bluuebunny/crossref_metadata_2025 huggingface dataset:
Leopold Trénor Palavicino, a través de la Biografia d’un president de Lo Rat Penat, ja mort, amb descripció de les seues activitats relacionades amb aquest centre, d’Amèlia Comba Comba (1965)
Authors: Pastor Banyuls Víctor
Published: June 2021

Resum: Aquest article analitza l’escriptor Leopold Trénor Palavicino a partir de la informació de la biografia escrita per Amèlia Comba en 1965. Les pàgines de l’autora aporten una perspectiva més ajustada al perfil del literat. Trénor, provinent de família noble, esdevé un poeta de base catòlica, capaç de representar organitzacions com Lo Rat Penat, des d’on va treballar incansablement per recuperar la llengua, la literatura i el patrimoni valencians.Paraules clau: Leopold Trénor, Amèlia Comba, Lo Rat Penat, valencianisme, poesia Abstract: This paper analyses the writer Leopold Trénor Palavicino based on information from the biography written by Amèlia Comba in 1965. the author’s pages provide a more in-depth perspective on the writer’s profile. Trénor, coming from a noble family, becomes a Catholic poet who can represent organizations like Lo Rat Penat, where he worked tirelessly to recover the Valencian language, literature and cultural heritage.Keywords: Leopold Trénor, Amèlia Comba, Lo Rat Penat, valencianisme, poetry
Ressenya a Furió, Antoni. Quinze dones valencianes. Catarroja-Barcelona: Afers, 2020.
Authors: Pérez Rodríguez María Luisa
Published: June 2021

Ressenya a Furió, Antoni. Quinze dones valencianes. Catarroja-Barcelona: Afers, 2020. 419 pp. ISBN: 978-84-16260-79-9
Presentació Scripta 17
Authors: Escartí Soriano Vicent Josep
Published: June 2021

Índex i presentació
Pore mutation N617D in the skeletal muscle DHPR blocks Ca2+ influx due to atypical high-affinity Ca2+ binding
Authors: Dayal Anamika , Fernández-Quintero Monica L , Liedl Klaus R , Grabner Manfred
Published: June 2021

Skeletal muscle excitation-contraction (EC) coupling roots in Ca2+-influx-independent inter-channel signaling between the sarcolemmal dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) in the sarcoplasmic reticulum. Although DHPR Ca2+ influx is irrelevant for EC coupling, its putative role in other muscle-physiological and developmental pathways was recently examined using two distinct genetically engineered mouse models carrying Ca2+ non-conducting DHPRs: DHPR(N617D) (Dayal et al., 2017) and DHPR(E1014K) (Lee et al., 2015). Surprisingly, despite complete block of DHPR Ca2+-conductance, histological, biochemical, and physiological results obtained from these two models were contradictory. Here, we characterize the permeability and selectivity properties and henceforth the mechanism of Ca2+ non-conductance of DHPR(N617). Our results reveal that only mutant DHPR(N617D) with atypical high-affinity Ca2+ pore-binding is tight for physiologically relevant monovalent cations like Na+ and K+. Consequently, we propose a molecular model of cooperativity between two ion selectivity rings formed by negatively charged residues in the DHPR pore region.
Targeting a cell surface vitamin D receptor on tumor-associated macrophages in triple-negative breast cancer
Authors: Staquicini Fernanda I , Hajitou Amin , Driessen Wouter HP , Proneth Bettina , Cardó-Vila Marina , Staquicini Daniela I , Markosian Christopher , Hoh Maria , Cortez Mauro , Hooda-Nehra Anupama , Jaloudi Mohammed , Silva Israel T , Buttura Jaqueline , Nunes Diana N , Dias-Neto Emmanuel , Eckhardt Bedrich , Ruiz-Ramírez Javier , Dogra Prashant , Wang Zhihui , Cristini Vittorio , Trepel Martin , Anderson Robin , Sidman Richard L , Gelovani Juri G , Cristofanilli Massimo , Hortobagyi Gabriel N , Bhujwalla Zaver M , Burley Stephen K , Arap Wadih , Pasqualini Renata
Published: June 2021

Triple-negative breast cancer (TNBC) is an aggressive tumor with limited treatment options and poor prognosis. We applied the in vivo phage display technology to isolate peptides homing to the immunosuppressive cellular microenvironment of TNBC as a strategy for non-malignant target discovery. We identified a cyclic peptide (CSSTRESAC) that specifically binds to a vitamin D receptor, protein disulfide-isomerase A3 (PDIA3) expressed on the cell surface of tumor-associated macrophages (TAM), and targets breast cancer in syngeneic TNBC, non-TNBC xenograft, and transgenic mouse models. Systemic administration of CSSTRESAC to TNBC-bearing mice shifted the cytokine profile toward an antitumor immune response and delayed tumor growth. Moreover, CSSTRESAC enabled ligand-directed theranostic delivery to tumors and a mathematical model confirmed our experimental findings. Finally, in silico analysis showed PDIA3-expressing TAM in TNBC patients. This work uncovers a functional interplay between a cell surface vitamin D receptor in TAM and antitumor immune response that could be therapeutically exploited.
Rampant tooth loss across 200 million years of frog evolution
Authors: Paluh Daniel J , Riddell Karina , Early Catherine M , Hantak Maggie M , Jongsma Gregory FM , Keeffe Rachel M , Magalhães Silva Fernanda , Nielsen Stuart V , Vallejo-Pareja María Camila , Stanley Edward L , Blackburn David C
Published: June 2021

