemborexant 5 mg [LEM5] or lemborexant 10 mg [LEM10]) after 2 weeks of LEM treatment. Results Enrollment began July 15, 2019. It was initially projected that approximately 110 subjects would be screened to provide about 60 subjects for randomization across 3 treatment arms. Interim data will be presented (planned cutoff date Jan 08, 2020). Conclusion This pilot study will help inform on dosing guidance when transitioning a patient from a GABA-ergic drug to an orexin receptor antagonist. Support Eisai Inc.

Coping with Disease in Multiple Sclerosis Patients : A Concept Analysis

Background and Objective: Coping with disease can lead to disease recovery and improve quality of life in people living with multiple sclerosis; therefore, correct definition of this concept is essential. Different dimensions of coping have been emphasized in various studies. This study was aimed to define, clarify and analyzing its concept in people with multiple sclerosis. Materials and methods: In this study, analysis was conducted using the hybrid model in three phases. In the theoretical phase, literature on coping with MS was reviewed until 2016. In the field work phase, in-depth interviews were conducted with 11 people with MS. The conventional content analysis was used in two theoretical and field work phases using Graneheim and Lundman stages. Then, the results of two phases were combined in the final analysis phase. Results and Discussion: The literature review in the theoretical phase revealed five features of coping: accepting the current situation, Self-regulation, Self-efficacy, Multi-dimensional, complex and dynamic nature and Maintenance of effect balance. In the field work phase, maintenance and development of human interactions were added to the features of the concept. Conclusion: Considering these characteristics is necessary in planning to improve coping and quality of life for people living with MS. Bangladesh Journal of Medical Science Vol.19(1) 2020 p.64-72

Short-term synaptic dynamics control the activity phase of neurons in an oscillatory network

In oscillatory systems, neuronal activity phase is often independent of network frequency. Such phase maintenance requires adjustment of synaptic input with network frequency, a relationship that we explored using the crab, Cancer borealis, pyloric network. The burst phase of pyloric neurons is relatively constant despite a > two fold variation in network frequency. We used noise input to characterize how input shape influences burst delay of a pyloric neuron, and then used dynamic clamp to examine how burst phase depends on the period, amplitude, duration, and shape of rhythmic synaptic input. Phase constancy across a range of periods required a proportional increase of synaptic duration with period. However, phase maintenance was also promoted by an increase of amplitude and peak phase of synaptic input with period. Mathematical analysis shows how short-term synaptic plasticity can coordinately change amplitude and peak phase to maximize the range of periods over which phase constancy is achieved.

Short-Term Synaptic Dynamics Control the Activity Phase of Neurons in an Oscillatory Network

In oscillatory systems, neuronal activity phase is often independent of network frequency. Such phase maintenance requires adjustment of synaptic input with network frequency, a relationship that we explored using the crab, Cancer borealis, pyloric network. The burst phase of pyloric neurons is relatively constant despite a >2-fold variation in network frequency. We used noise input to characterize how input shape influences burst delay of a pyloric neuron, and then used dynamic clamp to examine how burst phase depends on the period, amplitude, duration, and shape of rhythmic synaptic input. Phase constancy across a range of periods required a proportional increase of synaptic duration with period. However, phase maintenance was also promoted by an increase of amplitude and peak phase of synaptic input with period. Mathematical analysis shows how short-term synaptic plasticity can coordinately change amplitude and peak phase to maximize the range of periods over which phase constancy is achieved.

Metabolic Alkalosis

Metabolic alkalosis is a common clinical problem encountered by the nephrologist. An understanding of the pathogenesis of this electrolyte disorder, which includes a generative and a maintenance phase, is essential to elucidating the etiology and deciding on the appropriate treatment. Metabolic alkalosis is characterized by an increase in pH, a decrease in [H+], and an increase in [HCO3–]. The generative phase of metabolic alkalosis involves either loss of acid (e.g., gastrointestinal losses), gain of bicarbonate (e.g., antacids), or cellular shift (e.g., hypokalemia). The maintenance phase involves impairment of the renal handling of bicarbonate (decreased glomerular filtration, increased bicarbonate tubular reabsorption). We discuss the different etiologies, such as chloride depletion (e.g., vomiting), potassium depletion (e.g., primary hyperaldosteronism), and hypercalcemic states (e.g., milk-alkali syndrome). This review also discusses the symptoms, diagnosis, and prognosis of metabolic alkalosis. A diagnostic algorithm based on volume status and urine electrolytes will help differentiate the different etiologies. Treatment options are summarized based on chloride-sensitive or chloride-resistant metabolic alkalosis. This review contains 5 figures, 3 tables and 12 references Key words: chloride resistance, chloride sensitivity, generative phase, maintenance phase, metabolic alkalosis, syndromes with metabolic alkalosis

Metabolic Alkalosis

Metabolic alkalosis is a common clinical problem encountered by the nephrologist. An understanding of the pathogenesis of this electrolyte disorder, which includes a generative and a maintenance phase, is essential to elucidating the etiology and deciding on the appropriate treatment. Metabolic alkalosis is characterized by an increase in pH, a decrease in [H+], and an increase in [HCO3–]. The generative phase of metabolic alkalosis involves either loss of acid (e.g., gastrointestinal losses), gain of bicarbonate (e.g., antacids), or cellular shift (e.g., hypokalemia). The maintenance phase involves impairment of the renal handling of bicarbonate (decreased glomerular filtration, increased bicarbonate tubular reabsorption). We discuss the different etiologies, such as chloride depletion (e.g., vomiting), potassium depletion (e.g., primary hyperaldosteronism), and hypercalcemic states (e.g., milk-alkali syndrome). This review also discusses the symptoms, diagnosis, and prognosis of metabolic alkalosis. A diagnostic algorithm based on volume status and urine electrolytes will help differentiate the different etiologies. Treatment options are summarized based on chloride-sensitive or chloride-resistant metabolic alkalosis. This review contains 5 figures, 3 tables and 12 references Key words: chloride resistance, chloride sensitivity, generative phase, maintenance phase, metabolic alkalosis, syndromes with metabolic alkalosis