bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Respiration Response to Rainfall Modulated by Plant Phenology in a Montane Meadow, East River, Colorado, USA
Authors: Winnick Matthew J. , Lawrence Corey R. , McCormick Maeve , Druhan Jennifer L. , Maher Kate
Published: October 2020

Soil respiration is a primary component of the terrestrial carbon cycle. However, predicting the response of soil respiration to climate change remains a challenge due to the complex interactions between environmental drivers, especially plant phenology, temperature, and soil moisture. In this study, we use a 1‐D diffusion‐reaction model to calculate depth‐resolved CO2 production rates from soil CO2 concentrations and surface efflux observations in a subalpine meadow in the East River watershed, CO. Modeled rates are compared to in situ soil temperature and moisture conditions and MODIS satellite enhanced vegetation index (EVI) representing plant phenology across three hydrologically distinct growing seasons from 2016–2018. While soil respiration correlated with temperature on diel timescales (p < 0.05), seasonal variability was dominated by soil moisture and plant phenology (p < 0.05). We observed significant respiration increases in response to precipitation events; however, magnitude and duration were significantly higher in 2017 than 2016 despite similar wetting characteristics. Based on MODIS EVI, we suggest that the respiration response to rainfall is controlled by plant phenology, which in turn reflects the capacity of plants to respond to precipitation via increased photosynthesis and autotrophic respiration, behavior that is not captured in typical soil respiration pulse models. Projected changes in montane climate such as earlier snowmelt and prolonged fore‐summer drought may decrease soil respiration fluxes by decreasing the overlap between peak productivity and the summer monsoon. Finally, we observed significant late season CO2 fluxes from the deep subsoil (>165 cm) that support growing evidence for the importance of subsoil processes in driving integrated respiration fluxes.
Impact of novel coronavirus disease (COVID-19) on Egyptian dentists’ fear and dental practice (a cross-sectional survey)
Authors: Aly Mariam Mohsen , Elchaghaby Marwa Aly
Published: October 2020

Objectives

This study aimed to evaluate the fear of infection among Egyptian dentists practicing during the current coronavirus disease 2019 (COVID-19) pandemic and to explore the dentist’s knowledge about guidelines to fight the virus and to assess various modifications in dental practice.

Methods

An online survey was submitted to dental professionals. Data were collected through a validated questionnaire consisting of 23 closed-ended questions. The gathered data were statistically analyzed.

Results

An overall 216 dentists completed the survey. A total of 200 (92.6%) dental professionals were afraid of becoming infected with COVID-19 while 196 (90.7%) became anxious to treat patients showing suspicious symptoms. The majority of the participants were aware of the mode of transmission of COVID-19 and a lot of them were updated with the current Disease Control and Prevention (CDC) or World Health Organization (WHO) guidelines for cross-infection control.

Conclusions

COVID-19 pandemic has a significant impact on dental professionals.
Splicing factor SF3B1 promotes endometrial cancer progression via regulating KSR2 RNA maturation
Authors: Popli Pooja , Richters Megan M. , Chadchan Sangappa B. , Kim Tae Hoon , Tycksen Eric , Griffith Obi , Thaker Premal H. , Griffith Malachi , Kommagani Ramakrishna
Published: October 2020

Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the United States. Here, in an attempt to identify new prognostic and therapeutic targets, we focused on a new area for this cancer—alternative mRNA splicing—and investigated whether splicing factor, SF3B1, plays an important role in endometrial cancer pathogenesis. Using a tissue microarray, we found that human endometrial tumors expressed more SF3B1 protein than non-cancerous tissues. Furthermore, SF3B1 knockdown reduced in vitro proliferation, migration, and invasion of the endometrial cancer cell lines Ishikawa and AN3CA. Similarly, the SF3B1 inhibitor, Pladienolide-B (PLAD-B), reduced the Ishikawa and AN3CA cell proliferation and invasion in vitro. Moreover, PLAD-B reduced tumor growth in an orthotopic endometrial cancer mouse model. Using RNA-Seq approach, we identified ~2000 differentially expressed genes (DEGs) with SF3B1 knockdown in endometrial cancer cells. Additionally, alternative splicing (AS) events analysis revealed that SF3B1 depletion led to alteration in multiple categories of AS events including alternative exon skipping (ES), transcript start site usage (TSS), and transcript termination site (TTS) usage. Subsequently, bioinformatics analysis showed KSR2 as a potential candidate for SF3B1-mediated functions in endometrial cancer. Specifically, loss of SF3B1 led to decrease in KSR2 expression, owing to reduced maturation of KSR2 pre-mRNA to a mature RNA. Importantly, we found rescuing the KSR2 expression with SF3B1 knockdown partially restored the cell growth of endometrial cancer cells. Taken together, our data suggest that SF3B1 plays a crucial oncogenic role in the tumorigenesis of endometrial cancer and hence may support the development of SF3B1 inhibitors to treat this disease.
USP7 mediates pathological hepatic de novo lipogenesis through promoting stabilization and transcription of ZNF638
Authors: Ni Wenkai , Lin Shengli , Bian Saiyan , Zheng Wenjie , Qu Lishuai , Fan Yihui , Lu Cuihua , Xiao Mingbing , Zhou Pinghong
Published: October 2020

Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dysregulation remains largely unknown. Ubiquitination of proteins in hepatocytes has been shown to be widely involved in lipid metabolism of liver. Here, we revealed that Ubiquitin-specific peptidase 7 (USP7), a deubiquitinase (DUB), played key roles in DNL through regulation of zinc finger protein 638 (ZNF638) in hepatocytes. USP7 has been shown not only to interact with and deubiquitylate ZNF638, but also to facilitate the transcription of ZNF638 via the stabilization of cAMP responsive element binding protein (CREB). USP7/ZNF638 axis selectively increased the cleavage of sterol regulatory element binding protein (SREBP1C) through AKT/mTORC1/S6K signaling, and formed USP7/ZNF638/SREBP1C nuclear complex to regulate lipogenesis-associated enzymes, including acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), and Stearoyl-CoA desaturase (SCD). In the mice liver steatosis model induced by fructose, USP7 or ZNF638 abrogation significantly ameliorated disease progression. Furthermore, USP7/ZNF638 axis participated in the progression of lipogenesis-associated HCC. Our results have uncovered a novel mechanism of hepatic DNL, which might be beneficial to the development of new therapeutic targets for hepatic lipogenesis-associated diseases.
Long noncoding RNA FGF14-AS2 inhibits breast cancer metastasis by regulating the miR-370-3p/FGF14 axis
Authors: Jin Yucui , Zhang Ming , Duan Rui , Yang Jiashu , Yang Ying , Wang Jue , Jiang Chaojun , Yao Bing , Li Lingyun , Yuan Hongyan , Zha Xiaoming , Ma Changyan
Published: October 2020

Long noncoding RNAs (lncRNAs) have emerged as important regulators in cancers, including breast cancer. However, the overall biological roles and clinical significance of most lncRNAs are not fully understood. This study aimed to elucidate the potential role of a novel lncRNA FGF14-AS2 and the mechanisms underlying metastasis in breast cancer. The lncRNA FGF14-AS2 was significantly downregulated in breast cancer tissues; patients with lower FGF14-AS2 expression had advanced clinical stage. In vitro and in vivo assays of FGF14-AS2 alterations revealed a complex integrated phenotype affecting breast cancer cell migration, invasion, and tumor metastasis. Mechanistically, FGF14-AS2 functioned as a competing endogenous RNA of miR-370-3p, thereby leading to the activation of its coding counterpart, FGF14. Clinically, we observed increased miR-370-3p expression in breast cancer tissues, whereas FGF14 expression was decreased in breast cancer tissues compared to the adjacent normal breast tissues. FGF14-AS2 expression was significantly negatively correlated with miR-370-3p expression, and correlated positively to FGF14 expression. Collectively, our findings support a model in which the FGF14-AS2/miR-370-3p/FGF14 axis is a critical regulator in breast cancer metastasis, suggesting a new therapeutic direction in breast cancer.
Autism spectrum disorder-like behavior caused by reduced excitatory synaptic transmission in pyramidal neurons of mouse prefrontal cortex
Authors: Sacai Hiroaki , Sakoori Kazuto , Konno Kohtarou , Nagahama Kenichiro , Suzuki Honoka , Watanabe Takaki , Watanabe Masahiko , Uesaka Naofumi , Kano Masanobu
Published: October 2020

Autism spectrum disorder (ASD) is thought to result from deviation from normal development of neural circuits and synaptic function. Many genes with mutation in ASD patients have been identified. Here we report that two molecules associated with ASD susceptibility, contactin associated protein-like 2 (CNTNAP2) and Abelson helper integration site-1 (AHI1), are required for synaptic function and ASD-related behavior in mice. Knockdown of CNTNAP2 or AHI1 in layer 2/3 pyramidal neurons of the developing mouse prefrontal cortex (PFC) reduced excitatory synaptic transmission, impaired social interaction and induced mild vocalization abnormality. Although the causes of reduced excitatory transmission were different, pharmacological enhancement of AMPA receptor function effectively restored impaired social behavior in both CNTNAP2- and AHI1-knockdown mice. We conclude that reduced excitatory synaptic transmission in layer 2/3 pyramidal neurons of the PFC leads to impaired social interaction and mild vocalization abnormality in mice.
Interglacials of the Quaternary defined by northern hemispheric land ice distribution outside of Greenland
Authors: Köhler Peter , van de Wal Roderik S. W.
Published: October 2020

Glacial/interglacial dynamics during the Quaternary were suggested to be mainly driven by obliquity (41-kyr periodicity), including irregularities during the last 1 Myr that resulted in on average 100-kyr cycles. Here, we investigate this so-called Mid-Pleistocene Transition via model-based deconvolution of benthic δ18O, redefining interglacials by lack of substantial northern hemispheric land ice outside of Greenland. We find that in 67%, 88% and 52% of the obliquity cycles during the early, middle and late Quaternary, respectively, a glacial termination is realized leading to irregular appearances of new interglacials during various parts of the last 2.6 Myr. This finding suggests that the proposed idea of terminations leading to new interglacials in the Quaternary as obliquity driven with growing influence of land ice volume on the timing of deglaciations during the last 1 Myr might be too simple. Alternatively, the land ice-based definition of interglacials needs revision if applied to the entire Quaternary.
Cathepsin D deficiency in mammary epithelium transiently stalls breast cancer by interference with mTORC1 signaling
Authors: Ketterer Stephanie , Mitschke Julia , Ketscher Anett , Schlimpert Manuel , Reichardt Wilfried , Baeuerle Natascha , Hess Maria Elena , Metzger Patrick , Boerries Melanie , Peters Christoph , Kammerer Bernd , Brummer Tilman , Steinberg Florian , Reinheckel Thomas
Published: October 2020