Teeth are present in most clades of vertebrates but have been lost completely several times in actinopterygian fishes and amniotes. Using phenotypic data collected from over 500 genera via micro-computed tomography, we provide the first rigorous assessment of the evolutionary history of dentition across all major lineages of amphibians. We demonstrate that dentition is invariably present in caecilians and salamanders, but teeth have been lost completely more than 20 times in frogs, a much higher occurrence of edentulism than in any other vertebrate group. The repeated loss of teeth in anurans is associated with a specialized diet of small invertebrate prey as well as shortening of the lower jaw, but it is not correlated with a reduction in body size. Frogs provide an unparalleled opportunity for investigating the molecular and developmental mechanisms of convergent tooth loss on a large phylogenetic scale.
Contingency and chance erase necessity in the experimental evolution of ancestral proteins
Authors: Xie Victoria Cochran , Pu Jinyue , Metzger Brian PH , Thornton Joseph W , Dickinson Bryan C
Published: June 2021

The roles of chance, contingency, and necessity in evolution are unresolved because they have never been assessed in a single system or on timescales relevant to historical evolution. We combined ancestral protein reconstruction and a new continuous evolution technology to mutate and select proteins in the B-cell lymphoma-2 (BCL-2) family to acquire protein–protein interaction specificities that occurred during animal evolution. By replicating evolutionary trajectories from multiple ancestral proteins, we found that contingency generated over long historical timescales steadily erased necessity and overwhelmed chance as the primary cause of acquired sequence variation; trajectories launched from phylogenetically distant proteins yielded virtually no common mutations, even under strong and identical selection pressures. Chance arose because many sets of mutations could alter specificity at any timepoint; contingency arose because historical substitutions changed these sets. Our results suggest that patterns of variation in BCL-2 sequences – and likely other proteins, too – are idiosyncratic products of a particular and unpredictable course of historical events.
Frecuencia de enteroparásitos en primates Cebidae y Callitrichidae del Zoológico de Cali, Colombia: implicaciones zoonóticas
Authors: Zapata-Valencia Jorge Iván , Ortega-Valencia Sebastián , Silva-Cuero Yisther Katherine , Castillo-Castillo Lina Sofía , Ortega-Ruíz Laura Sofía , Cardona-Ortiz Adriana , Peña-Stadlin Juliana
Published: June 2021

Introducción. Los enteroparásitos pueden generar problemas en animales bajo cuidado humano en zoológicos y centros de acogida. Los animales silvestres presentan bajas cargas parasitarias, pero estas pueden ser mayores y llevar a manifestaciones clínicas cuando se trata de animales resguardados en recintos, lo que aumenta los gastos en tratamientos y cuidados médicos. Por otro lado, algunos enteroparásitos pueden causar infecciones zoonóticas en los cuidadores, los visitantes y otros animales del zoológico, así como afectar los programas de recuperación de especies amenazadas de extinción.Objetivos. Determinar la presencia y prevalencia de enteroparásitos con potencial de transmisión zoonótica en primates de las familias Cebidae y Callitrichidae del Zoológico de Cali, entre septiembre y noviembre de 2017.Materiales y métodos. Se hizo un estudio transversal prospectivo, para lo cual se recolectaron muestras seriadas de 50 individuos pertenecientes a siete especies de dos familias de primates y se analizaron mediante examen coprológico, flotación y coloración Kinyoun, entre septiembre y noviembre de 2017.Resultados. Según su prevalencia, los géneros de parásitos hallados en las siete especies de primates evaluadas, fueron Blastocystis spp., Trichomonas spp., Giardia spp., Entamoeba spp., Strongyloides spp., Cyclospora sp. y Trichuris sp.Conclusiones. Por lo menos, seis de los géneros de parásitos identificados tienen implicaciones zoonóticas, lo cual hace necesario establecer las posibles vías de infección de los primates del Zoológico de Cali e implementar protocolos de manejo que reduzcan el riesgo de transmisión a los humanos y a otros animales de la colección. Además, se presenta la información relevante sobre el potencial zoonótico de los enteroparásitos hallados.
Characterization of an outbreak of malaria in a non-endemic zone on the coastal region of Ecuador
Authors: Morales Diego Omar , Quinatoa Paul Andrés , Cagua Jaen Carlos
Published: June 2021

Introduction: Malaria is a vector-borne disease widely distributed in the Amazon region and the coastal area of northern Ecuador. Its epidemiology involves related factors such as human settlements, vector reproduction sites, mobility, productive activity, and the response capacity of health systems, among others.Objective: To describe malaria transmission by Plasmodium vivax in a non-endemic area of Ecuador by analyzing the epidemiological and entomological factors involved.Materials and methods: We conducted the epidemiological study of the cases reported in the Salinas canton and the characterization of vector breeding sites through captures of larvae and adult mosquitoes by human capture of resting mosquitoes.Results: We detected 21 cases of malaria with local transmission related to the presence of initial cases in Venezuelan migrant patients and identified Anopheles albimanus as the predominant vector in natural breeding sites such as estuaries, wells, and water channels.Conclusions: We detected an outbreak of malaria triggered by imported cases from Venezuela. Climatic, social, environmental, and ecological conditions have favored the development of the vector maintaining the transmission cycle. Strategies to control imported malaria should be multiple including early case detection and control of productive breeding sites to avoid local transmission.
Malaria en poblaciones con ocupación minera, Colombia, 2012-2018
Authors: Salas Daniela , Sánchez Dora Yurany , Achury Germán , Escobar-Díaz Fabio
Published: June 2021

