bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity
Authors: Yan Chenxu , Zeng Tianshu , Lee Kailun , Nobis Max , Loh Kim , Gou Luoning , Xia Zefeng , Gao Zhongmin , Bensellam Mohammed , Hughes Will , Lau Jackie , Zhang Lei , Ip Chi Kin , Enriquez Ronaldo , Gao Hanyu , Wang Qiao-Ping , Wu Qi , Haigh Jody J. , Laybutt D. Ross , Timpson Paul , Herzog Herbert , Shi Yan-Chuan
Published: May 2021

Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism of peripheral Y1R, via the non-brain penetrable antagonist BIBO3304, leads to a significant reduction in body weight gain due to enhanced EE thereby reducing fat mass. Specifically thermogenesis in brown adipose tissue (BAT) due to elevated UCP1 is enhanced accompanied by extensive browning of white adipose tissue both in mice and humans. Importantly, selective ablation of Y1R from adipocytes protects against diet-induced obesity. Furthermore, peripheral specific Y1R antagonism also improves glucose homeostasis mainly driven by dynamic changes in Akt activity in BAT. Together, these data suggest that selective peripheral only Y1R antagonism via BIBO3304, or a functional analogue, could be developed as a safer and more effective treatment option to mitigate diet-induced obesity.
CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion
Authors: Li Zhiqian , Marcel Nimi , Devkota Sushil , Auradkar Ankush , Hedrick Stephen M. , Gantz Valentino M. , Bier Ethan
Published: May 2021

CRISPR-based active genetic elements, or gene-drives, copied via homology-directed repair (HDR) in the germline, are transmitted to progeny at super-Mendelian frequencies. Active genetic elements also can generate widespread somatic mutations, but the genetic basis for such phenotypes remains uncertain. It is generally assumed that such somatic mutations are generated by non-homologous end-joining (NHEJ), the predominant double stranded break repair pathway active in somatic cells. Here, we develop CopyCatcher systems in Drosophila to detect and quantify somatic gene conversion (SGC) events. CopyCatchers inserted into two independent genetic loci reveal unexpectedly high rates of SGC in the Drosophila eye and thoracic epidermis. Focused RNAi-based genetic screens identify several unanticipated loci altering SGC efficiency, one of which (c-MYC), when downregulated, promotes SGC mediated by both plasmid and homologous chromosome-templates in human HEK293T cells. Collectively, these studies suggest that CopyCatchers can serve as effective discovery platforms to inform potential gene therapy strategies.
A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia
Authors: Fan Shengjie , Xu Yuanzhong , Lu Yungang , Jiang Zhiying , Li Hongli , Morrill Jessie C. , Cai Jing , Wu Qi , Xu Yong , Xue Mingshan , Arenkiel Benjamin R. , Huang Cheng , Tong Qingchun
Published: May 2021

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepRArc) are selectively activated in T1D. Activation of LepRArc neurons, Arc GABAergic (GABAArc) neurons, or arcuate AgRP neurons, is able to reverse the leptin’s rescuing effect. Conversely, inhibition of GABAArc neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin’s rescuing effects. Finally, T1D LepRArc neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepRArc neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepRArc neurons through reversing energy deprivation.
Regulating coordination number in atomically dispersed Pt species on defect-rich graphene for n-butane dehydrogenation reaction
Authors: Chen Xiaowen , Peng Mi , Cai Xiangbin , Chen Yunlei , Jia Zhimin , Deng Yuchen , Mei Bingbao , Jiang Zheng , Xiao Dequan , Wen Xiaodong , Wang Ning , Liu Hongyang , Ma Ding
Published: May 2021

