bluuebunny/crossref_metadata_2025 huggingface dataset:
A structure-based computational workflow to predict liability and binding modes of small molecules to hERG
Authors: Kalyaanamoorthy Subha , Lamothe Shawn M. , Hou Xiaoqing , Moon Tae Chul , Kurata Harley T. , Houghton Michael , Barakat Khaled H.
Published: October 2020

Off-target interactions of drugs with the human ether-à-go-go related gene 1 (hERG1) channel have been associated with severe cardiotoxic conditions leading to the withdrawal of many drugs from the market over the last decades. Consequently, predicting drug-induced hERG-liability is now a prerequisite in any drug discovery campaign. Understanding the atomic level interactions of drug with the channel is essential to guide the efficient development of safe drugs. Here we utilize the recent cryo-EM structure of the hERG channel and describe an integrated computational workflow to characterize different drug-hERG interactions. The workflow employs various structure-based approaches and provides qualitative and quantitative insights into drug binding to hERG. Our protocol accurately differentiated the strong blockers from weak and revealed three potential anchoring sites in hERG. Drugs engaging in all these sites tend to have high affinity towards hERG. Our results were cross-validated using a fluorescence polarization kit binding assay and with electrophysiology measurements on the wild-type (WT-hERG) and on the two hERG mutants (Y652A-hERG and F656A-hERG), using the patch clamp technique on HEK293 cells. Finally, our analyses show that drugs binding to hERG disrupt and hijack certain native—structural networks in the channel, thereby, gaining more affinity towards hERG.
Human placental uptake of glutamine and glutamate is reduced in fetal growth restriction
Authors: McIntyre Kirsty R. , Vincent Kirsty M. M. , Hayward Christina E. , Li Xiaojia , Sibley Colin P. , Desforges Michelle , Greenwood Susan L. , Dilworth Mark R.
Published: October 2020

Fetal growth restriction (FGR) is a significant risk factor for stillbirth, neonatal complications and adulthood morbidity. Compared with those of appropriate weight for gestational age (AGA), FGR babies have smaller placentas with reduced activity of amino acid transporter systems A and L, thought to contribute to poor fetal growth. The amino acids glutamine and glutamate are essential for normal placental function and fetal development; whether transport of these is altered in FGR is unknown. We hypothesised that FGR is associated with reduced placental glutamine and glutamate transporter activity and expression, and propose the mammalian target of rapamycin (mTOR) signaling pathway as a candidate mechanism. FGR infants [individualised birth weight ratio (IBR) < 5th centile] had lighter placentas, reduced initial rate uptake of 14C-glutamine and 14C-glutamate (per mg placental protein) but higher expression of key transporter proteins (glutamine: LAT1, LAT2, SNAT5, glutamate: EAAT1) versus AGA [IBR 20th–80th]. In further experiments, in vitro exposure to rapamycin inhibited placental glutamine and glutamate uptake (24 h, uncomplicated pregnancies) indicating a role of mTOR in regulating placental transport of these amino acids. These data support our hypothesis and suggest that abnormal glutamine and glutamate transporter activity is part of the spectrum of placental dysfunction in FGR.
Internet addiction among adolescents in Macau and mainland China: prevalence, demographics and quality of life
Authors: Xu Dan-Dan , Lok Ka-In , Liu Huan-Zhong , Cao Xiao-Lan , An Feng-Rong , Hall Brian J. , Ungvari Gabor S. , Lei Si-Man , Xiang Yu-Tao
Published: October 2020

Internet addiction (IA) is common among adolescents and significantly determined by sociocultural and economic factors. The aim of this study was to compare the prevalence of IA among adolescents between Macau and mainland China and also examine its association with quality of life. A total of 2892 secondary school students were included. Standardized instruments were used to measure IA, depressive symptoms and quality of life. The overall prevalence of IA was 23.7%, with 32.5% in Macau and 19.8% in mainland China. Students in Macau were more likely to suffer from IA than those in mainland China (OR = 2.15, p < 0.001). Correlates of IA included being in higher school grades, poor academic performance, and more severe depressive symptoms. Students with IA reported lower quality of life in physical, psychological, social, and environmental domains. IA is common among Chinese adolescents, particularly in Macau. Considering the negative impact of IA on health and quality of life, regular screening and effective interventions should be undertaken for young Internet users.
Effects of pre-oxidation on the corrosion behavior of pure Ti under coexistence of solid NaCl deposit and humid oxygen at 600 °C: the diffusion of chlorine
Authors: Fan Lei , Liu Li , Lv Yuhai , Wang Hao , Fu Anqing , Yuan Juntao , Li Ying , Wang Fuhui , Yin Chengxian
Published: October 2020

The effect of pre-oxidation on the corrosion behavior of pure Ti covered with a solid NaCl deposit in the humid O2 flow at 600 °C is studied. The oxide scale, formed by pre-oxidation, protects the substrate from the NaCl induced corrosion during the initial stage. However, the corrosion of the pre-oxidized sample is severely accelerated by solid NaCl after an incubation period. The chlorine, generated from the decomposition of solid NaCl, diffuses into the oxide/substrate interface as ions during the incubation period, which was observed by ToF–SIMS. The chlorine at the oxide/substrate interface induces the fast corrosion after the incubation period although the pre-oxidation scale is complete and compact.
Chronic lymphocytic leukemia-associated paraneoplastic pemphigus: potential cause and therapeutic strategies
Authors: Cao Lei , Wang Fei , Du Xin-Yi , Zhu Hua-Yuan , Wang Li , Xu Wei , Li Jian-Yong , Fan Lei
Published: October 2020