Introducción. La malaria representa uno de los mayores desafíos de salud pública, principalmente en los países pobres. Ciertas características sociales de Colombia, como la migración, el trabajo informal y la escasez económica, favorecen la minería ilegal. El análisis de la situación de la malaria en estas áreas permite establecer una guía para la prevención, el control y el tratamiento de la enfermedad en los programas de salud pública existentes.Objetivo. Describir la situación de la malaria en las poblaciones mineras colombianas entre el 2012 y el 2018.Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo que incluyó la creación de gráficos y mapas. Para el análisis estadístico se utilizaron la correlación de Pearson y el índice de Moran.Resultados. Entre el 2012 y el 2018, se notificaron 44.032 casos de malaria en la población minera, 43.900 de malaria no complicada y 132 de malaria complicada, así como tres muertes, dos por Plasmodium vivax y una por infección mixta. Hubo una disminución del 44,7 % de los casos en el período evaluado. La tasa de riesgo en el 2012 fue de 2,5 casos por 1.000 habitantes; el 87,3 % de los casos se presentó en hombres y el 37,9 % en personas entre los 20 y los 29 años, en tanto que el 46,7 % de la población estudiada estaba conformada por afrocolombianos. Se encontró una posible correlación lineal positiva moderada entre mayor la actividad minera, mayor el número de casos de malaria en mineros. El índice de Moran global evidenció una agrupación espacial significativa de los casos de malaria en zonas con industria minera en los municipios del Pacífico colombiano.Conclusiones. La disminución en la notificación de casos durante el período evaluado podría atribuirse a un subregistro del Sistema de Vigilancia en Salud Pública (Sivigila), ya que la mayoría de los mineros no tienen trabajos formales, lo que dificulta su acceso a los servicios de salud. Se recomienda un estudio de cohorte en áreas endémicas para establecer una relación directa entre la explotación minera y la presencia de casos de malaria.
Connecting virtual reality and ecology: a new tool to run seamless immersive experiments in R
Authors: Vercelloni Julie , Peppinck Jon , Santos-Fernandez Edgar , McBain Miles , Heron Grace , Dodgen Tanya , Peterson Erin E. , Mengersen Kerrie
Published: June 2021

Virtual reality (VR) technology is an emerging tool that is supporting the connection between conservation research and public engagement with environmental issues. The use of VR in ecology consists of interviewing diverse groups of people while they are immersed within a virtual ecosystem to produce better information than more traditional surveys. However, at present, the relatively high level of expertise in specific programming languages and disjoint pathways required to run VR experiments hinder their wider application in ecology and other sciences. We present R2VR, a package for implementing and performing VR experiments in R with the aim of easing the learning curve for applied scientists including ecologists. The package provides functions for rendering VR scenes on web browsers with A-Frame that can be viewed by multiple users on smartphones, laptops, and VR headsets. It also provides instructions on how to retrieve answers from an online database in R. Three published ecological case studies are used to illustrate the R2VR workflow, and show how to run a VR experiments and collect the resulting datasets. By tapping into the popularity of R among ecologists, the R2VR package creates new opportunities to address the complex challenges associated with conservation, improve scientific knowledge, and promote new ways to share better understanding of environmental issues. The package could also be used in other fields outside of ecology.
Robust proportional overlapping analysis for feature selection in binary classification within functional genomic experiments
Authors: Hamraz Muhammad , Gul Naz , Raza Mushtaq , Khan Dost Muhammad , Khalil Umair , Zubair Seema , Khan Zardad
Published: June 2021

In this paper, a novel feature selection method called Robust Proportional Overlapping Score (RPOS), for microarray gene expression datasets has been proposed, by utilizing the robust measure of dispersion, i.e., Median Absolute Deviation (MAD). This method robustly identifies the most discriminative genes by considering the overlapping scores of the gene expression values for binary class problems. Genes with a high degree of overlap between classes are discarded and the ones that discriminate between the classes are selected. The results of the proposed method are compared with five state-of-the-art gene selection methods based on classification error, Brier score, and sensitivity, by considering eleven gene expression datasets. Classification of observations for different sets of selected genes by the proposed method is carried out by three different classifiers, i.e., random forest, k-nearest neighbors (k-NN), and support vector machine (SVM). Box-plots and stability scores of the results are also shown in this paper. The results reveal that in most of the cases the proposed method outperforms the other methods.
A new pterosaur tracksite from the Lower Cretaceous of Wuerho, Junggar Basin, China: inferring the first putative pterosaur trackmaker
Authors: Li Yang , Wang Xiaolin , Jiang Shunxing
Published: June 2021

