bluuebunny/crossref_metadata_2025 huggingface dataset:
The PINK1 repertoire: Not just a one trick pony
Authors: Pollock Liam , Jardine Jane , Urbé Sylvie , Clague Michael J.
Published: October 2021

PTEN‐induced kinase 1 (PINK1) is a Parkinson's disease gene that acts as a sensor for mitochondrial damage. Its best understood role involves phosphorylating ubiquitin and the E3 ligase Parkin (PRKN) to trigger a ubiquitylation cascade that results in selective clearance of damaged mitochondria through mitophagy. Here we focus on other physiological roles of PINK1. Some of these also lie upstream of Parkin but others represent autonomous functions, for which alternative substrates have been identified. We argue that PINK1 orchestrates a multi‐arm response to mitochondrial damage that impacts on mitochondrial architecture and biogenesis, calcium handling, transcription and translation. We further discuss a role for PINK1 in immune signalling co‐ordinated at mitochondria and consider the significance of a freely diffusible cleavage product, that is constitutively generated and degraded under basal conditions.
A novel stability‐indicating HPLC method for the determination of enantiomeric purity of eluxadoline drug: Amylose tris(3,5‐dichlorophenyl carbamate) stationary phase
Authors: Yerra Sudhakar , Sharma Hemantkumar , B Sreenivasulu , K Mohana Naidu , B Venkateswara Rao
Published: October 2021

A simple and sensitive stability‐indicating chiral HPLC method has been developed and validated per International Conference on Harmonization guidelines for the determination of enantiomeric purity of eluxadoline (Exdl). The impact of different mobile phase compositions and chiral stationary phases on the separation of Exdl enantiomer along with process‐ and degradation‐related impurities has been studied. Homogeneity of Exdl and stable results of Exdl enantiomer in all degraded samples reveal the fact that the proposed method was specific (stability indicating). Amylose tris(3,5‐dichlorophenyl carbamate) stationary phase column Chiralpak IE‐3 (150 × 4.6 mm, 3 μm) provided better resolution with polar organic solvents than cellulose derivative, crown ether, and zwitterion stationary phases and nonpolar solvents. The mobile phase consisted of acetonitrile, tetrahydrofuran, methanol, butylamine, and acetic acid in the ratio of 500:500:20:2:1.5 (v/v/v/v/v). Isocratic elution was performed at a flow rate of 1.0 mL/min, column temperature of 35°C, injection volume of 10 μL, and UV detection of 240 nm. The United States Pharmacopeia (USP) resolution of the Exdl enantiomer was found to be more than 4.0 within a 65‐min run time. Exdl enantiomer detector response linearity over the concentration range of 0.859–4.524 μg/mL was found to be R2 = 0.9985. The limit of detection, limit of quantification, and average percentage recovery values were established as 0.283 μg/mL, 0.859 μg/mL, and 96.0, respectively.
Corporate accountability for biodiversity and species extinction: Evidence from organisations reporting on their impacts on nature
Authors: Hassan Abeer , Roberts Lee , Rodger Kimberly
Published: October 2021

The aim of this paper is to investigate to what extent organisations disclose on accountability for biodiversity and species extinction (B/E). We present some examples of what disclosure looks like from forward‐thinking companies that have been engaging in tremendous efforts to protect and preserve nature. Our justification for this paper is to provide guidance and encourage other companies to disclose transparently. We believe that B/E accountability is essential in post Covid‐19 reporting as the lack of valuing, promoting and investing in biodiversity is considered to be one of the main drivers of the Covid‐19 pandemic. The study's sample is the Top 200 companies from the Fortune Global with the years 2012, 2014 and 2016 and companies' websites in 2019. We believe that our paper is providing some guidance on how to repair nature and eliminate biodiversity loss. This is because organisations are reliant on natural capital resources for survival. Also, biodiversity loss and extinction can significantly affect social, economic and financial viability for survival. Our results have some implications for practitioners, policymakers and academics.
Does green transformational leadership lead to green innovation? The role of green thinking and creative process engagement
Authors: Begum Saira , Ashfaq Muhammad , Xia Enjun , Awan Usama
Published: October 2021

This study aims to provide an understanding of the role of green transformational leadership (GTL) and green innovation practices in organizations through cognitive processes: green thinking and creative process engagement (CPE). Using a survey questionnaire, we collected data from 342 respondents from high‐tech industries located in China. The data were examined through structural equation modeling (variance‐based) to analyze the hypotheses. The findings of the study show that GTL has a substantial effect on green thinking, CPE, and green innovation. The findings further reveal that green thinking and CPE mediate the relationship between GTL and green innovation. Green thinking and creative processes have become instrumental tools in fostering green innovation. Thus, this investigation provides novel insights into how to promote GTL and cognitive processes in organizations to solicit green innovation.
Polylysine for skin regeneration: A review of recent advances and future perspectives
Authors: Zarrintaj Payam , Ghorbani Sadegh , Barani Mahmood , Singh Chauhan Narendra Pal , Khodadadi Yazdi Mohsen , Saeb Mohammad Reza , Ramsey Joshua D. , Hamblin Michael R. , Mozafari Masoud , Mostafavi Ebrahim
Published: October 2021

