bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionarily recent dual obligatory symbiosis among adelgids indicates a transition between fungus- and insect-associated lifestyles
Authors: Szabó Gitta , Schulz Frederik , Manzano-Marín Alejandro , Toenshoff Elena Rebecca , Horn Matthias
Published: July 2021

Adelgids (Insecta: Hemiptera: Adelgidae) form a small group of insects but harbor a surprisingly diverse set of bacteriocyte-associated endosymbionts, which suggest multiple replacement and acquisition of symbionts over evolutionary time. Specific pairs of symbionts have been associated with adelgid lineages specialized on different secondary host conifers. Using a metagenomic approach, we investigated the symbiosis of the Adelges laricis/Adelgestardus species complex containing betaproteobacterial (“Candidatus Vallotia tarda”) and gammaproteobacterial (“Candidatus Profftia tarda”) symbionts. Genomic characteristics and metabolic pathway reconstructions revealed that Vallotia and Profftia are evolutionary young endosymbionts, which complement each other’s role in essential amino acid production. Phylogenomic analyses and a high level of genomic synteny indicate an origin of the betaproteobacterial symbiont from endosymbionts of Rhizopus fungi. This evolutionary transition was accompanied with substantial loss of functions related to transcription regulation, secondary metabolite production, bacterial defense mechanisms, host infection, and manipulation. The transition from fungus to insect endosymbionts extends our current framework about evolutionary trajectories of host-associated microbes.
No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing
Authors: Cole John J. , McColl Alison , Shaw Robin , Lynall Mary-Ellen , Cowen Philip J. , de Boer Peter , Drevets Wayne C. , Harrison Neil , Pariante Carmine , Pointon Linda ,   NIMA consortium, Goodyear Carl , Bullmore Edward , Cavanagh Jonathan
Published: July 2021

The increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation forthe variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence, with consistent meta-analytic data implicating raised proinflammatory cytokines such as IL6, IL1β and TNF. Among the potential mechanisms linking immunobiological changes to affective neurobiology is the accelerated biological ageing seen in MDD, particularly via the senescence associated secretory phenotype (SASP). However, the cellular source of immunobiological markers remains unclear. Pre-clinical evidence suggests a role for peripheral blood mononuclear cells (PBMC), thus here we aimed to explore the transcriptomic profile using RNA sequencing in PBMCs in a clinical sample of people with various levels of depression and treatment response comparing it with that in healthy controls (HCs). There were three groups with major depressive disorder (MDD): treatment-resistant (n = 94), treatment-responsive (n = 47) and untreated (n = 46). Healthy controls numbered 44. Using PBMCs gene expression analysis was conducted using RNAseq to a depth of 54.5 million reads. Differential gene expression analysis was performed using DESeq2. The data showed no robust signal differentiating MDD and HCs. There was, however, significant evidence of elevated biological ageing in MDD vs HC. Biological ageing was evident in these data as a transcriptional signature of 888 age-associated genes (adjusted p < 0.05, absolute log2fold > 0.6) that also correlated strongly with chronological age (spearman correlation coefficient of 0.72). Future work should expand clinical sample sizes and reduce clinical heterogeneity. Exploration of RNA-seq signatures in other leukocyte populations and single cell RNA sequencing may help uncover more subtle differences. However, currently the subtlety of any PBMC signature mitigates against its convincing use as a diagnostic or predictive biomarker.
Discovery of SARS-CoV-2-E channel inhibitors as antiviral candidates
Authors: Wang Yi , Fang Sui , Wu Yan , Cheng Xi , Zhang Lei-ke , Shen Xu-rui , Li Shuang-qu , Xu Jian-rong , Shang Wei-juan , Gao Zhao-bing , Xia Bing-qing
Published: July 2021

Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral analysis, 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiological experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (KD) of 22.14 μM in surface plasmon resonance assay. Molecular modeling and docking analysis revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.
Autophagy-related circRNA evaluation reveals hsa_circ_0001747 as a potential favorable prognostic factor for biochemical recurrence in patients with prostate cancer
Authors: Zhong Chuanfan , Wu Kaihui , Wang Shuo , Long Zining , Yang Taowei , Zhong Weibo , Tan Xiao , Wang Zixian , Li Chuanyin , Lu Jianming , Mao Xiangming
Published: July 2021