We report the discovery of 114 small pterosaur footprints preserved in a greyish-green fine sandstone slab comprising 57 manus imprints and 57 pes imprints. Due to the chaotic distribution of footprints, the trackways are difficult to recognize. The pes imprints are sub-triangular and enlongate, the metatarsal part is roughly subequal to the digital part. The manus imprints are asymmetrical, longer than wide, and the lengths of digits I–III gradually increase. According to the diagnostic features of the Wuerho small pterosaur tracks, the present set was classified as Pteraichnus and is different from the nine reported valid ichnospecies of Pteraichnus. We therefore propose a new ichnospecies, Pteraichnus wuerhoensis isp. nov. The description is based on the anatomical characteristics (lengths of digits I–IV, length of digital part, length of metatarsal part) extracted from the pes imprints and comparisons with the pes bone fossils of Noripterus complicidens. We infer that the footprints were probably left by N. complicidens and the total width of the wings was presumably 2–2.3 m. In addition, the high density (365 per square meter) and varied sizes of the Wuerho small pterosaur tracks suggest that many pterosaurs of different ages lived in Huangyangquan Reservoir tracksite 1 area. Thus the trackmakers may have had gregarious behavior.
Early maternal separation is not associated with changes in telomere length in domestic kittens (Felis catus)
Authors: Delgado Mikel , Buffington C.A. Tony , Bain Melissa , Smith Dana L. , Vernau Karen
Published: June 2021

Objective

Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S).

Results

A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F1, 76.2 = 3.35, p = 0.07), orphan status (F1, 56.5 = 0.44, p = 0.51), time point (F1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.
Changes in the stoichiometry of Castanopsis fargesii along an elevation gradient in a Chinese subtropical forest
Authors: Liu Danping , Zheng Dexiang , Xu Yaoyao , Chen Yifei , Wang Hesong , Wang Ku , Liao Xiaoli , Chen Changxiong , Xia Jiangjiang , Jin Shaofei
Published: June 2021

Elevation is important for determining the nutrient biogeochemical cycle in forest ecosystems. Changes in the ecological stoichiometry of nutrients along an elevation gradient can be used to predict how an element cycle responds in the midst of global climate change. We investigated changes in concentrations of and relationships between nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) in the leaves and roots of the dominant tree species, Castanopsis fargesii, along an elevation gradient (from 500 to 1,000 m above mean sea level) in a subtropical natural forest in China. We analyzed correlations between C. fargesii’s above-ground biomass and stoichiometry with environmental factors. We also analyzed the soil and plant stoichiometry of this C. fargesii population. Our results showed that leaf N decreased while leaf K and Ca increased at higher elevations. Meanwhile, leaf P showed no relationship with elevation. The leaf N:P indicated that C. fargesii was limited by N. Elevation gradients contributed 46.40% of the total variance of ecological stoichiometry when assessing environmental factors. Our research may provide a theoretical basis for the biogeochemical cycle along with better forest management and fertilization for this C. fargesii population.
Numerical Study of the Performance of a Double-Insulated Barbecue Oven: Implication for Energy Savings and Thermal Comfort
Authors: Igo Serge Wendsida , Sawadogo Gaël Lassina , Ouedraogo Drissa , Compaoré Abdoulaye , Namoano David , Bathiébo Joseph Dieudonné
Published: June 2021

This work is devoted to a numerical study of the performance of a double insulated barbecue oven using terracotta bricks and plywood. The numerical methodology is based on the nodal method and the heat transfer equations have been established by performing an energy balance on each node. The equations obtained were then discretized using an implicit finite difference scheme and solved by the Gauss algorithm. The numerical results validated by the experiment show that this double insulation considerably reduces the energy losses through the walls of the oven. However, the addition of plywood does not significantly change the energy savings compared to simple terracotta insulation but does drop the external wall temperatures. Thus, for 4 cm of thickness of terracotta bricks and 1 cm of plywood, the energy savings (compared to the non-insulated oven) are of the order of 70% and the temperature of the outer walls of the oven does not exceed not 60°C, which ensures better thermal comfort for users.
Repercussion of telemonitoring as a self-care strategy for diabetes mellitus people / Repercussão do telemonitoramento como estratégia para o autocuidado às pessoas com diabetes mellitus
Authors: Duarte Cíntia Araujo , Berardinelli Lina Marcia Migueis , Sabóia Vera Maria , Ramos de Oliveira Julianna Pereira , Silva Gabriela Francisco
Published: June 2021

RESUMO Objetivo: analisar as produções científicas sobre o telemonitoramento e suas repercussões no acompanhamento do autocuidado de pessoas com Diabetes Mellitus tipo 2 (DM2). Métodos: trata-se de revisão integrativa da literatura, realizada nas bases de dados BVS (LILACS, BDENF, MEDLINE) e PUBMED nos meses de junho a julho de 2018, com recorte temporal de cinco anos. Resultados: a amostra é constituída de 10 artigos sobre a temática e, a partir de associações temáticas, foi nomeada em duas categorias: repercussão da estratégia telefônica para o autocuidado e estratégia telefônica: controle e eficácia. Conclusão: o uso do telemonitoramento no acompanhamento de pessoas com DM2 teve boa repercussão e serviu como apoio, educação em saúde e monitoramento dos níveis glicêmicos. Dessa forma, houve melhorias no comportamento de saúde e satisfação com o serviço recebido e, com isso, demonstrou eficácia para o autocuidado.
Binding and/or hydrolysis of purine‐based nucleotides is not required for IM30 ring formation
Authors: Siebenaller Carmen , Schlösser Lukas , Junglas Benedikt , Schmidt‐Dengler Martina , Jacob Dominik , Hellmann Nadja , Sachse Carsten , Helm Mark , Schneider Dirk
Published: June 2021

