bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusobacterium nucleatum: a novel immune modulator in breast cancer?
Authors: Little Alexa , Tangney Mark , Tunney Michael M. , Buckley Niamh E.
Published: April 2023

Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacteriumFusobacterium nucleatumin breast cancer.F. nucleatumis enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests thatF. nucleatummodulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, andF. nucleatumspecifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence ofF. nucleatumin the development and treatment of breast cancer.
Legibility and Burden: Representing Immigrants’ Winnable Claims to Humanitarian Status
Authors: Yu Lilly
Published: April 2023

In the United States, legal representation increases the likelihood that undocumented immigrants win legal claims. Yet private attorneys are expensive, and free and low-cost attorneys are scarce. How do legal services providers make representation decisions when demand outweighs capacity? Drawing on interviews with attorneys in thirty-eight nonprofit organizations who represent affirmative, humanitarian status seekers, this article describes how lawyers face pressure to represent winnable cases. Attorneys assess case winnability in two ways. First, attorneys aim to maximize clients’ cultural legibility as “deserving immigrant victims.” Simultaneously, attorneys aim to minimize case representation burden by considering the time, resources, and expertise needed to represent each claim. Attorneys assess both cultural legibility and case burden at every stage of the representation process (client selection, attorney assignment, relief pursual, and application production). In doing so, attorneys try to represent clients as the most deserving of status and in the most efficient way. These findings extend past research on attorneys’ selection processes that occur well before a client’s application is filed with the federal immigration bureaucracy. By highlighting how attorneys’ constrained decisions exacerbate legal stratification, these findings complicate calls for an immigrant legal inclusion strategy that depends on the labor of attorneys rather than on changes to the state’s demands on immigrants themselves.
PERFORMING AUSTRALIAN ELECTROACOUSTIC WORKS FOR THE PAETZOLD CONTRABASS RECORDER
Authors: Blackburn Alana
Published: April 2023

A striking instrumental design innovation in recent years has been the development of the Paetzold ‘square bass’ bass recorders, sparking interest among performers and composers to develop a new approach to contemporary performance practice and electroacoustic composition. This article examines two works by Australian composers that have been performed by the author. Both pieces are written for the Paetzold contrabass recorder in F, applying its unique sound palette within different compositional approaches and structures. The electroacoustic works surveyed also use a fixed media soundscape drawing on varying levels of gesture and improvisation from the live performer(s). The works present different relationships between the pre-recorded soundscape and the contrabass recorder and provide an opportunity for the performer to experiment with the large range of sounds possible. This article also serves as a summary of tools, sounds and techniques for composers interested in writing for the instrument.
PARALLELS AND DIVERGENCES: THREE CASE STUDIES IN THE MUSIC OF MICHAEL HERSCH
Authors: Fox Christopher
Published: April 2023

This article focuses on three recent works by the American composer Michael Hersch: the script of storms (2018), for soprano and orchestra, the chamber opera Poppaea (2019) and the 11-hour trilogy of works that have the overall title sew me into a shroud of leaves (2001–16). A discussion of aspects of these three scores will consider Hersch's deployment of a stylistically consistent musical language, his involvement with the work of the writers Fawsi Karim and Christopher Middleton and his articulation of often substantial spans of time.
Identifying factors that shape whether digital food marketing appeals to children
Authors: Valderrama Camilo E , Olstad Dana Lee , Lee Yun Yun , Lee Joon
Published: April 2023

Objective:

Children are frequently exposed to unhealthy food marketing on digital media. This marketing contains features that often appeal to children, such as cartoons or bold colours. Additional factors can also shape whether marketing appeals to children. In this study, in order to assess the most important predictors of child appeal in digital food marketing, we used machine learning to examine how marketing techniques and children’s socio-demographic characteristics, weight, height, BMI, frequency of screen use and dietary intake influence whether marketing instances appeal to children.

Design:

We conducted a pilot study with thirty-nine children. Children were divided into thirteen groups, in which they evaluated whether food marketing instances appealed to them. Children’s agreement was measured using Fleiss’ kappa and the S score. Text, labels, objects and logos extracted from the ads were combined with children’s variables to build four machine-learning models to identify the most important predictors of child appeal.

Setting:

Households in Calgary, Alberta, Canada.

Participants:

39 children aged 6–12 years.

Results:

Agreement between children was low. The models indicated that the most important predictors of child appeal were the text and logos embedded in the food marketing instances. Other important predictors included children’s consumption of vegetables and soda, sex and weekly hours of television.

