bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-lapse single-cell transcriptomics reveals modulation of histone H3 for dormancy breaking in fission yeast
Authors: Tsuyuzaki Hayato , Hosokawa Masahito , Arikawa Koji , Yoda Takuya , Okada Naoyuki , Takeyama Haruko , Sato Masamitsu
Published: March 2020

How quiescent cells break dormancy is a key issue in eukaryotic cells including cancer. Fungal spores, for example, remain quiescent for long periods until nourished, although the mechanisms by which dormancy is broken remain enigmatic. Transcriptome analysis could provide a clue, but methods to synchronously germinate large numbers of spores are lacking, and thus it remains a challenge to analyse gene expression upon germination. Hence, we develop methods to assemble transcriptomes from individual, asynchronous spore cells of fission yeast undergoing germination to assess transcriptomic changes over time. The virtual time-lapse analyses highlights one of three copies of histone H3 genes whose transcription fluctuates during the initial stage of germination. Disruption of this temporal fluctuation causes defects in spore germination despite no visible defects in other stages of the life cycle. We conclude that modulation of histone H3 expression is a crucial ‘wake-up’ trigger at dormancy breaking.
Fresh groundwater discharge insignificant for the world’s oceans but important for coastal ecosystems
Authors: Luijendijk Elco , Gleeson Tom , Moosdorf Nils
Published: March 2020

The flow of fresh groundwater may provide substantial inputs of nutrients and solutes to the oceans. However, the extent to which hydrogeological parameters control groundwater flow to the world’s oceans has not been quantified systematically. Here we present a spatially resolved global model of coastal groundwater discharge to show that the contribution of fresh groundwater accounts for ~0.6% (0.004%–1.3%) of the total freshwater input and ~2% (0.003%–7.7%) of the solute input for carbon, nitrogen, silica and strontium. However, the coastal discharge of fresh groundwater and nutrients displays a high spatial variability and for an estimated 26% (0.4%–39%) of the world’s estuaries, 17% (0.3%–31%) of the salt marshes and 14% (0.1–26%) of the coral reefs, the flux of terrestrial groundwater exceeds 25% of the river flux and poses a risk for pollution and eutrophication.
First draft genome for the sand-hopper Trinorchestia longiramus
Authors: Patra Ajit Kumar , Chung Oksung , Yoo Ji Yong , Kim Min Seop , Yoon Moon Geun , Choi Jeong-Hyeon , Yang Youngik
Published: March 2020

Crustacean amphipods are important trophic links between primary producers and higher consumers. Although most amphipods occur in or around aquatic environments, the family Talitridae is the only family found in terrestrial and semi-terrestrial habitats. The sand-hopper Trinorchestia longiramus is a talitrid species often found in the sandy beaches of South Korea. In this study, we present the first draft genome assembly and annotation of this species. We generated ~380.3 Gb of sequencing data assembled in a 0.89 Gb draft genome. Annotation analysis estimated 26,080 protein-coding genes, with 89.9% genome completeness. Comparison with other amphipods showed that T. longiramus has 327 unique orthologous gene clusters, many of which are expanded gene families responsible for cellular transport of toxic substances, homeostatic processes, and ionic and osmotic stress tolerance. This first talitrid genome will be useful for further understanding the mechanisms of adaptation in terrestrial environments, the effects of heavy metal toxicity, as well as for studies of comparative genomic variation across amphipods.
Comprehensive analyses of the annexin (ANN) gene family in Brassica rapa, Brassica oleracea and Brassica napus reveals their roles in stress response
Authors: He Xin , Liao Li , Xie Sai , Yao Min , Xie Pan , Liu Wei , Kang Yu , Huang Luyao , Wang Mei , Qian Lunwen , Liu Zhongsong , Guan Chunyun , Guan Mei , Hua Wei
Published: March 2020

Annexins (ANN) are a multigene, evolutionarily conserved family of calcium-dependent and phospholipid-binding proteins that play important roles in plant development and stress resistance. However, a systematic comprehensive analysis of ANN genes of Brassicaceae species (Brassica rapa, Brassica oleracea, and Brassica napus) has not yet been reported. In this study, we identified 13, 12, and 26 ANN genes in B. rapa, B. oleracea, and B. napus, respectively. About half of these genes were clustered on various chromosomes. Molecular evolutionary analysis showed that the ANN genes were highly conserved in Brassicaceae species. Transcriptome analysis showed that different group ANN members exhibited varied expression patterns in different tissues and under different (abiotic stress and hormones) treatments. Meanwhile, same group members from Arabidopsis thaliana, B. rapa, B. oleracea, and B. napus demonstrated conserved expression patterns in different tissues. The weighted gene coexpression network analysis (WGCNA) showed that BnaANN genes were induced by methyl jasmonate (MeJA) treatment and played important roles in jasmonate (JA) signaling and multiple stress response in B. napus.
Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration
Authors: Dirscherl Konstantin , Schläpfer Martin , Roth Z’graggen Birgit , Wenger Roland H , Booy Christa , Flury-Frei Renata , Fatzer Rita , Aloman Costica , Bartosch Birke , Parent Romain , Kurtcuoglu Vartan , de Zélicourt Diane , Spahn Donat R. , Beck Schimmer Beatrice , Schadde Erik
Published: March 2020

