bluuebunny/crossref_metadata_2025 huggingface dataset:
La moda y sus formas: nueva propuesta didáctica en la EASD de València
Authors: Torralba Nieves , Martínez Escutia Jose
Published: November 2017

Resumen: La propuesta didáctica detallada en este artículo deriva del cambio del plan curricular de los Estudios Superiores de Diseño de Moda, que comportó una nueva metodología, en concreto, para la asignatura Diseño Básico. Tal renovación se muestra como resultado de la línea de investigación Moda contemporánea. Los modelos y el Contexto, del ISEACV. En esta línea, bajo el título “Las formas de la moda”, se desarrolló la investigación que congregó un corpus teórico-práctico para la asignatura mencionada, propia de la especialidad de Diseño de Moda, impartida en la EASD de València. Al desarrollo de la metodología, de marcado carácter interdisciplinar y sustentada por bases teóricas aquí referidas, se añade la visibilidad que propició la exposición Las formas de la moda / The Forms of Fashion, la cual aglutinó las propuestas de estudiantes que cursaron la asignatura Diseño Básico. Palabras clave: diseño moda, diseño básico, análisis formal, silueta, tendencias, composición. Abstract: The didactic proposal described in this article comes from the change in the Fashion Design Studies curriculum, which introduced a new methodology, more specifically for the Basic Design course. The change is the result of ISEACV’s investigation into Contemporary Fashion. Models and Context. Following this line of research, “Las formas de la moda” involved a process of experimentation that led to a theoretical-practical corpus of work within the Fashion Design course given at EASD València. In developing the methodology, with a strong interdisciplinary character underpinned on the aforementioned theoretical guidelines, the exhibition Las formas de la moda / The Forms of Fashion added heightened visibility, by bringing together the proposals created by the students taking the Basic Design course. Keywords: fashion design, basic design, formal analysis, silhouette, trends, composition.http://dx.doi.org/10.7203/eari.8.10017
Diálogos y otras ausencias a través de la obra de Pepe Espaliú
Authors: Braza Alba , Noguerol Luis
Published: November 2017

Resumen: El presente artículo cuenta la experiencia del taller didáctico Diálogos y otras ausencias a través de la obra de Pepe Espaliú realizado en el IVAM con motivo de la exposición dedicada al artista Pepe Espaliú.Dicho taller estuvo diseñado y dirigido a estudiantes de grado de magisterio y  de grado y posgrado en bellas artes conformándose como una propuesta didáctica basada en dinámicas de grupo con las cuales se favoreció la creación de vínculos con la obra del artista propuesto, con sus referentes artísticos y con otras producciones de interés para  abordar cuestiones como son el cuerpo, el deseo, la  enfermedad, la disidencia, la homosexualidad, el estigma, la ausencia y la soledad.A partir de una primera toma de contacto a través de un cuestionario en línea de carácter anónimo, durante la sesión en el museo se dio lugar a un intenso intercambio de experiencias, empatías y reflexiones que quedaron escritas a modo de relato y que se compartieron a través del debate reafirmando la posición de un público emancipado, autónomo y generador de contenidos mediante la proyección de su bagaje personal y cultural. Palabras clave: mediación artística, educación y museos, compromiso social, trabajo colaborativo, diversidad sexual, sida. Abstract: The present article is focused on the didactic workshop Dialogs and other absences throughout the Pepe Espaliú work performed in the IVAM museum motivated in the exposition dedicated to the artist Pep Espaliú. The aforementioned workshop was designed and addressed to Teaching Degree students, Arts Degree with the aim to be a didactic proposal based on group dynamics by which the linking between the artist; his artistic references and other interesting productions were favoured in order to discuss questions such as the body, the desire, the disease, the dissent, the homosexuality, the stigma, the absence and the solitude.After the first touch base with an anonymous questionnaire, during the session an exciting debate in which empathies and reflexions were written as a short story that was shared within the debate reinforcing the position of an emancipated public, autonomous and builder of contents by means of their own personal and cultural knowledge. Keywords: artistic education; education and museums; social commitment; collaborative work; sexual diversity, aids.http://dx.doi.org/10.7203/eari.8.10048
Comparative analysis of the microRNA transcriptome between yak and cattle provides insight into high-altitude adaptation
Authors: Guan Jiuqiang , Long Keren , Ma Jideng , Zhang Jinwei , He Dafang , Jin Long , Tang Qianzi , Jiang Anan , Wang Xun , Hu Yaodong , Tian Shilin , Jiang Zhi , Li Mingzhou , Luo Xiaolin
Published: November 2017

