bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals
Authors: Lam S. D. , Bordin N. , Waman V. P. , Scholes H. M. , Ashford P. , Sen N. , van Dorp L. , Rauer C. , Dawson N. L. , Pang C. S. M. , Abbasian M. , Sillitoe I. , Edwards S. J. L. , Fraternali F. , Lees J. G. , Santini J. M. , Orengo C. A.
Published: October 2020

SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.
Non-targeted urine metabolomics and associations with prevalent and incident type 2 diabetes
Authors: Salihovic Samira , Broeckling Corey D. , Ganna Andrea , Prenni Jessica E. , Sundström Johan , Berne Christian , Lind Lars , Ingelsson Erik , Fall Tove , Ärnlöv Johan , Nowak Christoph
Published: October 2020

Better risk prediction and new molecular targets are key priorities in type 2 diabetes (T2D) research. Little is known about the role of the urine metabolome in predicting the risk of T2D. We aimed to use non-targeted urine metabolomics to discover biomarkers and improve risk prediction for T2D. Urine samples from two community cohorts of 1,424 adults were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). In a discovery/replication design, three out of 62 annotated metabolites were associated with prevalent T2D, notably lower urine levels of 3-hydroxyundecanoyl-carnitine. In participants without diabetes at baseline, LASSO regression in the training set selected six metabolites that improved prediction of T2D beyond established risk factors risk over up to 12 years' follow-up in the test sample, from C-statistic 0.866 to 0.892. Our results in one of the largest non-targeted urinary metabolomics study to date demonstrate the role of the urine metabolome in identifying at-risk persons for T2D and suggest urine 3-hydroxyundecanoyl-carnitine as a biomarker candidate.
Association of left atrial pressure with late gadolinium enhancement extent in patient who underwent catheter ablation for atrial fibrillation
Authors: Roh Seung-Young , Lee Dae In , Hwang Sung Ho , Lee Kwang-No , Baek Yong-soo , Iqbal Mohammad , Kim Dong-Hyeok , Ahn Jinhee , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon
Published: October 2020

Atrial remodeling with fibrosis has been well-described in patients with atrial fibrillation (AF). We hypothesized that the left atrial (LA)-late gadolinium enhancement (LGE) extent on cardiac magnetic resonance (CMR) imaging is associated with LA pressure and can be a marker for suitable candidates for non-paroxysmal AF ablation. A total of 173 AF patients with an LA-LGE area on CMR imaging were enrolled. The clinical parameters, including invasively measured LA pressure, were compared between the patients with extensive LA-LGE (E-LGE, LGE extent ≥ 20%, n = 78) and those with small LA-LGE (S-LGE, LGE extent < 20%, n = 95). The E-LGE group had higher peak LA pressures than the S-LGE group (23 versus 19 mmHg, p < 0.001). The E-LGE group had more patients with non-paroxysmal AF (non-PAF) (51% vs. 34%), heart failure (9% vs. 0%), and higher NT pro-B-type natriuretic peptide (472 vs. 265 pg/ml) (all p < 0.05). LA pressure ≥ 21 mmHg was an independent predictor of E-LGE (OR = 2.218; p = 0.019). In the paroxysmal AF (PAF) subgroup, freedom from atrial arrhythmia after catheter ablation was not different (81% vs 86%, log-rank p = 0.529). However, in the non-PAF subgroup, it was significantly higher in the S-LGE group than in the E-LGE group (81% vs 55%, log-rank p = 0.014). Increased LA pressure was related to the LA-LGE extent. LA-LGE was a good predictor of outcome after catheter ablation, but only in patients with non-PAF.
Publisher Correction: Association between admission criteria and body composition among young children with moderate acute malnutrition, a cross-sectional study from Burkina Faso
Authors: Fabiansen Christian , Cichon Bernardette , Yaméogo Charles W. , Iuel-Brockdorf Ann-Sophie , Phelan Kevin P. Q. , Wells Jonathan C. , Ritz Christian , Filteau Suzanne , Briend André , Christensen Vibeke B. , Ashorn Per , Michaelsen Kim F. , Shepherd Susan , Friis Henrik
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Brew temperature, at fixed brew strength and extraction, has little impact on the sensory profile of drip brew coffee
Authors: Batali Mackenzie E. , Ristenpart William D. , Guinard Jean-Xavier
Published: October 2020

The brew temperature is widely considered a key parameter affecting the final quality of coffee, with a temperature near 93 °C often described as optimal. In particular, drip brewers that do not achieve a minimum brew temperature of 92 °C within a prescribed time period fail their certification. There is little empirical evidence in terms of rigorous sensory descriptive analysis or consumer preference testing, however, to support any particular range of brew temperatures. In this study, we drip-brewed coffee to specific brew strengths, as measured by total dissolved solids (TDS), and extraction yields, as measured by percent extraction (PE), spanning the range of the classic Coffee Brewing Control Chart. Three separate brew temperatures of 87 °C, 90 °C, or 93 °C were tested, adjusting the grind size and overall brew time as necessary to achieve the target TDS and PE. Although the TDS and PE both significantly affected the sensory profile of the coffee, surprisingly the brew temperature had no appreciable impact. We conclude that brew temperature should be considered as only one of several parameters that affect the extraction dynamics, and that ultimately the sensory profile is governed by differences in TDS and PE rather than the brew temperature, at least over the range of temperatures tested.
Diurnal stability of cell-free DNA and cell-free RNA in human plasma samples
Authors: Wagner Josiah T. , Kim Hyun Ji , Johnson-Camacho Katie C. , Kelley Taylor , Newell Laura F. , Spellman Paul T. , Ngo Thuy T. M.
Published: October 2020