IM30, the inner membrane‐associated protein of 30 kDa, is conserved in cyanobacteria and chloroplasts. Although its exact physiological function is still mysterious, IM30 is clearly essential for thylakoid membrane biogenesis and/or dynamics. Recently, a cryptic IM30 GTPase activity has been reported, albeit thus far no physiological function has been attributed to this. Yet, it is still possible that GTP binding/hydrolysis affects formation of the prototypical large homo‐oligomeric IM30 ring and rod structures. Here, we show that the Synechocystis sp. PCC 6803 IM30 protein in fact is an NTPase that hydrolyzes GTP and ATP, but not CTP or UTP, with about identical rates. While IM30 forms large oligomeric ring complexes, nucleotide binding and/or hydrolysis are clearly not required for ring formation.
The precise magic of CRISPR
Authors: Kondrashov Alexander
Published: June 2021

In this issue of FEBS Open Bio, Shen Li et al., in the laboratory of Hector L. Franco (University of North Carolina), provide a proof‐of‐principle solution for correcting all copies of a gene in the widely used MCF7 breast cancer cell line. The gene for the FOXA1 pioneer transcription factor is localised on chromosome 14, which is present at least 4–5 times in MCF7 cells. To achieve their goal, the authors used a ‘classical’ version of the CRISPR/Cas9 system. Both sgRNA and Cas9 components were expressed from a single vector, which also has a puromycin resistance cassette; this is an essential module for the chosen strategy, because it ensures expression of both sgRNA and Cas9 in selected cells. A targeting template in the form of nonlinearised plasmid was shown to have the best efficiency and was used to introduce a substitution at position 295 in the gene encoding FOXA1 to change a codon encoding lysine into a codon encoding glutamine (K295Q). The strategy suggested by Li and co‐authors is an important development towards genome editing of multiple copy genes in a polyploid environment like cancer cells. One important application of the technique could be in creating models to study the role of single nucleotide polymorphisms in cancer progression and metastasis. Isogenic cancer lines carrying polymorphic variants of key drug targets could be used to optimise anticancer treatment protocols, laying a foundation for personalised therapy.
Retroviral Replication
Authors: Pedersen Finn Skou , Mikkelsen Jacob Giehm
Published: June 2021

Retroviruses, are enveloped animal ribonucleic acid (RNA) viruses that replicate via a deoxyribonucleic acid (DNA) intermediate, which is integrated into the host genome as a provirus. Expression of viral RNA and proteins from proviral DNA utilises the transcription and translation machinery of the host. Retrovirus particles are assembled through protein–protein, protein–RNA and protein–lipid interactions, released from the cell by budding and subsequently matured by a viral protease. Interaction of the viral envelope protein with a target cell receptor triggers entry of the viral nucleoprotein core by fusion of viral and cellular membranes. After entry, the viral enzymes reverse transcriptase and integrase mediate reverse transcription of viral RNA and integration of the resulting double‐stranded DNA copy of the viral genome, respectively. A provirus can be transmitted through the germ line from parents to offspring as an endogenous retrovirus. Multiple steps of retroviral replication can be targeted by host cell restriction factors in a complex interplay of virus–host interactions.

Key Concepts

Reverse transcription and integration into the host genome are hallmarks of retroviral replication.

The viral RNA genome contains a packaging signal for selective encapsidation into viral particles and a binding site for a tRNA primer for initiation of reverse transcription.

The integrated virus contains long‐terminal repeats harbouring signals for transcriptional initiation and polyadenylation, which define the retroviral transcription unit.

Open reading frames for Gag, Pol and Env are found in all retroviruses, but some retroviruses encode additional proteins such as Tat and Rev of HIV‐1.

A stop codon between gag and pol can be bypassed by readthrough or frameshifting during translation of retroviral mRNA to make the Gag–Pol polyprotein.

Retroviruses have specialised strategies for export of unspliced genomic‐length viral RNA from the nucleus.

The metastable retroviral envelope protein drives the fusion of viral and cellular membranes by a type I fusion mechanism to allow retroviral entry in a receptor‐dependent manner.

The retroviral protease is required for maturation of viral particles after their release from producer cells by budding.

A retrovirus can integrate into the genome of germ cells and become part of the genetic material transmitted from parents to offspring.

A provirus can be maintained through species diversification as an endogenous retrovirus that may serve as a marker of phylogenetic relationship and evolutionary distance.

A battery of diverse host cell restriction factors operates at multiple steps of retroviral replication.
Protozoan Pathogens: Identification
Authors: Walochnik Julia , Aspöck Horst
Published: June 2021

The identification of protozoan pathogens is based on direct detection of the respective causative agents in clinical specimens and/or detection of specific immune reactions of the host. Protozoan diagnostics still relies on microscopy; however, in the past years, molecular methods, particularly PCR‐based techniques, have gained more and more importance. One of the big advantages of molecular techniques is that they usually allow identification below the genus level, which is often impossible by light microscopy. Serological tests are of great value in all tissue parasites and generally in most extraintestinal infections, while they only have limited importance in acute infections with short incubation times and in immunocompromised patients. Rapid and easy‐to‐use test systems are available for several important protozoan parasites and serve particularly well in the field setting.

