bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, attenuates anxiety-related behavior in a rodent post-traumatic stress disorder model
Authors: Yamanashi Takehiko , Iwata Masaaki , Shibushita Midori , Tsunetomi Kyohei , Nagata Mayu , Kajitani Naofumi , Miura Akihiko , Matsuo Ryoichi , Nishiguchi Tsuyoshi , Kato Takahiro A. , Setoyama Daiki , Shirayama Yukihiko , Watanabe Ken , Shinozaki Gen , Kaneko Koichi
Published: December 2020

Accumulating evidence suggests that elevated inflammation contributes to the pathophysiology of post-traumatic stress disorder (PTSD) and that anti-inflammatory drugs might be a new treatment strategy for PTSD. It has been reported that beta-hydroxybutyrate (BHB), one of the main ketone bodies produced, can have an anti-inflammatory and antidepressant effect. Here, we investigated the potential anti-anxiety and anti-inflammatory effects of BHB using a rodent PTSD model, induced by single prolonged stress (SPS). Male, Sprague–Dawley rats were employed in this study. Repeated administration of BHB attenuated SPS-induced anxiety-related behaviors evaluated by the elevated plus maze test. SPS increased the serum levels of TNF-α and IL-1β. In contrast, BHB administration partially attenuated the increase of serum TNF-α. These findings demonstrate that BHB exerts its anxiolytic effects, possibly by inhibiting systemic TNF-α. Hence, BHB may be a novel therapeutic candidate for the treatment of PTSD.
Systematic review and meta-analysis of the associations of vegan and vegetarian diets with inflammatory biomarkers
Authors: Menzel Juliane , Jabakhanji Afraa , Biemann Ronald , Mai Knut , Abraham Klaus , Weikert Cornelia
Published: December 2020

Plant-based diets like vegetarian or vegan diets might influence circulating levels of inflammatory biomarkers, thereby reducing the risk of chronic diseases. This systematic review and meta-analysis aimed to investigate the associations of veganism and vegetarianism with circulating inflammatory biomarkers in comparison to omnivores. Literature search was conducted in Pubmed and EMBASE until April 2020 and mean differences of biomarkers were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1 receptor antagonist (IL-1 RA), tumor necrosis factor-alpha (TNF-ɑ), E-selectin, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), adiponectin, omentin-1 and resistin. Of initially identified 1073 publications, 21 cross-sectional studies met the inclusion criteria and were included in the systematic review and meta-analysis. Vegan diet was associated with lower levels of CRP compared to omnivores [mean difference − 0.54 mg/l, 95%-CI: − 0.79 to − 0.28, p < 0.0001]. This association was less pronounced in vegetarians [mean difference − 0.25 mg/l, 95%-CI: − 0.49 to 0.00, p = 0.05]. In patients with impaired kidney function, the association between vegetarian nutrition and CRP was much stronger with − 3.91 mg/l (95%-CI: − 5.23 to − 2.60; p < 0.0001). No substantial effects were observed for all other inflammatory biomarkers. Despite strong associations between CRP and a vegan or vegetarian diet were seen, further research is needed, as most inflammatory biomarkers were investigated only in single studies so far.
Production of the antimicrobial compound tetrabromopyrrole and the Pseudomonas quinolone system precursor, 2-heptyl-4-quinolone, by a novel marine species Pseudoalteromonas galatheae sp. nov.
Authors: Paulsen Sara Skøtt , Isbrandt Thomas , Kirkegaard Markus , Buijs Yannick , Strube Mikael Lenz , Sonnenschein Eva C. , Larsen Thomas O. , Gram Lone
Published: December 2020

Novel antimicrobials are urgently needed due to the rapid spread of antibiotic resistant bacteria. In a genome-wide analysis of Pseudoalteromonas strains, one strain (S4498) was noticed due to its potent antibiotic activity. It did not produce the yellow antimicrobial pigment bromoalterochromide, which was produced by several related type strains with which it shared less than 95% average nucleotide identity. Also, it produced a sweet-smelling volatile not observed from other strains. Mining the genome of strain S4498 using the secondary metabolite prediction tool antiSMASH led to eight biosynthetic gene clusters with no homology to known compounds, and synteny analyses revealed that the yellow pigment bromoalterochromide was likely lost during evolution. Metabolome profiling of strain S4498 using HPLC-HRMS analyses revealed marked differences to the type strains. In particular, a series of quinolones known as pseudanes were identified and verified by NMR. The characteristic odor of the strain was linked to the pseudanes. The highly halogenated compound tetrabromopyrrole was detected as the major antibacterial component by bioassay-guided fractionation. Taken together, the polyphasic analysis demonstrates that strain S4498 belongs to a novel species within the genus Pseudoalteromonas, and we propose the name Pseudoalteromonas galatheae sp. nov. (type strain S4498T = NCIMB 15250T = LMG 31599T).
Cell–cell fusion of mesenchymal cells with distinct differentiations triggers genomic and transcriptomic remodelling toward tumour aggressiveness
Authors: Delespaul Lucile , Gélabert Caroline , Lesluyes Tom , Le Guellec Sophie , Pérot Gaëlle , Leroy Laura , Baud Jessica , Merle Candice , Lartigue Lydia , Chibon Frédéric
Published: December 2020