Prostate cancer (PCa) is a common high-incidence malignancy in men, some of whom develop biochemical recurrence (BCR) in the advanced stage. However, there are currently no accurate prognostic indicators of BCR in PCa. The aim of our study was to identify an autophagy-related circular RNA prognostic factor of BCR for patients with PCa. In this study, immunochemistry revealed that the classic autophagy marker MAP1LC3B was positively correlated with Gleason score. Least absolute shrinkage and selector operator regression were conducted to develop a novel prognostic model with tenfold cross-validation and an L1 penalty. Five autophagy-related circRNA signatures were included in the prognostic model. Patients with PCa were ultimately divided into high- and low-risk groups, based on the median risk score. Patients with PCa, who had a high risk score, were more likely to develop BCR in a shorter period of time. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent variable for predicting BCR in PCa. In addition, a prognostic nomogram integrated with the risk score and numerous clinicopathological parameters was developed to accurately predict 3- and 5-year BCR of patients with PCa. Finally, the hsa_circ_0001747 signature was selected for further experimental verification in vitro and in vivo, which showed that downregulated hsa_circ_0001747 might facilitate PCa via augmenting autophagy. Our findings indicate that the autophagy-related circRNA signature hsa_circ_0001747 may serve as a promising indicator for BCR prediction in patients with PCa.
Quantifying the contribution of Neanderthal introgression to the heritability of complex traits
Authors: McArthur Evonne , Rinker David C. , Capra John A.
Published: July 2021

Eurasians have ~2% Neanderthal ancestry, but we lack a comprehensive understanding of the genome-wide influence of Neanderthal introgression on modern human diseases and traits. Here, we quantify the contribution of introgressed alleles to the heritability of more than 400 diverse traits. We show that genomic regions in which detectable Neanderthal ancestry remains are depleted of heritability for all traits considered, except those related to skin and hair. Introgressed variants themselves are also depleted for contributions to the heritability of most traits. However, introgressed variants shared across multiple Neanderthal populations are enriched for heritability and have consistent directions of effect on several traits with potential relevance to human adaptation to non-African environments, including hair and skin traits, autoimmunity, chronotype, bone density, lung capacity, and menopause age. Integrating our results, we propose a model in which selection against introgressed functional variation was the dominant trend (especially for cognitive traits); however, for a few traits, introgressed variants provided beneficial variation via uni-directional (e.g., lightening skin color) or bi-directional (e.g., modulating immune response) effects.
Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics
Authors: Beckert Bertrand , Leroy Elodie C. , Sothiselvam Shanmugapriya , Bock Lars V. , Svetlov Maxim S. , Graf Michael , Arenz Stefan , Abdelshahid Maha , Seip Britta , Grubmüller Helmut , Mankin Alexander S. , Innis C. Axel , Vázquez-Laslop Nora , Wilson Daniel N.
Published: July 2021

Macrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.
Structure of the mini-RNA-guided endonuclease CRISPR-Cas12j3
Authors: Carabias Arturo , Fuglsang Anders , Temperini Piero , Pape Tillmann , Sofos Nicholas , Stella Stefano , Erlendsson Simon , Montoya Guillermo
Published: July 2021

CRISPR-Cas12j is a recently identified family of miniaturized RNA-guided endonucleases from phages. These ribonucleoproteins provide a compact scaffold gathering all key activities of a genome editing tool. We provide the first structural insight into the Cas12j family by determining the cryoEM structure of Cas12j3/R-loop complex after DNA cleavage. The structure reveals the machinery for PAM recognition, hybrid assembly and DNA cleavage. The crRNA-DNA hybrid is directed to the stop domain that splits the hybrid, guiding the T-strand towards the catalytic site. The conserved RuvC insertion is anchored in the stop domain and interacts along the phosphate backbone of the crRNA in the hybrid. The assembly of a hybrid longer than 12-nt activates catalysis through key functional residues in the RuvC insertion. Our findings suggest why Cas12j unleashes unspecific ssDNA degradation after activation. A site-directed mutagenesis analysis supports the DNA cutting mechanism, providing new avenues to redesign CRISPR-Cas12j nucleases for genome editing.
A machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer’s disease
Authors: Huang Yanting , Sun Xiaobo , Jiang Huige , Yu Shaojun , Robins Chloe , Armstrong Matthew J. , Li Ronghua , Mei Zhen , Shi Xiaochuan , Gerasimov Ekaterina Sergeevna , De Jager Philip L. , Bennett David A. , Wingo Aliza P. , Jin Peng , Wingo Thomas S. , Qin Zhaohui S.
Published: July 2021

