bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental Liver Metastasis Mouse Model Suitable for Short and Long‐Term Intravital Imaging
Authors: Marvin Dieuwke L. , ten Dijke Peter , Ritsma Laila
Published: May 2021

The liver is a frequent site of cancer metastasis, but current treatment options for cancer patients with liver metastasis are limited, resulting in poor prognosis. Colonization of the liver by cancer cells is a multistep and temporally controlled process. Investigating this process in biological relevant settings in a dynamic manner may lead to new therapeutic avenues. Experimental mouse models of liver metastasis combined with high‐resolution microscopy methods can facilitate study of the mechanisms that underlie the outgrowth of cancer cells in the liver. Intravital imaging can provide information on the behavior of tumor cells in their biological setting, in time frames of hours to days. In this unit, we describe the experimental induction of liver metastasis through administration of cancer cells into mice via mesenteric vein injection. The behavior of these injected cells can then be studied using intravital imaging by surgical exposure or through an abdominal imaging window. The approach is described for use with an upright multiphoton microscope, making it widely applicable. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Inducing liver metastasis through mesenteric vein injection

Basic Protocol 2: Short‐term imaging of tumor cells in mouse liver

Basic Protocol 3: Long‐term imaging of tumor cells in mouse liver using an abdominal imaging window
Recovering Individual Genomes from Metagenomes Using MaxBin 2.0
Authors: Wu Yu‐Wei , Singer Steven W.
Published: May 2021

It is critical to identify individual genomes from microbiomic samples in order to carry out analysis of the microbes. Methods based on existing databases, however, may have limited capabilities in elucidating and quantifying the microbes due to the largely unidentified microbial species in natural or human‐associated environments. We thus developed a database‐free method, MaxBin 2.0, to aid in the process of recovering microbial genomes from metagenomes in a de novo manner. The recovery of individual genomes allows analysis of the microbiome in terms of a collection of microbial genomes so that one can understand the functional roles of each species. The data of individual microbes may then be analyzed collectively to untangle the interactions between different microbial organisms. By reporting the genome abundance information for co‐assembled metagenomes, one may also identify which microorganisms dominate the microbiome and which species may co‐occur from the MaxBin 2.0 results. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Recovering genomes from one shotgun metagenome with coverage information

Basic Protocol 2: Recovering genomes from one shotgun metagenome without coverage information

Basic Protocol 3: Recovering genomes given multiple shotgun metagenomes with coverage information for each metagenome

Basic Protocol 4: Recovering genomes given multiple shotgun metagenomes without coverage information

Support Protocol 1: MaxBin installation

Support Protocol 2: Assembling and co‐assembling NGS reads
Direct CatalyticN‐Alkylation of α‐Amino Acid Esters and Amides Using Alcohols with High Retention of Stereochemistry
Authors: Yan Tao , Feringa Ben L. , Barta Katalin
Published: May 2021

The direct functionalization of naturally abundant chiral scaffolds such as α‐amino acid esters or amides with widely abundant alcohols, without any racemization, is a demanding transformation that is of central importance for the synthesis of bio‐active compounds. Herein a robust and general method was developed for the directN‐alkylation of α‐amino acid esters and amides with alcohols. This powerful ruthenium‐catalyzed methodology is atom‐economic, base‐free, and allowed for excellent retention of stereochemical integrity. The use of diphenylphosphate as additive was crucial for significantly enhancing reactivity and product selectivity. Notably, the only by‐product was water and both substrates could be potentially derived from renewable resources.
Non‐Flammable and Highly Concentrated Carbonate Ester‐Free Electrolyte Solutions for 5 V‐Class Positive Electrodes in Lithium‐Ion Batteries
Authors: Doi Takayuki , Taccori Romain Jun , Fujii Ryo , Nagashima Tsuyoshi , Endo Takatsugu , Kimura Yoshifumi , Inaba Minoru
Published: May 2021

Non‐flammable and highly concentrated electrolyte solutions were designed using tris(2,2,2‐trifluoroethyl) phosphate (TFEP) as a main solvent toward a radical improvement in the safety and energy density of lithium‐ion batteries. Unlike conventional carbonate ester‐based solutions, simple TFEP‐based electrolyte solutions were not intrinsically compatible with 5 V‐class LiNi0.5Mn1.5O4 positive electrodes, even at high concentrations. Based on the degradation mechanism that was analyzed by Raman spectroscopy, scanning electron microscopy/energy dispersive X‐ray spectroscopy, and X‐ray photoelectron spectroscopy, a fluorinated diluent of methyl 3,3,3‐trifluoropropionate (FMP) was introduced to suppress the decomposition of LiBF4 and TFEP at high potentials. A nearly saturated LiBF4/TFEP+FMP electrolyte solution with a specific composition improved the charge and discharge performance of a LiNi0.5Mn1.5O4 electrode, and the solution structure was studied by pulsed‐field‐gradient NMR spectroscopy.
Crystal Phase Effects on the Gas‐Phase Ketonization of Small Carboxylic Acids over TiO2 Catalysts
Authors: Fufachev Egor V. , Weckhuysen Bert M. , Bruijnincx Pieter C. A.
Published: May 2021