Many emerging technologies are reliant on circulating cell-free DNA (cfDNA) and cell-free RNA (cfRNA) applications in the clinic. However, the impact of diurnal cycles or daily meals on circulating analytes are poorly understood and may be confounding factors when developing diagnostic platforms. To begin addressing this knowledge gap, we obtained plasma from four healthy donors serially sampled five times during 12 h in a single day. For all samples, we measured concentrations of cfDNA and cfRNA using both bulk measurements and gene-specific digital droplet PCR. We found no significant variation attributed to blood draw number for the cfDNA or cfRNA. This indicated that natural diurnal cycles and meal consumption do not appear to significantly affect abundance of total cfDNA, total cfRNA, or our two selected cfRNA transcripts. Conversely, we observed significant variation between individual donors for cfDNA and one of the cfRNA transcripts. The results of this work suggest that it will be important to consider patient-specific baselines when designing reliable circulating cfDNA or cfRNA clinical assays.
Comparison of postoperative outcomes between patients with positive and negative straight leg raising tests who underwent full-endoscopic transforaminal lumbar discectomy
Authors: Wei Fei-long , Gao Haoran , Yan Xiaodong , Yuan Yifang , Qian Shu , Gao Quanyou , Guo Shikong , Xue Weigao , Qian Jixian , Zhou Chengpei
Published: October 2020

Full-endoscopic transforaminal lumbar discectomy (FETD) is increasingly used in patients with lumbar disc herniation (LDH). There is little knowledge on the related factors, including the straight leg raising test (SLR), that influence the operation. Consecutive patients with LDH who came to our hospital from August 2015 to September 2016 and underwent FETD surgery were included. Four kinds of scores, including the VAS (lumbar/leg), ODI and JOA values, were measured and reassessed after FETD to assess the surgical outcomes. There was a statistically significant difference between the scores before surgery and at each postoperative follow-up. In addition, the increase in the JOA score postoperatively was statistically significant compared with that before surgery. There were statistically significant differences among the three subpopulations [patients considered SLR positive (0°–30°), SLR positive (31°–60°) and SLR negative (61°–)] in the changes in the VAS (leg), ODI and JOA values. However, there were no statistically significant differences among the three subpopulations [patients considered SLR positive (0°–30°), SLR positive (31°–60°) and SLR negative (61°–)] in the changes in VAS score (lumbar). FETD showed great effectiveness in treating patients with lumbar disc herniation. Patients who were SLR negative may receive greater benefit from FETD.
The phenotypic characteristic observed by cardiac magnetic resonance in a PLN-R14del family
Authors: Jiang Xincheng , Xu Yuanwei , Sun Jiayu , Wang Lili , Guo Xinli , Chen Yucheng
Published: October 2020

Phospholamban (PLN) is an important regulator for sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA), which uptakes Ca2+ to SR during the diastolic phase of cardiomyocytes to maintain intracellular calcium homeostasis. Mutations on PLN result in intracellular calcium disorder, myocardial contraction defect, and eventually heart failure and/or malignant ventricular arrhythmia. Since 2003, several kinds of PLN mutations have been identified in familial dilated cardiomyopathy (DCM) patients, illustrating a few clinical characteristics that differs from classical DCM patients. Herein, we report a large PLN-R14del family with typical clinical characteristics reported including relatively late-onset clinical symptoms, low-voltage in ECG, as well as frequent ventricular arrythmias. Moreover, members underwent cardiac magnetic resonance (CMR) examination showed a strikingly similar pattern of late gadolinium enhancement (LGE)—Sub-epicardial involvement in the left ventricular (LV) lateral wall with or without linear mid-wall enhancement in the interventricular septum. The former one can also present in younger PLN-R14del carriers despite completely normal LV structure and function. Meanwhile, T1 mapping also found significantly increased extracellular volume (ECV) in PLN-R14del carriers. These findings highlight the special role of CMR to phenotyping PLN-induced cardiomyopathy patients and distinguish them from other types of cardiomyopathy.
Application of a self-injection locked cyan laser for Barium ion cooling and spectroscopy
Authors: Savchenkov Anatoliy A. , Christensen Justin E. , Hucul David , Campbell Wesley C. , Hudson Eric R. , Williams Skip , Matsko Andrey B.
Published: October 2020