There have been several attempts to find promising biomaterials for skin regeneration, among which polylysine (a homopolypeptide) has shown benefits in the regeneration and treatment of skin disorders. This class of biomaterials has shown exceptional abilities due to their macromolecular structure. Polylysine‐based biomaterials can be used as tissue engineering scaffolds for skin regeneration, and as drug carriers or even gene delivery vectors for the treatment of skin diseases. In addition, polylysine can play a preservative role in extending the lifetime of skin tissue by minimizing the appearance of photodamaged skin. Research on polylysine is growing today, opening new scenarios that expand the potential of these biomaterials from traditional treatments to a new era of tissue regeneration. This review aims to address the basic concepts, recent trends, and prospects of polylysine‐based biomaterials for skin regeneration. Undoubtedly, this class of biomaterials needs further evaluations and explorations, and many critical questions have yet to be answered.
Integrated analysis of patients with KEAP1/NFE2L2/CUL3 mutations in lung adenocarcinomas
Authors: Jin Xing , Zheng Yuansheng , Chen Zhencong , Wang Fei , Bi Guoshu , Li Ming , Liang Jiaqi , Sui Qihai , Bian Yunyi , Hu Zhengyang , Qiao Yulei , Xu Songtao
Published: October 2021

Objectives

To explore the clinical features, molecular characteristics, and immune landscape of lung adenocarcinoma patients with KEAP1/NFE2L2/CUL3 mutations.

Methods

The multi‐omics data from the GDC‐TCGA LUAD project of The Cancer Genome Atlas (TCGA) database were downloaded from the Xena browser. The estimate of the immune infiltration was implemented by using the GSVA analysis and CIBERSORT. The status of KEAP1/NFE2L2/CUL3 mutation in 50 LUAD samples of our department was detected by using Sanger sequencing, following the relative expression level of differentially expressed genes (DEGs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) was validated by IHC and real‐time quantitative polymerase chain reaction (RT‐qPCR).

Results

The Kaplan–Meier and multivariable Cox regression analyses demonstrated that KEAP1/NFE2L2/CUL3 mutations had independent prognostic value for OS and PFS in LUAD patients. The differential analysis detected 207 upregulated genes (like GSR/UGT1A6) and 447 downregulated genes (such as PIGR). GO, KEGG, and GSEA analyses demonstrated that DEGs were enriched in glutamate metabolism and the immune response. The constructed ceRNA network shows the linkage of differential lncRNAs and mRNAs. Three hundred and nine somatic mutations were detected, alterations in immune infiltration DNA methylations and stemness scores were also founded between the two groups. Eight mutated LUAD patients were detected by Sanger DNA sequencing in 50 surgical patients. GSR and UGT1A6 were validated to express higher in the Mut group, whereas the expression of PIGR was restrained. Furthermore, the IHC staining conducted on paraffin‐embedded tissue emphasizes the consistency of our result.

Conclusion

This research implemented the comprehensive analysis of KEAP1/NFE2L2/CUL3 somatic mutations in the LUAD patients. Compared with the wild type of LUAD patients, the Mut group shows a large difference in clinical features, RNA sequence, DNA methylation, and immune infiltrations, indicating complex mechanism oncogenesis and also reveals potential therapeutic targets.
Trends in grain quality of starch, protein, fat and lysine content for normal maize varieties in China since the 1960s
Authors: Lu Quanwei , Lu Chen , Zhou Zhenxing , Qin Xiaoliang , Xue Jiquan , Siddique Kadambot H. M.
Published: October 2021

Background and objectives

In China, breeders overlook changes in grain quality traits of starch, protein, and fat content that occur concurrently in normal maize (Zea mays L.). Here, we collected data for 436 single‐cross normal maize varieties released since the 1960s and 258 landraces from China's three main agroecological regions to investigate how grain quality traits have changed over time.

Findings

Since the 1960s, crude starch content has increased and protein content has decreased in northern China, crude starch content has increased and fat content has decreased in southwestern China and the Yellow‐Huai River Valley, and lysine content has increased in southwestern China only. In the 2010s, northern China and the Yellow‐Huai River Valley had the highest crude starch content, southwestern China had the highest crude protein content, and northern China had the highest crude fat content.

Conclusions

Breeding since the 1960s has significantly changed the composition of maize seeds in the three main maize growing regions of China.

