bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full quantum mechanical modeling of the enzyme-substrate system: how laccase detoxifies aflatoxin
Authors: Zaccaria Marco , Dawson William , Kish Darius , Reverberi Massimo , Domin Marek , Dellafiora Luca , Nakajima Takahito , Genovese Luigi , Momeni Babak 
Published: March 2020

AbstractThis work focuses on: 1) the development of a methodology to perform a full Quantum Mechanics (QM) characterization of enzymatic activity; 2) the development of a rational approach to laccase engineering as a food bioremediator. Aflatoxins are among the most dangerous natural carcinogens, and regularly contaminate reserves of staple crops worldwide. Decontamination of aflatoxin-polluted food is of great interest for ensuring food safety, and bioremediation is regarded as the most promising solution. The fungal isoforms of laccase display the rare potential to detoxify aflatoxin by tackling its aromatic moieties.. Yet, because of a generally low efficiency, large-scale application of naturally occurring isoforms has so far been unfeasible. We perform a combination of quantitative experimentation and quantum mechanical modeling on aflatoxin and reveal that: (1) detoxification efficiency is limited by the low enzymatic affinity for the substrate; and (2) aflatoxin is not detoxified by oxidative activity of laccase alone, but requires additional stimulation from the environment. QM modeling also allowed identification of the residues in the laccase tertiary structure that determine affinity of the enzymatic pocket for aflatoxin. We conclude that, for our case-study, a full QM approach is mandatory as a first step towards rational optimization. We detail a feasible approach towards this endeavor and argue that our full QM characterization can serve as a roadmap for enzyme development in other applications pertaining laccase as well as other enzymes.
Visuospatial n-back test for early detection of mild cognitive impairment in patients with Parkinson’s Disease : an fMRI study
Authors: Kawashima Shoji , Shimizu Yoko , Ueki Yoshino , Matsukawa Noriyuki 
Published: March 2020

AbstractBackgroundCognitive impairment is a common symptom in the patients with Parkinson’s disease (PD). In delineating a therapeutic plan, the early diagnosis of mild cognitive impairment in PD (PD-MCI) is important. Patients with PD-MCI have severe impairment in frontal executive function and/or visuospatial recognition. However, the clinical assessment of these functions is not routinely performed.MethodIn this study, we aimed to clarify the advantage of visuospatial version of the n-back test as a tool for the early detection of neuropsychological change in the patients with PD-MCI. The score of 0-back test reflects visuospatial recognition, and the scores of 1-back and 2-back reflect visuospatial working memory. PD-MCI was classified according to the criteria provided by the Movement Disorder Society Task Force for mild cognitive impairment in PD. We recruited 13 patients with PD-MCI, and 15 patients with cognitive normal PD. Using functional MRI (fMRI), we also aimed to clarify the specific brain regions associated with the impairment of visuospatial working memory.ResultWe demonstrated that the correct answer rate of patients with PD-MCI was lower in the 2-back test than patients with PD-CN. However, we did not find statistical difference in the 0-back test. These results indicate the preservation of visuospatial recognition and the impairment of visuospatial working memory in the patients with PD-MCI. We revealed the reduced activation within the middle frontal gyrus (MFG) and the inferior parietal lobule (IPL) during the 2-back test in the patients with PD-MCI. It may be associated with the severity of cortico-striatal dysfunction in the dopaminergic neural network which is associated with Lewy body pathology.ConclusionThe visuospatial n-back test has advantages for use in rapid and early detection of impaired visual recognition and working memory. The combination of functional neuroimaging and neuropsychological tests may provide markers for the increased risk of dementia before the development of an irreversible disease-specific pathology.
SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation
Authors: Le Linh , Escobar Iliana E. , Ho Tina , Lefkovith Ariel J. , Latteri Emily , Dennis Megan K. , Haltaufderhyde Kirk D. , Sviderskaya Elena V. , Bennett Dorothy C. , Oancea Elena , Marks Michael S. 
Published: March 2020