The choice of TiO2 crystal phase (i. e., anatase, rutile, or brookite) greatly influences catalyst performance in the gas‐phase ketonization of small volatile fatty acids, such as acetic acid and propionic acid. Rutile TiO2 was found to perform best, combining superior activity, as exemplified by an exceptional reaction rate of 141.8 mmol h−1 gcat−1 (at 425 °C and 24 h−1) with excellent ketone selectivity when propionic acid was used. Brookite, to the best of our knowledge never reported before as a viable ketonization catalyst, was found to outperform the well‐studied anatase phase, but not rutile. Operando Fourier‐transform IR spectroscopy measurements combined with on‐line mass spectrometry showed that bidentate carboxylates were the most abundant surface species on the rutile and brookite surfaces, while on anatase both monodentate and bidentate carboxylates co‐existed. The bidendate carboxylates were thought to be precursors to the active ketonization species, likely monodentate intermediates more prone to C−C coupling. Ketonization activity did not directly correlate with acidity; the observed, strong crystal phase effect did suggest that ketonization activity is influenced strongly by geometrical factors that determine the ease of formation of the relevant surface intermediates.
Novel high‐affinity EGFRvIII‐specific chimeric antigen receptor T cells effectively eliminate human glioblastoma
Authors: Abbott Rebecca C , Verdon Daniel J , Gracey Fiona M , Hughes‐Parry Hannah E , Iliopoulos Melinda , Watson Katherine A , Mulazzani Matthias , Luong Kylie , D’Arcy Colleen , Sullivan Lucy C , Kiefel Ben R , Cross Ryan S , Jenkins Misty R
Published: May 2021

Objectives

The increasing success of Chimeric Antigen Receptor (CAR) T cell therapy in haematological malignancies is reinvigorating its application in many other cancer types and with renewed focus on its application to solid tumors. We present a novel CAR against glioblastoma, an aggressive, malignant glioma, with a dismal survival rate for which treatment options have remained unchanged for over a decade.

Methods

We use the human Retained Display (ReD) antibody platform (Myrio Therapeutics) to identify a novel single‐chain variable fragment (scFv) that recognises epidermal growth factor receptor mutant variant III (EGFRvIII), a common and tumor‐specific mutation found in glioblastoma. We use both in vitro functional assays and an in vivo orthotopic xenograft model of glioblastoma to examine the function of our novel CAR, called GCT02, targeted using murine CAR T cells.

Results

Our EGFRvIII‐specific scFv was found to be of much higher affinity than reported comparators reverse‐engineered from monoclonal antibodies. Despite the higher affinity, GCT02 CAR T cells kill equivalently but secrete lower amounts of cytokine. In addition, GCT02‐CAR T cells also mediate rapid and complete tumor elimination in vivo.

Conclusion

We present a novel EGFRvIII‐specific CAR, with effective antitumor functions both in in vitro and in a xenograft model of human glioblastoma.
Hybrid communication architecture in VANETs via named data network
Authors: Raissi Khadija , Ben Gouissem Bechir
Published: May 2021

The limitations of the transmission control protocol/Internet protocol (TCP/IP) model have given birth to a new futuristic trend called named data networking (NDN), focusing on retrieving the desired data by using content names instead of host addresses. In this context, we proposed another NDN architecture named hybrid communication in vehicular ad hoc networks (VANETs) via named data network (HCIV‐NDN) to reduce packet loss, eliminate the unnecessary message exchange, and to assume that in one cluster not all receivers nodes rebroadcast. Also, it investigates the NDN concept to vehicle to road side unit (V2R), vehicle‐to‐vehicle (V2V), and road side unit to infrastructure (R2I) plus vehicle‐to‐infrastructure (V2I) communications to enlarge the connectivity of vehicles. The vehicles are clustered and can communicate with the base station, with road side unit (RSU), and among them to define a new data dissemination protocol. Hence, the HCIV‐NDN mechanism applies two types of timers to select some farthest nodes as forwarder to rebroadcast packets at different times. Thus, we study the performance of our HCIV‐NDN with node density effects for smart cities and then we compare it with the existing location‐based deferred broadcast (LBDB) scheme. Simulation results exhibited that HCIV‐NDN scheme achieves more than 90% in terms of the cache‐hit ratio when the percent of consumers interested in the same data is about 50%. Then it performs better than LBDB in terms of satisfaction ratio, packet loss ratio, and the average delay in a suburban scenario.
Review of opportunistic network: Assessing past, present, and future
Authors: Sachdeva Rahul , Dev Amita
Published: May 2021

Opportunistic networks aim to deal with the unpredictable environment for data communication. Messages in opportunistic networks need to be stored with the node in the absence of any suitable forwarder. With such a store‐carry‐forward paradigm, it aims to eliminate challenges of no pre‐determined/fixed connectivity, absence of direct/in‐direct routes from source to destination, and high error rate and delay in the network. Node carrying message roams in the network to find a suitable forwarding node. In this study, the survey for various routing protocols and mobility models for opportunistic networks is discussed along with tools available for simulations of opportunistic networks. Further, various challenges in opportunistic networks such as storage management, congestion management, and energy constraints are discussed. Many applications for the opportunistic network, along with real‐time case study, are presented in the paper. The objective of the study is to provide future direction to the researchers, along with the systematic review. Hence, future objectives are discussed to mitigate the challenges faced in the current scenario. Also, based upon the study, it is observed that most researchers have taken epidemic, ProPHET, and spray and wait routing protocols as their base of study. Performance analysis for these protocols is done using opportunistic network environment (ONE) simulator.
Cytological features of a complete hydatidiform mole in a cervicovaginal smear: A case report
Authors: Naveed Hania , Yaqoob Nausheen , Kiran Ayesha , Hasan Sheema Habib Ul
Published: May 2021