Alzheimer’s disease (AD) is influenced by both genetic and environmental factors; thus, brain epigenomic alterations may provide insights into AD pathogenesis. Multiple array-based Epigenome-Wide Association Studies (EWASs) have identified robust brain methylation changes in AD; however, array-based assays only test about 2% of all CpG sites in the genome. Here, we develop EWASplus, a computational method that uses a supervised machine learning strategy to extend EWAS coverage to the entire genome. Application to six AD-related traits predicts hundreds of new significant brain CpGs associated with AD, some of which are further validated experimentally. EWASplus also performs well on data collected from independent cohorts and different brain regions. Genes found near top EWASplus loci are enriched for kinases and for genes with evidence for physical interactions with known AD genes. In this work, we show that EWASplus implicates additional epigenetic loci for AD that are not found using array-based AD EWASs.
Spin defects in hBN as promising temperature, pressure and magnetic field quantum sensors
Authors: Gottscholl Andreas , Diez Matthias , Soltamov Victor , Kasper Christian , Krauße Dominik , Sperlich Andreas , Kianinia Mehran , Bradac Carlo , Aharonovich Igor , Dyakonov Vladimir
Published: July 2021

Spin defects in solid-state materials are strong candidate systems for quantum information technology and sensing applications. Here we explore in details the recently discovered negatively charged boron vacancies (VB−) in hexagonal boron nitride (hBN) and demonstrate their use as atomic scale sensors for temperature, magnetic fields and externally applied pressure. These applications are possible due to the high-spin triplet ground state and bright spin-dependent photoluminescence of the VB−. Specifically, we find that the frequency shift in optically detected magnetic resonance measurements is not only sensitive to static magnetic fields, but also to temperature and pressure changes which we relate to crystal lattice parameters. We show that spin-rich hBN films are potentially applicable as intrinsic sensors in heterostructures made of functionalized 2D materials.
CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells
Authors: Koda Yuzo , Teratani Toshiaki , Chu Po-Sung , Hagihara Yuya , Mikami Yohei , Harada Yosuke , Tsujikawa Hanako , Miyamoto Kentaro , Suzuki Takahiro , Taniki Nobuhito , Sujino Tomohisa , Sakamoto Michiie , Kanai Takanori , Nakamoto Nobuhiro
Published: July 2021

Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease that can progress to liver fibrosis. Recent clinical advance suggests a reversibility of liver fibrosis, but the cellular and molecular mechanisms underlying NASH resolution remain unclarified. Here, using a murine diet-induced NASH and the subsequent resolution model, we demonstrate direct roles of CD8+ tissue-resident memory CD8+ T (CD8+ Trm) cells in resolving liver fibrosis. Single-cell transcriptome analysis and FACS analysis revealed CD69+CD103−CD8+ Trm cell enrichment in NASH resolution livers. The reduction of liver CD8+ Trm cells, maintained by tissue IL-15, significantly delayed fibrosis resolution, while adoptive transfer of these cells protected mice from fibrosis progression. During resolution, CD8+ Trm cells attracted hepatic stellate cells (HSCs) in a CCR5-dependent manner, and predisposed activated HSCs to FasL-Fas-mediated apoptosis. Histological assessment of patients with NASH revealed CD69+CD8+ Trm abundance in fibrotic areas, further supporting their roles in humans. These results highlight the undefined role of liver CD8+ Trm in fibrosis resolution.
Harmful R-loops are prevented via different cell cycle-specific mechanisms
Authors: San Martin-Alonso Marta , Soler-Oliva María E. , García-Rubio María , García-Muse Tatiana , Aguilera Andrés
Published: July 2021

Identifying how R-loops are generated is crucial to know how transcription compromises genome integrity. We show by genome-wide analysis of conditional yeast mutants that the THO transcription complex, prevents R-loop formation in G1 and S-phase, whereas the Sen1 DNA-RNA helicase prevents them only in S-phase. Interestingly, damage accumulates asymmetrically downstream of the replication fork in sen1 cells but symmetrically in the hpr1 THO mutant. Our results indicate that: R-loops form co-transcriptionally independently of DNA replication; that THO is a general and cell-cycle independent safeguard against R-loops, and that Sen1, in contrast to previously believed, is an S-phase-specific R-loop resolvase. These conclusions have important implications for the mechanism of R-loop formation and the role of other factors reported to affect on R-loop homeostasis.
Tailored growth of single-crystalline InP tetrapods
Authors: Kim Youngsik , Choi Hyekyoung , Lee Yeunhee , Koh Weon-kyu , Cho Eunhye , Kim Taewan , Kim Hamin , Kim Yong-Hyun , Jeong Hu Young , Jeong Sohee
Published: July 2021

Despite the technological importance of colloidal covalent III-V nanocrystals with unique optoelectronic properties, their synthetic process still has challenges originating from the complex energy landscape of the reaction. Here, we present InP tetrapod nanocrystals as a crystalline late intermediate in the synthetic pathway that warrants controlled growth. We isolate tetrapod intermediate species with well-defined surfaces of (110) and ($$\bar{1}\bar{1}\bar{1}$$