Cathepsin D (CTSD) is a lysosomal protease and a marker of poor prognosis in breast cancer. However, the cells responsible for this association and the function of CTSD in cancer are still incompletely understood. By using a conditional CTSD knockout mouse crossed to the transgenic MMTV-PyMT breast cancer model we demonstrate that CTSD deficiency in the mammary epithelium, but not in myeloid cells, blocked tumor development in a cell-autonomous manner. We show that lack of CTSD impaired mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling and induced reversible cellular quiescence. In line, CTSD-deficient tumors started to grow with a two-month delay and quiescent Ctsd-/- tumor cells re-started proliferation upon long-term culture. This was accompanied by rewiring of oncogenic gene expression and signaling pathways, while mTORC1 signaling remained permanently disabled in CTSD-deficient cells. Together, these studies reveal a tumor cell-autonomous effect of CTSD deficiency, and establish a pivotal role of this protease in the cellular response to oncogenic stimuli.
Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAFV600 melanoma cells
Authors: Smith Lorey K. , Parmenter Tiffany , Gould Cathryn M. , Madhamshettiwar Piyush B. , Sheppard Karen E. , Simpson Kaylene J. , McArthur Grant A.
Published: October 2020

Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is critical in order to improve efficacy of these therapies in the clinic and delay onset of resistance. Glycolysis has emerged as a key feature of the BRAF inhibitor response in melanoma cells, and importantly, the metabolic response to vemurafenib in melanoma patients can predict patient outcome. Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.
Electricity from lignocellulosic substrates by thermophilic Geobacillus species
Authors: Shrestha Namita , Tripathi Abhilash Kumar , Govil Tanvi , Sani Rajesh Kumar , Urgun-Demirtas Meltem , Kasthuri Venkateswaran , Gadhamshetty Venkataramana
Published: October 2020

Given our vast lignocellulosic biomass reserves and the difficulty in bioprocessing them without expensive pretreatment and fuel separation steps, the conversion of lignocellulosic biomass directly into electricity would be beneficial. Here we report the previously unexplored capabilities of thermophilic Geobacillus sp. strain WSUCF1 to generate electricity directly from such complex substrates in microbial fuel cells. This process obviates the need for exogenous enzymes and redox mediator supplements. Cyclic voltammetry and chromatography studies revealed the electrochemical signatures of riboflavin molecules that reflect mediated electron transfer capabilities of strain WSUCF1. Proteomics and genomics analysis corroborated that WSUCF1 biofilms uses type-II NADH dehydrogenase and demethylmenaquinone methyltransferase to transfer the electrons to conducting anode via the redox active pheromone lipoproteins localized at the cell membrane.
Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice
Authors: El Bissati Kamal , Zhou Ying , Paulillo Sara M. , Raman Senthil K. , Karch Christopher P. , Reed Steve , Estes Ashley , Estes Amber , Lykins Joseph , Burkhard Peter , McLeod Rima
Published: October 2020

Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses againstToxoplasma gondiiin HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+T cells,CD4+T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.
Shopper intent prediction from clickstream e-commerce data with minimal browsing information
Authors: Requena Borja , Cassani Giovanni , Tagliabue Jacopo , Greco Ciro , Lacasa Lucas
Published: October 2020

We address the problem of user intent prediction from clickstream data of an e-commerce website via two conceptually different approaches: a hand-crafted feature-based classification and a deep learning-based classification. In both approaches, we deliberately coarse-grain a new clickstream proprietary dataset to produce symbolic trajectories with minimal information. Then, we tackle the problem of trajectory classification of arbitrary length and ultimately, early prediction of limited-length trajectories, both for balanced and unbalanced datasets. Our analysis shows that k-gram statistics with visibility graph motifs produce fast and accurate classifications, highlighting that purchase prediction is reliable even for extremely short observation windows. In the deep learning case, we benchmarked previous state-of-the-art (SOTA) models on the new dataset, and improved classification accuracy over SOTA performances with our proposed LSTM architecture. We conclude with an in-depth error analysis and a careful evaluation of the pros and cons of the two approaches when applied to realistic industry use cases.
Bisindolylpyrrole triggers transient mitochondrial permeability transitions to cause apoptosis in a VDAC1/2 and cyclophilin D-dependent manner via the ANT-associated pore
Authors: Koushi Masami , Aoyama Yasunori , Kamei Yoshiko , Asakai Rei
Published: October 2020

Bisindolylpyrrole at 0.1 μM is cytoprotective in 2% FBS that is counteracted by cyclosporin-A (CsA), an inhibitor of cyclophilin-D (CypD). We hypothesized that the cytoprotective effect might be due to transient mitochondrial permeability transition (tPT). This study tested the hypothesis that bisindolylpyrrole can trigger tPT extensively, thereby leading to cell death under certain conditions. Indeed, CsA-sensitive tPT-mediated apoptosis could be induced by bisindolylpyrrole at > 5 μM in HeLa cells cultured in 0.1% FBS, depending on CypD and VDAC1/2, as shown by siRNA knockdown experiments. Rat liver mitochondria also underwent swelling in response to bisindolylpyrrole, which proceeded at a slower rate than Ca2+-induced swelling, and which was blocked by the VDAC inhibitor tubulin and the ANT inhibitor bongkrekate, indicating the involvement of the ANT-associated, smaller pore. We examined why 0.1% FBS is a prerequisite for apoptosis and found that apoptosis is blocked by PKC activation, which is counteracted by the overexpressed defective PKCε. In mitochondrial suspensions, bisindolylpyrrole triggered CsA-sensitive swelling, which was suppressed selectively by pretreatment with PKCε, but not in the co-presence of tubulin. These data suggest that upon PKC inactivation the cytoprotective compound bisindolylpyrrole can induce prolonged tPT causing apoptosis in a CypD-dependent manner through the VDAC1/2-regulated ANT-associated pore.
Role of a genetic variation in the microRNA-4421 binding site of ERP29 regarding risk of oropharynx cancer and prognosis
Authors: Carron Juliana , Costa Ana Paula Dalla , Rinck-Junior José Augusto , Mariano Fernanda Viviane , de Sá Carvalho Benilton , Lima Carmen Silvia Passos , Lourenço Gustavo Jacob
Published: October 2020