Exfoliated trophoblastic cells can be seen in a cervicovaginal smear in cases of normal pregnancy or gestational trophoblastic disease (GTD) and can mimic high‐grade squamous intraepithelial lesion (HSIL) or malignancy. Although they appear highly anaplastic, cytological features such as high nuclear to cytoplasmic ratio, irregular nuclear contours and scanty basophilic cytoplasm admixed with cytologically benign squamoid and endocervical cells can aid in differentiating them from malignant cells. We present a case of a 37‐year‐old woman with abnormal uterine bleeding for 3‐months. There was no history of recent pregnancy or previous GTD. Her cervicovaginal smear showed a hypercellular smear exhibiting cytologically benign superficial and intermediate squamous cells along with clusters of benign endocervical cells with interspersed mononucleate cells. These mononucleate cells were large, with a hyperchromatic, pleomorphic nuclei, and scant basophilic cytoplasm. Cytological features were suggestive of trophoblastic cells and workup for pregnancy and GTD was advised. Her laboratory investigations showed markedly raised levels of β human chorionic gonadotropins (β‐HCG) and ultrasound showed a uterine mass with snowstorm appearance. A uterine evacuation was performed after which histopathological examination showed microscopic features consistent with a complete hydatidiform mole. The rare presence of trophoblastic cells in a cervicovaginal smear can easily be confused with malignant cells and can be misleading to the pathologist. Trophoblastic cells should always be kept in mind when evaluating a cytology smear of a young patient irrespective of gestational status.
Ultrasound‐guided fine needle aspiration cytology of angiosarcoma of head and neck: a review of cytomorphologic features and discussion of diagnostic pitfall of aspiration cytology of vascular lesions
Authors: Khandakar Binny , Chen Hua
Published: May 2021

Angiosarcoma is a rare malignant tumor of vascular origin (<2% of sarcomas). It represents <1% of all head‐neck malignancies. A cytological diagnosis on fine needle aspiration (FNA) is extremely difficult. Most tumors yield a predominantly hemorrhagic aspirate with only rare neoplastic cells, a diagnostic pitfall of aspiration cytology of vascular lesions. An 81‐year‐old male, 2 years status post resection of a nasal tip angiosarcoma and adjuvant radiation therapy, presented to another institution with an enlarging left neck mass of 2 months duration. Outside FNA diagnosis of cyst was made. Patient was referred to our institution for a pathologist‐performed ultrasound‐guided FNA. Ultrasound examination revealed a hypoechoic cystic left neck mass. Direct smears showed blood with occassional single malignant spindled to epithelioid cells, with some cells showing “spider‐leg” like cytoplasmic processes/projections and “tadpole/fiber” like morphology. Immunohistochemistry performed on cell block sections revealed the tumor cells to be positive for D2‐40, CD31 and CD34, supported a diagnosis of regional recurrent angiosarcoma. Left neck dissection showed recurrent high‐grade angiosarcoma infiltrating periparotid soft tissues and metastatic angiosarcoma involving multiple lymph nodes. A diagnosis of angiosarcoma on FNA samples can be challenging, as the aspirate may contain only rare tumor cells hidden in a background of abundant blood. Such cases require careful screening to avoid an incorrect diagnosis of inadequate or cyst contents. This short review highlights key cytomorphologic features of angiosarcoma, includes novel cytologic features of angiosarcoma which has not been described previously and also discusses challenges and diagnostic pitfalls of FNA of vascular lesions.
Quality of father–child relationships as a predictor of sleep developments during preschool years
Authors: Tétreault Émilie , Bernier Annie , Matte‐Gagné Célia
Published: May 2021

Substantial developmental changes in sleep occur during the preschool period, but few studies have investigated the factors that forecast these developments. The aim of this study was to examine whether three aspects of father–child relationships in toddlerhood predicted individual differences in developmental patterns of change in five actigraphy‐derived sleep variables during the preschool period (N = 67; sleep assessed yearly between 2 and 4 years). In a predominantly White and middle‐to‐higher income sample, paternal mind‐mindedness and quality of father–child interactions were assessed during father–child free play at 18 months and fathers self‐reported on their involvement in childrearing at age 2. Multilevel growth modeling revealed that children whose father made more mind‐related comments during father–child interactions had a higher proportion of sleep taking place during nighttime as well as shorter daytime and total sleep duration at 2 years. This was, however, followed by a relative leveling off (i.e., less rapid change) of these sleep features between 2 and 4 years. Given previous studies documenting that nighttime sleep proportion increases while daytime and total sleep duration decrease during preschool years, the findings suggest that children who are exposed to more paternal mind‐mindedness may reach more mature sleep patterns earlier in development.
EPO transgene detection in dried blood spots for antidoping application
Authors: Marchand Alexandre , Roulland Ingrid , Semence Florian , Ericsson Magnus
Published: May 2021