Significance and novelty

This study provides a worthy summary of the changes in grain quality traits of normal maize varieties in China in the last 50 years and insights into developing strategies for breeding grain quality.
Epidural abscess and spondylitis caused by Veillonella parvula in a man on hemodialysis
Authors: Kurihara Masaru , Tamaki Itaru , Tokuda Yasuharu
Published: October 2021

Veillonella species rarely cause serious infections, but the incidence of infection has been increasing among immunocompromised individuals. This case of an epidural abscess and spondylitis caused by Veillonella parvula in a hemodialysis patient illustrates the importance of performing anaerobic blood culture in immunocompromised patients with signs of infection.
Inverting the Stereoselectivity of an NADH‐Dependent Imine‐Reductase Variant
Authors: Stockinger Peter , Borlinghaus Niels , Sharma Mahima , Aberle Benjamin , Grogan Gideon , Pleiss Jürgen , Nestl Bettina M.
Published: October 2021

Imine reductases (IREDs) offer biocatalytic routes to chiral amines and have a natural preference for the NADPH cofactor. In previous work, we reported enzyme engineering of the (R)‐selective IRED from Myxococcus stipitatus (NADH‐IRED‐Ms) yielding a NADH‐dependent variant with high catalytic efficiency. However, no IRED with NADH specificity and (S)‐selectivity in asymmetric reductions has yet been reported. Herein, we applied semi‐rational enzyme engineering to switch the selectivity of NADH‐IRED‐Ms. The quintuple variant A241V/H242Y/N243D/V244Y/A245L showed reverse stereopreference in the reduction of the cyclic imine 2‐methylpyrroline compared to the wild‐type and afforded the (S)‐amine product with >99 % conversion and 91 % enantiomeric excess. We also report the crystal‐structures of the NADPH‐dependent (R)‐IRED‐Ms wild‐type enzyme and the NADH‐dependent NADH‐IRED‐Ms variant and molecular dynamics (MD) simulations to rationalize the inverted stereoselectivity of the quintuple variant.
Selective Oxidation of Benzyl Alcohol in the Aqueous Phase by TiO2‐Based Photocatalysts: A Review
Authors: Luong Giang Kim Thi , Ku Young
Published: October 2021

Production processes of benzaldehyde have been studied intensively due to its wide range of applications in the industry. The selective oxidation of benzyl alcohol to benzaldehyde by TiO2 is promising as it can occur under mild conditions without toxic by‐products. This article mainly describes the challenges in the photooxidation of benzyl alcohol and the strategies to enhance both the efficiency and selectivity for benzaldehyde. Visible‐light response, charge separation, morphology, and reaction conditions have been listed as critical factors for this process. Different modification methods to improve the insufficient photocatalytic activity of TiO2, such as surface adjustments, metal/non‐metal doping, or semiconductor coupling, are presented. The perspectives for further research in this field are also discussed.
NMR Crystallography Reveals Carbonate Induced Al‐Ordering in ZnAl Layered Double Hydroxide
Authors: Radhakrishnan Sambhu , Lauwers Karl , Chandran C. Vinod , Trébosc Julien , Pulinthanathu Sree Sreeprasanth , Martens Johan A. , Taulelle Francis , Kirschhock Christine E. A. , Breynaert Eric
Published: October 2021

Layered double hydroxides (LDHs) serve a score of applications in catalysis, drug delivery, and environmental remediation. Smarter crystallography, combining X‐ray diffraction and NMR spectroscopy revealed how interplay between carbonate and pH determines the LDH structure and Al ordering in ZnAl LDH. Carbonate intercalated ZnAl LDHs were synthesized at different pH (pH 8.5, pH 10.0, pH 12.5) with a Zn/Al ratio of 2, without subsequent hydrothermal treatment to avoid extensive recrystallisation. In ideal configuration, all Al cations should be part of the LDH and be coordinated with 6 Zn atoms, but NMR revealed two different Al local environments were present in all samples in a ratio dependent on synthesis pH. NMR‐crystallography, integrating NMR spectroscopy and X‐ray diffraction, succeeded to identify them as Al residing in the highly ordered crystalline phase, next to Al in disordered material. With increasing synthesis pH, crystallinity increased, and the side phase fraction decreased. Using 1H−13C, 13C−27Al HETCOR NMR in combination with 27Al MQMAS, 27Al‐DQ‐SQ measurements and Rietveld refinement on high‐resolution PXRD data, the extreme anion exchange selectivity of these LDHs for CO32− over HCO3− was linked to strict Al and CO32−ordering in the crystalline LDH. Even upon equilibration of the LDH in pure NaHCO3 solutions, only CO32− was adsorbed by the LDH. This reveals the structure directing role of bivalent cations such as CO32− during crystallization of [M2+4M3+2(OH)2]2+[A2−]1⋅yH2O LDH phases.
Metal Centers as Nucleophiles: Oxymoron of Halogen Bond‐Involving Crystal Engineering
Authors: Ivanov Daniil M. , Bokach Nadezhda A. , Yu. Kukushkin Vadim , Frontera Antonio
Published: October 2021