Metal nanoparticle (NP), cluster and isolated metal atom (or single atom, SA) exhibit different catalytic performance in heterogeneous catalysis originating from their distinct nanostructures. To maximize atom efficiency and boost activity for catalysis, the construction of structure–performance relationship provides an effective way at the atomic level. Here, we successfully fabricate fully exposed Pt3 clusters on the defective nanodiamond@graphene (ND@G) by the assistance of atomically dispersed Sn promoters, and correlated the n-butane direct dehydrogenation (DDH) activity with the average coordination number (CN) of Pt-Pt bond in Pt NP, Pt3 cluster and Pt SA for fundamentally understanding structure (especially the sub-nano structure) effects on n-butane DDH reaction at the atomic level. The as-prepared fully exposed Pt3 cluster catalyst shows higher conversion (35.4%) and remarkable alkene selectivity (99.0%) for n-butane direct DDH reaction at 450 °C, compared to typical Pt NP and Pt SA catalysts supported on ND@G. Density functional theory calculation (DFT) reveal that the fully exposed Pt3 clusters possess favorable dehydrogenation activation barrier of n-butane and reasonable desorption barrier of butene in the DDH reaction.
An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness
Authors: Liu Lei , Tao Tianyu , Liu Shihua , Yang Xia , Chen Xuwei , Liang Jiaer , Hong Ruohui , Wang Wenting , Yang Yi , Li Xiaoyi , Zhang Youhong , Li Quanfeng , Liang Shujun , Yu Haocheng , Wu Yun , Guo Xinyu , Lai Yan , Ding Xiaofan , Guan Hongyu , Wu Jueheng , Zhu Xun , Yuan Jie , Li Jun , Su Shicheng , Li Mengfeng , Cai Xiuyu , Cai Junchao , Tian Han
Published: May 2021

Notch signaling represents a key mechanism mediating cancer metastasis and stemness. To understand how Notch signaling is overactivated to couple tumor metastasis and self-renewal in NSCLC cells, we performed the current study and showed that RFC4, a DNA replication factor amplified in more than 40% of NSCLC tissues, directly binds to the Notch1 intracellular domain (NICD1) to competitively abrogate CDK8/FBXW7-mediated degradation of NICD1. Moreover, RFC4 is a functional transcriptional target gene of Notch1 signaling, forming a positive feedback loop between high RFC4 and NICD1 levels and sustained overactivation of Notch signaling, which not only leads to NSCLC tumorigenicity and metastasis but also confers NSCLC cell resistance to treatment with the clinically tested drug DAPT against NICD1 synthesis. Furthermore, together with our study, analysis of two public datasets involving more than 1500 NSCLC patients showed that RFC4 gene amplification, and high RFC4 and NICD1 levels were tightly correlated with NSCLC metastasis, progression and poor patient prognosis. Therefore, our study characterizes the pivotal roles of the positive feedback loop between RFC4 and NICD1 in coupling NSCLC metastasis and stemness properties and suggests its therapeutic and diagnostic/prognostic potential for NSCLC therapy.
YAP promotes the activation of NLRP3 inflammasome via blocking K27-linked polyubiquitination of NLRP3
Authors: Wang Dan , Zhang Yening , Xu Xueming , Wu Jianfeng , Peng Yue , Li Jing , Luo Ruiheng , Huang Lingmin , Liu Liping , Yu Songlin , Zhang Ningjie , Lu Ben , Zhao Kai
Published: May 2021

The transcription coactivator YAP plays a vital role in Hippo pathway for organ-size control and tissue homeostasis. Recent studies have demonstrated YAP is closely related to immune disorders and inflammatory diseases, but the underlying mechanisms remain less defined. Here, we find that YAP promotes the activation of NLRP3 inflammasome, an intracellular multi-protein complex that orchestrates host immune responses to infections or sterile injuries. YAP deficiency in myeloid cells significantly attenuates LPS-induced systemic inflammation and monosodium urate (MSU) crystals-induced peritonitis. Mechanistically, YAP physically interacts with NLRP3 and maintains the stability of NLRP3 through blocking the association between NLRP3 and the E3 ligase β-TrCP1, the latter increases the proteasomal degradation of NLRP3 via K27-linked ubiquitination at lys380. Together, these findings establish a role of YAP in the activation of NLRP3 inflammasome, and provide potential therapeutic target to treat the NLRP3 inflammasome-related diseases.
Metal-organic framework membranes with single-atomic centers for photocatalytic CO2 and O2 reduction
Authors: Hao Yu-Chen , Chen Li-Wei , Li Jiani , Guo Yu , Su Xin , Shu Miao , Zhang Qinghua , Gao Wen-Yan , Li Siwu , Yu Zi-Long , Gu Lin , Feng Xiao , Yin An-Xiang , Si Rui , Zhang Ya-Wen , Wang Bo , Yan Chun-Hua
Published: May 2021

