bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing genetic histories and social organisation in Neolithic and Bronze Age Croatia
Authors: Freilich Suzanne , Ringbauer Harald , Los Dženi , Novak Mario , Pavičić Dinko Tresić , Schiffels Stephan , Pinhasi Ron
Published: August 2021

Ancient DNA studies have revealed how human migrations from the Neolithic to the Bronze Age transformed the social and genetic structure of European societies. Present-day Croatia lies at the heart of ancient migration routes through Europe, yet our knowledge about social and genetic processes here remains sparse. To shed light on these questions, we report new whole-genome data for 28 individuals dated to between ~ 4700 BCE–400 CE from two sites in present-day eastern Croatia. In the Middle Neolithic we evidence first cousin mating practices and strong genetic continuity from the Early Neolithic. In the Middle Bronze Age community that we studied, we find multiple closely related males suggesting a patrilocal social organisation. We also find in that community an unexpected genetic ancestry profile distinct from individuals found at contemporaneous sites in the region, due to the addition of hunter-gatherer-related ancestry. These findings support archaeological evidence for contacts with communities further north in the Carpathian Basin. Finally, an individual dated to Roman times exhibits an ancestry profile that is broadly present in the region today, adding an important data point to the substantial shift in ancestry that occurred in the region between the Bronze Age and today.
Comparative analysis of nuclear and mitochondrial DNA from tissue and liquid biopsies of colorectal cancer patients
Authors: Haupts Anna , Vogel Anne , Foersch Sebastian , Hartmann Monika , Maderer Annett , Wachter Nicolas , Huber Tobias , Kneist Werner , Roth Wilfried , Lang Hauke , Moehler Markus , Hartmann Nils
Published: August 2021

The current standard for molecular profiling of colorectal cancer (CRC) is using resected or biopsied tissue specimens. However, they are limited regarding sampling frequency, representation of tumor heterogeneity, and sampling can expose patients to adverse side effects. The analysis of cell-free DNA (cfDNA) from blood plasma, which is part of a liquid biopsy, is minimally invasive and in principle enables detection of all tumor-specific mutations. Here, we analyzed cfDNA originating from nucleus and mitochondria and investigated their characteristics and mutation status in a cohort of 18 CRC patients and 10 healthy controls using targeted next-generation sequencing (NGS) and digital PCR. Longitudinal analyses of nuclear cfDNA level and size during chemotherapy revealed a decreasing cfDNA content and a shift from short to long fragments, indicating an appropriate therapy response, while shortened cfDNAs and increased cfDNA content corresponded with tumor recurrence. Comparative NGS analysis of nuclear tissue and plasma DNA demonstrated a good patient-level concordance and cfDNA revealed additional variants in three of the cases. Analysis of mitochondrial cfDNA surprisingly revealed a higher plasma copy number in healthy subjects than in CRC patients. These results highlight the potential clinical utility of liquid biopsies in routine diagnostics and surveillance of CRC patients as complementation to tissue biopsies or as an attractive alternative in cases where tissue biopsies are risky or the quantity/quality does not allow testing.
Dynamics of cocoa fermentation and its effect on quality
Authors: Calvo Ana M. , Botina Blanca L. , García Maria C. , Cardona William A. , Montenegro Andrea C. , Criollo Jenifer
Published: August 2021

Several research efforts on cocoa have been focused on parameters for controlling the transformation process to guarantee homogeneity and quality of cocoa beans, the main raw material in the chocolate industry. The main changes that determine the final quality of cocoa—and also the product’s homogeneity—occur during fermentation, given the great number of factors that affect the process. This research seeks to identify the most relevant factors affecting quality in order to offer higher-quality and more homogeneous cocoa for the chocolate industry. The dynamics of the fermentation process were observed in three contrasting locations, monitoring different variables and evaluating the final quality of the cocoa. Results show that temperature and pH profile are the key factors to be monitored and controlled in order to achieve high-quality cocoa beans.
Characterization and clinical implications of ankle impedance during walking in chronic stroke
Authors: Shorter Amanda L. , Richardson James K. , Finucane Suzanne B. , Joshi Varun , Gordon Keith , Rouse Elliott J.
Published: August 2021

Individuals post-stroke experience persisting gait deficits due to altered joint mechanics, known clinically as spasticity, hypertonia, and paresis. In engineering, these concepts are described as stiffness and damping, or collectively as joint mechanical impedance, when considered with limb inertia. Typical clinical assessments of these properties are obtained while the patient is at rest using qualitative measures, and the link between the assessments and functional outcomes and mobility is unclear. In this study we quantify ankle mechanical impedance dynamically during walking in individuals post-stroke and in age-speed matched control subjects, and examine the relationships between mechanical impedance and clinical measures of mobility and impairment. Perturbations were applied to the ankle joint during the stance phase of walking, and least-squares system identification techniques were used to estimate mechanical impedance. Stiffness of the paretic ankle was decreased during mid-stance when compared to the non-paretic side; a change independent of muscle activity. Inter-limb differences in ankle joint damping, but not joint stiffness or passive clinical assessments, strongly predicted walking speed and distance. This work provides the first insights into how stroke alters joint mechanical impedance during walking, as well as how these changes relate to existing outcome measures. Our results inform clinical care, suggesting a focus on correcting stance phase mechanics could potentially improve mobility of chronic stroke survivors.
Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies
Authors: Männistö Satu , Harald Kennet , Härkänen Tommi , Maukonen Mirkka , Eriksson Johan G. , Heikkinen Sanna , Jousilahti Pekka , Kaartinen Niina E. , Kanerva Noora , Knekt Paul , Koskinen Seppo , Laaksonen Maarit A. , Malila Nea , Rissanen Harri , Pitkäniemi Janne
Published: August 2021