Compact, high power lasers with narrow linewidth are important tools for the manipulation of quantum systems. We demonstrate a compact, self-injection locked, Fabry-Perot semiconductor laser diode with high output power at 493 nm. A high quality factor magnesium fluoride whispering gallery mode resonator enables both high passive stability and 1 kHz instantaneous linewidth. We use this laser for laser-cooling, in-situ isotope purifcation, and probing barium atomic ions confined in a radio-frequency ion trap. The results here demonstrate the suitability of these lasers in trapped ion quantum information processing and for probing weak coherent optical transitions.
Brain structural and functional differences between pure menstrual migraine and menstrually-related migraine
Authors: Xu Tao , Zhang Yutong , Wang Chen , Liao Huaqiang , Zhou Siyuan , Li Dehua , Huang Siying , Shi Yu , Wang Ziwen , Chen Jiao , Liang Fan-Rong , Zhao Ling
Published: October 2020

The pathophysiological differences between menstrually-related migraine (MRM) and pure menstrual migraine (PMM) are largely unclear. The aim of this study was to investigate the potential differences in brain structure and function between PMM and MRM. Forty-eight menstrual migraine patients (32 MRM; 16 PMM) were recruited for this study. Voxel-based morphometry (VBM) was applied on structural magnetic resonance imaging (sMRI), and the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in resting state functional MRI (rsfMRI) were calculated. No significant between-group difference was observed in the grey matter volume (GMV). MRM patients exhibited lower ALFF values at the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC) than PMM patients. Moreover, the MRM group showed significantly higher ReHo values in the DLPFC. Higher values in the mPFC were related to higher expression of calcitonin gene-associated peptide (CGRP) in the PMM group (r = 0.5,P = 0.048). Combined ALFF and ReHo analyses revealed significantly different spontaneous neural activity in the DLPFC and mPFC, between MRM and PMM patients, and ALFF values in the mPFC were positively correlated with CGRP expression, in the PMM group. This study enhances our understanding of the relationship between neural abnormalities and CGRP expression in individuals with PMM.
Evidence of drought memory in Dipteryx alata indicates differential acclimation of plants to savanna conditions
Authors: Alves Rauander D. F. B. , Menezes-Silva Paulo E. , Sousa Leticia F. , Loram-Lourenço Lucas , Silva Maria L. F. , Almeida Sabrina E. S. , Silva Fabiano G. , Perez de Souza Leonardo , Fernie Alisdair R. , Farnese Fernanda S.
Published: October 2020

The remarkable phytogeographic characteristics of the Brazilian savanna (Cerrado) resulted in a vegetation domain composed of plants with high structural and functional diversity to tolerate climate extremes. Here we used a key Cerrado species (Dipteryx alata) to evaluate if species of this domain present a mechanism of stress memory, responding more quickly and efficiently when exposed to recurrent drought episodes. The exposure of D. alata seedlings to drought resulted in several changes, mainly in physiological and biochemical traits, and these changes differed substantially when the water deficit was imposed as an isolated event or when the plants were subjected to drought cycles, suggesting the existence of a drought memory mechanism. Plants submitted to recurrent drought events were able to maintain essential processes for plant survival when compared to those submitted to drought for the first time. This differential acclimation to drought was the result of orchestrated changes in several metabolic pathways, involving differential carbon allocation for defense responses and the reprogramming and coordination of primary, secondary and antioxidant metabolism. The stress memory in D. alata is probably linked the evolutionary history of the species and reflects the environment in which it evolved.
Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics
Authors: Benjumeda Wijnhoven Isabel , Vallejos Raúl , Santibanez Juan F. , Millán Carola , Vivanco Juan F.
Published: October 2020

The combination of biomaterials and stem cells for clinical applications constitute a great challenge in bone tissue engineering. Hence, cellular networks derived from cells-biomaterials crosstalk have a profound influence on cell behaviour and communication, preceding proliferation and differentiation. The purpose of this study was to investigate in vitro cellular networks derived from human gingival mesenchymal stem cells (hGMSCs) and calcium phosphate (CaP) bioceramic interaction. Biological performance of CaP bioceramic and hGMSCs interaction was evaluated through cell adhesion and distribution, cellular proliferation, and potential osteogenic differentiation, at three different times: 5 h, 1 week and 4 weeks. Results confirmed that hGMSCs met the required MSCs criteria while displaying osteogenic differentiaton capacities. We found a significant increase of cellular numbers and proliferation levels. Also, protein and mRNA OPN expression were upregulated in cells cultured with CaP bioceramic by day 21, suggesting an osteoinductible effect of the CaP bioceramic on hGMSCs. Remarkably, CaP bioceramic aggregations were obtained through hGMSCs bridges, suggesting the in vitro potential of macrostructures formation. We conclude that hGMSCs and CaP bioceramics with micro and macropores support hGMSC adhesion, proliferation and osteogenic differentiation. Our results suggest that investigations focused on the interface cells-biomaterials are essential for bone tissue regenerative therapies.
Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms
Authors: Corso Claudia Rita , Stipp Maria Carolina , Radulski Débora Rasec , Mariott Marihá , da Silva Luisa Mota , de Souza Ramos Edneia Amancio , Klassen Giseli , Queiroz Telles José Ederaldo , Oliveira Cristhian Santos , Stefanello Maria Élida Alves , Verhoeven Arthur J. , Oude Elferink Ronald P. J. , Acco Alexandra
Published: October 2020

Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys, in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N-acetyl-β-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo, cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.
The recurrence rate of ovarian endometrioma in women aged 40–49 years and impact of hormonal treatment after conservative surgery
Authors: Lee Nara , Min Seunggi , Won Seyeon , Cho Yeon Jean , Kim Miseon , Kim Mi Kyoung , Jung Yong Wook , Yun Bo Seong , Seong Seok Ju , Kim Mi-La
Published: October 2020

The aim of this study was to evaluate the rate of and risk factors for recurrence ovarian endometrioma after conservative surgery in patients aged 40–49 years. This retrospective, single-center study included 408 women between January 2008 and November 2018. All patients underwent ovarian cyst enucleation, were pathologically diagnosed with ovarian endometrioma and were followed up for ≥ 6 months. Recurrence was defined as a cystic mass with diameter ≥ 2 cm detected by sonography. Recurrence rate after conservative surgery and risk factor of recurrence were analyzed. The median follow-up duration after surgery was 32.0 ± 25.9 months (range 6–125 months). Ovarian endometrioma recurred in 34 (8.3%) of included women and median time to recurrence was 22.4 ± 18.2 months. The cumulative recurrences rate at 12, 24, 36, and 60 months were 3.7%, 6.7%, 11.1%, and 16.7%, respectively. Recurrence was correlated with multilocular cysts (p = 0.038), previous surgical history of ovarian endometrioma (p = 0.006) and salpingectomy (p = 0.043), but not use or duration of post-operative medication. In multivariate analysis, large cyst size (> 5.5 cm) was only risk factor for recurrence in this age group. Post-operative medication did not reduce disease recurrence rate, and thus may be administered for endometriosis-associated pain rather than to prevent recurrence in patients aged 40–49 years.
Saturation transfer difference NMR on the integral trimeric membrane transport protein GltPh determines cooperative substrate binding
Authors: Hall Jenny L. , Sohail Azmat , Cabrita Eurico J. , Macdonald Colin , Stockner Thomas , Sitte Harald H. , Angulo Jesus , MacMillan Fraser
Published: October 2020

Saturation-transfer difference (STD) NMR spectroscopy is a fast and versatile method which can be applied for drug-screening purposes, allowing the determination of essential ligand binding affinities (KD). Although widely employed to study soluble proteins, its use remains negligible for membrane proteins. Here the use of STD NMR for KD determination is demonstrated for two competing substrates with very different binding affinities (low nanomolar to millimolar) for an integral membrane transport protein in both detergent-solubilised micelles and reconstituted proteoliposomes. GltPh, a homotrimeric aspartate transporter from Pyrococcus horikoshii, is an archaeal homolog of mammalian membrane transport proteins—known as excitatory amino acid transporters (EAATs). They are found within the central nervous system and are responsible for fast uptake of the neurotransmitter glutamate, essential for neuronal function. Differences in both KD’s and cooperativity are observed between detergent micelles and proteoliposomes, the physiological implications of which are discussed.
Combination therapy of cold atmospheric plasma (CAP) with temozolomide in the treatment of U87MG glioblastoma cells
Authors: Gjika Eda , Pal-Ghosh Sonali , Kirschner Megan E. , Lin Li , Sherman Jonathan H. , Stepp Mary Ann , Keidar Michael
Published: October 2020

Cold atmospheric plasma (CAP) technology, a relatively novel technique mainly investigated as a stand-alone cancer treatment method in vivo and in vitro, is being proposed for application in conjunction with chemotherapy. In this study, we explore whether CAP, an ionized gas produced in laboratory settings and that operates at near room temperature, can enhance Temozolomide (TMZ) cytotoxicity on a glioblastoma cell line (U87MG). Temozolomide is the first line of treatment for glioblastoma, one of the most aggressive brain tumors that remains incurable despite advancements with treatment modalities. The cellular response to a single CAP treatment followed by three treatments with TMZ was monitored with a cell viability assay. According to the cell viability results, CAP treatment successfully augmented the effect of a cytotoxic TMZ dose (50 μM) and further restored the effect of a non-cytotoxic TMZ dose (10 μM). Application of CAP in conjunction TMZ increased DNA damage measured by the phosphorylation of H2AX and induced G2/M cell cycle arrest. These findings were supported by additional data indicating reduced cell migration and increased αvβ3 and αvβ5 cell surface integrin expression as a result of combined CAP–TMZ treatment. The data presented in this study serve as evidence that CAP technology can be a suitable candidate for combination therapy with existing chemotherapeutic drugs. CAP can also be investigated in future studies for sensitizing glioblastoma cells to TMZ and other drugs available in the market.
FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: a comparative study with mouse islets and rat INS-1E cells
Authors: Lorza-Gil Estela , Kaiser Gabriele , Rexen Ulven Elisabeth , König Gabriele M. , Gerst Felicia , Oquendo Morgana Barroso , Birkenfeld Andreas L. , Häring Hans-Ulrich , Kostenis Evi , Ulven Trond , Ullrich Susanne
Published: October 2020

