bluuebunny/crossref_metadata_2025_split huggingface dataset:
MMP8 increases tongue carcinoma cell–cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5
Authors: Juurikka K. , Dufour A. , Pehkonen K. , Mainoli B. , Campioni Rodrigues P. , Solis N. , Klein T. , Nyberg P. , Overall C. M. , Salo T. , Åström P. 
Published: May 2021

AbstractMatrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.
A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity
Authors: Yang Ren , Deng Yao , Huang Baoying , Huang Lei , Lin Ang , Li Yuhua , Wang Wenling , Liu Jingjing , Lu Shuaiyao , Zhan Zhenzhen , Wang Yufei , A Ruhan , Wang Wen , Niu Peihua , Zhao Li , Li Shiqiang , Ma Xiaopin , Zhang Luyao , Zhang Yujian , Yao Weiguo , Liang Xingjie , Zhao Jincun , Liu Zhongmin , Peng Xiaozhong , Li Hangwen , Tan Wenjie 
Published: May 2021

AbstractAlthough inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
Design of synthetic human gut microbiome assembly and butyrate production
Authors: Clark Ryan L. , Connors Bryce M. , Stevenson David M. , Hromada Susan E. , Hamilton Joshua J. , Amador-Noguez Daniel , Venturelli Ophelia S. 
Published: May 2021

AbstractThe capability to design microbiomes with predictable functions would enable new technologies for applications in health, agriculture, and bioprocessing. Towards this goal, we develop a model-guided approach to design synthetic human gut microbiomes for production of the health-relevant metabolite butyrate. Our data-driven model quantifies microbial interactions impacting growth and butyrate production separately, providing key insights into ecological mechanisms driving butyrate production. We use our model to explore a vast community design space using a design-test-learn cycle to identify high butyrate-producing communities. Our model can accurately predict community assembly and butyrate production across a wide range of species richness. Guided by the model, we identify constraints on butyrate production by high species richness and key molecular factors driving butyrate production, including hydrogen sulfide, environmental pH, and resource competition. In sum, our model-guided approach provides a flexible and generalizable framework for understanding and accurately predicting community assembly and metabolic functions.
Advances in heterometallic ring-opening (co)polymerisation catalysis
Authors: Gruszka Weronika , Garden Jennifer A. 
Published: May 2021

AbstractTruly sustainable plastics require renewable feedstocks coupled with efficient production and end-of-life degradation/recycling processes. Some of the most useful degradable materials are aliphatic polyesters, polycarbonates and polyamides, which are often prepared via ring-opening (co)polymerisation (RO(CO)P) using an organometallic catalyst. While there has been extensive research into ligand development, heterometallic cooperativity offers an equally promising yet underexplored strategy to improve catalyst performance, as heterometallic catalysts often exhibit significant activity and selectivity enhancements compared to their homometallic counterparts. This review describes advances in heterometallic RO(CO)P catalyst design, highlighting the overarching structure-activity trends and reactivity patterns to inform future catalyst design.
Aspiration dynamics generate robust predictions in heterogeneous populations
Authors: Zhou Lei , Wu Bin , Du Jinming , Wang Long 
Published: May 2021

AbstractUpdate rules, which describe how individuals adjust their behavior over time, affect the outcome of social interactions. Theoretical studies have shown that evolutionary outcomes are sensitive to model details when update rules are imitation-based but are robust when update rules are self-evaluation based. However, studies of self-evaluation based rules have focused on homogeneous population structures where each individual has the same number of neighbors. Here, we consider heterogeneous population structures represented by weighted networks. Under weak selection, we analytically derive the condition for strategy success, which coincides with the classical condition of risk-dominance. This condition holds for all weighted networks and distributions of aspiration levels, and for individualized ways of self-evaluation. Our findings recover previous results as special cases and demonstrate the universality of the robustness property under self-evaluation based rules. Our work thus sheds light on the intrinsic difference between evolutionary dynamics under self-evaluation based and imitation-based update rules.
Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans
Authors: Koneru Sneha L. , Hintze Mark , Katsanos Dimitris , Barkoulas Michalis 
Published: May 2021