Paraneoplastic pemphigus (PNP) is a severe autoimmune syndrome commonly triggered by neoplasms. The prognosis of CLL-associated PNP is dismal due to its refractory course and secondary infection and no standard treatment was recommended. We retrospectively reported six CLL with PNP cases from 842 cases of CLL including diagnosis, treatment and prognosis. The median time between the initial of CLL to PNP was 36 months while the median overall survival from the diagnosis of PNP was 26 months. And three cases died of lung infection while 5 developed pulmonary symptoms. And 5 cases received fludarabine-based chemotherapy before developing PNP, which suggesting fludarabine was one of potential causes of PNP. For the treatment, five patients were rescued by combined regimens including rituximab, methylprednisolone, immunoglobulin, fresh frozen plasma and the last received ibrutinib combined with short-term prednisone. Fludarabine-based regimen may be one of the potential causes of PNP. The combined regimen might shed a new light, while ibrutinib is a promising drug for CLL with PNP, but needs much more evidence. PNP should be carefully treated to guide early diagnosis and intervention for a better prognosis.
Differential side-effects of Bacillus thuringiensis bioinsecticide on non-target Drosophila flies
Authors: Babin Aurélie , Nawrot-Esposito Marie-Paule , Gallet Armel , Gatti Jean-Luc , Poirié Marylène
Published: October 2020

Bioinsecticides based on Bacillus thuringiensis (Bt) spores and toxins are increasingly popular alternative solutions to control insect pests, with potential impact of their accumulation in the environment on non-target organisms. Here, we tested the effects of chronic exposure to commercial Bt formulations (Bt var. kurstaki and israelensis) on eight non-target Drosophila species present in Bt-treated areas, including D. melanogaster (four strains). Doses up to those recommended for field application (~ 106 Colony Forming Unit (CFU)/g fly medium) did not impact fly development, while no fly emerged at ≥ 1000-fold this dose. Doses between 10- to 100-fold the recommended one increased developmental time and decreased adult emergence rates in a dose-dependent manner, with species-and strain-specific effect amplitudes. Focusing on D. melanogaster, development alterations were due to instar-dependent larval mortality, and the longevity and offspring number of adult flies exposed to bioinsecticide throughout their development were moderately influenced. Our data also suggest a synergy between the formulation compounds (spores, cleaved toxins, additives) might induce the bioinsecticide effects on larval development. Although recommended doses had no impact on non-target Drosophila species, misuse or local environmental accumulation of Bt bioinsecticides could have side-effects on fly populations with potential implications for their associated communities.
In silico analysis and in vivo assessment of a novel epitope-based vaccine candidate against uropathogenic Escherichia coli
Authors: Hasanzadeh Sara , Habibi Mehri , Shokrgozar Mohammad Ali , Ahangari Cohan Reza , Ahmadi Khadijeh , Asadi Karam Mohammad Reza , Bouzari Saeid
Published: October 2020

Uropathogenic Escherichia coli (UPEC) are common pathogens in urinary tract infections (UTIs), which show resistance to antibiotics. Therefore, there is a need for a vaccine to reduce susceptibility to the infection. In the present study, bioinformatics approaches were employed to predict the best B and T-cell epitopes of UPEC virulence proteins to develop a multiepitope vaccine candidate against UPEC. Then, the efficacy of the candidate was studied with and without Freund adjuvant. Using bioinformatics methods, 3 epitope-rich domains of IutA and FimH antigens were selected to construct the fusion. Molecular docking and Molecular dynamics (MD) simulation were employed to investigate in silico interaction between designed vaccine and Toll-like receptor 4 (TLR4). Our results showed that the levels of IgG and IgA antibodies were improved in the serum and mucosal samples of the vaccinated mice, and the IgG responses were maintained for at least 6 months. The fusion protein was also able to enhance the level of cytokines IFN.γ (Th1), IL.4 (Th2), and IL.17. In challenge experiments, all vaccine combinations showed high potency in the protection of the urinary tract even after 6 months post first injection. The present study indicates that the designed candidate is able to evoke strong protective responses which warrant further studies.
Regulating soil bacterial diversity, community structure and enzyme activity using residues from golden apple snails
Authors: Wang Jiaxin , Lu Xuening , Zhang Jiaen , Wei Guangchang , Xiong Yue
Published: October 2020

It has been shown that the golden apple snail (GAS, Pomacea canaliculata), which is a serious agricultural pest in Southeast Asia, can provide a soil amendment for the reversal of soil acidification and degradation. However, the impact of GAS residue (i.e., crushed, whole GAS) on soil bacterial diversity and community structure remains largely unknown. Here, a greenhouse pot experiment was conducted and 16S rRNA gene sequencing was used to measure bacterial abundance and community structure in soils amended with GAS residue and lime. The results suggest that adding GAS residue resulted in a significant variation in soil pH and nutrients (all P < 0.05), and resulted in a slightly alkaline (pH = 7.28–7.75) and nutrient-enriched soil, with amendment of 2.5–100 g kg−1 GAS residue. Soil nutrients (i.e., NO3-N and TN) and TOC contents were increased (by 132–912%), and some soil exocellular enzyme activities were enhanced (by 2–98%) in GAS residue amended soil, with amendment of 1.0–100 g kg−1 GAS residue. Bacterial OTU richness was 19% greater at the 2.5 g kg−1 GAS residue treatment than the control, while it was 40% and 53% lower at 100 g kg−1 of GAS residue and 50 g kg−1 of lime amended soils, respectively. Firmicutes (15–35%) was the most abundant phylum while Bacterioidetes (1–6%) was the lowest abundant one in GAS residue amended soils. RDA results suggest that the contents of soil nutrients (i.e., NO3-N and TN) and soil TOC explained much more of the variations of bacterial community than pH in GAS residue amended soil. Overuse of GAS residue would induce an anaerobic soil environment and reduce bacterial OTU richness. Soil nutrients and TOC rather than pH might be the main factors that are responsible for the changes of bacterial OTU richness and bacterial community structure in GAS residue amended soil.
SecY-mediated quality control prevents the translocation of non-gated porins
Authors: Jung Sebastian , Bader Verian , Natriashvili Ana , Koch Hans-Georg , Winklhofer Konstanze F. , Tatzelt Jörg
Published: October 2020

