bluuebunny/crossref_metadata_2025 huggingface dataset:
La sustentabilidad del cambio social. Factores positivos en la consolidación de empresas recuperadas por sus trabajadores en Argentina.
Authors: Kasparian Denise , Rebón Julián
Published: April 2020

En la Argentina, las empresas recuperadas por sus trabajadores refieren a procesos de reconversión de empresas capitalistas en cooperativas de trabajo originados en la acción colectiva de los asalariados en defensa de su fuente laboral. A partir del interés por las transformaciones que estas empresas han podido sostener y consolidar en el tiempo, el presente artículo se propone analizar los factores positivos para su consolidación en tanto empresas cooperativas. La estrategia metodológica se basa en el análisis singular y comparado de empresas recuperadas. Las técnicas utilizadas son la entrevista semi-estructurada a informantes clave de las empresas, la observación no participante y el análisis documental. En nuestra hipótesis, los principales factores que colaboran positivamente en los logros alcanzados son: los recursos que se heredan de la empresa fallida, la hegemonía de un proyecto cooperativo que le otorga relevancia a la gestión económica, la tenencia legal de los medios de producción, la producción de bienes y servicios competitivos mercantilmente en un marco de intercambios económicos plurales, así como la participación en redes político-sociales.
Economía social y solidaria y agroecología en cooperativas de agricultura familiar en Brasil como forma de desarrollo de una agricultura sostenible
Authors: Schwab do Nascimento Fabio , Calle-Collado Ángel , Muñoz Benito Rocío
Published: April 2020

El objetivo de este artículo es comprender cómo la Economía Social y Solidaria (ESS) y la Agroecología pueden contribuir a la sostenibilidad económica, social, ecológica y política de la agricultura familiar en Brasil. Para ello, se expondrán sus dimensiones y las diferentes formas de obtener la viabilidad de determinadas explotaciones familiares. Como metodología de investigación se ha empleado el uso de indicadores de sostenibilidad creados por los autores para realizar los análisis de las experiencias de cooperativas de agricultores familiares en Brasil. Las cooperativas seleccionadas fueron las pertenecientes a la Asociación de Agricultores Ipê y Antonio Prado (AECIA) en la ciudad de Antonio Prado localizada en el estado de Rio Grande do Sul (Brasil) y la Cooperativa IRITUIA en la ciudad de Irituia en el estado de Pará (Brasil) como locus de la investigación. Los resultados de la investigación apuntan a que existen diferencias entre las cooperativas estudiadas en cuanto a la viabilidad productiva, social, política y económica tanto desde la ESS como desde la Agroecología, de manera que AECIA ofrece mejores valores en todos los atributos estudiados frente a la Cooperativa de Irituia.
Current challenges and prospective analysis of the Third Sector of Social Action (TSSA) in Spain
Authors: Marban Gallego Vicente , Pérez Yruela Manuel , Rodríguez Cabrero Gregorio
Published: April 2020

This paper analyses the current conditions and future challenges faced by the Third Sector of Social Action (TSSA) in Spain to consolidate itself as an institutional sphere of sustainable welfare and as a strategic actor in the development of social policies.The empirical basis of this work has been obtained with the use of qualitative methods such as in-depth interviews, focus groups and the mixed method of Delphi. The use of these methods is aimed at interpreting TSSA leaders’ discourses, the collective voice of Non-governmental organisations (NGO) managers and representatives, and the opinions of experts on: the nature and past development of the sector.This research was carried out under the support of the Mechanism of the European Economic Area 2009-2014, in the framework of the Active Citizenship Programme (Eea Grants) and by the PECOTSAS Project of the State Plan for Scientific and Technical Research and Innovation 2013-2016 of the Ministry of Economy, Industry and Competitiveness (ref CSO2017-85486-P).The text is structured as follows. First, we analyse the institutional nature of the TSSA and how it has combined powerful organisational growth with an adaptation to what we define as the European logic of the Third Sector (TS) in recent decades. Subsequently, we examine the current conditioning factors of the TSSA’s development in Spain including the impact of the 2008 economic crisis, financing capacity, modes of social action and relations with the State and the private sector companies. Finally, we assess the challenges faced by the TSSA in the coming years in terms of financial and institutional sustainability and its capacity to influence public policies. The results have been useful for the elaboration of the III Strategic Plan of the Third Sector of Social Action (2017-2021
Rol de la Economía Social y la Universidad en orden a un emprendimiento basado en el conocimiento tecnológico y los valores
Authors: Julia Igual Juan Francisco , Meliá Martí Elena , Miranda Ribera Eduardo
Published: April 2020

