bluuebunny/crossref_metadata_2025 huggingface dataset:
tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application
Authors: Li Xizhe , Liu Xianyu , Zhao Deze , Cui Weifang , Wu Yingfang , Zhang Chunfang , Duan Chaojun
Published: September 2021

tRNAs are a group of conventional noncoding RNAs (ncRNAs) with critical roles in the biological synthesis of proteins. Recently, tRNA-derived small RNAs (tsRNAs) were found to have important biological functions in the development of human diseases including carcinomas, rather than just being considered pure degradation material. tsRNAs not only are abnormally expressed in the cancer tissues and serum of cancer patients, but also have been suggested to regulate various vital cancer hallmarks. On the other hand, the application of tsRNAs as biomarkers and therapeutic targets is promising. In this review, we focused on the basic characteristics of tsRNAs, and their biological functions known thus far, and explored the regulatory roles of tsRNAs in cancer hallmarks including proliferation, apoptosis, metastasis, tumor microenvironment, drug resistance, cancer stem cell phenotype, and cancer cell metabolism. In addition, we also discussed the research progress on the application of tsRNAs as tumor biomarkers and therapeutic targets.
Field-induced quantum spin disordered state in spin-1/2 honeycomb magnet Na2Co2TeO6
Authors: Lin Gaoting , Jeong Jaehong , Kim Chaebin , Wang Yao , Huang Qing , Masuda Takatsugu , Asai Shinichiro , Itoh Shinichi , Günther Gerrit , Russina Margarita , Lu Zhilun , Sheng Jieming , Wang Le , Wang Jiucai , Wang Guohua , Ren Qingyong , Xi Chuanying , Tong Wei , Ling Langsheng , Liu Zhengxin , Wu Liusuo , Mei Jiawei , Qu Zhe , Zhou Haidong , Wang Xiaoqun , Park Je-Geun , Wan Yuan , Ma Jie
Published: September 2021

Spin-orbit coupled honeycomb magnets with the Kitaev interaction have received a lot of attention due to their potential of hosting exotic quantum states including quantum spin liquids. Thus far, the most studied Kitaev systems are 4d/5d-based honeycomb magnets. Recent theoretical studies predicted that 3d-based honeycomb magnets, including Na2Co2TeO6 (NCTO), could also be a potential Kitaev system. Here, we have used a combination of heat capacity, magnetization, electron spin resonance measurements alongside inelastic neutron scattering (INS) to study NCTO’s quantum magnetism, and we have found a field-induced spin disordered state in an applied magnetic field range of 7.5 T < B (⊥ b-axis) < 10.5 T. The INS spectra were also simulated to tentatively extract the exchange interactions. As a 3d-magnet with a field-induced disordered state on an effective spin-1/2 honeycomb lattice, NCTO expands the Kitaev model to 3d compounds, promoting further interests on the spin-orbital effect in quantum magnets.
Characterising proteolysis during SARS-CoV-2 infection identifies viral cleavage sites and cellular targets with therapeutic potential
Authors: Meyer Bjoern , Chiaravalli Jeanne , Gellenoncourt Stacy , Brownridge Philip , Bryne Dominic P. , Daly Leonard A. , Grauslys Arturas , Walter Marius , Agou Fabrice , Chakrabarti Lisa A. , Craik Charles S. , Eyers Claire E. , Eyers Patrick A. , Gambin Yann , Jones Andrew R. , Sierecki Emma , Verdin Eric , Vignuzzi Marco , Emmott Edward
Published: September 2021

SARS-CoV-2 is the causative agent behind the COVID-19 pandemic, responsible for over 170 million infections, and over 3.7 million deaths worldwide. Efforts to test, treat and vaccinate against this pathogen all benefit from an improved understanding of the basic biology of SARS-CoV-2. Both viral and cellular proteases play a crucial role in SARS-CoV-2 replication. Here, we study proteolytic cleavage of viral and cellular proteins in two cell line models of SARS-CoV-2 replication using mass spectrometry to identify protein neo-N-termini generated through protease activity. We identify previously unknown cleavage sites in multiple viral proteins, including major antigens S and N: the main targets for vaccine and antibody testing efforts. We discover significant increases in cellular cleavage events consistent with cleavage by SARS-CoV-2 main protease, and identify 14 potential high-confidence substrates of the main and papain-like proteases. We show that siRNA depletion of these cellular proteins inhibits SARS-CoV-2 replication, and that drugs targeting two of these proteins: the tyrosine kinase SRC and Ser/Thr kinase MYLK, show a dose-dependent reduction in SARS-CoV-2 titres. Overall, our study provides a powerful resource to understand proteolysis in the context of viral infection, and to inform the development of targeted strategies to inhibit SARS-CoV-2 and treat COVID-19.
Next generation reservoir computing
Authors: Gauthier Daniel J. , Bollt Erik , Griffith Aaron , Barbosa Wendson A. S.
Published: September 2021