There is limited evidence for any dietary factor, except alcohol, in breast cancer (BC) risk. Therefore, studies on a whole diet, using diet quality indices, can broaden our insight. We examined associations of the Nordic Diet (mNDI), Mediterranean diet (mMEDI) and Alternative Healthy Eating Index (mAHEI) with postmenopausal BC risk. Five Finnish cohorts were combined including 6374 postmenopausal women with dietary information. In all, 8–9 dietary components were aggregated in each index, higher total score indicating higher adherence to a healthy diet. Cox proportional hazards regression was used to estimate the combined hazard ratio (HR) and 95% confidence interval (CI) for BC risk. During an average 10-year follow-up period, 274 incident postmenopausal BC cases were diagnosed. In multivariable models, the HR for highest vs. lowest quintile of index was 0.67 (95 %CI 0.48–1.01) for mNDI, 0.88 (0.59–1.30) for mMEDI and 0.89 (0.60–1.32) for mAHEI. In this combined dataset, a borderline preventive finding of high adherence to mNDI on postmenopausal BC risk was found. Of the indices, mNDI was more based on the local food culture than the others. Although a healthy diet has beneficially been related to several chronic diseases, the link with the etiology of postmenopausal BC does not seem to be that obvious.
Comparison of early F-18 Florbetaben PET/CT to Tc-99m ECD SPECT using voxel, regional, and network analysis
Authors: Kwon Soo Jin , Ha Seunggyun , Yoo Sang-Won , Shin Na-Young , O Joo Hyun , Yoo Ie Ryung , Kim Joong-Seok
Published: August 2021

This study aimed to validate early-phase F-18 Florbetaben positron emission tomography (eFBB PET) as a brain perfusion test and determine the optimal reference region. A total of 27 patients with early Parkinson’s disease with Tc-99m ethyl cysteinate dimer single photon emission tomography (ECD SPECT) and FBB PET were included. Six reference regions, including whole brain (GN), pons, central white matter (CWM), whole cerebellum (WC), WC with brain stem (WC + B), and cerebellar grey matter (CG), were applied to obtain SUVR using cortex volume-of-interest (VOI). Reference regions of WC (r 0.886), WC + B (r 0.897), and CG (r 0.904) had highest correlation values of cortex-VOI SUVR between both perfusion images (all p < 0.001). Early-phase FBB PET had a significant linear correlation of CG-normalized SUVR of the cortex, basal ganglia, thalamus, and midbrain with ECD SPECT in voxel-wise analysis (FDR adjusted-p < 0.05). Early-phase FBB PET extracts more ICNS than ECD SPECT, as 9 ICNS and 4 ICNs, respectively. Both eFBB PET and ECD SPECT well discriminated PD from DLB (Area-under-curve of receiver-operating-characteristics, 0.911 for eFBB PET, 0.922 for ECD SPECT). Our findings suggest that eFBB PET is a reliable perfusion test based on a high correlation with ECD SPECT using cerebellum-based normalization methods.
Derivation of unifying formulae for convective heat transfer in compressible flow fields
Authors: Zhao Bo
Published: August 2021

Although many theoretical and experimental studies on convective heat transfer exist, the consistent analytical expression of advection heat flux vector in convection as well as its reference temperature in the thermal driving force remains unclear. Here we show theoretically and experimentally the unifying formulae for three-dimensional (3D) heat flux vector of forced and natural convections for compressible laminar flows based on the first law of thermodynamics. It is indicated for a single-phase compressible fluid that advection is no other than heat transfer owing to mass flow in the forms of enthalpy and mechanical energy by gross fluid movement, driven by the temperature difference between the fluid temperature and the potential temperature associated with the relevant adiabatic work done. A simple formula for the total convective heat flux vector of natural convection is also suggested and reformulated in terms of logarithmic density difference as the thermal driving force. The theoretical calculations agree well with the laminar flow experiment results. Our discovery of advection heat transfer for compressible flows caused by the temperature differential in which the potential temperature is regarded as the unifying reference temperature represents a previously unknown thermal driving mechanism. This work would bring fundamental insights into the physical mechanism of convective heat transfer, and opens up new avenue for the design, calculation and thermal management of the 3D convection heat flux problems using the novel thermal driving force for compressible laminar and turbulent flows.
A new tropical cyclone surge index incorporating the effects of coastal geometry, bathymetry and storm information
Authors: Islam Md. Rezuanul , Lee Chia-Ying , Mandli Kyle T. , Takagi Hiroshi
Published: August 2021

