bluuebunny/crossref_metadata_2025 huggingface dataset:
Drice restrains Diap2-mediated inflammatory signalling and intestinal inflammation
Authors: Kietz Christa , Mohan Aravind K. , Pollari Vilma , Tuominen Ida-Emma , Ribeiro Paulo S. , Meier Pascal , Meinander Annika
Published: July 2021

The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place in the epithelial cells of the gut and trachea, and for mounting systemic immune responses in the cells of the fat body. We have found that transgenic expression of Diap2 leads to a spontaneous induction of NF-κB target genes, inducing chronic inflammation in the Drosophila midgut, but not in the fat body. Drice is a Drosophila effector caspase known to interact and form a stable complex with Diap2. We have found that this complex formation induces its subsequent degradation, thereby regulating the amount of Diap2 driving NF-κB signalling in the intestine. Concordantly, loss of Drice activity leads to accumulation of Diap2 and to chronic intestinal inflammation. Interestingly, Drice does not interfere with pathogen-induced signalling, suggesting that it protects from immune responses induced by resident microbes. Accordingly, no inflammation was detected in transgenic Diap2 flies and Drice-mutant flies reared in axenic conditions. Hence, we show that Drice, by restraining Diap2, halts unwanted inflammatory signalling in the intestine.
Ocular benzalkonium chloride exposure: problems and solutions
Authors: Goldstein Michael H. , Silva Fabiana Q. , Blender Nysha , Tran Trung , Vantipalli Srilatha
Published: July 2021

Preservatives in multidose formulations of topical ophthalmic medications are crucial for maintaining sterility but can be toxic to the ocular surface. Benzalkonium chloride (BAK)—used in approximately 70% of ophthalmic formulations—is well known to cause cytotoxic damage to conjunctival and corneal epithelial cells, resulting in signs and symptoms of ocular surface disease (OSD) including ocular surface staining, increased tear break-up time, and higher OSD symptom scores. These adverse effects are more problematic with chronic exposure, as in lifetime therapy for glaucoma, but can also manifest after exposure as brief as seven days. Multiple strategies are available to minimize or eliminate BAK exposure, among them alternative preservatives, preservative-free formulations including sustained release drug delivery platforms, and non-pharmacological therapies for common eye diseases and conditions. In this paper, we review the cytotoxic and clinical effects of BAK on the ocular surface and discuss existing and emerging options for ocular disease management that can minimize or eliminate BAK exposure.
Lanthanum(III) triggers AtrbohD- and jasmonic acid-dependent systemic endocytosis in plants
Authors: Cheng Mengzhu , Wang Lihong , Zhou Qing , Chao Daiyin , Nagawa Shingo , He Ding , Zhang Jiazhi , Li Hui , Tan Li , Gu Zhenhong , Huang Xiaohua , Yang Zhenbiao
Published: July 2021

Trivalent rare earth elements (REEs) are widely used in agriculture. Aerially applied REEs enter leaf epidermal cells by endocytosis and act systemically to improve the growth of the whole plant. The mechanistic basis of their systemic activity is unclear. Here, we show that treatment of Arabidopsis leaves with trivalent lanthanum [La(III)], a representative of REEs, triggers systemic endocytosis from leaves to roots. La(III)-induced systemic endocytosis requires AtrbohD-mediated reactive oxygen species production and jasmonic acid. Systemic endocytosis impacts the accumulation of mineral elements and the development of roots consistent with the growth promoting effects induced by aerially applied REEs. These findings provide insights into the mechanistic basis of REE activity in plants.
Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins
Authors: Singh Nilmani , Reyes-Ordoñez Adriana , Compagnone Michael A. , Moreno Jesus F. , Leslie Benjamin J. , Ha Taekjip , Chen Jie
Published: July 2021

Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employ a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. Of 67 human PH domain-containing proteins initially examined, 36 (54%) are found to have affinity for PIPs with various specificity, the majority of which have not been reported before. Further investigation of ARHGEF3 reveals distinct structural requirements for its binding to PI(4,5)P2 and PI(3,5)P2, and functional relevance of its PI(4,5)P2 binding. We generate a recursive-learning algorithm based on the assay results to analyze the sequences of 242 human PH domains, predicting that 49% of them bind PIPs. Twenty predicted binders and 11 predicted non-binders are assayed, yielding results highly consistent with the prediction. Taken together, our findings reveal unexpected lipid-binding specificity of PH domain-containing proteins.
Polarization-transparent silicon photonic add-drop multiplexer with wideband hitless tuneability
Authors: Morichetti Francesco , Milanizadeh Maziyar , Petrini Matteo , Zanetto Francesco , Ferrari Giorgio , de Aguiar Douglas Oliveira , Guglielmi Emanuele , Sampietro Marco , Melloni Andrea
Published: July 2021

Flexible optical networks require reconfigurable devices with operation on a wavelength range of several tens of nanometers, hitless tuneability (i.e. transparency to other channels during reconfiguration), and polarization independence. All these requirements have not been achieved yet in a single photonic integrated device and this is the reason why the potential of integrated photonics is still largely unexploited in the nodes of optical communication networks. Here we report on a fully-reconfigurable add-drop silicon photonic filter, which can be tuned well beyond the extended C-band (almost 100 nm) in a complete hitless (>35 dB channel isolation) and polarization transparent (1.2 dB polarization dependent loss) way. This achievement is the result of blended strategies applied to the design, calibration, tuning and control of the device. Transmission quality assessment on dual polarization 100 Gbit/s (QPSK) and 200 Gbit/s (16-QAM) signals demonstrates the suitability for dynamic bandwidth allocation in core networks, backhaul networks, intra- and inter-datacenter interconnects.
Effective variant filtering and expected candidate variant yield in studies of rare human disease
Authors: Pedersen Brent S. , Brown Joe M. , Dashnow Harriet , Wallace Amelia D. , Velinder Matt , Tristani-Firouzi Martin , Schiffman Joshua D. , Tvrdik Tatiana , Mao Rong , Best D. Hunter , Bayrak-Toydemir Pinar , Quinlan Aaron R.
Published: July 2021

In studies of families with rare disease, it is common to screen for de novo mutations, as well as recessive or dominant variants that explain the phenotype. However, the filtering strategies and software used to prioritize high-confidence variants vary from study to study. In an effort to establish recommendations for rare disease research, we explore effective guidelines for variant (SNP and INDEL) filtering and report the expected number of candidates for de novo dominant, recessive, and autosomal dominant modes of inheritance. We derived these guidelines using two large family-based cohorts that underwent whole-genome sequencing, as well as two family cohorts with whole-exome sequencing. The filters are applied to common attributes, including genotype-quality, sequencing depth, allele balance, and population allele frequency. The resulting guidelines yield ~10 candidate SNP and INDEL variants per exome, and 18 per genome for recessive and de novo dominant modes of inheritance, with substantially more candidates for autosomal dominant inheritance. For family-based, whole-genome sequencing studies, this number includes an average of three de novo, ten compound heterozygous, one autosomal recessive, four X-linked variants, and roughly 100 candidate variants following autosomal dominant inheritance. The slivar software we developed to establish and rapidly apply these filters to VCF files is available at https://github.com/brentp/slivar under an MIT license, and includes documentation and recommendations for best practices for rare disease analysis.
Longitudinal evolution of non-motor symptoms in early Parkinson’s disease: a 3-year prospective cohort study
Authors: Ou Ruwei , Hou Yanbing , Wei Qianqian , Lin Junyu , Liu Kuncheng , Zhang Lingyu , Jiang Zheng , Cao Bei , Zhao Bi , Song Wei , Shang Huifang
Published: July 2021

The progression of global non-motor symptoms (NMS) in Chinese patients with Parkinson’s disease (PD) has not been explored. We aimed to examine the longitudinal evolution of overall NMS in a 3-year prospective Chinese cohort with early-stage PD. We included 224 patients with early PD who underwent annual evaluation of motor and non-motor symptoms. NMS was assessed using the non-motor symptoms scale (NMSS). We observed an increased number of NMS in the majority of the NMSS domains except mood/apathy and sexual dysfunctions. Significant deterioration was observed in the sleep/fatigue, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, and miscellaneous domains during the follow-up (P < 0.05). Notably, the number and the score of sexual dysfunctions decreased with the progression of the disease. All NMSS domains showed a small effect size from baseline to 1-, 2-, and 3-year follow-ups (effect size < 0.5). The generalized estimating equations model indicated that the total number of NMS was significantly associated with age and the Unified Parkinson’s Disease Rating Scale (UPDRS) III score (P < 0.05). Multiple logistic regression indicated that a high number of NMS at baseline was associated with a 3-point, a 6-point, and a 9-point increase in the UPDRS III score from baseline to 1-year (odds ratio [OR] 1.074, P = 0.017), 2-year (OR 1.113, P = 0.001), and 3-year (OR 1.117, P < 0.001), respectively. Our study indicated that overall NMS evolution in early PD is mild and multidimensional; a high NMS burden in early PD predicts the faster motor progression of PD. Our study is helpful for understanding the longitudinal evolution of NMS in PD.
Selectively targeting haemagglutinin antigen to chicken CD83 receptor induces faster and stronger immunity against avian influenza
Authors: Shrestha Angita , Sadeyen Jean-Remy , Lukosaityte Deimante , Chang Pengxiang , Smith Adrian , Van Hulten Marielle , Iqbal Munir
Published: July 2021

The immunogenicity and protective efficacy of vaccines can be enhanced by the selective delivery of antigens to the antigen-presenting cells (APCs). In this study, H9N2 avian influenza virus haemagglutinin (HA) antigen, was targeted by fusing it to single-chain fragment variable (scFv) antibodies specific to CD83 receptor expressed on chicken APCs. We observed an increased level of IFNγ, IL6, IL1β, IL4, and CxCLi2 mRNA upon stimulation of chicken splenocytes ex vivo by CD83 scFv targeted H9HA. In addition, CD83 scFv targeted H9HA induced higher serum haemagglutinin inhibition activity and virus neutralising antibodies compared to untargeted H9HA, with induction of antibodies as early as day 6 post primary vaccination. Furthermore, chickens vaccinated with CD83 scFv targeted H9HA showed reduced H9N2 challenge virus shedding compared to untargeted H9HA. These results suggest that targeting antigens to CD83 receptors could improve the efficacy of poultry vaccines.
Structural and functional characterization of the intracellular filament-forming nitrite oxidoreductase multiprotein complex
Authors: Chicano Tadeo Moreno , Dietrich Lea , de Almeida Naomi M. , Akram Mohd. , Hartmann Elisabeth , Leidreiter Franziska , Leopoldus Daniel , Mueller Melanie , Sánchez Ricardo , Nuijten Guylaine H. L. , Reimann Joachim , Seifert Kerstin-Anikó , Schlichting Ilme , van Niftrik Laura , Jetten Mike S. M. , Dietl Andreas , Kartal Boran , Parey Kristian , Barends Thomas R. M.
Published: July 2021

Nitrate is an abundant nutrient and electron acceptor throughout Earth’s biosphere. Virtually all nitrate in nature is produced by the oxidation of nitrite by the nitrite oxidoreductase (NXR) multiprotein complex. NXR is a crucial enzyme in the global biological nitrogen cycle, and is found in nitrite-oxidizing bacteria (including comammox organisms), which generate the bulk of the nitrate in the environment, and in anaerobic ammonium-oxidizing (anammox) bacteria which produce half of the dinitrogen gas in our atmosphere. However, despite its central role in biology and decades of intense study, no structural information on NXR is available. Here, we present a structural and biochemical analysis of the NXR from the anammox bacterium Kuenenia stuttgartiensis, integrating X-ray crystallography, cryo-electron tomography, helical reconstruction cryo-electron microscopy, interaction and reconstitution studies and enzyme kinetics. We find that NXR catalyses both nitrite oxidation and nitrate reduction, and show that in the cell, NXR is arranged in tubules several hundred nanometres long. We reveal the tubule architecture and show that tubule formation is induced by a previously unidentified, haem-containing subunit, NXR-T. The results also reveal unexpected features in the active site of the enzyme, an unusual cofactor coordination in the protein’s electron transport chain, and elucidate the electron transfer pathways within the complex.
Transcriptome of rat subcortical white matter and spinal cord after spinal injury and cortical stimulation
Authors: Kondiles Bethany R. , Wei Haichao , Chaboub Lesley S. , Horner Philip J. , Wu Jia Qian , Perlmutter Steve I.
Published: July 2021

Spinal cord injury disrupts ascending and descending neural signals causing sensory and motor dysfunction. Neuromodulation with electrical stimulation is used in both clinical and research settings to induce neural plasticity and improve functional recovery following spinal trauma. However, the mechanisms by which electrical stimulation affects recovery remain unclear. In this study we examined the effects of cortical electrical stimulation following injury on transcription at several levels of the central nervous system. We performed a unilateral, incomplete cervical spinal contusion injury in rats and delivered stimulation for one week to the contralesional motor cortex to activate the corticospinal tract and other pathways. RNA was purified from bilateral subcortical white matter and 3 levels of the spinal cord. Here we provide the complete data set in the hope that it will be useful for researchers studying electrical stimulation as a therapy to improve recovery from the deficits associated with spinal cord injury.
A simple microscopy setup for visualizing cellular responses to DNA damage at particle accelerator facilities
Authors: Qian Haibin , Hoebe Ron A. , Faas Michel R. , van Goethem Marc Jan , van der Graaf Emiel R. , Meyer Christoph , Kiewiet Harry , Brandenburg Sytze , Krawczyk Przemek M.
Published: July 2021

Cellular responses to DNA double-strand breaks (DSBs) not only promote genomic integrity in healthy tissues, but also largely determine the efficacy of many DNA-damaging cancer treatments, including X-ray and particle therapies. A growing body of evidence suggests that activation of the mechanisms that detect, signal and repair DSBs may depend on the complexity of the initiating DNA lesions. Studies focusing on this, as well as on many other radiobiological questions, require reliable methods to induce DSBs of varying complexity, and to visualize the ensuing cellular responses. Accelerated particles of different energies and masses are exceptionally well suited for this task, due to the nature of their physical interactions with the intracellular environment, but visualizing cellular responses to particle-induced damage - especially in their early stages - at particle accelerator facilities, remains challenging. Here we describe a straightforward approach for real-time imaging of early response to particle-induced DNA damage. We rely on a transportable setup with an inverted fluorescence confocal microscope, tilted at a small angle relative to the particle beam, such that cells can be irradiated and imaged without any microscope or beamline modifications. Using this setup, we image and analyze the accumulation of fluorescently-tagged MDC1, RNF168 and 53BP1—key factors involved in DSB signalling—at DNA lesions induced by 254 MeV α-particles. Our results provide a demonstration of technical feasibility and reveal asynchronous initiation of accumulation of these proteins at different individual DSBs.
Tree-aggregated predictive modeling of microbiome data
Authors: Bien Jacob , Yan Xiaohan , Simpson Léo , Müller Christian L.
Published: July 2021

Modern high-throughput sequencing technologies provide low-cost microbiome survey data across all habitats of life at unprecedented scale. At the most granular level, the primary data consist of sparse counts of amplicon sequence variants or operational taxonomic units that are associated with taxonomic and phylogenetic group information. In this contribution, we leverage the hierarchical structure of amplicon data and propose a data-driven and scalable tree-guided aggregation framework to associate microbial subcompositions with response variables of interest. The excess number of zero or low count measurements at the read level forces traditional microbiome data analysis workflows to remove rare sequencing variants or group them by a fixed taxonomic rank, such as genus or phylum, or by phylogenetic similarity. By contrast, our framework, which we call  (ee-ggregation of ompositional data), learns data-adaptive taxon aggregation levels for predictive modeling, greatly reducing the need for user-defined aggregation in preprocessing while simultaneously integrating seamlessly into the compositional data analysis framework. We illustrate the versatility of our framework in the context of large-scale regression problems in human gut, soil, and marine microbial ecosystems. We posit that the inferred aggregation levels provide highly interpretable taxon groupings that can help microbiome researchers gain insights into the structure and functioning of the underlying ecosystem of interest.
Automatic segmentation of skin cells in multiphoton data using multi-stage merging
Authors: Prinke Philipp , Haueisen Jens , Klee Sascha , Rizqie Muhammad Qurhanul , Supriyanto Eko , König Karsten , Breunig Hans Georg , Piątek Łukasz
Published: July 2021

We propose a novel automatic segmentation algorithm that separates the components of human skin cells from the rest of the tissue in fluorescence data of three-dimensional scans using non-invasive multiphoton tomography. The algorithm encompasses a multi-stage merging on preprocessed superpixel images to ensure independence from a single empirical global threshold. This leads to a high robustness of the segmentation considering the depth-dependent data characteristics, which include variable contrasts and cell sizes. The subsequent classification of cell cytoplasm and nuclei are based on a cell model described by a set of four features. Two novel features, a relationship between outer cell and inner nucleus (OCIN) and a stability index, were derived. The OCIN feature describes the topology of the model, while the stability index indicates segment quality in the multi-stage merging process. These two new features, combined with the local gradient magnitude and compactness, are used for the model-based fuzzy evaluation of the cell segments. We exemplify our approach on an image stack with 200 × 200 × 100  μm3, including the skin layers of the stratum spinosum and the stratum basale of a healthy volunteer. Our image processing pipeline contributes to the fully automated classification of human skin cells in multiphoton data and provides a basis for the detection of skin cancer using non-invasive optical biopsy.
Analysing omics data sets with weighted nodes networks (WNNets)
Authors: Tosadori Gabriele , Di Silvestre Dario , Spoto Fausto , Mauri Pierluigi , Laudanna Carlo , Scardoni Giovanni
Published: July 2021

Current trends in biomedical research indicate data integration as a fundamental step towards precision medicine. In this context, network models allow representing and analysing complex biological processes. However, although effective in unveiling network properties, these models fail in considering the individual, biochemical variations occurring at molecular level. As a consequence, the analysis of these models partially loses its predictive power. To overcome these limitations, Weighted Nodes Networks (WNNets) were developed. WNNets allow to easily and effectively weigh nodes using experimental information from multiple conditions. In this study, the characteristics of WNNets were described and a proteomics data set was modelled and analysed. Results suggested that degree, an established centrality index, may offer a novel perspective about the functional role of nodes in WNNets. Indeed, degree allowed retrieving significant differences between experimental conditions, highlighting relevant proteins, and provided a novel interpretation for degree itself, opening new perspectives in experimental data modelling and analysis. Overall, WNNets may be used to model any high-throughput experimental data set requiring weighted nodes. Finally, improving the power of the analysis by using centralities such as betweenness may provide further biological insights and unveil novel, interesting characteristics of WNNets.
The association between environmental exposures to chlordanes, adiposity and diabetes-related features: a systematic review and meta-analysis
Authors: Mendes Vânia , Ribeiro Cláudia , Delgado Inês , Peleteiro Bárbara , Aggerbeck Martine , Distel Emilie , Annesi-Maesano Isabella , Sarigiannis Denis , Ramos Elisabete
Published: July 2021

Chlordane compounds (CHLs) are components of technical chlordane listed in the Stockholm convention on persistent organic pollutants identified as endocrine disrupting chemicals (EDCs) and may interfere with hormone biosynthesis, metabolism or action resulting in an unbalanced hormonal function. There is increasing scientific evidence showing EDCs as risk factors in the pathogenesis and development of obesity and obesity-related metabolic syndromes such as type 2 diabetes, but there is no systematized information on the effect of CHLs in humans. Our aim is to identify the epidemiological data on the association between CHLs with adiposity and diabetes using a systematic approach to identify the available data and summarizing the results through meta-analysis. We searched PubMed and Web of Science from inception up to 15 February 2021, to retrieve original data on the association between chlordanes, and adiposity or diabetes. For adiposity, regression coefficients and Pearson or Spearman correlation coefficients were extracted and converted into standardized regression coefficients. Data were combined using fixed effects meta-analyses to compute summary regression coefficients and corresponding 95% confidence intervals (95% CI). For the association between chlordanes and diabetes, Odds ratios (ORs) were extracted and the DerSimonian and Laird method was used to compute summary estimates and respective 95% CI. For both, adjusted estimates were preferred, whenever available. Among 31 eligible studies, mostly using a cross-sectional approach, the meta-analysis for adiposity was possible only for oxychlordane and transchlordane, none of them were significantly associated with adiposity [(β = 0.04, 95% CI 0.00; 0.07, I2 = 89.7%)] and (β = 0.02, 95% CI − 0.01; 0.06), respectively. For diabetes, the estimates were positive for all compounds but statistically significant for oxychlordane [OR = 1.96 (95% CI 1.19; 3.23)]; for trans-nonachlor [OR = 2.43 (95% CI 1.64; 3.62)] and for heptachlor epoxide [OR = 1.88 (95% CI 1.42; 2.49)]. Our results support that among adults, the odds of having diabetes significantly increase with increasing levels of chlordanes. The data did not allow to reach a clear conclusion regarding the association with adiposity.
Microarray-based selection of a serum biomarker panel that can discriminate between latent and active pulmonary TB
Authors: Li Zhihui , Hu Jianjun , Liu Pengchong , Cui Dan , Di Hongqin , Wu Shucai
Published: July 2021

Bacterial culture of M. tuberculosis (MTB), the causative agent of tuberculosis (TB), from clinical specimens is the gold standard for laboratory diagnosis of TB, but is slow and culture-negative TB cases are common. Alternative immune-based and molecular approaches have been developed, but cannot discriminate between active TB (ATB) and latent TB (LTBI). Here, to identify biomarkers that can discriminate between ATB and LTBI/healthy individuals (HC), we profiled 116 serum samples (HC, LTBI and ATB) using a protein microarray containing 257 MTB secreted proteins, identifying 23 antibodies against MTB antigens that were present at significantly higher levels in patients with ATB than in those with LTBI and HC (Fold change > 1.2; p < 0.05). A 4-protein biomarker panel (Rv0934, Rv3881c, Rv1860 and Rv1827), optimized using SAM and ROC analysis, had a sensitivity of 67.3% and specificity of 91.2% for distinguishing ATB from LTBI, and 71.2% sensitivity and 96.3% specificity for distinguishing ATB from HC. Validation of the four candidate biomarkers in ELISA assays using 440 serum samples gave consistent results. The promising sensitivity and specificity of this biomarker panel suggest it merits further investigation for its potential as a diagnostic for discriminating between latent and active TB.
Impact of quality of life related to foot problems: a case–control study
Authors: López-López Daniel , Pérez-Ríos Mónica , Ruano-Ravina Alberto , Losa-Iglesias Marta Elena , Becerro-de-Bengoa-Vallejo Ricardo , Romero-Morales Carlos , Calvo-Lobo Cesar , Navarro-Flores Emmanuel
Published: July 2021

Foot problems are highly prevalent conditions, being a frequent reason for medical and podiatric consultation. The aim of this study was to compare the differences of quality of life (QoL) related to foot health in people with and without the presence of foot problems. A case–control study was carried out in an outpatient centre, where a clinician recorded data related to sociodemographic and clinical characteristics. In addition, self-reported data on foot health-related quality of life were recorded using the Spanish version of the Foot Health Status Questionnaire. The sample consisted of 498 participants (249 cases and 249 controls), with a median age of 30 years and an interquartile range of 23 years. The differences between the groups were statistically significant for gender, age, footwear, general health, foot health, and physical activity. Cases showed lower scores for the domain of footwear, physical activity and vitality compared to controls. Foot pathologies have a negative impact on quality of life related to foot health, and the domains of footwear, general health and physical activity seem to be the factors that are associated with the presence of alterations and foot deformities.
Improved optical properties of perovskite solar cells by introducing Ag nanopartices and ITO AR layers
Authors: Chen Yangxi , Du Chaoling , Sun Lu , Fu Tianyi , Zhang Ruxin , Rong Wangxu , Cao Shuiyan , Li Xiang , Shen Honglie , Shi Daning
Published: July 2021

Embedded noble metal nanostructures and surface anti-reflection (AR) layers affect the optical properties of methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells significantly. Herein, by employing a combined finite element method and genetic algorithm approach, we report five different types of CH3NH3PbI3 perovskite solar cells by introducing embedded Ag nanoparticles within the CH3NH3PbI3 layer and/or top ITO cylinder grating as an AR layer. The maximum photocurrent was optimized to reach 23.56 mA/cm2, which was 1.09/1.17 times higher than Tran’s report/ flat cases. It is also comparable with values (23.6 mA/cm2) reported in the literature. The calculations of the electric field and charge carrier generation rate of the optimized solar cell further confirms this improvement than flat cases. It attributes to the synergistic effect of the embedded Ag nanoparticles and ITO AR layer. The results obtained herein hold great promise for future boosting the optical efficiency of perovskite solar cells.
Development of custom lead shield and strainer for targeted irradiation for mice in the gamma cell chamber
Authors: Hasan Nurhaslina , Sham Nur Fatihah Ronny , Karim Muhammad Khalis Abdul , Fuad Syed Baharom Syed Ahmad , Hasani Narimah Abdul Hamid , Omar Effat , Ibahim Mohammad Johari
Published: July 2021

We presented a development of a custom lead shield and mouse strainer for targeted irradiation from the gamma-cell chamber. This study was divided into two parts i.e., to (i) fabricate the shield and strainer from a lead (Pb) and (ii) optimize the irradiation to the mice-bearing tumour model with 2 and 8 Gy absorbed doses. The lead shielding was fabricated into a cuboid shape with a canal on the top and a hole on the vertical side for the beam path. Respective deliveries doses of 28 and 75 Gy from gamma-cell were used to achieve 2 and 8 Gy absorbed doses at the tumour sites.
Study on the optimal position of the roof low roadway based on the response surface methodology
Authors: Zhu Hongqing , Fang Shuhao , Huo Yujia , Liao Qi , Hu Lintao , Zhang Yilong , Li Feng
Published: July 2021

For determine the optimum position of the roof low roadway, the optimal solution is derived according to the response surface methodology. The UDEC numerical simulation of the overburden gives the porosity distribution of the strike fractured zone, the upper limit heights of the caving zone and the fractured zone are obtained as 18 m and 65 m, respectively. Based on the porosity distribution, the FLUENT numerical models of the goaf zone, air inlet roadway, air return roadway, working face and roof low roadway were established to simulate the gas concentration in the upper corner and gas drainage volume in roof low roadway during mining. Using the vertical and horizontal distance of the roof low roadway as the influencing factors, the experimental scheme of the position of the roof low roadway was designed according to the response surface method, and the response values were obtained from the FLUENT simulation experiments, predicting that the vertical and horizontal distances of the roof low roadway were 7.7 m and 5.9 m respectively when the interaction between the gas concentration in the upper corner and gas drainage volume in roof low roadway was optimal. Field tests showed that the average gas concentration in the upper corner and the average gas drainage volume in roof low roadway were 0.432% and 40.861 m3/min respectively, both of which were less than 10% of the error from the simulations. The design of the roof low roadway has effectively managed the gas accumulation problem in the upper corner.
Growth and autolysis of the kefir yeast Kluyveromyces marxianus in lactate culture
Authors: Lo Shou-Chen , Yang Chia-Yin , Mathew Dony Chacko , Huang Chieh-Chen
Published: July 2021

Kluyveromyces marxianus is a yeast that could be identified from kefir and can use a broad range of substrates, such as glucose and lactate, as carbon sources. The lactate produced in kefir culture can be a substrate for K. marxianus. However, the complexity of the kefir microbiota makes the traits of K. marxianus difficult to study. In this research, we focused on K. marxianus cultured with lactate as the sole carbon source. The optimal growth and released protein in lactate culture were determined under different pH conditions, and the LC–MS/MS-identified proteins were associated with the tricarboxylic acid cycle, glycolysis pathway, and cellular stress responses in cells, indicating that autolysis of K. marxianus had occurred under the culture conditions. The abundant glyceraldehyde-3-phosphate dehydrogenase 1 (GAP1) was cocrystallized with other proteins in the cell-free fraction, and the low transcription level of the GAP1 gene indicated that the protein abundance under autolysis conditions was dependent on protein stability. These results suggest that lactate induces the growth and autolysis of K. marxianus, releasing proteins and peptides. These findings can be fundamental for K. marxianus probiotic and kefir studies in the future.
Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury
Authors: Collins Kelsey H. , Schwartz Drew J. , Lenz Kristin L. , Harris Charles A. , Guilak Farshid
Published: July 2021

Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. The purpose of this study was to evaluate the relationship between the gut microbiota and knee cartilage damage while controlling for adiposity, high fat diet, and joint injury using lipodystrophic (LD) mice. LD and littermate control (WT) mice were fed a high fat diet, chow diet, or were rescued with fat implantation, then challenged with destabilization of the medial meniscus surgery to induce osteoarthritis (OA). 16S rRNA sequencing was conducted on feces. MaAslin2 was used to determine associations between taxonomic relative abundance and OA severity. While serum LPS levels between groups were similar, synovial fluid LPS levels were increased in both limbs of HFD WT mice compared to all groups, except for fat transplanted animals. The Bacteroidetes:Firmicutes ratio of the gut microbiota was significantly reduced in HFD and OA-rescued animals when compared to chow. Nine novel significant associations were found between gut microbiota taxa and OA severity. These findings suggest the presence of causal relationships the gut microbiome and cartilage health, independent of diet or adiposity, providing potential therapeutic targets through manipulation of the microbiome.
Forest canopy mitigates soil N2O emission during hot moments
Authors: Mander Ülo , Krasnova Alisa , Escuer-Gatius Jordi , Espenberg Mikk , Schindler Thomas , Machacova Katerina , Pärn Jaan , Maddison Martin , Megonigal J. Patrick , Pihlatie Mari , Kasak Kuno , Niinemets Ülo , Junninen Heikki , Soosaar Kaido
Published: July 2021

Riparian forests are known as hot spots of nitrogen cycling in landscapes. Climate warming speeds up the cycle. Here we present results from a multi-annual high temporal-frequency study of soil, stem, and ecosystem (eddy covariance) fluxes of N2O from a typical riparian forest in Europe. Hot moments (extreme events of N2O emission) lasted a quarter of the study period but contributed more than half of soil fluxes. We demonstrate that high soil emissions of N2O do not escape the ecosystem but are processed in the canopy. Rapid water content change across intermediate soil moisture was a major determinant of elevated soil emissions in spring. The freeze-thaw period is another hot moment. However, according to the eddy covariance measurements, the riparian forest is a modest source of N2O. We propose photochemical reactions and dissolution in canopy-space water as reduction mechanisms.
Combined FGFR and Akt pathway inhibition abrogates growth of FGFR1 overexpressing EGFR-TKI-resistant NSCLC cells
Authors: Terp Mikkel G. , Jacobsen Kirstine , Molina Miguel Angel , Karachaliou Niki , Beck Hans C. , Bertran-Alamillo Jordi , Giménez-Capitán Ana , Cardona Andrés F. , Rosell Rafael , Ditzel Henrik J.
Published: July 2021

EGFR tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients is inevitable. Identification of resistance mechanisms and corresponding targeting strategies can lead to more successful later-line treatment in many patients. Using spectrometry-based proteomics, we identified increased fibroblast growth factor receptor 1 (FGFR1) expression and Akt activation across erlotinib, gefitinib, and osimertinib EGFR-TKI-resistant cell line models. We show that while combined EGFR-TKI and FGFR inhibition showed some efficacy, simultaneous inhibition of FGFR and Akt or PI3K induced superior synergistic growth inhibition of FGFR1-overexpressing EGFR-TKI-resistant NSCLC cells. This effect was confirmed in vivo. Only dual FGFR and Akt inhibition completely blocked the resistance-mediating signaling pathways downstream of Akt. Further, increased FGFR1 expression was associated with significantly lower PFS in EGFR-TKI-treated NSCLC patients, and increased FGFR1 were demonstrated in a few post- vs. pre-EGFR-TKI treatment clinical biopsies. The superior therapeutic benefit of combining FGFR and Akt inhibitors provide the rationale for clinical trials of this strategy.
Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals
Authors: Kiwimagi Katherine A. , Letendre Justin H. , Weinberg Benjamin H. , Wang Junmin , Chen Mingzhe , Watanabe Leandro , Myers Chris J. , Beal Jacob , Wong Wilson W. , Weiss Ron
Published: July 2021

Many synthetic gene circuits are restricted to single-use applications or require iterative refinement for incorporation into complex systems. One example is the recombinase-based digitizer circuit, which has been used to improve weak or leaky biological signals. Here we present a workflow to quantitatively define digitizer performance and predict responses to different input signals. Using a combination of signal-to-noise ratio (SNR), area under a receiver operating characteristic curve (AUC), and fold change (FC), we evaluate three small-molecule inducible digitizer designs demonstrating FC up to 508x and SNR up to 3.77 dB. To study their behavior further and improve modularity, we develop a mixed phenotypic/mechanistic model capable of predicting digitizer configurations that amplify a synNotch cell-to-cell communication signal (Δ SNR up to 2.8 dB). We hope the metrics and modeling approaches here will facilitate incorporation of these digitizers into other systems while providing an improved workflow for gene circuit characterization.
Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy
Authors: He Michael Y. , Halford Michael M. , Liu Ruofei , Roy James P. , Grant Zoe L. , Coultas Leigh , Thio Niko , Gilan Omer , Chan Yih-Chih , Dawson Mark A. , Achen Marc G. , Stacker Steven A.
Published: July 2021

Angiogenesis underlies development, physiology and pathogenesis of cancer, eye and cardiovascular diseases. Inhibiting aberrant angiogenesis using anti-angiogenic therapy (AAT) has been successful in the clinical treatment of cancer and eye diseases. However, resistance to AAT inevitably occurs and its molecular basis remains poorly understood. Here, we uncover molecular modifiers of the blood endothelial cell (EC) response to a widely used AAT bevacizumab by performing a pooled genetic screen using three-dimensional microcarrier-based cell culture and CRISPR–Cas9. Functional inhibition of the epigenetic reader BET family of proteins BRD2/3/4 shows unexpected mitigating effects on EC survival and/or proliferation upon VEGFA blockade. Moreover, transcriptomic and pathway analyses reveal an interaction between epigenetic regulation and anti-angiogenesis, which may affect chromosomal structure and activity in ECs via the cell cycle regulator CDC25B phosphatase. Collectively, our findings provide insight into epigenetic regulation of the EC response to VEGFA blockade and may facilitate development of quality biomarkers and strategies for overcoming resistance to AAT.
Non-flipping DNA glycosylase AlkD scans DNA without formation of a stable interrogation complex
Authors: Ahmadi Arash , Till Katharina , Backe Paul Hoff , Blicher Pernille , Diekmann Robin , Schüttpelz Mark , Glette Kyrre , Tørresen Jim , Bjørås Magnar , Rowe Alexander D. , Dalhus Bjørn
Published: July 2021

The multi-step base excision repair (BER) pathway is initiated by a set of enzymes, known as DNA glycosylases, able to scan DNA and detect modified bases among a vast number of normal bases. While DNA glycosylases in the BER pathway generally bend the DNA and flip damaged bases into lesion specific pockets, the HEAT-like repeat DNA glycosylase AlkD detects and excises bases without sequestering the base from the DNA helix. We show by single-molecule tracking experiments that AlkD scans DNA without forming a stable interrogation complex. This contrasts with previously studied repair enzymes that need to flip bases into lesion-recognition pockets and form stable interrogation complexes. Moreover, we show by design of a loss-of-function mutant that the bimodality in scanning observed for the structural homologue AlkF is due to a key structural differentiator between AlkD and AlkF; a positively charged β-hairpin able to protrude into the major groove of DNA.
Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms
Authors: Brechbühl Julien , Lopes Ana Catarina , Wood Dean , Bouteiller Sofiane , de Vallière Aurélie , Verdumo Chantal , Broillet Marie-Christine
Published: July 2021

COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent’s nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.
Neutralising SARS-CoV-2 RBD-specific antibodies persist for at least six months independently of symptoms in adults
Authors: Wagner Angelika , Guzek Angela , Ruff Johanna , Jasinska Joanna , Scheikl Ute , Zwazl Ines , Kundi Michael , Stockinger Hannes , Farcet Maria R. , Kreil Thomas R. , Hoeltl Eva , Wiedermann Ursula
Published: July 2021

Background

In spring 2020, at the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Europe, we set up an assay system for large-scale testing of virus-specific and neutralising antibodies including their longevity.

Methods

We analysed the sera of 1655 adult employees for SARS-CoV-2-specific antibodies using the S1 subunit of the spike protein of SARS-CoV-2. Sera containing S1-reactive antibodies were further evaluated for receptor-binding domain (RBD)- and nucleocapsid protein (NCP)-specific antibodies in relation to the neutralisation test (NT) results at three time points over six months.

Results

We detect immunoglobulin G (IgG) and/or IgA antibodies reactive to the S1 protein in 10.15% (n = 168) of the participants. In total, 0.97% (n = 16) are positive for S1-IgG, 0.91% (n = 15) were S1-IgG- borderline and 8.28% (n = 137) exhibit only S1-IgA antibodies. Of the 168 S1-reactive sera, 8.33% (n = 14) have detectable RBD-specific antibodies and 6.55% (n = 11) NCP-specific antibodies. The latter correlates with NTs (kappa coefficient = 0.8660) but start to decline after 3 months. RBD-specific antibodies correlate most closely with the NT (kappa = 0.9448) and only these antibodies are stable for up to six months. All participants with virus-neutralising antibodies report symptoms, of which anosmia and/or dysgeusia correlate most closely with the detection of virus-neutralising antibodies.

Conclusions

RBD-specific antibodies are most reliably detected post-infection, independent of the number/severity of symptoms, and correlate with neutralising antibodies at least for six months. They thus qualify best for large-scale seroepidemiological evaluation of both antibody reactivity and virus neutralisation.
Dispersion-enhancing surface treatment of AuNPs for a reduced probe loading and detection limit using t-SPR detection
Authors: Yeung Wing Kiu , Lo Shu-Cheng , Wang Sheng-Hann , Wei Pei-Kuen , Cheng Ji-Yen
Published: July 2021

A nanoplasmonic platform for oligonucleotide detection is developed. Functionalized unmodified PEG-Au was used as an SPR signal amplifier. The SPR sensor exhibited high sensitivity with a detection limit of 100 aM. The platform was able to detect a single mismatch sequence.
Tuning water adsorption, stability, and phase in Fe-MIL-101 and Fe-MIL-88 analogs with amide functionalization
Authors: Kuznicki Andrew , Lorzing Gregory R. , Bloch Eric D.
Published: July 2021

Straightforward ligand functionalization can be utilized to tune the properties of iron(iii) metal–organic frameworks.
Solution NMR of synthetic cavity containing supramolecular systems: what have we learned on and from?
Authors: Cohen Yoram , Slovak Sarit , Avram Liat
Published: July 2021

NMR has played a pivotal role in the study of host–guest complexes and supramolecular systems. Here selected examples are used to demonstrate the impact and the added values of using multi-parametric NMR when studying such systems in solution.
Active site engineering of atomically dispersed transition metal–heteroatom–carbon catalysts for oxygen reduction
Authors: Zhu Jiawei , Mu Shichun
Published: July 2021

Active site engineering of atomically dispersed transition metal–heteroatom–carbon (TM–H–C) catalysts comprises atomic-scale tunable site configuration, active site propagation, structural evolution and multi-active center creation.
A high contrast mechanochromic luminescent diacetylene-linked bis-benzothiadiazole derivative
Authors: Echeverri Marcelo , Ruiz Constanza , Gómez-Lor Berta
Published: July 2021

A rod-shaped self-assembling diacetylene-linked bis-benzothiadiazole derivative presents a high contrast luminescence phase transformation upon shearing which is reversed upon heating.
Can bulk nanobubbles be stabilized by electrostatic interaction?
Authors: Wang Shuo , Zhou Limin , Gao Yongxiang
Published: July 2021

The effect of the charges on the pressure inside nanobubbles is much smaller than previously predicted.
Carboxyl groups do not play the major role in binding metal cations by graphene oxide
Authors: Shayimova Julia , Amirov Rustem R. , Iakunkov Artem , Talyzin Alexandr , Dimiev Ayrat M.
Published: July 2021

Interactions of Mn2+ ions with graphene oxides, prepared by Hummers' (HGO) and Brodie's (BGO) methods are investigated by means of the NMR relaxation. Metal ions are bound efficiently by BGO, containing a negligibly small quantity of carboxyl groups.
Molecular simulation of polymer crystallization under chain and space confinement
Authors: Ming Yongqiang , Zhou Zhiping , Hao Tongfan , Nie Yijing
Published: July 2021

The tethering point can be used as a nucleation site.
Correlating solvation with conformational pathways of proteins in alcohol–water mixtures: a THz spectroscopic insight
Authors: Pyne Partha , Das Mahanta Debasish , Gohil Himanshu , Prabhu S. S. , Mitra Rajib Kumar
Published: July 2021

Water, being an active participant in most of the biophysical processes, is important to trace how protein solvation changes as its conformation evolves in the presence of solutes or co-solvents.