Extensive and in-depth investigations of high-altitude adaptation have been carried out at the level of morphology, anatomy, physiology and genomics, but few investigations focused on the roles of microRNA (miRNA) in high-altitude adaptation. We examined the differences in the miRNA transcriptomes of two representative hypoxia-sensitive tissues (heart and lung) between yak and cattle, two closely related species that live in high and low altitudes, respectively. In this study, we identified a total of 808 mature miRNAs, which corresponded to 715 pre-miRNAs in the two species. The further analysis revealed that both tissues showed relatively high correlation coefficient between yak and cattle, but a greater differentiation was present in lung than heart between the two species. In addition, miRNAs with significantly differentiated patterns of expression in two tissues exhibited co-operation effect in high altitude adaptation based on miRNA family and cluster. Functional analysis revealed that differentially expressed miRNAs were enriched in hypoxia-related pathways, such as the HIF-1α signaling pathway, the insulin signaling pathway, the PI3K-Akt signaling pathway, nucleotide excision repair, cell cycle, apoptosis and fatty acid metabolism, which indicated the important roles of miRNAs in high altitude adaptation. These results suggested the diverse degrees of miRNA transcriptome variation in different tissues between yak and cattle, and suggested extensive roles of miRNAs in high altitude adaptation.
TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration
Authors: Gooskens Saskia L. , Klasson Timothy D. , Gremmels Hendrik , Logister Ive , Pieters Robert , Perlman Elizabeth J. , Giles Rachel H. , van den Heuvel‐Eibrink Mary M.
Published: October 2017

We recently identified hypermethylation at the gene promoter of transcription factor 21 (TCF21) in clear cell sarcoma of the kidney (CCSK), a rare pediatric renal tumor. TCF21 is a transcription factor involved in tubular epithelial development of the kidney and is a candidate tumor suppressor. As there are no in vitro models of CCSK, we employed a well‐established clear cell renal cell carcinoma (ccRCC) cell line, 786‐O, which also manifests high methylation at the TCF21 promoter, with consequent low TCF21 expression. The tumor suppressor function of TCF21 has not been functionally addressed in ccRCC cells; we aimed to explore the functional potential of TCF21 expression in ccRCC cells in vitro. 786‐O clones stably transfected with either pBABE‐TCF21‐HA construct or pBABE vector alone were functionally analyzed. We found that ectopic expression of TCF21 in 786‐O cells results in a trend toward decreased cell proliferation (not significant) and significantly decreased migration compared with mock‐transfected 786‐O cells. Although the number of colonies established in colony formation assays was not different between 786‐O clones, colony size was significantly reduced in 786‐O cells expressing TCF21. To investigate whether the changes in migration were due to epithelial‐to‐mesenchymal transition changes, we interrogated the expression of selected epithelial and mesenchymal markers. Although we observed upregulation of mRNA and protein levels of epithelial marker E‐cadherin in clones overexpressing TCF21, this did not result in surface expression of E‐cadherin as measured by fluorescence‐activated cell sorting and immunofluorescence. Furthermore, mRNA expression of the mesenchymal markers vimentin (VIM) and SNAI1 was not significantly decreased in TCF21‐expressing 786‐O cells, while protein levels of VIM were markedly decreased. We conclude that re‐expression of TCF21 in renal cancer cells that have silenced their endogenous TCF21 locus through hypermethylation results in reduced clonogenic proliferation, reduced migration, and reduced mesenchymal‐like characteristics, suggesting a tumor suppressor function for transcription factor 21.
Study of Plasmonic Resonances on Platonic Solids
Authors: Tzarouchis Dimitrios C. , Ylä‐Oijala Pasi , Sihvola Ari
Published: October 2017

In this study we discuss the plasmonic subwavelength scattering resonances of five regular polyhedra, that is, the Platonic solids tetrahedron, hexahedron, octahedron, dodecahedron, and icosahedron. A brief discussion regarding their geometrical characteristics and the numerical method used in the study is given. All results are compared with the benchmark case of a sphere, in order to observe how the geometry of the solid affects the spectral characteristics. The principal finding is that the shift of the main dipole resonance exhibits a solid vertex hierarchical order; in other words, the position of the resonance correlates with the solid angle of the vertex of the given solid. This is in contrast with the hedra‐hierarchical order found for the electrostatic dielectric response of these solids. These results can create new avenues for applications and devices that require plasmonic particles with on‐demand functionalities.
Norovirus
Authors: Iturriza‐Gómara Miren , Harris John
Published: October 2017

Norovirus infections are the leading cause of acute gastroenteritis globally. Despite the increasing recognition of norovirus infections in various animal species, there is to date no evidence of an animal reservoir for human norovirus, and transmission of norovirus is primarily person‐to‐person. Contaminated food, water and environment act as important amplifiers for infection. Human noroviruses are very diverse; however, one genotype GII‐4 predominates globally and is responsible for nearly half of all the infections and for a higher proportion of the outbreaks. Recently,
in vitro
systems for the propagation of human noroviruses have been developed, and there is an expectation that in the coming years, these will provide new insights into the molecular biology of human noroviruses and a better understanding of factors that determine susceptibility to and protection form infection. Host genetic factors and comorbidities in addition to potentially modifiable factors such as microbiome and use of certain treatment and drugs are increasingly recognised as important drivers of susceptibility to infection.

Key Concepts

Norovirus is the leading cause of acute gastroenteritis in humans.

Transmission of norovirus is predominantly person‐to‐person and is greatly amplified via contaminated food, water and environment.

Glycans act as attachment factors that mediate viral infection and cell entry and potentially drive host restriction.

New
in vitro
systems have recently been developed for human norovirus replication: B cell‐ and stem cell‐derived enteroids.

Virus diversity and host genetic and acquired factors are important drivers of susceptibility to infection.