This study presents a new storm surge hazard potential index (SSHPI) for estimating tropical cyclone (TC) induced peak surge levels at a coast. The SSHPI incorporates parameters that are often readily available at real-time: intensity in 10-min maximum wind speed, radius of 50-kt wind, translation speed, coastal geometry, and bathymetry information. The inclusion of translation speed and coastal geometry information lead to improvements of the SSHPI to other existing surge indices. A retrospective analysis of SSHPI using data from 1978–2019 in Japan suggests that this index captures historical events reasonably well. In particular, it explains ~ 66% of the observed variance and ~ 74% for those induced by TCs whose landfall intensity was larger than 79-kt. The performance of SSHPI is not sensitive to the type of coastal geometry (open coasts or semi-enclosed bays). Such a prediction methodology can decrease numerical computation requirements, improve public awareness of surge hazards, and may also be useful for communicating surge risk.
DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death
Authors: Bonassi Stefano , Ceppi Marcello , Møller Peter , Azqueta Amaya , Milić Mirta , Neri Monica , Brunborg Gunnar , Godschalk Roger , Koppen Gudrun , Langie Sabine A. S. , Teixeira João Paulo , Bruzzone Marco , Da Silva Juliana , Benedetti Danieli , Cavallo Delia , Ursini Cinzia Lucia , Giovannelli Lisa , Moretti Silvia , Riso Patrizia , Del Bo’ Cristian , Russo Patrizia , Dobrzyńska Malgorzata , Goroshinskaya Irina A. , Surikova Ekaterina I. , Staruchova Marta , Barančokova Magdalena , Volkovova Katarina , Kažimirova Alena , Smolkova Bozena , Laffon Blanca , Valdiglesias Vanessa , Pastor Susana , Marcos Ricard , Hernández Alba , Gajski Goran , Spremo-Potparević Biljana , Živković Lada , Boutet-Robinet Elisa , Perdry Hervé , Lebailly Pierre , Perez Carlos L. , Basaran Nursen , Nemeth Zsuzsanna , Safar Anna , Dusinska Maria , Collins Andrew ,   for the hCOMET project, Anderson Diana , Andrade Vanessa , Pereira Cristiana Costa , Costa Solange , Gutzkow Kristine B. , Ladeira Carina , Moretti Massimo , Costa Carla , Orlow Irene , Rojas Emilio , Pourrut Bertrand , Kruszewski Marcin , Knasmueller Siegfried , Shaposhnikov Sergey , Žegura Bojana , Stopper Helga
Published: August 2021

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan–Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06–1.90) for overall mortality, and 1.94 (1.04–3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.
Notch1 haploinsufficiency in mice accelerates adipogenesis
Authors: Yamaguchi Kazutoshi , Hayashi Motoharu , Uchida Yasuhiro , Cheng Xian Wu , Nakayama Takayuki , Matsushita Tadashi , Murohara Toyoaki , Takeshita Kyosuke
Published: August 2021

Notch signaling has been recognized recently as a key regulator of metabolism. Here, we determined the role of Notch1 in adipogenesis in wild-type (WT) and Notch1 hetero-mutant (N1+/−) mice provided with 12-week normal or high-fat diet. Haploinsufficiency of Notch1 was associated with adipose tissue accumulation despite similar food intake. White adipose tissue (WAT) of N1+/− showed accumulation of adipogenic cells (CD34+CD68+ cells), crown-like structures, and upregulation of cell proliferation markers (cyclin D1 and Ki67). Notch1 expression in WAT reached peak levels in 8-week-old WT mice in parallel with fat accumulation, especially under HF/HS-feeding, whereas such increment was blunted in N1+/− mice. Downstream of Notch1 haploinsufficiency, over-expression of adipogenic factors PPARγ and C/EBPα was noted following down-regulation of downstream transcriptional factors of Notch signaling (Hes-1, Pref-1, and Sox9). Both pharmacological Notch signal inhibition and Notch1 knockdown enhanced adipogenesis of 3T3-L1 preadipocytes. N1+/− mice showed impaired glucose and insulin tolerance with downregulation of IRS-1 and GLUT4 in WAT after high-fat diet. Taken together, our results suggest that haploinsufficiency of Notch1 promotes fat accumulation and adipogenesis and provides a mechanistic link between Notch signaling and development of metabolic syndrome.
The Penn State Protein Ladder system for inexpensive protein molecular weight markers
Authors: Santilli Ryan T. , Williamson John E. , Shibata Yoshitaka , Sowers Rosalie P. , Fleischman Andrew N. , Tan Song
Published: August 2021

We have created the Penn State Protein Ladder system to produce protein molecular weight markers easily and inexpensively (less than a penny a lane). The system includes plasmids which express 10, 15, 20, 30, 40, 50, 60, 80 and 100 kD proteins inE. coli. Each protein migrates appropriately on SDS-PAGE gels, is expressed at very high levels (10–50 mg per liter of culture), is easy to purify via histidine tags and can be detected directly on Western blots via engineered immunoglobulin binding domains. We have also constructed plasmids to express 150 and 250 kD proteins. For more efficient production, we have created two polycistronic expression vectors which coexpress the 10, 30, 50, 100 kD proteins or the 20, 40, 60, 80 kD proteins. 50 ml of culture is sufficient to produce 20,000 lanes of individual ladder protein or 3750 lanes of each set of coexpressed ladder proteins. These Penn State Protein Ladder expression plasmids also constitute useful reagents for teaching laboratories to demonstrate recombinant expression inE. coliand affinity protein purification, and to research laboratories desiring positive controls for recombinant protein expression and purification.
Metabolic, structural, and proteomic changes in Candida albicans cells induced by the protein-carbohydrate fraction of Dendrobaena veneta coelomic fluid
Authors: Fiołka Marta J. , Czaplewska Paulina , Wójcik-Mieszawska Sylwia , Lewandowska Aleksandra , Lewtak Kinga , Sofińska-Chmiel Weronika , Buchwald Tomasz
Published: August 2021