Hoy en día se reconocen las sociedades más desarrolladas por contar con un emprendimiento innovador que hace un uso intensivo del conocimiento y utiliza las tecnologías más avanzadas. Estas sociedades, si además de economías competitivas pretenden ser sociedades más justas, solidarias y sostenibles deben también emprender con valores que les conduzcan a ello. El presente trabajo pretende abordar la necesidad de avanzar en una economía más intensiva en conocimiento, especialmente tecnológico, que permita afrontar el reto que supone la llamada 4ª revolución tecnológica, contribuyendo al desarrollo de una sociedad más competitiva y al mismo tiempo con valores. Así, este trabajo realiza una revisión de la realidad de la universidad española, y de su papel ante el reto tecnológico. Además, efectúa un análisis de la presencia y peso de la economía social en aquellos sectores más identificados con la llamada cuarta revolución industrial, y establece que no existen diferencias de ámbito económico-financiero que puedan explicar la previamente constatada menor presencia de las fórmulas de economía social frente a las de capital. De la revisión y el análisis efectuado, este trabajo concluye que para que se avance en esta economía competitiva y con valores, es crucial el papel de la universidad, fomentando y desarrollando un emprendimiento innovador, inteligente y con valores. En las últimas cuatro décadas la Economía Social ha experimentado un importante avance en términos cuantitativos y cualitativos, y también lo ha hecho el emprendimiento, en particular, el universitario, contribuyendo a avanzar en la generación de una economía con mayor uso del conocimiento y, sobre todo, con valores. Sin embargo, continúa siendo necesario impulsar el uso de fórmulas de Economía Social en el emprendimiento derivado del ecosistema universitario, y con ello su grado de presencia en los sectores tecnológicos más avanzados, y en particular en los más estrechamente vinculados a la llamada cuarta revolución industrial.
Nudos en el acompañamiento y la formación en las Empresas de Inserción: agenda de temas pendientes
Authors: Marhuenda Fluixá Fernando , Martínez-Rueda Natxo , Aróstegui Barandica Igone , Galarreta Lasa Javier
Published: April 2020

Las Empresas de Inserción son organizaciones complejas que afrontan diversos desafíos para lograr sus objetivos económicos y sociales. En el contexto español, han experimentado un desarrollo notable en los últimos años, en la medida que se están mostrando como un programa de inserción sociolaboral eficaz para responder a necesidades complejas de inserción laboral.En este artículo, adoptando un enfoque holístico, se describen las prácticas de formación y acompañamiento y su relación con otras dimensiones del funcionamiento de las EI. A partir de ello, se identifican los principales retos que tanto profesionales como investigadores tienen que afrontar para mejorar la empleabilidad de las personas trabajadoras de inserción. Para ello, se ha realizado un análisis de contenido de los informes de investigación de 10 EI del estado español que, resultado de un proceso de observación no participante y entrevistas en profundidad, han elaborado una pareja de investigadores y que han sido validados por cada empresa.Como resultados, se identifican, en primer lugar, diferentes factores organizacionales que influyen en el desarrollo de los procesos de acompañamiento y cualificación, entre los que destacan las relaciones que la EI mantiene con el mercado de trabajo ordinario y las diferentes formas en las que se organizan los procesos productivos. En segundo lugar, se describen las características de los procesos de acompañamiento, analizando sus niveles de estructuración y las fases en las que se articula. En tercer lugar, con relación a los procesos formativos se describen sus diferentes modalidades, con especial referencia a la conciencia y rol de las personas trabajadoras de inserción. Este análisis multidimensional, sirve de base para formular la agenda de temas que tanto investigadores como profesionales tienen que considerar en los próximos año.
Some results of studying the impact of digital technologies upon learning activities
Authors: Burtseva Elvira Vitaljevna , Chepak Olga , Kulikova Olga
Published: April 2020

The subject of this research is the implementation of digital technologies in educational process of a university. The goal consists in studying the impact of digital technologies upon the students’ learning activities. The article presents the results of questionnaire-based survey among students by the three question pools. In the course of research, the author examines such aspects of the problem, as the positive and negative impact of technologies upon learning activities of the students of digital generation. Particular attention is given to consideration of students’ attitude on digitalization of higher education. The opinions of pedagogues on the results of conducted research are presented. The scientific novelty lies in mainstreaming the question on the negative impact of digital technologies upon learning activities of the modern generation of students that deserves special attention. On the background of common passion of the scholars of researchers and pedagogues for the ideas of digitalization of education, when digital technologies are viewed as virtually the key factor for modernization of educational process; second come the problems of growing pathological dependence of youth on digital technologies, undesired to switch to digitalized educational process to the disadvantage of communication in social networks and pleasant pastime online. The problem of the negative effect of digital technologies on learning activities must be recognized in order to find the ways for its solution.
Quantifying Travel Physical Energy Expenditure for Urban Travellers – A Case Study of Beijing
Authors: Hong Xin , Meng Lingyun , An Jian
Published: April 2020