The host microbiome has been recognised as an important factor for susceptibility to norovirus infection and clearance.
Protein Production for Biotechnology
Authors: Korajczyk Peter J , Zerbs Sarah , Collart Frank R
Published: October 2017

Purified proteins are useful as experimental tools, commercial products and therapeutics for the treatment of disease. The benefits of these products are dependent on specific qualities such as protein functionality, yield and purity. To meet these protein production criteria, a vast repertoire of constructs, genetic tools, methods and host organisms has been developed to enable multiple approaches for the production of diverse protein products. Consideration of the advantages and limitations of various heterologous expression systems is necessary to ensure that the resulting proteins will be useful for the specific needs of the intended project. Multiple approaches are often evaluated to accommodate the wide diversity in protein characteristics and functions. A systematic approach is outlined for evaluation of protein properties incorporating the requirements for the intended use of protein production to provide a reliable strategy for the selection of appropriate system(s) for large‐scale protein production.

Key Concepts

Controlled production of purified proteins is necessary for scientific research and has many therapeutic and commercial applications.

The intended use of a protein product strongly influences the methods selected for protein production.

Each biological expression system has unique advantages, disadvantages and requirements for protein production.

Multiple technological approaches and hosts may be screened to meet project requirements.

In vitro
expression methods allow for the systematic development of proteins with unique modifications or properties.

A large resource of technological materials in support of protein production enables the generation of products with substantial economic and scientific interest.
Single‐Step Method of Total
RNA
Isolation by Guanidine–Phenol Extraction
Authors: Chomczynski Piotr , Wilfinger William , Mackey Karol
Published: October 2017

The original single‐step method is the first procedure to isolate purified total ribonucleic acid (RNA) from a variety of sources including tissues and cells from human, animal, plant, yeast, bacterial and viral origins, without the requirement of high‐speed ultracentrifugation. This method is based on liquid‐phase separation resulting in sequestration of pure RNA into the aqueous phase. RNA is precipitated from the aqueous phase, dissolved, reprecipitated and washed with alcohol before the final solubilisation step. The entire procedure can be completed in less than 4 h and it provides RNA that is suitable for many sensitive downstream applications such as RNase protection assays, northern blotting, RNA sequencing studies and reverse transcription‐polymerase chain reaction. This pioneering methodology has served as the impetus for the development of newer and improved RNA extraction methodology that now enables investigators to extract and purify RNA in less than 60 min. Some of these newer methods do not require a halogenated organic solvent, or combine the single‐step method with column purification of the RNA.

Key Concepts

Enzymes within living cells rapidly degrade RNA after a tissue sample is removed from the donor. To prevent RNA degradation, tissue samples that cannot be immediately processed must be rapidly frozen with dry ice or liquid nitrogen and stored frozen at −80°C until the RNA can be extracted.

At the time of RNA extraction, frozen cells or tissues must be immersed in the denaturing solution and rapidly homogenised before the tissue thaws in order to inactivate RNAse and avoid RNA degradation.

The quality of the recovered RNA is dependent on a delicate balance of salt concentration and optimal pH. Overloading the extraction solution with too much tissue or diluting the denaturing solution beyond what is specified in the protocol will impact the quality of the resulting RNA.

The extraction of RNA from samples that have a high buffering capacity, such as blood, plasma or tissue culture medium, requires greater care in order to maintain optimal salt balance and pH control.

Overdrying of the RNA pellets will degrade RNA and impede RNA solubilisation.

RNA should be solubilised at a concentration that will be appropriate for meaningful spectrophotometric quantitation as well as subsequent downstream molecular biology applications.

Enzymes that are involved in RNA degradation are ubiquitous and special care must be taken to avoid RNAse contamination during RNA solubilisation and storage.
Oxidative Phosphorylation System: Nuclear Genes and Genetic Disease
Authors: Sánchez‐Caballero Laura , Baertling Fabian , Nijtmans Leo , Smeitink Jan AM
Published: October 2017

The mitochondrial oxidative phosphorylation (OXPHOS) system is located in the inner mitochondrial membrane, and it is the major energy provider of the cell. It consists of five multiprotein complexes (complex I–V). Defects in one or several of these enzymes cause mitochondrial disorders. Identifying underlying mutations within the nuclear genome has been an arduous task until the widespread use of whole exome sequencing in recent years. Since then, a big effort has been put into deciphering underlying mutations in nuclear genes that directly or indirectly affect the OXPHOS system. This led to the discovery of a great number of new gene defects involved in these multifaceted diseases. These findings not only improved the diagnostic process but also helped to understand the mechanisms behind mitochondrial diseases and laid the groundwork for novel approaches to therapy.

Key Concepts

Mitochondrial diseases are caused by a deficient pyruvate oxidation that involves the Krebs cycle and the oxidative phosphorylation (OXPHOS) system.

The OXPHOS system comprises the four respiratory chain enzymes (complexes I–IV) and complex V, also termed ATP synthase.

Defects in one or several of these enzymes cause mitochondrial disorders and give rise to a broad spectrum of clinical signs and symptoms ranging from mild adult‐onset myopathy to neonatal-onset fatal multisystem disease.