The isolated protein-polysaccharide fraction (AAF) from the coelomic fluid of Dendrobaena veneta earthworm shows effective activity against Candida albicans yeast. Fungal cells of the clinical strain after incubation with the active fraction were characterized by disturbed cell division and different morphological forms due to the inability to separate the cells from each other. Staining of the cells with acridine orange revealed a change in the pH of the AAF-treated cells. It was observed that, after the AAF treatment, the mitochondrial DNA migrated towards the nuclear DNA, whereupon both merged into a single nuclear structure, which preceded the apoptotic process. Cells with a large nucleus were imaged with the scanning electron cryomicroscopy (Cryo-SEM) technique, while enlarged mitochondria and the degeneration of cell structures were shown by transmission electron microscopy (TEM). The loss of the correct cell shape and cell wall integrity was visualized by both the TEM and SEM techniques. Mass spectrometry and relative quantitative SWATH MS analysis were used to determine the reaction of the C. albicans proteome to the components of the AAF fraction. AAF was observed to influence the expression of mitochondrial and oxidative stress proteins. The oxidative stress in C. albicans cells caused by the action of AAF was demonstrated by fluorescence microscopy, proteomic methods, and XPS spectroscopy. The secondary structure of AAF proteins was characterized by Raman spectroscopy. Analysis of the elemental composition of AAF confirmed the homogeneity of the preparation. The observed action of AAF, which targets not only the cell wall but also the mitochondria, makes the preparation a potential antifungal drug killing the cells of the C. albicans pathogen through apoptosis.
RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues
Authors: Li Manci , Schwabenlander Marc D. , Rowden Gage R. , Schefers Jeremy M. , Jennelle Christopher S. , Carstensen Michelle , Seelig Davis , Larsen Peter A.
Published: August 2021

Chronic wasting disease (CWD) is a prion disease circulating in wild and farmed cervid populations throughout North America (United States and Canada), Europe (Finland, Norway, Sweden), and South Korea. CWD is a long-term threat to all cervid populations and to cervid hunting heritage, with the potential to cause substantial economic losses across multiple sectors. In North America, hunting and farming industries focused on the processing and consumption of white-tailed deer (WTD) venison are particularly vulnerable to CWD prion contamination, as millions of WTD are consumed annually. Real-time quaking-induced conversion (RT-QuIC) is a highly sensitive assay amplifying misfolded CWD prions in vitro and has facilitated CWD prion detection in a variety of tissues and excreta. To date, no study has comprehensively examined CWD prion content across bulk skeletal muscle tissues harvested from individual CWD infected WTD. Here, we use RT-QuIC to characterize prion-seeding activity in a variety of skeletal muscles from both wild and farmed CWD-positive WTD. We successfully detected CWD prions in muscles commonly used for consumption (e.g., backstrap, tenderloin, etc.) as well as within tongue and neck samples of WTD. Our results suggest that CWD prions are distributed across the skeletal muscles of infected WTD. We posit that RT-QuIC will be a useful tool for monitoring CWD prions in venison and that the method (with additional protocol optimization and high-throughput functionality) could be used to reduce and/or prevent CWD prions from entering animal and human food chains.
Anatomy of Cowper’s gland in humans suggesting a secretion and emission mechanism facilitated by cooperation of striated and smooth muscles
Authors: Muro Satoru , Suriyut Janyaruk , Akita Keiichi
Published: August 2021

This study presents the detailed anatomy of the Cowper’s gland in humans. Elucidating the mechanism of secretion and emission of the Cowper’s gland requires analysis of the muscles around the Cowper’s gland. We hypothesized that the Cowper’s gland involves not only smooth muscle but also the striated muscles of the pelvic floor. Here, we provide comprehensive and three-dimensional anatomy of the Cowper’s gland and its surrounding structures, which overcomes the current local and planar understanding. In this study, seven male corpses of body donors were used to conduct macroscopic anatomy, histology, and three-dimensional reconstruction. The Cowper’s gland was surrounded laterally and posterosuperiorly by striated and smooth muscles, respectively. The striated muscle bundle was connected from the superficial transverse perineal muscle, levator ani, and external anal sphincter to the external urethral sphincter (rhabdosphincter). The smooth muscle was part of the deep transverse perineal muscle and entered between the bilateral Cowper’s glands and lobules. Our findings indicate that the secretion and emission of the Cowper’s gland in humans are carried out through the cooperation of striated and smooth muscles.
Long noncoding RNA landscapes specific to benign and malignant thyroid neoplasms of distinct histological subtypes
Authors: Yakushina Valentina D. , Strelnikov Vladimir V. , Tanas Alexander S. , Lavrov Alexander V.
Published: August 2021