The expression of short chain fatty acid receptors FFA2 and FFA3 in pancreatic islets raised interest in using them as drug targets for treating hyperglycemia in humans. This study aims to examine the efficacy of synthetic FFA2- and FFA3-ligands to modulate glucose-stimulated insulin secretion (GSIS) in human pseudoislets which display intact glucose responsiveness. The FFA2-agonists 4-CMTB and TUG-1375 inhibited GSIS, an effect reversed by the FFA2-antagonist CATPB. GSIS itself was not augmented by CATPB. The FFA3-agonists FHQC and 1-MCPC did not affect GSIS in human pseudoislets. For further drug evaluation we used mouse islets. The CATPB-sensitive inhibitory effect of 100 µM 4-CMTB on GSIS was recapitulated. The inhibition was partially sensitive to the Gi/o-protein inhibitor pertussis toxin. A previously described FFA2-dependent increase of GSIS was observed with lower concentrations of 4-CMTB (10 and 30 µM). The stimulatory effect of 4-CMTB on secretion was prevented by the Gq-protein inhibitor FR900359. As in human pseudoislets, in mouse islets relative mRNA levels were FFAR2 > FFAR3 and FFA3-agonists did not affect GSIS. The FFA3-agonists, however, inhibited GSIS in a pertussis toxin-sensitive manner in INS-1E cells and this correlated with relative mRNA levels of Ffar3 > > Ffar2. Thus, in humans, when FFA2-activation impedes GSIS, FFA2-antagonism may reduce glycemia.
Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells
Authors: Youn Yuna , Lee Jong-chan , Kim Jaihwan , Kim Jae Hyeong , Hwang Jin-Hyeok
Published: October 2020

Cell division cycle 6 (Cdc6) plays key roles in regulating DNA replication, and activation and maintenance of cell cycle check points. In addition, Cdc6 exerts oncogenic properties via genomic instability associated with incomplete DNA replication. This study aimed to examine the effects of Cdc6 on pancreatic cancer (PC) cells. Our results showed that Cdc6 expression was higher in clinical PC specimens (based on analysis of the GEPIA database) and cell lines, and the high Cdc6 expression was associated with poorer survival in The Cancer Genome Atlas-PC cohort. In addition, Cdc6-depleted PC cells significantly inhibited cell proliferation and colony formation, delayed G2/M cell cycle progression, and increased expression of p-histone H3 and cyclin A2 levels. These observations could be explained by Cdc6 depletion leading to multipolar and split spindles via centrosome amplification and microtubule disorganization which eventually increases chromosome missegregation. Furthermore, Cdc6-depleted PC cells showed significantly increased apoptosis, which was consistent with increased caspase-9 and caspase-3 activation. Collectively, our results demonstrated that Cdc6-depleted PC cells are arrested in mitosis and eventually undergo cell death by induced multipolar spindles, centrosome aberrations, microtubule disorganization, and chromosome instability. In conclusion, Cdc6 may be a potential biomarker and therapeutic target for PC.
Miniaturization re-establishes symmetry in the wing folding patterns of featherwing beetles
Authors: Petrov Pyotr N. , Farisenkov Sergey E. , Polilov Alexey A.
Published: October 2020

Most microinsects have feather-like bristled wings, a state known as ptiloptery, but featherwing beetles (family Ptiliidae) are unique among winged microinsects in their ability to fold such wings. An asymmetrical wing folding pattern, found also in the phylogenetically related rove beetles (Staphylinidae), was ancestral for Ptiliidae. Using scanning electron, confocal laser scanning, and optical microscopy, high-speed video recording, and 3D reconstruction, we analyze in detail the symmetrical wing folding pattern and the mechanism of the folding and unfolding of the wings in Acrotrichis sericans (Coleoptera: Ptiliidae) and show how some of the smaller featherwing beetles have reverted to strict symmetry in their wing folding. The wings are folded in three phases by bending along four lines (with the help of wing folding patches on the abdominal tergites) and locked under the closed elytra; they unfold passively in two phases, apparently with the help of the elasticity provided by resilin unevenly distributed in the wing and of convexities forming in the cross-sections of the unfolding wing, making it stiffer. The minimum duration of folding is 3.5 s; unfolding is much more rapid (minimum duration lowest recorded in beetles, 0.038 s). The folding ratio of A. sericans is 3.31 (without setae), which is greater than in any beetle in which it has been measured. The symmetrical wing folding pattern found in A. sericans and in all of the smallest ptiliids, in which ptiloptery is especially pronounced, is the only known example of symmetry re-established during miniaturization. This direction of evolution is remarkable because miniaturization is known to result in various asymmetries, while in this case miniaturization was accompanied by reversal to symmetry, probably associated with the evolution of ptiloptery. Our results on the pattern and mechanisms of wing folding and unfolding can be used in robotics for developing miniature biomimetic robots: the mechanisms of wing folding and unfolding in Ptiliidae present a challenge to engineers who currently work at designing ever smaller flying robots and may eventually produce miniature robots with foldable wings.
The effect of slope aspect on vegetation attributes in a mountainous dry valley, Southwest China
Authors: Yang Jie , El-Kassaby Yousry A. , Guan Wenbin
Published: October 2020