Portal vein ligation (PVL) induces liver growth prior to resection. Associating liver partition and portal vein ligation (PVL plus transection=ALPPS) or the addition of the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) to PVL both accelerate growth via stabilization of HIF-α subunits. This study aims at clarifying the crosstalk of hepatocytes (HC), hepatic stellate cells (HSC) and liver sinusoidal endothelial cells (LSEC) in accelerated liver growth. In vivo, liver volume, HC proliferation, vascular density and HSC activation were assessed in PVL, ALPPS, PVL+DMOG and DMOG alone. Proliferation of HC, HSC and LSEC was determined under DMOG in vitro. Conditioned media experiments of DMOG-exposed cells were performed. ALPPS and PVL+DMOG accelerated liver growth and HC proliferation in comparison to PVL. DMOG alone did not induce HC proliferation, but led to increased vascular density, which was also observed in ALPPS and PVL+DMOG. Activated HSC were detected in ALPPS, PVL+DMOG and DMOG, again not in PVL. In vitro, DMOG had no proliferative effect on HC, but conditioned supernatant of DMOG-treated HSC induced VEGF-dependent proliferation of LSEC. Transcriptome analysis confirmed activation of proangiogenic factors in hypoxic HSC. Hypoxia signaling in HSC induces VEGF-dependent angiogenesis. HSC play a crucial role in the cellular crosstalk of rapid liver regeneration.
Modifiable risk factors for 9-year mortality in older English and Brazilian adults: The ELSA and SIGa-Bagé ageing cohorts
Authors: Kessler Marciane , Thumé Elaine , Scholes Shaun , Marmot Michael , Facchini Luiz Augusto , Nunes Bruno Pereira , Machado Karla Pereira , Soares Mariangela Uhlmann , de Oliveira Cesar
Published: March 2020

To quantify and compare 9-year all-cause mortality risk attributable to modifiable risk factors among older English and Brazilian adults. We used data for participants aged 60 years and older from the English Longitudinal Study of Ageing (ELSA) and the Bagé Cohort Study of Ageing (SIGa-Bagé). The five modifiable risk factors assessed at baseline were smoking, hypertension, diabetes, obesity and physical inactivity. Deaths were identified through linkage to mortality registers. For each risk factor, estimated all-cause mortality hazard ratios (HR) and population attributable fractions (PAF) were adjusted by age, sex, all other risk factors and socioeconomic position (wealth) using Cox proportional hazards modelling. We also quantified the risk factor adjusted wealth gradients in mortality, by age and sex. Among the participants, 659 (ELSA) and 638 (SIGa-Bagé) died during the 9-year follow-up. Mortality rates were higher in SIGa-Bagé. HRs and PAFs showed more similarities than differences, with physical inactivity (PAF 16.5% ELSA; 16.7% SIGa-Bagé) and current smoking (PAF 4.9% for both cohorts) having the strongest association. A clear graded relationship existed between the number of risk factors and subsequent mortality. Wealth gradients in mortality were apparent in both cohorts after full adjustment, especially among men aged 60–74 in ELSA. A different pattern was found among older women, especially in SIGa-Bagé. These findings call attention for the challenge to health systems to prevent and modify the major risk factors related to non-communicable diseases, especially physical inactivity and smoking. Furthermore, wealth inequalities in mortality persist among older adults.
APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice
Authors: Area-Gomez Estela , Larrea Delfina , Pera Marta , Agrawal Rishi R. , Guilfoyle David N. , Pirhaji Leila , Shannon Kathleen , Arain Hirra A. , Ashok Archana , Chen Qiuying , Dillman Allissa A. , Figueroa Helen Y. , Cookson Mark R. , Gross Steven S. , Fraenkel Ernest , Duff Karen E. , Nuriel Tal
Published: March 2020

The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason for the association between APOE4 and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing that APOE4 negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of APOE4′s role in AD pathogenesis, we performed a transcriptomics analysis of APOE4 vs. APOE3 expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of aged APOE mice. This study revealed EC-specific upregulation of genes related to oxidative phosphorylation (OxPhos). Follow-up analysis utilizing the Seahorse platform showed decreased mitochondrial respiration with age in the hippocampus and cortex of APOE4 vs. APOE3 mice, but not in the EC of these mice. Additional studies, as well as the original transcriptomics data, suggest that multiple bioenergetic pathways are differentially regulated by APOE4 expression in the EC of aged APOE mice in order to increase the mitochondrial coupling efficiency in this region. Given the importance of the EC as one of the first regions to be affected by AD pathology in humans, the observation that the EC is susceptible to differential bioenergetic regulation in response to a metabolic stressor such as APOE4 may point to a causative factor in the pathogenesis of AD.
Melinjo seed extract increases adiponectin multimerization in physiological and pathological conditions
Authors: Oniki Kentaro , Kawakami Taisei , Nakashima Azusa , Miyata Keishi , Watanabe Takehisa , Fujikawa Haruka , Nakashima Ryunosuke , Nasu Aoi , Eto Yuka , Takahashi Noriki , Nohara Hirofumi , Suico Mary Ann , Kotani Shunsuke , Obata Yui , Sakamoto Yuki , Seguchi Yuri , Saruwatari Junji , Imafuku Tadashi , Watanabe Hiroshi , Maruyama Toru , Kai Hirofumi , Shuto Tsuyoshi
Published: March 2020

