bluuebunny/crossref_metadata_2025 huggingface dataset:
An analytical retrospective study to determine the prevalence of childhood obesity and assess the effectiveness of current surveillance
Authors: Mclean Lucille , Phillips Richard
Published: August 2020

Background:

The childhood obesity epidemic is a public health crisis. Most surveillance occurs in primary care, yet there is limited guidance for the detection and management of childhood obesity.

Aims and methodology:

We sought to establish the overweight and obesity prevalence in children aged 4–11 years old in a single primary care centre. Furthermore, we assessed whether appropriate weight management referrals were considered and determined the average duration since children last had their height and weight measured.

Findings:

We detected overweight or obesity status in 29.0% of our cohort, and only one-third (31.1%) of eligible children had evidence that appropriate weight management referral was considered. The average duration since last height and weight measurement was 20.3 months.

Discussion:

Childhood obesity requires an effective and inclusive solution, and in this report, we explore whether increased surveillance is necessary and how we might achieve this.
Passive Seismic Imaging of Near Vertical Structures Around the SAFOD Site, California, Jointly Using Scattered P and SH Waves
Authors: Chang Kai , Zhang Haijiang
Published: August 2020

To better illuminate structural discontinuities around the San Andreas Fault Observatory at Depth (SAFOD) site, following the previous study of Zhang et al. (2009), we have extended the Generalized Radon Transform (GRT) method to jointly use scattered P and SH waves from abundant local earthquakes recorded by a local dense seismic network. A hybrid imaging condition is applied to extract consistent structures from scattered P and SH images. In this way, more robust structure information can be determined from separate images with potential artifacts. For the transverse component waveforms, coherent S‐S scattered waves after the direct SH waves can be clearly identified, and they are less interfered with by other scattered and converted waves compared to scattered P‐P waves on the vertical component. Similar to Zhang, Wang, et al. (2009), near‐vertical reflectors are imaged on both sides of the San Andreas Fault (SAF) with scattered SH waves, which is generally consistent with the imaging results using scattered P‐P waves from local earthquakes and a wide‐angle active seismic reflection profile. Compared to the P‐P scattering imaging result, the imaging result using scattered SH waves has higher resolution due to shorter S wavelength and cleaner S‐S scattered waveforms, and the SAF, as well as other reflectors around it, is better resolved. Although the resolution of the joint image obtained by combining separate imaging results from different scattered waves may be degraded, it is able to more robustly characterize strong structure discontinuities using passive seismic sources.
Liver progenitor cell-driven liver regeneration
Authors: So Juhoon , Kim Angie , Lee Seung-Hoon , Shin Donghun
Published: August 2020

The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver diseases. Hepatocyte-driven liver regeneration that involves the proliferation of preexisting hepatocytes is a primary regeneration mode. On the other hand, liver progenitor cell (LPC)-driven liver regeneration that involves dedifferentiation of biliary epithelial cells or hepatocytes into LPCs, LPC proliferation, and subsequent differentiation of LPCs into hepatocytes is a secondary mode. This secondary mode plays a significant role in liver regeneration when the primary mode does not effectively work, as observed in severe liver injury settings. Thus, promoting LPC-driven liver regeneration may be clinically beneficial to patients with severe liver diseases. In this review, we describe the current understanding of LPC-driven liver regeneration by exploring current knowledge on the activation, origin, and roles of LPCs during regeneration. We also describe animal models used to study LPC-driven liver regeneration, given their potential to further deepen our understanding of the regeneration process. This understanding will eventually contribute to developing strategies to promote LPC-driven liver regeneration in patients with severe liver diseases.
Opto-thermoelectric microswimmers
Authors: Peng Xiaolei , Chen Zhihan , Kollipara Pavana Siddhartha , Liu Yaoran , Fang Jie , Lin Linhan , Zheng Yuebing
Published: August 2020

Inspired by the “run-and-tumble” behaviours of Escherichia coli (E. coli) cells, we develop opto-thermoelectric microswimmers. The microswimmers are based on dielectric-Au Janus particles driven by a self-sustained electrical field that arises from the asymmetric optothermal response of the particles. Upon illumination by a defocused laser beam, the Janus particles exhibit an optically generated temperature gradient along the particle surfaces, leading to an opto-thermoelectrical field that propels the particles. We further discover that the swimming direction is determined by the particle orientation. To enable navigation of the swimmers, we propose a new optomechanical approach to drive the in-plane rotation of Janus particles under a temperature-gradient-induced electrical field using a focused laser beam. Timing the rotation laser beam allows us to position the particles at any desired orientation and thus to actively control the swimming direction with high efficiency. By incorporating dark-field optical imaging and a feedback control algorithm, we achieve automated propelling and navigation of the microswimmers. Our opto-thermoelectric microswimmers could find applications in the study of opto-thermoelectrical coupling in dynamic colloidal systems, active matter, biomedical sensing, and targeted drug delivery.
Viral elements and their potential influence on microbial processes along the permanently stratified Cariaco Basin redoxcline
Authors: Mara Paraskevi , Vik Dean , Pachiadaki Maria G , Suter Elizabeth A , Poulos Bonnie , Taylor Gordon T , Sullivan Matthew B , Edgcomb Virginia P
Published: August 2020