ABSTRACTSLC45A2encodes a putative transporter expressed primarily in pigment cells.SLC45A2mutations and polymorphisms cause oculocutaneous albinism (OCA) and pigmentation variation, but neither SLC45A2 localization and function nor how gene variants affect these properties are known. We show that SLC45A2 localizes to mature melanosomes that only partially overlap with a cohort expressing the chloride channel OCA2. SLC45A2 expressed ectopically in HeLa cells localizes to lysosomes and raises lysosomal pH, suggesting that, like OCA2, SLC45A2 in melanocytes de-acidifies maturing melanosomes to support melanin synthesis. Analyses of SLC45A2- and OCA2-deficient mouse melanocytes show that SLC45A2 functions later during melanosome maturation than OCA2, and that OCA2 overexpression compensates for loss of SLC45A2 expression in pigmentation. The light skin-associated SLC45A2 allelic F374 variant restores only moderate pigmentation to SLC45A2-deficient melanocytes because of low level expression in melanosomes due to rapid proteasome-independent degradation. Our data indicate that SLC45A2 maintains melanosome neutralization – initially orchestrated by transient OCA2 activity – to support melanization at late stages of melanosome maturation, and that a common variant imparts reduced activity due to protein instability.
Proteomics support the threespine stickleback egg coat as a protective oocyte envelope
Authors: Killingbeck Emily E. , Wilburn Damien B. , Merrihew Gennifer E. , MacCoss Michael J. , Swanson Willie J. 
Published: March 2020

AbstractAfter the end of the last ice age, ancestrally marine threespine stickleback fish (Gasterosteus aculeatus) have undergone an adaptive radiation into freshwater environments throughout the Northern Hemisphere, creating an excellent model system for studying molecular adaptation and speciation. Stickleback populations are reproductively isolated to varying degrees, despite the fact that they can be crossed in the lab to produce viable offspring. Ecological and behavioral factors have been suggested to underlie incipient stickleback speciation. However, reproductive proteins represent a previously unexplored driver of speciation. As mediators of gamete recognition during fertilization, reproductive proteins both create and maintain species boundaries. Gamete recognition proteins are also frequently found to be rapidly evolving, and their divergence may culminate in reproductive isolation and ultimately speciation. As an initial investigation into the contribution of reproductive proteins to stickleback reproductive isolation, we characterized the egg coat proteome of threespine stickleback eggs. In agreement with other teleosts, we find that stickleback egg coats are comprised of homologs to the zona pellucida (ZP) proteins ZP1 and ZP3. We explore aspects of stickleback ZP protein biology, including glycosylation, disulfide bonding, and sites of synthesis, and find many substantial differences compared to their mammalian homologs. Furthermore, molecular evolutionary analyses indicate thatZP3, but notZP1, has experienced positive Darwinian selection across teleost fish. Taken together, these changes to stickleback ZP protein architecture suggest that the egg coats of stickleback fish, and perhaps fish more generally, have evolved to fulfill a more protective functional role than their mammalian counterparts. Data are available via ProteomeXchange with identifiers PXD017488 and PXD017489.
Design of hybrid electric heavy fuel MALE ISR UAV enabling technologies for military operations
Authors: Fioriti Marco , Vaschetto Silvio , Corpino Sabrina , Premoli Giovanna 
Published: March 2020

Purpose
This paper aims to present the main results achieved in the frame of the TIVANO national-funded project which may anticipate, in a stepped approach, the evolution and the design of the enabling technologies needed for a hybrid/electric medium altitude long endurance (MALE) unmanned aerial vehicle (UAV) to perform persistent intelligence surveillance reconnaissance (ISR) military operations.

Design/methodology/approach
Different architectures of hybrid-propulsion system are analyzed pointing out their operating modes to select the more suitable architecture for the reference aircraft. The selected architecture is further analyzed together with its electric power plant branch focusing on electric system architecture and the selected electric machine. A final comparison between the hybrid and standard propulsion is given at aircraft level.

Findings
The use of hybrid propulsion may lead to a reduction of the total aircraft mass and an increase in safety level. However, this result comes together with a reduced performance in climb phase.