Impairments in OXPHOS functionality can not only be caused by mutations in genes encoding subunits of the respective complex but also by defects in nuclear genes encoding proteins required for OXPHOS complex biogenesis, mitochondrial translation, or mitochondrial redox homeostasis.
Segmental Duplications and Genetic Disease
Authors: Yilmaz Feyza , Shaikh Tamim H , Emanuel Beverly S
Published: October 2017

The human genome contains many different types of repetitive DNA elements that vary by size and copy number. Segmental duplications (SDs) are one such class of repetitive elements that are relatively large in size, have low copy number in the genome and their copies share high levels of sequence identity with each other. These characteristic features of SDs make them excellent substrates for genomic rearrangements, resulting from aberrant recombination between the highly identical copies. Several of the genomic rearrangements mediated by SDs lead to copy number variations of large genomic regions containing many genes. Consequently, SD‐mediated rearrangements are often associated with genetic diseases that manifest as syndromes characterised by multiple congenital anomalies due to dosage imbalance of one or more genes.

Key Concepts

Segmental duplications are repetitive DNA elements in the human genome.

Segmental duplications mediate genomic rearrangements associated with many genomic diseases.

Segmental duplications mediate genomic rearrangements via nonallelic homologous recombination (NAHR), or they can stimulate or promote rearrangements via nonhomologous end‐joining (NHEJ) or replication‐based mechanism (RBM).

Segmental duplications have been associated with both recurrent and nonrecurrent chromosomal rearrangements including microdeletions, microduplications, translocations, inversions and other complex rearrangements.

Segmental duplications have played an important role in the human genome evolution, genetic variation and disease predisposition.
The Genetics of Autism
Authors: Warrier Varun , Baron‐Cohen Simon
Published: October 2017

Autism spectrum conditions (henceforth ‘autism’) refer to a group of neurodevelopmental conditions involving difficulties in social interaction and communication and unusually repetitive and restricted behaviours and interest. Twin and family studies have established a significant heritability for autism. Autism is polygenic with variations across the allele frequency spectrum contributing to risk. Early linkage and candidate gene association studies were statistically underpowered to identify significant loci. Current genome‐wide association studies have identified significant positive genetic correlation between autism and various measures of cognition. The use of genetic microarrays and next‐generation DNA sequencing has identified tens of genes and copy number variants associated with autism. In addition, RNA microarray and sequencing studies of postmortem brain samples have identified transcriptionally altered genes and pathways in autism. Multiple lines of evidence converge on altered glial, synaptic and chromatin pathways as contributing to autism risk.

Key Concepts

Autism spectrum conditions (autism) represent a group of genetically and phenotypically heterogeneous neurodevelopmental conditions.

Autism is highly heritable as evidenced by twin studies, familial recurrence and molecular genetic analyses.

Autism is highly polygenic with common genetic variation, rare genetic variation and structural variation contributing to genetic risk.

Human DNA microarray and next‐generation sequencing of large cohorts have identified tens of associated genes and genetic loci.

Genome‐wide association studies point to significant heritability and genetic correlation with measures of cognition.

RNA sequencing and microarray studies have identified transcriptionally dysregulated genes in the autism postmortem cortex.

Pathway analysis across different genetic data sets identified synaptic and neuronal pathways, chromatin remodelling and a role for microglia and astrocytes.
Biobanking for Genetic Diseases
Authors: Filocamo Mirella , Casareto Lorena , Baldo Chiara
Published: October 2017

Biobanks are bioresources of human samples linked to relevant personal and health data of the participants, which are collected, processed and stored in an organised system. Their primary purpose is to provide biospecimens for researchers to help improve knowledge on human health and diseases, while appropriately protecting the interests, rights and privacy of the participants.

The biobanking community poses a variety of legal, ethical, social and regulatory challenges, particularly involved in genetic diseases, to be overcome because of the sensitive data they store. A crucial avenue for a biobank to build and maintain public trust is therefore through the development of governance mechanisms ensuring that, in pursuing its remit, the biobank acts in compliance with the applicable laws and regulations of the country in which it is located, as well as the international regulations in order to ease the cross‐border sample exchange and the international cooperation of biobanks.

Key Concepts

Biobanks are collections of human samples linked to relevant personal and health data of the participants, organised and managed in a systematic way.

Primary purpose of biobanks is to help improve knowledge on human health and diseases.

Biobanking poses a variety of challenges including ethical, legal and social issues (ELSI).

Because of the preciousness of the samples and the sensitive nature of the data stored in biobanks, proper governance is essential to protecting confidentiality, choices and rights of participants.

As critical components in the field of clinical practice and basic research, biobanks develop standard operating procedures devoted to collect, process, store, retrieve and transfer to researchers a set of biospecimens and associated information.

In the field of rare diseases (RDs), collectively affecting 6–8% of the population, international cooperation among RD‐biobanks is fundamental for sharing and achieving a critical mass of samples and data for basic, translational and clinical research.