Conclusions:

Text and logos embedded in the food marketing instances were the most important predictors of child appeal. The low agreement among children shows that the extent to which different marketing strategies appeal to children varies.
Environmental Controls of Size Distribution of Modern Planktonic Foraminifera in the Tropical Indian Ocean
Authors: Adebayo Michael B. , Bolton Clara T. , Marchant Ross , Bassinot Franck , Conrod Sandrine , de Garidel‐Thoron Thibault
Published: April 2023

Paleoceanographic studies often rely on abundance changes in microfossil species, with little consideration for characteristics such as organism size, which may also be related to environmental changes. Using a tropical Indian Ocean (TIO) core‐top data set, we test the Optimum size‐hypothesis (OSH), investigating whether relative abundance or environmental variables are better descriptors of planktonic foraminifera species' optimum conditions. We also investigate the environmental drivers of whole‐assemblage planktonic foraminiferal test size variation in the TIO. We use an automated imaging and sorting system (MiSo) to identify planktonic foraminiferal species, analyze their morphology, and quantify fragmentation rate using machine learning techniques. Machine model accuracy is confirmed by comparison with human classifiers (97% accuracy). Data for 33 environmental parameters were extracted from modern databases and, through exploratory factor analysis and regression models, we explore relationships between planktonic foraminiferal size and oceanographic parameters in the TIO. Results show that the size frequency distribution of most planktonic foraminifera species is unimodal, with some larger species showing multimodal distributions. Assemblage size95/5 (95th percentile size) increases with increasing species diversity, and this is attributed to vertical niche separation induced by thermal stratification. Our test for the OSH reveals that relative abundance is not a good predictor of species' optima and within‐species size95/5 response to environmental parameters is species‐specific, with parameters related to carbonate ion concentration, temperature, and salinity being primary drivers. At the species and assemblage levels, our analyses indicate that carbonate ion concentration and temperature play important roles in determining size trends in TIO planktonic foraminifera.
The Effect of Zooplankton on the Distributions of Dimethyl Sulfide and Dimethylsulfoniopropionate in the Bohai and Yellow Seas
Authors: Yu Juan , Wang Su , Lai Jing‐Guang , Tian Ji‐Yuan , Zhang Hao‐Quan , Yang Gui‐Peng , Chen Rong
Published: April 2023

Dimethyl sulfide (DMS) and its precursor dimethylsulfoniopropionate (DMSP) are ubiquitous sulfur compounds in the ocean. DMS is emitted into the atmosphere and has potential climatic effects. The distributions of DMS and DMSP are affected by various biological factors (i.e., bacterial catabolism and phytoplankton and zooplankton community composition). The horizontal and vertical distributions of DMSP, DMSP lyase activity (DLA), DMS, and the abundances of bacteria, DMSP‐consuming bacteria, dimethyl sulfoxide‐consuming bacteria, and picophytoplankton were investigated in the Bohai Sea (BS) and Yellow Sea (YS) during autumn 2020. DLA was significantly correlated with chlorophyll a, DMS, and dissolved DMSP concentrations. Our data show that bacteria Clade_I SAR11 was a significant contributor to DLA. A dilution experiment indicated that the highest microzooplankton grazing rate coincided with the highest DMS concentration and DMS production rate. A proportion of 16%–62% of the DMSPt was converted to DMS in the dilution experiment. Copepods dominated the mesozooplankton community. Calanus sinicus was the predominant copepod in the BS and YS. C. sinicus grazing stimulated DMS production. DMS concentration increased 299% after C. sinicus grazing on physically broken algal cells for 48 hr. These results will help with a better understanding of the control of DMS and DMSP concentrations by zooplankton and the DMS release mechanisms that occur through zooplankton grazing.
Integrating planar photonics for multi-beam generation and atomic clock packaging on chip
Authors: Ropp Chad , Zhu Wenqi , Yulaev Alexander , Westly Daron , Simelgor Gregory , Rakholia Akash , Lunden William , Sheredy Dan , Boyd Martin M. , Papp Scott , Agrawal Amit , Aksyuk Vladimir
Published: April 2023

The commercialization of atomic technologies requires replacing laboratory-scale laser setups with compact and manufacturable optical platforms. Complex arrangements of free-space beams can be generated on chip through a combination of integrated photonics and metasurface optics. In this work, we combine these two technologies using flip-chip bonding and demonstrate an integrated optical architecture for realizing a compact strontium atomic clock. Our planar design includes twelve beams in two co-aligned magneto-optical traps. These beams are directed above the chip to intersect at a central location with diameters as large as 1 cm. Our design also includes two co-propagating beams at lattice and clock wavelengths. These beams emit collinearly and vertically to probe the center of the magneto-optical trap, where they will have diameters of ≈100 µm. With these devices we demonstrate that our integrated photonic platform is scalable to an arbitrary number of beams, each with different wavelengths, geometries, and polarizations.
Detector-grade perovskite single-crystal wafers via stress-free gel-confined solution growth targeting high-resolution ionizing radiation detection
Authors: Song Yilong , Wang Lixiang , Shi Yongqiang , Bi Weihui , Chen Jianwu , Hao Mingwei , Wang Anran , Yang Xueying , Sun Yuan , Yu Fan , Li Liansheng , Fang Yanjun , Yang Deren , Dong Qingfeng
Published: April 2023