The main types of thyroid neoplasms, follicular adenoma (FA), follicular thyroid carcinoma (FTC), classical and follicular variants of papillary carcinoma (clPTC and fvPTC), and anaplastic thyroid carcinoma (ATC), differ in prognosis, progression rate and metastatic behaviour. Specific patterns of lncRNAs involved in the development of clinical and morphological features can be presumed. LncRNA landscapes within distinct benign and malignant histological variants of thyroid neoplasms were not investigated. The aim of the study was to discover long noncoding RNA landscapes common and specific to major benign and malignant histological subtypes of thyroid neoplasms. LncRNA expression in FA, FTC, fvPTC, clPTC and ATC was analysed with comprehensive microarray and RNA-Seq datasets. Putative biological functions were evaluated via enrichment analysis of coexpressed coding genes. In the results, lncRNAs common and specific to FTC, clPTC, fvPTC, and ATC were identified. The discovered lncRNAs are putatively involved in L1CAM interactions, namely, pre-mRNA processing (lncRNAs specific to FTC); PCP/CE and WNT pathways (lncRNAs specific to fvPTC); extracellular matrix organization (lncRNAs specific to clPTC); and the cell cycle (lncRNAs specific to ATC). Known oncogenic and suppressor lncRNAs (RMST, CRNDE, SLC26A4-AS1, NR2F1-AS1, and LINC00511) were aberrantly expressed in thyroid carcinomas. These findings enhance the understanding of lncRNAs in the development of subtype-specific features in thyroid cancer.
Longitudinal analysis of antibody decay in convalescent COVID-19 patients
Authors: Xia Weiming , Li Mingfei , Wang Ying , Kazis Lewis E. , Berlo Kim , Melikechi Noureddine , Chiklis Gregory R.
Published: August 2021

Determining the sustainability of antibodies targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for predicting immune response against the Coronavirus disease 2019 (COVID-19). To quantify the antibody decay rates among the varying levels of anti-nucleocapsid (anti-N) Immunoglobulin G (IgG) in convalescent COVID-19 patients and estimate the length of time they maintained SARS-CoV-2 specific antibodies, we have collected longitudinal blood samples from 943 patients over the course of seven months after their initial detection of SARS-CoV-2 virus by RT-PCR. Anti-N IgG levels were then quantified in these blood samples. The primary study outcome was the comparison of antibody decay rates from convalescent patients with high or low initial levels of antibodies using a mixed linear model. Additional measures include the length of time that patients maintain sustainable levels of anti-N IgG. Antibody quantification of blood samples donated by the same subject multiple times shows a gradual decrease of IgG levels to the cutoff index level of 1.4 signal/cut-off (S/C) on the Abbott Architect SARS-CoV-2 IgG test. In addition, this study shows that antibody reduction rate is dependent on initial IgG levels, and patients with initial IgG levels above 3 S/C show a significant 1.68-fold faster reduction rate compared to those with initial IgG levels below 3 S/C. For a majority of the donors naturally occurring anti-N antibodies were detected above the threshold for only four months after infection with SARS-CoV-2. This study is clinically important for the prediction of immune response capacity in COVID-19 patients.
Numerical investigation of effects of incisor angle on production of sibilant /s/
Authors: Lu HsuehJui , Yoshinaga Tsukasa , Li ChungGang , Nozaki Kazunori , Iida Akiyoshi , Tsubokura Makoto
Published: August 2021

The effects of the inclination angle of the incisor on the speech production of the fricative consonant /s/ was investigated using an implicit compressible flow solver. The hierarchical structure grid was applied to reduce the grid generation time for the vocal tract geometry. The airflow and sound during the pronunciation of /s/ were simulated using the adaptively switched time stepping scheme, and the angle of the incisor in the vocal tract was changed from normal position up to 30°. The results showed that increasing the incisor angle affected the flow configuration and moved the location of the high turbulence intensity region thereby decreased the amplitudes of the sound in the frequency range from 8 to 12 kHz. Performing the Fourier transform on the velocity fluctuation, we found that the position of large magnitudes of the velocity at 10 kHz shifted toward the lip outlet when the incisor angle was increased. In addition, separate acoustic simulations showed that the shift in the potential sound source position decreased the far-field sound amplitudes above 8 kHz. These results provide the underlying insights necessary to design dental prostheses for the production of sibilant fricatives.
Secretome screening reveals immunomodulating functions of IFNα-7, PAP and GDF-7 on regulatory T-cells
Authors: Ding Mei , Malhotra Rajneesh , Ottosson Tomas , Lundqvist Magnus , Mebrahtu Aman , Brengdahl Johan , Gehrmann Ulf , Bäck Elisabeth , Ross-Thriepland Douglas , Isaksson Ida , Magnusson Björn , Sachsenmeier Kris F. , Tegel Hanna , Hober Sophia , Uhlén Mathias , Mayr Lorenz M. , Davies Rick , Rockberg Johan , Schiavone Lovisa Holmberg
Published: August 2021