To ease an international cooperation, biobanks also need to act in compliance with international regulations.
Vertebrate Embryo: Myogenesis and Muscle Development
Authors: Robson Lesley G
Published: October 2017

The formation and patterning of three types of muscle tissues are found in vertebrates: smooth, cardiac and skeletal. All three muscle types share the property that they contract to move substances around the body (smooth and cardiac) or move and stabilise the skeleton (skeletal). Although there are common signalling pathways utilised by all muscle types, each utilises a unique pathway. The varied origins of myogenic cells and the important role of local signals coordinate the correct migration from their site of origin to final location. The local environmental signals also coordinate proliferation and expansion of myogenic precursors and finally the correct patterning, orientation and differentiation of myogenic cells. It is also evidenced that the environment continues to have an important role in the regenerative and growth of muscle tissue postnatally.

Key Concepts

That often the same signalling pathways are used independent of the phenotype of muscle being produced.

Although many different cell lineages are used to produce smooth muscle, cardiac and skeletal muscles use more specific cell lineages.

The environment that myogenic cells inhabit often helps to specify the early myogenic specification pathway and the later patterning of the differentiating myogenic cells into specific muscle groups and fibre types.

The regenerative capacity in the postnatal muscle tissue is also regulated by the environment.
Alpha‐Synuclein
Authors: Cremades Nunilo
Published: October 2017

α‐Synuclein (αS) is a presynaptic small protein that has attracted much interest because its aggregation and accumulation in the form of amyloid fibrils is the hallmark of a range of neurodegenerative disorders, collectively referred to as synucleinopathies. Despite intense research on this protein since it was first identified two decades ago as the major component of the proteinaceous intracellular inclusion characteristics of Parkinson disease, there is still no consensus on the physiological function of the protein and much remains to be established on the molecular basis of its toxicity. Recently, important steps have been undertaken to identify the different conformational states that this protein is able to adopt and elucidate their role in physiological and pathological conditions.

Key Concepts

The physiological function(s) of α‐synuclein remains controversial, although recent evidences suggest a major regulatory role in synapsis.

At physiological conditions, α‐synuclein is in a dynamic equilibrium between a membrane‐bound α‐helical (likely multimeric) conformation and a cytosolic intrinsically disordered (monomeric) conformation.

α‐Synuclein aggregation and fibril formation likely play a central role in Parkinson disease and other neurodegenerative disorders.

Different strains or fibril polymorphs of α‐synuclein have different degrees of infectivity and might be associated with distinct types of pathologies.

Different mechanisms of formation of α‐synuclein amyloid aggregates have been observed
in vitro
, but their relative relevance
in vivo
remains unknown.

Recent studies support the idea that multiple aggregated species of α‐synuclein can be generated through diverse misfolding pathways during the process of amyloid aggregation and could play distinct roles during the development of disease.

Combined methods to target specifically different α‐synuclein conformations could potentially prevent α‐synuclein‐associated toxicity.
Molecular Genetics of Common Variable Immunodeficiency
Authors: Bogaert Delfien J , Dullaers Melissa , De Baere Elfride , Haerynck Filomeen
Published: October 2017

Common variable immunodeficiency (CVID) is one of the most frequently diagnosed primary immunodeficiencies (PIDs) characterised by antibody deficiency, poor responses to vaccination and an increased susceptibility to infections and complications due to immune dysregulation. The clinical diagnosis of CVID is an umbrella covering an immunologically and genetically heterogeneous group of diseases. To date, 22 disease‐causing genes have been associated with monogenic forms of CVID, encompassing 2–10% of reported cases. However, these genetic subtypes are now considered to account for distinct disease entities and have been removed from under the CVID umbrella. Furthermore, accumulating data suggest that the majority of CVID patients have a complex or multifactorial disorder, in which multiple genetic, epigenetic and/or environmental factors are involved. Genetic testing for monogenic causes should especially be performed in CVID patients with early onset of disease, noninfectious complications, a positive family history and/or consanguineous parents, since this could be important for genetic counselling, follow up and/or treatment decisions.

Key Concepts

CVID is a diagnosis of exclusion, encompassing a clinically, immunologically and genetically heterogeneous group of PID patients.

Monogenic defects have so far been reported in 2–10% of CVID patients.

The majority of CVID patients are believed to have a complex or multifactorial aetiology.

Patients in whom a monogenic cause is identified are no longer classified under CVID, but under separate disease entities (IUIS classification).

A monogenic cause of CVID is more probable in case of early onset of disease, complications of immune dysregulation, a positive family history and/or consanguinity.

Especially in CVID patients with early onset of disease and/or noninfectious complications, genetic workup should be performed to identify or exclude an underlying monogenic cause since this could be important for patient management decisions.
Mechanisms and Roles of Mitophagy
Authors: Vigié Pierre , Bhatia‐Kiššová Ingrid , Camougrand Nadine
Published: October 2017

Mitochondria are highly dynamic organelles that provide essential metabolic functions and represent the major bioenergetic hub of eukaryotic cells. Mitochondrial dysfunctions are implicated in numerous diseases. Therefore, maintenance of a healthy pool of mitochondria is required for cellular function and survival. Mitochondrial quality control is secured by several mechanisms that act at different levels: proteases and chaperones, the ubiquitin‐proteasome system (UPS) and mitophagy. Multiple mitophagy programs either operate independently or undergo crosstalk and require modulated receptor activities in the mitochondrial membranes. In mammals, different mitophagy effectors have been characterised, such as the receptors NIX, BNIP3, FUNDC1, BCL2L13, Prohibitin2, cardiolipin and PINK1/Parkin pathway.