Cell–cell fusion is a physiological process that is hijacked during oncogenesis and promotes tumour evolution. The main known impact of cell fusion is to promote the formation of metastatic hybrid cells following fusion between mobile leucocytes and proliferating tumour cells. We show here that cell fusion between immortalized myoblasts and transformed fibroblasts, through genomic instability and expression of a specific transcriptomic profile, leads to emergence of hybrid cells acquiring dissemination properties. This is associated with acquisition of clonogenic ability by fused cells. In addition, by inheriting parental properties, hybrid tumours were found to mimic the histological characteristics of a specific histotype of sarcomas: undifferentiated pleomorphic sarcomas with incomplete muscular differentiation. This finding suggests that cell fusion, as macroevolution event, favours specific sarcoma development according to the differentiation lineage of parent cells.
Improved mitochondrial function in salmon (Salmo salar) following high temperature acclimation suggests that there are cracks in the proverbial ‘ceiling’
Authors: Gerber Lucie , Clow Kathy A. , Mark Felix C. , Gamperl Anthony K.
Published: December 2020

Mitochondrial function can provide key insights into how fish will respond to climate change, due to its important role in heart performance, energy metabolism and oxidative stress. However, whether warm acclimation can maintain or improve the energetic status of the fish heart when exposed to short-term heat stress is not well understood. We acclimated Atlantic salmon, a highly aerobic eurythermal species, to 12 and 20 °C, then measured cardiac mitochondrial functionality and integrity at 20 °C and at 24, 26 and 28 °C (this species’ critical thermal maximum ± 2 °C). Acclimation to 20 °C vs. 12 °C enhanced many aspects of mitochondrial respiratory capacity and efficiency up to 24 °C, and preserved outer mitochondrial membrane integrity up to 26 °C. Further, reactive oxygen species (ROS) production was dramatically decreased at all temperatures. These data suggest that salmon acclimated to ‘normal’ maximum summer temperatures are capable of surviving all but the most extreme ocean heat waves, and that there is no ‘tradeoff’ in heart mitochondrial function when Atlantic salmon are acclimated to high temperatures (i.e., increased oxidative phosphorylation does not result in heightened ROS production). This study suggests that fish species may show quite different acclimatory responses when exposed to prolonged high temperatures, and thus, susceptibility to climate warming.
Region-specific Foxp2 deletions in cortex, striatum or cerebellum cannot explain vocalization deficits observed in spontaneous global knockouts
Authors: Urbanus Bastiaan H. A. , Peter Saša , Fisher Simon E. , De Zeeuw Chris I.
Published: December 2020

FOXP2 has been identified as a gene related to speech in humans, based on rare mutations that yield significant impairments in speech at the level of both motor performance and language comprehension. Disruptions of the murine orthologue Foxp2 in mouse pups have been shown to interfere with production of ultrasonic vocalizations (USVs). However, it remains unclear which structures are responsible for these deficits. Here, we show that conditional knockout mice with selective Foxp2 deletions targeting the cerebral cortex, striatum or cerebellum, three key sites of motor control with robust neural gene expression, do not recapture the profile of pup USV deficits observed in mice with global disruptions of this gene. Moreover, we observed that global Foxp2 knockout pups show substantive reductions in USV production as well as an overproduction of short broadband noise “clicks”, which was not present in the brain region-specific knockouts. These data indicate that deficits of Foxp2 expression in the cortex, striatum or cerebellum cannot solely explain the disrupted vocalization behaviours in global Foxp2 knockouts. Our findings raise the possibility that the impact of Foxp2 disruption on USV is mediated at least in part by effects of this gene on the anatomical prerequisites for vocalizing.
Ultrafast carbothermal reduction of silica to silicon using a CO2 laser beam
Authors: Maeng Seok-Ho , Lee Hakju , Park Min Soo , Park Suhyun , Jeong Jaeki , Kim Seongbeom
Published: December 2020

We report the extraction of silicon via a carbothermal reduction process using a CO2 laser beam as a heat source. The surface of a mixture of silica and carbon black powder became brown after laser beam irradiation for a few tens of seconds, and clear peaks of crystalline silicon were observed by Raman shift measurements, confirming the successful carbothermal reduction of silica. The influence of process parameters, including the laser beam intensity, radiation time, nitrogen gas flow in a reaction chamber, and the molar ratios of silica/carbon black of the mixture, on the carbothermal reduction process is explained in detail.
High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents
Authors: Behbehani Haider , Aryan Fatemah A. , Dawood Kamal M. , Ibrahim Hamada Mohamed
Published: December 2020