AbstractA fundamental question in medical genetics is how the genetic background modifies the phenotypic outcome of mutations. We address this question by focusing on the seam cells, which display stem cell properties in the epidermis ofCaenorhabditis elegans. We demonstrate that a putative null mutation in the GATA transcription factoregl-18, which is involved in seam cell fate maintenance, is more tolerated in the CB4856 isolate from Hawaii than the lab reference strain N2 from Bristol. We identify multiple quantitative trait loci (QTLs) underlying the difference in phenotype expressivity between the two isolates. These QTLs reveal cryptic genetic variation that reinforces seam cell fate through potentiating Wnt signalling. Within one QTL region, a single amino acid deletion in the heat shock protein HSP-110 in CB4856 is sufficient to modify Wnt signalling and seam cell development, highlighting that natural variation in conserved heat shock proteins can shape phenotype expressivity.
Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice
Authors: Wang Qian , Kong Ying , Wu Ding-Yu , Liu Ji-Hong , Jie Wei , You Qiang-Long , Huang Lang , Hu Jian , Chu Huai-De , Gao Feng , Hu Neng-Yuan , Luo Zhou-Cai , Li Xiao-Wen , Li Shu-Ji , Wu Zhao-Fa , Li Yu-Long , Yang Jian-Ming , Gao Tian-Ming 
Published: May 2021

AbstractAutism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.
Time series of useful energy consumption patterns for energy system modeling
Authors: Priesmann Jan , Nolting Lars , Kockel Christina , Praktiknjo Aaron 
Published: May 2021

AbstractThe analysis of energy scenarios for future energy systems requires appropriate data. However, while more or less detailed data on energy production is often available, appropriate data on energy consumption is often scarce. In our JERICHO-E-usage dataset, we provide comprehensive data on useful energy consumption patterns for heat, cold, mechanical energy, information and communication, and light in high spatial and temporal resolution. Furthermore, we distinguish between residential, industrial, commerce, and mobility consumers. For our dataset, we aggregate bottom-up data and disaggregate top-down data both to the NUTS2 level. The NUTS2 level serves as an interface to validate our combined method approach and the calculations. We combine a multitude of data sources such as weather time series, standard load profiles, census data, movement data, and employment figures to increase the scope, validity, and reproducibility for energy system modeling. The focus of our JERICHO-E-usage dataset on useful energy consumption might be of particular interest to researchers who analyze energy scenarios where renewable electricity is largely substituted for fossil fuel (sector coupling).
To drain or not to drain: the association between residual intraperitoneal gas and post-laparoscopic shoulder pain for laparoscopic cholecystectomy
Authors: Yang Shun-Chin , Chang Kuang-Yi , Wei Ling-Fang , Shyr Yi-Ming , Ho Chiu-Ming 
Published: May 2021

AbstractResidual intra-peritoneal gas may be associated with post-laparoscopic shoulder pain (PLSP), which is a frequently and disturbance compliant after surgery. Herein, we aimed to examine whether expiring residual gas via a surgical drain reduces the frequency and intensity of PLSP in the first day after laparoscopic cholecystectomy. 448 participants were enrolled in this prospective cohort study. The incidence and severity of PLSP after surgery were recorded. Of these, the cumulative incidence of PLSP in the drain group was lower particularly at the 12th postoperative hour (18.3% vs. 27.6%;P = 0.022), 24th postoperative hour (28.8% vs. 38.1%;P = 0.039), and throughout the first postoperative day (P = 0.035). The drain group had less severe PLSP (crude Odds ratio, 0.66;P = .036). After adjustment using inverse probability of treatment weighting, the drain group also had a significant lower PLSP incidence (adjusted hazard ratio = 0.61,P < 0.001), and less severe PLSP (adjusted odds ratio = 0.56,P < 0.001). In conclusion, the maneuver about passive force to expel residual gas, surgical drain use, contributes to reduce the incidence and severity of PLSP, suggesting that to minimize residual gas at the end of surgery is useful to attenuate PLSP.
Therapeutic effects and prognostic factors of 125I brachytherapy for pelvic recurrence after early cervical cancer surgery
Authors: Wang Rui , Zhu Jinhu , Yang Shu , Chen Xiaoqin , Gu Cairu , Liang Tong , Li Ling , Liu Dan , Cao Yanqing 
Published: May 2021