The demand for sustainable energy has motivated the development of artificial photosynthesis. Yet the catalyst and reaction interface designs for directly fixing permanent gases (e.g. CO2, O2, N2) into liquid fuels are still challenged by slow mass transfer and sluggish catalytic kinetics at the gas-liquid-solid boundary. Here, we report that gas-permeable metal-organic framework (MOF) membranes can modify the electronic structures and catalytic properties of metal single-atoms (SAs) to promote the diffusion, activation, and reduction of gas molecules (e.g. CO2, O2) and produce liquid fuels under visible light and mild conditions. With Ir SAs as active centers, the defect-engineered MOF (e.g. activated NH2-UiO-66) particles can reduce CO2 to HCOOH with an apparent quantum efficiency (AQE) of 2.51% at 420 nm on the gas-liquid-solid reaction interface. With promoted gas diffusion at the porous gas-solid interfaces, the gas-permeable SA/MOF membranes can directly convert humid CO2 gas into HCOOH with a near-unity selectivity and a significantly increased AQE of 15.76% at 420 nm. A similar strategy can be applied to the photocatalytic O2-to-H2O2 conversions, suggesting the wide applicability of our catalyst and reaction interface designs.
The histone variant H2A.W and linker histone H1 co-regulate heterochromatin accessibility and DNA methylation
Authors: Bourguet Pierre , Picard Colette L. , Yelagandula Ramesh , Pélissier Thierry , Lorković Zdravko J. , Feng Suhua , Pouch-Pélissier Marie-Noëlle , Schmücker Anna , Jacobsen Steven E. , Berger Frédéric , Mathieu Olivier
Published: May 2021

In flowering plants, heterochromatin is demarcated by the histone variant H2A.W, elevated levels of the linker histone H1, and specific epigenetic modifications, such as high levels of DNA methylation at both CG and non-CG sites. How H2A.W regulates heterochromatin organization and interacts with other heterochromatic features is unclear. Here, we create a h2a.w null mutant via CRISPR-Cas9, h2a.w-2, to analyze the in vivo function of H2A.W. We find that H2A.W antagonizes deposition of H1 at heterochromatin and that non-CG methylation and accessibility are moderately decreased in h2a.w-2 heterochromatin. Compared to H1 loss alone, combined loss of H1 and H2A.W greatly increases accessibility and facilitates non-CG DNA methylation in heterochromatin, suggesting co-regulation of heterochromatic features by H2A.W and H1. Our results suggest that H2A.W helps maintain optimal heterochromatin accessibility and DNA methylation by promoting chromatin compaction together with H1, while also inhibiting excessive H1 incorporation.
On-chip spectrometers using stratified waveguide filters
Authors: Li Ang , Fainman Yeshaiahu
Published: May 2021

We present an ultra-compact single-shot spectrometer on silicon platform for sparse spectrum reconstruction. It consists of 32 stratified waveguide filters (SWFs) with diverse transmission spectra for sampling the unknown spectrum of the input signal and a specially designed ultra-compact structure for splitting the incident signal into those 32 filters with low power imbalance. Each SWF has a footprint less than 1 µm × 30 µm, while the 1 × 32 splitter and 32 filters in total occupy an area of about 35 µm × 260 µm, which to the best of our knowledge, is the smallest footprint spectrometer realized on silicon photonic platform. Experimental characteristics of the fabricated spectrometer demonstrate a broad operating bandwidth of 180 nm centered at 1550 nm and narrowband peaks with 0.45 nm Full-Width-Half-Maximum (FWHM) can be clearly resolved. This concept can also be implemented using other material platforms for operation in optical spectral bands of interest for various applications.
ZBP1 not RIPK1 mediates tumor necroptosis in breast cancer
Authors: Baik Jin Young , Liu Zhaoshan , Jiao Delong , Kwon Hyung-Joon , Yan Jiong , Kadigamuwa Chamila , Choe Moran , Lake Ross , Kruhlak Michael , Tandon Mayank , Cai Zhenyu , Choksi Swati , Liu Zheng-gang
Published: May 2021