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.
MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting
Authors: Straub Tamara , Nave Julia , Bouvain Pascal , Akbarzadeh Mohammad , Dasa Siva Sai Krishna , Kistner Julia , Ding Zhaoping , Marzoq Aseel , Stepanow Stefanie , Becker Katrin , Hesse Julia , Köhrer Karl , Flögel Ulrich , Ahmadian Mohammad R. , French Brent A. , Schrader Jürgen , Temme Sebastian
Published: December 2020

After myocardial infarction (MI), epicardial cells reactivate their embryonic program, proliferate and migrate into the damaged tissue to differentiate into fibroblasts, endothelial cells and, if adequately stimulated, to cardiomyocytes. Targeting epicardium-derived stromal cells (EpiSC) by specific ligands might enable the direct imaging of EpiSCs after MI to better understand their biology, but also may permit the cell-specific delivery of small molecules to improve the post-MI healing process. Therefore, the aim of this study was to identify specific peptides by phage display screening to enable EpiSC specific cargo delivery by active targeting. To this end, we utilized a sequential panning of a phage library on cultured rat EpiSCs and then subtracted phage that nonspecifically bound blood immune cells. EpiSC specific phage were analyzed by deep sequencing and bioinformatics analysis to identify a total of 78 300 ± 31 900 different, EpiSC-specific, peptide insertion sequences. Flow cytometry of the five most highly abundant peptides (EP1, -2, –3, -7 or EP9) showed strong binding to EpiSCs but not to blood immune cells. The best binding properties were found for EP9 which was further studied by surface plasmon resonance (SPR). SPR revealed rapid and stable association of EpiSCs with EP9. As a negative control, THP-1 monocytes did not associate with EP9. Coupling of EP9 to perfluorocarbon nanoemulsions (PFCs) resulted in the efficient delivery of 19F cargo to EpiSCs and enabled their visualization by 19F MRI. Moreover, active targeting of EpiSCs by EP9-labelled PFCs was able to outcompete the strong phagocytic uptake of PFCs by circulating monocytes. In summary, we have identified a 7-mer peptide, (EP9) that binds to EpiSCs with high affinity and specificity. This peptide can be used to deliver small molecule cargos such as contrast agents to permit future in vivo tracking of EpiSCs by molecular imaging and to transfer small pharmaceutical molecules to modulate the biological activity of EpiSCs.
Surface functionalisation of poly-APO-b-polyol ester cross-linked copolymers as core–shell nanoparticles for targeted breast cancer therapy
Authors: Tajau Rida , Rohani Rosiah , Abdul Hamid Siti Selina , Adam Zainah , Mohd Janib Siti Najila , Salleh Mek Zah
Published: December 2020

Polymeric nanoparticles (NPs) are commonly used as nanocarriers for drug delivery, whereby their sizes can be altered for a more efficient delivery of therapeutic active agents with better efficacy. In this work, cross-linked copolymers acted as core–shell NPs from acrylated palm olein (APO) with polyol ester were synthesized via gamma radiation-induced reversible addition-fragmentation chain transfer (RAFT) polymerisation. The particle diameter of the copolymerised poly(APO-b-polyol ester) core–shell NPs was found to be less than 300 nm, have a low molecular weight (MW) of around 24 kDa, and showed a controlled MW distribution of a narrow polydispersity index (PDI) of 1.01. These properties were particularly crucial for further use in designing targeted NPs, with inclusion of peptide for the targeted delivery of paclitaxel. Moreover, the characterisation of the synthesised NPs using Fourier Transform-Infrared (FTIR) and Neutron Magnetic Resonance (NMR) analyses confirmed the possession of biodegradable hydrolysed ester in its chemical structures. Therefore, it can be concluded that the synthesised NPs produced may potentially contribute to better development of a nano-structured drug delivery system for breast cancer therapy.
Microchemical analysis of Leonardo da Vinci’s lead white paints reveals knowledge and control over pigment scattering properties
Authors: Gonzalez Victor , Hageraats Selwin , Wallez Gilles , Eveno Myriam , Ravaud Elisabeth , Réfrégiers Matthieu , Thoury Mathieu , Menu Michel , Gourier Didier
Published: December 2020

Leonardo da Vinci (1452–1519) is a key artistic and scientific figure of the Renaissance. He is renowned for his science of art, taking advantage of his acute observations of nature to achieve striking pictorial results. This study describes the analysis of an exceptional sample from one of Leonardo’s final masterpieces: The Virgin and Child with St. Anne (Musée du Louvre, Paris, France). The sample was analyzed at the microscale by synchrotron-based hyperspectral photoluminescence imaging and high-angular X-ray diffraction. The results demonstrate Leonardo’s use of two subtypes of lead white pigment, thus revealing how he must have possessed a precise knowledge of his materials; carefully selecting them according to the aesthetical results he aimed at achieving in each painting. This work provides insights on how Leonardo obtained these grades of pigment and proposes new clues regarding the optical and/or working properties he may have tried to achieve.
Noninvasive and portable stroke type discrimination and progress monitoring based on a multichannel microwave transmitting–receiving system
Authors: Xu Jia , Chen Jingbo , Yu Wei , Zhang Haisheng , Wang Feng , Zhuang Wei , Yang Jun , Bai Zelin , Xu Lin , Sun Jian , Jin Gui , Nian Yongjian , Qin Mingxin , Chen Mingsheng
Published: December 2020