AbstractTo investigate the efficacy of 125I seed implantation in the treatment regimen of pelvic recurrence after early cervical cancer surgery and to analyse prognostic factors. To evaluate efficacy and analyse prognostic factors of 125I seed implantation for pelvic recurrence after early cervical cancer surgery. A prospective study was conducted on 62 patients who experienced pelvic recurrence after early cervical cancer surgery between August 2005 and September 2015. The 62 patients were treated and assessed in 2 groups (n = 30). All 62 patients were randomized into two groups that received two different treatment regimens: the treatment group (n = 30), which received 125I particle implantation therapy, and the control group (n = 32), which received whole-pelvic irradiation using the anteroposterior/posteroanterior field and cisplatin-based concurrent chemoradiation therapy. The efficacy/efficiency of 125I seed implantation and prognostic factors were analysed by logistic regression. Overall survival was determined by Kaplan–Meier analysis. Multivariate analysis results were obtained by the Cox proportional hazards regression model. The effective control rates at 1, 3, 6 and 12 months were 76.7%, 80.0%, 83.3%, and 86.7% in the 125I particle implantation group. The total effective control rates at 1, 3, 6 and 12 months were 65.6%, 65.5%, 62.5%, and 71.9% in the chemoradiotherapy group. Significant differences were observed between the two groups. The overall survival rates at 1, 2, 3, 4, and 5 years and the median overall were 96.7%, 93.3%, 86.7%, 71.9%, 65.6% and 4.34 years, respectively, in the 125I seed implantation group and 81.3%, 71.9%, 62.5%, 56.3%, 53.1% and 3.59 years, respectively, in the control group. There were statistically significant differences in survival rates depending on the diameter of the largest recurrent pelvic tumour (χ2 = 6.611, P = 0.010). The multivariate analysis showed that the survival rates were related to the diameter of the largest recurrent pelvic tumour (χ2 = 4.538, P = 0.033). 125I implantation is an effective, safe, and promising method for the treatment of pelvic recurrence after early cervical cancer surgery. The diameter of the recurrent pelvic tumour was identified as a significant independent prognostic factor in patients who received 125I implantation.
Assessing the solar variability signature in climate variables by information theory and wavelet coherence
Authors: Mares Ileana , Dobrica Venera , Mares Constantin , Demetrescu Crisan 
Published: May 2021

AbstractThe present study aims to investigate the possible influence of solar/geomagnetic forcing on climate variables, such as the drought index, Danube discharge and large-scale atmospheric indices. Our analysis was performed separately for each season for two time periods, 1901–2000 and 1948–2000. The relationship between terrestrial variables and external indices was established based on the application of (1) information theory elements, namely, synergy, redundancy, total correlation, transfer entropy and (2) wavelet coherence analysis. Bandpass filtering has also been applied. The most significant signature of the solar/geomagnetic forcing in the climate variables was obtained for the data smoothed by the bandpass filter. According to our results, significant solar/geomagnetic forcing appears in the terrestrial variables with a delay of 2–3 years.
A three-dimensional musculoskeletal model of the dog
Authors: Stark Heiko , Fischer Martin S. , Hunt Alexander , Young Fletcher , Quinn Roger , Andrada Emanuel 
Published: May 2021