Travel physical energy expenditure for travellers has impact on travel mode choice behaviour. However, quantitative study on travel physical energy expenditure is rare. In this paper, the concept of travel physical energy expenditure coefficient has been presented. A case study has been carried out of young travellers in Beijing to get the value of physical energy expenditure per unit time under three transport modes, walking, car and public transportation. A series of experiments have been designed and conducted, which consider influence factors including age, gender, travel mode, riding posture, luggage level and crowded level. By analysing the travel data of money, travel time and physical energy expenditure, we determined that the value of travel physical energy expenditure coefficient δ is 0.058 RMB/KJ, which means that travellers can pay 0.058 RMB to reduce 1 KJ physical energy expenditure. Next, a travel mode choice model has been proposed using a multinomial logit model (MNL), considering economic cost, time cost and physical energy cost. Finally, the case study based on OD from Xizhimen to Tiantongyuan in Beijing was conducted. It is verified that it will be in better agreement with the actual travel behaviour when we take the physical energy expenditure for different types of travellers into account.
Ordered Generalized Extreme Value Model as a Tool for Demand Modelling of Discretionary Trips
Authors: Elmorssy Mahmoud , Tezcan Huseyin Onur
Published: April 2020

Although the four-step model is the most common method in transportation demand modelling, it is exposed to a considerable criticism in terms of representing the actual choice behaviours of travellers. For example, the four steps are presented in a fixed sequence and independently from each other. Such assumption may be correct in case of obligatory trips (e.g. work trips) where travellers’ behaviour has usually no effect on trip generation or trip distribution stages. However, in discretionary trips, they may simultaneously decide on various trip dimensions. This paper tries to overcome the limitations of traditional four-step model associated with discretionary trips by using a joint discrete choice modelling approach that represents destination, departure time and travel mode choices under a unified framework. The proposed model to be used is the Ordered Generalized Extreme Value model where potential spatial correlation among discretionary destinations can be considered as well. The research methodology has been tested by using shopping and entertainment trips data of Eskisehir city in Turkey. The proposed framework seemed to be more effective and offered an accurate alternative to the first three stages of the traditional four-step model in a setting with a limited number of discretionary destinations.
Selecting Inter-city Transportation Routes in Complex Terrains Using Quantitative Methods – A Case Study from Northern Yunnan, China
Authors: Xia Jisheng , Dong Pinliang , Zhao Zhifang
Published: April 2020

A variety of factors are involved in inter-city transportation route selection in the areas of complex terrain. With the help of Geographic Information System (GIS), three quantitative methods were employed to determine the transport routes between 44 cities in Northern Yunnan (China), an area with alpine valleys, Karst mountains, and plateau basins. The network analysis in GIS was used to find the routes based on the Transport Suitability Evaluation (TSE) map, which was produced from several factors, including population density, terrain slope, vertical terrain dissection, landslide and mud-flock area, land cover types, and Normalized Difference Vegetation Index (NDVI). Analytic Hierarchy Process (AHP), Grey Relational Analysis (GRA), and Delphi analysis were used to collect and calculate suitability values of these factors. Finally, all the routes connecting 44 cities of Northern Yunnan formed a network which could provide reference for route selection planning in the area.
Cell-type diversity and regionalized gene expression in the planarian intestine
Authors: Forsthoefel David J , Cejda Nicholas I , Khan Umair W , Newmark Phillip A
Published: April 2020

Proper function and repair of the digestive system are vital to most animals. Deciphering the mechanisms involved in these processes requires an atlas of gene expression and cell types. Here, we applied laser-capture microdissection (LCM) and RNA-seq to characterize the intestinal transcriptome of Schmidtea mediterranea, a planarian flatworm that can regenerate all organs, including the gut. We identified hundreds of genes with intestinal expression undetected by previous approaches. Systematic analyses revealed extensive conservation of digestive physiology and cell types with other animals, including humans. Furthermore, spatial LCM enabled us to uncover previously unappreciated regionalization of gene expression in the planarian intestine along the medio-lateral axis, especially among intestinal goblet cells. Finally, we identified two intestine-enriched transcription factors that specifically regulate regeneration (hedgehog signaling effector gli-1) or maintenance (RREB2) of goblet cells. Altogether, this work provides resources for further investigation of mechanisms involved in gastrointestinal function, repair and regeneration.
Proteome dynamics during homeostatic scaling in cultured neurons
Authors: Dörrbaum Aline Ricarda , Alvarez-Castelao Beatriz , Nassim-Assir Belquis , Langer Julian D , Schuman Erin M
Published: April 2020

Protein turnover, the net result of protein synthesis and degradation, enables cells to remodel their proteomes in response to internal and external cues. Previously, we analyzed protein turnover rates in cultured brain cells under basal neuronal activity and found that protein turnover is influenced by subcellular localization, protein function, complex association, cell type of origin, and by the cellular environment (Dörrbaum et al., 2018). Here, we advanced our experimental approach to quantify changes in protein synthesis and degradation, as well as the resulting changes in protein turnover or abundance in rat primary hippocampal cultures during homeostatic scaling. Our data demonstrate that a large fraction of the neuronal proteome shows changes in protein synthesis and/or degradation during homeostatic up- and down-scaling. More than half of the quantified synaptic proteins were regulated, including pre- as well as postsynaptic proteins with diverse molecular functions.
Farming system shapes traits and composition of spider assemblages in Mediterranean cherry orchards
Authors: Rosas-Ramos Natalia , Baños-Picón Laura , Tormos José , Asís Josep D.
Published: April 2020