The modification of gene expression to treat diseases is a field of research with exponential growth. As doping in sport closely follows emerging therapies, a surveillance of the modification of gene expression to enhance performance is needed. The gene coding for erythropoietin (EPO) is one target of interest. Since 2010, several protocols have been proposed to identify EPO gene doping by focusing on the presence in blood of a transgene that differ in size from the endogenous gene sequence, normally found in the human DNA. In this work, our aim was to validate an easily applicable method for EPO gene doping detection in dried blood spots (DBS). We evaluated the detection of EPO transgene in 20‐μl DBS after the spike of a plasmid carrying the EPO transgene in whole blood. Three different DBS were compared: Nucleic‐Card™, Whatman® 903, and the volumetric 20‐μl VAMS™. Detection was performed with real‐time polymerase chain reaction (PCR) and validated with two Taqman assays (one commercial and one custom) specific for the EPO transgene. The initial testing procedure could be done using one assay (custom) and the confirmation using the second one (commercial Taqman) with a final check of the size of the PCR product. Starting from 20‐μl dried blood, 1000 copies of EPO transgene could efficiently be detected with the three types of DBS, VAMS showing a slightly better sensitivity. No loss of sensitivity was observed after 1‐month storage of DBS at room temperature. This method could be applied to DBS collected during doping controls and allows reanalysis.
Demographic and ecogeographic factors limit wild grapevine spread at the southern edge of its distribution range
Authors: Rahimi Oshrit , Ohana‐Levi Noa , Brauner Hodaya , Inbar Nimrod , Hübner Sariel , Drori Elyashiv
Published: May 2021

The spatial distribution of plants is constrained by demographic and ecogeographic factors that determine the range and abundance of the species. Wild grapevine (Vitis vinifera ssp. sylvestris) is distributed from Switzerland in the north to Israel in the south. However, little is known about the ecogeographic constraints of this species and its genetic and phenotypic characteristics, especially at the southern edge of its distribution range in the Levant region. In this study, we explore the population structure of southern Levantine wild grapevines and the correlation between demographic and ecogeographic characteristics. Based on our genetic analysis, the wild grapevine populations in this region can be divided into two major subgroups in accordance with a multivariate spatial and ecogeographical clustering model. The identified subpopulations also differ in morphological traits, mainly leaf hairiness which may imply adaptation to environmental stress. The findings suggest that the Upper Jordan River population was spread to the Sea of Galilee area and that a third smaller subpopulation at the south of the Golan Heights may represent a distinguished gene pool or a recent establishment of a new population. A spatial distribution model indicated that distance to water sources, Normalized difference vegetation index, and precipitation are the main environmental factors constraining V. v. sylvestris distribution at its southern distribution range. These factors in addition to limited gene flow between populations prevent further spread of wild grapevines southwards to semi‐arid regions.
Challenges and opportunities for comparative studies of survival rates: An example with male pinnipeds
Authors: Brusa Jamie L. , Rotella Jay J. , Banner Katharine M. , Hutchins Patrick R.
Published: May 2021

Survival rates are a central component of life‐history strategies of large vertebrate species. However, comparative studies seldom investigate interspecific variation in survival rates with respect to other life‐history traits, especially for males. The lack of such studies could be due to the challenges associated with obtaining reliable datasets, incorporating information on the 0–1 probability scale, or dealing with several types of measurement error in life‐history traits, which can be a computationally intensive process that is often absent in comparative studies. We present a quantitative approach using a Bayesian phylogenetically controlled regression with the flexibility to incorporate uncertainty in estimated survival rates and quantitative life‐history traits while considering genetic similarity among species and uncertainty in relatedness. As with any comparative analysis, our approach makes several assumptions regarding the generalizability and comparability of empirical data from separate studies. Our model is versatile in that it can be applied to any species group of interest and include any life‐history traits as covariates. We used an unbiased simulation framework to provide “proof of concept” for our model and applied a slightly richer model to a real data example for pinnipeds. Pinnipeds are an excellent taxonomic group for comparative analysis, but survival rate data are scarce. Our work elucidates the challenges associated with addressing important questions related to broader ecological life‐history patterns and how survival–reproduction trade‐offs might shape evolutionary histories of extant taxa. Specifically, we underscore the importance of having high‐quality estimates of age‐specific survival rates and information on other life‐history traits that reasonably characterize a species for accurately comparing across species.
Microhabitat distribution of aquatic oligochaete communities in the Western Balkans peat bog
Authors: Brigić Andreja , Alegro Antun , Gottstein Sanja , Kerovec Mladen
Published: May 2021

Peat bog pools are rare and fragmented in the Western Balkans. Thus, aquatic macroinvertebrate diversity and the implications for microhabitat loss in these ecosystems are poorly known. Aquatic oligochaetes, widely used as indicators, were sampled using a benthos net in the largest and oldest Croatian bog, in four main water body types: a pond, a deep pool, a shallow pool and a ditch. As these microhabitats lack spatial replication both in the studied bog and in the region, we applied a nested study design with replicates sampled over time. We found a species‐rich aquatic oligochaete fauna, with 11 taxa recorded. Oligochaete communities were strongly affected by vegetation complexity and the morphology of bog water bodies, namely, their size and depth. As revealed by generalised linear mixed models (GLMMs), taxon richness and abundance were significantly higher in the ditch than in other water body types. This could be attributed to the vegetation complexity, supporting many different niches and providing allochthonous food supplies for oligochaetes. The various bog pools contribute to regional biodiversity and promote distinct patterns in the spatial distribution of oligochaetes. However, the predominance of ubiquitous oligochaetes, with high taxon richness, might indicate the degradation of the studied peat bog. This was further confirmed by the spread of vascular plants to the bog area and higher pH water values. All these warning signals suggest that hydro‐ecological conditions should be urgently improved in order to preserve communities in the bog studied.
Non‐additive effects of foundation species determine the response of aquatic ecosystems to nutrient perturbation
Authors: Lürig Moritz D. , Narwani Anita , Penson Hannele , Wehrli Bernhard , Spaak Piet , Matthews Blake
Published: May 2021