Solution-processed organic‒inorganic halide perovskite (OIHP) single crystals (SCs) have demonstrated great potential in ionizing radiation detection due to their outstanding charge transport properties and low-cost preparation. However, the energy resolution (ER) and stability of OIHP detectors still lag far behind those of melt-grown inorganic perovskite and commercial CdZnTe counterparts due to the absence of detector-grade high-quality OIHP SCs. Here, we reveal that the crystallinity and uniformity of OIHP SCs are drastically improved by relieving interfacial stress with a facial gel-confined solution growth strategy, thus enabling the direct preparation of large-area detector-grade SC wafers up to 4 cm with drastically suppressed electronic and ionic defects. The resultant radiation detectors show both a small dark current below 1 nA and excellent baseline stability of 4.0 × 10−8 nA cm−1 s−1 V−1, which are rarely realized in OIHP detectors. Consequently, a record high ER of 4.9% at 59.5 keV is achieved under a standard 241Am gamma-ray source with an ultralow operating bias of 5 V, representing the best gamma-ray spectroscopy performance among all solution-processed semiconductor radiation detectors ever reported.
Exploring the nonlinear piezoresistive effect of 4H-SiC and developing MEMS pressure sensors for extreme environments
Authors: Wu Chen , Fang Xudong , Kang Qiang , Fang Ziyan , Wu Junxia , He Hongtao , Zhang Dong , Zhao Libo , Tian Bian , Maeda Ryutaro , Jiang Zhuangde
Published: April 2023

Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from −50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from −50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (−0.067% FS/°C) in the range of −50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H2SO4 and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.
PRMT1 reverts the immune escape of necroptotic colon cancer through RIP3 methylation
Authors: Zhang Lian , He Yujiao , Jiang Yi , Wu Qi , Liu Yanchen , Xie Qingqiang , Zou Yuxiu , Wu Jiaqian , Zhang Chundong , Zhou Zhongjun , Bian Xiu-Wu , Jin Guoxiang
Published: April 2023

Necroptosis plays a double-edged sword role in necroptotic cancer cell death and tumor immune escape. How cancer orchestrates necroptosis with immune escape and tumor progression remains largely unclear. We found that RIP3, the central activator of necroptosis, was methylated by PRMT1 methyltransferase at the amino acid of RIP3 R486 in human and the conserved amino acid R479 in mouse. The methylation of RIP3 by PRMT1 inhibited the interaction of RIP3 with RIP1 to suppress RIP1-RIP3 necrosome complex, thereby blocking RIP3 phosphorylation and necroptosis activation. Moreover, the methylation-deficiency RIP3 mutant promoted necroptosis, immune escape and colon cancer progression due to increasing tumor infiltrated myeloid-derived immune suppressor cells (MDSC), while PRMT1 reverted the immune escape of RIP3 necroptotic colon cancer. Importantly, we generated a RIP3 R486 di-methylation specific antibody (RIP3ADMA). Clinical patient samples analysis revealed that the protein levels of PRMT1 and RIP3ADMA were positively correlated in cancer tissues and both of them predicted the longer patient survival. Our study provides insights into the molecular mechanism of PRMT1-mediated RIP3 methylation in the regulation of necroptosis and colon cancer immunity, as well as reveals PRMT1 and RIP3ADMA as the valuable prognosis markers of colon cancer.
Mn(I)-catalyzed sigmatropic rearrangement of β, γ-unsaturated alcohols
Authors: Yang Can , Zhou Xiaoyu , Shen Lixing , Ke Zhuofeng , Jiang Huanfeng , Zeng Wei
Published: April 2023

Sigmatropic rearrangement provides a versatile strategy to site-selectively reorganize carbon-skeleton with high atom- and step-economy. Herein, we disclose a Mn(I)-catalyzed sigmatropic rearrangement of β, γ-unsaturated alcohols via C-C σ bond activation. A variety of α-aryl-allylic alcohols and α-aryl-propargyl alcohols could undergo in-situ 1,2- or 1,3- sigmatropic rearrangements to allow for converting to complex structural arylethyl- and arylvinyl- carbonyl compounds under a simple catalytic system. More importantly, this catalysis model can be further applied to assemble macrocyclic ketones through bimolecular [2n + 4] coupling-cyclization and monomolecular [n + 1] ring-extension. The presented skeleton rearrangement would be a useful tool complementary to the traditional molecular rearrangement.
Large piezoelectric response in a Jahn-Teller distorted molecular metal halide
Authors: Wang Sasa , Khan Asif Abdullah , Teale Sam , Xu Jian , Parmar Darshan H. , Zhao Ruyan , Grater Luke , Serles Peter , Zou Yu , Filleter Tobin , Seferos Dwight S. , Ban Dayan , Sargent Edward H.
Published: April 2023