Habitat properties, including crop type, farming system, management practices, or topographic features such as the hillside aspect, may act as environmental filters that select organisms sharing traits compatible with those conditions. The more environmentally-friendly management practices implemented in organic farming seem to benefit a range of taxa, but the extent of those benefits is not well understood. In cherry orchards of the Jerte Valley (Extremadura, western Spain), we explored the response of spider assemblages to the farming system (organic and conventional) and the hillside aspect (sunny or shady) from a taxonomical, behavioral, and morphological perspective. Spiders from both the canopy and soil surface were collected and identified to family. According to their foraging strategy, spiders were sorted in guilds and, for a selected family in each guild, body size was measured on each captured individual. Spider traits and composition were determined by local factors derived from farming system, and by climate conditions associated to the hillside aspect. In taxonomical terms, spiders benefit from organic farming and by the shady aspect. However, from a behavioral perspective, spiders with different foraging strategies exhibit strong variations in their response to the evaluated factors. From a morphological perspective, body size within guilds is differently conditioned by management practices that constitute conditioning disturbance events for each guild, resulting in selecting small individuals. The observed differences in taxonomical, behavioral, and morphological responses of spider communities to habitat properties highlight the importance of examining their assemblages from different perspectives when assessing how they respond to changes in management practices and topographic features.
Fish and fisheries in hot water: What is happening and how do we adapt?
Authors: Pinsky Malin L. , Fenichel Eli , Fogarty Michael , Levin Simon , McCay Bonnie , St. Martin Kevin , Selden Rebecca L. , Young Talia
Published: April 2020

Rapid climate changes are currently driving substantial reorganizations of marine ecosystems around the world. A key question is how these changes will alter the provision of ecosystem services from the ocean, particularly from fisheries. To answer this question, we need to understand not only the ecological dynamics of marine systems, but also human adaptation and feedbacks between humans and the rest of the natural world. In this review, we outline what we have learned from research primarily in continental shelf ecosystems and fishing communities of North America. Key findings are that marine animals are highly sensitive to warming and are responding quickly to changes in water temperature, and that such changes are often happening faster than similar processes on land. Changes in species distributions and productivity are having substantial impacts on fisheries, including through changing catch compositions and longer distances traveled for fishing trips. Conflicts over access to fisheries have also emerged as species distributions are no longer aligned with regulations or catch allocations. These changes in the coupled natural‐human system have reduced the value of ecosystem services from some fisheries and risk doing so even more in the future. Going forward, substantial opportunities for more effective fisheries management and operations, marine conservation, and marine spatial planning are likely possible through greater consideration of climate information over time‐scales from years to decades.
Neuronal Calcium Sensor 1 is up‐regulated in response to stress to promote cell survival and motility in cancer cells
Authors: Grosshans Henrike K. , Fischer Tom T. , Steinle Julia A. , Brill Allison L. , Ehrlich Barbara E.
Published: April 2020

Changes in intracellular calcium (Ca2+) signaling can modulate cellular machinery required for cancer progression. Neuronal calcium sensor 1 (NCS1) is a ubiquitously expressed Ca2+‐binding protein that promotes tumor aggressiveness by enhancing cell survival and metastasis. However, the underlying mechanism by which NCS1 contributes to increased tumor aggressiveness has yet to be identified. In this study, we aimed to determine (a) whether NCS1 expression changes in response to external stimuli, (b) the importance of NCS1 for cell survival and migration, and (c) the cellular mechanism(s) through which NSC1 modulates these outcomes. We found that NCS1 abundance increases under conditions of stress, most prominently after stimulation with the pro‐inflammatory cytokine tumor necrosis factor α, in a manner dependent on nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB). We found that NFκB signaling is activated in human breast cancer tissue, which was accompanied by an increase in NCS1 mRNA expression. Further exploration into the relevance of NCS1 in breast cancer progression showed that knockout of NCS1 (NCS1 KO) caused decreased cell survival and motility, increased baseline intracellular Ca2+ levels, and decreased inositol 1,4,5‐trisphosphate‐mediated Ca2+ responses. Protein kinase B (Akt) activity was decreased in NCS1 KO cells, which could be rescued by buffering intracellular Ca2+. Conversely, Akt activity was increased in cells overexpressing NCS1 (NCS1 OE). We therefore conclude that NCS1 acts as cellular stress response protein up‐regulated by stress‐induced NFκB signaling and that NCS1 influences cell survival and motility through effects on Ca2+ signaling and Akt pathway activation.
Sol–Gel‐Based Advanced Porous Silica Materials for Biomedical Applications
Authors: Lei Qi , Guo Jimin , Noureddine Achraf , Wang Aixia , Wuttke Stefan , Brinker C. Jeffrey , Zhu Wei
Published: April 2020