1

¯

1

¯

1

¯

) via the suppression of further growth. An additional precursor supply at low temperature induces $$[\bar{1}\bar{1}\bar{1}]$$

[

1

¯

1

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1

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]

-specific growth, whereas the [110]-directional growth occurs over the activation barrier of 65.7 kJ/mol at a higher temperature, thus finalizes into the (111)-faceted tetrahedron nanocrystals. We address the use of late intermediates with well-defined facets at the sub-10 nm scale for the tailored growth of covalent III-V nanocrystals and highlight the potential for the directed approach of nanocrystal synthesis.
Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production
Authors: Perez-Frances Marta , van Gurp Léon , Abate Maria Valentina , Cigliola Valentina , Furuyama Kenichiro , Bru-Tari Eva , Oropeza Daniel , Carreaux Taïna , Fujitani Yoshio , Thorel Fabrizio , Herrera Pedro L.
Published: July 2021

The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon β-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.
Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis
Authors: Chang Martin C. , Eslami Zohreh , Ennis Marguerite , Goodwin Pamela J.
Published: July 2021

Crown-like structures of the breast (CLS-B), defined by the clustering of macrophages (identified using CD68 immunohistochemical staining) to surround a dying adipocyte, are a sign of adipose-tissue inflammation. In human cohorts, CLS-B positively correlates with older age, obesity, dyslipidemia and higher levels of glucose, insulin, C-reactive protein and IL-6. In an existing cohort of early-stage breast cancer patients, CLS-B were identified using H&E stained histologic sections (hCLS-B), and by CD68 immunohistochemistry (CD68 + CLS-B). We examined associations of H&E and CD68-detected CLS-B with clinicopathologic features using χ2 tests, with metabolic factors using Wilcoxon rank sum tests and with disease free and overall survival using Cox regression models. hCLS-B were detected in 59 of 163 patients with slides (36.2%) and CD68 + CLS-B in 37 of 119 patients with paraffin blocks (31.1%). hCLS-B were positively correlated with higher weight (p = 0.003), BMI (p = 0.0008) and C-reactive protein (p = 0.045). CD68 + CLS-B were positively correlated with higher weight (p = 0.006), BMI p = 0.001), leptin (p = 0.034), insulin (p = 0.008) and Homeostasis Model Assessment (p = 0.027). CD68 + CLS-B were associated with poor distant disease-free with a hazard ratio (HR) of 2.81, 95% confidence interval (CI) 1.20–6.57, and overall survival with HR 3.97 (1.66–9.48), while hCLS-B were not associated with either: HR for distant recurrence 0.59 (0.26–1.30); HR for death 1.04 (0.50–2.16). The presence of hCLS-B and of CD68 + CLS-B were associated with obesity; CD68 + CLS-B were associated with insulin resistance and adverse prognosis. Similar patterns were not seen for hCLS-B. Research is needed to understand the biologic basis for these differences.
The critical role of hot carrier cooling in optically excited structural transitions
Authors: Liu Wen-Hao , Luo Jun-Wei , Li Shu-Shen , Wang Lin-Wang
Published: July 2021

The hot carrier cooling occurs in most photoexcitation-induced phase transitions (PIPTs), but its role has often been neglected in many theoretical simulations as well as in proposed mechanisms. Here, by including the previously ignored hot carrier cooling in real-time time-dependent density functional theory (rt-TDDFT) simulations, we investigated the role of hot carrier cooling in PIPTs. Taking IrTe2 as an example, we reveal that the cooling of hot electrons from the higher energy levels of spatially extended states to the lower energy levels of the localized Ir–Ir dimer antibonding states strengthens remarkably the atomic driving forces and enhances atomic kinetic energy. These two factors combine to dissolute the Ir–Ir dimers on a timescale near the limit of atomic motions, thus initiating a deterministic kinetic phase transition. We further demonstrate that the subsequent cooling induces nonradiative recombination of photoexcited electrons and holes, leading to the ultrafast recovery of the Ir–Ir dimers observed experimentally. These findings provide a complete picture of the atomic dynamics in optically excited structural phase transitions.
Lateralized effects of deep brain stimulation in Parkinson’s disease: evidence and controversies
Authors: Lin Zhengyu , Zhang Chencheng , Li Dianyou , Sun Bomin
Published: July 2021

