Prescribing and adjusting exercise training in chronic respiratory diseases – Expert-based practical recommendations

Background International guidelines recommend endurance (ET) and strength training (ST) in patients with chronic respiratory diseases (CRDs), but only provide rough guidance on how to set the initial training load. This may unintentionally lead to practice variation and inadequate training load adjustments. This study aimed to develop practical recommendations on tailoring ET and ST based on practices from international experts from the field of exercise training in CRDs. Methods 35 experts were invited to address a 64-item online survey about how they prescribe and adjust exercise training. Results Cycling (97%) and walking (86%) were the most commonly implemented ET modalities. Continuous endurance training (CET, 83%) and interval endurance training (IET, 86%) were the frequently applied ET types. Criteria to prescribe IET instead of CET were: patients do not tolerate CET due to dyspnoea at the initial training session (79%), intense breathlessness during initial exercise assessment (76%), and/or profound exercise-induced oxygen desaturation (59%). For ST, most experts (68%) recommend 3 sets per exercise; 62% of experts set the intensity at a specific load that patients can tolerate for a range of 8 to 15 repetitions per set. Also, 56% of experts advise patients to approach local muscular exhaustion at the end of a single ST set. Conclusions The experts´ practices were summarized to develop practical recommendations in the form of flowcharts on how experts apply and adjust CET, IET, and ST in patients with CRDs. These recommendations may guide health care professionals to optimize exercise training programs in patients with CRDs

The DOK long-term experiment - lessons learned from 40 years of interdisciplinary research

The world’s growing population calls for sustainable food production within the limits of planetary boundaries. With respect to nitrogen and phosphorus cycling, the loss of biodiversity, land use change and the emission of greenhouse gases, four of these boundaries have been crossed already. Although fragmented knowledge of effects of different cropping systems on these focal planetary boundaries exists, there is a lack of comprehensive data from comparative cropping system experiments over the long run. Four decades back, farmers and researchers co-designed a system comparison experiment, located in Therwil (Basel-Land) Switzerland, comprising a seven-year ley crop rotation. Two conventional (with and without manure), and two organic systems (biodynamic and bioorganic) are compared. This experiment has served as a platform for national and international interdisciplinary research teams in the field of agronomy, soil quality, biodiversity, plant nutrition, food quality, sustainability assessment and modelling. Results of the 40years old DOK experiment show that organic systems, receiving distinctly less external inputs (chemical N, P, K and pesticides), maintained a higher biodiversity and produced lower greenhouse gas emissions. Yield averages over 40 years were 20% lower in organic systems across all crops. A nitrogen balance, including biological nitrogen fixation and stock changes of soil nitrogen, revealed a surplus for all manured systems, whereas the conventional system with sole mineral fertiliser was well balanced. Soil nitrogen stocks only increased slightly in the biodynamic system receiving composted manure. The biodynamic soil showed also increased soil organic carbon stocks, while the conventional soil receiving only mineral fertilizer acted as source for atmospheric CO2. A climate impact analyses encountering nitrous oxide, methane and soil organic matter changes resulted in lower CO2eq emissions in organic compared to the conventional systems, both area and yield scaled. Biodiversity and especially biomass of invertebrate fauna and plant seeds was enhanced in the organically managed systems. Our results demonstrate that organic cropping systems can contribute to a more sustainable production with respect to key planetary boundaries. To further improve system performance, yield gaps between organic and conventional systems need to be reduced by adapted cultivars, more effective organic plant protection and by closing urban and rural nutrient cycles

Non-host resistance to penetration and hyphal growth of Magnaporthe oryzae in Arabidopsis

Rice blast caused by Magnaporthe oryzae is a devastating disease of rice. Mechanisms of rice resistance to blast have been studied extensively, and the rice–M. oryzae pathosystem has become a model for plant–microbe interaction studies. However, the mechanisms of non-host resistance (NHR) to rice blast in other plants remain poorly understood. We found that penetration resistance to M. oryzae in multiple mutants, including pen2 NahG pmr5 agb1 and pen2 NahG pmr5 mlo2 plants, was severely compromised and that fungal growth was permitted in penetrated epidermal cells. Furthermore, rice Pi21 enhanced movement of infection hyphae from penetrated Arabidopsis epidermal cells to adjacent mesophyll cells. These results indicate that PEN2, PMR5, AGB1, and MLO2 function in both penetration and post-penetration resistance to M. oryzae in Arabidopsis, and suggest that the absence of rice Pi21 contributed to Arabidopsis NHR to M. oryzae

Multilayered Mechanism of CD4 Downregulation by HIV-1 Vpu Involving Distinct ER Retention and ERAD Targeting Steps

A key function of the Vpu protein of HIV-1 is the targeting of newly-synthesized CD4 for proteasomal degradation. This function has been proposed to occur by a mechanism that is fundamentally distinct from the cellular ER-associated degradation (ERAD) pathway. However, using a combination of genetic, biochemical and morphological methodologies, we find that CD4 degradation induced by Vpu is dependent on a key component of the ERAD machinery, the VCP-UFD1L-NPL4 complex, as well as on SCFβ-TrCP-dependent ubiquitination of the CD4 cytosolic tail on lysine and serine/threonine residues. When degradation of CD4 is blocked by either inactivation of the VCP-UFD1L-NPL4 complex or prevention of CD4 ubiquitination, Vpu still retains the bulk of CD4 in the ER mainly through transmembrane domain interactions. Addition of a strong ER export signal from the VSV-G protein overrides this retention. Thus, Vpu exerts two distinct activities in the process of downregulating CD4: ER retention followed by targeting to late stages of ERAD. The multiple levels at which Vpu engages these cellular quality control mechanisms underscore the importance of ensuring profound suppression of CD4 to the life cycle of HIV-1

Evolutionary history of Serpulaceae (Basidiomycota): molecular phylogeny, historical biogeography and evidence for a single transition of nutritional mode

<p>Abstract</p> <p>Background</p> <p>The fungal genus <it>Serpula </it>(Serpulaceae, Boletales) comprises several saprotrophic (brown rot) taxa, including the aggressive house-infecting dry rot fungus <it>Serpula lacrymans</it>. Recent phylogenetic analyses have indicated that the ectomycorrhiza forming genera <it>Austropaxillus </it>and <it>Gymnopaxillus </it>cluster within <it>Serpula</it>. In this study we use DNA sequence data to investigate phylogenetic relationships, historical biogeography of, and nutritional mode transitions in Serpulaceae.</p> <p>Results</p> <p>Our results corroborate that the two ectomycorrhiza-forming genera, <it>Austropaxillus </it>and <it>Gymnopaxillus</it>, form a monophyletic group nested within the saprotrophic genus <it>Serpula</it>, and that the <it>Serpula </it>species <it>S. lacrymans </it>and <it>S. himantioides </it>constitute the sister group to the <it>Austropaxillus</it>-<it>Gymnopaxillus </it>clade. We found that both vicariance (Beringian) and long distance dispersal events are needed to explain the phylogeny and current distributions of taxa within Serpulaceae. Our results also show that the transition from brown rot to mycorrhiza has happened only once in a monophyletic Serpulaceae, probably between 50 and 22 million years before present.</p> <p>Conclusions</p> <p>This study supports the growing understanding that the same geographical barriers that limit plant- and animal dispersal also limit the spread of fungi, as a combination of vicariance and long distance dispersal events are needed to explain the present patterns of distribution in Serpulaceae. Our results verify the transition from brown rot to ECM within Serpulaceae between 50 and 22 MyBP.</p

Protein quality control: the who’s who, the where’s and therapeutic escapes

In cells the quality of newly synthesized proteins is monitored in regard to proper folding and correct assembly in the early secretory pathway, the cytosol and the nucleoplasm. Proteins recognized as non-native in the ER will be removed and degraded by a process termed ERAD. ERAD of aberrant proteins is accompanied by various changes of cellular organelles and results in protein folding diseases. This review focuses on how the immunocytochemical labeling and electron microscopic analyses have helped to disclose the in situ subcellular distribution pattern of some of the key machinery proteins of the cellular protein quality control, the organelle changes due to the presence of misfolded proteins, and the efficiency of synthetic chaperones to rescue disease-causing trafficking defects of aberrant proteins

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

Evidence confirms an anthropic origin of Amazonian Dark Earths

Archaeology of the America