Porous silica‐based materials have burgeoning applications ranging from fillers and additives, to adsorbents, catalysts, and recently therapeutic agents and vaccines in nanomedicine. The preponderance of these materials is made by sol–gel processing wherein soluble silica precursors are reacted to form amorphous networks composed of siloxane bonds. The facile sol–gel approach allows for an unlimited variety of binary tertiary and more complex chemical compositions including organic ligands and networks resulting in so‐called organic–inorganic hybrid materials. Here, a brief review of the recent progress in sol–gel‐derived silica materials prepared as particles, thin films, biosilica/silica bioreplicas (of molecules, cells and organisms), and their related preparation, properties, and bioapplications is provided. First, it highlights the recent achievements of mesoporous silica nanoparticles in biomedical applications, including therapeutic agent delivery, multimodal imaging and theranostics, and bone tissue engineering and repair. Second, the research in evaporation‐induced self‐assembly (EISA)‐based mesostructured silica thin films and cell‐directed EISA in bio/nano interfaces for various bioapplications, such as bioactive coatings, biosensing, and living cell immobilization, has been reviewed. Third, the pioneering work in biomimetic silicification/immobilization of biomolecules and bio‐organisms and silica bioreplication of complex bio‐organisms is summarized. Finally, it is concluded with personal perspectives on the directions of future work on this field.
A Transparent, Wearable Fluorescent Mouthguard for High‐Sensitive Visualization and Accurate Localization of Hidden Dental Lesion Sites
Authors: Li Xuemeng , Luo Chongdai , Fu Quanying , Zhou Cuiping , Ruelas Marina , Wang Yingshuting , He Jinxu , Wang Yangyang , Zhang Yu Shrike , Zhou Jianhua
Published: April 2020

Accurate detection and early diagnosis of oral diseases such as dental caries and periodontitis, can be potentially achieved by detecting the secretion of volatile sulfur compounds (VSCs) in oral cavities. Current diagnostic approaches for VSCs can detect the existence and concentrations, yet are not capable of locating the dental lesion sites. Herein, the development of a unique approach for accurately locating dental lesion sites using a fluorescent mouthguard consisting of the zinc oxide–poly(dimethylsiloxane) (ZnO‐PDMS) nanocomposite to detect the local release of VSCs is reported. The ZnO‐PDMS mouthguard displays a highly sensitive and selective response to VSCs, and exhibits high fluorescent stability, good biocompatibility, and low biological toxicity in normal physiological environments. Then, the wearable ZnO‐PDMS mouthguard is demonstrated to be able to identify the precise locations of lesion sites in human subjects. Combined with image analysis, the mouthguards successfully uncover the precise locations of dental caries, allowing convenient screening of hidden dental lesion sites that are oftentimes omitted by dentists. Due to low cost, long‐term stability, and good patient compliance, the proposed wearable mouthguard is suitable for large‐scale production and enables widely applicable, preliminary yet accurate screening of dental lesions prior to dental clinics and routine physical examinations.
Simultaneously Achieving Ultrahigh Sensitivity and Wide Detection Range for Stretchable Strain Sensors with an Interface‐Locking Strategy
Authors: Lin Waner , He Chubin , Huang Huayi , Zhao Wenyu , Qiu Yanbing , Guan Xiao , Zhang Qi , Wang Ziya , Peng Zhengchun
Published: April 2020

The development of stretchable strain sensors is crucial for the implementation of electronic skins and wearable electronics. Resistive‐type strain sensors are typically composed of an electrically conductive sensing layer coupled to a stretchable substrate. When a sensor is stretched, microstructural changes in the sensing layer lead to a strain‐dependent change in resistance. However, strain sensors with high sensitivity and specificity often suffer from a limited detection range along with reliability issues. Here, a novel strain sensor composed of Ag particles and long‐range entangled carbon nanotubes (CNTs) with a special composite design is proposed, in which a strain‐induced self‐locking effect is introduced at the interface between the CNT film and a percolating network consisting of Ag particle filler. As a result, the sensors achieve significantly enhanced performance such as large stretchability (≥120%), high gauge factor (3990.8), fast response time (<33 ms), and high mechanical durability. A range of wearable applications including radial artery, facial expression, and joint motion monitoring are demonstrated, which range from minute deformation to excessive stretching of the sensor.
Catalytic Asymmetric Halohydroxylation of α,β‐Unsaturated Ketones with Water as the Nucleophile
Authors: Li Weiwei , Zhou Pengfei , Li Gonglin , Lin Lili , Feng Xiaoming
Published: April 2020

The catalytic asymmetric halohydroxylation of α,β‐unsaturated ketones with water as the nucleophile has been realized by applying a chiral N,N′‐dioxide/Fe(OTf)2 complex as the catalyst. Bromo‐, chloro‐ and iodo‐hydroxylations were all suitable in this catalytic system. A variety of α‐halo‐β‐hydroxy ketones were obtained in often good yields with generally high dr and ee values. Besides, a Michael/α‐halogenation process was considered more possible and a possible transition state model was proposed to explain the origin of stereoselectivity.