Piezoelectric materials convert between mechanical and electrical energy and are a basis for self-powered electronics. Current piezoelectrics exhibit either large charge (d33) or voltage (g33) coefficients but not both simultaneously, and yet the maximum energy density for energy harvesting is determined by the transduction coefficient:d33*g33. In prior piezoelectrics, an increase in polarization usually accompanies a dramatic rise in the dielectric constant, resulting in trade off betweend33andg33. This recognition led us to a design concept: increase polarization through Jahn-Teller lattice distortion and reduce the dielectric constant using a highly confined 0D molecular architecture. With this in mind, we sought to insert a quasi-spherical cation into a Jahn-Teller distorted lattice, increasing the mechanical response for a large piezoelectric coefficient. We implemented this concept by developing EDABCO-CuCl4(EDABCO = N-ethyl-1,4-diazoniabicyclo[2.2.2]octonium), a molecular piezoelectric with ad33of 165 pm/V andg33of ~2110 × 10−3 V m N−1, one that achieved thusly a combined transduction coefficient of 348 × 10−12 m3 J−1. This enables piezoelectric energy harvesting in EDABCO-CuCl4@PVDF (polyvinylidene fluoride) composite film with a peak power density of 43 µW/cm2(at 50 kPa), the highest value reported for mechanical energy harvesters based on heavy-metal-free molecular piezoelectric.
Comparative analysis of dimension reduction methods for cytometry by time-of-flight data
Authors: Wang Kaiwen , Yang Yuqiu , Wu Fangjiang , Song Bing , Wang Xinlei , Wang Tao
Published: April 2023

While experimental and informatic techniques around single cell sequencing (scRNA-seq) are advanced, research around mass cytometry (CyTOF) data analysis has severely lagged behind. CyTOF data are notably different from scRNA-seq data in many aspects. This calls for the evaluation and development of computational methods specific for CyTOF data. Dimension reduction (DR) is one of the critical steps of single cell data analysis. Here, we benchmark the performances of 21 DR methods on 110 real and 425 synthetic CyTOF samples. We find that less well-known methods like SAUCIE, SQuaD-MDS, and scvis are the overall best performers. In particular, SAUCIE and scvis are well balanced, SQuaD-MDS excels at structure preservation, whereas UMAP has great downstream analysis performance. We also find that t-SNE (along with SQuad-MDS/t-SNE Hybrid) possesses the best local structure preservation. Nevertheless, there is a high level of complementarity between these tools, so the choice of method should depend on the underlying data structure and the analytical needs.
Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis
Authors: Houlder E. L. , Costain A. H. , Nambuya I. , Brown S. L. , Koopman J. P. R. , Langenberg M. C. C. , Janse J. J. , Hoogerwerf M. A. , Ridley A. J. L. , Forde-Thomas J. E. , Colombo S. A. P. , Winkel B. M. F. , Galdon A. A. , Hoffmann K. F. , Cook P. C. , Roestenberg M. , Mpairwe H. , MacDonald A. S.
Published: April 2023

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.
Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria
Authors: Shuoker Bashar , Pichler Michael J. , Jin Chunsheng , Sakanaka Hiroka , Wu Haiyang , Gascueña Ana Martínez , Liu Jining , Nielsen Tine Sofie , Holgersson Jan , Nordberg Karlsson Eva , Juge Nathalie , Meier Sebastian , Morth Jens Preben , Karlsson Niclas G. , Abou Hachem Maher
Published: April 2023

The mucolytic human gut microbiota specialist Akkermansia muciniphila is proposed to boost mucin-secretion by the host, thereby being a key player in mucus turnover. Mucin glycan utilization requires the removal of protective caps, notably fucose and sialic acid, but the enzymatic details of this process remain largely unknown. Here, we describe the specificities of ten A. muciniphila glycoside hydrolases, which collectively remove all known sialyl and fucosyl mucin caps including those on double-sulfated epitopes. Structural analyses revealed an unprecedented fucosidase modular arrangement and explained the sialyl T-antigen specificity of a sialidase of a previously unknown family. Cell-attached sialidases and fucosidases displayed mucin-binding and their inhibition abolished growth of A. muciniphila on mucin. Remarkably, neither the sialic acid nor fucose contributed to A. muciniphila growth, but instead promoted butyrate production by co-cultured Clostridia. This study brings unprecedented mechanistic insight into the initiation of mucin O-glycan degradation by A. muciniphila and nutrient sharing between mucus-associated bacteria.
NAD+ repletion with niacin counteracts cancer cachexia
Authors: Beltrà Marc , Pöllänen Noora , Fornelli Claudia , Tonttila Kialiina , Hsu Myriam Y. , Zampieri Sandra , Moletta Lucia , Corrà Samantha , Porporato Paolo E. , Kivelä Riikka , Viscomi Carlo , Sandri Marco , Hulmi Juha J. , Sartori Roberta , Pirinen Eija , Penna Fabio
Published: April 2023