The hemorrhagic and the ischemic types of stroke have similar symptoms in the early stage, but their treatments are completely different. The timely and effective discrimination of the two types of stroke can considerable improve the patients' prognosis. In this paper, a 16-channel and noncontact microwave-based stroke detection system was proposed and demonstrated for the potential differentiation of the hemorrhagic and the ischemic stroke. In animal experiments, 10 rabbits were divided into two groups. One group consisted of five cerebral hemorrhage models, and the other group consisted of five cerebral ischemia models. The two groups were monitored by the system to obtain the Euclidean distance transform value of microwave scattering parameters caused by pathological changes in the brain. The support vector machine was used to identify the type and the severity of the stroke. Based on the experiment, a discrimination accuracy of 96% between hemorrhage and ischemia stroke was achieved. Furthermore, the potential of monitoring the progress of intracerebral hemorrhage or ischemia was evaluated. The discrimination of different degrees of intracerebral hemorrhage achieved 86.7% accuracy, and the discrimination of different severities of ischemia achieved 94% accuracy. Compared with that with multiple channels, the discrimination accuracy of the stroke severity with a single channel was only 50% for the intracerebral hemorrhage and ischemia stroke. The study showed that the microwave-based stroke detection system can effectively distinguish between the cerebral hemorrhage and the cerebral ischemia models. This system is very promising for the prehospital identification of the stroke type due to its low cost, noninvasiveness, and ease of operation.
Cascade synthesis and optoelectronic applications of intermediate bandgap Cu3VSe4 nanosheets
Authors: Liu Mimi , Lai Cheng-Yu , Zhang Meng , Radu Daniela R.
Published: December 2020

Two-dimensional (2D) ternary materials recently generated interest in optoelectronics and energy-related applications, alongside their binary counterparts. To date, only a few naturally occurring layered 2D ternary materials have been explored. The plethora of benefits owed to reduced dimensionality prompted exploration of expanding non-layered ternary chalcogenides into the 2D realm. This work presents a templating method that uses 2D transition metal dichalcogenides as initiators to be converted into the corresponding ternary chalcogenide upon addition of copper, via a solution-phase synthesis, conducted in high boiling point solvents. The process starts with preparation of VSe2 nanosheets, which are next converted into Cu3VSe4 sulvanite nanosheets (NSs) which retain the 2D geometry while presenting an X-ray diffraction pattern identical with the one for the bulk Cu3VSe4. Both the scanning electron microscopy and transmission microscopy electron microscopy show the presence of quasi-2D morphology. Recent studies of the sulfur-containing sulvanite Cu3VS4 highlight the presence of an intermediate bandgap, associated with enhanced photovoltaic (PV) performance. The Cu3VSe4 nanosheets reported herein exhibit multiple UV–Vis absorption peaks, related to the intermediate bandgaps similar to Cu3VS4 and Cu3VSe4 nanocrystals. To test the potential of Cu3VSe4 NSs as an absorber for solar photovoltaic devices, Cu3VSe4 NSs thin-films deposited on FTO were subjected to photoelectrochemical testing, showing p-type behavior and stable photocurrents of up to ~ 0.036 mA/cm2. The photocurrent shows a ninefold increase in comparison to reported performance of Cu3VSe4 nanocrystals. This proves that quasi-2D sulvanite nanosheets are amenable to thin-film deposition and could show superior PV performance in comparison to nanocrystal thin-films. The obtained electrical impedance spectroscopy signal of the Cu3VSe4 NSs-FTO based electrochemical cell fits an equivalent circuit with the circuit elements of solution resistance (Rs), charge-transfer resistance (Rct), double-layer capacitance (Cdl), and Warburg impedance (W). The estimated charge transfer resistance value of 300 Ω cm2 obtained from the Nyquist plot provides an insight into the rate of charge transfer on the electrode/electrolyte interface.
A protein of the metallo-hydrolase/oxidoreductase superfamily with both beta-lactamase and ribonuclease activity is linked with translation in giant viruses
Authors: Colson Philippe , Pinault Lucile , Azza Said , Armstrong Nicholas , Chabriere Eric , La Scola Bernard , Pontarotti Pierre , Raoult Didier
Published: December 2020