Little is known about viruses in oxygen-deficient water columns (ODWCs). In surface ocean waters, viruses are known to act as gene vectors among susceptible hosts. Some of these genes may have metabolic functions and are thus termed auxiliary metabolic genes (AMGs). AMGs introduced to new hosts by viruses can enhance viral replication and/or potentially affect biogeochemical cycles by modulating key microbial pathways. Here we identify 748 viral populations that cluster into 94 genera along a vertical geochemical gradient in the Cariaco Basin, a permanently stratified and euxinic ocean basin. The viral communities in this ODWC appear to be relatively novel as 80 of these viral genera contained no reference viral sequences, likely due to the isolation and unique features of this system. We identify viral elements that encode AMGs implicated in distinctive processes, such as sulfur cycling, acetate fermentation, signal transduction, [Fe–S] formation, and N-glycosylation. These AMG-encoding viruses include two putative Mu-like viruses, and viral-like regions that may constitute degraded prophages that have been modified by transposable elements. Our results provide an insight into the ecological and biogeochemical impact of viruses oxygen-depleted and euxinic habitats.
Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia
Authors: Deyà-Martínez A. , Alonso-Saladrigues A. , García A. P. , Faura A. , Torrebadell M. , Vlagea A. , Català A. , Esteve-Solé A. , Juan M. , Rives S. , Alsina L.
Published: August 2020

CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9–24.9). Median follow-up after infusion was 7.1 months (0.5–42). BCA was observed 7 days after infusion (3–8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41–99) and 13% undetectable IgA levels at 185 days (11–308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.
Yap haploinsufficiency leads to Müller cell dysfunction and late-onset cone dystrophy
Authors: Masson Christel , García-García Diana , Bitard Juliette , Grellier Élodie-Kim , Roger Jérôme E. , Perron Muriel
Published: August 2020

Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine its function in adult neural retina, where YAP expression is restricted to Müller glia. We first discovered an unexpected temporal dynamic of gene compensation. At postnatal stages, Taz upregulation occurs, leading to a gain of function-like phenotype characterised by EGFR signalling potentiation and delayed cell-cycle exit of retinal progenitors. In contrast, Yap+/− adult retinas no longer exhibit TAZ-dependent dosage compensation. In this context, Yap haploinsufficiency in aged individuals results in Müller glia dysfunction, late-onset cone degeneration, and reduced cone-mediated visual response. Alteration of glial homeostasis and altered patterns of cone opsins were also observed in Müller cell-specific conditional Yap-knockout aged mice. Together, this study highlights a novel YAP function in Müller cells for the maintenance of retinal tissue homeostasis and the preservation of cone integrity. It also suggests that YAP haploinsufficiency should be considered and explored as a cause of cone dystrophies in human.
DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes
Authors: Johnson Darren C. , Okondo Marian C. , Orth Elizabeth L. , Rao Sahana D. , Huang Hsin-Che , Ball Daniel P. , Bachovchin Daniel A.
Published: August 2020

Canonical inflammasomes are innate immune signaling platforms that are formed in response to intracellular pathogen-associated signals and trigger caspase-1-dependent pyroptosis. Inflammasome formation and signaling is thought to mainly occur in myeloid cells, and in particular monocytes and macrophages. Here we show that small molecule inhibitors of dipeptidyl peptidases 8 and 9 (DPP8/9), which activate the related CARD8 and NLRP1 inflammasomes, also activate pyroptosis in human and rodent resting lymphocytes. We found that both CD4+and CD8+T cells were particularly sensitive to these inhibitors, although the sensitivity of T cells, like macrophages, varied considerably between species. In human T cells, we show that CARD8 mediates DPP8/9 inhibitor-induced pyroptosis. Intriguingly, although activated human T cells express the key proteins known to be required for CARD8-mediated pyroptosis, these cells were completely resistant to DPP8/9 inhibitors. Overall, these data show that resting lymphoid cells can activate at least one inflammasome, revealing additional cell types and states poised to undergo rapid pyroptotic cell death in response to danger-associated signals.
SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs
Authors: Chen Qun , Zhang Fan , Dong Lei , Wu Huimin , Xu Jie , Li Hanqin , Wang Jin , Zhou Zhen , Liu Chunyan , Wang Yanbo , Liu Yuyan , Lu Liangsheng , Wang Chen , Liu Minghui , Chen Xi , Wang Cheng , Zhang Chunni , Li Dangsheng , Zen Ke , Wang Fangyu , Zhang Qipeng , Zhang Chen-Yu
Published: August 2020

Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression, but the absorption mechanism remains unknown. Here, we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs. SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs. Notably, we identified the stomach as the primary site for dietary microRNA absorption, which is dramatically attenuated in the stomachs of SIDT1-deficient mice. Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent. Furthermore, oral administration of plant-derived miR2911 retards liver fibrosis, and this protective effect was abolished in SIDT1-deficient mice. Our findings reveal a major mechanism underlying the absorption of dietary microRNAs, uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.
Stunting in infancy, pubertal trajectories and adult body composition: the Birth to Twenty Plus cohort, South Africa
Authors: Chidumwa Glory , Said-Mohamed Rihlat , Nyati Lukhanyo H. , Mpondo Feziwe , Chikowore Tinashe , Prioreschi Alessandra , Kagura Juliana , Ware Lisa J. , Micklesfield Lisa K. , Norris Shane A.
Published: August 2020

Background/objectives

Childhood rapid growth and earlier puberty onset have been associated with adult obesity. However, the association between childhood stunting, pubertal timing and adult obesity is unclear. We examined whether the relationship between stunting at age 2 years (y) and body composition at 23 years is mediated by adolescent body mass index, and pubertal development, using the Birth-to-Twenty Plus cohort (South Africa).

Subjects/methods

For 1036 participants, data on anthropometrics between birth and 23 years, maternal factors, and pubertal development (Tanner scale at 9–16 years) were collected. Stunting at 2 years (height-for-age z-score < −2), 5–18 years BMI-for-age trajectories, pubertal development trajectories, and DXA-derived fat mass (FM) and fat free mass (FFM) at 23 years were determined. Data were analysed using hierarchical regressions and structural equation models.

Results

Stunting was directly associated with slower pubertal development and with shorter adult stature, but was not associated with adolescent BMI trajectories, adult FM or FFM. However, stunting was indirectly associated with adult FM and FFM through the direct associations between slower pubertal development and lower FM and between shorter height and lower FFM. BMI trajectories were independently associated with FM and FFM.

Conclusions

Being stunted in this population predicted adult body composition through slower pubertal development and shorter adult stature.
A Japanese boy with NAA10-related syndrome and hypertrophic cardiomyopathy
Authors: Shishido Ayumi , Morisada Naoya , Tominaga Kenta , Uemura Hiroyasu , Haruna Akiko , Hanafusa Hiroaki , Nozu Kandai , Iijima Kazumoto
Published: August 2020

NAA10-related syndrome is an extremely rare X-chromosomal disorder, the symptoms of which include intellectual disability (ID), ocular anomalies, or congenital heart diseases, such as hypertrophic cardiomyopathy (HCM). Here, we describe a 4-year-old Japanese male patient who exhibited mild ID, HCM, and specific facial features. A hemizygous mutation (NM_003491.3: c.455_458del, p. Thr152Argfs*6) in exon 7 of NAA10 was detected. We recommend that patients undergo precise medical follow-up considering the characteristics of NAA10-related syndrome.
SLIT2/ROBO1-signaling inhibits macropinocytosis by opposing cortical cytoskeletal remodeling
Authors: Bhosle Vikrant K. , Mukherjee Tapas , Huang Yi-Wei , Patel Sajedabanu , Pang Bo Wen , Liu Guang-Ying , Glogauer Michael , Wu Jane Y. , Philpott Dana J. , Grinstein Sergio , Robinson Lisa A.
Published: August 2020

Macropinocytosis is essential for myeloid cells to survey their environment and for growth of RAS-transformed cancer cells. Several growth factors and inflammatory stimuli are known to induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation of Roundabout receptors by Slit ligands inhibits directional migration of many cell types, including immune cells and cancer cells. We report that SLIT2 inhibits macropinocytosis in vitro and in vivo by inducing cytoskeletal changes in macrophages. In mice, SLIT2 attenuates the uptake of muramyl dipeptide, thereby preventing NOD2-dependent activation of NF-κB and consequent secretion of pro-inflammatory chemokine, CXCL1. Conversely, blocking the action of endogenous SLIT2 enhances CXCL1 secretion. SLIT2 also inhibits macropinocytosis in RAS-transformed cancer cells, thereby decreasing their survival in nutrient-deficient conditions which resemble tumor microenvironment. Our results identify SLIT2 as a physiological inhibitor of macropinocytosis and challenge the conventional notion that signals that enhance macropinocytosis negatively regulate cell migration, and vice versa.
Distinct fibroblast subsets regulate lacteal integrity through YAP/TAZ-induced VEGF-C in intestinal villi
Authors: Hong Seon Pyo , Yang Myung Jin , Cho Hyunsoo , Park Intae , Bae Hosung , Choe Kibaek , Suh Sang Heon , Adams Ralf H. , Alitalo Kari , Lim Daesik , Koh Gou Young
Published: August 2020