Reservoir computing is a best-in-class machine learning algorithm for processing information generated by dynamical systems using observed time-series data. Importantly, it requires very small training data sets, uses linear optimization, and thus requires minimal computing resources. However, the algorithm uses randomly sampled matrices to define the underlying recurrent neural network and has a multitude of metaparameters that must be optimized. Recent results demonstrate the equivalence of reservoir computing to nonlinear vector autoregression, which requires no random matrices, fewer metaparameters, and provides interpretable results. Here, we demonstrate that nonlinear vector autoregression excels at reservoir computing benchmark tasks and requires even shorter training data sets and training time, heralding the next generation of reservoir computing.
NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs
Authors: Zong Le , Tanaka-Yano Mayuri , Park Bongsoo , Yanai Hagai , Turhan Ferda T. , Croteau Deborah L. , Tian Jane , Fang Evandro F. , Bohr Vilhelm A. , Beerman Isabel
Published: September 2021

NAD+ supplementation has significant benefits in compromised settings, acting largely through improved mitochondrial function and DNA repair. Elevating NAD+ to physiological levels has been shown to improve the function of some adult stem cells, with implications that these changes will lead to sustained improvement of the tissue or system. Here, we examined the effect of elevating NAD+ levels in models with reduced hematopoietic stem cell (HSC) potential, ATM-deficient and aged WT mice, and showed that supplementation of nicotinamide riboside (NR), a NAD+ precursor, improved lymphoid lineage potential during supplementation. In aged mice, this improved lymphoid potential was maintained in competitive transplants and was associated with transcriptional repression of myeloid gene signatures in stem and lineage-committed progenitor cells after NR treatment. However, the altered transcriptional priming of the stem cells toward lymphoid lineages was not sustained in the aged mice after NR removal. These data characterize significant alterations to the lineage potential of functionally compromised HSCs after short-term exposure to NR treatment.
Predicting cancer drug TARGETS - TreAtment Response Generalized Elastic-neT Signatures
Authors: Rydzewski Nicholas R. , Peterson Erik , Lang Joshua M. , Yu Menggang , Laura Chang S. , Sjöström Martin , Bakhtiar Hamza , Song Gefei , Helzer Kyle T. , Bootsma Matthew L. , Chen William S. , Shrestha Raunak M. , Zhang Meng , Quigley David A. , Aggarwal Rahul , Small Eric J. , Wahl Daniel R. , Feng Felix Y. , Zhao Shuang G.
Published: September 2021

We are now in an era of molecular medicine, where specific DNA alterations can be used to identify patients who will respond to specific drugs. However, there are only a handful of clinically used predictive biomarkers in oncology. Herein, we describe an approach utilizing in vitro DNA and RNA sequencing and drug response data to create TreAtment Response Generalized Elastic-neT Signatures (TARGETS). We trained TARGETS drug response models using Elastic-Net regression in the publicly available Genomics of Drug Sensitivity in Cancer (GDSC) database. Models were then validated on additional in-vitro data from the Cancer Cell Line Encyclopedia (CCLE), and on clinical samples from The Cancer Genome Atlas (TCGA) and Stand Up to Cancer/Prostate Cancer Foundation West Coast Prostate Cancer Dream Team (WCDT). First, we demonstrated that all TARGETS models successfully predicted treatment response in the separate in-vitro CCLE treatment response dataset. Next, we evaluated all FDA-approved biomarker-based cancer drug indications in TCGA and demonstrated that TARGETS predictions were concordant with established clinical indications. Finally, we performed independent clinical validation in the WCDT and found that the TARGETS AR signaling inhibitors (ARSI) signature successfully predicted clinical treatment response in metastatic castration-resistant prostate cancer with a statistically significant interaction between the TARGETS score and PSA response (p = 0.0252). TARGETS represents a pan-cancer, platform-independent approach to predict response to oncologic therapies and could be used as a tool to better select patients for existing therapies as well as identify new indications for testing in prospective clinical trials.
Pathways to Parkinson’s disease: a spotlight on 14-3-3 proteins
Authors: Giusto E. , Yacoubian T. A. , Greggio E. , Civiero L.
Published: September 2021

14-3-3s represent a family of highly conserved 30 kDa acidic proteins. 14-3-3s recognize and bind specific phospho-sequences on client partners and operate as molecular hubs to regulate their activity, localization, folding, degradation, and protein–protein interactions. 14-3-3s are also associated with the pathogenesis of several diseases, among which Parkinson’s disease (PD). 14-3-3s are found within Lewy bodies (LBs) in PD patients, and their neuroprotective effects have been demonstrated in several animal models of PD. Notably, 14-3-3s interact with some of the major proteins known to be involved in the pathogenesis of PD. Here we first provide a detailed overview of the molecular composition and structural features of 14-3-3s, laying significant emphasis on their peculiar target-binding mechanisms. We then briefly describe the implication of 14-3-3s in the central nervous system and focus on their interaction with LRRK2, α-Synuclein, and Parkin, three of the major players in PD onset and progression. We finally discuss how different types of small molecules may interfere with 14-3-3s interactome, thus representing a valid strategy in the future of drug discovery.
Early EEG responses to pre-electoral survey items reflect political attitudes and predict voting behavior
Authors: Galli Giulia , Angelucci Davide , Bode Stefan , De Giorgi Chiara , De Sio Lorenzo , Paparo Aldo , Di Lorenzo Giorgio , Betti Viviana
Published: September 2021