This review highlights recent studies discovering unconventional halogen bonding (HaB) that involves positively charged metal centers. These centers provide their filled d‐orbitals for HaB, and thus behave as nucleophilic components toward the noncovalent interaction. This role of some electron‐rich transition metal centers can be considered an oxymoron in the sense that the metal is, in most cases, formally cationic; consequently, its electron donor function is unexpected. The importance of Ha⋅⋅⋅d‐[M] (Ha=halogen; M is Group 9 (Rh, Ir), 10 (Ni, Pd, Pt), or 11 (Cu, Au)) interactions in crystal engineering is emphasized by showing remarkable examples (reported and uncovered by our processing of the Cambridge Structural Database), where this Ha⋅⋅⋅d‐[M] directional interaction guides the formation of solid supramolecular assemblies of different dimensionalities.
Bilayer rGO‐Based Photothermal Evaporator for Efficient Solar‐Driven Water Purification[]**
Authors: Dong Weichao , Wang Yuchao , Zhang Yajing , Song Xiangju , Peng Hui , Jiang Heqing
Published: October 2021

Interfacial evaporation has emerged as a promising approach to produce freshwater. However, an urgent concern is that, due to the illegal discharge of industrial wastewater, most water bodies are polluted by trace volatile organic compounds (VOCs), which are easily volatilized and enriched in the collected water during the interfacial evaporation process. Herein, a bilayer photothermal evaporator was reasonably designed for contaminated water purification. The bottom hydrophilic rGO‐sodium alginate (SA) sheets purposefully disintegrate water transport channels, thus quickly removing VOCs through physical adsorption. The rGO‐SA‐TiO2 upper layer sufficiently absorbs incident light and therefore persistently generates reactive oxidizing species to degrade upward VOCs. Notably, the oriented microchannels inside the evaporator allow sustained light reflections to improve the utilization of solar energy. The evaporation rate can reach 1.63 kg m−2 h−1 with a considerably high VOC removal efficiency of up to 96 %. Such an integrated bilayer evaporator provides an effective strategy to obtain clean water via solar distillation.
Indandione‐Terminated Quinoidal Compounds for Low‐Bandgap Small Molecules with Strong Near‐Infrared Absorption: Effect of Conjugation Length on the Properties
Authors: Sun Lei , Du Tian , Wang Cheng , Geng Dongling , Li Lin , Han Yang , Deng Yunfeng
Published: October 2021

Low‐bandgap organic semiconductors have attracted much attention for their multiple applications in optoelectronics. However, the realization of narrow bandgap is challenging particularly for small molecules. Herein, we have synthesized four quinoidal compounds, i. e.,QSN3,QSN4,QSN5andQSN6, with electron rich S,N‐heteroacene as the quinoidal core and indandione as the end‐groups. The optical bandgap of the quinoidal compounds is systematically decreased with the extension of quinoidal skeleton, while maintaining stable closed‐shell ground state.QSN6absorbs an intense absorption in the first and second near‐infrared region in the solid state, and has extremely low optical bandgap of 0.74 eV. Cyclic voltammetry analyses reveal that the lowest unoccupied molecular orbital (LUMO) energy levels of the four quinoidal compounds all lie below −4.1 eV, resulting in good electron‐transporting characteristics in organic thin‐film transistors. These results demonstrated that the combination of π‐extended quinoidal core and end‐groups in quinoidal compounds is an effective strategy for the synthesis of low‐bandgap small molecules with good stability.
Characterizing the tumor microenvironment in rare renal cancer histological types
Authors: Synnott Naoise C , Poeta Maria Luana , Costantini Manuela , Pfeiffer Ruth M , Li Mengying , Golubeva Yelena , Lawrence Scott , Mutreja Karun , Amoreo Carla , Dabrowska Malgorzata , Simone Giuseppe , Pescarmona Edoardo , Lenz Petra , Olanich Mary , Duggan Maire , Abubakar Mustapha , Fazio Vito Michele , Gallucci Michele , Sentinelli Steno , Landi Maria Teresa
Published: October 2021

The tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance‐dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.
The impact of the COVID‐19 pandemic on pediatric cancer care
Authors: Moreira Daniel C.
Published: October 2021

This editorial contextualizes the work by Sharma et al on the effects of the COVID‐19 pandemic on pediatric cancer care in India.
Giant cell tumor of soft tissue: FNA cytopathology of 4 cases, review of the literature, and comparison with giant cell tumor of bone
Authors: Wakely Paul E.
Published: October 2021

Background

The cytopathology of a giant cell tumor of soft tissue (GCT‐ST), a fibrohistiocytic neoplasm distinct from other giant cell–rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT‐ST fine‐needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs).

Methods

The authors' cytopathology files were searched for GCT‐ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques.