Emerging evidence suggests that intestinal stromal cells (IntSCs) play essential roles in maintaining intestinal homeostasis. However, the extent of heterogeneity within the villi stromal compartment and how IntSCs regulate the structure and function of specialized intestinal lymphatic capillary called lacteal remain elusive. Here we show that selective hyperactivation or depletion of YAP/TAZ in PDGFRβ+ IntSCs leads to lacteal sprouting or regression with junctional disintegration and impaired dietary fat uptake. Indeed, mechanical or osmotic stress regulates IntSC secretion of VEGF-C mediated by YAP/TAZ. Single-cell RNA sequencing delineated novel subtypes of villi fibroblasts that upregulate Vegfc upon YAP/TAZ activation. These populations of fibroblasts were distributed in proximity to lacteal, suggesting that they constitute a peri-lacteal microenvironment. Our findings demonstrate the heterogeneity of IntSCs and reveal that distinct subsets of villi fibroblasts regulate lacteal integrity through YAP/TAZ-induced VEGF-C secretion, providing new insights into the dynamic regulatory mechanisms behind lymphangiogenesis and lymphatic remodeling.
Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr−/− mice
Authors: Tao Huan , Huang Jiansheng , Yancey Patricia G. , Yermalitsky Valery , Blakemore John L. , Zhang Youmin , Ding Lei , Zagol-Ikapitte Irene , Ye Fei , Amarnath Venkataraman , Boutaud Olivier , Oates John A. , Roberts L. Jackson , Davies Sean S. , Linton MacRae F.
Published: August 2020

Lipid peroxidation generates reactive dicarbonyls including isolevuglandins (IsoLGs) and malondialdehyde (MDA) that covalently modify proteins. Humans with familial hypercholesterolemia (FH) have increased lipoprotein dicarbonyl adducts and dysfunctional HDL. We investigate the impact of the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in Ldlr−/− mice, a model of FH. Compared to hypercholesterolemic Ldlr−/− mice treated with vehicle or 4-HOBA, a nonreactive analogue, 2-HOBA decreases atherosclerosis by 60% in en face aortas, without changing plasma cholesterol. Ldlr−/− mice treated with 2-HOBA have reduced MDA-LDL and MDA-HDL levels, and their HDL display increased capacity to reduce macrophage cholesterol. Importantly, 2-HOBA reduces the MDA- and IsoLG-lysyl content in atherosclerotic aortas versus 4-HOBA. Furthermore, 2-HOBA reduces inflammation and plaque apoptotic cells and promotes efferocytosis and features of stable plaques. Dicarbonyl scavenging with 2-HOBA has multiple atheroprotective effects in a murine FH model, supporting its potential as a therapeutic approach for atherosclerotic cardiovascular disease.
Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn’s disease
Authors: Zhang Xu , Ning Zhibin , Mayne Janice , Yang Yidai , Deeke Shelley A. , Walker Krystal , Farnsworth Charles L. , Stokes Matthew P. , Couture Jean-François , Mack David , Stintzi Alain , Figeys Daniel
Published: August 2020

Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn’s disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.
Demonstration of chip-based coupled degenerate optical parametric oscillators for realizing a nanophotonic spin-glass
Authors: Okawachi Yoshitomo , Yu Mengjie , Jang Jae K. , Ji Xingchen , Zhao Yun , Kim Bok Young , Lipson Michal , Gaeta Alexander L.
Published: August 2020

The need for solving optimization problems is prevalent in various physical applications, including neuroscience, network design, biological systems, socio-economics, and chemical reactions. Many of these are classified as non-deterministic polynomial-time hard and thus become intractable to solve as the system scales to a large number of elements. Recent research advances in photonics have sparked interest in using a network of coupled degenerate optical parametric oscillators (DOPOs) to effectively find the ground state of the Ising Hamiltonian, which can be used to solve other combinatorial optimization problems through polynomial-time mapping. Here, using the nanophotonic silicon-nitride platform, we demonstrate a spatial-multiplexed DOPO system using continuous-wave pumping. We experimentally demonstrate the generation and coupling of two microresonator-based DOPOs on a single chip. Through a reconfigurable phase link, we achieve both in-phase and out-of-phase operation, which can be deterministically achieved at a fast regeneration speed of 400 kHz with a large phase tolerance.
Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy
Authors: Duan Jia , Shen Dan-dan , Zhou X. Edward , Bi Peng , Liu Qiu-feng , Tan Yang-xia , Zhuang You-wen , Zhang Hui-bing , Xu Pei-yu , Huang Si-Jie , Ma Shan-shan , He Xin-heng , Melcher Karsten , Zhang Yan , Xu H. Eric , Jiang Yi
Published: August 2020

Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species
Authors: Dong Yanan , Yang Peiju , Zhao Shizhen , Li Yuehui
Published: August 2020

Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO2/NH3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.
Micro-environmental sensing by bone marrow stroma identifies IL-6 and TGFβ1 as regulators of hematopoietic ageing
Authors: Valletta Simona , Thomas Alexander , Meng Yiran , Ren Xiying , Drissen Roy , Sengül Hilal , Di Genua Cristina , Nerlov Claus
Published: August 2020

Hematopoietic ageing involves declining erythropoiesis and lymphopoiesis, leading to frequent anaemia and decreased adaptive immunity. How intrinsic changes to the hematopoietic stem cells (HSCs), an altered microenvironment and systemic factors contribute to this process is not fully understood. Here we use bone marrow stromal cells as sensors of age-associated changes to the bone marrow microenvironment, and observe up-regulation of IL-6 and TGFβ signalling-induced gene expression in aged bone marrow stroma. Inhibition of TGFβ signalling leads to reversal of age-associated HSC platelet lineage bias, increased generation of lymphoid progenitors and rebalanced HSC lineage output in transplantation assays. In contrast, decreased erythropoiesis is not an intrinsic property of aged HSCs, but associated with decreased levels and functionality of erythroid progenitor populations, defects ameliorated by TGFβ-receptor and IL-6 inhibition, respectively. These results show that both HSC-intrinsic and -extrinsic mechanisms are involved in age-associated hematopoietic decline, and identify therapeutic targets that promote their reversal.
Discovery of flat seismic reflections in the mantle beneath the young Juan de Fuca Plate
Authors: Qin Yanfang , Singh Satish C. , Grevemeyer Ingo , Marjanović Milena , Roger Buck W.
Published: August 2020

Crustal properties of young oceanic lithosphere have been examined extensively, but the nature of the mantle lithosphere underneath remains elusive. Using a novel wide-angle seismic imaging technique, here we show the presence of two sub-horizontal reflections at ∼11 and ∼14.5 km below the seafloor over the 0.51–2.67 Ma old Juan de Fuca Plate. We find that the observed reflectors originate from 300–600-m-thick layers, with an ∼7–8% drop in P-wave velocity. They could be explained either by the presence of partially molten sills or frozen gabbroic sills. If partially molten, the shallower sill would define the base of a thin lithosphere with the constant thickness (11 km), requiring the presence of a mantle thermal anomaly extending up to 2.67 Ma. In contrast, if these reflections were frozen melt sills, they would imply the presence of thick young oceanic lithosphere (20–25 km), and extremely heterogeneous upper mantle.
CRISPR GUARD protects off-target sites from Cas9 nuclease activity using short guide RNAs
Authors: Coelho Matthew A. , De Braekeleer Etienne , Firth Mike , Bista Michal , Lukasiak Sebastian , Cuomo Maria Emanuela , Taylor Benjamin J. M.
Published: August 2020

Precise genome editing using CRISPR-Cas9 is a promising therapeutic avenue for genetic diseases, although off-target editing remains a significant safety concern. Guide RNAs shorter than 16 nucleotides in length effectively recruit Cas9 to complementary sites in the genome but do not permit Cas9 nuclease activity. Here we describe CRISPR Guide RNA Assisted Reduction of Damage (CRISPR GUARD) as a method for protecting off-targets sites by co-delivery of short guide RNAs directed against off-target loci by competition with the on-target guide RNA. CRISPR GUARD reduces off-target mutagenesis while retaining on-target editing efficiencies with Cas9 and base editor. However, we discover that short guide RNAs can also support base editing if they contain cytosines within the deaminase activity window. We explore design rules and the universality of this method through in vitro studies and high-throughput screening, revealing CRISPR GUARD as a rapidly implementable strategy to improve the specificity of genome editing for most genomic loci. Finally, we create an online tool for CRISPR GUARD design.
Electronic correlations and transport in iron at Earth’s core conditions
Authors: Pourovskii L. V. , Mravlje J. , Pozzo M. , Alfè D.
Published: August 2020

The transport properties of iron under Earth’s inner core conditions are essential input for the geophysical modelling but are poorly constrained experimentally. Here we show that the thermal and electrical conductivity of iron at those conditions remains high even if the electron-electron-scattering (EES) is properly taken into account. This result is obtained by ab initio simulations taking into account consistently both thermal disorder and electronic correlations. Thermal disorder suppresses the non-Fermi-liquid behavior of the body-centered cubic iron phase, hence, reducing the EES; the total calculated thermal conductivity of this phase is 220 Wm−1 K−1 with the EES reduction not exceeding 20%. The EES and electron-lattice scattering are intertwined resulting in breaking of the Matthiessen’s rule with increasing EES. In the hexagonal close-packed iron the EES is also not increased by thermal disorder and remains weak. Our main finding thus holds for the both likely iron phases in the inner core.
Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: a case–control study
Authors: Pelletier Jean-Pierre , Raynauld Jean-Pierre , Abram François , Dorais Marc , Paiement Patrice , Martel-Pelletier Johanne
Published: August 2020