Practical implications
This study can be used as a reference for similar studies and it provides a detailed description of propulsion operating modes, power management, electric system and machine architecture.

Originality/value
This study presents a novel application of hybrid propulsion focusing on a three tons class MALE UAV for ISR missions. It provides new operating modes of the propulsion system and a detailed electric architecture of its powertrain branch and machine. Some considerations on noise emissions and infra-red traceability of this propulsion, at aircraft level.
The power of an intersectionality framework in teacher education
Authors: Leckie Alisa , Buser De Maya 
Published: March 2020

Purpose
The purpose of this study is to describe the use of an intersectionality framework to analyze and incorporate teachers’ lived experiences into critical professional development.

Design/methodology/approach
Researchers used qualitative coding based on the matrix of oppression and privilege (Ferber and O’Reilly Herrera, 2013) to analyze teachers’ multicultural autobiographies. Connections between multicultural autobiographies were then made between other course reflections and lesson plans that were developed throughout the 150 h of professional development.

Findings
Findings evidence the multiple sites of oppression and privilege, the importance of spaces and relationships in locating ourselves and others on the matrix and the possibilities for transferring knowledge to professional practice.

Research limitations/implications
The authors do recognize the limitations of their study. Although the participants were from differing educational contexts and backgrounds, the sample size was small. Additional studies of this nature can expand our understanding of privilege, oppression and the impact of critical professional development for educators. Our society, and therefore the education system, continues to become more culturally and linguistically diverse, and it is incumbent upon us as educators and researchers to identify effective approaches for preparing both teachers and students for a changing world.

Practical implications
The power of the matrix framework in pedagogical settings is that it facilitates the recognition and analysis of individual social locations and their relationships to various systems of inequality. Most importantly, analyzing both privilege and oppression allows individuals and instructors to reflect on their own experiences and initiate conversations that reduce the animosity toward those who have different experiences.

Originality/value
This study is significant, in that it offers a framework that addresses the perceived disconnect between teachers and their increasingly culturally and linguistically diverse student population (Banks and Banks, 2013; Darling-Hammond and Bransford, 2005).
Configurational crop heterogeneity increases within‐field plant diversity
Authors: Alignier Audrey , Solé‐Senan Xavier O. , Robleño Irene , Baraibar Bàrbara , Fahrig Lenore , Giralt David , Gross Nicolas , Martin Jean‐Louis , Recasens Jordi , Sirami Clélia , Siriwardena Gavin , Bosem Baillod Aliette , Bertrand Colette , Carrié Romain , Hass Annika , Henckel Laura , Miguet Paul , Badenhausser Isabelle , Baudry Jacques , Bota Gerard , Bretagnolle Vincent , Brotons Lluis , Burel Françoise , Calatayud François , Clough Yann , Georges Romain , Gibon Annick , Girard Jude , Lindsay Kathryn , Minano Jesus , Mitchell Scott , Patry Nathalie , Poulin Brigitte , Tscharntke Teja , Vialatte Aude , Violle Cyrille , Yaverscovski Nicole , Batáry Péter 
Published: March 2020

Abstract

Increasing landscape heterogeneity by restoring semi‐natural elements to reverse farmland biodiversity declines is not always economically feasible or acceptable to farmers due to competition for land. We hypothesized that increasing the heterogeneity of the crop mosaic itself, hereafter referred to as crop heterogeneity, can have beneficial effects on within‐field plant diversity.

Using a unique multi‐country dataset from a cross‐continent collaborative project covering 1,451 agricultural fields within 432 landscapes in Europe and Canada, we assessed the relative effects of compositional and configurational crop heterogeneity on within‐field plant diversity components. We also examined how these relationships were modulated by the position within the field.

We found strong positive effects of configurational crop heterogeneity on within‐field plant alpha and gamma diversity in field interiors. These effects were as high as the effect of semi‐natural cover. In field borders, effects of crop heterogeneity were limited to alpha diversity. We suggest that a heterogeneous crop mosaic may overcome the high negative impact of management practices on plant diversity in field interiors, whereas in field borders, where plant diversity is already high, landscape effects are more limited.