Results

Four cases of GCT‐ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28‐75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT‐ST, atypical myxoid lesion with giant cells, and benign with osteoclast‐like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology.

Conclusions

GCT‐ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT‐ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast‐like giant cells.
Smart Two‐Dimensional Membranes for Molecular Separations
Authors: Rouhani Hadi , Ying Yunpan , Zhao Dan
Published: October 2021

Membrane‐based separation technologies are gaining prominence in energy‐efficient separation processes. Smart membranes, which change their physical or chemical characteristics in response to environmental stimuli, are attractive membrane candidates. This review summarizes the recent development and applications of smart membranes based on two‐dimensional (2D) materials, mainly focusing on their design, fabrication, and applications in molecular separations. Furthermore, stimuli for triggering smart 2D membranes are classified and explained. Finally, we propose areas for improvement and further development for future studies, such as the issues of complicated fabrication, long term stability in real operating conditions, and responding to different environmental stimuli at the same time.
A new method for textile pattern recognition and recoloring
Authors: Zheng Dejun
Published: October 2021

Textile pattern recognition and recoloring separates a fabric image into different color regions and changes colors of the regions in the fabric image. A new method for textile pattern recognition and recoloring is proposed. The proposed method consists of two main steps. First, the binary images are recognized through a series of image enhancement techniques, such as the color‐encoding algorithm, the edge‐based filtering algorithm, and a multiphase image segmentation model. Second, the regions of interest are recolored with different recoloring methods based on intrinsic image decomposition and grayscale image recoloring. Experimental results and comparisons demonstrate that the main disadvantages and difficulties of using palette‐based methods in textile pattern recoloring have been overcome by the proposed method. The proposed method is effective in inhibiting tiny region effects and preserving the geometry structures of textile patterns. It can be applied to recognize and recolor different kinds of fabric images, including the Jacquard, the embroidered, and the printed fabric images.
Semi‐Mechanistic PK/PD Modeling and Simulation of Irreversible BTK Inhibition to Support Dose Selection of Tirabrutinib in Subjects with RA
Authors: Meng Amy , Humeniuk Rita , Jürgensmeier Juliane M. , Hsueh Chia‐Hsiang , Matzkies Franziska , Grant Ethan , Truong Hoa , Billin Andrew N. , Yu Helen , Feng Joy , Kwan Ellen , Tarnowski Thomas , Nelson Cara H.
Published: October 2021

Tirabrutinib is an irreversible, small‐molecule Bruton’s tyrosine kinase (BTK) inhibitor, which was approved in Japan (VELEXBRU) to treat B‐cell malignancies and is in clinical development for inflammatory diseases. As an application of model‐informed drug development, a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for irreversible BTK inhibition of tirabrutinib was developed to support dose selection in clinical development, based on clinical PK and BTK occupancy data from two phase I studies with a wide range of PK exposures in healthy volunteers and in subjects with rheumatoid arthritis. The developed model adequately described and predicted the PK and PD data. Overall, the model‐based simulation supported a total daily dose of at least 40 mg, either q.d. or b.i.d., with adequate BTK occupancy (> 90%) for further development in inflammatory diseases. Following the PK/PD modeling and simulation, the relationship between model‐predicted BTK occupancy and preliminary clinical efficacy data was also explored and a positive trend was identified between the increasing time above adequate BTK occupancy and better efficacy in treatment for RA by linear regression.
BIA‐ALCL diagnosis on CytoLyt fixed ThinPrep, cell block and immunohistochemistry
Authors: Everest Sedef , Virk Renu , Gonzalez Abel
Published: October 2021

Breast implant associated anaplastic large cell lymphoma (BIA‐ALCL) is an emergent rare T cell non‐Hodgkin lymphoma arising in association with a breast implant, particularly textured ones. Recent guidelines list cytopathological examination as the first essential step for diagnosis, routinely followed by CD30 immunohistochemistry (IHC) and flow cytometry (FC) for a T cell clone. The majority of BIA‐ALCL literature regarding cytopathological evaluation describes morphology based on various preparation methods limited to cytospins and smears with the exception of at least one case report detailing cytomorphological and IHC findings on ThinPrep. This case report details initial diagnosis of BIA‐ALCL rendered with CytoLyt prepared ThinPrep and cell block, including the specific antibodies used for IHC. The ThinPrep slide showed numerous singly dispersed large, atypical cells with abundant cytoplasm containing irregular nuclei with dispersed chromatin and prominent nucleoli in a background of macrophages, inflammatory cells and granular debris. TIA‐1 and CD30 along with other T‐cell markers, including specific antibodies, remains immunoreactive in tissue collected in CytoLyt solution. Cell size reduction, artifactual lymphoid cell aggregation and prominent nucleoli in benign and reactive conditions are among other ThinPrep cellular alterations pathologists should bear in mind.
What are the different styles of calcite precipitation within a hyperalkaline leachate? A sedimentological Anthropocene case study
Authors: Bastianini Laura , Rogerson Mike , Mercedes‐Martín Ramon , Prior Timothy J. , Mayes William M.
Published: October 2021

