Characterisation of the interactions between the KSHV ORF57 protein and the human TREX complex

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human oncovirus associated with multiple malignancies, including Kaposi’s sarcoma (KS). Like all herpesviruses, KSHV can establish either a latent or a lytic infection in host cells. During latency the virus remains in a dormant state, with limited gene expression. After reactivation, KSHV enters the lytic life cycle, characterised by production of infectious virions and subsequent dissemination of the virus from its latent reservoir. Importantly, lytic replication is critical for KS tumourigenesis. KSHV replicates in the nucleus of the host cell and requires cellular mRNA export factors to efficiently export viral mRNAs from the nucleus, allowing their translation in the cytoplasm. But while mammalian mRNA export is linked to splicing, the majority of the KSHV genome encodes intronless mRNAs, prompting the virus to circumvent this step. KSHV therefore expresses ORF57, a multifunctional protein essential for lytic replication. ORF57 recruits members of the cellular human transcription/export (hTREX) complex to form an export competent viral ribonucleoprotein particle (vRNP), facilitating efficient nuclear export of intronless KSHV mRNAs. This study presents a novel mechanism for the specific disruption of the vRNP and subsequent inhibition of virus lytic replication. Results suggest an ATP-cycle dependent remodelling of hTREX, which affects the ability of ORF57 to interact and form an export competent vRNP. Specifically, inhibiting ATP hydrolysis by the hTREX component and ATPase UAP56 prevents ORF57 from recruiting the hTREX complex, while key components of the endogenous complex remain able to interact. Following this finding, UAP56 was targeted by small molecule inhibitors, using a structure-based drug design approach, to prevent ATP hydrolysis and thereby inhibiting vRNP formation. Strikingly, a hit compound identified was shown to disrupt formation of the vRNP, lytic protein expression and infectious virion production, while allowing endogenous hTREX formation within a therapeutic window, where no cytotoxicity was observed. Bearing in mind the conserved mechanism for herpesvirus intronless mRNA export, this study finally presents a series of compounds that are able to prevent both KSHV and HSV-1 lytic replication

An empirical investigation of wood product information valued by young consumers

Recent media reports regarding wood products question the trustworthiness of wood origin declaration, the sustainability of production methods and the product quality. In light of this question, it becomes important to ensure consumer trust in wood and wood-based products. Current research indicates that providing product information enhances product trust and purchase intentions, while young consumers in particular seek detailed product information. However, it is necessary to determine which wood product information young consumers strongly value because providing a high amount leads to information overload. As information needs may vary between different consumer segments, the present work aims at identifying segments of young consumers and their preferred wood-product information. The importance of different wood product information items concerning the purchase decision was investigated with a German-language online survey (N = 185, age range 18–30). A cluster analysis revealed four consumer segments. Thereof, three segments (an environmentally oriented, an environmentally and quality oriented, and a quality oriented segment) valued the provision of wood product information. The preferred information types differed among the three segments. Overall, this paper provides insights into young consumers' preferences for wood product information and the consumer segments on which marketing should focus

Traceability system for capturing, processing and providing consumer-relevant information about wood products: System solution and its economic feasibility

Current research and practice reports indicate the existence of purchase barriers concerning eco-friendly products, e.g. wood products. These can be ascribed to consumers' mistrust regarding the non-observable environmental impact of wood products. To counter the mistrust, wood products are commonly endowed with eco-labels, which may be perceived mostly as a marketing tool, therefore not fulfilling their intended purpose. Current studies have shown that providing consumers with wood product information based on traceability systems increases product trust and purchase intentions, with those information items most valued by consumers being identified as well. Based on this, the paper proposes a traceability information system for the capturing, processing, and provision of product information using examples of wood furniture. Furthermore, a cost-benefit model for the proposed solution is developed. The calculations indicate the possibility of implementing traceability at the item level based on a four-layer system architecture enabling the capture and delivery of all information valued by consumers at acceptable costs. The proposed system helps to overcome purchase barriers of eco-friendly products, increasing consumers' product trust and purchase intentions

Improved resource efficiency and cascading utilisation of renewable materials

In light of various environmental problems and challenges concerning resource allocation, the utilisation of renewable resources is increasingly important for the efficient use of raw materials. Therefore, cascading utilisation (i.e., the multiple material utilisations of renewable resources prior to their conversion into energy) and approaches that aim to further increase resource efficiency (e.g., the utilisation of by-products) can be considered guiding principles. This paper therefore introduces the Special Volume “Improved Resource Efficiency and Cascading Utilisation of Renewable Materials”. Because both research aspects, resource efficiency and cascading utilisation, belong to several disciplines, the Special Volume adopts an interdisciplinary perspective and presents 16 articles, which can be divided into four subjects: Innovative Materials based on Renewable Resources and their Impact on Sustainability and Resource Efficiency, Quantitative Models for the Integrated Optimisation of Production and Distribution in Networks for Renewable Resources, Information Technology-based Collaboration in Value Generating Networks for Renewable Resources, and Consumer Behaviour towards Eco-friendly Products. The interdisciplinary perspective allows a comprehensive overview of current research on resource efficiency, which is supplemented with 15 book reviews showing the extent to which textbooks of selected disciplines already refer to resource efficiency. This introductory article highlights the relevance of the four subjects, presents summaries of all papers, and discusses future research directions. The overall contribution of the Special Volume is that it bridges the resource efficiency research of selected disciplines and that it presents several approaches for more environmentally sound production and consumption