Self-reports are conventionally used to measure political preferences, yet individuals may be unable or unwilling to report their political attitudes. Here, in 69 participants we compared implicit and explicit methods of political attitude assessment and focused our investigation on populist attitudes. Ahead of the 2019 European Parliament election, we recorded electroencephalography (EEG) from future voters while they completed a survey that measured levels of agreement on different political issues. An Implicit Association Test (IAT) was administered at the end of the recording session. Neural signals differed as a function of future vote for a populist or mainstream party and of whether survey items expressed populist or non-populist views. The combination of EEG responses and self-reported preferences predicted electoral choice better than traditional socio-demographic and ideological variables, while IAT scores were not a significant predictor. These findings suggest that measurements of brain activity can refine the assessment of socio-political attitudes, even when those attitudes are not based on traditional ideological divides.
Real-time observation of nucleation and growth of Au on CdSe quantum dot templates
Authors: Paul Neelima , Huang Junyu , Liu Chang , Lin Taidong , Ouyang Chenghao , Liu Zhaoyu , Chen Chunfeng , Chen Zhongyi , Weng Zhiyin , Schwartzkopf Matthias , Roth Stephan V. , Müller-Buschbaum Peter , Paul Amitesh
Published: September 2021

Semiconductor quantum dot (QD) arrays can be useful for optical devices such as lasers, solar cells and light-emitting diodes. As the size distribution influences the band-gap, it is worthwhile to investigate QDs prepared using different solvents because each of them could influence the overall morphology differently, depending on the ligand network around individual QDs. Here, we follow the nucleation and growth of gold (Au) on CdSe QD arrays to investigate the influence of surface ligands and thereby realized interparticle distance between QDs on Au growth behaviour. We particularly emphasize on the monolayer stage as the Au decoration on individual QDs is expected at this stage. Therefore, we sputter-deposit Au on each QD array to investigate the morphological evolution in real-time using time-resolved grazing-incidence small-angle X-ray scattering (GISAXS). The growth kinetics - independent of the template - signifies that the observed template-mediated nucleation is limited only to the very first few monolayers. Delicate changes in the Au growth morphology are seen in the immediate steps following the initial replicated decoration of the QD arrays. This is followed by a subsequent clustering and finally a complete Au coverage of the QD arrays.
Decomposition of peatland DOC affected by root exudates is driven by specific r and K strategic bacterial taxa
Authors: Mastný Jiří , Bárta Jiří , Kaštovská Eva , Picek Tomáš
Published: September 2021

In peatlands, decomposition of organic matter is limited by harsh environmental conditions and low decomposability of the plant material. Shifting vegetation composition fromSphagnumtowards vascular plants is expected in response to climate change, which will lead to increased root exudate flux to the soil and stimulation of microbial growth and activity. We aimed to evaluate the effect of root exudates on the decomposition of recalcitrant dissolved organic carbon (DOC) and to identify microorganisms involved in this process. The exudation was mimicked by an addition of a mixture of13C labelled compounds into the recalcitrant DOC in two realistic levels; 2% and 5% of total DOC and peatland porewater with added root exudates was incubated under controlled conditions in the lab. The early stage of incubation was characterized by a relative increase of r-strategic bacteria mainly fromGammaproteobacteriaandBacteriodetes phyla within the microbial community and their preferential use of the added compounds. At the later stage,AlphaproteobacteriaandAcidobacteriamembers were the dominating phyla, which metabolized both the transformed13C compounds and the recalcitrant DOC. Only higher exudate input (5% of total DOC) stimulated decomposition of recalcitrant DOC compared to non-amended control. The most important taxa with a potential to decompose complex DOC compounds were identified as:Mucilaginibacter(Bacteriodetes),BurkholderiaandPseudomonas(Gammaproteobacteria) among r-strategists andBryocellaandCandidatus Solibacter(Acidobacteria) among K-strategists. We conclude that increased root exudate inputs and their increasing C/N ratio stimulate growth and degradation potential of both r-strategic and K-strategic bacteria, which make the system more dynamic and may accelerate decomposition of peatland recalcitrant DOC.
Tetraploids expanded beyond the mountain niche of their diploid ancestors in the mixed-ploidy grass Festuca amethystina L.
Authors: Kiedrzyński Marcin , Zielińska Katarzyna M. , Jedrzejczyk Iwona , Kiedrzyńska Edyta , Tomczyk Przemysław P. , Rewicz Agnieszka , Rewers Monika , Indreica Adrian , Bednarska Iryna , Stupar Vladimir , Roleček Jan , Šmarda Petr
Published: September 2021