This study aims to compare the fabrics of anthropogenic carbonates downstream of lime and steel disposal sites with models of carbonate precipitation from natural systems to elucidate potential drivers, precipitation mechanisms, morphological similarities, predictability in 3D facies distributions and depositional models of these systems. For this purpose, a combination of sedimentological, mineralogical and geochemical approaches is conducted including the analysis of microfacies (petrographic microscope and electron microscopy), X‐ray diffraction and hydrochemistry. The data show that both anthropogenic and natural systems exhibit clear proximal, middle and distal zones of carbonate precipitation. The main macroscopic differences are the dominance of swamp environments in the proximal zone and the prevalence of tufa‐like barrage‐and‐pool sequences in the middle and distal zones. Microfabrics in anthropogenic sites are comparable to travertines but lack the sub‐surface facies and at extreme pH exhibit sparry crusts without clear equivalents in travertines. This sedimentology of anthropogenic carbonates shows that calcite mineral formation is complex and not homogeneous or purely driven by thermodynamic processes. Considering the sedimentology of these human‐induced systems will help us understand precipitation mechanisms which will aid both efforts to utilise anthropogenic alkaline wastes for carbon capture and manage their environmental impacts.
Program builds self‐awareness in students with autism
Authors: Enos Gary A.
Published: October 2021

Students with autism at Bellevue College in Washington have seen dramatically improved achievement and retention through participation in the Neurodiversity Navigators program. Program designer and Director Sara Sanders Gardner discussed the initiative's efforts to build a stronger sense of self in students.
The new dual gastric inhibitory peptide/glucagon‐like peptide 1 agonist tirzepatide in type 2 diabetes: Is the future bright?
Authors: Papachristou Stella , Popovic Djordje S. , Papanas Nikolaos
Published: October 2021

Tirzepatide is a dual gastric inhibitory peptide/glucagon‐like peptide 1 (GIP/GLP‐1) receptor agonist formulated as a synthetic linear peptide, based on the native GIP sequence. It has a prolonged half‐life of 5 days, which enables once‐weekly dosing. Studies have hitherto demonstrated its superiority in achieving optimal glycaemic control and body weight management, as compared with various agents used in the treatment of type 2 diabetes mellitus (T2DM), including GLP‐1 receptor agonists. Thus, it is expected to enrich our therapeutic armamentarium in T2DM. However, further experience, notably longer follow‐up data and information on cardiovascular effects, is still needed.
Systematic expression analysis of plasticity‐related genes in mouse brain development brings PRG4 into play
Authors: Gross Isabel , Tschigor Tabea , Salman Angelina L. , Yang Fan , Luo Jiankai , Vonk Danara , Hipp Mark S. , Neidhardt John , Bräuer Anja U.
Published: October 2021

Background

Plasticity‐related genes (Prgs/PRGs) or lipid phosphate phosphatase‐related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain‐specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation.

Results

We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio‐temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non‐neuronal cell lines, and does not localize to the plasma membrane of filopodia.

Conclusion

We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling.
Chemical disturbance cues in aquatic systems: a review and prospectus
Authors: Crane Adam L. , Bairos‐Novak Kevin R. , Goldman Jack A. , Brown Grant E.
Published: October 2021

In the natural environment, animals can face potentially dangerous and often regular exposure to major environmental fluctuations such as flash flooding and drought, or the approach of a predator. For many aquatic species, exposure to these ecological disturbances triggers the release of “disturbance cues” – generally characterized as chemicals released when animals are startled but not injured. While the chemistry of such cues remains largely unexplored, they appear to provide early warning information to nearby individuals, potentially leading to behavioral decisions that increase overall fitness, particularly for social species that may coordinate group defense. In the literature, disturbance cues have received little attention relative to other chemical cues, such as damage‐released alarm cues. However, recent advances in the study of disturbance cue communication have led an uptick in research on the subject. Here, we review the existing literature on responses to disturbance cues in aquatic systems. Although the majority of studies involve behavioral responses to a simulated predator approach, we describe various disturbance types across a broad range of taxa. We discuss the ecological implications of disturbance cues, including their role in risk assessment, signaling, learning, and species specificity. We also address several methodological challenges for this developing field of study, as well as the ethical and conservation implications of this research going forward. Future research on disturbance cues should address a number of key unknowns, including questions regarding disturbance cue chemistry, function, and generality.
Improved inferences about landscape connectivity from spatial capture–recapture by integration of a movement model
Authors: Dupont Gates , Linden Daniel W. , Sutherland Chris
Published: October 2021