Key Concepts

Mitophagy is a process that degrades mitochondria selectively via autophagy.

Mitophagy operates at the organelle scale.

Proteases, chaperones and ubiquitin‐proteasome system operate at the molecular level.

PINK1/Parkin‐dependent and PINK1/Parkin‐independent pathways regulate mitophagy in mammals.

Receptors localised in mitochondrial membranes play a role in mitophagy.
Genome im Fokus: Entwicklung und Anwendungen von CRISPR‐Cas9‐Bildgebungstechnologien
Authors: Knight Spencer C. , Tjian Robert , Doudna Jennifer A.
Published: October 2017

Die Entdeckung der CRISPR‐Cas9‐Endonuklease ermöglicht die einfache Genom‐Editierung von lebenden Zellen und Organismen. Katalytisch deaktivierte Cas9 (dCas9) behält die Fähigkeit, DNA in einer RNA‐abhängigen Weise zu binden, und wurde zusätzlich als ein Werkzeug für die Transkriptionsmodulation, die Epigenom‐Editierung und die genomische Bildgebung entwickelt. Dieser Aufsatz zeigt die jüngsten Fortschritte und Herausforderungen bei der Entwicklung von dCas9 für die Bildgebung genomischer Loci auf. Die Entstehung und Weiterentwicklung dieser Technologie bietet das Potenzial, neue mechanistische Fragen über die Chromosomendynamik und die dreidimensionale Genomorganisation in vivo zu beantworten.
Thioamide‐Directed Cobalt(III)‐Catalyzed Selective Amidation of C(sp3)−H Bonds
Authors: Tan Peng Wen , Mak Adrian M. , Sullivan Michael B. , Dixon Darren J. , Seayad Jayasree
Published: October 2017

A mild, oxidant‐free, and selective Cp*CoIII‐catalyzed amidation of thioamides with robust dioxazolone amidating agents via C(sp3)−H bond activation to generate the desired amidated products is reported. The method is efficient and allows for the C−H amidation of a wide range of functionalized thioamides with aryl‐, heteroaryl‐, and alkyl‐substituted dioxazolones under the Cp*CoIII‐catalyzed conditions. The observed regioselectivity towards primary C(sp3)−H activation is supported by computational studies and the cyclometalation is proposed to proceed by means of an external carboxylate‐assisted concerted metalation/deprotonation mechanism. The reported method is a rare example of the use of a directing group other than the commonly used pyridine and quinolone classes for Cp*CoIII‐catalyzed C(sp3)−H functionalization and the first to exploit thioamides.
Identification of key residues modulating the stereoselectivity of nitrile hydratase toward rac‐mandelonitrile by semi‐rational engineering
Authors: Cheng Zhongyi , Peplowski Lukasz , Cui Wenjing , Xia Yuanyuan , Liu Zhongmei , Zhang Jialei , Kobayashi Michihiko , Zhou Zhemin
Published: October 2017

Optically pure compounds are important in the synthesis of fine chemicals. Using directed evolution of enzymes to obtain biocatalysts that can selectively produce high‐value chiral chemicals is often time‐, money‐, and resource‐intensive; traditional semi‐rational designs based on structural data and docking experiments are still limited due to the lack of accurate selection of hot‐spot residues. In this study, through ligand‐protein collision counts based on steered molecular dynamics simulation, we accurately identified four residues related to improving nitrile hydratase stereoselectivity toward rac‐mandelonitrile (MAN). All the four selected residues had numerous collisions with rac‐MAN. Five mutants significantly shifting stereoselectivity towards (S)‐MAN were obtained from site‐saturation mutagenesis, one of them, at position βPhe37, exhibiting efficient production of (S)‐MAN with 96.8% eep, was isolated and further analyzed. The increased pulling force observed during SMD simulation was found to be in good coincidence with the formation of hydrogen bonds between (R)‐MAN and residue βHis37. (R)‐MAN had to break these barriers to enter the active site of nitrile hydratase and S selectivity was thus improved. The results indicated that combining steered molecular dynamics simulation with a traditional semi‐rational design significantly reduced the select range of hot‐spot residues for the evolution of NHase stereoselectivity, which could serve as an alternative for the modulation of enzyme stereoselectivity.
Perovskite Solar Cells: From the Laboratory to the Assembly Line
Authors: Abate Antonio , Correa‐Baena Juan‐Pablo , Saliba Michael , Su'ait Mohd Sukor , Bella Federico
Published: October 2017

Despite the fact that perovskite solar cells (PSCs) have a strong potential as a next‐generation photovoltaic technology due to continuous efficiency improvements and the tunable properties, some important obstacles remain before industrialization is feasible. For example, the selection of low‐cost or easy‐to‐prepare materials is essential for back‐contacts and hole‐transporting layers. Likewise, the choice of conductive substrates, the identification of large‐scale manufacturing techniques as well as the development of appropriate aging protocols are key objectives currently under investigation by the international scientific community. This Review analyses the above aspects and highlights the critical points that currently limit the industrial production of PSCs and what strategies are emerging to make these solar cells the leaders in the photovoltaic field.
Regression analysis of bivariate current status data under the proportional hazards model
Authors: Hu Tao , Zhou Qingning , Sun Jianguo
Published: October 2017