The bilateral effects of deep brain stimulation (DBS) on motor and non-motor symptoms of Parkinson’s disease (PD) have been extensively studied and reviewed. However, the unilateral effects—in particular, the potential lateralized effects of left- versus right-sided DBS—have not been adequately recognized or studied. Here we summarized the current evidence and controversies in the literature regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. Publications in English language before February 2021 were obtained from the PubMed database and included if they directly compared the effects of unilateral versus contralateral side DBS on motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving subthalamic nucleus (STN) DBS while the potential lateralized effects of globus pallidus interna (GPi) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the verbal fluency, in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, surgical planning, and postoperative management that ultimately benefit patients.
Demonstrating the power of quantum computers, certification of highly entangled measurements and scalable quantum nonlocality
Authors: Bäumer Elisa , Gisin Nicolas , Tavakoli Armin
Published: July 2021

Increasingly sophisticated quantum computers motivate the exploration of their abilities in certifying genuine quantum phenomena. Here, we demonstrate the power of state-of-the-art IBM quantum computers in correlation experiments inspired by quantum networks. Our experiments feature up to 12 qubits and require the implementation of paradigmatic Bell-State Measurements for scalable entanglement-swapping. First, we demonstrate quantum correlations that defy classical models in up to nine-qubit systems while only assuming that the quantum computer operates on qubits. Harvesting these quantum advantages, we are able to certify 82 basis elements as entangled in a 512-outcome measurement. Then, we relax the qubit assumption and consider quantum nonlocality in a scenario with multiple independent entangled states arranged in a star configuration. We report quantum violations of source-independent Bell inequalities for up to ten qubits. Our results demonstrate the ability of quantum computers to outperform classical limitations and certify scalable entangled measurements.
Variational quantum algorithm with information sharing
Authors: Self Chris N. , Khosla Kiran E. , Smith Alistair W. R. , Sauvage Frédéric , Haynes Peter D. , Knolle Johannes , Mintert Florian , Kim M. S.
Published: July 2021

We introduce an optimisation method for variational quantum algorithms and experimentally demonstrate a 100-fold improvement in efficiency compared to naive implementations. The effectiveness of our approach is shown by obtaining multi-dimensional energy surfaces for small molecules and a spin model. Our method solves related variational problems in parallel by exploiting the global nature of Bayesian optimisation and sharing information between different optimisers. Parallelisation makes our method ideally suited to the next generation of variational problems with many physical degrees of freedom. This addresses a key challenge in scaling-up quantum algorithms towards demonstrating quantum advantage for problems of real-world interest.
Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients
Authors: Schwarz Erica L. , Kelly John M. , Blum Kevin M. , Hor Kan N. , Yates Andrew R. , Zbinden Jacob C. , Verma Aekaansh , Lindsey Stephanie E. , Ramachandra Abhay B. , Szafron Jason M. , Humphrey Jay D. , Shin’oka Toshiharu , Marsden Alison L. , Breuer Christopher K.
Published: July 2021

In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.
Mammals fail to regenerate organs when wound contraction drives scar formation
Authors: Yannas Ioannis V. , Tzeranis Dimitrios S.
Published: July 2021

To understand why mammals generally do not regenerate injured organs, we considered the exceptional case of spontaneous skin regeneration in the early lamb fetus. Whereas during the early fetal stage skin wounds heal by regeneration, in the late fetal stage, and after birth, skin wounds close instead by scar formation. We review independent evidence that this switch in wound healing response coincides with the onset of wound contraction, which is also enabled during late fetal gestation. The crucial role of wound contraction in determining the wound healing outcome in adults has been demonstrated in three mammalian models of severe injury (excised guinea pig skin, transected rat sciatic nerve, excised rabbit conjunctival stroma) where grafting the injury with DRT, a contraction-blocking scaffold of highly-specific structure, altered significantly the wound healing outcome. While spontaneous healing resulted in scar formation in these animal models, DRT grafting significantly reduced the extent of wound contraction, prevented scar synthesis, and resulted in partial regeneration. These findings, as well as independent data from species that heal spontaneously via regeneration, point to a striking hypothesis: The process of regeneration lies dormant in mammals until appropriately activated by injury. In spontaneous wound healing of the late fetus and in adult mammals, wound contraction impedes such endogenous regeneration mechanisms. However, engineered treatments, such as DRT, that block wound contraction can cancel its effects and favor wound healing by regeneration instead of scar formation.
A critical review of point-of-use drinking water treatment in the United States
Authors: Wu Jishan , Cao Miao , Tong Draco , Finkelstein Zach , Hoek Eric M. V.
Published: July 2021