Eutrophication is a persistent threat to aquatic ecosystems worldwide. Foundation species, namely those that play a central role in the structuring of communities and functioning of ecosystems, are likely important for the resilience of aquatic ecosystems in the face of disturbance. However, little is known about how interactions among such species influence ecosystem responses to nutrient perturbation. Here, using an array (N = 20) of outdoor experimental pond ecosystems (15,000 L), we manipulated the presence of two foundation species, the macrophyte Myriophyllum spicatum and the mussel Dreissena polymorpha, and quantified ecosystem responses to multiple nutrient disturbances, spread over two years. In the first year, we added five nutrient pulses, ramping up from 10 to 50 μg P/L over a 10‐week period from mid‐July to mid‐October, and in the second year, we added a single large pulse of 50 μg P/L in mid‐October. We used automated sondes to measure multiple ecosystems properties at high frequency (15‐minute intervals), including phytoplankton and dissolved organic matter fluorescence, and to model whole‐ecosystem metabolism. Overall, both foundation species strongly affected the ecosystem responses to nutrient perturbation, and, as expected, initially suppressed the increase in phytoplankton abundance following nutrient additions. However, when both species were present, phytoplankton biomass increased substantially relative to other treatment combinations: non‐additivity was evident for multiple ecosystem metrics following the nutrient perturbations in both years but was diminished in the intervening months between our perturbations. Overall, these results demonstrate how interactions between foundation species can cause surprisingly strong deviations from the expected responses of aquatic ecosystems to perturbations such as nutrient additions.
Environmental DNA detection of the giant freshwater crayfish (Astacopsis gouldi)
Authors: Trujillo‐Gonzalez Alejandro , Hinlo Rheyda , Godwin Sam , Barmuta Leon A. , Watson Anne , Turner Perpetua , Koch Amy , Gleeson Dianne
Published: May 2021

The giant freshwater crayfish, Astacopsis gouldi Clark, 1936, is an endangered endemic freshwater species native to Northern Tasmania. Habitat loss, fishing pressure, and climate change have been identified as threatening processes. The Australian government approved a recovery plan for A. gouldi in 2017 that requires routine population surveys to assess the impact of ongoing threats and recovery actions. We developed a novel species‐specific probe‐based assay targeting a 219 bp fragment in the Cytochrome Oxidase 1 gene region to detect traces of A. gouldi DNA in environmental samples as a cost‐effective, sensitive, and non‐invasive surveillance method to assess the presence of this endangered species. We tested assay specificity against ten crayfish species commonly found in Tasmania within the Astacopsis, Cherax, Geocharax, Engaeus, and Ombrastacoides genera and determined assay sensitivity using tissue‐derived genomic DNA and synthetic oligo standards designed for A. gouldi. We then tested water samples collected from aquaria and natural freshwater streams in Northern Tasmania with known occurrence of A. gouldi, as well as one site with no known A. gouldi occurrence. The probe‐based assay designed in this study successfully detected A. gouldi DNA and eDNA with a 10 copies/µl limit of detection and showed no amplification of non‐targeted co‐existing crayfish species. We successfully detected the presence of A. gouldi eDNA in water samples from six sites with known occurrences of the species. There was no detection from the negative site. This study validates the use of eDNA‐based detection of A. gouldi by real‐time PCR as a non‐invasive monitoring tool to assist field monitoring, assessment, and complement ongoing recovery actions to protect habitable ecosystems of A. gouldi.
Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients – a prospective cohort study
Authors: Itzhaki Ben Zadok Osnat , Shaul Aviv A. , Ben‐Avraham Binyamin , Yaari Vicky , Ben Zvi Haim , Shostak Yael , Pertzov Barak , Eliakim‐Raz Noa , Abed Galia , Abuhazira Miriam , Barac Yaron D. , Mats Israel , Kramer Mordechai R. , Aravot Dan , Kornowski Ran , Ben‐Gal Tuvia
Published: May 2021

Aims

To assess the short‐term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single‐centre cohort study of HTx recipients who received a two‐dose SARS‐CoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech).

Methods and results

Whole blood for anti‐spike IgG (S‐IgG) antibodies was drawn at days 21–26 and at days 35–40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44–69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6–14) years. Only 15% of HTx recipients demonstrated the presence of positive S‐IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54–229) AU/mL]. Overall, 49% of HTx recipients induced S‐IgG antibodies in response to either the first or the full two‐dose vaccine schedule [GMT 426 (IQR 106–884) AU/mL]. Older age [68 (IQR 59–70) years vs. 46 (IQR 34–63) years, P = 0.034] and anti‐metabolite‐based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non‐responders to the first vaccine dose became S‐IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S‐IgG antibodies following SARS‐CoV‐2 two‐dose vaccine.