We conducted a two-stage association study on patients with oropharynx (OP) squamous cell carcinoma (SCC) and healthy controls to identify single nucleotide variants (SNVs) located at the microRNA (miR)-binding sites of carcinogenesis genes associated with risk and prognosis of the disease. In stage 1, 49 patients and 49 controls were analyzed using Genome-Wide Human SNV Arrays to identify variants in the 3′-untranslated region (3′-UTR) of carcinogenesis-related genes, and one SNV was selected for data validation in stage 2 by TaqMan assays in 250 OPSCC patients and 250 controls. TheERP29c.*293A > G (rs7114) SNV located at miR-4421 binding site was selected for data validation among 46 SNVs. The ERp29 and miR-4421 levels were evaluated by quantitative-PCR and Western blotting. Interaction between miR-4421 with 3′-UTR ofERP29was evaluated by luciferase reporter assay. Event-free survival (EFS) was calculated by Kaplan–Meier and Cox methods.ERP29GG variant genotype was more common in OPSCC patients than in controls (6.4%vs3.6%,p = 0.02; odds ratio: 5.67; 95% confidence interval (CI) 1.27–25.26). Shorter EFS were seen in the base of tongue (BT) SCC patients with GG genotype (0.0%vs36.2%,p = 0.01; hazard ratio: 2.31; 95% CI: 1.03–5.15). Individuals withERP29AG or GG genotypes featured lower levels ofERP29mRNA (p = 0.005), ERp29 protein (p < 0.001) and higher levels of miR-4421 (p = 0.02). The miR-4421 showed more efficient binding with 3′-UTR of the variant G allele when compared with wild-type allele A (p = 0.001). Our data suggest thatERP29rs7114 SNV may alter the risk and prognosis of OPSCC due to variation in the ERp29 production possibly modulated by miR-4421.
A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle
Authors: Gehrke Lilian J. , Upadhyay Maulik , Heidrich Kristin , Kunz Elisabeth , Klaus-Halla Daniela , Weber Frank , Zerbe Holm , Seichter Doris , Graf Alexander , Krebs Stefan , Blum Helmut , Capitan Aurélien , Thaller Georg , Medugorac Ivica
Published: October 2020

Polledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at thepolledlocus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del;Del11) in the second exon ofZEB2gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product ofZEB2by almost 91%. Moreover, we showed that all animals carryingDel11mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations inZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting onlyZEB2and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly thatZEB2plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals.
Effects of olanzapine treatment on lipid profiles in patients with schizophrenia: a systematic review and meta-analysis
Authors: Li Rong , Zhang Yiqi , Zhu Wenqiang , Ding Chen , Dai Wenjie , Su Xin , Dai Wen , Xiao Jingmei , Xing Zhenhua , Huang Xiansheng
Published: October 2020

Olanzapine-induced dyslipidemia significantly increases the risk of cardiovascular disease in patients with schizophrenia. However, the clinical features of olanzapine-induced dyslipidemia remain hitherto unclear because of inconsistencies in the literature. This meta-analysis thus investigated the effects of olanzapine treatment on lipid profiles among patients with schizophrenia. Studies of the effects of olanzapine on lipids were obtained through the PubMed, Web of science, The Cochrane Library and Embase databases (up to January 1, 2020). Twenty-one studies and 1790 schizophrenia patients who received olanzapine therapy were included in our analysis. An olanzapine-induced increase was observed in plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels in patients with schizophrenia (all P < 0.05). Moreover, the time points analyzed included the following: baseline, 4 weeks, 6 weeks, 8 weeks, 12 weeks, and ≥ 24 weeks (data of ≥ 24 weeks were integrated). The significant elevation of TG, TC, and LDL-C was observed in patients with schizophrenia already by 4 weeks of olanzapine therapy (all P < 0.05), with no obvious changes observed in high-density lipoprotein cholesterol (HDL-C) (P > 0.05). In conclusion, olanzapine-induced dyslipidemia, characterized by increased TG, TC, and LDL-C levels, was observed in patients with schizophrenia already by 4 weeks of olanzapine treatment.
Inhibition of O-GlcNAc transferase activates tumor-suppressor gene expression in tamoxifen-resistant breast cancer cells
Authors: Barkovskaya Anna , Seip Kotryna , Prasmickaite Lina , Mills Ian G. , Moestue Siver A. , Itkonen Harri M.
Published: October 2020