Regulatory T cells (Tregs) are the key cells regulating peripheral autoreactive T lymphocytes. Tregs exert their function by suppressing effector T cells. Tregs have been shown to play essential roles in the control of a variety of physiological and pathological immune responses. However, Tregs are unstable and can lose the expression of FOXP3 and suppressive functions as a consequence of outer stimuli. Available literature suggests that secreted proteins regulate Treg functional states, such as differentiation, proliferation and suppressive function. Identification of secreted proteins that affect Treg cell function are highly interesting for both therapeutic and diagnostic purposes in either hyperactive or immunosuppressed populations. Here, we report a phenotypic screening of a human secretome library in human Treg cells utilising a high throughput flow cytometry technology. Screening a library of 575 secreted proteins allowed us to identify proteins stabilising or destabilising the Treg phenotype as suggested by changes in expression of Treg marker proteins FOXP3 and/or CTLA4. Four proteins including GDF-7, IL-10, PAP and IFNα-7 were identified as positive regulators that increased FOXP3 and/or CTLA4 expression. PAP is a phosphatase. A catalytic-dead version of the protein did not induce an increase in FOXP3 expression. Ten interferon proteins were identified as negative regulators that reduced the expression of both CTLA4 and FOXP3, without affecting cell viability. A transcriptomics analysis supported the differential effect on Tregs of IFNα-7 versus other IFNα proteins, indicating differences in JAK/STAT signaling. A conformational model experiment confirmed a tenfold reduction in IFNAR-mediated ISG transcription for IFNα-7 compared to IFNα-10. This further strengthened the theory of a shift in downstream messaging upon external stimulation. As a summary, we have identified four positive regulators of FOXP3 and/or CTLA4 expression. Further exploration of these Treg modulators and their method of action has the potential to aid the discovery of novel therapies for both autoimmune and infectious diseases as well as for cancer.
The effects of feeding and starvation on antioxidant defence, fatty acid composition and lipid peroxidation in reared Oncorhynchus mykiss fry
Authors: Zengin Hatayi
Published: August 2021

The effects of feeding and starvation have been studied with respect to oxidative stress and enzymatic antioxidant activities in the whole body of 4 cm rainbow trout fry Oncorhynchus mykiss (Walbaum 1792). The experiment was conducted for 28 days. The selected biomarkers for the study were determined, including non-enzymic scavengers glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) contents and a number of enzymes are known to have major antioxidant activity, such as activities of süperoksit dismutaz (SOD), catalase (CAT), glutatyon peroksidaz (GSHpx), glutatyon Redüktaz (GR) and Glutatyon-S-Transferaz (GST). There is an endogenous cellular glutathione pool which consists of two forms of glutathione, i.e. the GSH and the GSSG. Oxidative damage was measured by the formation of MDA as an indication of lipid peroxidation. The activities of SOD in 14th and 28th day and the activity of CAT in 14th day were increased significantly during the 28 days of starvation. GSHpx and GR activities in starved fry decreased significantly in 28th day. GST activity in all starved fry showed the most significant increases the period of 28 days starving. The highest ΣSFA (Total Saturated Fatty Acid) content was obtained from 28 day starved fry. In starved fry, there was an apparent preference in utilization of C18:1n-9 than in the fed fry. In both starved and fed fry, C16:1n-7 was preferentially kept during the same period. Fry kept 28 days under starvation conditions exhausted C15:0, C17:0, C18:3n-6, C22:0, C24:0. They utilized less C20:5n-3 acid and conserved strongly C22:6n-3 acid. Concentrations of C20:5n-3, C22:5n-3, C22:6n-3 and total n-3 fatty acids significantly increased and C18:3n-3 significantly decreased in the whole body of starved fry during starvation period. A significant increase in the concentrations of C22:5n-3 and C22:6n-3 was determined in the fed fries in the last 2 weeks. Fat-soluble vitamins, cholesterol, stigmasterol and β-sitosterol levels were also determined in the same period of O. mykiss fry.
A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma
Authors: Liu Yang , Wu Qiuhong , Fan Xuejiao , Li Wen , Li Xiaogang , Zhu Hui , Zhou Qinghua , Yu Jinming
Published: August 2021

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.
Preparation of siRNA–PLGA/Fabʹ–PLGA mixed micellar system with target cell-specific recognition
Authors: Hazekawa Mai , Nishinakagawa Takuya , Mori Takeshi , Yoshida Miyako , Uchida Takahiro , Ishibashi Daisuke
Published: August 2021

Small interfering RNAs (siRNAs) are susceptible to nucleases and degrade quickly in vivo. Moreover, siRNAs demonstrate poor cellular uptake and cannot cross the cell membrane because of its polyanionic characteristics. To overcome these challenges, an intelligent gene delivery system that protects siRNAs from nucleases and facilitates siRNA cellular uptake is required. We previously reported the potential of siRNA-poly(d,l-lactic-co-glycolic acid; PLGA) micelles as an effective siRNA delivery tool in a murine peritoneal dissemination model by local injection. However, there was no effective formulation for siRNA delivery to target cells via intravenous injection. This study aimed to prepare siRNA–PLGA/Fabʹ–PLGA mixed micelles for siRNA delivery to target floating cells and evaluate its formulation in vitro. As the target siRNA protein in CEMx174, CyclinB1 levels were significantly reduced when siRNA–PLGA/Fabʹ–PLGA mixed micelles were added to cells compared with siRNA–PLGA micelles. siRNA–PLGA/Fabʹ–PLGA mixed micelles have high cell permeability and high target cell accumulation by endocytosis because flow cytometry detected labeling micelles in target cells. This study supports siRNA–PLGA/Fabʹ–PLGA mixed micelles as an effective siRNA delivery tool. This formulation can be administered systemically in dosage form against target cells, including cancer metastasis or blood cancer.
Reusable surface amplified nanobiosensor for the sub PFU/mL level detection of airborne virus
Authors: Shin Junghyun , Kim Hyeong Rae , Bae Pan Kee , Yoo Haneul , Kim Jeongsu , Choi Yoonji , Kang Aeyeon , Yun Wan S. , Shin Yong Beom , Hwang Jungho , Hong Seunghun
Published: August 2021