Although intra-articular corticosteroid injections (IACI) are commonly used for the treatment of knee osteoarthritis (OA), there is controversy regarding possible deleterious effects on joint structure. In this line, this study investigates the effects of IACI on the evolution of knee OA structural changes and pain. Participants for this nested case–control study were from the Osteoarthritis Initiative. Knees of participants who had received an IACI and had magnetic resonance images (MRI) were named cases (n = 93), and each matched with one control (n = 93). Features assessed at the yearly visits and their changes within the follow-up period were from MRI (cartilage volume, meniscal thickness, bone marrow lesions, bone curvature, and synovial effusion size), X-ray (joint space width), and clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain score) data. Participants who received IACI experienced a transient and significantly greater rate of loss of the meniscal thickness (p = 0.006) and joint space width (p = 0.011) in the knee medial compartment in the year they received the injection, compared to controls. No significant effect of the IACI was found on the rate of cartilage loss nor on any other knee structural changes or WOMAC pain post-treatment. In conclusion, a single IACI in knee OA was shown to be safe with no negative impact on structural changes, but there was a transient meniscal thickness reduction, a phenomenon for which the clinical relevance is at present unknown.
Publisher Correction: Minimally Invasive Hemostatic Materials: Tackling a Dilemma of Fluidity and Adhesion by Photopolymerization in situ
Authors: Zhang Yun , Song Dandan , Huang Hong , Liang Zhiling , Liu Houhe , Huang Yugang , Zhong Cheng , Ye Guodong
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Compression and stretch sensitive submucosal neurons of the porcine and human colon
Authors: Filzmayer Anna Katharina , Elfers Kristin , Michel Klaus , Buhner Sabine , Zeller Florian , Demir Ihsan Ekin , Theisen Jörg , Schemann Michael , Mazzuoli-Weber Gemma
Published: August 2020

The pig is commonly believed to be a relevant model for human gut functions—however, there are only a few comparative studies and none on neural control mechanisms. To address this lack we identified as one central aspect mechanosensitive enteric neurons (MEN) in porcine and human colon. We used neuroimaging techniques to record responses to tensile or compressive forces in submucous neurons. Compression and stretch caused Ca-transients and immediate spike discharge in 5–11% of porcine and 15–24% of human enteric neurons. The majority of these MEN exclusively responded to either stimulus quality but about 9% responded to both. Most of the MEN expressed choline acetyltransferase and substance P; nitric oxide synthase-positive MEN primarily occurred in distal colon. The findings reveal common features of MEN in human and pig colon which we interpret as a result of species-independent evolutionary conservation rather than a specific functional proximity between the two species.
Effect of kaempferol on the transgenic Drosophila model of Parkinson’s disease
Authors: Rahul  , Naz Falaq , Jyoti Smita , Siddique Yasir Hasan
Published: August 2020

The present study was aimed to study the effect of kaempferol, on the transgenic Drosophila model of Parkinson’s disease. Kaempferol was added in the diet at final concentration of 10, 20, 30 and 40 µM and the effect was studied on various cognitive and oxidative stress markers. The results of the study showed that kaempferol, delayed the loss of climbing ability as well as the activity of PD flies in a dose dependent manner compared to unexposed PD flies. A dose-dependent reduction in oxidative stress markers was also observed. Histopathological examination of fly brains using anti-tyrosine hydroxylase immunostaining has revealed a significant dose-dependent increase in the expression of tyrosine hydroxylase in PD flies exposed to kaempferol. Molecular docking results revealed that kaempferol binds to human alpha synuclein at specific sites that might results in the inhibition of alpha synuclein aggregation and prevents the formation of Lewy bodies.
Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis
Authors: Sailem Heba Z. , Al Haj Zen Ayman
Published: August 2020

Angiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. Chemical genetic screening of endothelial tube formation provides a robust approach for identifying signalling components that impact microvascular network morphology as well as endothelial cell biology. However, the analysis of the resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 characterised drugs, we found that drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed that a group of glutamate receptor antagonists enhances branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes is associated with the prognosis of Alzheimer’s patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesis-related diseases.
Campylobacter infections expected to increase due to climate change in Northern Europe
Authors: Kuhn Katrin Gaardbo , Nygård Karin Maria , Guzman-Herrador Bernardo , Sunde Linda Selje , Rimhanen-Finne Ruska , Trönnberg Linda , Jepsen Martin Rudbeck , Ruuhela Reija , Wong Wai Kwok , Ethelberg Steen
Published: August 2020