Proteins with a metallo-beta-lactamase (MBL) fold have been largely studied in bacteria in the framework of resistance to beta-lactams, but their spectrum of activities is broader. We show here that the giant Tupanvirus also encodes a MBL fold-protein that has orthologs in other giant viruses, a deep phylogenetic root and is clustered with tRNases. This protein is significantly associated with translation components in giant viruses. After expression in Escherichia coli, it was found to hydrolyse nitrocefin, a beta-lactam, and penicillin G. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, the tupanvirus MBL fold-protein was not active on single- or double-stranded DNA, but degraded RNAs from bacteria and Acanthamoeba castellanii, the tupanvirus amoebal host. This activity was not neutralized by sulbactam. Overall, our results still broaden the host range of MBL fold-proteins, showing dual beta-lactamase/nuclease activities in giant viruses.
Defining intraspecific conservation units in the endemic Cuban Rock Iguanas (Cyclura nubila nubila)
Authors: Shaney Kyle J. , Diaz-Ramirez L. Grisell , Espindola Sayra , Castañeda-Rico Susette , Berovides-Álvarez Vicente , Vázquez-Domínguez Ella
Published: December 2020

Defining conservation units is an important step in species management and requires interpretation of the genetic diversity and ecological function of the taxon being considered. We used the endemic Cuban Rock Iguanas (Cyclura nubila nubila) as a model to highlight this challenge and examined patterns of its intraspecific genetic diversity across Cuba. We evaluated nuclear (microsatellite loci) and mitochondrial diversity across eight populations from the island and its off-shore cays, and applied the population genetics results for assignment of Management Unit (MU) status and Evolutionary Significant Units (ESUs) based on phylogeographic and time of divergence information. We identified at least six distinct Cuban Rock Iguana MUs, encompassing demographically isolated and genetically differentiated populations across Cuba, most with low effective population size, declining populations, and with high risk of inbreeding and genetic drift. Hence, each MU should be considered of urgent conservation priority. Given the key ecological seed dispersal role ofC. n. nubila, the disappearance of any MU could trigger the loss of local ecological functional diversity and major negative impacts on their ecosystems. Two divergent ESUs were also identified, exhibiting an historical east–west geographic separation on Cuba. Based on a Caribbean phylogeographic assessment, our findings strengthen the conclusion that all geographically and evolutionarily differentiatedCycluraspecies and subspecies across the archipelago warrant ESU distinction.
FKBPL is associated with metabolic parameters and is a novel determinant of cardiovascular disease
Authors: Januszewski Andrzej S. , Watson Chris J. , O’Neill Vikki , McDonald Kenneth , Ledwidge Mark , Robson Tracy , Jenkins Alicia J. , Keech Anthony C. , McClements Lana
Published: December 2020

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.
Gene expression profiling in neuronal cells identifies a different type of transcriptome modulated by NF-Y
Authors: Yamanaka Tomoyuki , Miyazaki Haruko , Tosaki Asako , Maity Sankar N. , Shimogori Tomomi , Hattori Nobutaka , Nukina Nobuyuki
Published: December 2020

A heterotrimeric transcription factor NF-Y is crucial for cell-cycle progression in various types of cells. In contrast, studies using NF-YA knockout mice have unveiled its essential role in endoplasmic reticulum (ER) homeostasis in neuronal cells. However, whether NF-Y modulates a different transcriptome to mediate distinct cellular functions remains obscure. Here, we knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and mouse brain striatal cells, and performed gene expression profiling. We found that down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. This contrasts with the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that the transcriptomic difference was not correlated with DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration could be involved in this cell type-specific gene modulation.
The antipredator benefits of postural camouflage in peppered moth caterpillars
Authors: Rowland Hannah M. , Burriss Robert P. , Skelhorn John
Published: December 2020

Camouflage is the most common form of antipredator defense, and is a textbook example of natural selection. How animals’ appearances prevent detection or recognition is well studied, but the role of prey behavior has received much less attention. Here we report a series of experiments with twig-mimicking larvae of the American peppered mothBiston betulariathat test the long-held view that prey have evolved postures that enhance their camouflage, and establish how food availability and ambient temperature affect these postures. We found that predators took longer to attack larvae that were resting in a twig-like posture than larvae resting flat against a branch. Larvae that were chilled or food restricted (manipulations intended to energetically stress larvae) adopted a less twig-like posture than larvae that were fed ad libitum. Our findings provide clear evidence that animals gain antipredator benefits from postural camouflage, and suggest that benefits may come at an energetic cost that animals are unwilling or unable to pay under some conditions.
Composition rules of Ni-base single crystal superalloys and its influence on creep properties via a cluster formula approach
Authors: Chen Chen , Wang Qing , Dong Chuang , Zhang Yu , Dong Honggang
Published: December 2020

The present work investigated the composition evolution of the TMS series of Ni-base single crystal (SC) superalloys in light of the cluster formula approach systematically. The cluster formula of SC superalloys could be expressed with $${[}\overline{{{\text{Al}}}} {-} \overline{{{\text{Ni}}}} 12{](}\overline{{{\text{Al}}}} {, }\overline{{{\text{Cr}}}} {)}m$$