One promising area in understanding the responses of plants to ongoing global climate change is the adaptative effect of polyploidy. This work examines whether there is a coupling between the distribution of cytotypes and their biogeographical niche, and how different niches will affect their potential range. The study uses a range of techniques including flow cytometry, gradient and niche analysis, as well as distribution modelling. In addition, climatic, edaphic and habitat data was used to analyse environmental patterns and potential ranges of cytotypes in the first wide-range study ofFestuca amethystina—a mixed-ploidy mountain grass. The populations were found to be ploidy homogeneous and demonstrate a parapatric pattern of cytotype distribution. Potential contact zones have been identified. The tetraploids have a geographically broader distribution than diploids; they also tend to occur at lower altitudes and grow in more diverse climates, geological units and habitats. Moreover, tetraploids have a more extensive potential range, being six-fold larger than diploids. Montane pine forests were found to be a focal environment suitable for both cytotypes, which has a central place in the environmental space of the whole species. Our findings present polyploidy as a visible driver of geographical, ecological and adaptive variation within the species.
Quantitative assessment of the vertebral pneumaticity in an anhanguerid pterosaur using micro-CT ﻿scanning
Authors: Buchmann Richard , Holgado Borja , Sobral Gabriela , dos Santos Avilla Leonardo , Rodrigues Taissa
Published: September 2021

Research on the postcranial skeletal pneumaticity in pterosaurs is common in the literature, but most studies present only qualitative assessments. When quantitative, they are done on isolated bones. Here, we estimate the Air Space Proportion (ASP) obtained from micro-CT scans of the sequence from the sixth cervical to the fourth dorsal vertebra of an anhanguerine pterosaur to understand how pneumaticity is distributed in these bones. Pneumatisation of the vertebrae varied between 68 and 72% of their total volume. The neural arch showed higher ASP in all vertebrae. Anhanguerine vertebral ASP was generally higher than in sauropod vertebrae but lower than in most extant birds. The ASP observed here is lower than that calculated for the appendicular skeleton of other anhanguerian pterosaurs, indicating the potential existence of variation between axial and appendicular pneumatisation. The results point to a pattern in the distribution of the air space, which shows an increase in the area occupied by the trabecular bone in the craniocaudal direction of the vertebral series and, in each vertebra, an increase of the thickness of the trabeculae in the zygapophyses. This indicates that the distribution of pneumatic diverticula in anhanguerine vertebrae may not be associated with stochastic patterns.
Biomarkers of cellular aging during a controlled human malaria infection
Authors: Miglar Aurelie , Reuling Isaie J. , Yap Xi Zen , Färnert Anna , Sauerwein Robert W. , Asghar Muhammad
Published: September 2021

Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections. We demonstrate that already low levels ofPlasmodium falciparumimpact cellular aging by inducing high levels of inflammation and redox-imbalance; and that cellular senescence reversed after treatment and parasite clearance. This study provides insights into the complex relationship of telomere length, cellular senescence, telomerase expression and aging-related processes during a single malaria infection.
Contribution of conspecific negative density dependence to species diversity is increasing towards low environmental limitation in Japanese forests
Authors: Fibich Pavel , Ishihara Masae I. , Suzuki Satoshi N. , Doležal Jiří , Altman Jan
Published: September 2021

Species coexistence is a result of biotic interactions, environmental and historical conditions. The Janzen-Connell hypothesis assumes that conspecific negative density dependence (CNDD) is one of the local processes maintaining high species diversity by decreasing population growth rates at high densities. However, the contribution of CNDD to species richness variation across environmental gradients remains unclear. In 32 large forest plots all over the Japanese archipelago covering > 40,000 individual trees of > 300 species and based on size distributions, we analysed the strength of CNDD of individual species and its contribution to species number and diversity across altitude, mean annual temperature, mean annual precipitation and maximum snow depth gradients. The strength of CNDD was increasing towards low altitudes and high tree species number and diversity. The effect of CNDD on species number was changing across altitude, temperature and snow depth gradients and their combined effects contributed 11–18% of the overall explained variance. Our results suggest that CNDD can work as a mechanism structuring forest communities in the Japanese archipelago. Strong CNDD was observed to be connected with high species diversity under low environmental limitations where local biotic interactions are expected to be stronger than in niche-based community assemblies under high environmental filtering.
Palaeoclimate has a major effect on the diversity of endemic species in the hotspot of mountain biodiversity in Tajikistan
Authors: Raduła Małgorzata , Świerszcz Sebastian , Nobis Marcin , Nowak Sylwia , Nobis Agnieszka , Nowak Arkadiusz
Published: September 2021