Conclusions

The generally achieved protection from SARS‐CoV‐2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.
CXCR3 and CXCR5 are highly expressed in HIV‐1‐specific CD8 central memory T cells from infected patients
Authors: Olivo Anaëlle , Lécuroux Camille , Bitu Marie , Avettand‐Fenoel Véronique , Boufassa Faroudy , Essat Asma , Meyer Laurence , Doisne Jean‐Marc , Favier Benoit , Vaslin Bruno , Schlecht‐Louf Géraldine , Noël Nicolas , Goujard Cécile , Lambotte Olivier , Bourgeois Christine
Published: May 2021

New ways of characterizing CD8+ memory T cell responses in chronic infections are based on the measurement of chemokine receptor expression (CXCR3, CXCR5, and CX3CR1). We applied these novel phenotyping strategies to chronic HIV infection by comparing healthy donors (HDs), HIV‐infected patients receiving antiretroviral therapy (ART), and spontaneous HIV controllers (HICs). In all groups, the memory cells exhibited high proportion of CXCR3+ cells. Proportions of CXCR5+ and CX3CR1+ cells were preferentially observed among central memory cells (Tcm) and effector memory cells (Tem) respectively.

Chronic controlled HIV infection impacted the chemokine receptor profile of both HIV‐specific and nonspecific CD8+ T cells. In total CD8+ T cells, the proportions of CXCR3–CXCR5–CX3CR1–Tcm and Tem were lower in HIV‐infected patients than in HDs with subtle differences between ART and HICs. Such phenotyping strategy also revealed differences in exhaustion and senescence phenotypes, the CXCR3+CXCR5+CX3CR1– being more exhausted and senescent than the CXCR3+CXCR5–CX3CR1– Tcm fraction. Among HIV‐specific CD8+ T cells, the vast majority of Tcm cells were CXCR3+ and CXCR5+ cells in contrast with their nonspecific counterparts.

In conclusion, the addition of migration markers contributes to better characterize Tcm/Tem compartment.
Epigenetic regulation in antiviral innate immunity
Authors: Wang Xiao , Xia Huawei , Liu Shengde , Cao Lili , You Fuping
Published: May 2021

Emerging life‐threatening viruses have posed great challenges to public health. It is now increasingly clear that epigenetics plays a role in shaping host‐virus interactions and there is a great need for a more thorough understanding of these intricate interactions through the epigenetic lens, which may represent potential therapeutic opportunities in the clinic. In this review, we highlight the current understanding of the roles of key epigenetic regulators — chromatin remodeling and histone modification — in modulating chromatin openness during host defense against virus. We also discuss how the RNA modification m6A (N6‐methyladenosine) affects fundamental aspects of host‐virus interactions. We conclude with future directions for uncovering more detailed functions that epigenetic regulation exerts on both host cells and viruses during infection.
Coordination Features of the 1,3,5‐Triazapentadienyl Ligand in Alkyl Complexes of Rare‐Earth Metals
Authors: Rad'kova Natalia Yu. , Kovylina Tatyana A. , Cherkasov Anton V. , Lyssenko Konstantin A. , Ob'edkov Anatoly M. , Trifonov Alexander A.
Published: May 2021

The reactions of 1,3,5‐triazapentadiene 2,6‐iPr2C6H3NC(Ph)NC(Ph)NHC6H3iPr2‐2,6 (1) with Ln(CH2SiMe3)3(THF)2 (Ln=Y, Lu) in hexane afford bis(alkyl) complexes [2,6‐iPr2C6H3NC(Ph)NC(Ph)NC6H3iPr2‐2,6]Ln(CH2SiMe3)2(THF) (Ln=Y (2), Lu (3)) in 58 (2) and 62 (3) % yields. The X‐ray diffraction study revealed that in 3 the triazapentadienyl ligand coordinates with the Lu3+ ion in “amidinate” fashion resulting in the formation of a four‐membered metallocycle. In contrast, the reaction of 1 with the scandium analogue Sc(CH2SiMe3)3(THF)2 in toluene proceeds with the cleavage of C−N bond of 1,3,5‐triazapentadiene and leads to the formation of a dinuclear monoalkyl complex [{μ2‐2,6‐iPr2C6H3NC(Ph)N}Sc(CH2SiMe3)(THF)]2 (4) in 43 % yield. Complex 4 features κ2‐N,N‐coordination of the residual dianionic {μ2‐2,6‐iPr2C6H3NC(Ph)N}2− ligand μ‐bridging two Sc3+ centers. Alkyl complexes 2–4 were evaluated as pre‐catalysts for isoprene polymerization and hydrosilylation of unsaturated substrates with PhSiH3.
A Tea Saponin‐Carbohydrate‐Protein Complex Could Be One Key Emulsifiable Compound in the Emulsion Formed during Aqueous Extraction of Camellia Oil
Authors: Yang Jian‐Yuan , Li Jing , Wang Mei , Zheng Liu‐Feng , Peng Bin , Zou Xian‐Guo , Yin Yu‐Long , Deng Ze‐Yuan
Published: May 2021

The oil/water (O/W) emulsions are spontaneously formed during the process of aqueous extraction of camellia oil which indicates that there are natural emulsifiers with excellent emulsifying capacity exist in Camellia oleifera Abel. seeds. To explore the formation mechanism of these emulsions, a strongly emulsifiable component, a tea saponin‐carbohydrate‐protein complex (TCPC), is separated and purified by means of chromatography. Its physicochemical properties are characterized by the fourier transform infrared, thermogravimetric analysis, and scanning electron microscopy. The emulsifying properties of O/W emulsions prepared with TCPC (pH 7.0) are investigated systematically. The results show that the emulsions are remarkably stable over a wide range of pH values (5–11), ionic strength (0–200 mm NaCl), thermal treatment (60–90 °C; 30 min), and even after 14 days storage at room temperature (10–25 °C). Moreover, the rheological properties reveal that all determined emulsions show typical pseudoplastic fluid characteristics and shear‐thinning flow behavior. However, the emulsions are unstable during freeze‐thaw cycle. These results imply that TCPC may be one key emulsifiable compound during aqueous extraction of camellia oil.