[

Al
¯

-

Ni
¯

12

]
(

Al
¯

,

Cr
¯

)
m

, in which all the alloying elements were classified into three groups, Al series ($$\overline{{{\text{Al}}}}$$

Al
¯

), Cr series ($$\overline{{{\text{Cr}}}}$$

Cr
¯

), and Ni series ($$\overline{{{\text{Ni}}}}$$

Ni
¯

). It was found that the total atom number (Z) of the cluster formula units for TMS series of superalloys varies from Z ~ 17 to Z ~ 15.5, and then to Z ~ 16 with the alloy development from the 1st to the 6th generation, in which the superalloys with prominent creep resistance possess an ideal cluster formula of $${[}\overline{{{\text{Al}}}} {-} \overline{{{\text{Ni}}}} 12{](}\overline{{{\text{Al}}}} 1.5\overline{{{\text{Cr}}}} 1.5{)}$$

[

Al
¯

-

Ni
¯

12

]
(

Al
¯

1.5

Cr
¯

1.5
)

with Z = 16. Similar tendency of composition evolution also appears in the PWA and CMSX series of SC superalloys. Typical TMS series of superalloys with prominent creep properties generally exhibit a moderate lattice misfit of γ/γ′ which could render alloys with appropriate particle size of cuboidal γ′ precipitates to acquire a maximum strength increment by precipitation strengthening mechanism. More importantly, the relationship between the lattice misfit (δ) of γ/γ′ and the creep rupture lifetime (tr) of superalloys was then established, showing a linear correlation in the form of lgtr–lg|δ|3/2 at both conditions of 900 °C/392 MPa and 1100 °C/137 MPa. Combined with the lattice misfit, the cluster formula approach would provide a new way to modify or optimize the compositions of Ni-base superalloys for further improvement of creep property.
Sleep apnea and diabetes mellitus are independently associated with cardiovascular events and hospitalization for heart failure after coronary artery bypass grafting
Authors: Aung Aye-Thandar , Koo Chieh-Yang , Tam Wilson W. , Chen Zhengfeng , Kristanto William , Sim Hui-Wen , Kojodjojo Pipin , Kofidis Theodoros , Lee Chi-Hang
Published: December 2020

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (−), sleep apnea (−) DM (+), and sleep apnea (−) DM (−) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (−), 13% in the sleep apnea (−) DM (+), and 5% in the sleep apnea (−) DM (−) groups. Using sleep apnea (−) DM (−) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7–6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0–52.3; p < 0.001). Sleep apnea and DM have independent effects on the prognosis of patients undergoing CABG.

Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.
Genomic recombination events may reveal the evolution of coronavirus and the origin of SARS-CoV-2
Authors: Zhu Zhenglin , Meng Kaiwen , Meng Geng
Published: December 2020

To trace the evolution of coronaviruses and reveal the possible origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), we collected and thoroughly analyzed 29,452 publicly available coronavirus genomes, including 26,312 genomes of SARS-CoV-2 strains. We observed coronavirus recombination events among different hosts including 3 independent recombination events with statistical significance between some isolates from humans, bats and pangolins. Consistent with previous records, we also detected putative recombination between strains similar or related to Bat-CoV-RaTG13 and Pangolin-CoV-2019. The putative recombination region is located inside the receptor-binding domain (RBD) of the spike glycoprotein (S protein), which may represent the origin of SARS-CoV-2. Population genetic analyses provide estimates suggesting that the putative introduced genetic sequence within the RBD is undergoing directional evolution. This may result in the adaptation of the virus to hosts. Unsurprisingly, we found that the putative recombination region in S protein was highly diverse among strains from bats. Bats harbor numerous coronavirus subclades that frequently participate in recombination events with human coronavirus. Therefore, bats may provide a pool of genetic diversity for the origin of SARS-CoV-2.
Comparison of the amniotic fluid and fetal urine peptidome for biomarker discovery in renal developmental disease
Authors: Fédou Camille , Breuil Benjamin , Golovko Igor , Decramer Stéphane , Magalhães Pedro , Muller Françoise , Dreux Sophie , Zürbig Petra , Klein Julie , Schanstra Joost P. , Buffin-Meyer Bénédicte
Published: December 2020

Production of amniotic fluid (AF) is view as predominately driven by excretion of fetal urine (FU). However, the origin of AF peptides, often considered as potential biomarkers of developmental diseases, has never been investigated. Here, we evaluated the FU origin of AF peptides and if the AF peptide content can be used as a surrogate of FU. The abundance of endogenous peptides was analyzed by capillary electrophoresis coupled to mass spectrometry in 216 AF and 64 FU samples. A total of 2668 and 3257 peptides was found in AF and FU respectively. The AF peptidome largely overlapped with the FU peptidome, ranging from 54% in the second pregnancy trimester to 65% in the third trimester. Examination of a subset of 16 paired AF and FU samples revealed that 67 peptides displayed a significant positively correlated abundance in AF and FU, strongly suggesting that their presence in AF was directly associated to FU excretion. As proof-of-concept we showed that measuring the AF abundance of these 67 peptides of FU origin allowed prediction of postnatal renal survival in fetuses with posterior urethral valves. These results demonstrate that the AF peptidome can be considered as a good surrogate of the FU peptidome.
Functionalization of amyloid fibrils via the Bri2 BRICHOS domain
Authors: Biverstål Henrik , Kumar Rakesh , Schellhaus Anna Katharina , Sarr Médoune , Dantuma Nico P. , Abelein Axel , Johansson Jan
Published: December 2020