Understanding how broad‐scale patterns in animal populations emerge from individual‐level processes is an enduring challenge in ecology that requires investigation at multiple scales and perspectives. Complementary to this need for diverse approaches is the recent focus on integrated modeling in statistical ecology. Population‐level processes represent the core of spatial capture–recapture (SCR), with many methodological extensions that have been motivated by standing ecological theory and data‐integration opportunities. The extent to which these recent advances offer inferential improvements can be limited by the data requirements for quantifying individual‐level processes. This is especially true for SCR models that use non‐Euclidean distance to relax the restrictive assumption that individual space use is stationary and symmetrical to make inferences about landscape connectivity. To meet the challenges of scale and data quality, we propose integrating an explicit movement model with non‐Euclidean SCR for joint estimation of a shared cost parameter between individual and population processes. Here, we define a movement kernel for step selection that uses “ecological distance” instead of Euclidean distance to quantify availability for each movement step in terms of landscape cost. We compare performance of our integrated model to that of existing SCR models using realistic animal movement simulations and data collected on black bears. We demonstrate that an integrated approach offers improvements both in terms of bias and precision in estimating the shared cost parameter over models fit to spatial encounters alone. Simulations suggest these gains were only realized when step lengths were small relative to home range size, and estimates of density were insensitive to whether or not an integrated approach was used. By combining the fine spatiotemporal scale of individual movement processes with the estimation of population density in SCR, integrated approaches such as the one we develop here have the potential to unify the fields of movement, population, and landscape ecology and improve our understanding of landscape connectivity.
The disruption of a keystone interaction erodes pollination and seed dispersal networks
Authors: Vitali Agustin , Sasal Yamila , Vázquez Diego P. , Miguel M. Florencia , Rodríguez‐Cabal Mariano A.
Published: October 2021

Understanding the impacts of global change on ecological communities is a major challenge in modern ecology. The gain or loss of particular species and the disruption of key interactions are both consequences and drivers of global change that can lead to the disassembly of ecological networks. We examined whether the disruption of a hummingbird–mistletoe–marsupial mutualism by the invasion of non‐native species can have cascading effects on both pollination and seed dispersal networks in the temperate forest of Patagonia, Argentina. We focused on network motifs, subnetworks composed of a small number of species exhibiting particular patterns of interaction, to examine the structure and diversity of mutualistic networks. We found that the hummingbird–mistletoe–marsupial mutualism plays a critical role in the community by increasing the complexity of pollination and seed dispersal networks through supporting a high diversity of interactions. Moreover, we found that the disruption of this tripartite mutualism by non‐native ungulates resulted in diverse indirect effects that led to less complex pollination and seed dispersal networks. Our results demonstrate that the gains and losses of particular species and the alteration of key interactions can lead to cascading effects in the community through the disassembly of mutualistic networks.
Emergent properties of microbial communities drive accelerated biogeochemical cycling in disturbed temperate forests
Authors: Osburn Ernest D. , Badgley Brian D. , Strahm Brian D. , Aylward Frank O. , Barrett J. E.
Published: October 2021

Despite ever‐increasing availability of detailed information about microbial community structure, relationships of microbial diversity with ecosystem functioning remain unclear. We investigated these relationships at the Coweeta Hydrologic Laboratory, where past forest disturbances (e.g., clear‐cut) have altered both ecosystem processes (e.g., increased N export) and microbial communities (e.g., increased bacterial diversity). We sampled soils from disturbed and adjacent reference forests, characterized resident microbial communities, and measured several microbial C‐cycle and N‐cycle process rates. Microbial communities from historically disturbed soils exhibited altered ecosystem functioning, including generally higher rates of C‐ and N‐cycle processes. Disturbed soil microbial communities also exhibited altered ecosystem multifunctionality, a composite variable consisting of all measured process rates as well as extracellular enzyme activities. Although we found few relationships between ecosystem functions and microbial alpha diversity, all functions were correlated with microbial community composition metrics, particularly r:K strategist ratios of bacterial phyla. Additionally, for both ecosystem multifunctionality and specific processes (i.e., C‐ and N‐mineralization), microbial metrics significantly improved models seeking to explain variation in process rates. Our work sheds light on the links between microbial communities and ecosystem functioning and identifies specific microbial metrics important for modeling ecosystem responses to environmental change.
Phylogenetic conservatism explains why plants are more likely to produce fleshy fruits in the tropics
Authors: Wang Gang , Ives Anthony R. , Zhu Hua , Tan Yunhong , Chen Si‐Chong , Yang Jie , Wang Bo
Published: October 2021