Synthesis and applications. Our study shows that increasing configurational crop heterogeneity is beneficial to within‐field plant diversity. It opens up a new effective and complementary way to promote farmland biodiversity without taking land out of agricultural production. We therefore recommend adopting manipulation of crop heterogeneity as a specific, effective management option in future policy measures, perhaps adding to agri‐environment schemes, to contribute to the conservation of farmland plant diversity.
Salmonella persistence in soil depends on reciprocal interactions with indigenous microorganisms
Authors: Schierstaedt Jasper , Jechalke Sven , Nesme Joseph , Neuhaus Klaus , Sørensen Søren J. , Grosch Rita , Smalla Kornelia , Schikora Adam 
Published: March 2020

SummaryFresh fruits and vegetables have numerous benefits to human health. Unfortunately, their consumption is increasingly associated with food‐borne diseases, Salmonella enterica being their most frequent cause in Europe. Agricultural soils were postulated as reservoir of human pathogens, contributing to the contamination of crops during the growing period. Since the competition with the indigenous soil microbiota for colonization sites plays a major role in the success of invading species, we hypothesized that reduced diversity will enhance the chance of Salmonella to successfully establish in agricultural environments. We demonstrated that the abundance of Salmonella drastically decreased in soil with highly diverse indigenous prokaryotic community, while in soil with reduced prokaryotic diversity, Salmonella persisted for a long period. Furthermore, in communities with low diversity, Salmonella had an impact on the abundance of other taxa. The high physiological plasticity allows Salmonella to use agricultural soils as alternative habitat which might provide a route of animal/human infections. In addition, adjusted transcriptional profile with amino acid biosynthesis and the glyoxylate cycle most prominently regulated, suggests an adaptation to the soil environment. Our results underline the importance of the maintenance of diverse soil microbiome as a part of strategy aiming at reduced risk of food‐borne salmonellosis outbreaks.
Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor: A retrospective multicenter study of its real‐world efficacy and safety in advanced/recurrent non‐small cell lung carcinoma
Authors: Kishikawa Takayuki , Kasai Takashi , Okada Masahiko , Nakachi Ichiro , Soda Sayo , Arai Ryo , Takigami Ayako , Sata Masafumi 
Published: March 2020

AbstractBackgroundOsimertinib is recommended for T790M mutation‐positive advanced non‐small cell lung cancer (NSCLC) resistant to first‐ and second‐generation epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs). Recently, some reports exist on the real‐world use of osimertinib; however, reports involving third/later‐line use are few. Hence, this study was conducted to evaluate the efficacy and safety of osimertinib used in various treatment lines for T790M‐positive NSCLC patients.MethodsThis retrospective, observational, multicenter study included T790M‐positive advanced/recurrent NSCLC patients treated with osimertinib from May 2016 to March 2018. The clinical characteristics, efficacy, and adverse events were retrospectively investigated. The Kaplan‐Meier method was used to analyze progression‐free survival (PFS) and overall survival (OS). PFS‐associated clinical characteristics were evaluated using the Cox proportional hazards model.ResultsThe objective response rate (ORR) and disease control rate (DCR) were 60.7% and 91.1%, respectively; the median PFS was 11.0 months. There were no significant differences in the median PFS for patients treated with osimertinib as second‐line and third−/later‐line (14.5 vs. 11.0 months respectively, P = 0.327). Analysis using the Cox proportional hazards model for clinical features affecting PFS also revealed no significant factors. Adverse events of grade ≥ 3 were reported in 15 patients (26.8%); the most common were anemia (n = 3) and cutaneous toxicity (n = 3). Grade 4 neutropenia was observed in one patient; any‐grade pneumonitis was observed in six patients (10.7%), including one with grade 3 pneumonitis.ConclusionsOsimertinib demonstrated efficacy even when administered as third−/later‐line treatment to NSCLC patients. Osimertinib‐related pneumonitis was observed more frequently than previously reported.Key pointsSignificant findings of the studyOsimertinib shows efficacy even as later‐line treatment in T790M mutation‐positive NSCLC patients previously treated with EGFR‐TKIs. However, the incidence of ≥ grade 3 adverse events, especially pneumonitis, was higher than that previously reported by other studies.What this study addsOsimertinib was approved for previously EGFR‐TKI‐treated EGFR T790M‐positive NSCLC. With the increasing frequency of its use as first‐line treatment, this study provides valuable evidence for the efficacy and safety of osimertinib for previously EGFR‐TKI‐treated NSCLC.
Histamine receptors mediate contraction of reticular groove smooth muscle of adult goats
Authors: Aneesha V. A. , Gopi Renjith P. , Kumawat Sanjay , Susanth V. S. , Vineetha S. , Kumar Dinesh 
Published: March 2020