Tumor necrosis happens commonly in advanced solid tumors. We reported that necroptosis plays a major role in tumor necrosis. Although several key necroptosis regulators including receptor interacting protein kinase 1 (RIPK1) have been identified, the regulation of tumor necroptosis during tumor development remains elusive. Here, we report that Z-DNA-binding protein 1 (ZBP1), not RIPK1, mediates tumor necroptosis during tumor development in preclinical cancer models. We found that ZBP1 expression is dramatically elevated in necrotic tumors. Importantly, ZBP1, not RIPK1, deletion blocks tumor necroptosis during tumor development and inhibits metastasis. We showed that glucose deprivation triggers ZBP1-depedent necroptosis in tumor cells. Glucose deprivation causes mitochondrial DNA (mtDNA) release to the cytoplasm and the binding of mtDNA to ZBP1 to activate MLKL in a BCL-2 family protein, NOXA-dependent manner. Therefore, our study reveals ZBP1 as the key regulator of tumor necroptosis and provides a potential drug target for controlling tumor metastasis.
Unified theory for light-induced halide segregation in mixed halide perovskites
Authors: Chen Zehua , Brocks Geert , Tao Shuxia , Bobbert Peter A.
Published: May 2021

Mixed halide perovskites that are thermodynamically stable in the dark demix under illumination. This is problematic for their application in solar cells. We present a unified thermodynamic theory for this light-induced halide segregation that is based on a free energy lowering of photocarriers funnelling to a nucleated phase with different halide composition and lower band gap than the parent phase. We apply the theory to a sequence of mixed iodine-bromine perovskites. The spinodals separating metastable and unstable regions in the composition-temperature phase diagrams only slightly change under illumination, while light-induced binodals separating stable and metastable regions appear signalling the nucleation of a low-band gap iodine-rich phase. We find that the threshold photocarrier density for halide segregation is governed by the band gap difference of the parent and iodine-rich phase. Partial replacement of organic cations by cesium reduces this difference and therefore has a stabilizing effect.
Gut microbiome modulates Drosophila aggression through octopamine signaling
Authors: Jia Yicong , Jin Shan , Hu Kunkun , Geng Lei , Han Caihong , Kang Ruxue , Pang Yuxin , Ling Erjun , Tan Eng King , Pan Yufeng , Liu Wei
Published: May 2021

Gut microbiome profoundly affects many aspects of host physiology and behaviors. Here we report that gut microbiome modulates aggressive behaviors in Drosophila. We found that germ-free males showed substantial decrease in inter-male aggression, which could be rescued by microbial re-colonization. These germ-free males are not as competitive as wild-type males for mating with females, although they displayed regular levels of locomotor and courtship behaviors. We further found that Drosophila microbiome interacted with diet during a critical developmental period for the proper expression of octopamine and manifestation of aggression in adult males. These findings provide insights into how gut microbiome modulates specific host behaviors through interaction with diet during development.
Unravelling the electron injection/transport mechanism in organic light-emitting diodes
Authors: Sasaki Tsubasa , Hasegawa Munehiro , Inagaki Kaito , Ito Hirokazu , Suzuki Kazuma , Oono Taku , Morii Katsuyuki , Shimizu Takahisa , Fukagawa Hirohiko
Published: May 2021

Although significant progress has been made in the development of light-emitting materials for organic light-emitting diodes along with the elucidation of emission mechanisms, the electron injection/transport mechanism remains unclear, and the materials used for electron injection/transport have been basically unchanged for more than 20 years. Here, we unravelled the electron injection/transport mechanism by tuning the work function near the cathode to about 2.0 eV using a superbase. This extremely low-work function cathode allows direct electron injection into various materials, and it was found that organic materials can transport electrons independently of their molecular structure. On the basis of these findings, we have realised a simply structured blue organic light-emitting diode with an operational lifetime of more than 1,000,000 hours. Unravelling the electron injection/transport mechanism, as reported in this paper, not only greatly increases the choice of materials to be used for devices, but also allows simple device structures.
Community composition of microbial microcosms follows simple assembly rules at evolutionary timescales
Authors: Meroz Nittay , Tovi Nesli , Sorokin Yael , Friedman Jonathan
Published: May 2021