OmpC and OmpF are among the most abundant outer membrane proteins in E. coli and serve as hydrophilic channels to mediate uptake of small molecules including antibiotics. Influx selectivity is controlled by the so-called constriction zone or eyelet of the channel. Mutations in the loop domain forming the eyelet can disrupt transport selectivity and thereby interfere with bacterial viability. In this study we show that a highly conserved motif of five negatively charged amino acids in the eyelet, which is critical to regulate pore selectivity, is also required for SecY-mediated transport of OmpC and OmpF into the periplasm. Variants with a deleted or mutated motif were expressed in the cytosol and translocation was initiated. However, after signal peptide cleavage, import into the periplasm was aborted and the mutated proteins were redirected to the cytosol. Strikingly, reducing the proof-reading capacity of SecY by introducing the PrlA4 substitutions restored transport of OmpC with a mutated channel domain into the periplasm. Our study identified a SecY-mediated quality control pathway to restrict transport of outer membrane porin proteins with a deregulated channel activity into the periplasm.
Cryo-electron microscopy structure of the 70S ribosome from Enterococcus faecalis
Authors: Murphy Eileen L. , Singh Kavindra V. , Avila Bryant , Kleffmann Torsten , Gregory Steven T. , Murray Barbara E. , Krause Kurt L. , Khayat Reza , Jogl Gerwald
Published: October 2020

Enterococcus faecalis is a gram-positive organism responsible for serious infections in humans, but as with many bacterial pathogens, resistance has rendered a number of commonly used antibiotics ineffective. Here, we report the cryo-EM structure of the E. faecalis 70S ribosome to a global resolution of 2.8 Å. Structural differences are clustered in peripheral and solvent exposed regions when compared with Escherichia coli, whereas functional centres, including antibiotic binding sites, are similar to other bacterial ribosomes. Comparison of intersubunit conformations among five classes obtained after three-dimensional classification identifies several rotated states. Large ribosomal subunit protein bL31, which forms intersubunit bridges to the small ribosomal subunit, assumes different conformations in the five classes, revealing how contacts to the small subunit are maintained throughout intersubunit rotation. A tRNA observed in one of the five classes is positioned in a chimeric pe/E position in a rotated ribosomal state. The 70S ribosome structure of E. faecalis now extends our knowledge of bacterial ribosome structures and may serve as a basis for the development of novel antibiotic compounds effective against this pathogen.
Food-borne Lactiplantibacillus plantarum protect normal intestinal cells against inflammation by modulating reactive oxygen species and IL-23/IL-17 axis
Authors: Prete Roberta , Garcia-Gonzalez Natalia , Di Mattia Carla D. , Corsetti Aldo , Battista Natalia
Published: October 2020

Food-associated Lactiplantibacillus plantarum (Lpb. plantarum) strains, previously classified as Lactobacillus plantarum, are a promising strategy to face intestinal inflammatory diseases. Our study was aimed at clarifying the protective role of food-borne Lpb. plantarum against inflammatory damage by testing the scavenging microbial ability both in selected strains and in co-incubation with normal mucosa intestinal cells (NCM460). Here, we show that Lpb. plantarum endure high levels of induced oxidative stress through partially neutralizing reactive oxygen species (ROS), whereas they elicit their production when co-cultured with NCM460. Moreover, pre-treatment with food-borne Lpb. plantarum significantly reduce pro-inflammatory cytokines IL-17F and IL-23 levels in inflamed NCM460 cells. Our results suggest that food-vehicled Lpb. plantarum strains might reduce inflammatory response in intestinal cells by directly modulating local ROS production and by triggering the IL-23/IL-17 axis with future perspectives on health benefits in the gut derived by the consumption of functional foods enriched with selected strains.
Exponentially decaying modes and long-term prediction of sea ice concentration using Koopman mode decomposition
Authors: Hogg James , Fonoberova Maria , Mezić Igor
Published: October 2020