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.
Oral supplementation of nicotinamide riboside alters intestinal microbial composition in rats and mice, but not humans
Authors: Peluso A. Augusto , Lundgaard Agnete T. , Babaei Parizad , Mousovich-Neto Felippe , Rocha Andréa L. , Damgaard Mads V. , Bak Emilie G. , Gnanasekaran Thiyagarajan , Dollerup Ole L. , Trammell Samuel A. J. , Nielsen Thomas S. , Kern Timo , Abild Caroline B. , Sulek Karolina , Ma Tao , Gerhart-Hines Zach , Gillum Matthew P. , Arumugam Manimozhiyan , Ørskov Cathrine , McCloskey Douglas , Jessen Niels , Herrgård Markus J. , Mori Marcelo A. S. , Treebak Jonas T.
Published: April 2023

The gut microbiota impacts systemic levels of multiple metabolites including NAD+precursors through diverse pathways. Nicotinamide riboside (NR) is an NAD+precursor capable of regulating mammalian cellular metabolism. Some bacterial families express the NR-specific transporter,PnuC. We hypothesized that dietary NR supplementation would modify the gut microbiota across intestinal sections. We determined the effects of 12 weeks of NR supplementation on the microbiota composition of intestinal segments of high-fat diet-fed (HFD) rats. We also explored the effects of 12 weeks of NR supplementation on the gut microbiota in humans and mice. In rats, NR reduced fat mass and tended to decrease body weight. Interestingly, NR increased fat and energy absorption but only in HFD-fed rats. Moreover, 16S rRNA gene sequencing analysis of intestinal and fecal samples revealed an increased abundance of species withinErysipelotrichaceaeandRuminococcaceaefamilies in response to NR.PnuC-positive bacterial strains within these families showed an increased growth rate when supplemented with NR. The abundance of species within theLachnospiraceaefamily decreased in response to HFD irrespective of NR. Alpha and beta diversity and bacterial composition of the human fecal microbiota were unaltered by NR, but in mice, the fecal abundance of species withinLachnospiraceaeincreased while abundances ofParasutterellaandBacteroides doreispecies decreased in response to NR. In conclusion, oral NR altered the gut microbiota in rats and mice, but not in humans. In addition, NR attenuated body fat mass gain in rats, and increased fat and energy absorption in the HFD context.
Skeletal muscle gene expression dysregulation in long-term spaceflights and aging is clock-dependent
Authors: Malhan Deeksha , Yalçin Müge , Schoenrock Britt , Blottner Dieter , Relógio Angela
Published: April 2023

The circadian clock regulates cellular and molecular processes in mammals across all tissues including skeletal muscle, one of the largest organs in the human body. Dysregulated circadian rhythms are characteristic of aging and crewed spaceflight, associated with, for example, musculoskeletal atrophy. Molecular insights into spaceflight-related alterations of circadian regulation in skeletal muscle are still missing. Here, we investigated potential functional consequences of clock disruptions on skeletal muscle using published omics datasets obtained from spaceflights and other clock-altering, external (fasting and exercise), or internal (aging) conditions on Earth. Our analysis identified alterations of the clock network and skeletal muscle-associated pathways, as a result of spaceflight duration in mice, which resembles aging-related gene expression changes observed in humans on Earth (e.g., ATF4 downregulation, associated with muscle atrophy). Furthermore, according to our results, external factors such as exercise or fasting lead to molecular changes in the core-clock network, which may compensate for the circadian disruption observed during spaceflights. Thus, maintaining circadian functioning is crucial to ameliorate unphysiological alterations and musculoskeletal atrophy reported among astronauts.
Dopamine facilitates the translation of physical exertion into assessments of effort
Authors: Padmanabhan Purnima , Casamento-Moran Agostina , Kim Aram , Gonzalez Anthony J. , Pantelyat Alexander , Roemmich Ryan T. , Chib Vikram S.
Published: April 2023

Our assessments of effort are critically shaped by experiences of exertion. However, it is unclear how the nervous system transforms physical exertion into assessments of effort. Availability of the neuromodulator dopamine influences features of motor performance and effort-based decision-making. To test dopamine’s role in the translation of effortful exertion into assessments of effort, we had participants with Parkinson’s disease, in dopamine depleted (OFF dopaminergic medication) and elevated (ON dopaminergic medication) states, exert levels of physical exertion and retrospectively assess how much effort they exerted. In a dopamine-depleted state, participants exhibited increased exertion variability and over-reported their levels of exertion, compared to the dopamine-supplemented state. Increased exertion variability was associated with less accurate effort assessment and dopamine had a protective influence on this effect, reducing the extent to which exertion variability corrupted assessments of effort. Our findings provide an account of dopamine’s role in the translation of features of motor performance into judgments of effort, and a potential therapeutic target for the increased sense of effort observed across a range of neurologic and psychiatric conditions.
Regulation of human trophoblast gene expression by endogenous retroviruses
Authors: Frost Jennifer M. , Amante Samuele M. , Okae Hiroaki , Jones Eleri M. , Ashley Brogan , Lewis Rohan M. , Cleal Jane K. , Caley Matthew P. , Arima Takahiro , Maffucci Tania , Branco Miguel R.
Published: April 2023

The placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate genetic variation and affect host gene regulation, may have helped to define species-specific trophoblast gene expression programs. Here we assess the contribution of transposable elements to human trophoblast gene expression as enhancers or promoters. Using epigenomic data from primary human trophoblast and trophoblast stem-cell lines, we identified multiple endogenous retrovirus families with regulatory potential that lie close to genes with preferential expression in trophoblast. These largely primate-specific elements are associated with inter-species gene expression differences and are bound by transcription factors with key roles in placental development. Using genetic editing, we demonstrate that several elements act as transcriptional enhancers of important placental genes, such as CSF1R and PSG5. We also identify an LTR10A element that regulates ENG expression, affecting secretion of soluble endoglin, with potential implications for preeclampsia. Our data show that transposons have made important contributions to human trophoblast gene regulation, and suggest that their activity may affect pregnancy outcomes.
Synthesis of innovative and sustainable gelatin@graphene oxide-crosslinked-zirconium silicate@gelatin nanobiosorbent for effective biosorption of basic fuchsin dye
Authors: Mahmoud Mohamed E. , Nabil Gehan M. , Elsayed Sarah M. , Rashad Amal R.
Published: April 2023

Most dye stuffs and coloring materials are mainly categorized as hazardous pollutants in water effluents due to their nature as non-biodegradable, highly toxic and extremely carcinogenic. For this reason, rapid and efficient eradication of waste dyes from wastewaters before discharging into water streams must be accomplished by an acceptable approach as adsorption technique. Therefore, the present study is aimed and devoted to synthesize a novel nanobiosorbent from three different constituents, gelatin (Gel) as a sustainable natural product, graphene oxide (GO) as an example of highly stable carbonaceous material and zirconium silicate (ZrSiO4) as an example of combined metal oxides for the formation of Gel@GO-F-ZrSiO4@Gel by using formaldehyde (F) as a cross-linkage reagent. Several characterization techniques as FT-IR were employed to identify the incorporated surface reactive Functionalities in Gel@GO-F-ZrSiO4@Gel as –OH, =NH, –NH2, –COOH and C=O, etc. The morphology for particle shape and size of Gel@GO-F-ZrSiO4@Gel were confirmed from the SEM and TEM analyses providing 15.75- 32.79 nm. The surface area was determined by the BET and found to correspond to 219.46 m2 g-1. Biosorptive removal of basic fuchsin (BF) pollutant as an example of a widely applicable dye in various activities was monitored and optimized under the influence of pH (2–10), reaction time (1–30 min), initial BF pollutant concentration (5–100 mg L−1), nanobiosorbent dosage (5–60 mg), temperature (30–60 °C) and interfering ions. The maximum biosorptive removal values of BF dye were established as 96.0 and 95.2% using 5 and 10 mg L−1, respectively at the recommended pH 7 condition. The Thermodynamic parameters demonstrated that the BF dye adsorption onto Gel@GO-F-ZrSiO4@Gel was taken place via spontaneous and endothermic reaction. Chemisorption is the predominant adsorption mechanism by forming multilayers upon nonhomogeneous surface in accordance with Freundlich model hypothesis. The applicability of the optimized Gel@GO-F-ZrSiO4@Gel in biosorptive removal of BF pollutant from real water sample was successfully accomplished by the batch technique. Thus, this study clearly shows that Gel@GO-F-ZrSiO4@Gel exhibited significant influences on remediation of industrial effluents containing BF pollutant with superior efficiency.
Machine learning unifies flexibility and efficiency of spinodal structure generation for stochastic biomaterial design
Authors: Wang Zhuo , Dabaja Rana , Chen Lei , Banu Mihaela
Published: April 2023

Porous biomaterials design for bone repair is still largely limited to regular structures (e.g. rod-based lattices), due to their easy parameterization and high controllability. The capability of designing stochastic structure can redefine the boundary of our explorable structure–property space for synthesizing next-generation biomaterials. We hereby propose a convolutional neural network (CNN) approach for efficient generation and design of spinodal structure—an intriguing structure with stochastic yet interconnected, smooth, and constant pore channel conducive to bio-transport. Our CNN-based approach simultaneously possesses the tremendous flexibility of physics-based model in generating various spinodal structures (e.g. periodic, anisotropic, gradient, and arbitrarily large ones) and comparable computational efficiency to mathematical approximation model. We thus successfully design spinodal bone structures with target anisotropic elasticity via high-throughput screening, and directly generate large spinodal orthopedic implants with desired gradient porosity. This work significantly advances stochastic biomaterials development by offering an optimal solution to spinodal structure generation and design.
Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites
Authors: Fam Marina Sherif , Sedky Christine Adel , Turky Nancy Osama , Breitinger Hans-Georg , Breitinger Ulrike
Published: April 2023