magnified image
Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) ‐ outcomes and mutation profile from venetoclax resistant MCL patients
Authors: Zhao Shuangtao , Kanagal‐Shamanna Rashmi , Navsaria Lucy , Ok Chi Young , Zhang Shaojun , Nomie Krystle , Han Guangchun , Hao Dapeng , Hill Holly A. , Jiang Changying , Yao Yixin , Nastoupil Loretta , Westin Jason , Fayad Luis , Nair Ranjit , Steiner Raphel , Ahmed Sairah , Samaniego Felipe , Iyer Swaminathan P. , Oriabure Onyeka , Chen Wendy , Song Xingzhi , Zhang Jianhua , Badillo Maria , Moghrabi Omar , Aranda Jorge , Tang Guilin , Yin C. Cameron , Patel Keyur , Medeiros Leonard Jeffrey , Li Shaoying , Vega Francisco , Thirumurthi Selvi , Xu Guofan , Neelapu Sattva , Flowers Christopher R. , Romaguera Jorge , Fowler Nathan , Wang Linghua , Wang Michael L. , Jain Preetesh
Published: April 2020

Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax‐based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole‐exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2‐4‐fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non‐BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.
Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms
Authors: Irmen Friederike , Horn Andreas , Mosley Philip , Perry Alistair , Petry‐Schmelzer Jan Niklas , Dafsari Haidar S. , Barbe Michael , Visser‐Vandewalle Veerle , Schneider Gerd‐Helge , Li Ningfei , Kübler Dorothee , Wenzel Gregor , Kühn Andrea A.
Published: April 2020

Objective

Subthalamic nucleus deep brain stimulation (STN‐DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non‐motor DBS effects is not well‐characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN‐DBS, which have been reported to improve, worsen, or remain unchanged.

Methods

Depressive symptoms before and after STN‐DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross‐validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test‐set for which depressive symptom change was predicted.

Results

Structural connectivity was linked to depressive symptom change under STN‐DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training‐set map predicted changes in depressive symptoms in the independent test‐set. Worsening of depressive symptoms was associated with left prefrontal connectivity.

Interpretation

Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN‐DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms. ANN NEUROL 2020;87:962–975
Nanogel Multienzyme Mimics Synthesized by Biocatalytic ATRP and Metal Coordination for Bioresponsive Fluorescence Imaging
Authors: Qi Meiyuan , Pan Hui , Shen Hongdou , Xia Xianmeng , Wu Chu , Han Xiaoke , He Xingyue , Tong Wei , Wang Xia , Wang Qigang
Published: April 2020

The design of enzyme mimics from stable and nonprotein systems is especially attractive for applications in highly specific cancer diagnosis and treatment, and it has become an emerging field in recent years. Herein, metal crosslinked polymeric nanogels (MPGs) were prepared using FeII ion coordinated biocompatible acryloyl‐lysine polymer brushes obtained from an enzyme‐catalyzed atomic transfer radical polymerization (ATRPase) method. The monoatomic and highly dispersed Fe ions in the MPGs serve as efficient crosslinkers of the gel network, and also as active centers of multienzyme mimics of superoxide dismutase (SOD) and peroxidase (POD). The catalytic activities were compared to those of conventional Fe‐based nanozymes. Studies on both cells and animals verify that efficient reactive oxygen species (ROS) responsive biofluorescence imaging can be successfully realized using the MPGs.
Demineralized whey–gelatin composite films: Effects of composition on film formation, mechanical, and physical properties
Authors: de Jesus Gabriela Leticia , Baldasso Camila , Marcílio Nilson Romeu , Tessaro Isabel Cristina
Published: April 2020

In this study, the objective was to prepare and characterize films with different concentrations of demineralized whey (3–10%) and gelatin (1–3%) containing glycerol (10–70%) as a plasticizer and chitosan or nanochitosan as an additive. Mechanical properties, thickness, grammage, opacity, moisture content, water, and ethanol solubilities of the obtained films were determined. The formation of films without glycerol and gelatin was not possible. A higher gelatin concentration led to more desirable mechanical properties. Thickness, grammage, opacity, and moisture content remained almost constant after increasing gelatin concentration. Heightening glycerol concentrations raised water and ethanol solubility. Despite presenting high water solubility, the films showed low ethanol solubility. The formulation containing whey (3%), glycerol (20%), gelatin (3%), and chitosan (0.1%) resulted in the highest performing film concerning physical and mechanical aspects. Through Fourier transform infrared spectroscopy analysis, it was possible to observe the displacement and the frequency reduction of the band near 3,300 cm−1, revealing different protein interactions. It indicates that hydrogen bonds occur between the amino group and OH of the protein molecules reducing film hydrophilicity. Contact angle measurements also showed a less hydrophilic character. The films present the potential to prolong the shelf life of food, such as dairy products.
Assessment of the potential bactericide effect of self‐cleaning floors: a proposed protocol
Authors: Szabó‐Bárdos Erzsébet , Kulcsár Petra , Kováts Nóra , Békéssy Zsófia , Eck‐Varanka Bettina , Horváth Ottó
Published: April 2020