Managing and engineering microbial communities relies on the ability to predict their composition. While progress has been made on predicting compositions on short, ecological timescales, there is still little work aimed at predicting compositions on evolutionary timescales. Therefore, it is still unknown for how long communities typically remain stable after reaching ecological equilibrium, and how repeatable and predictable are changes when they occur. Here, we address this knowledge gap by tracking the composition of 87 two- and three-species bacterial communities, with 3–18 replicates each, for ~400 generations. We find that community composition typically changed during evolution, but that the composition of replicate communities remained similar. Furthermore, these changes were predictable in a bottom-up approach—changes in the composition of trios were consistent with those that occurred in pairs during coevolution. Our results demonstrate that simple assembly rules can hold even on evolutionary timescales, suggesting it may be possible to forecast the evolution of microbial communities.
Publisher Correction: Spatial modeling of biological patterns shows multiscale organization of Arabidopsis thaliana heterochromatin
Authors: Arpòn Javier , Sakai Kaori , Gaudin Valérie , Andrey Philippe
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mechanisms of halosulfuron methyl pesticide biosorption onto neem seeds powder
Authors: Haq Atta ul , Saeed Muhammad , Usman Muhammad , Zahoor Ameer Fawad , Anjum Muhammad Naveed , Maqbool Tahir , Naheed Shazia , Kashif Muhammad
Published: May 2021

The current investigation was designed to remove halosulfuron methyl from aqueous media by means of neem seed powder (NSP) in batch modes. Characterizations of NSP were carried out by using EDX, SEM, FTIR, point of zero charge and surface analysis. Optimum operation conditions were scrutinized by studying the influence of different factors like solution pH, dose of NSP, contact time, initial halosulfuron methyl concentration and temperature. Result indicates the dependency of the removal of halosulfuron methyl on solution pH and maximal removal (54%) was achieved in acidic medium (i.e. pH 3.0). To identify the chemical surface of NSP, point of zero charge of NSP was determined and was found to be 6.5 which imply that the surface of NSP is positively charged below pH 6.6 and favored the anionic sorption. Kinetics of halosulfuron methyl were demonstrated well by pseudo second order due to highest R2 (0.99) owing to the nearness between experimental and calculated sorption capacities. Isotherm results imply that Langmuir was found to the principal model to explain the removal of halosulfuron methyl and maximum monolayer sorption capacity was determined to be 200 mg g−1. Thermodynamic parameters like ΔH°, ΔG° and ΔS° were calculated from van’t Hoff plot and were found negative which suggest that removal of halosulfuron methyl is exothermic and spontaneous at low temperature. These outcomes insinuate that neem seed power may be a valuable, inexpensive and ecofriendly biosorbent for the removal of pesticides.
A unified resource and configurable model of the synapse proteome and its role in disease
Authors: Sorokina Oksana , Mclean Colin , Croning Mike D. R. , Heil Katharina F. , Wysocka Emilia , He Xin , Sterratt David , Grant Seth G. N. , Simpson T. Ian , Armstrong J. Douglas
Published: May 2021

Genes encoding synaptic proteins are highly associated with neuronal disorders many of which show clinical co-morbidity. We integrated 58 published synaptic proteomic datasets that describe over 8000 proteins and combined them with direct protein–protein interactions and functional metadata to build a network resource that reveals the shared and unique protein components that underpin multiple disorders. All the data are provided in a flexible and accessible format to encourage custom use.
DNA methylation landscape of 16 canine somatic tissues by methylation-sensitive restriction enzyme-based next generation sequencing
Authors: Yamazaki Jumpei , Matsumoto Yuki , Jelinek Jaroslav , Ishizaki Teita , Maeda Shingo , Watanabe Kei , Ishihara Genki , Yamagishi Junya , Takiguchi Mitsuyoshi
Published: May 2021