Melinjo seed extract (MSE) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin C, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSE supplementation increases the adiponectin (APN) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet- or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/total APN in relation to the genes regulating APN multimerization, including DsbA-L. Furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. In addition, the administration of MSE to HFD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW APN in serum and the mRNA levels of ADIPOQ and DsbA-L in adipose tissue. The present study suggests that MSE may exert beneficial effects via APN multimerization in relation to the induction of DsbA-L under both physiological and obese conditions.
Bridging substrate intake kinetics and bacterial growth phenotypes with flux balance analysis incorporating proteome allocation
Authors: Zeng Hong , Yang Aidong
Published: March 2020

Empirical kinetic models such as the Monod equation have been widely applied to relate the cell growth with substrate availability. The Monod equation shares a similar form with the mechanistically-based Michaelis-Menten kinetics for enzymatic processes, which has provoked long-standing and un-concluded conjectures on their relationship. In this work, we integrated proteome allocation principles into a Flux Balance Analysis (FBA) model of Escherichia coli, which quantitatively revealed potential mechanisms that underpin the phenomenological Monod parameters: the maximum specific growth rate could be dictated by the abundance of growth-controlling proteome and growth-pertinent proteome cost; more importantly, the Monod constant (Ks) was shown to relate to the Michaelis constant for substrate transport (Km,g), with the link being dependent on the cell’s metabolic strategy. Besides, the proposed model was able to predict glucose uptake rate at given external glucose concentration through the size of available proteome resource for substrate transport and its enzymatic cost, while growth rate and acetate overflow were accurately simulated for two E. coli strains. Bridging the enzymatic kinetics of substrate intake and overall growth phenotypes, this work offers a mechanistic interpretation to the empirical Monod law, and demonstrates the potential of coupling local and global cellular constrains in predictive modelling.
Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness
Authors: Hermann Bertrand , Raimondo Federico , Hirsch Lukas , Huang Yu , Denis-Valente Mélanie , Pérez Pauline , Engemann Denis , Faugeras Frédéric , Weiss Nicolas , Demeret Sophie , Rohaut Benjamin , Parra Lucas C. , Sitt Jacobo D. , Naccache Lionel
Published: March 2020

Severe brain injuries can lead to long-lasting disorders of consciousness (DoC) such as vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS). While behavioral assessment remains the gold standard to determine conscious state, EEG has proven to be a promising complementary tool to monitor the effect of new therapeutics. Encouraging results have been obtained with invasive electrical stimulation of the brain, and recent studies identified transcranial direct current stimulation (tDCS) as an effective approach in randomized controlled trials. This non-invasive and inexpensive tool may turn out to be the preferred treatment option. However, its mechanisms of action and physiological effects on brain activity remain unclear and debated. Here, we stimulated 60 DoC patients with the anode placed over left-dorsolateral prefrontal cortex in a prospective open-label study. Clinical behavioral assessment improved in twelve patients (20%) and none deteriorated. This behavioral response after tDCS coincided with an enhancement of putative EEG markers of consciousness: in comparison with non-responders, responders showed increases of power and long-range cortico-cortical functional connectivity in the theta-alpha band, and a larger and more sustained P300 suggesting improved conscious access to auditory novelty. The EEG changes correlated with electric fields strengths in prefrontal cortices, and no correlation was found on the scalp. Taken together, this prospective intervention in a large cohort of DoC patients strengthens the validity of the proposed EEG signatures of consciousness, and is suggestive of a direct causal effect of tDCS on consciousness.
Preparation of macroporous transition metal hydroxide monoliths via a sol-gel process accompanied by phase separation
Authors: Liu Fu , Feng Daoyan , Yang Hui , Guo Xingzhong
Published: March 2020

Three-dimensional transition metal hydroxide monoliths were facilely fabricated by a sol-gel process accompanied by phase separation in the presence of polyacrylic acid (PAA) and propylene oxide (PO). In the typical ZnCl2-PAA-PO system, PAA is used as a phase separation inducer as well as a framework former to control the phase separation and the formation of macrostructures, whereas PO works as a proton scavenger to initiate the gelation of the system and freeze the macrostructures. Appropriate amount of PAA, PO and solvents allow the formation of zinc (Zn) hydroxide monolith with cocontinuous skeletons and interconnected macropores, and the construction mechanism and characteristics of macrostructure are also investigated. The resultant dried gels are amorphous Zn hydroxide monolith with a narrow macropore size distribution (~1 μm). This approach is further used to successfully prepare macroporous single or binary composite transition metal hydroxide monoliths.
Genome-based Salmonella serotyping as the new gold standard
Authors: Banerji Sangeeta , Simon Sandra , Tille Andreas , Fruth Angelika , Flieger Antje
Published: March 2020