Ketogenic diet and fasting diet as Nutritional Approaches in Multiple Sclerosis (NAMS): protocol of a randomized controlled study

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting diets (FDs) and ketogenic diets (KDs) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KDs and FDs on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate whether a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. METHODS: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions: a KD with a restricted carbohydrate intake of 20-40 g/day; a FD with a 7-day fast every 6 months and 14-h daily intermittent fasting in between; and a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. DISCUSSION: Preclinical data suggest that a KD and a FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and a FD on disease progression of MS

Differences Between Omnivores and Vegetarians in Personality Profiles, Values, and Empathy: A Systematic Review

Numerous medical studies have documented vegetarian diets as having various health benefits. Studies have also compared vegetarians with other dietary groups from a socio-psychological perspective. The objective of this review is to investigate the differences between vegetarians and omnivores in terms of their personality profiles, values, and empathy skills. A search was conducted across three electronic databases. Non-randomized, observational, cross-sectional, and cohort studies were eligible. Outcomes provided information about the differences between the above-mentioned dietary groups regarding their personality profiles, values, and empathy skills. A shortened version of the Newcastle-Ottawa Scale was used to assess the risk of bias for the included studies. Of the 2,513 different studies found, 25 (total number of participants n = 23,589) were ultimately included. These studies indicate that vegetarians significantly differ from omnivores in their personalities, values, and ability to be empathetic. Omnivorism is associated with an increased orientation toward social dominance, greater right-wing authoritarianism, and, in line with this, a stronger tendency to be prejudiced. Vegetarianism is associated with greater openness and empathy. The values of vegetarians are based more on universalism, hedonism, stimulation, and self-direction, whereas the values of omnivores are based more on the idea of power. To answer a narrowly defined and clear question, issues such as animal ethics, animal rights, and environmental protection are not considered in this review. The findings of this review, showing marked differences in personality correlating to the choice of diet and the increasing influence of plant-based diets on a global level, indicate that further studies about vegetarianism are warranted

Kaposi's sarcoma-associated herpesvirus ORF57 protein: exploiting all stages of viral mRNA processing

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms

Portal hypertension in common variable immunodeficiency disorders – a single center analysis on clinical and immunological parameter in 196 patients

BackgroundLiver manifestations and in particular portal hypertension (PH) contribute significantly to morbidity and mortality of patients with common variable immunodeficiency disorders (CVID). Screening strategies and early detection are limited due to the lack of specific diagnostic tools.MethodsWe evaluated clinical, immunological, histological, and imaging parameters in CVID patients with clinical manifestation of portal hypertension (CVID+PH).ResultsPortal hypertension was present in 5.6% of CVID patients and was associated with high clinical burden and increased mortality (18%). Longitudinal data on clinical and immunological parameters in patients before and during clinically manifest portal hypertension revealed a growing splenomegaly and increasing gamma-glutamyl transferase (GGT) and soluble interleukin 2 receptor (SIL-2R) levels with decreasing platelets over time. While ultrasound of the liver failed to detect signs of portal hypertension in most affected patients, transient elastography was elevated in all patients. All CVID+PH patients had reduced naïve CD45RA+CD4+ T-cells (mean of 6,2%). The frequency of severe B-lymphocytopenia (Euroclass B-) was higher in CVID+PH patients. The main histological findings included lymphocytic infiltration, nodular regenerative hyperplasia-like changes (NRH-LC), and porto(-septal) fibrosis.ConclusionCVID patients with lower naïve CD45RA+CD4+ T-cells or severely reduced B-cells might be at higher risk for portal hypertension. The combination of biochemical (increasing sIL-2R, GGT, and decreasing platelets) and imaging parameters (increasing splenomegaly) should raise suspicion of the beginning of portal hypertension

Why it is time to look beyond algal genes in photosynthetic slugs

Eukaryotic organelles depend on nuclear genes to perpetuate their biochemical integrity. This is true for mitochondria in all eukaryotes and plastids in plants and algae. Then how do kleptoplasts, plastids that are sequestered by some sacoglossan sea slugs, survive in the animals' digestive gland cells in the absence of the algal nucleus encoding the vast majority of organellar proteins? For almost two decades, lateral gene transfer (LGT) from algae to slugs appeared to offer a solution, but RNA-seq analysis, later supported by genome sequencing of slug DNA, failed to find any evidence for such LGT events. Yet, isolated reports continue to be published and are readily discussed by the popular press and social media, making the data on LGT and its support for kleptoplast longevity appear controversial. However, when we take a sober look at the methods used, we realize that caution is warranted in how the results are interpreted. There is no evidence that the evolution of kleptoplasty in sea slugs involves LGT events. Based on what we know about photosystem maintenance in embryophyte plastids, we assume kleptoplasts depend on nuclear genes. However, studies have shown that some isolated algal plastids are, by nature, more robust than those of land plants. The evolution of kleptoplasty in green sea slugs involves many promising and unexplored phenomena, but there is no evidence that any of these require the expression of slug genes of algal origin