In a period of ongoing climate changes, identifying drivers of overall and endemic species diversity is a key element in constructing new ecological patterns and determining the main goals of conservation. Such studies are especially crucial if they concern biodiversity hotspot areas. In this study, we explore patterns and drivers of plant endemism (the proportion of endemic plant species to overall plant species richness; PE) in Tajikistan. We used three groups of climatic measures featuring the contemporary and glacial climates as well as climatic changes since the Last Glacial Maximum in the Pleistocene (LGM). To explore relationships between PE and climatic groups, and the most important climatic variables, we applied the Generalised Additive Model and regression trees method respectively. Glacial climate predicted PE variation the most (74.3%), followed by climate stability (55.4%) and current climate (62.4%). The most important variables represented change in precipitation of driest quarter, glacial mean annual temperature and current annual precipitation. LGM climate and its change to date have the greatest influence on contemporary PE patterns in Tajikistan, revealing the evolutionary dependencies between limited-range plants and past climate. Accordingly, annual temperature and precipitation regimes have been the most crucial drivers of PE since the LGM until today. The study revealed the dependence of the PE on a stabilized water-energy supply. The changing temperature and precipitations regimes during the ongoing climate warming may, therefore, increases the threat to geographically isolated cryophilous plants of Tajikistan, while their escape potential to suitable cold habitats is highly topographically limited.
A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis
Authors: Uyar Olus , Plante Pier-Luc , Piret Jocelyne , Venable Marie-Christine , Carbonneau Julie , Corbeil Jacques , Boivin Guy
Published: September 2021

Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.
Effect of density, phonon scattering and nanoporosity on the thermal conductivity of anisotropic cellulose nanocrystal foams
Authors: Apostolopoulou-Kalkavoura Varvara , Munier Pierre , Dlugozima Lukasz , Heuthe Veit-Lorenz , Bergström Lennart
Published: September 2021

Anisotropic cellulose nanocrystal (CNC) foams with densities between 25 and 130 kg m−3 (CNC25 –CNC130) were prepared by directional ice-templating of aqueous dispersions. Estimates of the solid and gas conduction contributions to the thermal conductivity of the foams using a parallel resistor model showed that the relatively small increase of the radial thermal conductivity with increasing foam density can be attributed to interfacial phonon scattering. The foam wall nanoporosity and, to a lesser extent, the orientation of the CNC particles and alignment of the columnar macropores, also influence the insulation performance of the foams. The insight on the importance of phonon scattering for the thermal insulation properties of nanocellulose foams provides useful guidelines for tailoring nanofibrillar foams for super-insulating applications.
Relationship of low molecular weight fluorophore levels with clinical factors and fenofibrate effects in adults with type 2 diabetes
Authors: Januszewski Andrzej S. , Chen David , Scott Russell S. , O’Connell Rachel L. , Aryal Nanda R. , Sullivan David R. , Watts Gerald F. , Taskinen Marja-Riitta , Barter Philip J. , Best James D. , Simes R. John , Keech Anthony C. , Jenkins Alicia J.
Published: September 2021

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04–0.16, allp < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (allp ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trendp < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.
An experimentally validated fading model for THz wireless systems
Authors: Papasotiriou Evangelos N. , Boulogeorgos Alexandros-Apostolos A. , Haneda Katsuyuki , de Guzman Mar Francis , Alexiou Angeliki
Published: September 2021

As the wireless world moves towards the sixth generation (6G) era, the demand of supporting bandwidth-hungry applications in ultra-dense deployments becomes more and more imperative. Driven by this requirement, both the research and development communities have turned their attention into the terahertz (THz) band, where more than$$20\,{\text {GHz}}$$20GHzof contiguous bandwidth can be exploited. As a result, novel wireless system and network architectures have been reported promising excellence in terms of reliability, massive connectivity, and data-rates. To assess their feasibility and efficiency, it is necessary to develop stochastic channel models that account for the small-scale fading. However, to the best of our knowledge, only initial steps have been so far performed. Motivated by this, this contribution is devoted to take a new look to fading in THz wireless systems, based on three sets of experimental measurements. In more detail, measurements, which have been conducted in a shopping mall, an airport check-in area, and an entrance hall of a university towards different time periods, are used to accurately model the fading distribution. Interestingly, our analysis shows that conventional distributions, such as Rayleigh, Rice, and Nakagami-m, lack fitting accuracy, whereas, the more general, yet tractable,$$\alpha $$α–$$\mu $$μdistribution has an almost-excellent fit. In order to quantify their fitting efficiency, we used two well-defined and widely-accepted tests, namely the Kolmogorov–Smirnov and the Kullback–Leibler tests. By accurately modeling the THz wireless channel, this work creates the fundamental tools of developing the theoretical and optimization frameworks for such systems and networks.
Achieving broad absorption band and high incident angles by stochastically-distributed oblique-flat-sheet metamaterial perfect absorbers
Authors: Lu Cheng-Yu , Chung Chin-Chien , Yen Ta-Jen , Huang Tsung-Yu
Published: September 2021