We developed a reusable surface-amplified nanobiosensor for monitoring airborne viruses with a sub-PFU/mL level detection limit. Here, sandwich structures consisted of magnetic particles functionalized with antibodies, target viruses, and alkaline phosphatases (ALPs) were formed, and they were magnetically concentrated on Ni patterns near an electrochemical sensor transducer. Then, the electrical signals from electrochemical markers generated by ALPs were measured with the sensor transducer, enabling highly-sensitive virus detection. The sandwich structures in the used sensor chip could be removed by applying an external magnetic field, and we could reuse the sensor transducer chip. As a proof of concepts, the repeated detection of airborne influenza virus using a single sensor chip was demonstrated with a detection limit down to a sub-PFU/mL level. Using a single reusable sensor transducer chip, the hemagglutinin (HA) of influenza A (H1N1) virus with different concentrations were measured down to 10 aM level. Importantly, our sensor chip exhibited reliable sensing signals even after more than 18 times of the repeated HA sensing measurements. Furthermore, airborne influenza viruses collected from the air could be measured down to 0.01 PFU/mL level. Interestingly, the detailed quantitative analysis of the measurement results revealed the degradation of HA proteins on the viruses after the air exposure. Considering the ultrasensitivity and reusability of our sensors, it can provide a powerful tool to help preventing epidemics by airborne pathogens in the future.
Calcium silicate-based cements cause environmental stiffness and show diverse potential to induce osteogenesis in human osteoblastic cells
Authors: Santiago Marcos Coelho , Gomes-Cornélio Ana Lívia , de Oliveira Laudimar Alves , Tanomaru-Filho Mario , Salles Loise Pedrosa
Published: August 2021

Calcium silicate-based cements differ markedly in their radiopacifiers and the presence of calcium sulfate, aluminates, carbonates and other components that can affect their biological properties. This study aimed to compare the biological properties of six calcium silicate cements in human osteoblastic cell culture (Saos-2 cells): Bio-C Repair (Bio-C), PBS HP (PBS-HP), Biodentine (Biodentine), MTA Repair HP (MTA-HP), NeoMTA Plus (NeoMTA-P), and ProRoot MTA (ProRoot). After exposure to these materials, the cells were analyzed by MTT, wound healing, cell migration, and alkaline phosphatase activity (ALP) assays, real-time PCR (qPCR) analysis of the osteogenesis markers (osteocalcin or bone gamma-carboxyglutamate protein, BGLAP; alkaline phosphatase, ALPL; bone sialoprotein or secreted phosphoprotein 1, BNSP), and alizarin red staining (ARS). Curiously, the migration rates were low 24–48 h after exposure to the materials, despite the cells showing ideal rates of viability. The advanced and intermediate cell differentiation markers BGLAP and BNSP were overexpressed in the Bio-C, MTA-HP, and ProRoot groups. Only the Biodentine group showed ALPL overexpression, a marker of initial differentiation. However, the enzymatic activity was high in all groups except Biodentine. The mineralization area was significantly large in the NeoMTA-P, ProRoot, PBS-HP, MTA-HP, and Bio-C groups. The results showed that cellular environmental stiffness, which impairs cell mobility and diverse patterns of osteogenesis marker expression, is a consequence of cement exposure. Environmental stiffness indicates chemical and physical stimuli in the microenvironment; for instance, the release of cement compounds contributes to calcium phosphate matrix formation with diverse stiffnesses, which could be essential or detrimental for the migration and differentiation of osteoblastic cells. Cells exposed to Bio-C, PBS-HP, ProRoot, NeoMTA-P, and MTA-HP seemed to enter the advanced or intermediate differentiation phases early, which is indicative of the diverse potential of cements to induce osteogenesis. Cements that quickly stimulate osteoblast differentiation may be ideal for reparative and regenerative purposes since they promptly lead to dentin or bone deposition.
Optimizing cerebral perfusion and hemodynamics during cardiopulmonary bypass through cannula design combining in silico, in vitro and in vivo input
Authors: Hugenroth Kristin , Borchardt Ralf , Ritter Philine , Groß-Hardt Sascha , Meyns Bart , Verbelen Tom , Steinseifer Ulrich , Kaufmann Tim A. S. , Engelmann Ulrich M.
Published: August 2021

Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.
Recovery of phosphorus as soluble phosphates from aqueous solutions using chitosan hydrogel sorbents
Authors: Jóźwiak Tomasz , Kowalkowska Agata , Filipkowska Urszula , Struk-Sokołowska Joanna , Bolozan Ludmila , Gache Luminita , Ilie Marius
Published: August 2021