Practical Applications: Aqueous extraction is a promising technique for edible oil extraction from Camellia oleifera Abel. seeds because of its nutrition, safety and economy. However, the oil/water emulsions formed during the process of aqueous extraction of camellia oil, which makes oil hard to be separated. TCPC with excellent emulsifying activity and emulsion stability was separated and characterized, which could be regarded as a potential target to obtain free oil by frozen/thawed method. Thus, it could be contributing to the industrial application of aqueous extraction of camellia oil.
Design and Characteristics of Novel Sensory and Nutritionally Oriented Olive, Seed, and Nut Virgin Oils’ Blendings
Authors: González‐Gamallo Sergio , Salvador María Desamparados , Fregapane Giuseppe
Published: May 2021

Virgin olive oil is considered a key component of the Mediterranean Diet, while nut and seed “cold‐pressed” oils stand out as an interesting ingredient due to the growing consumer demand toward so‐called gourmet and healthy oils. The main objective of this work is the development and characterization of novel virgin vegetal oils based on blendings of virgin olive oil with virgin oils obtained from seeds (sesame and flaxseed) and nuts (hazelnut and pistachio) of interest due to their peculiar nutritional and organoleptic characteristics. Oil formulations elaborated with 5% of sesame oils achieve a high content in vitamin E (842 mg kg−1, 11.8 mg per standard 14 g oil dose, corresponding to an 80% of the recommended daily intake) and with 10% of flaxseed a high level in essential α‐linolenic acid (6.4%, 0.90 mg per dose corresponding to a 66% of the recommended daily intake). In addition, sensory analysis shows that blends enriched with both 50% hazelnut oil and 75% pistachio oil not only maintain the typical aroma of virgin olive oil, but incorporate the characteristic nutty, roasty, seed‐like, and sweet sensory attributes of nuts, providing an added value to the consumers.
Ruthenium(II)‐Catalyzed Cross‐Coupling of Benzoyl Formic Acids with Toluenes: Synthesis of 2‐Phenylacetophenones
Authors: Yang Shan , Dai Chenyang , Chen Yujie , Jiang Yaqiqi , Shu Sai , Huang Zhibin , Zhao Yingsheng
Published: May 2021

Herein, we report a direct method to synthesize 2‐phenylacetophenone through a ruthenium(II)‐catalyzed cross‐coupling reaction between acyl and benzyl radical. The various derivatives of 2‐phenylacetophenone were prepared easily in moderate to good yields. These reactions provide a straightforward pathway to synthesize a variety of ketones bearing various functional groups.
Efficient Synthesis of Polysubstituted Furans through a Base‐Promoted Oxacyclization of (Z)‐2‐En‐4‐yn‐1‐ols
Authors: Hrizi Asma , Thiery Emilie , Romdhani‐Younes Moufida , Jacquemin Johan , Thibonnet Jérôme
Published: May 2021

An efficient base catalyzed oxacyclization of Z‐enynols has been developed under transition metal‐free reaction conditions, thus resulting in a variety of new di‐, tri‐, and tetra‐substituted furans. This approach allowed us to obtain 32 new compounds. Furthermore, DFT calculations were realized to depict a relationship between the natural population analysis and experimental results with alkyl or aryl groups for the synthesis of 2‐benzylfuran. A one‐pot Sonogashira/oxacyclization approach offers a flexible, robust and efficient alternative to base catalyzed cyclization is also carried out.
Ring Expansion to 8‐Membered Silacycles through Formal Cross‐Dimerization of 5‐Membered Palladacycles with Silacyclobutanes
Authors: Wang Xi–Chao , Wang Hao‐Ran , Xu Xiufang , Zhao Dongbing
Published: May 2021

Investigations of the sila‐8‐membered ring fused biaryls are of high significance for the discovery of new drug lead compounds. However, such compounds are still unknown due to the synthetic challenge. Herein, we describe the chemo‐ and regio‐selective cross‐dimerization of 5‐membered palladacycles with silacyclobutanes enabled by Pd‐catalytic conditions, which constitutes an expedient ring expansion route to the sila‐8‐membered ring fused biaryl skeletons.
MWCNT‐Organoimido Polyoxomolybdate Hybrid Material: Analytical Applications for Amperometric Sensing of Hydrogen Peroxide
Authors: Mujica Michael López , Sotomayor‐Santander Ilania , Hermosilla‐Ibáñez Patricio , Oyarzun‐Ampuero Felipe , Rodríguez Marcela C. , Rivas Gustavo A. , Venegas‐Yazigi Diego , Bollo Soledad
Published: May 2021

We report a hybrid material obtained by dispersing the polyoxometalate n‐[Bu4‐N]2[Mo6O18NC13H9] functionalized with 2‐aminofluorene (POMAF) and multi‐walled carbon nanotubes (MWCNTs) in 1,3‐dioxolane (MWCNT‐ POMAF). We demonstrate the peroxidase‐like activity of the hybrid material and its application for the amperometric quantification of hydrogen peroxide at −0.450 V previous drop‐coating at glassy carbon electrodes, with a linear range between 1.0 μM and 6.0 μM and a detection limit of 330 nM. The reproducibility was 2.2 % using one MWCNTs‐POMAF dispersion, and 3.9 % using 4 different dispersions. The sensor was successfully used for the quantification of hydrogen peroxide in enriched milk samples.
Purification and characterization of the receptor‐binding domain of SARS‐CoV‐2 spike protein from Escherichia coli
Authors: He Yunxia , Qi Jinming , Xiao Lucheng , Shen Lijuan , Yu Weili , Hu Tao
Published: May 2021