In this study, we probed the importance of O-GlcNAc transferase (OGT) activity for the survival of tamoxifen-sensitive (TamS) and tamoxifen-resistant (TamR) breast cancer cells. Tamoxifen is an antagonist of estrogen receptor (ERα), a transcription factor expressed in over 50% of breast cancers. ERα-positive breast cancers are successfully treated with tamoxifen; however, a significant number of patients develop tamoxifen-resistant disease. We show that in vitro development of tamoxifen-resistance is associated with increased sensitivity to the OGT small molecule inhibitor OSMI-1. Global transcriptome profiling revealed that TamS cells adapt to OSMI-1 treatment by increasing the expression of histone genes. This is known to mediate chromatin compaction. In contrast, TamR cells respond to OGT inhibition by activating the unfolded protein response and by significantly increasing ERRFI1 expression. ERRFI1 is an endogenous inhibitor of ERBB-signaling, which is a known driver of tamoxifen-resistance. We show that ERRFI1 is selectively downregulated in ERα-positive breast cancers and breast cancers driven by ERBB2. This likely occurs via promoter methylation. Finally, we show that increased ERRFI1 expression is associated with extended survival in patients with ERα-positive tumors (p = 9.2e−8). In summary, we show that tamoxifen-resistance is associated with sensitivity to OSMI-1, and propose that this is explained in part through an epigenetic activation of the tumor-suppressor ERRFI1 in response to OSMI-1 treatment.
Observational learning of fear in real time procedure
Authors: Szczepanik Michał , Kaźmierowska Anna M. , Michałowski Jarosław M. , Wypych Marek , Olsson Andreas , Knapska Ewelina
Published: October 2020

Learning to avoid threats often occurs by observing others. Most previous research on observational fear learning (OFL) in humans has used pre-recorded standardized video of an actor and thus lacked ecological validity. Here, we aimed to enhance ecological validity of the OFL by engaging participants in a real-time observational procedure (35 pairs of healthy male friends, age 18–27). One of the participants watched the other undergo a differential fear conditioning task, in which a conditioned stimulus (CS+) was paired with an aversive electric shock and another stimulus (CS−) was always safe. Subsequently, the CS+ and CS− were presented to the observer to test the OFL. While the friend’s reactions to the shock elicited strong skin conductance responses (SCR) in all observers, subsequent differential SCRs (CS+ > CS−) were found only when declarative knowledge of the CS+/US contingency (rated by the participants) was acquired. Contingency-aware observers also showed elevated fear potentiated startle responses during both CS+ and CS− compared to baseline. We conclude that our real-time procedure can be effectively used to study OFL. The procedure allowed for dissecting two components of the OFL: an automatic emotional reaction to the response of the demonstrator and learning about stimulus contingency.
Neopterin and biopterin levels and tryptophan degradation in patients with diabetes
Authors: Gürcü Sinem , Girgin Gözde , Yorulmaz Göknur , Kılıçarslan Bilge , Efe Belgin , Baydar Terken
Published: October 2020

This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.
Nosema ceranae causes cellular immunosuppression and interacts with thiamethoxam to increase mortality in the stingless bee Melipona colimana
Authors: Macías-Macías José O. , Tapia-Rivera José C. , De la Mora Alvaro , Tapia-González José M. , Contreras-Escareño Francisca , Petukhova Tatiana , Morfin Nuria , Guzman-Novoa Ernesto
Published: October 2020

The microsporidian parasite Nosema ceranae and neonicotinoid insecticides affect the health of honey bees (Apis mellifera). However, there is limited information about the effect of these stressors on other pollinators such as stingless bees (Hymenoptera: Meliponini). We examined the separate and combined effects of N. ceranae and the neonicotinoid thiamethoxam at field-exposure levels on the survivorship and cellular immunity (hemocyte concentration) of the stingless bee Melipona colimana. Newly-emerged bees were subjected to four treatments provided in sucrose syrup: N. ceranae spores, thiamethoxam, thiamethoxam and N. ceranae, and control (bees receiving only syrup). N. ceranae developed infections of > 467,000 spores/bee in the group treated with spores only. However, in the bees subjected to both stressors, infections were < 143,000 spores/bee, likely due to an inhibitory effect of thiamethoxam on the microsporidium. N. ceranae infections did not affect bee survivorship, but thiamethoxam plus N. ceranae significantly increased mortality. Hemocyte counts were significantly lower in N. ceranae infected-bees than in the other treatments. These results suggest that N. ceranae may infect, proliferate and cause cellular immunosuppression in stingless bees, that exposure to sublethal thiamethoxam concentrations is toxic to M. colimana when infected with N. ceranae, and that thiamethoxam restrains N. ceranae proliferation. These findings have implications on pollinators’ conservation.
Revisiting peptidoglycan sensing: interactions with host immunity and beyond
Authors: Crump Geneva Maddison , Zhou Junhui , Mashayekh Siavash , Grimes Catherine L.
Published: October 2020

Interactions between host immune cells and bacterial peptidoglycan fragments play a pivotal role in a variety of human diseases.
Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide
Authors: Wu Liang , Wimmer Norbert , Davies Gideon J. , Ferro Vito
Published: October 2020

Crystal structures with human heparanase provide the first ever observation of a substrate in an activated 1S3 conformation.
Binding of divalent cations to acetate: molecular simulations guided by Raman spectroscopy
Authors: Mendes de Oliveira Denilson , Zukowski Samual R. , Palivec Vladimir , Hénin Jérôme , Martinez-Seara Hector , Ben-Amotz Dor , Jungwirth Pavel , Duboué-Dijon Elise
Published: October 2020