Amyloid fibrils are mechanically robust and partly resistant to proteolytic degradation, making them potential candidates for scaffold materials in cell culture, tissue engineering, drug delivery and other applications. Such applications of amyloids would benefit from the possibility to functionalize the fibrils, for example by adding growth factors or cell attachment sites. The BRICHOS domain is found in a family of human proteins that harbor particularly amyloid-prone regions and can reduce aggregation as well as toxicity of several different amyloidogenic peptides. Recombinant human (rh) BRICHOS domains have been shown to bind to the surface of amyloid-β (Aβ) fibrils by immune electron microscopy. Here we produce fusion proteins between mCherry and rh Bri2 BRICHOS and show that they can bind to different amyloid fibrils with retained fluorescence of mCherry in vitro as well as in cultured cells. This suggests a “generic” ability of the BRICHOS domain to bind fibrillar surfaces that can be used to synthesize amyloid decorated with different protein functionalities.
Enhanced neutrophil apoptosis accompanying myeloperoxidase release during hemodialysis
Authors: Fukushi Taro , Yamamoto Tae , Yoshida Mai , Fujikura Emi , Miyazaki Mariko , Nakayama Masaaki
Published: December 2020

Biocompatibility of hemodialysis (HD) systems have been considerably improved. However, mortality and morbidity rates of patients have remained high, raising questions regarding the biocompatibility of current systems. In the present study, 70 patients on regular HD (51 males; mean age, 63 years; median duration of HD, 18 months) with high-performance membrane (polysulfone, 77%; polymethylmethacrylate, 23%) at Tohoku University Hospital were examined. Blood samples before and after HD, were subjected to measure apoptosis cells of white blood cells, plasma levels of the following molecules: myeloperoxidase (MPO), pentraxin 3 (PTX3), angiogenin, complements, and 17 cytokines. The main findings were as follows: significant decreases in leukocyte counts by dialysis, significant increases in apoptosis-positive leukocytes by dialysis (neutrophils and monocytes), and significant decrease in plasma angiogenin accompanying increase in plasma MPO and PTX3 levels, with no or only marginal changes in plasma pro-inflammatory cytokine levels and complement products by dialysis. The findings underlined the unsolved issue of bio-incompatibility of HD systems, and suggest the possible pathology of neutrophil apoptosis accompanying MPO release for the development of microinflammation in patients on HD.
Negative play contagion in calves
Authors: Größbacher Verena , Lawrence Alistair B. , Winckler Christoph , Špinka Marek
Published: December 2020

Play is a strong outwardly directed, emotional behaviour and can contagiously spread between individuals. It has been suggested that high-playing animals could ‘seed’ play in others, spreading positive affective states. Despite the current interest in play contagion there has been no previous attempt to measure the strength of the play contagion effect. The calf (Bos taurus) is ideal for testing the strength of play contagion as play in calves is strongly related to energy intake from milk. We manipulated play in calves through their milk allowances and housed the calves in uniform groups all on the same milk allowance (high = UHigh or low = ULow) or in mixed groups with calves in the same group receiving either a high (= MHigh) or low (= MLow) milk allowance. We measured locomotor play using accelerometers on two consecutive days when calves were four and eight weeks old, in order to study play contagion over a protracted developmental window. We anticipated that differences in the level of play contagion between treatment groups would result in difference in the play levels observed in the MLow and ULow individuals. Contrary to our expectations we found that spontaneous play was suppressed in the high-milk calves housed in mixed groups (MHigh), in comparison to calves housed with group mates all receiving high-milk (UHigh). These results are the first to quantify a negative play contagion effect, particularly in a situation of long-term contact, and may suggest that negative contagion has a stronger effect on play behaviour than positive contagion.
Acromioclavicular and sternoclavicular joint dislocations indicate severe concomitant thoracic and upper extremity injuries in severely injured patients
Authors: Bakir M. Sinan , Lefering Rolf , Haralambiev Lyubomir , Kim Simon , Ekkernkamp Axel , Gümbel Denis , Schulz-Drost Stefan
Published: December 2020