Salmonella enterica is the second most reported bacterial cause of food-borne infections in Europe. Therefore molecular surveillance activities based on pathogen subtyping are an important measure of controlling Salmonellosis by public health agencies. In Germany, at the federal level, this work is carried out by the National Reference Center for Salmonella and other Bacterial Enteric Pathogens (NRC). With rise of next generation sequencing techniques, the NRC has introduced whole-genome-based typing methods for S. enterica in 2016. In this study we report on the feasibility of genome-based in silico serotyping in the German setting using raw sequence reads. We found that SeqSero and seven gene MLST showed 98% and 95% concordance, respectively, with classical serotyping for the here evaluated serotypes, including the most common German serotypes S. Enteritidis and S. Typhimurium as well as less frequently found serotypes. The level of concordance increased to >99% when the results of both in silico methods were combined. However, both tools exhibited misidentification of monophasic variants, in particular monophasic S. Typhimurium and therefore need to be fine-tuned for reliable detection of this epidemiologically important variant. We conclude that with adjustments Salmonella genome-based serotyping might become the new gold standard.
Signals of anticipation of reward and of mean reward rates in the human brain
Authors: Viviani Roberto , Dommes Lisa , Bosch Julia , Steffens Michael , Paul Anna , Schneider Katharina L. , Stingl Julia C. , Beschoner Petra
Published: March 2020

Theoretical models of dopamine function stemming from reinforcement learning theory have emphasized the importance of prediction errors, which signal changes in the expectation of impending rewards. Much less is known about the effects of mean reward rates, which may be of motivational significance due to their role in computing the optimal effort put into exploiting reward opportunities. Here, we used a reinforcement learning model to design three functional neuroimaging studies and disentangle the effects of changes in reward expectations and mean reward rates, showing recruitment of specific regions in the brainstem regardless of prediction errors. While changes in reward expectations activated ventral striatal areas as in previous studies, mean reward rates preferentially modulated the substantia nigra/ventral tegmental area, deep layers of the superior colliculi, and a posterior pontomesencephalic region. These brainstem structures may work together to set motivation and attentional efforts levels according to perceived reward opportunities.
Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines
Authors: Kotaki Ryutaro , Kawashima Masaharu , Yamamoto Yuichiro , Higuchi Hiroshi , Nagashima Etsuko , Kurosaki Natsumi , Takamatsu Masako , Kikuti Yara Yukie , Imadome Ken-Ichi , Nakamura Naoya , Kotani Ai
Published: March 2020

Latent infection of Epstein-Barr virus (EBV) is associated with a poor prognosis in patients with B cell malignancy. We examined whether dasatinib, a multi kinase inhibitor, which is broadly used for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia is effective on EBV-positive B cell malignancies, using lymphoblastoid cell lines (LCLs) in vitro and in vivo. As a result, in vitro experiments showed that dasatinib induced cell death of the EBV-LCLs which was not accompanied with a lytic reactivation of EBVs. To evaluate the effectiveness in EBV latency type III represented by immunodeficiency lymphoma, LCL-inoculated immunodeficient NOD/shi-scid/Il2rgnul (NOG) mice were treated with dasatinib. However, in vivo experiments revealed that dasatinib treatment exacerbated tumor cell infiltration into the spleen of LCL-inoculated NOG mice, whereas tumor size at the inoculated site was not affected by the treatment. These results suggest that dasatinib exacerbates the pathogenesis at least in some situations although the drug is effective in vitro. Hence, we should carefully examine a possibility of dasatinib repositioning for EBV+ B cell malignancies.
Parcellation of the neonatal cortex using Surface-based Melbourne Children’s Regional Infant Brain atlases (M-CRIB-S)
Authors: Adamson Chris L. , Alexander Bonnie , Ball Gareth , Beare Richard , Cheong Jeanie L. Y. , Spittle Alicia J. , Doyle Lex W. , Anderson Peter J. , Seal Marc L. , Thompson Deanne K.
Published: March 2020