Sea ice cover in the Arctic and Antarctic is an important indicator of changes in the climate, with important environmental, economic and security consequences. The complexity of the spatio-temporal dynamics of sea ice makes it difficult to assess the temporal nature of the changes—e.g. linear or exponential—and their precise geographical loci. In this study, Koopman Mode Decomposition (KMD) is applied to satellite data of sea ice concentration for the Northern and Southern hemispheres to gain insight into the temporal and spatial dynamics of the sea ice behavior and to predict future sea ice behavior. We observe spatial modes corresponding to the mean and annual variation of Arctic and Antarctic sea ice concentration and observe decreases in the mean sea ice concentration from early to later periods, as well as corresponding shifts in the locations that undergo significant annual variation in sea ice concentration. We discover exponentially decaying spatial modes in both hemispheres and discuss their precise spatial extent, and also perform predictions of future sea ice concentration. The Koopman operator-based, data-driven decomposition technique gives insight into spatial and temporal dynamics of sea ice concentration not apparent in traditional approaches.
Diagnostic values of Xpert MTB/RIF, T-SPOT.TB and adenosine deaminase for HIV-negative tuberculous pericarditis in a high burden setting: a prospective observational study
Authors: Hu Xu , Xing Baochun , Wang Wei , Yang Pengwei , Sun Yumei , Zheng Xiangyang , Shang Yaomin , Chen Feifei , Liu Nai , Yang Lu , Zhao Yue , Tan Jiao , Zhang Xueya , Wang Yan , Zhang Zhengxun , Liu Yaqian
Published: October 2020

The diagnosis of tuberculous pericarditis (TBP) remains challenging. This prospective study evaluated the diagnostic value of Xpert MTB/RIF (Xpert) and T-SPOT.TB and adenosine deaminase (ADA) for TBP in a high burden setting. A total of 123 HIV-negative patients with suspected TBP were enrolled at a tertiary referral hospital in China. Pericardial fluids were collected and subjected to the three rapid tests, and the results were compared with the final confirmed diagnosis. Of 105 patients in the final analysis, 39 (37.1%) were microbiologically, histopathologically or clinically diagnosed with TBP. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) for Xpert were 66.7%, 98.5%, 96.3%, 83.3%, 44.0, 0.338, and 130.0, respectively, compared to 92.3%, 87.9%, 81.8%, 95.1%, 7.6, 0.088, and 87.0, respectively, for T-SPOT.TB, and 82.1%, 92.4%, 86.5%, 89.7%, 10.8, 0.194, and 55.8, respectively, for ADA (≥ 40 U/L). ROC curve analysis revealed a cut-off point of 48.5 spot-forming cells per million pericardial effusion mononuclear cells for T-SPOT.TB, which had a DOR value of 183.8, while a cut-off point of 41.5 U/L for ADA had a DOR value of 70.9. Xpert (Step 1: rule-in) followed by T-SPOT.TB [cut-off point] (Step 2: rule-out) showed the highest DOR value of 252.0, with only 5.7% (6/105) of patients misdiagnosed. The two-step algorithm consisting of Xpert and T-SPOT.TB could offer rapid and accurate diagnosis of TBP.
Waist-to-height ratio is a better discriminator of cardiovascular disease than other anthropometric indicators in Kurdish adults
Authors: Pasdar Yahya , Moradi Shima , Moludi Jalal , Saiedi Somaiyeh , Moradinazar Mehdi , Hamzeh Behrooz , Jafarabadi Mohammad Asghari , Najafi Farid
Published: October 2020

It has been suggested that abdominal obesity might be a better cardiovascular diseases (CVDs) discriminator than overall obesity. The most appropriate obesity measures for estimating CVD events in Kurdish populations have not been well-recognized. The objective of the present study was, therefore, to determine the cutoff points of BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist to height ratio (WHtR) as the diagnostic cut-offs to discriminate the prevalent cardiovascular diseases. The data collected from Ravansar Non-Communicable Disease (RaNCD) cohort, the first Kurdish population-based study, was analyzed. The information related to BMI, WC, WHR and WHtR of 10,065 adult participants in the age range of 35–65 was analyzed in this study. Receiver operating characteristic (ROC) analyses were conducted to evaluate the optimum cut-off values and to predict the incidence of cardiac events. The results showed that WHtR had the largest areas under the ROC curve for cardiac events in both male and female participants, and this was followed by WHR, WC, and BMI. The optimal cut-off values for determining the cardiac events in the Kurdish population were BMI = 27.02 kg/m2 for men and BMI = 27.60 kg/m2 for women, WC = 96.05 cm in men and 99.5 cm for women, WHRs = 0.96 in both sexes, and WHtR = 0.56 for men and 0.65 for women. The current study, therefore, showed that WHtR might serve as a better index of prevalent cardiac event than BMI, WHR and WC.
Silencing of Testin expression is a frequent event in spontaneous lymphomas from Trp53-mutant mice
Authors: Weeks Robert J. , Ludgate Jackie L. , Le Mée Gwenn , Khanal Rubina , Mehta Sunali , Williams Gail , Slatter Tania L. , Braithwaite Antony W. , Morison Ian M.
Published: October 2020