In this work, we integrated a periodic seed layer and oblique deposition method to fabricate a stochastically-distributed oblique-flat-sheet metamaterial perfect absorber (MPA). Such design could increase its absorption bandwidth and tolerance to high angle-incidence due to the fact that various oblique flat sheets offer different resonance conditions while even a single oblique flat sheet could provide different optical paths for resonance. On the other hand, a seed layer could reduce uncertainty regarding to direct oblique deposition and provide abilities to manipulate the bandwidth of the MPA. We also setup a simulation model in the aids of Visual Basic Application and examined the absorption behavior of the MPA under TM and TE oblique incidence that could achieve high absorbance under 80° and 60° incidence, respectively. Finally, in measurement, the fabricated sample owns 65% absorbance within 80–250 THz and over 90% absorbance within 250–320 THz at x-polarization normal incidence; as for the y-polarization normal incidence, we could achieve overall 70% absorbance within 80–300 THz. The measured results reveal similar tendency compared to the simulated ones.
Thermal growth in solar water pump using Prandtl–Eyring hybrid nanofluid: a solar energy application
Authors: Jamshed Wasim , Nasir Nor Ain Azeany Mohd , Isa Siti Suzilliana Putri Mohamed , Safdar Rabia , Shahzad Faisal , Nisar Kottakkaran Sooppy , Eid Mohamed R. , Abdel-Aty Abdel-Haleem , Yahia I. S.
Published: September 2021

Nowadays, with the advantages of nanotechnology and solar radiation, the research of Solar Water Pump (SWP) production has become a trend. In this article, Prandtl–Eyring hybrid nanofluid (P-EHNF) is chosen as a working fluid in the SWP model for the production of SWP in a parabolic trough surface collector (PTSC) is investigated for the case of numerous viscous dissipation, heat radiations, heat source, and the entropy generation analysis. By using a well-established numerical scheme the group of equations in terms of energy and momentum have been handled that is called the Keller-box method. The velocity, temperature, and shear stress are briefly explained and displayed in tables and figures. Nusselt number and surface drag coefficient are also being taken into reflection for illustrating the numerical results. The first finding is the improvement in SWP production is generated by amplification in thermal radiation and thermal conductivity variables. A single nanofluid and hybrid nanofluid is very crucial to provide us the efficient heat energy sources. Further, the thermal efficiency of MoS2–Cu/EO than Cu–EO is between 3.3 and 4.4% The second finding is the addition of entropy is due to the increasing level of radiative flow, nanoparticles size, and Prandtl–Eyring variable.
Identification of candidate regulators of mandibular bone loss in FcγRIIB-/- Mice
Authors: Sakunrangsit Nithidol , Pholtaisong Jatuphol , Sucharitakul Jeerus , Wanna-udom Sasithorn , Prombutara Pinidphon , Pisitkun Prapaporn , Leelahavanichkul Asada , Aporntewan Chatchawit , Greenblatt Matthew B. , Lotinun Sutada
Published: September 2021

Patients with systemic lupus erythematosus (SLE) have increased inflammatory cytokines, leading to periodontitis and alveolar bone loss. However, the mechanisms driving this phenomenon are still unknown. Here, we have identified novel therapeutic targets for and mediators of lupus-mediated bone loss using RNA-sequencing (RNA-seq) in a FcγRIIB-/- mouse model of lupus associated osteopenia. A total of 2,710 upregulated and 3,252 downregulated DEGs were identified. The GO and KEGG annotations revealed that osteoclast differentiation, bone mineralization, ossification, and myeloid cell development were downregulated. WikiPathways indicated that Hedgehog, TNFα NF-κB and Notch signaling pathway were also decreased. We identified downregulated targets, Sufu and Serpina12, that have important roles in bone homeostasis. Sufu and Serpina12 were related to Hedgehog signaling proteins, including Gli1, Gli2, Gli3, Ptch1, and Ptch2. Gene knockdown analysis demonstrated that Sufu, and Serpina12 contributed to osteoclastogenesis and osteoblastogenesis, respectively. Osteoclast and osteoblast marker genes were significantly decreased in Sufu-deficient and Serpina12-deficient cells, respectively. Our results suggest that alterations in Hedgehog signaling play an important role in the pathogenesis of osteopenia in FcγRIIB-/- mice. The novel DEGs and pathways identified in this study provide new insight into the underlying mechanisms of mandibular bone loss during lupus development.
Topological heterogeneity and evaporation dynamics of irregular water droplets
Authors: Kim Yeseul , Gonçalves Marta , Kim Deok-Ho , Weon Byung Mook
Published: September 2021

Water droplets sitting between wires are ubiquitous in nature and industry, often showing irregular (non-spherical) droplet shapes. To understand their topological singularity and evaporation mechanism, measuring volume changes of irregular water droplets is essential but highly challenging for small-volume water droplets. Here we experimentally explore topological heterogeneity and evaporation dynamics for irregular water droplets between wires with four-dimensional X-ray microtomography that directly provides images in three spatial dimensions as a function of time, enabling us to get three-dimensional structural and geometric information changes with time. We find that the topological heterogeneity of an irregular droplet is due to the local contact lines and the evaporation dynamics of an irregular droplet is governed by the effective contact radius. This study may offer an opportunity to understand how the topological heterogeneity contributes to the evaporation dynamics of irregular water droplets.
HTSQualC is a flexible and one-step quality control software for high-throughput sequencing data analysis
Authors: Bedre Renesh , Avila Carlos , Mandadi Kranthi
Published: September 2021