Ensuring safe water supply for communities across the United States is a growing challenge due to aging infrastructure, impaired source water, strained community finances, etc. In 2019, about 6% of public water utilities in the U.S. had a health-based violation. Due to the high risk of exposure to various contaminants in drinking water, point-of-use (POU) drinking water treatment is rapidly growing in popularity in the U.S. and beyond. POU treatment technologies include various combinations of string-wound sediment filters, activated carbon, modified carbon, ion exchange and redox media filters, reverse osmosis membranes, and ultraviolet lamps depending on the contaminants of concern. While the technologies are well-proven, highly commoditized, and cost-effective, most systems offer little in the way of real-time performance monitoring or interactive technology like other smart home appliances (e.g., thermostats, smoke detectors, doorbells, etc.). Herein, we review water quality regulations and violations in the U.S. as well as state-of-the-art POU technologies and systems with an emphasis on their effectiveness at removing the contaminants most frequently reported in notices of violations. We conclude by briefly reviewing emerging smart water technologies and the needs for advances in the state-of-the-art technologies. The smartness of commercially available POU water filters is critiqued and a definition of smart water filter is proposed.
A bibliometric study on biomimetic and bioinspired membranes for water filtration
Authors: Goel Gaurav , Hélix-Nielsen Claus , Upadhyaya Hari M. , Goel Saurav
Published: July 2021

Insights into the biological channels and synthetic pore-forming assemblies have elucidated many fundamental aspects of selective water and solute transport over the last few decades. This has led to the development of novel technologies with unique selectivity and permeability. In terms of membrane separation technology, this development has proceeded by adapting either of two approaches: (i) one where biological channel proteins are reconstituted in suitable materials mimicking the biological bilayer membrane and (ii) one where selective transport is mimicked in synthetic structures. The development of water filtration membranes in the former approach takes advantage of aquaporin proteins as representative building blocks and that of carbon nanotubes and molecular pore-forming assemblies in the latter approach. The first approach is often referred to as the field dominated bybiomimetic membranesand the latter referred to asartificial water channels. In this study, a bibliometric analysis was conducted to investigate trends in these two areas based on growing publication trends, peer-reviewed journal selection, countries, institutions, authors, and collaborative networks. A total of 3199 records available from Scopus between 1962 and 2021 were extracted and analyzed. The results showed strong international collaborations and highlighted leading researchers and hubs of excellence in these two areas. This is very timely considering that the UN climate change conference (COP26) in Glasgow, UK later this year will bring focus to the global need for water treatment technologies. This work can serve as a quick reference for early-career researchers and industries working in the area of membrane development for water purification/filtration.
PET/MRI of glucose metabolic rate, lipid content and perfusion in human brown adipose tissue
Authors: Lundström Elin , Andersson Jonathan , Engström Mathias , Lubberink Mark , Strand Robin , Ahlström Håkan , Kullberg Joel
Published: July 2021

This study evaluated the MRI-derived fat fraction (FF), from a Cooling-reheating protocol, for estimating the cold-induced brown adipose tissue (BAT) metabolic rate of glucose (MRglu) and changes in lipid content, perfusion and arterial blood volume (VA) within cervical-supraclavicular fat (sBAT). Twelve volunteers underwent PET/MRI at baseline, during cold exposure and reheating. For each temperature condition, perfusion and VA were quantified with dynamic [15O]water-PET, and FF, with water-fat MRI. MRglu was assessed with dynamic [18F]fluorodeoxyglucose-PET during cold exposure. sBAT was defined using anatomical criteria, and its subregion sBATHI, by MRglu > 11 μmol/100 cm3/min. For all temperature conditions, sBAT-FF correlated negatively with sBAT-MRglu (ρ ≤ − 0.87). After 3 h of cold, sBAT-FF decreased (− 2.13 percentage points) but tended to normalize during reheating although sBATHI-FF remained low. sBAT-perfusion and sBAT-VA increased during cold exposure (perfusion: + 5.2 ml/100 cm3/min, VA: + 4.0 ml/100 cm3). sBAT-perfusion remained elevated and sBAT-VA normalized during reheating. Regardless of temperature condition during the Cooling-reheating protocol, sBAT-FF could predict the cold-induced sBAT-MRglu. The FF decreases observed after reheating were mainly due to lipid consumption, but could potentially be underestimated due to intracellular lipid replenishment. The influence of perfusion and VA, on the changes in FF observed during cold exposure, could not be ruled out.
New evidence of a Roman road in the Venice Lagoon (Italy) based on high resolution seafloor reconstruction
Authors: Madricardo Fantina , Bassani Maddalena , D’Acunto Giuseppe , Calandriello Antonio , Foglini Federica
Published: July 2021