The tumour suppressor gene, TES, is frequently methylated in many human tumours. Previously, we demonstrated that TES promoter methylation and transcriptional silencing was the most common molecular abnormality detected in childhood acute lymphoblastic leukaemia (ALL). Trp53-mutant mouse models predominantly develop B- and T-cell lymphomas, which are widely considered equivalent to childhood T and B ALL. In this study, we examined expression of Tes transcript and Testin protein in spontaneous tumours obtained from three Trp53-mutant mouse models. Using immunohistochemistry, we report that 47% of lymphomas lacked Testin protein compared to only 7% of non-lymphoid tumours. Further examination of the lymphomas from Trp53-null and Trp53-mΔpro homozygous mutant mice revealed that 63% and 69% respectively of the isolated lymphomas were Testin negative, which is similar to reported rates in childhood T-ALL. Surprisingly, lymphomas from Trp53-Δ122 mice were frequently Testin positive (> 60%), suggesting that the presence of the Trp53-Δ122 protein appeared to mitigate the requirement for Tes silencing in lymphomagenesis. Quantitative RT-PCR results confirmed that this lack of Testin protein was due to Tes transcriptional silencing, although bisulfite sequencing demonstrated that this was not due to promoter methylation. These results are consistent with the Testin protein having lymphoid tumour suppressor activity in both mice and humans.
Comparison of inspiratory and expiratory lung and lobe volumes among supine, standing, and sitting positions using conventional and upright CT
Authors: Yamada Yoshitake , Yamada Minoru , Chubachi Shotaro , Yokoyama Yoichi , Matsuoka Shiho , Tanabe Akiko , Niijima Yuki , Murata Mitsuru , Fukunaga Koichi , Jinzaki Masahiro
Published: October 2020

Currently, no clinical studies have compared the inspiratory and expiratory volumes of unilateral lung or of each lobe among supine, standing, and sitting positions. In this prospective study, 100 asymptomatic volunteers underwent both low-radiation-dose conventional (supine position, with arms raised) and upright computed tomography (CT) (standing and sitting positions, with arms down) during inspiration and expiration breath-holds and pulmonary function test (PFT) on the same day. We compared the inspiratory/expiratory lung/lobe volumes on CT in the three positions. The inspiratory and expiratory bilateral upper and lower lobe and lung volumes were significantly higher in the standing/sitting positions than in the supine position (5.3–14.7% increases, all P < 0.001). However, the inspiratory right middle lobe volume remained similar in the three positions (all P > 0.15); the expiratory right middle lobe volume was significantly lower in the standing/sitting positions (16.3/14.1% decrease) than in the supine position (both P < 0.0001). The Pearson’s correlation coefficients (r) used to compare the total lung volumes on inspiratory CT in the supine/standing/sitting positions and the total lung capacity on PFT were 0.83/0.93/0.95, respectively. The r values comparing the total lung volumes on expiratory CT in the supine/standing/sitting positions and the functional residual capacity on PFT were 0.83/0.85/0.82, respectively. The r values comparing the total lung volume changes from expiration to inspiration on CT in the supine/standing/sitting positions and the inspiratory capacity on PFT were 0.53/0.62/0.65, respectively. The study results could impact preoperative CT volumetry of the lung in lung cancer patients (before lobectomy) for the prediction of postoperative residual pulmonary function, and could be used as the basis for elucidating undetermined pathological mechanisms. Furthermore, in addition to morphological evaluation of the chest, inspiratory and expiratory upright CT may be used as an alternative tool to predict lung volumes such as total lung capacity, functional residual capacity, and inspiratory capacity in situation in which PFT cannot be performed such as during an infectious disease pandemic, with relatively more accurate predictability compared with conventional supine CT.
Assessing harbour porpoise carcasses potentially subjected to grey seal predation
Authors: van Neer Abbo , Gross Stephanie , Kesselring Tina , Grilo Miguel L. , Ludes-Wehrmeister Eva , Roncon Giulia , Siebert Ursula
Published: October 2020

As a follow-up on the data presented for seals, we herein report and discuss outcomes resulting from a retrospective evaluation of harbour porpoise stranding and necropsy data from Schleswig–Holstein, Germany (n = 4463) to enable an objective evaluation of potential ecological effects of grey seal predation on porpoises. Results are compared to a recent case of definite grey seal predation as well as to reports from other countries. Porpoise carcasses potentially subject to grey seal predation show severe lacerations, with large parts of skin and underlying tissue being detached from the body. Loss of blubber tissue is common. Based on the occurrence frequencies of encountered lesions, a list of parameters as well as a complementary decision tree are suggested to be used for future assessments. The results shown add to an increasingly standardised assessment protocol of suspected grey seal predation cases making respective results comparable between different areas and countries. The usage of a standardised protocol may increase the awareness of grey seal predation and the reporting of such cases. By this, differences in the predation and feeding patterns as well as the potential ecological relevance of this behaviour may be elucidated.
Ab initio calculations of conduction band effective mass parameters of thermoelectric $${\hbox {Mg}}_{2} {\hbox {X}}_{1{-}x} {\hbox {Y}}_x$$ (X, Y = Si, Ge, Sn) alloys
Authors: Guerra Juan M. , Mahr Carsten , Giar Marcel , Czerner Michael , Heiliger Christian
Published: October 2020

Since there are still research interests in the physical properties of quasi-binary thermoelectric $${\hbox {Mg}}_{2} {\hbox {X}}_{1-x}{\hbox {Y}}_{x}$$

Mg
2

X

1
-
x

Y
x

alloys, with X, Y = Si, Ge, Sn, we present an ab initio analysis that yields the relative formation energy and effective masses of the conduction bands, in the whole compositional range x. We base our calculations on the full-relativistic Korringa, Kohn and Rostocker (KKR) Green’s functions formalism within the coherent potential approximation (CPA). Formation energies, measured relative to the end $${\hbox {Mg}}_{2} \hbox {X}$$

Mg
2

X

compounds, show no excess energy for the $${\hbox {Mg}}_{2} \hbox {Si} {-} {\hbox {Mg}}_{2} \hbox {Ge}$$

Mg
2

Si
-

Mg
2

Ge

substitution thus indicating a complete solubility. In contrast, concave and asymmetric formation energies for intermediate compositions in the $${\hbox {Mg}}_{2} \hbox {X} {-} {\hbox {Mg}}_{2} \hbox {Sn}$$