SARS‐CoV‐2 is responsible for a disruptive worldwide viral pandemic, and renders a severe respiratory disease known as COVID‐19. Spike protein of SARS‐CoV‐2 mediates viral entry into host cells by binding ACE2 through the receptor‐binding domain (RBD). RBD is an important target for development of virus inhibitors, neutralizing antibodies, and vaccines. RBD expressed in mammalian cells suffers from low expression yield and high cost. E. coli is a popular host for protein expression, which has the advantage of easy scalability with low cost. However, RBD expressed by E. coli (RBD‐1) lacks the glycosylation, and its antigenic epitopes may not be sufficiently exposed. In the present study, RBD‐1 was expressed by E. coli and purified by a Ni Sepharose Fast Flow column. RBD‐1 was structurally characterized and compared with RBD expressed by the HEK293 cells (RBD‐2). The secondary structure and tertiary structure of RBD‐1 were largely maintained without glycosylation. In particular, the major β‐sheet content of RBD‐1 was almost unaltered. RBD‐1 could strongly bind ACE2 with a dissociation constant (KD) of 2.98 × 10–8 M. Thus, RBD‐1 was expected to apply in the vaccine development, screening drugs and virus test kit.
Implications of an epidemiological study showing an association between in utero NDMA exposure and childhood cancer
Authors: Engelward Bevin P.
Published: May 2021

Exposure to N‐nitrosodimethylamine (NDMA) has recently been linked to a childhood cancer cluster in Wilmington, MA, which is home to the Olin Chemical Superfund Site. When it was discovered in the 1990's that 22 children in a town of under 22,000 people got cancer, the community took action and pressed for an investigation into the possibility that chemicals from the Olin Chemical site had contaminated their water. This led to the eventual discovery that NDMA was present in the town water supply. NDMA has long been known for its potent carcinogenicity in animal models, and so the community pointed to NDMA as a possible cause. This led to an investigation by the Massachusetts Department of Public Health, which, in 2021, released its findings showing an association between NDMA exposure in utero and childhood cancer. The mission of the NIEHS Superfund Research Program is to protect human health from hazardous substances. In 2017, in response to community concerns, a team at MIT created the MIT Superfund Research Program Center with a focus on research related to NDMA. Just 1 week prior to the release of the Department of Public Health study, the MIT Superfund Research Program Center published a manuscript in Cell Reports that identifies the Alkyladenine DNA glycosylase (AAG) as a possible genetic susceptibility factor. This commentary provides an author's perspective on the context and implications of this and related research.
Optimization Investigation on Air Phase Change Material Based Battery Thermal Management System
Authors: Lin Xiangwei , Zhang Xuelai , Liu Lu , Yang Mai
Published: May 2021

To ensure the normal operation of a battery pack, a battery thermal management system (BTMS) is required to control the temperature of batteries. Herein, the method using an artificial neural network (ANN) combined with a genetic algorithm (GA) is proposed to optimize the thermal performance of air phase change material (PCM) cooling based BTMS. The ANN is applied to describe the relationship between BTMS parameters (inlet air velocity, inlet air temperature, PCM thickness, battery unit spacing, and discharge rate) and battery pack thermal characteristics. The results show that the PCM thickness and battery unit spacing have little effect on the battery temperature. Then, the optimal parameter combinations of BTMS are solved by GA with the goal of minimizing the maximum temperature. The maximum relative error between simulation and prediction is 0.484 °C, which is only 1.3835% of the simulated value. The optimal parameter combinations help to slow down the temperature rise of the battery pack and delay the phase transition of PCM. The results indicate that the developed model can accurately describe the relationship between the BTMS parameters and battery temperature, which provides a time‐saving and efficient method for the optimal design of BTMS.
Techno‐Economic Model for Reactive Power Planning Using Series‐Shunt Compensation Devices Under Load Demand in Power Transmission Network
Authors: Karmakar Nihar , Bhattacharyya Biplab
Published: May 2021

This research article proposes a planning strategy of reactive power (VAR) in a power transmission system, because reactive power planning (RPP) is a topical issue in the energy sector. Basically, it is a qualitative effort to understand the mathematical principles, technical facets, and economic aspects with their utility in RPP prior to executing the proposed strategy through a unique solution model. Initially, the objective is formulated by measuring different cost components, such as VAR generation cost, line charging cost, flexible AC transmission system (FACTS) device operation cost, and cost due to real power loss. The vulnerable positions in the system are defined for the placement of FACTS devices after computing a set of mathematical methods. The installation bottlenecks of these devices are wiped out depending on some technical considerations and performances. Thereafter, a hybrid intelligence approach along with fundamental algorithms is applied to determine an optimal set of controlling variables in conjunction with active and VAR demand. The code profiling of the proposed approach is rendered on two interregional practical power networks. Finally, the responses of the benchmark functions and statistical outcomes are analyzed extensively to justify the trustworthiness of the proposed solution model.