Slope aspect plays a critical role in influencing vegetation pattern in semiarid area. The dry valleys of the Hengduan Mountains Region, southwestern China, are striking geographical landscape, suffering from severe ecological degradation. Here, we comprehensively investigated how slope aspect affects vegetation attributes in one of these valleys- the dry valley in the upper reaches of Min River. Three sites were selected along the valley and we quantitively examined the vegetation difference between slope aspects at the whole valley scale and each site level. We found significant vegetation differences between slope aspects in species composition, vegetative structure, and biodiversity pattern, which were in accordance with the observed significant difference in soil nutrient. Generally, north-facing slopes are associated with higher biomass, coverage and height, and species diversity than south-facing slopes. We also found between-aspect differences varied among the study sites, resulting in increased biomass, height, and β diversity differences, decreased density and coverage differences, and opposite trend observed in α diversity at relatively wet site. In conclusion, slope aspect had significant effect on vegetation attributes, which was significantly influenced by local climate (aridity) in terms of both strength and direction depending on the specific attributes investigated.
Lectin affinity chromatography and quantitative proteomic analysis reveal that galectin-3 is associated with metastasis in nasopharyngeal carcinoma
Authors: Aimjongjun Sathid , Reamtong Onrapak , Janvilisri Tavan
Published: October 2020

Nasopharyngeal carcinoma (NPC) is a serious cancer in East and Southeast Asia. Patients are often diagnosed at advanced stages, rendering treatment failure due to high potential of metastasis. This study identified lectin-binding glycoproteins with a potential role in NPC metastasis. Cell lysate and culture medium in highly metastatic 5-8F, and lowly-metastatic 6-10B NPC cell lines were fractionated by ConA- and WGA-affinity chromatography, and subjected to GeLC-MS/MS. A total of 232 and 197 proteins were identified in ConA-enriched fraction of 5-8F and 6-10B cell lysates respectively. In WGA-enriched fraction, 65 and 164 proteins were found in 5-8F and 6-10B cell lysates respectively. Proteins identified in culture medium for both cell lines were 223 and 85 for ConA-enriched fraction, and 94 and 124 for WGA-enriched fraction from 5-8F and 6-10B respectively. Differentially expressed proteins were functionally categorized into cell–cell adhesion, extracellular matrix, glycolysis, protein homeostasis and/or glycosylation enzymes, and lipid metabolism. Interestingly, Galectin-3 (Gal-3) was highly expressed in 5-8F cells but was lowly expressed in 6-10B cells. The Gal-3 knockdown in 5-8F cells, Gal-3 overexpression in 6-10B cells and treatment with Gal-3 inhibitor revealed that Gal-3 was responsible for metastatic phenotypes including adhesion, migration and invasion. So Galectin-3 may serve as a potential target for NPC therapeutic interventions.
Rainwater isotopes in central Vietnam controlled by two oceanic moisture sources and rainout effects
Authors: Wolf Annabel , Roberts William H. G. , Ersek Vasile , Johnson Kathleen R. , Griffiths Michael L.
Published: October 2020

The interpretation of palaeoclimate archives based on oxygen isotopes depends critically on a detailed understanding of processes controlling the isotopic composition of precipitation. In the summer monsoonal realm, like Southeast Asia, seasonally and interannually depleted oxygen isotope ratios in precipitation have been linked to the summer monsoon strength. However, in some regions, such as central Vietnam, the majority of precipitation falls outside the summer monsoon period. We investigate processes controlling stable isotopes in precipitation from central Vietnam by combining moisture uptake calculations with monthly stable isotope data observed over five years. We find that the isotopic seasonal cycle in this region is driven by a shift in moisture source from the Indian Ocean to the South China Sea. This shift is reflected in oxygen isotope ratios with low values (− 8 to − 10‰) during summer and high values during spring/winter (0 to − 3‰), while 70% of the annual rainfall occurs during autumn. Interannual changes in precipitation isotopes in central Vietnam are governed by the timing of the seasonal onset and withdrawal of the Intertropical Convergence Zone, which controls the amount of vapour contributed from each source.
3D DESI-MS lipid imaging in a xenograft model of glioblastoma: a proof of principle
Authors: Henderson Fiona , Jones Emrys , Denbigh Joanna , Christie Lidan , Chapman Richard , Hoyes Emmy , Claude Emmanuelle , Williams Kaye J. , Roncaroli Federico , McMahon Adam
Published: October 2020