We combine Raman-MCR vibrational spectroscopy experiments with ab initio and classical MD simulations to gain molecular insights into carboxylate–cation binding.
Artificial neural networks for the prediction of solvation energies based on experimental and computational data
Authors: Yang Jiyoung , Knape Matthias J. , Burkert Oliver , Mazzini Virginia , Jung Alexander , Craig Vincent S. J. , Miranda-Quintana Ramón Alain , Bluhmki Erich , Smiatek Jens
Published: October 2020

We present a machine learning approach based on artificial neural networks for the prediction of ion pair solvation energies.
Effects of paramagnetic fluctuations on the thermochemistry of MnO(100) surfaces in the oxygen evolution reaction
Authors: Yoon Sangmoon , Jin Kyoungsuk , Lee Sangmin , Nam Ki Tae , Kim Miyoung , Kwon Young-Kyun
Published: October 2020

We investigated the effects of paramagnetic (PM) fluctuations on the thermochemistry of the MnO(100) surface in the oxygen evolution reaction (OER) using the “noncollinear magnetic sampling method plus U” (NCMSM+U).
Cyclic (alkyl)(amino)carbenes in organic and organometallic methane C–H activation: a DFT and MCSCF study
Authors: Sun Zhicheng , Cundari Thomas R.
Published: October 2020

Density functional theory (DFT) and multi-configurational self-consistent field (MCSCF) calculations are used to investigate the electronic and steric properties of cyclic (alkyl)(amino)carbenes (CAACs).
Anisotropic dielectric behavior of layered perovskite-like Cs3Bi2I9 crystals in the terahertz region
Authors: Sun Qihao , Yang Wenhui , Cheng Yuanbo , Dong Jiangpeng , Zhu Mengqin , Zhang BinBin , Dubois Alain , Zhu Menghua , Jie Wanqi , Xu Yadong
Published: October 2020

Corresponding frequency domain spectrum and the calculated IR absorption spectrum of the Cs3Bi2I9 crystal at 0.1–4.0 THz.
Chemical reactivity from the vibrational ground-state level. The role of the tunneling path in the tautomerization of urea and derivatives
Authors: Mosquera-Lois Irea , Ferro-Costas David , Fernández-Ramos Antonio
Published: October 2020

Recent developments of low-temperature techniques are providing valuable knowledge about chemical processes that manifest in the quantum regimen.
Supramolecular hosts as in vivo sequestration agents for pharmaceuticals and toxins
Authors: Deng Chun-Lin , Murkli Steven L. , Isaacs Lyle D.
Published: October 2020

Supramolecular hosts can act as in vivo sequestration agents for pharmaceuticals and toxins.
Solvent-free ketalization of polyols over germanosilicate zeolites: the role of the nature and strength of acid sites
Authors: Podolean Iunia , Zhang Jin , Shamzhy Mariya , Pârvulescu Vasile I. , Čejka Jiří
Published: October 2020

Weak acid centers of germanosilicate zeolites can serve as active sites in ketalization reactions.
A supramolecular bifunctional iridium photoaminocatalyst for the enantioselective alkylation of aldehydes
Authors: Gualandi Andrea , Calogero Francesco , Martinelli Ada , Quintavalla Arianna , Marchini Marianna , Ceroni Paola , Lombardo Marco , Cozzi Pier Giorgio
Published: October 2020

The construction of a hybrid metal-organo-photoredox catalyst based on the conjugation of an imidazolidinone organocatalyst and Ir(ppy)2(bipy) (ppy = 2-phenylpyridine, bipy = bipyridine) is described.
In need of a second-hand? The second coordination sphere of ruthenium complexes enables water oxidation with improved catalytic activity
Authors: Matias Tiago A. , Keppler Artur F. , Bartoloni Fernando H.
Published: October 2020

A ligand dangling arm, acting as an intramolecular proton acceptor, drastically increasing the catalytic activity of Ru-complexes for water oxidation.
Crystal structure, phase transition and properties of indium(iii) sulfide
Authors: Wyżga Paweł , Carrillo-Cabrera Wilder , Akselrud Lev , Veremchuk Igor , Wagler Jörg , Hennig Christoph , Tsirlin Alexander A. , Leithe-Jasper Andreas , Kroke Edwin , Gumeniuk Roman
Published: October 2020

This report presents studies of crystal structures of α- and β-In2S3 as well as a mechanism of the 1st order α–β phase transition. The structural part is supported by an analysis of thermoelectric properties and by DFT calculations.
Skin-interfaced soft microfluidic systems with modular and reusable electronics for in situ capacitive sensing of sweat loss, rate and conductivity
Authors: Hourlier-Fargette Aurélie , Schon Stéphanie , Xue Yeguang , Avila Raudel , Li Weihua , Gao Yiwei , Liu Claire , Kim Sung Bong , Raj Milan S. , Fields Kelsey B. , Parsons Blake V. , Lee KunHyuck , Lee Jong Yoon , Chung Ha Uk , Lee Stephen P. , Johnson Michael , Bandodkar Amay J. , Gutruf Philipp , Model Jeffrey B. , Aranyosi Alexander J. , Choi Jungil , Ray Tyler R. , Ghaffari Roozbeh , Huang Yonggang , Rogers John A.
Published: October 2020

Stick-on electrodes capacitively coupled to single-use microfluidic channels enable contactless analysis of sweat in a soft wearable format with real-time wireless data collection.
A defective g-C3N4/RGO/TiO2composite from hydrogen treatment for enhanced visible-light photocatalytic H2production
Authors: Wang Jing , Sun Youcai , Fu Lijun , Sun Zhuang , Ou Man , Zhao Shulin , Chen Yuhui , Yu Fengjiao , Wu Yuping
Published: October 2020

g-C3N4/RGO/TiO2with nitrogen and oxygen vacancies possesses an efficient H2evolution rate, which exceeds that of g-C3N4/RGO/TiO2without vacancy defects.
Highly efficient bifunctional oxygen reduction/evolution activity of a non-precious nanocomposite derived from a tetrazine-COF
Authors: Roy Soumyabrata , Mari Subbareddy , Sai Manoj Kaja , Sarma Saurav Ch. , Sarkar Shreya , Peter Sebastian C.
Published: October 2020

Catalyst engineering of a COF derived Co doped graphitic carbon electrocatalyst exhibited oxygen reduction reaction activity comparable with that of state-of-the-art material Pt/C.
Investigation of strain behavior and carrier mobility of organic–inorganic hybrid perovskites: (C4H9NH3)2GeI4 and (C4H9NH3)2SnI4
Authors: Su Ye , Cao Shuo , Shi Li-Bin , Qian Ping
Published: October 2020

Two dimensional (2D) organic–inorganic hybrid perovskites have attracted great interest due to their tunable band gap and structural stability.
Ultra-high rate capability of the synergistically built dual nanostructure of NiCo2S4/nickel foam as an electrode in supercapacitors
Authors: Liu Pengfei , Liu Yuanyuan , Li Jing , Wang Meiri , Cui Hongtao
Published: October 2020

A dual nanostructure of NiCo2S4/nickel foam is built to achieve an electrode with structure-synergistical contribution from materials and current collectors.
In situ growth of urchin-like cobalt–chromium phosphide on 3D graphene foam for efficient overall water splitting
Authors: Li Kuang , Jian Xue , Li Shuo , Wang Weiwei , Lei Yuchen , Zhang Peilin , Liu Jinzhe , Zhou Chencheng , Chen Luyang
Published: October 2020

The CoCr-P@3DGF composite shows excellent activity and durability for overall water splitting due to Cr-doping and the 3DGF substrate.
Nitric oxide dioxygenation (NOD) reactions of CoIII-peroxo and NiIII-peroxo complexes: NODversusNO activation
Authors: Yenuganti Mahesh , Das Sandip , Kulbir  , Ghosh Somnath , Bhardwaj Prabhakar , Pawar Sonali Shivaji , Sahoo Subash Chandra , Kumar Pankaj
Published: October 2020

A comparative study of “nitric oxide dioxygenationversusdioxygen or nitric oxide activation”.
First series of mixed (PIII, SeIV)-heteroatomoriented rare-earth-embedded polyoxotungstates containing distinct building blocks
Authors: Liu Lulu , Jiang Jun , Liu Xiaoyi , Liu Guoping , Wang Dan , Chen Lijuan , Zhao Junwei
Published: October 2020

A series of unprecedented mixed heteroatoms-oriented rare-earth-embedded heteropolyoxotungstates 1–8 were prepared and the 1@CMWCNT-GCE electrochemical sensing performances toward DA and UA were studied.
Selective direct C–H polyfluoroarylation of electron-deficient N-heterocyclic compounds
Authors: Li Shun , Li Wen-Jing , Yang Xiao , Sun Rui , Tang Juan , Zheng Xue-Li , Yuan Mao-Ling , Li Rui-Xiang , Chen Hua , Fu Hai-Yan
Published: October 2020

An efficient protocol of C2-selective direct C–H polyfluoroarylation of six-membered N-heterocyclic compounds with polyfluorobenzoic acid via corresponding N-methyl quaternary ammonium salts.
Understanding the structure and dynamics of anti-inflammatory corticosteroid dexamethasone by solid state NMR spectroscopy
Authors: Dey Krishna Kishor , Ghosh Manasi
Published: October 2020

The structure and dynamics of dexamethasone is determined by measuring CSA tensor, site-specific spin–lattice relaxation time.
Controlling the concentration gradient in sequentially deposited bilayer organic solar cells via rubbing and annealing
Authors: Abdul Aziz Mohd Zaidan , Higashimine Koichi , Shioya Nobutaka , Shimoaka Takafumi , Hasegawa Takeshi , Sakai Heisuke , Vohra Varun , Murata Hideyuki
Published: October 2020

Rubbing the donor in bilayer organic solar cells promotes the formation of adequate concentration gradients in the active layers. The improved charge collection yields large enhancements in the performances of fullerene and non-fullerene solar cells.
Preoxidation-assisted nitrogen enrichment strategy to decorate porous carbon spheres for catalytic adsorption/oxidation of methyl mercaptan
Authors: Zhang Changming , Wang Yaqi , Zhang Xiaochao , Wang Rongxian , Kou Lifang , Li Rui , Fan Caimei
Published: October 2020

Porous carbon spheres with high surface area and microporous structure were synthesized from alkyl phenols and formaldehyde via suspension polymerization and steam activation.
Tunable electrical properties of carbon dot doped photo-responsive azobenzene–clay nanocomposites
Authors: Gogoi Jahnabi , Shishodia Shubham , Chowdhury Devasish
Published: October 2020

We demonstrate successful fabrication of an azobenzene–clay nanocomposite doped with electron-rich cysteine and methionine carbon dots with photo-switchable ac conductivity.
Fabrication of ideally ordered TiO2 through-hole membranes by two-layer anodization
Authors: Yanagishita Takashi , Hirose Haruto , Kondo Toshiaki , Schmuki Patrik , Masuda Hideki
Published: October 2020

Ideally ordered TiO2 through-hole membrane obtained through a two-layer anodization process.
Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy
Authors: Zhou Lihua , Wei Fangfang , Xiang Jingjing , Li Hongfeng , Li Chunbin , Zhang Pengfei , Liu Chuangjun , Gong Ping , Cai Lintao , Wong Keith Man-Chung
Published: October 2020

A design strategy for boosting the ROS generation of rhodamine-decorated cyclometallated iridium(iii) complexes by ligand regulation for endoplasmic reticulum-targeted precise photodynamic therapy.
Achieving a low-carbon future through the energy–chemical nexus in China
Authors: Li Yinan , Lan Song , Pérez-Ramírez Javier , Wang Xiaonan
Published: October 2020

The paper proposes the concept of sectoral nexus (energy–chemical nexus) in China for achieving its CO2 emission targets.
Inverse method based on 3D nonlinear physically constrained minimisation in the framework of traction force microscopy
Authors: Sanz-Herrera J. A. , Barrasa-Fano J. , Cóndor M. , Van Oosterwyck H.
Published: October 2020

We present a new inverse and physically-consistent traction force microscopy method developed and implemented in the context of 3D nonlinear elasticity. We prove its enhanced accuracy applying it to real cases of cells cultured in a 3D hydrogel.
Microphase separation in the melts of diblock copolymers with amphiphilic blocks
Authors: Filatov Dmitry A. , Govorun Elena N.
Published: October 2020

Amphiphilic polymer blocks can envelop the domains of major non-amphiphilic blocks in diblock copolymer melts: a theoretical study.
Chiral-filament self-assembly on curved manifolds
Authors: Rode Sebastian , Elgeti Jens , Gompper Gerhard
Published: October 2020

Chiral proteins can assemble as twisted ribbons on curved surfaces. Simulations of anisotropic building blocks on a cylindrical surface show a helical assembly with a preferred helix angle, and a power-law growth of the filament length in time.
Synergetic enhancement of energy harvesting performance in triboelectric nanogenerator using ferroelectric polarization for self-powered IR signaling and body activity monitoring
Authors: Sahu Manisha , Vivekananthan Venkateswaran , Hajra Sugato , K S Abisegapriyan , Maria Joseph Raj Nirmal Prashanth , Kim Sang-Jae
Published: October 2020

Improved energy harvesting performance in triboelectric nanogenerator using piezoelectric polarization for self-powered IR signaling and body activity monitoring.
High pressure chemical reactivity and structural study of the Na–P and Li–P systems
Authors: Leversee River A. , Rode Kristen , Greenberg Eran , Prakapenka Vitali B. , Smith Jesse S. , Kunz Martin , Pickard Chris J. , Stavrou Elissaios
Published: October 2020

Pressure enables the synthesis of (Na/Li)3P compounds at RT bypassing established chemical methods while at higher pressure, both undergo a pressure-induced phase transition.
Efficient microwave traps with markedly enhanced interfacial polarization and impedance matching enabled by dual-shelled, dual-cavity magnetic@dielectric hollow nanospheres
Authors: Hua Jiasong , Ma Wenjun , Liu Xiaoyun , Zhuang Qixin , Wu Zeyang , Huang Huang , Lin Shaoliang
Published: October 2020

Dual-shelled, dual-cavity Fe3O4@TiO2 hollow nanospheres exhibit an outstanding microwave absorption performance with a minimum reflection loss of −60.17 dB.
Identification of three molecular subtypes based on immune infiltration in ovarian cancer and its prognostic value
Authors: Liu Juan , Tan Zongjian , He Jun , Jin Tingting , Han Yuanyuan , Hu Li , Song Jukun , Huang Shengwen
Published: October 2020

Background: Increasing studies suggest that tumor immune infiltration is a relative factor of prognosis in ovarian cancer (OvCa). The present study explored the composition of tumor-infiltrating immune cells (TIICs) in OvCa using CIBERSORT algorithm and further assessed their values for prognosis and therapeutic strategies by molecular subtypes.

Methods: Publicly available databases including The Cancer Genome Atlas (TCGA) and GTEx were searched. Ovarian tumor samples were available from TCGA, and normal ovarian samples were obtained from the GTEx dataset. The relative proportions of immune cell profiling in OvCa and normal samples were evaluated by CIBERSORT algorithm. Association between each immune cell subtype and survival was inferred by the fractions of 22 immune cell types. “CancerSubtypes” R-package was employed to identify the three types of molecular classification and analyze the functional enrichment in each subclass. Response to immunotherapy and anticancer drug targets was predicted via TIDE algorithm and GDSC dataset.

Results: Substantial variation reflecting individual difference was identified between cancer and normal tissues in the immune infiltration profiles. T cells CD4 memory activated, macrophages M1 were associated with improved overall survival (OS) as evaluated by univariate Cox regression and multivariate Cox. Three subtypes were identified by ´CancerSubtypes’ R-package and every sub-cluster possessed specific immune cell characterization. Meanwhile, Cluster II exhibited poor prognosis and sensitive response to immunotherapy.

Conclusions: The cellular component of immune infiltration shows remarkable variation in OvCa. Profiling of immune infiltration is useful in prediction of prognosis of OvCa. The results from profiling might be considered in therapeutic modulation.