Longitudinal studies measuring changes in cortical morphology over time are best facilitated by parcellation schemes compatible across all life stages. The Melbourne Children’s Regional Infant Brain (M-CRIB) and M-CRIB 2.0 atlases provide voxel-based parcellations of the cerebral cortex compatible with the Desikan-Killiany (DK) and the Desikan-Killiany-Tourville (DKT) cortical labelling schemes. This study introduces surface-based versions of the M-CRIB and M-CRIB 2.0 atlases, termed M-CRIB-S(DK) and M-CRIB-S(DKT), with a pipeline for automated parcellation utilizing FreeSurfer and developing Human Connectome Project (dHCP) tools. Using T2-weighted magnetic resonance images of healthy neonates (n = 58), we created average spherical templates of cortical curvature and sulcal depth. Manually labelled regions in a subset (n = 10) were encoded into the spherical template space to construct M-CRIB-S(DK) and M-CRIB-S(DKT) atlases. Labelling accuracy was assessed using Dice overlap and boundary discrepancy measures with leave-one-out cross-validation. Cross-validated labelling accuracy was high for both atlases (average regional Dice = 0.79–0.83). Worst-case boundary discrepancy instances ranged from 9.96–10.22 mm, which appeared to be driven by variability in anatomy for some cases. The M-CRIB-S atlas data and automatic pipeline allow extraction of neonatal cortical surfaces labelled according to the DK or DKT parcellation schemes.
NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and response to TNF inhibitors: Results from the REPAIR consortium
Authors: Manuel Sánchez-Maldonado Jose , Martínez-Bueno Manuel , Canhão Helena , ter Horst Rob , Muñoz-Peña Sonia , Moñiz-Díez Ana , Rodríguez-Ramos Ana , Escudero Alejandro , Sorensen Signe B. , Hetland Merete L. , Ferrer Miguel A. , Glintborg Bente , Filipescu Ileana , Pérez-Pampin Eva , Conesa-Zamora Pablo , García Antonio , den Broeder Alfons , De Vita Salvatore , Hove Jacobsen Svend Erik , Collantes Eduardo , Quartuccio Luca , Netea Mihai G. , Li Yang , Fonseca João E. , Jurado Manuel , López-Nevot Miguel Ángel , Coenen Marieke J. H. , Andersen Vibeke , Cáliz Rafael , Sainz Juan
Published: March 2020

This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2rs11574851T allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA− = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2TT haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2rs1056890 SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2rs1005044C allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.
Expression and distribution of CD151 as a partner of alpha6 integrin in male germ cells
Authors: Jankovicova J. , Frolikova M. , Palenikova V. , Valaskova E. , Cerny J. , Secova P. , Bartokova M. , Horovska L. , Manaskova-Postlerova P. , Antalikova J. , Komrskova K.
Published: March 2020

The physiological importance of CD151 tetraspanin is known from somatic cells and its outside-in signalling through integrins was described. In male germ cells, two tetraspanins, CD9 and CD81, are involved in sperm-egg membrane fusion, and similarly to integrins, they occupy characteristic regions. We report here on a newly discovered presence of CD151 in sperm, and present its expression and distribution during spermatogenesis and sperm transition during the acrosome reaction. We traced CD151 gene and protein expression in testicular cell subpopulations, with strong enrichment in spermatogonia and spermatids. The testicular and epididymal localization pattern is designated to the sperm head primary fusion site called the equatorial segment and when compared to the acrosome vesicle status, CD151 was located into the inner acrosomal membrane overlying the nucleus. Moreover, we show CD151 interaction with α6 integrin subunit, which forms a dimer with β4 as a part of cis-protein interactions within sperm prior to gamete fusion. We used mammalian species with distinct sperm morphology and sperm maturation such as mouse and bull and compared the results with human. In conclusion, the delivered findings characterise CD151 as a novel sperm tetraspanin network member and provide knowledge on its physiology in male germ cells.
Poly(Ethylene Oxide)-based Electrolyte for Solid-State-Lithium-Batteries with High Voltage Positive Electrodes: Evaluating the Role of Electrolyte Oxidation in Rapid Cell Failure
Authors: Homann Gerrit , Stolz Lukas , Nair Jijeesh , Laskovic Isidora Cekic , Winter Martin , Kasnatscheew Johannes
Published: March 2020

Polyethylene oxide (PEO)-based solid polymer electrolytes (SPEs) typically reveal a sudden failure in Li metal cells particularly with high energy density/voltage positive electrodes, e.g. LiNi0.6Mn0.2Co0.2O2 (NMC622), which is visible in an arbitrary, time – and voltage independent, “voltage noise” during charge. A relation with SPE oxidation was evaluated, for validity reasons on different active materials in potentiodynamic and galvanostatic experiments. The results indicate an exponential current increase and a potential plateau at 4.6 V vs. Li|Li+, respectively, demonstrating that the main oxidation onset of the SPE is above the used working potential of NMC622 being < 4.3 V vs. Li|Li+. Obviously, the SPE│NMC622 interface is unlikely to be the primary source of the observed sudden failure indicated by the “voltage noise”. Instead, our experiments indicate that the Li | SPE interface, and in particular, Li dendrite formation and penetration through the SPE membrane is the main source. This could be simply proven by increasing the SPE membrane thickness or by exchanging the Li metal negative electrode by graphite, which both revealed “voltage noise”-free operation. The effect of membrane thickness is also valid with LiFePO4 electrodes. In summary, it is the cell set-up (PEO thickness, negative electrode), which is crucial for the voltage-noise associated failure, and counterintuitively not a high potential of the positive electrode.
Mitochondria as target to inhibit proliferation and induce apoptosis of cancer cells: the effects of doxycycline and gemcitabine
Authors: Dijk Sas N. , Protasoni Margherita , Elpidorou Marilena , Kroon Albert M. , Taanman Jan-Willem
Published: March 2020