Mg
2

X
-

Mg
2

Sn

alloys manifest a miscibility gap. With this basis, we compute and discuss the crossing of the conduction bands observed in n-type $${\hbox {Mg}}_{2} {\hbox {X}}_{1-x} {\hbox {Sn}}_x$$

Mg
2

X

1
-
x

Sn
x

materials. We present direction- and band-dependent effective masses using a generalized single parabolic band effective mass approximation to discuss anisotropic effects, to interpret available experimental and theoretical data, and to predict intermediate and not yet published transport parameters on these alloys.
Crystal structure of Epiphyas postvittana pheromone binding protein 3
Authors: Hamiaux Cyril , Carraher Colm , Löfstedt Christer , Corcoran Jacob A.
Published: October 2020

The insect olfactory system operates as a well-choreographed ensemble of molecules which functions to selectively translate volatile chemical messages present in the environment into neuronal impulses that guide insect behaviour. Of these molecules, binding proteins are believed to transport hydrophobic odorant molecules across the aqueous lymph present in antennal sensilla to receptors present in olfactory sensory neurons. Though the exact mechanism through which these proteins operate is still under investigation, these carriers clearly play a critical role in determining what an insect can smell. Binding proteins that transport important sex pheromones are colloquially named pheromone binding proteins (PBPs). Here, we have produced a functional recombinant PBP from the horticultural pest, Epiphyas postvittana (EposPBP3), and experimentally solved its apo-structure through X-ray crystallography to a resolution of 2.60 Å. Structural comparisons with related lepidopteran PBPs further allowed us to propose models for the binding of pheromone components to EposPBP3. The data presented here represent the first structure of an olfactory-related protein from the tortricid family of moths, whose members cause billions of dollars in losses to agricultural producers each year. Knowledge of the structure of these important proteins will allow for subsequent studies in which novel, olfactory molecule-specific insecticides can be developed.
Clinical utility of brain-derived neurotrophic factor as a biomarker with left ventricular echocardiographic indices for potential diagnosis of coronary artery disease
Authors: Monisha K. G. , Prabu Paramasivam , Chokkalingam M. , Murugesan Ram , Milenkovic Dragan , Ahmed Shiek S. S. J.
Published: October 2020

Brain-derived neurotrophic factor (BDNF) plays a central pivotal role in the development of the cardiovascular system. Recent evidence suggests that BDNF has adverse subclinical cardiac remodeling in participants with cardiovascular disease risk factors. Relating serum BDNF levels with two-dimensional echocardiographic indices will provide insights into the BDNF mediated pathophysiology in coronary artery disease (CAD) that may shed light upon potential diagnostic biomarkers. For the study, 221 participants were recruited and classified based on coronary angiogram examination as control (n = 105) and CAD (n = 116). All participants underwent routine blood investigation, two-dimensional echocardiography, and serum BDNF estimation. As a result, total cholesterol, triglyceride, low-density lipid, high-density lipid, HbA1c (glycosylated hemoglobin), serum creatinine, eosinophils, lymphocyte, monocytes, neutrophils, and platelets were significantly elevated in CAD individuals compared to controls. Notably, the serum BDNF was significantly lower in individuals with CAD (30.69 ± 5.45 ng/ml) than controls (46.58 ± 7.95 ng/ml). Multivariate regression analysis showed neutrophils, total cholesterol, left ventricular mass index, mitral inflow E/A ratio, and pulmonary vein AR duration were associated with low BDNF in CAD. Four independent support vector machine (SVM) models performed to ensure the BDNF level in the classification of CAD from healthy controls. Particularly, the model with serum BDNF concentration and blood parameters of CAD achieved significant improvement from 90.95 to 98.19% in detecting CAD from healthy controls. Overall, our analysis provides a significant molecular linkage between the serum BDNF level and cardiovascular function. Our results contribute to the emerging evidence of BDNF as a potential diagnostic value in CAD that might lead to clinical application.
Exhaustive identification of conserved upstream open reading frames with potential translational regulatory functions from animal genomes
Authors: Takahashi Hiro , Miyaki Shido , Onouchi Hitoshi , Motomura Taichiro , Idesako Nobuo , Takahashi Anna , Murase Masataka , Fukuyoshi Shuichi , Endo Toshinori , Satou Kenji , Naito Satoshi , Itoh Motoyuki
Published: October 2020

Upstream open reading frames (uORFs) are present in the 5′-untranslated regions of many eukaryotic mRNAs, and some peptides encoded by these regions play important regulatory roles in controlling main ORF (mORF) translation. We previously developed a novel pipeline, ESUCA, to comprehensively identify plant uORFs encoding functional peptides, based on genome-wide identification of uORFs with conserved peptide sequences (CPuORFs). Here, we applied ESUCA to diverse animal genomes, because animal CPuORFs have been identified only by comparing uORF sequences between a limited number of species, and how many previously identified CPuORFs encode regulatory peptides is unclear. By using ESUCA, 1517 (1373 novel and 144 known) CPuORFs were extracted from four evolutionarily divergent animal genomes. We examined the effects of 17 human CPuORFs on mORF translation using transient expression assays. Through these analyses, we identified seven novel regulatory CPuORFs that repressed mORF translation in a sequence-dependent manner, including one conserved only among Eutheria. We discovered a much higher number of animal CPuORFs than previously identified. Since most human CPuORFs identified in this study are conserved across a wide range of Eutheria or a wider taxonomic range, many CPuORFs encoding regulatory peptides are expected to be found in the identified CPuORFs.
VEGF knockdown enhances radiosensitivity of nasopharyngeal carcinoma by inhibiting autophagy through the activation of mTOR pathway
Authors: Chen Li , Lin Guoxiang , Chen Kaihua , Wan Fangzhu , Liang Renba , Sun Yongchu , Chen Xishan , Zhu Xiaodong
Published: October 2020

Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced the radioresistance of tumors. The purpose of this study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the underlying mechanisms. The radiosensitivity of NPC cells after VEGF silencing was detected by cell counting kit 8 (CCK-8) and clonogenic assay, while cell cycle and apoptosis were detected by flow cytometry. The processes of DNA damage, repair and autophagy were examined by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation studies. The effect of VEGF on radiosensitivity of NPC cells was investigated in vivo using a xenograft model. Furthermore, immunohistochemistry and TUNEL assays were used to verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion. Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of NPC cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in NPC cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through activation of the mTOR pathway. VEGF depletion increased radiosensitivity of NPC cells by suppressing autophagy via activation of the mTOR pathway.
Synthesis and structural characterization of Ca12Ga14O33
Authors: McCoy Sabrina E. A. , Salasin John R. , Everett S. Michelle , Rawn Claudia J.
Published: October 2020

Ca12Ga14O33 was successfully synthesized using a wet chemistry technique to promote the homogenous mixing of the Ca and Ga cations. Rietveld refinements on X-ray and neutron powder diffraction data confirm that the compound is isostructural to Ca12Al14O33, however, with a significantly larger lattice parameter allowing for the cages that result from the framework arrangement to expand. In naturally occurring Ca12Al14O33, the mineral mayenite, these cages are occupied by O2− anions, however, experimental studies exchanging the O2− anions with other anions has led to a host of applications, depending on the caged anion. The functional nature of the structure, where framework distortions coupled with cage occupants, are correlated to electronic band structure and modifications to the framework could lead to interesting physical properties. The phase evolution was tracked using thermogravimetric analysis and high temperature X-ray diffraction and showed a lower formation temperature for the Ca12Ga14O33 analogue compared to Ca12Al14O33 synthesized using the same wet chemistry technique. Analyzing both X-ray and neutron powder diffraction using the Rietveld method with two different starting models results in one structural model, with one Ca position and the caged O on a 24d special position, being preferred.
Applications of genotyping-by-sequencing (GBS) in maize genetics and breeding
Authors: Wang Nan , Yuan Yibing , Wang Hui , Yu Diansi , Liu Yubo , Zhang Ao , Gowda Manje , Nair Sudha K. , Hao Zhuanfang , Lu Yanli , San Vicente Felix , Prasanna Boddupalli M. , Li Xinhai , Zhang Xuecai
Published: October 2020

Genotyping-by-Sequencing (GBS) is a low-cost, high-throughput genotyping method that relies on restriction enzymes to reduce genome complexity. GBS is being widely used for various genetic and breeding applications. In the present study, 2240 individuals from eight maize populations, including two association populations (AM), backcross first generation (BC1), BC1F2, F2, double haploid (DH), intermated B73 × Mo17 (IBM), and a recombinant inbred line (RIL) population, were genotyped using GBS. A total of 955,120 of raw data for SNPs was obtained for each individual, with an average genotyping error of 0.70%. The rate of missing genotypic data for these SNPs was related to the level of multiplex sequencing: ~ 25% missing data for 96-plex and ~ 55% for 384-plex. Imputation can greatly reduce the rate of missing genotypes to 12.65% and 3.72% for AM populations and bi-parental populations, respectively, although it increases total genotyping error. For analysis of genetic diversity and linkage mapping, unimputed data with a low rate of genotyping error is beneficial, whereas, for association mapping, imputed data would result in higher marker density and would improve map resolution. Because imputation does not influence the prediction accuracy, both unimputed and imputed data can be used for genomic prediction. In summary, GBS is a versatile and efficient SNP discovery approach for homozygous materials and can be effectively applied for various purposes in maize genetics and breeding.
The duality between particle methods and artificial neural networks
Authors: Alexiadis A. , Simmons M. J. H. , Stamatopoulos K. , Batchelor H. K. , Moulitsas I.
Published: October 2020

The algorithm behind particle methods is extremely versatile and used in a variety of applications that range from molecular dynamics to astrophysics. For continuum mechanics applications, the concept of ‘particle’ can be generalized to include discrete portions of solid and liquid matter. This study shows that it is possible to further extend the concept of ‘particle’ to include artificial neurons used in Artificial Intelligence. This produces a new class of computational methods based on ‘particle-neuron duals’ that combines the ability of computational particles to model physical systems and the ability of artificial neurons to learn from data. The method is validated with a multiphysics model of the intestine that autonomously learns how to coordinate its contractions to propel the luminal content forward (peristalsis). Training is achieved with Deep Reinforcement Learning. The particle-neuron duality has the advantage of extending particle methods to systems where the underlying physics is only partially known, but we have observations that allow us to empirically describe the missing features in terms of reward function. During the simulation, the model evolves autonomously adapting its response to the available observations, while remaining consistent with the known physics of the system.
Mid-infrared spectroscopic screening of metabolic alterations in stress-exposed gilthead seabream (Sparus aurata)
Authors: de Magalhães Cláudia Raposo , Carrilho Raquel , Schrama Denise , Cerqueira Marco , Rosa da Costa Ana M. , Rodrigues Pedro M.
Published: October 2020