Use of high-throughput sequencing (HTS) has become indispensable in life science research. Raw HTS data contains several sequencing artifacts, and as a first step it is imperative to remove the artifacts for reliable downstream bioinformatics analysis. Although there are multiple stand-alone tools available that can perform the various quality control steps separately, availability of an integrated tool that can allow one-step, automated quality control analysis of HTS datasets will significantly enhance handling large number of samples parallelly. Here, we developed HTSQualC, a stand-alone, flexible, and easy-to-use software for one-step quality control analysis of raw HTS data. HTSQualC can evaluate HTS data quality and perform filtering and trimming analysis in a single run. We evaluated the performance of HTSQualC for conducting batch analysis of HTS datasets with 322 samples with an average ~ 1 M (paired end) sequence reads per sample. HTSQualC accomplished the QC analysis in ~ 3 h in distributed mode and ~ 31 h in shared mode, thus underscoring its utility and robust performance. In addition to command-line execution, we integrated HTSQualC into the free, open-source, CyVerse cyberinfrastructure resource as a GUI interface, for wider access to experimental biologists who have limited computational resources and/or programming abilities.
Analysis of atmospheric temperature data by 4D spatial–temporal statistical model
Authors: Xu Ke , Wang Yaqiong
Published: September 2021

The meteorological data such as temperature of the upper atmosphere is ssential for accurate weather forecasting. The Universal Rawinsonde Observation Program (RAOB) establishes an extensive radiosonde network worldwide to observe atmospheric meteorological data from the surface to the low stratosphere. The RAOB data data has very high accuracy but can offer a very limited spatial coverage. Meanwhile, ERA-Interim reanalysis data is widely available but with low-quality. We propose a 4D spatiotemporal statistical model which can make effective inferences from ERA-Interim reanalysis data to RAOB data. Finally, we can obtain a huge amount of RAOB data with high-quality and can offer a very wide spatial coverage. In empirical research, we collected data from 200 launch sites around the world in January 2015. The 4D spatiotemporal statistical model successfully analyzed the observation gaps at different pressure levels.
Synthesis of a novel ternary ZIF-8/GO/MgFe2O4 nanocomposite and its application in drug delivery
Authors: Sanaei-Rad Saleheh , Ghasemzadeh Mohammad Ali , Razavian Seyyed Mohammad Hossein
Published: September 2021

In recent year, metal–organic frameworks (MOFs) have been displayed to be a category of promising drug delivery systems because of their crystalline structure, the potential of further functionality, and high porosity. In this research, graphene oxide was synthesized from pure graphite via hummer method and then MgFe2O4 nanoparticles was incorporated into the synthesized ZIF-8 metal–organic frameworks which followed with loading on the surfaces of graphene oxide. In continue, tetracycline as an antibiotic drug was loaded on the surfaces and the cavities of the prepared nanocomposite. The outcomes of this research revealed that 90% of the tetracycline was loaded on the synthesized ZIF-8/GO/MgFe2O4 nanostructure. Next, drug release was done at pH: 5 and pH: 7.4 within 3 days, resulting about 88% and 92% release of the tetracycline, respectively. With using different spectroscopic methods like X-ray crystallography (XRD), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX/Mapping), Fourier transform infrared (FTIR), thermalgravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET), the structure of synthesized materials was confirmed. Furthermore, the antibiotic activity of tetracycline trapped into the ZIF-8/GO/MgFe2O4 was evaluated by agar-well diffusion method on both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria, which showed good antibacterial results.
Bacteriophage origin of some minimal ATP-dependent DNA ligases: a new structure from Burkholderia pseudomallei with striking similarity to Chlorella virus ligase
Authors: Pan Jolyn , Lian Kjersti , Sarre Aili , Leiros Hanna-Kirsti S. , Williamson Adele
Published: September 2021

DNA ligases, the enzymes responsible for joining breaks in the phosphodiester backbone of DNA during replication and repair, vary considerably in size and structure. The smallest members of this enzyme class carry out their functions with pared-down protein scaffolds comprising only the core catalytic domains. Here we use sequence similarity network analysis of minimal DNA ligases from all biological super kingdoms, to investigate their evolutionary origins, with a particular focus on bacterial variants. This revealed that bacterial Lig C sequences cluster more closely with Eukaryote and Archaeal ligases, while bacterial Lig E sequences cluster most closely with viral sequences. Further refinement of the latter group delineates a cohesive cluster of canonical Lig E sequences that possess a leader peptide, an exclusively bacteriophage group of T7 DNA ligase homologs and a group with high similarity to the Chlorella virus DNA ligase which includes both bacterial and viral enzymes. The structure and function of the bacterially-encoded Chlorella virus homologs were further investigated by recombinantly producing and characterizing, the ATP-dependent DNA ligase from Burkholderia pseudomallei as well as determining its crystal structure in complex with DNA. This revealed that the enzyme has similar activity characteristics to other ATP-dependent DNA ligases, and significant structural similarity to the eukaryotic virus Chlorella virus including the positioning and DNA contacts of the binding latch region. Analysis of the genomic context of the B. pseudomallei ATP-dependent DNA ligase indicates it is part of a lysogenic bacteriophage present in the B. pseudomallei chromosome representing one likely entry point for the horizontal acquisition of ATP-dependent DNA ligases by bacteria.
The macronuclear genome of the Antarctic psychrophilic marine ciliate Euplotes focardii reveals new insights on molecular cold adaptation
Authors: Mozzicafreddo Matteo , Pucciarelli Sandra , Swart Estienne C. , Piersanti Angela , Emmerich Christiane , Migliorelli Giovanna , Ballarini Patrizia , Miceli Cristina
Published: September 2021