Doxycycline has anti-tumour effects in a range of tumour systems. The aims of this study were to define the role mitochondria play in this process and examine the potential of doxycycline in combination with gemcitabine. We studied the adenocarcinoma cell line A549, its mitochondrial DNA-less derivative A549 ρ° and cultured fibroblasts. Treatment with doxycycline for 5 days resulted in a decrease of mitochondrial-encoded proteins, respiration and membrane potential, and an increase of reactive oxygen species in A549 cells and fibroblasts, but fibroblasts were less affected. Doxycycline slowed proliferation of A549 cells by 35%. Cellular ATP levels did not change. Doxycycline alone had no effect on apoptosis; however, in combination with gemcitabine given during the last 2 days of treatment, doxycycline increased caspase 9 and 3/7 activities, resulting in a further decrease of surviving A549 cells by 59% and of fibroblasts by 24% compared to gemcitabine treatment alone. A549 ρ° cells were not affected by doxycycline. Key effects of doxycycline observed in A549 cells, such as the decrease of mitochondrial-encoded proteins and surviving cells were also seen in the cancer cell lines COLO357 and HT29. Our results suggest that doxycycline suppresses cancer cell proliferation and primes cells for apoptosis by gemcitabine.
Transplantation of a 3D-printed tracheal graft combined with iPS cell-derived MSCs and chondrocytes
Authors: Kim In Gul , Park Su A. , Lee Shin-Hyae , Choi Ji Suk , Cho Hana , Lee Sang Jin , Kwon Yoo-Wook , Kwon Seong Keun
Published: March 2020

For successful tracheal reconstruction, tissue-engineered artificial trachea should meet several requirements, such as biocompatible constructs comparable to natural trachea, coverage with ciliated respiratory mucosa, and adequate cartilage remodeling to support a cylindrical structure. Here, we designed an artificial trachea with mechanical properties similar to the native trachea that can enhance the regeneration of tracheal mucosa and cartilage through the optimal combination of a two-layered tubular scaffold and human induced pluripotent stem cell (iPSC)-derived cells. The framework of the artificial trachea was fabricated with electrospun polycaprolactone (PCL) nanofibers (inner) and 3D-printed PCL microfibers (outer). Also, human bronchial epithelial cells (hBECs), iPSC-derived mesenchymal stem cells (iPSC-MSCs), and iPSC-derived chondrocytes (iPSC-Chds) were used to maximize the regeneration of tracheal mucosa and cartilagein vivo. After 2 days of cultivation using a bioreactor system, tissue-engineered artificial tracheas were transplanted into a segmental trachea defect (1.5-cm length) rabbit model. Endoscopy did not reveal granulation ingrowth into tracheal lumen. Alcian blue staining clearly showed the formation of ciliated columnar epithelium in iPSC-MSC groups. In addition, micro-CT analysis showed that iPSC-Chd groups were effective in forming neocartilage at defect sites. Therefore, this study describes a promising approach for long-term functional reconstruction of a segmental tracheal defect.
Visible photorelease of liquid biopsy markers following microfluidic affinity-enrichment
Authors: Pahattuge Thilanga N. , Jackson J. Matt , Digamber Rane , Wijerathne Harshani , Brown Virginia , Witek Malgorzata A. , Perera Chamani , Givens Richard S. , Peterson Blake R. , Soper Steven A.
Published: March 2020

We detail a heterobifunctional, 7-aminocoumarin photocleavable (PC) linker with unique properties to covalently attach Abs to surfaces and subsequently release them with visible light (400–450 nm).
Specific ion effects on the enzymatic activity of alcohol dehydrogenase fromSaccharomyces cerevisiae
Authors: Carucci Cristina , Raccis Francesco , Salis Andrea , Magner Edmond
Published: March 2020

The specific activity andVmax, but notKm, of alcohol dehydrogenase fromSaccharomyces cerevisiaeare ion specific.
Should we prefer inverse models in quantitative LIBS analysis?
Authors: Duponchel Ludovic , Bousquet Bruno , Pelascini Frédéric , Motto-Ros Vincent
Published: March 2020

The simple linear regression is one of the oldest statistical tools to predict a concentration from a measured signal. However, do we use the right independent and dependent variables in LIBS?
Molecular generation targeting desired electronic properties via deep generative models
Authors: Yuan Qi , Santana-Bonilla Alejandro , Zwijnenburg Martijn A. , Jelfs Kim E.
Published: March 2020

A generative recurrent neural network (RNN) model was developed to target and explore the chemical space of electronic donor–acceptor oligomers effectively.
CuBr2-catalyzed diastereoselective allylation: total synthesis of decytospolides A and B and their C6-epimers
Authors: Padhi Birakishore , Reddy G. Sudhakar , Mallampudi N. Arjunreddy , Choudhury Utkal Mani , Mohapatra Debendra K.
Published: March 2020

An efficient, cost effective and protecting group tolerant CuBr2-catalyzed synthesis of 2,6-trans-disubstituted tetrahydropyran with excellent diastereoselectivity, demonstrated in the total synthesis of decytospolides A and B and their C6-epimers.
Depletion attraction impairs the plasticity of emulsions flowing in a constriction
Authors: Golovkova Iaroslava , Montel Lorraine , Wandersman Elie , Bertrand Thibault , Prevost Alexis Michel , Pontani Lea-Laetitia
Published: March 2020