The antibacterial properties of self‐cleaning coatings are based on bactericide nanoparticles (NPs). Ecotoxicity of these NPs have been assessed mostly in suspension, using standard bioassays. Here a protocol is proposed to test actual coating samples, using the Vibrio fischeri bioluminescence inhibition bioassay. The protocol was designed to test bactericide properties of specially coated PVC floors being used in hospital environments under quasinatural conditions, such as prolonged exposure or room temperature. To take into consideration that the light output of the bacteria under prolonged exposure naturally changes, a correction factor is proposed.
Molecular binding scaffolds increase local substrate concentration enhancing the enzymatic hydrolysis of VX nerve agent
Authors: Lang Xuye , Hong Xiao , Baker Cetara A. , Otto Tamara C. , Wheeldon Ian
Published: April 2020

Kinetic enhancement of organophosphate hydrolysis is a long‐standing challenge in catalysis. For prophylactic treatment against organophosphate exposure, enzymatic hydrolysis needs to occur at high rates in the presence of low substrate concentrations and enzymatic activity should persist over days and weeks. Here, the conjugation of small DNA scaffolds was used to introduce substrate binding sites with micromolar affinity to VX, paraoxon, and methyl‐parathion in close proximity to the enzyme phosphotriesterase (PTE). The result was a decrease in KM and increase in the rate at low substrate concentrations. An optimized system for paraoxon hydrolysis decreased KM by 11‐fold, with a corresponding increase in second‐order rate constant. The initial rates of VX and methyl‐parathion hydrolysis were also increased by 3.1‐ and 6.7‐fold, respectively. The designed scaffolds not only increased the local substrate concentration, but they also resulted in increased stability and PTE‐DNA particle size tuning between 25 and ~150 nm. The scaffold engineering approach taken here is focused on altering the local chemical and physical microenvironment around the enzyme and is therefore compatible with active site engineering via combinatorial and computational approaches.
Reintervention or mortality within 90 days of bariatric surgery: population-based cohort study
Authors: Kauppila J H , Santoni G , Tao W , Lynge E , Koivukangas V , Tryggvadóttir L , Ness-Jensen E , Romundstad P , Pukkala E , von Euler-Chelpin M , Lagergren J
Published: April 2020

Background

Bariatric surgery carries a risk of severe postoperative complications, sometimes leading to reinterventions or even death. The incidence and risk factors for reintervention and death within 90 days after bariatric surgery are unclear, and were examined in this study.

Methods

This population-based cohort study included all patients who underwent bariatric surgery in one of the five Nordic countries between 1980 and 2012. Data on surgical and endoscopic procedures, diagnoses and mortality were retrieved from national high-quality and complete registries. Multivariable Cox regression analysis was used to calculate hazard ratios (HRs), adjusted for country, age, sex, co-morbidity, type of surgery and approach, year and hospital volume of bariatric surgery.

Results

Of 49 977 patients, 1111 (2·2 per cent) had a reintervention and 95 (0·2 per cent) died within 90 days of bariatric surgery. Risk factors for the composite outcome reintervention/mortality were older age (HR 1·65, 95 per cent c.i. 1·36 to 2·01, for age at least 50 years versus less than 30 years) and co-morbidity (HR 2·66, 1·53 to 4·62, for Charlson co-morbidity index score 2 or more versus 0). The risk of reintervention/mortality was decreased for vertical banded gastroplasty compared with gastric bypass (HR 0·37, 0·28 to 0·48) and more recent surgery (HR 0·51, 0·39 to 0·67, for procedures undertaken in 2010 or later versus before 2000). Sex, surgical approach (laparoscopic versus open) and hospital volume did not influence risk of reintervention/mortality, but laparoscopic surgery was associated with a lower risk of 90-day mortality (HR 0·29, 0·16 to 0·53).

Conclusion

Reintervention and death were uncommon events within 90 days of bariatric surgery even in this unselected nationwide cohort from five countries. Older patients with co-morbidities have an increased relative risk of these outcomes.
Bacterial Tropone Natural Products and Derivatives: Overview of their Biosynthesis, Bioactivities, Ecological Role and Biotechnological Potential
Authors: Duan Ying , Petzold Melanie , Saleem‐Batcha Raspudin , Teufel Robin
Published: April 2020

Tropone natural products are non‐benzene aromatic compounds of significant ecological and pharmaceutical interest. Herein, we highlight current knowledge on bacterial tropones and their derivatives such as tropolones, tropodithietic acid, and roseobacticides. Their unusual biosynthesis depends on a universal CoA‐bound precursor featuring a seven‐membered carbon ring as backbone, which is generated by a side reaction of the phenylacetic acid catabolic pathway. Enzymes encoded by separate gene clusters then further modify this key intermediate by oxidation, CoA‐release, or incorporation of sulfur among other reactions. Tropones play important roles in the terrestrial and marine environment where they act as antibiotics, algaecides, or quorum sensing signals, while their bacterial producers are often involved in symbiotic interactions with plants and marine invertebrates (e. g., algae, corals, sponges, or mollusks). Because of their potent bioactivities and of slowly developing bacterial resistance, tropones and their derivatives hold great promise for biomedical or biotechnological applications, for instance as antibiotics in (shell)fish aquaculture.
Keep Your Eye On…
Authors: Knopf Alison
Published: April 2020