Global climate change is predicted to alter precipitation and temperature patterns across the world, affecting a range of infectious diseases and particularly foodborne infections such as Campylobacter. In this study, we used national surveillance data to analyse the relationship between climate and campylobacteriosis in Denmark, Finland, Norway and Sweden and estimate the impact of climate changes on future disease patterns. We show that Campylobacter incidences are linked to increases in temperature and especially precipitation in the week before illness, suggesting a non-food transmission route. These four countries may experience a doubling of Campylobacter cases by the end of the 2080s, corresponding to around 6,000 excess cases per year caused only by climate changes. Considering the strong worldwide burden of campylobacteriosis, it is important to assess local and regional impacts of climate change in order to initiate timely public health management and adaptation strategies.
Analysis of small RNA populations generated in peanut leaves after exogenous application of dsRNA and dsDNA targeting aflatoxin synthesis genes
Authors: Power Imana L. , Faustinelli Paola C. , Orner Valerie A. , Sobolev Victor S. , Arias Renee S.
Published: August 2020

Previously, we have shown that RNA interference (RNAi) can prevent aflatoxin accumulation in transformed peanuts. To explore aflatoxin control by exogenous delivery of double-strand RNA (dsRNA) it is necessary to understand the generation of small RNA (sRNA) populations. We sequenced 12 duplicate sRNA libraries of in-vitro-grown peanut plants, 24 and 48 h after exogenous application of five gene fragments (RNAi-5x) related to aflatoxin biosynthesis in Aspergillus flavus. RNAi-5x was applied either as double-stranded RNA (dsRNA) or RNAi plasmid DNA (dsDNA). Small interfering RNAs (siRNAs) derived from RNAi-5x were significantly more abundant at 48 h than at 24 h, and the majority mapped to the fragment of aflatoxin efflux-pump gene. RNAi-5x-specific siRNAs were significantly, three to fivefold, more abundant in dsDNA than dsRNA treatments. Further examination of known micro RNAs related to disease-resistance, showed significant down-regulation of miR399 and up-regulation of miR482 in leaves treated with dsDNA compared to the control. These results show that sRNA sequencing is useful to compare exogenous RNAi delivery methods on peanut plants, and to analyze the efficacy of molecular constructs to generate siRNAs against specific gene targets. This work lays the foundation for non-transgenic delivery of RNAi in controlling aflatoxins in peanut.
Salt coatings functionalize inert membranes into high-performing filters against infectious respiratory diseases
Authors: Rubino Ilaria , Oh Euna , Han Sumin , Kaleem Sana , Hornig Alex , Lee Su-Hwa , Kang Hae-Ji , Lee Dong-Hun , Chu Ki-Back , Kumaran Surjith , Armstrong Sarah , Lalani Romani , Choudhry Shivanjali , Kim Chun Il , Quan Fu-Shi , Jeon Byeonghwa , Choi Hyo-Jick
Published: August 2020

Respiratory protection is key in infection prevention of airborne diseases, as highlighted by the COVID-19 pandemic for instance. Conventional technologies have several drawbacks (i.e., cross-infection risk, filtration efficiency improvements limited by difficulty in breathing, and no safe reusability), which have yet to be addressed in a single device. Here, we report the development of a filter overcoming the major technical challenges of respiratory protective devices. Large-pore membranes, offering high breathability but low bacteria capture, were functionalized to have a uniform salt layer on the fibers. The salt-functionalized membranes achieved high filtration efficiency as opposed to the bare membrane, with differences of up to 48%, while maintaining high breathability (> 60% increase compared to commercial surgical masks even for the thickest salt filters tested). The salt-functionalized filters quickly killed Gram-positive and Gram-negative bacteria aerosols in vitro, with CFU reductions observed as early as within 5 min, and in vivo by causing structural damage due to salt recrystallization. The salt coatings retained the pathogen inactivation capability at harsh environmental conditions (37 °C and a relative humidity of 70%, 80% and 90%). Combination of these properties in one filter will lead to the production of an effective device, comprehensibly mitigating infection transmission globally.
Redox-active, luminescent coordination nanosheet capsules containing magnetite
Authors: Arai Ryo , Li Mengjuan , Toyoda Ryojun , Maeda Hiroaki , Nishihara Hiroshi
Published: August 2020

Two-dimensional coordination nanosheets (CONASHs) are grown at the spherical liquid–liquid interface of a dichloromethane droplet in water to form zero-dimensional nano- and micro-capsules using a simple dropping method, a syringe-pump method, and an emulsion method. Reaction of 1,3,5-tris[4-(4′-2,2′:6′,2″-terpyridyl)phenyl]benzene (1) with Fe(BF4)2 affords electrochromic Fe(tpy)2 CONASH capsules and that of ligand 1 with ZnSO4 does photoluminescent Zn2(μ-O2SO2)2(tpy)2 CONASH capsules. Fe(tpy)2 CONASH capsules containing magnetite particles were produced by the syringe-pump method by adding magnetite to the aqueous phase, with the assembly and dispersion of the magnetite-containing CONASH capsules being easily controlled with a magnet. This indicates that physicochemically functional CONASH capsules are suitable for incorporating other functional materials to develop hybrid systems.
Spectral dependence of third-order susceptibility of Au triangular nanoplates
Authors: Zhang Boyi , Sato Rodrigo , Tanaka Miyoko , Takeda Yoshihiko
Published: August 2020