Desorption electrospray ionisation mass spectrometry (DESI-MS) can image hundreds of molecules in a 2D tissue section, making it an ideal tool for mapping tumour heterogeneity. Tumour lipid metabolism has gained increasing attention over the past decade; and here, lipid heterogeneity has been visualised in a glioblastoma xenograft tumour using 3D DESI-MS imaging. The use of an automatic slide loader automates 3D imaging for high sample-throughput. Glioblastomas are highly aggressive primary brain tumours, which display heterogeneous characteristics and are resistant to chemotherapy and radiotherapy. It is therefore important to understand biochemical contributions to their heterogeneity, which may be contributing to treatment resistance. Adjacent sections to those used for DESI-MS imaging were used for H&E staining and immunofluorescence to identify different histological regions, and areas of hypoxia. Comparing DESI-MS imaging with biological staining allowed association of different lipid species with hypoxic and viable tissue within the tumour, and hence mapping of molecularly different tumour regions in 3D space. This work highlights that lipids are playing an important role in the heterogeneity of this xenograft tumour model, and DESI-MS imaging can be used for lipid 3D imaging in an automated fashion to reveal heterogeneity, which is not apparent in H&E stains alone.
The immune receptor CD300e negatively regulates T cell activation by impairing the STAT1-dependent antigen presentation
Authors: Coletta Sara , Salvi Valentina , Della Bella Chiara , Bertocco Ambra , Lonardi Silvia , Trevellin Elisabetta , Fassan Matteo , D’Elios Mario M. , Vermi William , Vettor Roberto , Cagnin Stefano , Sozzani Silvano , Codolo Gaia , de Bernard Marina
Published: October 2020

CD300e is a surface receptor, expressed by myeloid cells, involved in the tuning of immune responses. CD300e engagement was reported to provide the cells with survival signals, to trigger the expression of activation markers and the release of pro-inflammatory cytokines. Hence, CD300e is considered an immune activating receptor. In this study, we demonstrate that the ligation of CD300e in monocytes hampers the expression of the human leukocyte antigen (HLA) class II, affecting its synthesis. This effect, which is associated with the transcription impairment of the signal transducer and activator of transcription 1 (STAT1), overcomes the capacity of interferon gamma (IFN-γ) to promote the expression of the antigen-presenting molecules. Importantly, the decreased expression of HLA-II on the surface of CD300e-activated monocytes negatively impacts their capacity to activate T cells in an antigen-specific manner. Notably, unlike in vitro- differentiated macrophages which do not express CD300e, the immune receptor is expressed by tissue macrophages. Taken together, our findings argue against the possibility that this molecule should be considered an activating immune receptor sensu stricto. Moreover, our results support the notion that CD300e might be a new player in the regulation of the expansion of T cell-mediated responses.
Relationships between a common Caribbean corallivorous snail and protected area status, coral cover, and predator abundance
Authors: Shaver Elizabeth C. , Renzi Julianna J. , Bucher Maite G. , Silliman Brian R.
Published: October 2020

As coral populations decline across the Caribbean, it is becoming increasingly important to understand the forces that inhibit coral survivorship and recovery. Predation by corallivores, such as the short coral snail Coralliophila abbreviata, are one such threat to coral health and recovery worldwide, but current understanding of the factors controlling corallivore populations, and therefore predation pressure on corals, remains limited. To examine the extent to which bottom-up forces (i.e., coral prey), top-down forces (i.e., predators), and marine protection relate to C. abbreviata distributions, we surveyed C. abbreviata abundance, percent coral cover, and the abundance of potential snail predators across six protected and six unprotected reefs in the Florida Keys. We found that C. abbreviata abundance was lower in protected areas where predator assemblages were also more diverse, and that across all sites snail abundance generally increased with coral cover. C. abbreviata abundance had strong, negative relationships with two gastropod predators—the Caribbean spiny lobster (Panulirus argus) and the grunt black margate (Anisotremus surinamensis), which may be exerting top-down pressure on C. abbreviata populations. Further, we found the size of C. abbreviata was also related to reef protection status, with larger C. abbreviata on average in protected areas, suggesting that gape-limited predators such as P. argus and A. surinamensis may alter size distributions by targeting small snails. Combined, these results provide preliminary evidence that marine protection in the Florida Keys may preserve critical trophic interactions that indirectly promote coral success via control of local populations of the common corallivorous snail C. abbreviata.
Short wavelength automated perimetry and standard automated perimetry in central serous chorioretinopathy
Authors: Zhou Han Peng , Asaoka Ryo , Inoue Tatsuya , Asano Shotaro , Murata Hiroshi , Hara Takumi , Makino So , Kadonosono Kazuaki , Obata Ryo
Published: October 2020

Short wavelength automated perimetry (SWAP) is known for detecting the early reduction of retinal sensitivity (RS) in glaucoma. It’s application in retinal diseases have also been discussed previously. We investigated the difference in RS measured between standard white-on-white automated perimetry (WW) and blue-on-yellow SWAP in central serous chorioretinopathy (CSC). The overall RS (W-RS, S-RS) as well as the RS inside and outside of the serous retinal detachment (SRD) region were investigated in 26 eyes of 26 CSC patients using WW and SWAP. The central retinal thickness, central choroidal thickness, SRD area (SRDa), and SRD height at the fovea were measured using optic coherence tomography. RS inside the SRD region was lower than that of outside for both perimetries (both p < 0.001). The difference between RS inside and outside of the SRD region was greater in SWAP compared to WW (p < 0.001). Univariate analysis revealed significant correlations between SRDa and both W-RS and S-RS (both p < 0.001); moreover, multivariate analysis indicated that only S-RS was selected as the optimal model for SRDa. Our study demonstrated that SWAP was detected the decrease in RS more accurately than WW in CSC. These results may suggest the usefulness of SWAP for detecting change of retinal function in CSC.
IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory
Authors: Brombacher T. M. , Berkiks I. , Pillay S. , Scibiorek M. , Moses B. O. , Brombacher F.
Published: October 2020