This article discusses the regression analysis of bivariate current status or case I interval‐censored failure time data under the marginal proportional hazards model. Several estimation procedures have been proposed for this problem, but each method either applies only to limited situations or no theoretical justification has been provided. Using Bernstein polynomials and the copula model we develop a sieve maximum likelihood estimation approach that applies to more general situations. In particular this method leaves the underlying copula model completely unspecified and can be easily implemented. The proposed estimators are shown to be strongly consistent and the asymptotic normality and efficiency of the regression parameter estimator are established. Simulation studies are conducted to assess the performance of the proposed method. An illustrative example is also provided.The Canadian Journal of Statistics45: 410–424; 2017 © 2017 Statistical Society of Canada
Polymer Segments at the Folding Limit: Raman Scattering for the Diglyme Benchmark
Authors: Bocklitz Sebastian , Suhm Martin A.
Published: October 2017

Methyl‐capped polyethers model flexible polar polymer chains. Their intrinsic all‐trans conformational preference gives way to folded conformations if the chain is sufficiently long. We find by Raman cryospectroscopy in the gas phase and quantum chemical calculations that diglyme still prefers the stretched state, although folded variants come very close in energy. Three‐body dispersion correction or higher‐order electron correlation is important to match experiments, despite the polar character of C−O bonds. This turns oligoglymes into challenging benchmark systems for a balanced description of intra‐chain torsion and inter‐segment van der Waals attraction.
Reliable effective number of breeders/adult census size ratios in seasonal‐breeding species: Opportunity for integrative demographic inferences based on capture–mark–recapture data and multilocus genotypes
Authors: Sánchez‐Montes Gregorio , Wang Jinliang , Ariño Arturo H. , Vizmanos José Luis , Martínez‐Solano Iñigo
Published: October 2017

The ratio of the effective number of breeders (Nb) to the adult census size (Na), Nb/Na, approximates the departure from the standard capacity of a population to maintain genetic diversity in one reproductive season. This information is relevant for assessing population status, understanding evolutionary processes operating at local scales, and unraveling how life‐history traits affect these processes. However, our knowledge on Nb/Na ratios in nature is limited because estimation of both parameters is challenging. The sibship frequency (SF) method is adequate for reliable Nb estimation because it is based on sibship and parentage reconstruction from genetic marker data, thereby providing demographic inferences that can be compared with field‐based information. In addition, capture–mark–recapture (CMR) robust design methods are well suited for Na estimation in seasonal‐breeding species. We used tadpole genotypes of three pond‐breeding amphibian species (Epidalea calamita, Hyla molleri, and Pelophylax perezi, n = 73–96 single‐cohort tadpoles/species genotyped at 15–17 microsatellite loci) and candidate parental genotypes (n = 94–300 adults/species) to estimate Nb by the SF method. To assess the reliability of Nb estimates, we compared sibship and parentage inferences with field‐based information and checked for the convergence of results in replicated subsampled analyses. Finally, we used CMR data from a 6‐year monitoring program to estimate annual Na in the three species and calculate the Nb/Na ratio. Reliable ratios were obtained for E. calamita (Nb/Na = 0.18–0.28) and P. perezi (0.5), but in H. molleri, Na could not be estimated and genetic information proved insufficient for reliable Nb estimation. Integrative demographic studies taking full advantage of SF and CMR methods can provide accurate estimates of the Nb/Na ratio in seasonal‐breeding species. Importantly, the SF method provides results that can be readily evaluated for reliability. This represents a good opportunity for obtaining robust demographic inferences with wide applications for evolutionary and conservation research.
Keystone nonconsumptive effects within a diverse predator community
Authors: Meadows Amanda J. , Owen Jeb P. , Snyder William E.
Published: October 2017

The number of prey killed by diverse predator communities is determined by complementarity and interference among predators, and by traits of particular predator species. However, it is less clear how predators' nonconsumptive effects (NCEs) scale with increasing predator biodiversity. We examined NCEs exerted on Culex mosquitoes by a diverse community of aquatic predators. In the field, mosquito larvae co‐occurred with differing densities and species compositions of mesopredator insects; top predator dragonfly naiads were present in roughly half of surveyed water bodies. We reproduced these predator community features in artificial ponds, exposing mosquito larvae to predator cues and measuring resulting effects on mosquito traits throughout development. Nonconsumptive effects of various combinations of mesopredator species reduced the survival of mosquito larvae to pupation, and reduced the size and longevity of adult mosquitoes that later emerged from the water. Intriguingly, adding single dragonfly naiads to ponds restored survivorship of larval mosquitoes to levels seen in the absence of predators, and further decreased adult mosquito longevity compared with mosquitoes emerging from mesopredator treatments. Behavioral observations revealed that mosquito larvae regularly deployed “diving” escape behavior in the presence of the mesopredators, but not when a dragonfly naiad was also present. This suggests that dragonflies may have relaxed NCEs of the mesopredators by causing mosquitoes to abandon energetically costly diving. Our study demonstrates that adding one individual of a functionally unique species can substantially alter community‐wide NCEs of predators on prey. For pathogen vectors like mosquitoes, this could in turn influence disease dynamics.
Environmental change, shifting distributions, and habitat conservation plans: A case study of the California gnatcatcher
Authors: Hulton VanTassel Heather L. , Bell Michael D. , Rotenberry John , Johnson Robert , Allen Michael F.
Published: October 2017