Stress triggers a battery of physiological responses in fish, including the activation of metabolic pathways involved in energy production, which helps the animal to cope with the adverse situation. Prolonged exposure to stressful farming conditions may induce adverse effects at the whole-animal level, impairing welfare. Fourier transform infrared (FTIR) spectroscopy is a rapid biochemical fingerprinting technique, that, combined with chemometrics, was applied to disclose the metabolic alterations in the fish liver as a result of exposure to standard stressful practices in aquaculture. Gilthead seabream (Sparus aurata) adults exposed to different stressors were used as model species. Spectra were preprocessed before multivariate statistical analysis. Principal components analysis (PCA) was used for pattern recognition and identification of the most discriminatory wavenumbers. Key spectral features were selected and used for classification using the k-nearest neighbour (KNN) algorithm to evaluate whether the spectral changes allowed for the reliable discrimination between experimental groups. PCA loadings suggested that major variations in the hepatic infrared spectra responsible for the discrimination between the experimental groups were due to differences in the intensity of absorption bands associated with proteins, lipids and carbohydrates. This broad-range technique can thus be useful in an exploratory approach before any targeted analysis.
Designing a multi-epitope peptide based vaccine against SARS-CoV-2
Authors: Singh Abhishek , Thakur Mukesh , Sharma Lalit Kumar , Chandra Kailash
Published: October 2020

COVID-19 pandemic has resulted in 16,114,449 cases with 646,641 deaths from the 217 countries, or territories as on July 27th 2020. Due to multifaceted issues and challenges in the implementation of the safety and preventive measures, inconsistent coordination between societies-governments and most importantly lack of specific vaccine to SARS-CoV-2, the spread of the virus that initially emerged at Wuhan is still uprising after taking a heavy toll on human life. In the present study, we mapped immunogenic epitopes present on the four structural proteins of SARS-CoV-2 and we designed a multi-epitope peptide based vaccine that, demonstrated a high immunogenic response with a vast application on world’s human population. On codon optimization and in-silico cloning, we found that candidate vaccine showed high expression in E. coli and immune simulation resulted in inducing a high level of both B-cell and T-cell mediated immunity. The results predicted that exposure of vaccine by administrating three injections significantly subsidized the antigen growth in the system. The proposed candidate vaccine found promising by yielding desired results and hence, should be validated by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.
Prevalence and risk factors of intrahepatic cholestasis of pregnancy in a Chinese population
Authors: Gao Xing-Xing , Ye Meng-Ying , Liu Yan , Li Jin-Yan , Li Li , Chen Wei , Lu Xue , Nie Guiying , Chen Yuan-Hua
Published: October 2020

Studies on the risk factors for intrahepatic cholestasis of pregnancy (ICP) in a population-based cohort are lacking. We assess the prevalence and risk factors of ICP in a Chinese population. In this study, a cohort study was conducted that included 12,200 eligible pregnant women. The overall incidence of ICP in this cohort was 6.06%. With increasing maternal age, the incidence of ICP decreased in women younger than 30 years of age but increased in those older than 30. With increasing pre-pregnancy BMI, the incidence of ICP decreased if the pre-pregnancy BMI was less than 23 kg/m2 but increased if it was 23 kg/m2 or higher. Further analysis showed that the risk of ICP increased when maternal age was < 25 years (Adjusted RR  2.01; 95% CI 1.64–2.47) or ≥ 35 years (Adjusted RR  1.34; 95% CI 1.02–1.76). Furthermore, an increased risk of ICP was associated with pre-pregnancy underweight (adjusted RR  1.27; 95% CI 1.04–1.56), inadequate gestational weight gain (GWG) (adjusted RR  1.58; 95% CI 1.28–1.96), lower maternal education (adjusted RR  2.96; 95% CI 2.35–3.74), multiparity (adjusted RR  1.54; 95% CI 1.23–1.93), and twin/multiple pregnancies (adjusted RR  2.12; 95% CI 1.25–3.58). Maternal age (< 25 or ≥ 35 years), underweight, inadequate GWG, lower maternal education, multiparity, and twin/multiple pregnancies were identified as risk factors of ICP.
Bidirectional-nonlinear threshold switching behaviors and thermally robust stability of ZnTe selectors by nitrogen annealing
Authors: Jang Gabriel , Park Mihyun , Hyeon Da Seul , Kim WooJong , Yang JungYup , Hong JinPyo
Published: October 2020

Three-dimensional stackable memory frames involving the integration of two-terminal scalable crossbar arrays are expected to meet the demand for high-density memory storage, fast switching speed, and ultra-low power operation. However, two-terminal crossbar arrays introduce an unintended sneak path, which inevitably requires bidirectional nonlinear selectors. In this study, the advanced threshold switching (TS) features of ZnTe chalcogenide material-based selectors provide bidirectional threshold switching behavior, nonlinearity of 104, switching speed of less than 100 ns, and switching endurance of more than 107. In addition, thermally robust ZnTe selectors (up to 400 ℃) can be obtained through the use of nitrogen-annealing treatment. This process can prevent possible phase separation phenomena observed in generic chalcogenide materials during thermal annealing which occurs even at a low temperature of 250 ℃. The possible characteristics of the electrically and thermally advanced TS nature are described by diverse structural and electrical analyses through the Poole–Frankel conduction model.