Like pro-inflammatory cytokines, the role of anti-inflammatory cytokines in both learning and memory has been investigated, revealing beneficial effects for both interleukin-4 and interleukin-13 via the common interleukin-4 receptor alpha chain complex. In this study, using the Morris water maze spatial task for cognition, we compared interleukin-4 receptor alpha- deficient mice and their ligands interleukin-4/ interleukin-13 double deficient mice, on a Balb/c background. We demonstrate that while interleukin-4/ interleukin-13 double deficient mice are significantly impaired in both learning and reference memory, interleukin-4 receptor alpha-deficiency impairs only reference memory, compared to the wild-type control mice. In order to better understand how interleukin-4 receptor alpha- deficient mice are able to learn but not remember, we investigated the BDNF/TrkB- and the ARC-signaling pathways. We show that interleukin-4 receptor alpha-deficiency disrupts activation of BDNF/TrkB- and ARC-signaling pathways during reference memory, while the pathway for spatial learning is spared.
Lower brain-derived neurotrophic factor levels are associated with age-related memory impairment in community-dwelling older adults: the Sefuri study
Authors: Mizoguchi Yoshito , Yao Hiroshi , Imamura Yoshiomi , Hashimoto Manabu , Monji Akira
Published: October 2020

The beneficial effects of brain-derived neurotrophic factor (BDNF)—a member of the neurotrophin family—on cognitive function or dementia are well established in both rodents and human beings. In contrast, little is known about the association of proBDNF—a precursor protein with opposing neuronal effects of BDNF—with cognitive function in non-demented older adults. We analyzed brain magnetic resonance imaging findings of 256 community-dwelling older adults (mean age of 68.4 years). Serum BDNF and proBDNF levels were measured by quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that older age, less physical activity, hippocampal atrophy, and lower BDNF levels were independently associated with memory impairment determined by the Rivermead Behavioral Memory Test. Path analysis based on structural equation modeling indicated that age, sport activity, hippocampal atrophy and BDNF but not proBDNF were individually associated with Rivermead Behavioral Memory Test scores. These findings suggest that impaired BDNF function, in addition to physical inactivity and hippocampal atrophy, is associated with age-related memory impairment. Therefore, BDNF may be a potential target for dementia prevention.
Health anxiety and attentional bias toward virus-related stimuli during the COVID-19 pandemic
Authors: Cannito Loreta , Di Crosta Adolfo , Palumbo Rocco , Ceccato Irene , Anzani Stefano , La Malva Pasquale , Palumbo Riccardo , Di Domenico Alberto
Published: October 2020

After the COVID-19 worldwide spread, evidence suggested a vast diffusion of negative consequences on people's mental health. Together with depression and sleep difficulties, anxiety symptoms seem to be the most diffused clinical outcome. The current contribution aimed to examine attentional bias for virus-related stimuli in people varying in their degree of health anxiety (HA). Consistent with previous literature, it was hypothesized that higher HA would predict attentional bias, tested using a visual dot-probe task, to virus-related stimuli. Participants were 132 Italian individuals that participated in the study during the lockdown phase in Italy. Results indicated that the HA level predicts attentional bias toward virus-related objects. This relationship is double mediated by the belief of contagion and by the consequences of contagion as assessed through a recent questionnaire developed to measure the fear for COVID-19. These findings are discussed in the context of cognitive-behavioral conceptualizations of anxiety suggesting a risk for a loop effect. Future research directions are outlined.
Transcriptome-wide analysis and modelling of prognostic alternative splicing signatures in invasive breast cancer: a prospective clinical study
Authors: Wang Linbang , Wang Yuanyuan , Su Bao , Yu Ping , He Junfeng , Meng Lei , Xiao Qi , Sun Jinhui , Zhou Kai , Xue Yuzhou , Tan Jinxiang
Published: October 2020

Aberrant alternative splicing (AS) has been highly involved in the tumorigenesis and progression of most cancers. The potential role of AS in invasive breast cancer (IBC) remains largely unknown. In this study, RNA sequencing of IBC samples from The Cancer Genome Atlas was acquired. AS events were screened by conducting univariate and multivariate Cox analysis and least absolute shrinkage and selection operator regression. In total, 2146 survival-related AS events were identified from 1551 parental genes, of which 93 were related to prognosis, and a prognostic marker model containing 14 AS events was constructed. We also constructed the regulatory network of splicing factors (SFs) and AS events, and identified DDX39B as the node SF gene, and verified the accuracy of the network through experiments. Next, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in triple negative breast cancer patients with different responses to neoadjuvant chemotherapy, and found that the exon-specific expression of EPHX2, C6orf141, and HERC4 was associated with the different status of patients that received neoadjuvant chemotherapy. In conclusion, this study found that DDX39B, EPHX2 (exo7), and HERC4 (exo23) can be used as potential targets for the treatment of breast cancer, which provides a new idea for the treatment of breast cancer.