AbstractThe domestic dog is interesting to investigate because of the wide range of body size, body mass, and physique in the many breeds. In the last several years, the number of clinical and biomechanical studies on dog locomotion has increased. However, the relationship between body structure and joint load during locomotion, as well as between joint load and degenerative diseases of the locomotor system (e.g. dysplasia), are not sufficiently understood. Collecting this data through in vivo measurements/records of joint forces and loads on deep/small muscles is complex, invasive, and sometimes unethical. The use of detailed musculoskeletal models may help fill the knowledge gap. We describe here the methods we used to create a detailed musculoskeletal model with 84 degrees of freedom and 134 muscles. Our model has three key-features: three-dimensionality, scalability, and modularity. We tested the validity of the model by identifying forelimb muscle synergies of a walking Beagle. We used inverse dynamics and static optimization to estimate muscle activations based on experimental data. We identified three muscle synergy groups by using hierarchical clustering. The activation patterns predicted from the model exhibit good agreement with experimental data for most of the forelimb muscles. We expect that our model will speed up the analysis of how body size, physique, agility, and disease influence neuronal control and joint loading in dog locomotion.
Digital dynamic discrimination of primary colorectal cancer using systemic indocyanine green with near-infrared endoscopy
Authors: Dalli Jeffrey , Loughman Eamon , Hardy Niall , Sarkar Anwesha , Khan Mohammad Faraz , Khokhar Haseeb A. , Huxel Paul , O’Shea Donal F. , Cahill Ronan A. 
Published: May 2021

AbstractAs indocyanine green (ICG) with near-infrared (NIR) endoscopy enhances real-time intraoperative tissue microperfusion appreciation, it may also dynamically reveal neoplasia distinctively from normal tissue especially with video software fluorescence analysis. Colorectal tumours of patients were imaged mucosally following ICG administration (0.25 mg/kg i.v.) using an endo-laparoscopic NIR system (PINPOINT Endoscopic Fluorescence System, Stryker) including immediate, continuous in situ visualization of rectal lesions transanally for up to 20 min. Spot and dynamic temporal fluorescence intensities (FI) were quantified using ImageJ (including videos at one frame/second, fps) and by a bespoke MATLAB® application that provided digitalized video tracking and signal logging at 30fps (Fluorescence Tracker App downloadable via MATLAB® file exchange). Statistical analysis of FI-time plots compared tumours (benign and malignant) against control during FI curve rise, peak and decline from apex. Early kinetic FI signal measurement delineated discriminative temporal signatures from tumours (n = 20, 9 cancers) offering rich data for analysis versus delayed spot measurement (n = 10 cancers). Malignant lesion dynamic curves peaked significantly later with a shallower gradient than normal tissue while benign lesions showed significantly greater and faster intensity drop from apex versus cancer. Automated tracker quantification efficiently expanded manual results and provided algorithmic KNN clustering. Photobleaching appeared clinically irrelevant. Analysis of a continuous stream of intraoperatively acquired early ICG fluorescence data can act as an in situ tumour-identifier with greater detail than later snapshot observation alone. Software quantification of such kinetic signatures may distinguish invasive from non-invasive neoplasia with potential for real-time in silico diagnosis.
An optogenetic method for investigating presynaptic molecular regulation
Authors: Kay Yuni , Herring Bruce E. 
Published: May 2021

AbstractWhile efficient methods are well established for studying postsynaptic protein regulation of glutamatergic synapses in the mammalian central nervous system, similarly efficient methods are lacking for studying proteins regulating presynaptic function. In the present study, we introduce an optical/electrophysiological method for investigating presynaptic molecular regulation. Here, using an optogenetic approach, we selectively stimulate genetically modified presynaptic CA3 pyramidal neurons in the hippocampus and measure optically-induced excitatory postsynaptic currents produced in unmodified postsynaptic CA1 pyramidal neurons. While such use of optogenetics is not novel, previous implementation methods do not allow basic quantification of the changes in synaptic strength produced by genetic manipulations. We find that incorporating simultaneous recordings of fiber volley amplitude provides a control for optical stimulation intensity and, as a result, creates a metric of synaptic efficacy that can be compared across experimental conditions. In the present study, we utilize our new method to demonstrate that inhibition of synaptotagmin 1 expression in CA3 pyramidal neurons leads to a significant reduction in Schaffer collateral synapse function, an effect that is masked with conventional electrical stimulation. Our hope is that this method will expedite our understanding of molecular regulatory pathways that govern presynaptic function.