Data structures for algebraic manipulation

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Sugary Logistics Gone Wrong:Membrane Trafficking and Congenital Disorders of Glycosylation

Contains fulltext : 225799.pdf (publisher's version ) (Open Access)Glycosylation is an important post-translational modification for both intracellular and secreted proteins. For glycosylation to occur, cargo must be transported after synthesis through the different compartments of the Golgi apparatus where distinct monosaccharides are sequentially bound and trimmed, resulting in increasingly complex branched glycan structures. Of utmost importance for this process is the intraorganellar environment of the Golgi. Each Golgi compartment has a distinct pH, which is maintained by the vacuolar H(+)-ATPase (V-ATPase). Moreover, tethering factors such as Golgins and the conserved oligomeric Golgi (COG) complex, in concert with coatomer (COPI) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion, efficiently deliver glycosylation enzymes to the right Golgi compartment. Together, these factors maintain intra-Golgi trafficking of proteins involved in glycosylation and thereby enable proper glycosylation. However, pathogenic mutations in these factors can cause defective glycosylation and lead to diseases with a wide variety of symptoms such as liver dysfunction and skin and bone disorders. Collectively, this group of disorders is known as congenital disorders of glycosylation (CDG). Recent technological advances have enabled the robust identification of novel CDGs related to membrane trafficking components. In this review, we highlight differences and similarities between membrane trafficking-related CDGs

Taming our wild data: On intercoder reliability in discourse research

Many research questions in the field of applied linguistics are answered by manually analyzing data collections or corpora: collections of spoken, written and/or visual communicative messages. In this kind of quantitative content analysis, the coding of subjective language data often leads to disagreement among raters. In this paper, we discuss causes of and solutions to disagreement problems in the analysis of discourse. We discuss crucial factors determining the quality and outcome of corpus analyses, and focus on the sometimes tense relation between reliability and validity. We evaluate formal assessments of intercoder reliability. We suggest a number of ways to improve the intercoder reliability, such as the precise specification of the variables and their coding categories and carving up the coding process into smaller substeps. The paper ends with a reflection on challenges for future work in discourse analysis, with special attention to big data and multimodal discourse

Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior: A Narrative Review and Conceptual Hypotheses

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness

A Micro-Costing Framework for Circulating Tumor DNA Testing in Dutch Clinical Practice

Circulating tumor DNA (ctDNA) is a promising new biomarker with multiple potential applications in cancer care. Estimating total cost of ctDNA testing is necessary for reimbursement and implementation, but challenging because of variations in workflow. We aimed to develop a micro-costing framework for consistent cost calculation of ctDNA testing. First, the foundation of the framework was built, based on the complete step-wise diagnostic workflow of ctDNA testing. Second, the costing method was set up, including costs for personnel, materials, equipment, overhead, and failures. Third, the framework was evaluated by experts and applied to six case studies, including PCR-, mass spectrometry–, and next-generation sequencing–based platforms, from three Dutch hospitals. The developed ctDNA micro-costing framework includes the diagnostic workflow from blood sample collection to diagnostic test result. The framework was developed from a Dutch perspective and takes testing volume into account. An open access tool is provided to allow for laboratory-specific calculations to explore the total costs of ctDNA testing specific workflow parameters matching the setting of interest. It also allows to straightforwardly assess the impact of alternative prices or assumptions on the cost per sample by simply varying the input parameters. The case studies showed a wide range of costs, from €168 to €7638 ($199 to$9124) per sample, and generated information. These costs are sensitive to the (coverage of) platform, setting, and testing volume

Characterizing and TRAPing a Social Stress-Activated Neuronal Ensemble in the Ventral Tegmental Area

Social stress is a major contributor to neuropsychiatric issues such as depression, substance abuse and eating disorders. The ventral tegmental area (VTA) is involved in the effects of stress on cognitive and emotional processes perturbed in these disorders. However, the VTA is a cellularly heterogeneous brain area and it remains unclear which of its neuronal populations make up the social stress-sensitive ensemble. The current study characterizes the molecular, topographical and functional properties of VTA social stress-activated cells. First, we used immunohistochemical analysis of Fos protein, a marker of recent increased neuronal activity, to show that acute social stress activates a mainly neuronal ensemble in the VTA (VTA Social stress neurons). Topographical analysis showed that this ensemble, which comprises ∼11% of all VTA neurons, occurs across VTA subregions. Further analysis showed that approximately half of the VTA Social stress neurons express the dopamine synthesis rate-limiting enzyme tyrosine hydroxylase (TH). In a minority of cases this occurred with coexpression of vesicular glutamate transporter 2 (Vglut2). Also part of the ensemble were VTA cells expressing just Vglut2 without TH, and cells expressing the vesicular GABA transporter (VGAT) without TH. Next, using targeted recombination in active populations (TRAP2), we showed that VTA Social stress neurons can be permanently tagged and made tractable for future functional investigations. Using a combination of TRAP2 and patch-clamp electrophysiology we demonstrate that VTA Social stress neurons exhibit higher excitability than their non-TRAPed neighbor cells. Overall, this study shows that acute social stress activates an ensemble of neurons throughout the VTA, comprising distinct molecular identities, and with specific electrophysiological features. It also identifies TRAP2 as a tool to make this ensemble tractable for future functional studies

Survival of Lactobacillus sakei during heating, drying and storage in the dried state when growth has occurred in the presence of sucrose or monosodium glutamate

Spray-dried cells of Lactobacillus sakei CTC 494 survived ca. 60% longer in the spray dried state when cells were grown in the presence of 20 g sucrose l)1 or 12.5 g monosodium glutamate l)1. No significant differences were observed in viability during storage in the freeze dried state with the addition of these compounds to the growth medium, nor in survival during a heat treatment (55ºC). Both sucrose and glutamate in the growth medium suppressed intracellular accumulation of total amino acids and changed the overall pattern of the individual amino acids. Glutamate in the growth medium enhanced intracellular glutamate by ca. 38