This study provides new evidence of the presence of an ancient Roman road in correspondence to a paleobeach ridge now submerged in the Venice Lagoon (Italy). New high resolution underwater seafloor data shed new light on the significance of the Roman remains in the lagoon. The interpretation of the data through archive and geo-archaeological research allowed a three-dimensional architectural reconstruction of the Roman road. The presence of the ancient Roman road confirms the hypothesis of a stable system of Roman settlements in the Venice Lagoon. The study highlights the significance of this road in the broader context of the Roman transport system, demonstrating once more the Roman ability to adapt and to handle complex dynamic environments that were often radically different from today.
Clinical and laboratory characteristics of symptomatic healthcare workers with suspected COVID-19: a prospective cohort study
Authors: Bal Antonin , Brengel-Pesce Karen , Gaymard Alexandre , Quéromès Grégory , Guibert Nicolas , Frobert Emilie , Bouscambert Maude , Trabaud Mary-Anne , Allantaz-Frager Florence , Oriol Guy , Cheynet Valérie , d’Aubarede Constance , Massardier-Pilonchery Amélie , Buisson Marlyse , Lupo Julien , Pozzetto Bruno , Poignard Pascal , Lina Bruno , Fassier Jean-Baptiste , Morfin Florence , Trouillet-Assant Sophie ,   COVID-SER Study group, Adnot Jerôme , Alfaiate Dulce , Bergeret Alain , Boibieux André , Bonnet Florent , Brunel-Dalmas Florence , Caire Eurydice , Charbotel Barbara , Chiarello Pierre , Cotte Laurent , d’Aubarede Constance , Durupt François , Escuret Vanessa , Fascia Pascal , Fontaine Juliette , Gaillot-Durand Lucie , Gillet Myriam , Godinot Matthieu , Gueyffier François , Josset Laurence , Lahousse Matthieu , Lozano Hélène , Makhloufi Djamila , Milon Marie-Paule , Moll Frédéric , Narbey David , Nazare Julie-Anne , Oria Fatima , Perry Marielle , Pitiot Virginie , Prudent Mélanie , Rabilloud Muriel , Samperiz Audrey , Schlienger Isabelle , Simon Chantal , Valette Martine
Published: July 2021

A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs (p = 0.07). The proportion of HCWs with a viral load > 5.0 log10 cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work.
Ecological effects on female bill colour explain plastic sexual dichromatism in a mutually-ornamented bird
Authors: Freitas Rita , Marques Cristiana , Cardoso Gonçalo C. , Trigo Sandra
Published: July 2021

Sex differences in ornamentation are common and, in species with conventional sex roles, are generally thought of as stable, due to stronger sexual selection on males. Yet, especially in gregarious species, ornaments can also have non-sexual social functions, raising the possibility that observed sex differences in ornamentation are plastic. For example, females may invest in costly ornamentation more plastically, to protect body and reproductive ability in more adverse ecological conditions. We tested this hypothesis with experimental work on the mutually-ornamented common waxbill (Estrilda astrild), supplementing their diets either with pigmentary (lutein, a carotenoid) or non-pigmentary (vitamin E) antioxidants, or alleviating winter cold temperature. We found that both lutein and vitamin E supplementation increased red bill colour saturation in females, reaching the same mean saturation as males, which supports the hypothesis that female bill colour is more sensitive to environmental or physiological conditions. The effect of vitamin E, a non-pigment antioxidant, suggests that carotenoids were released from their antioxidant functions. Alleviating winter cold did not increase bill colour saturation in either sex, but increased the stability of female bill colour over time, suggesting that female investment in bill colour is sensitive to cold-mediated stress. Together, results show that waxbill bill sexual dichromatism is not stable. Instead, sexual dichromatism can be modulated, and even disappear completely, due to ecology-mediated plastic adjustments in female bill colour.
Bioprocess development for biosorption of cobalt ions and Congo red from aquatic mixture using Enteromorpha intestinalis biomass as sustainable biosorbent
Authors: El-Naggar Noura El-Ahmady , Hamouda Ragaa A. , Abuelmagd Muhammad A. , Abdelgalil Soad A.
Published: July 2021

Because of the increased amount of cobalt and Congo red dye effluents attributable to the industrial operations, the capacity of Enteromorpha intestinalis biomass as a sustainable source to achieve significant biosorption percent for both pollutants from dual solution was assessed. A fifty batch FCCCD experiments for biosorption of cobalt ions and Congo red dye were performed. The complete removal of Congo red dye was obtained at 36th run using an initial pH value of 10, 1.0 g/L of Enteromorpha intestinalis biomass, 100 and 200 mg/L of Congo red and cobalt for a 20-min incubation time. Meanwhile, a cobalt removal percent of 85.22 was obtained at 35th run using a neutral pH of 7.0, 3.0 g/L of algal biomass, 150 and 120 mg/L of Congo red, and cobalt for a 60-min incubation time. For further illustration and to interpret how the biosorption mechanism was performed, FTIR analysis was conducted to inspect the role of each active group in the biosorption process, it can be inferred that –OH, C–H, C=O, O–SO3- and C–O–C groups were mainly responsible for Co2+ adsorption of from aqueous dual solution. Also, scan electron microscope revealed the appearance of new shiny particles biosorbed on E. intestinalis surface after the biosorption process. EDS analysis proved the presence of Co2+ on the algal surface after the biosorption process.
Assisted peritoneal dialysis: a feasible KRT modality for frail older patients with end-stage kidney disease (ESKD)
Authors: Song Qianhui , Yan Hao , Yu Zanzhe , Li Zhenyuan , Yuan Jiangzi , Ni Zhaohui , Fang Wei
Published: July 2021