We study the elasto-plastic behavior of dense attractive emulsions under mechanical perturbation. We find that attraction impairs plastic rearrangements in a constriction, thus leading to higher deformation levels of the droplets.
Functional comparison of paper-based immunoassays based on antibodies and engineered binding proteins
Authors: Sung Ki-Joo , Jabbour Al Maalouf Yara , Johns Quinlan R. , Miller Eric A. , Sikes Hadley D.
Published: March 2020

Analytical performance of an alternative binding protein (rcSso7d) and antibodies are compared in cellulose-based, full sandwich assays.
Diphenyl-1-pyrenylphosphine: photo-triggered AIE/ACQ transition with remarkable third-order nonlinear optical signal change
Authors: Xing Chang , Liu Jianxun , Chen Fang , Li Yuanyuan , Lv Changjian , Peng Qiuchen , Hou Hongwei , Li Kai
Published: March 2020

A propeller-like pyrene derivative is reported, which exhibits a unique photo-triggered AIE/ACQ transition with a remarkable third-order nonlinear optical signal change.
CO scission and reductive coupling of organic carbonyls by a redox-active diboraanthracene
Authors: Taylor Jordan W. , Harman W. Hill
Published: March 2020

A gold-stabilized diboraanthracene mediates reductive transformations of carbonyls, including C–O and C–C bond formation, and deoxygenation of acetone to propene and hydroxide.
Microwave-assisted synthesis followed by a reduction step: making persistent phosphors with a large storage capacity
Authors: Miranda de Carvalho José , Van der Heggen David , Martin Lisa I. D. J. , Smet Philippe F.
Published: March 2020

Microwave irradiation leads to highly homogeneous emitting sites, and large storage capacity in persistent luminescence materials after the reducing step.
Reduction chemistry of hexagonal boron nitride sheets and graphene: a comparative study on the effect of alkali atom doping on their chemical reactivity
Authors: Denis Pablo A. , Ullah Saif , Iribarne Federico
Published: March 2020

Functionalization of 2D BN dramatically increases the charge donated by lithium and 2D BN is no longer inert!
Acetylide-for-thiolate and thiolate-for-acetylide exchange on gold nanoclusters
Authors: Hosier Christopher A. , Anderson Ian D. , Ackerson Christopher J.
Published: March 2020

New ligand-exchange reactions are reported for thiolate- and acetylide-protected gold nanoclusters, which are rationalized through bond strengths and enthalpy arguments.
Diterpenes with bicyclo[2.2.2]octane moieties from the fungicolous fungus Xylaria longipes HFG1018
Authors: Chen He-Ping , Li Jing , Zhao Zhen-Zhu , Li Xinyang , Liu Shui-Lin , Wang Qing-Yuan , Liu Ji-Kai
Published: March 2020

Xylarilongipins A and B, along with their biosynthetic precursor hymatoxin L, were isolated from the culture broth of the fungicolous fungus Xylaria longipes HFG1018 inhabiting in the medicinal fungus Fomitopsis betulinus.
A modular approach for organizing dimeric coiled coils on peptoid oligomer scaffolds
Authors: Jiang Linhai , Kirshenbaum Kent
Published: March 2020

A peptoid oligomer macrocycle can be used as a scaffold for templating a dimeric coiled coil peptide assembly, substantially increasing its thermal stability.
ALD Al2O3 gate dielectric on the reduction of interface trap density and the enhanced photo-electric performance of IGO TFT
Authors: Chen Kuan-Yu , Yang Chih-Chiang , Huang Chun-Yuan , Su Yan-Kuin
Published: March 2020

The amorphous indium gallium oxide thin film transistor was fabricated using a cosputtering method.
Recruitment of receptors at supported lipid bilayers promoted by the multivalent binding of ligand-modified unilamellar vesicles
Authors: Di Iorio Daniele , Lu Yao , Meulman Joris , Huskens Jurriaan
Published: March 2020

The development of model systems that mimic biological interactions and allow the control of both receptor and ligand densities, is essential for a molecular understanding of biomolecular processes, such as the recruitment of receptors at interfaces.
Stigmasterol alleviates cerebral ischemia/reperfusion injury by attenuating inflammation and improving antioxidant defenses in rats
Authors: Liang Qilong , Yang Jun , He Jiaji , Chen Xiaoling , Zhang Hong , Jia Maolin , Liu Kai , Jia Chuangchuang , Pan Yanhong , Wei Jinwang
Published: March 2020