The early identification of developmental disorders

DBT in suicidal and self‐harming behavior in ASD

The role of genetics, not child‐rearing, in bipolar disorder
AA is better pathway to abstinence than psychotherapy
Authors: Knopf Alison
Published: April 2020

Many young people have alcohol use disorders (AUDs) that, if nipped in the bud, can prevent a lifetime of morbidity and early death. And absent any guarantee of a medication that works, many are referred to Alcoholics Anonymous (AA).
Enantioselective Synthesis of α‐Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α‐Thionitriles
Authors: Lauder Kate , Anselmi Silvia , Finnigan James D. , Qi Yuyin , Charnock Simon J. , Castagnolo Daniele
Published: April 2020

The enantioselective synthesis of α‐thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α‐thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good‐to‐excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.
Ein Hückelsches Riesenrad
Authors: Groß Michael
Published: April 2020

Die Hückel‐Regel, welche die aromatischen Eigenschaften der sechs delokalisierten π‐Elektronen des Benzols erklärt, wurde jetzt auch für riesige Ringsysteme mit bis zu 162 π‐Elektronen bestätigt. Die typischen Ringströme von aromatischen und anti‐aromatischen Molekülen lassen sich durch Redoxreaktionen oder durch geometrische Manipulationen an‐ und ausschalten.
Efficient Solar Evaporation by [Ni(Phen)3][V14O34Cl]Cl Hybrid Semiconductor Confined in Mesoporous Glass
Authors: Zhang Hongping , Wang Yan , Liu Yongguang , Zhao Mingming , Liu Congyan , Wang Yang , Albolkany Mohamed K. , Wu Niannian , Wang Min , Yang Luyun , Liu Bo
Published: April 2020

Efficient utilization of solar energy for water evaporation is an advanced and environmentally friendly technology to address the crisis of global drinking water shortages. This study concerns an efficient solar vapor generator comprised of a light‐absorbing and photothermal hybrid compound [Ni(Phen)3][V14O34Cl]Cl (NiV14) confined in mesoporous and hydrophilic glass (meso‐glass). The generator is floated in water by supporting it on a domestic melamine–formaldehyde (MF) foam to ensure evaporation at the water–air interface. The porous structures and poor thermal conductivities of the meso‐glass and MF foam contribute to enabling a consistent water supply, strong solar thermal localization, and less heat dissipation and convection. Associated with the strong photothermal role of NiV14, these synergistic effects lead to a water evaporation rate of 14.38 kg m−2 h−1 with total water evaporation efficiency of 111.4% under 6 suns and a daily solar water purification yield of 42.00 L m−2 under 1 sun irradiation. This solar evaporation system shows great promise for high‐efficiency water purification application.
UV radiation recruits CD4+GATA3+ and CD8+GATA3+ T cells while altering the lipid microenvironment following inflammatory resolution in human skin in vivo
Authors: Hawkshaw Nathan J , Pilkington Suzanne M , Murphy Sharon A , Al‐Gazaq Norah , Farrar Mark D , Watson Rachel EB , Nicolaou Anna , Rhodes Lesley E
Published: April 2020

Objectives

Solar ultraviolet radiation (UVR) has major adverse effects on human health. While the mechanisms responsible for induction of UVR‐induced inflammation are well‐documented, the mediation of its resolution and longer‐term adaptive homeostasis is unknown. Therefore, we examined the skin immune and lipid profile over time following UVR inflammation.

Methods

To investigate the self‐resolving events of UVR inflammation in vivo, human skin was exposed to a single pro‐inflammatory dose of UVR. Skin biopsies and suction blister fluid were taken at intervals up to 2 weeks post‐UVR. The immune infiltrate was quantified by immunohistochemistry, and lipid mediators were profiled by liquid chromatography/mass spectrometry.

Results

We identified that cellular resolution events including switching of macrophage phenotype apply to human sunburn. However, UVR‐induced inflammation in humans involves a post‐resolution phase that differs from other experimental models. We demonstrate that 2 weeks after the initiating UVR stimulus, there is considerable immune activity with CD8+GATA3+ T cells maintained in human skin. Our results challenge the dogma of CD4+FOXP3+ T cells being the main effector CD4+ T‐cell population following UVR, with CD4+GATA3+ T cells the dominant phenotype. Furthermore, lipid mediators are elevated 14 days post‐UVR, demonstrating the skin lipid microenvironment does not revert to the tissue setting occurring prior to UVR exposure.

Conclusion

We have identified for the first time that CD4+GATA3+ and CD8+GATA3+ T‐cell subpopulations are recruited to UVR‐inflamed human skin, demonstrating discrepancies between the adaptive UVR response in mice and humans. Future strategies to abrogate UVR effects may target these T‐cell subpopulations and also the persistent alteration of the lipid microenvironment post‐UVR.