We experimentally investigated the spectral dependence of the third-order susceptibility $$\chi^{\left( 3 \right)}$$

χ

3

of Au triangular nanoplates in a broad wavelength region (400–1,000 nm). Complex shaped plasmonic nanoparticles provide a promising route to achieve control of their optical properties at the nanoscale. However, little is known about the effects of geometrical parameters to the optical nonlinearities and underlying mechanisms of the plasmon modes. Here, we obtained the $$\chi^{\left( 3 \right)}$$

χ

3

of Au triangular nanoplates featuring a narrow plasmon resonance that is tunable in the visible and near-IR regions. This work demonstrates that the plasmonic triangular nanoplates simultaneously shows self-focusing and -defocusing, and saturable and reverse-saturable absorption properties at specific wavelength regions. Maximum amplitudes of real and imaginary components are − 6.8 × 10−18 m2/V2 at 668 nm and − 6.7 × 10−18 m2/V2 at 646 nm, respectively. Spectral dependence of the quantity $$\chi^{\left( 3 \right)}$$

χ

3

enables comparison between different shaped plasmonic NPs to boost active plasmonic applications performance.
Versatile formation of supported lipid bilayers from bicellar mixtures of phospholipids and capric acid
Authors: Sut Tun Naw , Yoon Bo Kyeong , Park Soohyun , Jackman Joshua A. , Cho Nam-Joon
Published: August 2020

Originally developed for the structural biology field, lipid bicelle nanostructures composed of long- and short-chain phospholipid molecules have emerged as a useful interfacial science tool to fabricate two-dimensional supported lipid bilayers (SLBs) on hydrophilic surfaces due to ease of sample preparation, scalability, and versatility. To improve SLB fabrication prospects, there has been recent interest in replacing the synthetic, short-chain phospholipid component of bicellar mixtures with naturally abundant fatty acids and monoglycerides, i.e., lauric acid and monocaprin. Such options have proven successful under specific conditions, however, there is room for devising more versatile fabrication options, especially in terms of overcoming lipid concentration-dependent SLB formation limitations. Herein, we investigated SLB fabrication by using bicellar mixtures consisting of long-chain phospholipid and capric acid, the latter of which has similar headgroup and chain length properties to lauric acid and monocaprin, respectively. Quartz crystal microbalance-dissipation, epifluorescence microscopy, and fluorescence recovery after photobleaching experiments were conducted to characterize lipid concentration-dependent bicelle adsorption onto silicon dioxide surfaces. We identified that uniform-phase SLB formation occurred independently of total lipid concentration when the ratio of long-chain phospholipid to capric acid molecules (“q-ratio”) was 0.25 or 2.5, which is superior to past results with lauric acid- and monocaprin-containing bicelles in which cases lipid concentration-dependent behavior was observed. Together, these findings demonstrate that capric acid-containing bicelles are versatile tools for SLB fabrication and highlight how the molecular structure of bicelle components can be rationally finetuned to modulate self-assembly processes at solid–liquid interfaces.
Decreased expression of the thyroid hormone-inactivating enzyme type 3 deiodinase is associated with lower survival rates in breast cancer
Authors: Goemann Iuri Martin , Marczyk Vicente Rodrigues , Recamonde-Mendoza Mariana , Wajner Simone Magagnin , Graudenz Marcia Silveira , Maia Ana Luiza
Published: August 2020

Thyroid hormones (THs) are critical regulators of cellular processes, while changes in their levels impact all the hallmarks of cancer. Disturbed expression of type 3 deiodinase (DIO3), the main TH-inactivating enzyme, occurs in several human neoplasms and has been associated with adverse outcomes. Here, we investigated the patterns of DIO3 expression and its prognostic significance in breast cancer. DIO3 expression was evaluated by immunohistochemistry in a primary cohort of patients with breast cancer and validated in a second cohort using RNA sequencing data from the TCGA database. DNA methylation data were obtained from the same database. DIO3 expression was present in normal and tumoral breast tissue. Low levels of DIO3 expression were associated with increased mortality in the primary cohort. Accordingly, lowDIO3mRNA levels were associated with an increased risk of death in a multivariate model in the validation cohort. DNA methylation analysis revealed that theDIO3gene promoter is hypermethylated in tumors when compared to normal tissue. In conclusion, DIO3 is expressed in normal and tumoral breast tissue, while decreased expression relates to poor overall survival in breast cancer patients. Finally, loss of DIO3 expression is associated with hypermethylation of the gene promoter and might have therapeutic implications.