SARS-CoV-2 has been responsible for the major worldwide pandemic of COVID-19. Despite the enormous success of vaccination campaigns, virus infections are still prevalent and effective antiviral therapies are urgently needed. Viroporins are essential for virus replication and release, and are thus promising therapeutic targets. Here, we studied the expression and function of recombinant ORF3a viroporin of SARS-CoV-2 using a combination of cell viability assays and patch-clamp electrophysiology. ORF3a was expressed in HEK293 cells and transport to the plasma membrane verified by a dot blot assay. Incorporation of a membrane-directing signal peptide increased plasma membrane expression. Cell viability tests were carried out to measure cell damage associated with ORF3a activity, and voltage-clamp recordings verified its channel activity. The classical viroporin inhibitors amantadine and rimantadine inhibited ORF3a channels. A series of ten flavonoids and polyphenolics were studied. Kaempferol, quercetin, epigallocatechin gallate, nobiletin, resveratrol and curcumin were ORF3a inhibitors, with IC50values ranging between 1 and 6 µM, while 6-gingerol, apigenin, naringenin and genistein were inactive. For flavonoids, inhibitory activity could be related to the pattern of OH groups on the chromone ring system. Thus, the ORF3a viroporin of SARS-CoV-2 may indeed be a promising target for antiviral drugs.
Ultra-thin Ag/Si heterojunction hot-carrier photovoltaic conversion Schottky devices for harvesting solar energy at wavelength above 1.1 µm
Authors: Su Zih-Chun , Chang Chung-Han , Jhou Jia-Ci , Lin Hsin-Ting , Lin Ching-Fuh
Published: April 2023

Traditional silicon solar cells can only absorb the solar spectrum at wavelengths below 1.1 μm. Here we proposed a breakthrough in harvesting solar energy below Si bandgap through conversion of hot carriers generated in the metal into a current using an energy barrier at the metal–semiconductor junction. Under appropriate conditions, the photo-excited hot carriers can quickly pass through the energy barrier and lead to photocurrent, maximizing the use of excitation energy and reducing waste heat consumption. Compared with conventional silicon solar cells, hot-carrier photovoltaic conversion Schottky device has better absorption and conversion efficiency for an infrared regime above 1.1 μm, expands the absorption wavelength range of silicon-based solar cells, makes more effective use of the entire solar spectrum, and further improves the photovoltaic performance of metal–silicon interface components by controlling the evaporation rate, deposition thickness, and annealing temperature of the metal layer. Finally, the conversion efficiency 3.316% is achieved under the infrared regime with a wavelength of more than 1100 nm and an irradiance of 13.85 mW/cm2.
A simple method to make, trap and deform a vesicle in a gel
Authors: Tapie Pierre , Prevost Alexis M. , Montel Lorraine , Pontani Léa-Laetitia , Wandersman Elie
Published: April 2023

We present a simple method to produce giant lipid pseudo-vesicles (vesicles with an oily cap on the top), trapped in an agarose gel. The method can be implemented using only a regular micropipette and relies on the formation of a water/oil/water double droplet in liquid agarose. We characterize the produced vesicle with fluorescence imaging and establish the presence and integrity of the lipid bilayer by the successful insertion of $$\alpha $$
α
-Hemolysin transmembrane proteins. Finally, we show that the vesicle can be easily mechanically deformed, non-intrusively, by indenting the surface of the gel.
New compartment model for COVID-19
Authors: Odagaki Takashi
Published: April 2023

The SIR or susceptible-infected-recovered model is the standard compartment model for understanding epidemics and has been used all over the world for COVID-19. While the SIR model assumes that infected patients are identical to symptomatic and infectious patients, it is now known that in COVID-19 pre-symptomatic patients are infectious and there are significant number of asymptomatic patients who are infectious. In this paper, population is separated into five compartments for COVID-19; susceptible individuals (S), pre-symptomatic patients (P), asymptomatic patients (A), quarantined patients (Q) and recovered and/or dead patients (R). The time evolution of population in each compartment is described by a set of ordinary differential equations. Numerical solution to the set of differential equations shows that quarantining pre-symptomatic and asymptomatic patients is effective in controlling the pandemic.
Food system actor perspectives on future-proofing European food systems through plant breeding
Authors: Stetkiewicz S. , Menary J. , Nair A. , Rufino M. , Fischer A. R. H. , Cornelissen M. , Guichaoua A. , Jorasch P. , Lemarié S. , Nanda A. K. , Wilhelm R. , Davies J. A. C.
Published: April 2023