Assisted PD is used as an alternative option for the growing group of frail, older ESKD patients unable to perform their own PD. This study was undertaken to investigate the outcomes of assisted PD in older patients by comparing assisted PD patients with self-care PD patients. This study included all patients aged 70 and above who started on PD in our hospital from 2009 to 2018. Patients were followed up until death, PD cessation or to the end of the study (December 31, 2019). Risk factors associated with mortality, peritonitis and technique failure were evaluated using both cause-specific hazards and subdistribution hazards models. 180 patients were enrolled, including 106 (58.9%) males with a median age of 77.5 (77.2–81.2) years. Among the 180 patients, 62 patients (34.4%) were assisted. Patients on assisted PD group were older, more likely to be female, more prevalent in DM and CVD, with a higher Charlson score than patients undergoing self-care PD (P all < 0.05). In the multivariable analysis, assisted patients had a comparable patient survival and peritonitis-free survival compared to self-care PD patients either in the Cox or in the FG models. According to a Cox model, the use of assisted PD was associated with a lower risk of technique failure (cs-HR 0.20, 95% CI 0.04–0.76), but the association lost its statistical significance in the Fine and Gray model. Our results suggest that assisted PD could be a safe and effective KRT modality for older ESKD patients who need assistance.
High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro
Authors: Gard A. L. , Luu R. J. , Miller C. R. , Maloney R. , Cain B. P. , Marr E. E. , Burns D. M. , Gaibler R. , Mulhern T. J. , Wong C. A. , Alladina J. , Coppeta J. R. , Liu P. , Wang J. P. , Azizgolshani H. , Fezzie R. Fennell , Balestrini J. L. , Isenberg B. C. , Medoff B. D. , Finberg R. W. , Borenstein J. T.
Published: July 2021

Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air–liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing. We apply this platform to influenza A virus and coronavirus infections, evaluating viral infection kinetics and antiviral agent dosing across multiple strains and donor populations of human primary cells. Human coronaviruses HCoV-NL63 and SARS-CoV-2 enter host cells via ACE2 and utilize the protease TMPRSS2 for spike protein priming, and we confirm their expression, demonstrate infection across a range of multiplicities of infection, and evaluate the efficacy of camostat mesylate, a known inhibitor of HCoV-NL63 infection. This new capability can be used to address a major gap in the rapid assessment of therapeutic efficacy of small molecules and antiviral agents against influenza and other respiratory viruses including coronaviruses.
Magnetic generation of normal pseudo-spin polarization in disordered graphene
Authors: Baghran R. , Tehranchi M. M. , Phirouznia A.
Published: July 2021

Spin to pseudo-spin conversion by which the non-equilibrium normal sublattice pseudo-spin polarization could be achieved by magnetic field has been proposed in graphene. Calculations have been performed within the Kubo approach for both pure and disordered graphene including vertex corrections of impurities. Results indicate that the normal magnetic field $$B_z$$

B
z

produces pseudo-spin polarization in graphene regardless of whether the contribution of vertex corrections has been taken into account or not. This is because of non-vanishing correlation between the $$\sigma _z$$

σ
z

and $$\tau _z$$

τ
z

provided by the co-existence of extrinsic Rashba and intrinsic spin–orbit interactions which combines normal spin and pseudo-spin. For the case of pure graphene, valley-symmetric spin to pseudo-spin response function is obtained. Meanwhile, by taking into account the vertex corrections of impurities the obtained response function is weakened by several orders of magnitude with non-identical contributions of different valleys. This valley-asymmetry originates from the inversion symmetry breaking generated by the scattering matrix. Finally, spin to pseudo-spin conversion in graphene could be realized as a practical technique for both generation and manipulation of normal sublattice pseudo-spin polarization by an accessible magnetic field in a easy way. This novel proposed effect not only offers the opportunity to selective manipulation of carrier densities on different sublattice but also could be employed in data transfer technology. The normal pseudo-spin polarization which manifests it self as electron population imbalance of different sublattices can be detected by optical spectroscopy measurements.