This manuscript presents new method of phosphorus recovery from aqueous solutions in a convenient form of readily-soluble phosphates using chitosan hydrogels. Non-modified chitosan hydrogel granules (CHs) and chitosan hydrogel granules crosslinked with epichlorohydrin (CHs-ECH) served as orthophosphate ion carriers. The developed method was based on cyclic sorption/desorption of orthophosphates, with desorption performed in each cycle to the same solution (the concentrate). The concentrations of orthophosphates obtained in the concentrates depended on, i.a., sorbent type, sorption pH, source solution concentration, and desorption pH. Phosphorus concentrations in the concentrates were even 30 times higher than these in the source solutions. The maximum concentrate concentrations reached 332.0 mg P-PO4/L for CHs and 971.6 mg P-PO4/L for CHs-ECH. The experimental series with CHs-ECH were characterized by higher concentrations of the obtained concentrate, however the concentrates were also more contaminated with Cl− and Na+ ions compared to series with CHs. The high content of chlorine and sodium ions in the concentrates was also favored by the low pH of sorption (pH < 4) and very high pH of desorption (pH > 12) in the cycles. After concentrate evaporation, phosphorus content in the sediment ranged from 17.81 to 19.83% for CHs and from 16.04 to 17.74% for CHs-ECH.
In vivo metabolizable branched poly(ester amide) based on inositol and amino acids as a drug nanocarrier for cancer therapy
Authors: Yuan Qijuan , Wang Li , Huang Jun , Zhao Wei , Wu Jun
Published: August 2021

Amino acid-based poly(ester amide) (PEA) has been utilized for various biomedical applications due to its tunable mechanical properties, good biocompatibility, and biodegradability.
Temperature rise of LaNi5-based alloys by hydrogen adsorption
Authors: Zhou Nanxu , Yamaguchi Masakuni , Miyaoka Hiroki , Kojima Yoshitsugu
Published: August 2021

The temperature rise of AB5-type alloy by H2 absorption was limited by their critical temperatures (Tc). The relation between H2 desorption temperatures of metal hydrides at atmospheric pressure and their Tc followed the Guldberg rule Tc = 3/2 Ts.
Three-dimensional covalent organic frameworks based on a π-conjugated tetrahedral node
Authors: Wu Miaomiao , Shan Zhen , Wang Jinjian , Gu Zhangjie , Wu Xiaowei , Xu Bingqing , Zhang Gen
Published: August 2021

Three fully conjugated 3D COFs with dia and pts topologies have been constructed from saddle-like cyclooctatetrathiophene (COTh) as π-conjugated tetrahedral node.
Hydrosilylative reduction of primary amides to primary amines catalyzed by a terminal [Ni–OH] complex
Authors: Pandey Pragati , Bera Jitendra K.
Published: August 2021

A terminal [Ni–OH] complex, stabilized by triflamide-tethered NHC ligands, selectively catalyses the deoxygenative reduction of primary amides to primary amines using phenylsilane as the reductant, without proceeding via a nitrile intermediate.
A novel ratiometric MALDI-MS quantitation strategy for alkaline phosphatase activity with a homogeneous reaction and a tunable dynamic range
Authors: Ma Rong-Na , Zhang Min , Hu Chao-Long , Pan Hui-Jing , Si Lei , Wang Huaisheng
Published: August 2021

A unique ratiometric MALDI-MS strategy based on a homogeneous enzymatic cleavage triggered double-signal output was designed for the convenient and reliable quantitation of alkaline phosphatase with a tunable dynamic range.
Metastable growth and infrared spectra of CuB2O4:Ni single crystals
Authors: Moshkina Evgeniya , Molokeev Maxim , Belskaya Nadejda , Nemtsev Ivan , Molchanova Anastasiia , Boldyrev Kirill
Published: August 2021

The formation of CuB2O4:Ni crystals in fluxes based on Li2WO4–Bi2O3–WO3 has been studied. A distinctive feature of the used flux growing mode is the metastable nature of nucleation. IR reflection and transmission spectra are presented.
A quantitative multiscale perspective on primary olefin formation from methanol
Authors: Omojola Toyin , Logsdail Andrew J. , van Veen André C. , Nastase Stefan Adrian F.
Published: August 2021

Our quantitative multi-scale perspective on the formation of the first C–C bond decouples the adsorption, desorption, reaction, and mobility of species and provides new insights that could guide rational catalyst design.
Subtle structure matters: boosting surface-directed photoelectron transfer via the introduction of specific monovalent oxygen vacancies in TiO2
Authors: Li Fei , Wang Dong , Gong Xue-Qing
Published: August 2021

A distinct role of monovalent Ov in boosting surface-directed electron-transfer was identified, highlighting the importance of subtle defect structures in photocatalysis.
Expression of concern: Preparation and characterization of nano-sized Pt–Ru/C catalysts and their superior catalytic activities for methanol and ethanol oxidation
Authors: Simpson Anna
Published: August 2021

Expression of concern for ‘Preparation and characterization of nano-sized Pt–Ru/C catalysts and their superior catalytic activities for methanol and ethanol oxidation’ by Selda Şen et al., Phys. Chem. Chem. Phys., 2011, 13, 6784–6792, DOI: 10.1039/C1CP20064J.
Constructing Ni-based confinement catalysts with advanced performances toward the CO2reforming of CH4: state-of-the-art review and perspectives
Authors: Xue Yingying , Xu Leilei , Chen Mindong , Wu Cai-e , Cheng Ge , Wang Ning , Hu Xun
Published: August 2021

The concept of Ni-based confinement catalysts has been proposed and developed to address the challenge of the thermal sintering of metallic Ni active sites during CRM by the space and/or lattice confinement effects.