Background/aims: The paper aimed to investigate the effects of Stigmasterol on inflammatory factors, antioxidant capacity, and apoptotic signaling pathways in brain tissue of rats with cerebral ischemia/reperfusion (I/R) injury. Methods: The neurological deficits of the rats were analyzed and HE staining was performed. The cerebral infarct volume was calculated by means of TTC staining, and neuronal apoptosis was detected by TUNEL staining. At the same time, the contents of glutathione peroxidase, glutathione, superoxide dismutase (SOD), nitric oxide, and malondialdehyde in brain tissue were measured. The expression of the relevant protein was detected by means of Western blotting. Results: The results showed that the neurological deficit score and infarct area of the I/R rats in the soy sterol treatment group were significantly lower than those in the I/R group. Moreover, the levels of carbon monoxide and malondialdehyde in the soysterol group were significantly lower than those in the I/R group, and the expressions of cyclooxygenase-2 (Cox-2) and NF-κB (p65) in the soysterol group were also significantly lower than those in the I/R group. The expression of Nrf2 (nucleus) and heme oxygenase-1 (HO-1) increased significantly, and the activities of antioxidant enzymes and SOD were increased. In addition, the stigmasterol treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, and up-regulate Bcl-Xl expression. Conclusion: Stigmasterol protects the brain from brain I/R damage by reducing oxidative stress and inflammation.
Dietary vitamin A intake and the risk of ovarian cancer: a meta-analysis
Authors: Wang Qiaoqiao , He Chaying
Published: March 2020

BACKGROUND: Previous studies have demonstrated some associations between dietary vitamin A intake and ovarian cancer risk with an inconsistent relationship. We therefore performed the present study to further explore the association between them.

METHODS: Databases of PubMed, Embase, and Web of Science were retrieved up to September 1, 2019. Summarized relative risk (RR) with corresponding 95% confidence intervals (CI) were calculated. Stata 14.0 software was used for data analysis.

RESULTS: Fifteen articles involving 4882 cases and 443,179 participants were included in this meta-analysis. A positive association between dietary vitamin A intake and ovarian cancer risk was found (RR = 0.816, 95%CI = 0.723–0.920, I2 = 48.4%, Pfor heterogeneity = 0.019). Significant association was also found in case–control studies (RR = 0.769, 95%CI = 0.655–0.902), but not in cohort studies. When we performed the analysis between ovarian cancer risk and geographic locations, we found an inverse association in North American populations (RR = 0.825, 95%CI = 0.720–0.946), instead of other populations.

CONCLUSIONS: In summary, findings from the present study suggested that higher dietary intake of vitamin A may contribute to the lower development of ovarian cancer, especially among North Americans.
New model for ecological assessment of comminution process in energy biomass processing chain
Authors: Kruszelnicka Weronika
Published: March 2020

Acquiring energy contained in the biomass structure requires its prior appropriate preparation. These treatments require some energy inputs, which significantly affects the reduction of the energy and environmental balance in the entire life cycle of energy biomass processing chain. In connection with the above, the aim of the work was to develop a methodology for ecological assessment of biomass grinding in the processing chain for energy purposes. The research problem was formulated as follows: is it possible to create an assessment model that takes into account the environmental inputs and benefits of the grinding process of biomass intended for further energy use (combustion); how the control variables of the grinding machine affect the ecological evaluation of the process. In response to the research problem, the original index of ecological assessment of the biomass grinding process was developed. The model was verified by assessing the process of rice and maize grinding on a real object - a five-disc mill, for various settings of grinding discs speed. It was found that the developed ecological assessment model allows comparison of grinding processes and indication of the process with a more favorable CO2 emission balance and its values depend on the control parameters of the mill.
Prediction of higher heating value of oat grain and straw biomass
Authors: Górnicki Krzysztof , Kaleta Agnieszka , Winiczenko Radosław
Published: March 2020

The aim of the study was modelling of HHV of oat (grain and straw) biomass. The content of ash, carbon, hydrogen, nitrogen, moisture, volatile materials and the higher heating value of oat (grain and straw) biomass was measured. The possibility of using twenty models from the literature to describe HHV of oat was examined. The following models: HHV=19.914-0.2324A and HHV=-3.0368+0.2218VM+0.2601FC are recommended for determining of HHV of oat (RMSE of the range 0.13-0.28). The models based on ultimate analysis gave worse results in determination of HHV for oat.
Modelling of biomass temperature in the drying process
Authors: Golisz Ewa , Jaros Małgorzata , Głowacki Szymon
Published: March 2020

The goal of the work was to propose and verify the model of temperature changes of the convective dried biomass depending on the drying time. The algebraic temperature model of the convective dried solid, giving the possibility of its direct calculation, was based on the logistic function of growth. Temperature model was verified for convective dried biomass: vegetable and wood (poplar and willow wood chips) significantly differing in initial moisture content. Parameter W in the temperature model, defined as the coefficient of temperature rate changes reaches greater values in higher temperature of drying air and for wood biomass which has lower initial moisture content. Empirically selected parameter W allows to verify the temperature model with the relative error less than 5%.
Analysis of possibilities of using biomass from cherry and morello cherry stones for energy purposes
Authors: Bryś Andrzej , Zielińska Joanna , Głowacki Szymon , Tulej Weronika , Bryś Joanna
Published: March 2020

Growing demand for energy and care about natural environment is the motivation to find alternative sources of energy. One of them is biomass from cherry and morello cherry stones, which is food processing industry waste. Stones have fairly good physical properties regarding material for combustion. Cherry and morello cherry crop in Poland is at the level of 200 thousand tons yearly, and processing them generates a considerable amount of waste that consists of stones, which may be used for energy purposes. In the work, the initial water content (u), curves of combustion in different temperatures, percentage ash content, heat of combustion and percentage share of stone in the whole fruit were determined.