Many species have already experienced distributional shifts due to changing environmental conditions, and analyzing past shifts can help us to understand the influence of environmental stressors on a species as well as to analyze the effectiveness of conservation strategies. We aimed to (1) quantify regional habitat associations of the California gnatcatcher (Polioptila californica); (2) describe changes in environmental variables and gnatcatcher distributions through time; (3) identify environmental drivers associated with habitat suitability changes; and (4) relate habitat suitability changes through time to habitat conservation plans. Southern California's Western Riverside County (WRC), an approximately 4,675 km2 conservation planning area. We assessed environmental correlates of distributional shifts of the federally threatened California gnatcatcher (hereafter, gnatcatcher) using partitioned Mahalanobis D2 niche modeling for three time periods: 1980–1997, 1998–2003, and 2004–2012, corresponding to distinct periods in habitat conservation planning. Highly suitable gnatcatcher habitat was consistently warmer and drier and occurred at a lower elevation than less suitable habitat and consistently had more CSS, less agriculture, and less chaparral. However, its relationship to development changed among periods, mainly due to the rapid change in this variable. Likewise, other aspects of highly suitable habitat changed among time periods, which became cooler and higher in elevation. The gnatcatcher lost 11.7% and 40.6% of highly suitable habitat within WRC between 1980–1997 to 1998–2003, and 1998–2003 to 2004–2012, respectively. Unprotected landscapes lost relatively more suitable habitat (−64.3%) than protected landscapes (30.5%). Over the past four decades, suitable habitat loss within WRC, especially between the second and third time periods, was associated with temperature‐related factors coupled with landscape development across coastal sage scrub habitat; however, development appears to be driving change more rapidly than climate change. Our study demonstrates the importance of providing protected lands for potential suitable habitat in future scenarios.
Evolution to environmental contamination ablates the circadian clock of an aquatic sentinel species
Authors: Coldsnow Kayla D. , Relyea Rick A. , Hurley Jennifer M.
Published: October 2017

Environmental contamination is a common cause of rapid evolution. Recent work has shown that Daphnia pulex, an important freshwater species, can rapidly evolve increased tolerance to a common contaminant, sodium chloride (NaCl) road salt. While such rapid evolution can benefit organisms, allowing them to adapt to new environmental conditions, it can also be associated with unforeseen tradeoffs. Given that exposure to environmental contaminants can cause circadian disruption, we investigated whether the circadian clock was affected by evolving a tolerance to high levels of road salt. By tracking the oscillations of a putative clock gene, period, we demonstrated that D. pulex express per mRNA with approximately 20‐hr oscillations under control conditions. This putative circadian rhythm was ablated in response to high levels of salinity; populations adapted to high NaCl concentrations exhibited an ablation of period oscillation. Moreover, we showed that while gene expression is increased in several other genes, including clock, actin, and Na+/K+‐ATPase, upon the adaptation to high levels of salinity, per expression is unique among the genes we tracked in that it is the only gene repressed in response to salt adaptation. These results suggest that rapid evolution of salt tolerance occurs with the tradeoff of suppressed circadian function. The resultant circadian disruption may have profound consequences to individuals, populations, and aquatic food webs by affecting species interactions. In addition, our research suggests that circadian clocks may also be disrupted by the adaptation to other environmental contaminants.
Degradation of Edible Oil During Deep‐Frying Process by Electron Spin Resonance Spectroscopy and Physicochemical Appreciation
Authors: Liu Ying , Wang Yuanpeng , Cao Peirang , Liu Yuanfa
Published: October 2017

During frying process of edible oil, lipid oxidation occurs, which is a complex process and involves free radical chain reactions. The impacts of oil with different fatty acid composition on free radicals were evaluated. An ESR study was performed to identify and quantify the formed radicals, along with the assessment of physicochemical parameters including peroxide value, oxidative stability, fatty acid composition, and volatile profile. Results showed an increase of formed free radicals in frying oils over frying time. Besides, frying oils with higher content of unsaturated fatty acids were more prone to be oxidized, as well as physicochemical parameters evidencing this phenomenon. Volatile compounds produced by β‐scission homolytic cleavage of peroxide group during thermal oxidation in frying oils were detected by GC‐MS/MS. Results implied major aldehyde volatile compounds were derived from hydroperoxide and oil with higher proportions of unsaturated fatty acids are more likely to produce volatile oxidation products.

In order to compare the degree of lipid oxidation in deep‐fried sunflower oil (high degree of unsaturation) and palm oil (high degree of saturation), the formed free radicals based on ESR, along with the assessment of physicochemical parameters including peroxide value, oxidative stability, fatty acid composition, and volatile profile to improve comprehensive assessment of degradation in oil with different fatty acid composition are investigated.