Crop improvement is a key innovation area in the pursuit of sustainable food systems. However, realising its potential requires integration of the needs and priorities of all agri-food chain stakeholders. In this study, we provide a multi-stakeholder perspective on the role of crop improvement in future-proofing the European food system. We engaged agri-business, farm- and consumer-level stakeholders, and plant scientists through an online survey and focus groups. Four of each group’s top five priorities were shared and related to environmental sustainability goals (water, nitrogen and phosphorus efficiency, and heat stress). Consensus was identified on issues including considering existing alternatives to plant breeding (e.g. management strategies), minimising trade-offs, and addressing geographical variation in needs. We conducted a rapid evidence synthesis on the impacts of priority crop improvement options, highlighting the urgent need for further research examining downstream sustainability impacts to identify concrete targets for plant breeding innovation as a food systems solution.
Suboptimal controller design of global active noise control system for various acoustic environments
Authors: Jeong Ikchae , Park Youngjin
Published: April 2023

Conventional active noise control (ANC) systems in enclosed spaces are not easy to implement experimentally because they require a large number of microphones to measure sound pressure in global areas. Even if such systems are possible, if there are any changes in the locations of noise sources or surrounding objects, or if ANC system moves to another enclosed space, an expensive and time-consuming experimental calibration is again required. Implementation of global ANC in enclosed spaces is thus difficult. Therefore, we designed a global ANC system that can be used in various acoustic environments. The main idea involves suboptimal open-loop controller design in the free field. By using an open-loop controller, a controller calibrated once can be used in various acoustic environments. A controller designed in the free field derive a suboptimal solution without bias toward a specific acoustic environment. For controller design in the free field, we propose an experimental calibration approach in which the arrangement and the number of control speakers and microphones are determined by the frequency range and radiation pattern of the noise source. We conducted simulations and experiments to show that the designed controller in the free field is sufficiently effective in other enclosed spaces.
Transcriptomic data meta-analysis reveals common and injury model specific gene expression changes in the regenerating zebrafish heart
Authors: Botos Marius Alexandru , Arora Prateek , Chouvardas Panagiotis , Mercader Nadia
Published: April 2023

Zebrafish have the capacity to fully regenerate the heart after an injury, which lies in sharp contrast to the irreversible loss of cardiomyocytes after a myocardial infarction in humans. Transcriptomics analysis has contributed to dissect underlying signaling pathways and gene regulatory networks in the zebrafish heart regeneration process. This process has been studied in response to different types of injuries namely: ventricular resection, ventricular cryoinjury, and genetic ablation of cardiomyocytes. However, there exists no database to compare injury specific and core cardiac regeneration responses. Here, we present a meta-analysis of transcriptomic data of regenerating zebrafish hearts in response to these three injury models at 7 days post injury (7dpi). We reanalyzed 36 samples and analyzed the differentially expressed genes (DEG) followed by downstream Gene Ontology Biological Processes (GO:BP) analysis. We found that the three injury models share a common core of DEG encompassing genes involved in cell proliferation, the Wnt signaling pathway and genes that are enriched in fibroblasts. We also found injury-specific gene signatures for resection and genetic ablation, and to a lower extent the cryoinjury model. Finally, we present our data in a user-friendly web interface that displays gene expression signatures across different injury types and highlights the importance to consider injury-specific gene regulatory networks when interpreting the results related to cardiac regeneration in the zebrafish. The analysis is freely available at: https://mybinder.org/v2/gh/MercaderLabAnatomy/PUB_Botos_et_al_2022_shinyapp_binder/HEAD?urlpath=shiny/bus-dashboard/.
Myopia prediction for children and adolescents via time-aware deep learning
Authors: Huang Junjia , Ma Wei , Li Rong , Zhao Na , Zhou Tao
Published: April 2023

This is a retrospective analysis. Quantitative prediction of the children’s and adolescents’ spherical equivalent based on their variable-length historical vision records. From October 2019 to March 2022, we examined uncorrected visual acuity, sphere, astigmatism, axis, corneal curvature and axial length of 75,172 eyes from 37,586 children and adolescents aged 6–20 years in Chengdu, China. 80% samples consist of the training set, the 10% form the validation set and the remaining 10% form the testing set. Time-Aware Long Short-Term Memory was used to quantitatively predict the children’s and adolescents’ spherical equivalent within two and a half years. The mean absolute prediction error on the testing set was 0.103 ± 0.140 (D) for spherical equivalent, ranging from 0.040 ± 0.050 (D) to 0.187 ± 0.168 (D) if we consider different lengths of historical records and different prediction durations. Time-Aware Long Short-Term Memory was applied to captured the temporal features in irregularly sampled time series, which is more in line with the characteristics of real data and thus has higher applicability, and helps to identify the progression of myopia earlier. The overall error 0.103 (D) is much smaller than the criterion for clinically acceptable prediction, say 0.75 (D).