Key Concepts

Of the around 100 protozoan species that can infect humans, some are of prime importance for human health, including the causative agents ofmalaria,amoebiasis,Chagas,leishmaniasisandsleeping sickness.

Several protozoan infections show a more severe progression in theimmunocompromised host, important examples being toxoplasmosis, cryptosporidiosis and visceral leishmaniasis.See also:Protozoan Pathogens of Humans

The size of protozoan pathogens varies from∼2 μm(amastigoteLeishmaniaspp.) to∼150 μm(Balantioides coli).See also:Protozoan Pathogens of Humans

As parasite density in stool or body fluids may vary, the collection ofrepeated samplesis often essential.

Propercollection, storage and transportof clinical specimens are of crucial importance for reliable laboratory diagnostics.

Accurate diagnosis includes both parasitedetectionand speciesidentification(in some cases: genotype/serotype).

In the past years,molecular methodshave gained more and more importance in diagnostics of protozoan infections, and also commercial test systems are now available for most protozoan pathogens.

In some cases,microscopic demonstrationof the causative agent in native material or stained smears remains thegold standard, for example in malaria or in active amoebic dysentery, giardiasis or also trichomoniasis.

Goodmicroscopic expertiseis essential: low parasite density and/or morphologic variability can result in false negative results, while pseudoparasites and artefacts are common causes of false positive results.

In many protozoan taxa, morphology alone does not provide enough information foridentification on or below the species level, which is today mostly based on molecular biological methods.
Renal Mononuclear Phagocytes in Lupus Nephritis
Authors: Davidson Anne
Published: June 2021

Renal mononuclear phagocytes are a highly pleiotropic group of immune cells of myeloid origin that play multiple protective and pathogenic roles in tissue homeostasis, inflammation, repair, and fibrosis. Infiltration of kidneys with these cells is a hallmark of lupus nephritis and is associated with more severe disease and with increased risk of progression to end‐stage renal disease. This review presents current knowledge of the diversity of these cells and their involvement in kidney inflammation and resolution and describes how they contribute to the chronic inflammation of lupus nephritis. A better understanding of the subset heterogeneity and diverse functions of mononuclear phagocytes in the lupus nephritis kidney should provide fertile ground for the development of new therapeutic approaches that promote the differentiation and survival of protective subsets while targeting pathogenic cell subsets that cause inflammation and fibrosis.
Environmental Air Pollution Is a Predictor of Poor Response to Biological Drugs in Chronic Inflammatory Arthritides
Authors: Adami Giovanni , Rossini Maurizio , Viapiana Ombretta , Orsolini Giovanni , Bertoldo Eugenia , Pontalti Marco , Benini Camilla , Fracassi Elena , Giollo Alessandro , Gatti Davide , Fassio Angelo
Published: June 2021

Background

There is increasing evidence that environmental air pollution is associated with the development of chronic inflammatory arthritides (CIA). The role of air pollutants on the biological treatment (biological disease‐modifying antirheumatic drugs [bDMARDs]) response of CIA is still unclear.

Methods

We retrieved longitudinal data on patients affected by CIA on biological therapies and on the daily concentration of air pollutants in the Verona area. We designed a case‐crossover study to compare the exposure to pollutants in the 60‐day period preceding a drug switch or swap due to disease progression referent to the 60‐day period preceding a visit with stable treatment for at least 6 months.

Results

A total of 1257 patients with CIA (863 with rheumatoid arthritis, 256 with psoriatic arthritis, and 138 with ankylosing spondylitis) with 5454 follow‐up visits were included in the study (median follow‐up 2.09 years [interquartile range: 0.82‐2.58 years]). A total of 282 patients were included in the case‐crossover study. We retrieved 13 636 daily air pollution records. We found that air pollutants’ concentrations were higher in the 60‐day period before a failure of bDMARD response and prior to a switch or swap compared with the period preceding a visit with stable bDMARD therapy for at least 6 months.

Conclusion

We found that environmental air pollution was a determinant of poor response to bDMARDs in a cohort of patients with CIA followed over a 5‐year period. An intervention aimed at decreasing fossil combustion emissions might have beneficial effects on biologic persistence rates of patients with CIA and economic expenditures related to switches and swaps.
Eligibility traces and forgetting factor in recursive least‐squares‐based temporal difference
Authors: Baldi Simone , Zhang Zichen , Liu Di
Published: June 2021

We propose a new reinforcement learning method in the framework of Recursive Least Squares‐Temporal Difference (RLS‐TD). Instead of using the standard mechanism of eligibility traces (resulting in RLS‐TD()), we propose to use the forgetting factor commonly used in gradient‐based or least‐square estimation, and we show that it has a similar role as eligibility traces. An instrumental variable perspective is adopted to formulate the new algorithm, referred to as RLS‐TD with forgetting factor (RLS‐TD‐f). An interesting aspect of the proposed algorithm is that it has an interpretation of a minimizer of an appropriate cost function. We test the effectiveness of the algorithm in a Policy Iteration setting, meaning that we aim to improve the performance of an initially stabilizing control policy (over large portion of the state space). We take a cart‐pole benchmark and an adaptive cruise control benchmark as experimental platforms.
Multi‐State Heterojunction Transistors Based on Field‐Effect Tunneling–Transport Transitions
Authors: Lim Dong Un , Jo Sae Byeok , Kang Joohoon , Cho Jeong Ho
Published: June 2021