AbstractThe present study was conducted to evaluate the effect of histamine and to characterise its receptor subtypes in reticular groove (RG) smooth muscle of adult goats. The studies were done using floor and lip regions of RG. We used tension experiments on smooth muscle of RG isolated from adult goat for functional characterisation of H1 and H2 receptors. Western blotting and immunohistochemistry experiments were conducted for molecular characterisation of these receptors. Histamine evoked concentration‐dependent contraction of isolated RG circular and longitudinal smooth muscle preparation. Pyrilamine antagonised the action of histamine. Histamine did not induce any relaxant effect on RG preparations. Additionally, cimetidine did not produce any significant effect on histamine‐induced response. Non‐selective histaminic receptor antagonist cyproheptadine attenuated the contraction response to histamine in the smooth muscle. Molecular characterisation and localisation of H1 and H2 receptor proteins confirmed the presence of these receptors in RG. It is most likely that histamine‐induced contractile effect in RG smooth muscle of goats is mediated by H1 histaminic receptors.
Maintenance therapy with ex vivo expanded lymphokine‐activated killer cells and rituximab in patients with follicular lymphoma is safe and may delay disease progression
Authors: López‐Díaz de Cerio Ascensión , García‐Muñoz Ricardo , Pena Esther , Panizo Ángel , Feliu Jesús , Giraldo Pilar , Rodríguez‐Calvillo Mercedes , Martínez‐Calle Nicolás , Grande Carlos , Olave María T. , Andrade‐Campos Marcio , Bandrés Eva , Núñez‐Córdoba Jorge M. , Inogés Susana , Panizo Carlos 
Published: March 2020

SummaryAnti‐cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post‐induction therapy, by enhancing antibody‐dependent cellular cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine‐activated killer (LAK) cells administered to FL‐remission patients are safe and improve anti‐CD20 efficacy. This open, prospective, phase II, single‐arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL‐remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL‐2) for 8 weeks, after which >5 × 108 LAK cells were injected. Patients were followed‐up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL‐2 (rhIL‐2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment‐related serious adverse events. Three patients had progressed by the end of follow‐up. After a median (interquartile range) follow‐up of 59.4 (43.8–70.9) months, 85% of patients remained progression free. No deaths occurred. Quality‐of‐life improved throughout the study. Post‐induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.
Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra
Authors: Rajagopal Keshava , Bryant Andrew J. , Sahay Sandeep , Wareing Nancy , Zhou Yang , Pandit Lavannya M. , Karmouty‐Quintana Harry 
Published: March 2020

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where the additional presence of pulmonary hypertension (PH) reduces survival. In particular, the presence of coexistent pulmonary vascular disease in patients with advanced lung parenchymal disease results in worse outcomes than either diagnosis alone. This is true with respect to the natural histories of these diseases, outcomes with medical therapies, and even outcomes following lung transplantation. Consequently, there is a striking need for improved treatments for PH in the setting of IPF. In this review, we summarize existing therapies from the perspective of molecular mechanisms underlying lung fibrosis and vasoconstriction/vascular remodelling and discuss potential future targets for pharmacotherapy.LINKED ARTICLESThis article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc