A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans.

The exosome complex is a major eukaryotic exoribonuclease that requires the SKI complex for its activity in the cytoplasm. In yeast, the Ski7 protein links both complexes, whereas a functional equivalent of the Ski7 has remained unknown in the human genome.Proteomic analysis revealed that a previously uncharacterized short splicing isoform of HBS1L (HBS1LV3) is the long-sought factor linking the exosome and SKI complexes in humans. In contrast, the canonical HBS1L variant, HBS1LV1, which acts as a ribosome dissociation factor, does not associate with the exosome and instead interacts with the mRNA surveillance factor PELOTA. Interestingly, both HBS1LV1 and HBS1LV3 interact with the SKI complex and HBS1LV1 seems to antagonize SKI/exosome supercomplex formation. HBS1LV3 contains a unique C-terminal region of unknown structure, with a conserved RxxxFxxxL motif responsible for exosome binding and may interact with the exosome core subunit RRP43 in a way that resembles the association between Rrp6 RNase and Rrp43 in yeast. HBS1LV3 or the SKI complex helicase (SKI2W) depletion similarly affected the transcriptome, deregulating multiple genes. Furthermore, half-lives of representative upregulated mRNAs were increased, supporting the involvement of HBS1LV3 and SKI2W in the same mRNA degradation pathway, essential for transcriptome homeostasis in the cytoplasm

BRAHMA ATPase of the SWI/SNF Chromatin Remodeling Complex Acts as a Positive Regulator of Gibberellin-Mediated Responses in Arabidopsis

SWI/SNF chromatin remodeling complexes perform a pivotal function in the regulation of eukaryotic gene expression. Arabidopsis (Arabidopsis thaliana) mutants in major SWI/SNF subunits display embryo-lethal or dwarf phenotypes, indicating their critical role in molecular pathways controlling development and growth. As gibberellins (GA) are major positive regulators of plant growth, we wanted to establish whether there is a link between SWI/SNF and GA signaling in Arabidopsis. This study revealed that in brm-1 plants, depleted in SWI/SNF BRAHMA (BRM) ATPase, a number of GA-related phenotypic traits are GA-sensitive and that the loss of BRM results in markedly decreased level of endogenous bioactive GA. Transcriptional profiling of brm-1 and the GA biosynthesis mutant ga1-3, as well as the ga1-3/brm-1 double mutant demonstrated that BRM affects the expression of a large set of GA-responsive genes including genes responsible for GA biosynthesis and signaling. Furthermore, we found that BRM acts as an activator and directly associates with promoters of GA3ox1, a GA biosynthetic gene, and SCL3, implicated in positive regulation of the GA pathway. Many GA-responsive gene expression alterations in the brm-1 mutant are likely due to depleted levels of active GAs. However, the analysis of genetic interactions between BRM and the DELLA GA pathway repressors, revealed that BRM also acts on GA-responsive genes independently of its effect on GA level. Given the central position occupied by SWI/SNF complexes within regulatory networks controlling fundamental biological processes, the identification of diverse functional intersections of BRM with GA-dependent processes in this study suggests a role for SWI/SNF in facilitating crosstalk between GA-mediated regulation and other cellular pathways

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.The authors thank Tania Bray, Jan Hempstead, Heather Mayne, Joanne Mulder-Brambleby, and Irene Wilson for their supporting contributions, and all patients and families affected by MCDs, who shared their needs and concerns for development of this project. Authors involved in study conception and design were P. Valent, S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, and C. Zubrinich. Authors involved in acquisition and review of data were S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F. Wimazal, T. Yigit, C. Zubrinich, and P. Valent. The Core Group (analysis and interpretation of data and drafting of the manuscript) include S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, and V.M. Slee. Critical revision was performed by S.V. Jennings, C.C. Finnerty, J.S. Hobart, M. Martín-Martínez, K.A. Sinclair, V.M. Slee, J. Agopian, C. Akin, I. Álvarez-Twose, P. Bonadonna, A.A. Bowman, K. Brockow, H. Bumbea, C. de Haro, J.S. Fok, K. Hartmann, N. Hegmann, O. Hermine, M. Kalisiak, C.H. Katelaris, J. Kurz, P. Marcis, D. Mayne, D. Mendoza, A. Moussy, G. Mudretzkyj, N. Nidelea Vaia, M. Niedoszytko, H. Oude Elberink, A. Orfao, D.H. Radia, S. Rosenmeier, E. Ribada, W. Schinhofen, J. Schwaab, F. Siebenhaar, M. Triggiani, G. Tripodo, R. Velazquez, Y. Wielink, F Wimazal, T. Yigit, C. Zubrinich, and P. Valent

Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders

Rapid Sampling of Molecular Motions with Prior Information Constraints

Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion

Przepływy ludności związane z zatrudnieniem na przykładzie gmin wiejskich województwa łódzkiego

The aim of the study was to identify directions of functional and spatial connections based on employment-related population movement. Two basic accessibility variables were adopted as the basis for analysis, namely distance and travel time. The spatial scope of the study was limited to selected rural communes of the Łódź Voivodship, which were characterised by a low rate of population movement to work, illustrating the ratio of the number of people coming to a given commune to work, to the number of people leaving the given commune to work in other territorial units. The indicator was calculated based on data from the Central Statistical Office regarding population movement. Distance and travel time were also analysed based on the statistical data of the Central Statistical Office in the scope of estimated distance and travel time from the commune being the place of residence to the commune of the workplace. Analysis showed that both the distance and time of commuting to work practically does not deviate from accepted values. In some cases, rural residents are willing to travel longer distances, and thus spend more time commuting to work. Decisions about daily commuting to work to the city are linked to the possibilities of taking up employment, although a short distance is not a sufficient and only criterion here. Underdeveloped cities are not thereby less attractive in terms of employment, however the interest of potential employees in them is much weaker than in the case of cities allowing for a proper matching of labour demand and supply.Celem badań była identyfikacja kierunków powiązań funkcjonalno-przestrzennych na podstawie przepływów ludności związanych z zatrudnieniem. Jako podstawę analizy przyjęto dwie bazowe zmienne dostępności: odległość i czas dojazdu. Zakres przestrzenny badania ograniczono do wybranych gmin wiejskich województwa łódzkiego, które charakteryzowały się niskim wskaźnikiem przepływów ludności do pracy, wyrażający stosunek liczby przyjeżdżających do pracy do danej gminy do liczby osób wyjeżdżających z danej gminy do pracy do innych jednostek. Wskaźnik obliczono na podstawie danych GUS dotyczących przepływów ludności. Odległość i czas przejazdu analizowano również na podstawie danych statystycznych GUS w zakresie szacowanej odległości i czasu przejazdu z gminy będącej miejscem zamieszkania do gminy miejsca pracy. Jak wykazała przeprowadzona analiza, odległość i czas dojazdów do pracy praktycznie nie odbiegały od akceptowanych wartości. W niektórych przypadkach mieszkańcy obszarów wiejskich gotowi byli pokonać większe odległości i tym samym poświęcić więcej czasu na dojazd do pracy. Decyzje o dobowych dojazdach do pracy do miasta były powiązane z możliwościami podjęcia zatrudnienia, przy czym niewielka odległość nie była wystarczającym i jedynym kryterium. Miasta słabo rozwinięte nie stają się tym samym mniej atrakcyjne pod względem zatrudnienia. W konsekwencji zainteresowanie nimi potencjalnych pracowników jest znacznie słabsze niż ma to miejsce w odniesieniu do miast pozwalających na właściwe dopasowanie popytu i podaży pracy

Źródła plazmy nietermicznej dla technologii ochrony środowiska

W większości instalacji wykorzystujących technicznie plazmę nietermiczną używa się wzbudzenia poprzez pole elektryczne. Szczególnie dynamicznie rozwijającym się polem zastosowań są układy przeznaczone do generacji plazmy nietermicznej na potrzeby technologii ochrony środowiska. Artykuł prezentuje krótki przegląd typowych źródeł, podając jednocześnie podstawowe, wykorzystywane w poszczególnych przypadkach układy zasilające ze szczególnym uwzględnieniem zasilaczy energoelektronicznych. Jako ilustrację wpływu doboru układu zasilającego do konkretnej aplikacji zaprezentowano wyniki pomiarów elektrycznych oraz kamerą iCCD pojedynczego układu rozładowczego dla różnych kształtów i typów napięcia.Proposed article describes basic properties of different supply systems for non-thermal, atmospheric pressure plasma devices. Different approaches are given ranging from AC supply, pulsed supplies, microwave beams and electron-beam sources with their basic electric properties. Main supply system configurations are given and typical reactor constructions are discussed with their basic properties. As an example a laboratory discharge cell investigations are presented having different supply voltage and current waveforms. ICCD camera imaging gives a clear evidence on supply voltage shape importance. Pulsed supply with large leakage inductance on the secondary side of a high-voltage transformer yields a more diffuse character. AC supply results in a well-known filamentary discharge with typical streamer channels

Method of active parasitic inductance change compensation for coreless transformers

Presented paper discusses a power electronic supply system topology for coreless transformers used in contactless energy transfer systems. Two models of such systems are presented based on circuit time domain analysis and FEM. An active compensator operation is discussed allowing for constant resonant frequency operation during transformer parameter change. Calculation results are presented and discussed

Resonant frequency stabilization technique in series-series contactless energy transfer systems

A technique for stabilization of resonant frequency is proposed in this paper. An additional power circuit, a compensator that allows keeping constant resonance frequency was introduced by the authors. In the presented solution the resonant circuit frequency stabilization is achieved by forcing a zero phase shift between the current and the voltage of the main switching module