A monolithic ternary logic transistor based on a vertically stacked double n‐type semiconductor heterostructure is presented. Incorporation of the organic heterostructure into the conventional metal‐oxide‐semiconductor field‐effect transistor (MOSFET) architecture induces the generation of stable multiple logic states in the device; these states can be further optimized to be equiprobable and distinctive, which are the most desirable and requisite properties for multivalued logic devices. A systematic investigation reveals that the electrical properties of the device are governed by not only the conventional field‐effect charge transport but also the field‐effect charge tunneling at the heterointerfaces, and thus, an intermediate state can be finely tuned by independently controlling the transition between the onsets of these two mechanisms. The achieved device performance agrees with the results of a numerical simulation based on a pseudo‐metal–insulator–metal model; the obtained findings therefore provide rational criteria for material selection in a simple energetic perspective. The operation of various ternary logic circuits based on the optimized multistate heterojunction transistors, including the NMIN and NMAX gates, is also demonstrated.
SPOP and OTUD7A Control EWS–FLI1 Protein Stability to Govern Ewing Sarcoma Growth
Authors: Su Siyuan , Chen Jianfeng , Jiang Yao , Wang Ying , Vital Tamara , Zhang Jiaming , Laggner Christian , Nguyen Kong T. , Zhu Zhichuan , Prevatte Alex W. , Barker Natalie K. , Herring Laura E. , Davis Ian J. , Liu Pengda
Published: June 2021

Chromosomal translocation results in development of an Ewing sarcoma breakpoint region 1‐Friend leukemia integration 1 (EWS–FLI1) fusion oncogene in the majority of Ewing sarcoma. The persistent dependence of the tumor for this oncoprotein points to EWS–FLI1 as an ideal drug target. Although EWS–FLI1 transcriptional targets and binding partners are evaluated, the mechanisms regulating EWS–FLI1 protein stability remain elusive. Speckle‐type POZ protein (SPOP) and OTU domain‐containing protein 7A (OTUD7A) are identified as the bona fide E3 ligase and deubiquitinase, respectively, that control EWS–FLI1 protein turnover in Ewing sarcoma. Casein kinase 1‐mediated phosphorylation of the VTSSS degron in the FLI1 domain enhances SPOP activity to degrade EWS–FLI1. Opposing this process, OTUD7A deubiquitinates and stabilizes EWS–FLI1. Depletion of OTUD7A in Ewing sarcoma cell lines reduces EWS–FLI1 protein abundance and impedes Ewing sarcoma growth in vitro and in mice. Performing an artificial‐intelligence‐based virtual drug screen of a 4‐million small molecule library, 7Ai is identified as a potential OTUD7A catalytic inhibitor. 7Ai reduces EWS–FLI1 protein levels and decreases Ewing sarcoma growth in vitro and in a xenograft mouse model. This study supports the therapeutic targeting of OTUD7A as a novel strategy for Ewing sarcoma bearing EWS–FLI1 and related fusions, and may also be applicable to other cancers dependent on aberrant FLI1 expression.
Health‐related quality of life with fixed‐duration venetoclax‐obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 CLL14 trial
Authors: Al‐Sawaf Othman , Gentile Brittany , Devine Jacob , Zhang Can , Sail Kavita , Tandon Maneesh , Fink Anna‐Maria , Kutsch Nadine , Wendtner Clemens‐Martin , Eichhorst Barbara , Hallek Michael , Fischer Kirsten
Published: June 2021

Chronic lymphocytic leukemia (CLL)‐related symptoms impair the well‐being of patients, making improvement of health‐related quality of life (QoL) a goal of treatment. The CLL14 trial demonstrated higher efficacy of fixed‐duration venetoclax‐obinutuzumab (Ven‐Obi) compared to chlorambucil‐obinutuzumab (Clb‐Obi) in patients with previously untreated CLL. To assess patients' QoL, the following patient‐reported outcomes (PRO) measures were assessed: the M.D. Anderson Symptom Inventory (MDASI) core instrument and CLL module and the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ‐C30). At treatment start, physical functioning (mean 75.9 [standard deviation (SD) ± 20.1] in the Clb‐Obi arm and 76.9 [±19.4] in the Ven‐Obi arm), role functioning (73.6 [±27.86] and 72.6 [±26.9]) and GHS/QoL (63.6 [±21.0] and 60.3 [±20.5]) were comparable between treatment arms per EORTC QLQ‐C30 scale scores. Baseline levels of physical and role functioning were maintained throughout treatment and follow‐up, with no relevant improvement or deterioration. On average, patients treated with Ven‐Obi showed a meaningful improvement of GHS/QoL during treatment and follow‐up by at least eight points at cycle three, whereas improvement was delayed until cycle eight with Clb‐Obi. According to MDASI scores, CLL symptoms (1.5 [±1.2] and 1.6 [±1.3]), core cancer symptoms (1.5 [±1.4] and 1.8 [±1.7]) and symptom interference (2.1 [±2.3] and 2.3 [±2.3]) were generally low and comparable between treatment arms at baseline and were maintained throughout treatment and follow‐up. This analysis demonstrates that the higher efficacy of Ven‐Obi is not associated with QoL impairment and that Ven‐Obi achieves early relief of CLL‐related symptoms in elderly unfit patients.
Thermal‐Responsive Polyoxometalate–Metalloviologen Hybrid: Reversible Intermolecular Three‐Component Reaction and Temperature‐Regulated Resistive Switching Behaviors
Authors: Huang You‐Ren , Lin Xiang‐Ling , Chen Bin , Zheng Hui‐Dong , Chen Zhi‐Rong , Li Hao‐Hong , Zheng Shou‐Tian
Published: June 2021