The macronuclear (MAC) genomes of ciliates belonging to the genus Euplotes species are comprised of numerous small DNA molecules, nanochromosomes, each typically encoding a single gene. These genomes are responsible for all gene expression during vegetative cell growth. Here, we report the analysis of the MAC genome from the Antarctic psychrophile Euplotes focardii. Nanochromosomes containing bacterial sequences were not found, suggesting that phenomena of horizontal gene transfer did not occur recently, even though this ciliate species has a substantial associated bacterial consortium. As in other euplotid species, E. focardii MAC genes are characterized by a high frequency of translational frameshifting. Furthermore, in order to characterize differences that may be consequent to cold adaptation and defense to oxidative stress, the main constraints of the Antarctic marine microorganisms, we compared E. focardii MAC genome with those available from mesophilic Euplotes species. We focussed mainly on the comparison of tubulin, antioxidant enzymes and heat shock protein (HSP) 70 families, molecules which possess peculiar characteristic correlated with cold adaptation in E. focardii. We found that α-tubulin genes and those encoding SODs and CATs antioxidant enzymes are more numerous than in the mesophilic Euplotes species. Furthermore, the phylogenetic trees showed that these molecules are divergent in the Antarctic species. In contrast, there are fewer hsp70 genes in E. focardii compared to mesophilic Euplotes and these genes do not respond to thermal stress but only to oxidative stress. Our results suggest that molecular adaptation to cold and oxidative stress in the Antarctic environment may not only be due to particular amino acid substitutions but also due to duplication and divergence of paralogous genes.
Association between pregravid liver enzyme levels and gestational diabetes in twin pregnancies: a secondary analysis of national cohort study
Authors: Park Jae-Young , Kim Woo Jeng , Chung Yoo Hyun , Kim Bongseong , Park Yonggyu , Park In Yang , Ko Hyun Sun
Published: September 2021

Multiple pregnancies are prone to gestational diabetes mellitus (GDM). This study investigated the association between pregravid liver enzyme levels and the development of GDM in a twin pregnancy. Women who had the National Health Screening Examination and delivered their twin babies within one year were enrolled. Pregravid liver enzyme levels were divided into high and low level. Risks for developing GDM by high levels of liver enzymes were analyzed, in subgroups by pregravid obesity or metabolic syndrome. Among the 4348 twin pregnancies, 369 women (8.5%) developed GDM not requiring insulin treatment (GDM − IT), and 119 women (2.7%) developed GDM requiring insulin treatment(GDM + IT). High levels of pregravid GGT and ALT were related to risks of GDM + IT not only in women with obesity or metabolic syndrome (odds ratio[OR] 6.348, 95% confidence interval [CI] 2.579–15.624 and OR 6.879, 95% CI 2.232–21.204, respectively), but also in women without obesity (OR 3.05, 95% CI 1.565–5.946) or without metabolic syndrome (OR 3.338, 95% CI 1.86–5.992), compared to in women with low levels of those. However, there were no significant associations in the pregravid ALT and GGT levels and risks for development of GDM − IT, unrelated to pregravid obesity or metabolic syndrome. Therefore, this study suggests that women with high levels of pregravid GGT and ALT need to recognize their increased risk of GDM + IT, regardless of pregravid obesity or MetS, when they get pregnant twin.
The effect of biologically active compounds in the mucus of slugs Limax maximus and Arion rufus on human skin cells
Authors: Leśków Anna , Tarnowska Małgorzata , Szczuka Izabela , Diakowska Dorota
Published: September 2021

Molluscs are one of the sources of biologically active substances, which are now intensively studied, especially for their anti-cancer properties. Malignant melanoma originates from melanocytes, develops very quickly and is associated with poor prognosis. Therefore, the aim of the study was to assess the properties of biologically active compounds in sterile mucus isolated from slugs Limax maximus and Arion rufus. Tested mucus were isolated using the new self-developed method which is safe for the environment and the animal donors. The impact of the mucus on human keratinocytes CCD 1106 KERTr and malignant melanoma cells A-375 was examined using MTT assay and SRB assay, which allowed us to determine the cell metabolic activity and cell number after treating them with slug mucus isolated from Limax maximus and Arion rufus decreased human keratinocytes and melanoma cells metabolic activity as well as manifested properties of reducing the number of cells in both tested cell lines, and therefore can be a source of biologically active substances with anticancer potential.