Plant functional traits often show strong latitudinal trends. To explain these trends, studies have often focused on environmental variables, correlations with other traits that themselves show latitudinal trends, and phylogenetic conservatism. However, few studies have systematically disentangled the relative contributions of these factors. Using a dataset consisting of 9,370 plant species from Southwest China, we investigated factors affecting fruit type (fleshy vs. dry): plant growth form, environmental constraints (summarized by climate region), and phylogenetic conservatism. Growth form and climate region are often cited in the literature as important explanations for the higher proportion of fleshy fruited species in the tropics. Nonetheless, in our analyses using partial R2, growth form and climate region explained only 1.7% and 0.3%, respectively, of the variance in fruit type in a model including phylogeny, while phylogenetic conservatism explained 79.5%. Furthermore, phylogenetic conservatism was evenly distributed along the phylogeny, implying that fruit type reflects both ancient and recent phylogenetic relationships. Our findings illustrate the value of parsing out the contributions of explanatory variables and phylogeny to the variance in species' traits. Methods using phylogenies that calculate partial R2 give a more informative tool than traditional methods to explore the phylogenetic patterns of functional traits.
Development of in‐wheel receiver coil for dynamic wireless power transfer
Authors: Shimizu Osamu , Utsu Takashi , Fujimoto Hiroshi , Gunji Daisuke , Kuwayama Isao
Published: October 2021

Short cruise range is one of the major limitations of electric vehicles. To address this problem, dynamic wireless power transfer has been proposed. However, the eddy current loss in foreign matter is one of the greatest disadvantages of dynamic wireless power transfer. Eddy current loss decreases efficiency of wireless power transfer and increases temperature of the foreign matter, which causes burning of the combustible materials around the foreign matter in the worst case. Herein, we propose a wireless power transfer system named in‐wheel coil wherein the magnetic flus in concentrated in the tires and wheels. In addition, we propose suitable materials for the tires and the wheels of the system, to reduce the eddy current loss, are proposed using actual measurement data.
Interleukin‐7‐dependent nonclassical monocytes and CD40 expression are affected in children with type 1 diabetes
Authors: Hehenkamp Paul , Hoffmann Maximilian , Kummer Sebastian , Reinauer Christina , Döing Carsten , Förtsch Katharina , Enczmann Jürgen , Balz Vera , Mayatepek Ertan , Meissner Thomas , Jacobsen Marc , Seyfarth Julia
Published: October 2021

The important role of IL‐7 in the generation of self‐reactive T‐cells in autoimmune diseases is well established. Recent studies on autoimmunity‐associated genetic polymorphisms indicated that differential IL‐7 receptor (IL‐7R) expression of monocytes may play a role in the underlying pathogenesis. The relevance of IL‐7‐mediated monocyte functions in type 1 diabetes remains elusive. In the present study, we characterized monocyte phenotype and IL‐7‐mediated effects in children with type 1 diabetes and healthy controls with multicolor flow cytometry and t‐distributed Stochastic Neighbor‐Embedded (t‐SNE)‐analyses. IL‐7R expression of monocytes rapidly increased in vitro and was boosted through LPS. In the presence of IL‐7, we detected lower monocyte IL‐7R expression in type 1 diabetes patients as compared to healthy controls. This difference was most evident for the subset of nonclassical monocytes, which increased after IL‐7 stimulation. t‐SNE analyses revealed IL‐7‐dependent differences in monocyte subset distribution and expression of activation and maturation markers (i.e., HLA‐DR, CD80, CD86, CD40). Notably, monocyte CD40 expression increased considerably by IL‐7 and CD40/IL‐7R co‐expression differed between patients and controls. This study shows the unique effects of IL‐7 on monocyte phenotype and functions. Lower IL‐7R expression on IL‐7‐induced CD40high monocytes and impaired IL‐7 response characterize monocytes from patients with type 1 diabetes.
A multifunctional mouse model to study the role of Samd3
Authors: Peters Annika E. , Knöpper Konrad , Grafen Anika , Kastenmüller Wolfgang
Published: October 2021

The capacity to develop immunological memory is a hallmark of the adaptive immune system. To investigate the role of Samd3 for cellular immune responses and memory development, we generated a conditional knock‐out mouse including a fluorescent reporter and a huDTR cassette for conditional depletion of Samd3‐expressing cells. Samd3 expression was observed in NK cells and CD8 T cells, which are known for their specific function against intracellular pathogens like viruses. After acute viral infections, Samd3 expression was enriched within memory precursor cells and the frequency of Samd3‐expressing cells increased during the progression into the memory phase. Similarly, during chronic viral infections, Samd3 expression was predominantly detected within precursors of exhausted CD8 T cells that are critical for viral control. At the functional level however, Samd3‐deficient CD8 T cells were not compromised in the context of acute infection with Vaccinia virus or chronic infection with Lymphocytic choriomeningitis virus. Taken together, we describe a novel multifunctional mouse model to study the role of Samd3 and Samd3‐expressing cells. We found that Samd3 is specifically expressed in NK cells, memory CD8 T cells, and precursor exhausted T cells during viral infections, while the molecular function of this enigmatic gene remains further unresolved.