The development of new‐type memristors with special performance is of great interest. Herein, an inorganic‐organic hybrid crystalline polyoxometalate (POM) with usual dynamic structures is reported and used as active material for fabricating memristor with unique temperature‐regulated resistive switching behaviors. The hybrid POM not only exhibits tunable thermochromic properties, but also thermal‐induced reversible aggregation and disaggregation reactions, leading to reversible structural transformations in SCSC fashion. Further, the memory device using the hybrid POM as active layer exhibits uncommon performance, which can keep resistive switching silent in the low temperature range of 30–150 °C, but show nonvolatile memory behavior in the high temperature range of 150–270 °C. Particularly, the silent and working states at three special temperatures (30, 150 and 270 °C) can be monitored by chromism. The correlation between structure and resistive switching property of the material has been discussed. The work demonstrates that crystalline inorganic‐organic hybrid POMs are promising materials for making memristors with superior performance.
Decatungstate‐Mediated C(sp3)–H Heteroarylation via Radical‐Polar Crossover in Batch and Flow
Authors: Wan Ting , Capaldo Luca , Laudadio Gabriele , Nyuchev Alexander V. , Rincón Juan A. , García‐Losada Pablo , Mateos Carlos , Frederick Michael O. , Nuño Manuel , Noël Timothy
Published: June 2021

Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp3)–H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical–polar crossover concept to access the direct net‐oxidative C(sp3)–H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous‐flow reactor technology. The developed protocol is also amenable to the late‐stage functionalization of biologically relevant molecules such as stanozolol, (−)‐ambroxide, podophyllotoxin, and dideoxyribose.
Zeolitic imidazolate frameworks (ZIF‐8, ZIF‐67, and ZIF‐L) for hydrogen production
Authors: Abdelhamid Hani Nasser
Published: June 2021

Hydride materials have good performance for hydrogen (H2) gas storage and release. The release of H2 gas from hydrides via the hydrolysis process can be improved or controlled using a catalyst. Herein, benzoic acid (BA) and hexamethylenetetramine (HMTA) modulate the synthesis of hierarchical porous zeolitic imidazolate framework‐8 (HFZIF‐8, Zn‐based metal organic frameworks [MOFs]), ZIF‐67 (Co‐based MOFs), and leaf‐like ZIF (ZIF‐L). The mechanistic study for the synthesis procedure of ZIF‐8 revealed an in situ synthesis of zinc hydroxide nitrate nanosheets (100‐ to 150‐nm thickness) with an interplanar distance of 0.97 nm between the layers of zinc hydroxide, Zn5(OH)82+. X‐ray diffraction (XRD) data indicated that benzoate ions replaced nitrate ions (2NO3−) between Zn5(OH)82+ layers leading to an increase in the interplanar distance (from 0.97 nm to 1.9 nm). Zinc hydroxide benzoate nanosheets showed a fast conversion into HPZIF‐8 at room temperature. The concentration of BA and HMTA tuned the porosity of HPZIF‐8, offering a hierarchical micropore–mesopore structure. The prepared materials increased the hydrolysis rate of sodium borohydride. ZIF‐8 and ZIF‐67 prepared using BA showed high catalytic performance in terms of efficiency and reaction time compared with other materials. The result's findings open new avenues for the synthesis of adequate materials for hydrogen generation via the hydrolysis of hydrides.
Exploring the functional relation of magnetic density and magnetocaloric effect based on a dinuclear system
Authors: Liu Zi‐Yuan , Huang Xu‐Ke , Chen Zi‐Lu , Liu Dong‐Cheng , Zou Hua‐Hong , Liang Fu‐Pei
Published: June 2021

Molecular magnetic refrigerating material is a kind of green and environmentally friendly materials, which achieve the purpose of cooling by its magnetocaloric effect. Magnetic density is crucial to the magnetocaloric effect of the complexes, and it is usually described by the parameters of Mw/NGd or metal/ligand mass ratio, which represents the content of Gd (III) in the complexes. In order to establish the functional relation between these parameters and magnetocaloric effect, doping is a credible method without changing the coordination environment of the system, which is realized by the process of increasing Gd (III) gradually in the diamagnetic complex. Hence, a diamagnetic dinuclear Y2, four doped samples Gd0.24Y1.76, Gd0.51Y1.49, Gd1.04Y0.96, and Gd1.46Y0.54, and a pure dinuclear Gd2 were synthesized and characterized. Through the measurement of magnetic properties and data fitting, the functional relations were obtained between these parameters and −ΔSm in this dinuclear system. It is the first time that the relationships are set up via experimental design, and it will contribute to observation and comprehension of how magnetic density affects the magnetocaloric effect. In addition, the −ΔSm of dinuclear Gd2 is 29.96 J kg−1 K−1, which is higher than most of the reported dinuclear Gd (III)‐based complexes.