Preliminary studies show that clavicle fractures (CF) are known as an indicator in the severely injured for overall injury severity that are associated with relevant concomitant injuries in the thorax and upper extremity. In this regard, little data is available for the rarer injuries of the sternoclavicular and acromioclavicular joints (SCJ and ACJ, respectively). Our study will answer whether clavicular joint injuries (CJI), by analogy, have a similar relevance for the severely injured. We performed an analysis from the TraumaRegister DGU (TR-DGU). The inclusion criterion was an Injury Severity Score (ISS) of at least 16. In the TR-DGU, the CJI were registered as one entity. The CJI group was compared with the CF and control groups (those without any clavicular injuries). Concomitant injuries were distinguished using the Abbreviated Injury Scale according to their severity. The inclusion criteria were met by n = 114,595 patients. In the case of CJI, n = 1228 patients (1.1%) were found to be less severely injured than the controls in terms of overall injury severity. Compared to the CF group (n = 12,030; 10.5%) with higher ISS than the controls, CJI cannot be assumed as an indicator for a more severe trauma; however, CF can. Concomitant injuries were more common for severe thoracic and moderate upper extremity injuries than other body parts for CJI. This finding confirms our hypothesis that CJI could be an indicator of further specific severe concomitant injuries. Despite the rather lower relevance of the CJI in the cohort of severely injured with regard to the overall injury severity, these injuries have their importance in relation to the indicator effect for thoracic concomitant injuries and concomitant injuries of the upper extremity. A limitation is the collective registration of SCJ and ACJ injuries as one entity in the TR-DGU. A distorted picture of the CJI in favor of ACJ injuries could arise from the significantly higher incidence of the ACJ dislocation compared to the SCJ. Therefore, these two injury entities should be recorded separately in the future, and prospective studies should be carried out in order to derive a standardized treatment strategy for the care of severely injured with the respective CJI.
Increased long-term health risks attributable to select volatile organic compounds in residential indoor air in southeast Louisiana
Authors: Wickliffe Jeffrey K. , Stock Thomas H. , Howard Jessi L. , Frahm Ericka , Simon-Friedt Bridget R. , Montgomery Krista , Wilson Mark J. , Lichtveld Maureen Y. , Harville Emily
Published: December 2020

Volatile organic compounds (VOCs) represent a broad class of chemicals, many of which can be found in indoor air including residential indoor air. VOCs derive from a variety of sources including cleaning products, cooking practices, fragrances and fresheners, hobbies and at-home work behaviors. This study examined residential indoor air in homes (n = 99) in southeast Louisiana using passive organic vapor monitors and gas chromatography/mass spectrometry to determine if select VOCs were present, at what concentrations, and if those posed any potential long-term health risks. Twenty-nine VOCs were targeted in cross-sectional analyses using a 48-h sampling period. Twelve VOCs were detected in most of the homes sampled including xylenes, pinenes, benzene, toluene, ethylbenzene, hexane, pentane, chloroform, and carbon tetrachloride. Concentrations of alkanes and BTEX compounds were highly correlated (Spearman’s r > 0.63, p < 0.0001). Using health risk measures (i.e. reference concentrations [RfCs] and inhalation unit risks [IURs]) available from the USEPA non-cancer risk assessments and cancer risk assessments were developed for some of these VOCs. Alkanes and BTEX compounds likely come from the same indoor source(s). Using existing health standards published by the USEPA, no unacceptable non-cancer risks were evident except under extremely high concentrations. Lifetime cancer risks, on the other hand, may well be considered unacceptable for chloroform and benzene (upper IUR) and for the combination of chloroform, benzene, and carbon tetrachloride. These exceeded a 1 in 10,000 cancer risk threshold in 35–50% of our simulations. Further study of residential indoor air in low-income women’s homes in this area is needed. Including a larger number of VOCs may reveal yet more potential health risks.
Characterization of regional meniscal cell and chondrocyte phenotypes and chondrogenic differentiation with histological analysis in osteoarthritic donor-matched tissues
Authors: Wang Jingsong , Roberts Sally , Kuiper Jan Herman , Zhang Weiguo , Garcia John , Cui Zhanfeng , Wright Karina
Published: December 2020

Meniscus degeneration is closely related to the progression of knee osteoarthritis (OA). However, there is currently a lack of quantitative and objective metrics to assess OA meniscal cell phenotypes. In this study we investigated the phenotypic markers and chondrogenic potency of avascular and vascular meniscal cells and chondrocytes from medial OA knee joints (n = 10). Flow cytometry results showed that a significantly greater percentage of meniscal cells were positive for CD49b, CD49c and CD166 compared to donor-matched chondrocytes after 14 days in monolayer culture. The integrins, CD49b and CD29, were expressed at a significantly higher level on avascular meniscal cells derived from tissues with a more degenerated inner border than non-degenerate menisci, suggesting that the integrin family may play an important role in meniscus OA pathology. Collagen fibres arranged in a “tree-like” formation within the meniscus appeared to have less blood vessels associated with them in the vascular region of the most degenerate menisci, which may indicate that such structures are involved in the pathological process. We have demonstrated that meniscal cells derived from the lateral meniscus in medial OA patients have chondrogenic capacity in vitro and hence could represent a potential cell source to consider for meniscus tissue engineering.