DNA methylation plays important functions in gene expression regulation that is involved in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in companion animals like dog. Using methylation-sensitive restriction enzyme-based next generation sequencing (Canine DREAM), we obtained canine DNA methylation maps of 16 somatic tissues from two dogs. In total, we evaluated 130,861 CpG sites. The majority of CpG sites were either highly methylated (> 70%, 52.5–64.6% of all CpG sites analyzed) or unmethylated (< 30%, 22.5–28.0% of all CpG sites analyzed) which are methylation patterns similar to other species. The overall methylation status of CpG sites across the 32 methylomes were remarkably similar. However, the tissue types were clearly defined by principle component analysis and hierarchical clustering analysis with DNA methylome. We found 6416 CpG sites located closely at promoter region of genes and inverse correlation between DNA methylation and gene expression of these genes. Our study provides basic dataset for DNA methylation profiles in dogs.
Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study
Authors: Kobayashi Sumitaka , Sata Fumihiro , Goudarzi Houman , Araki Atsuko , Miyashita Chihiro , Sasaki Seiko , Okada Emiko , Iwasaki Yusuke , Nakajima Tamie , Kishi Reiko
Published: May 2021

The effect of interactions between perfluorooctanesulfonic (PFOS)/perfluorooctanoic acid (PFOA) levels and nuclear receptor genotypes on fatty acid (FA) levels, including those of triglycerides, is not clear understood. Therefore, in the present study, we aimed to analyse the association of PFOS/PFOA levels and single-nucleotide polymorphisms (SNPs) in nuclear receptors with FA levels in pregnant women. We analysed 504 mothers in a birth cohort between 2002 and 2005 in Japan. Serum PFOS/PFOA and FA levels were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Maternal genotypes in PPARA (rs1800234; rs135561), PPARG (rs3856806), PPARGC1A (rs2970847; rs8192678), PPARD (rs1053049; rs2267668), CAR (rs2307424; rs2501873), LXRA (rs2279238) and LXRB (rs1405655; rs2303044; rs4802703) were analysed. When gene-environment interaction was considered, PFOS exposure (log10 scale) decreased palmitic, palmitoleic, and oleic acid levels (log10 scale), with the observed β in the range of − 0.452 to − 0.244; PPARGC1A (rs8192678) and PPARD (rs1053049; rs2267668) genotypes decreased triglyceride, palmitic, palmitoleic, and oleic acid levels, with the observed β in the range of − 0.266 to − 0.176. Interactions between PFOS exposure and SNPs were significant for palmitic acid (Pint = 0.004 to 0.017). In conclusion, the interactions between maternal PFOS levels and PPARGC1A or PPARD may modify maternal FA levels.
Numerical simulation of spatiotemporal red blood cell aggregation under sinusoidal pulsatile flow
Authors: Lee Cheong-Ah , Paeng Dong-Guk
Published: May 2021

Previous studies on red blood cell (RBC) aggregation have elucidated the inverse relationship between shear rate and RBC aggregation under Poiseuille flow. However, the local parabolic rouleaux pattern in the arterial flow observed in ultrasonic imaging cannot be explained by shear rate alone. A quantitative approach is required to analyze the spatiotemporal variation in arterial pulsatile flow and the resulting RBC aggregation. In this work, a 2D RBC model was used to simulate RBC motion driven by interactional and hydrodynamic forces based on the depletion theory of the RBC mechanism. We focused on the interaction between the spatial distribution of shear rate and the dynamic motion of RBC aggregation under sinusoidal pulsatile flow. We introduced two components of shear rate, namely, the radial and axial shear rates, to understand the effect of sinusoidal pulsatile flow on RBC aggregation. The simulation results demonstrated that specific ranges of the axial shear rate and its ratio with radial shear rate strongly affected local RBC aggregation and parabolic rouleaux formation. These findings are important, as they indicate that the spatiotemporal variation in shear rate has a crucial role in the aggregate formation and local parabolic rouleaux under pulsatile flow.
A study on the effects of regional differences on agricultural water resource utilization efficiency using super-efficiency SBM model
Authors: Huang Yujie , Huang Xianke , Xie Munan , Cheng Wei , Shu Qin
Published: May 2021

This study evaluated the water resource utilization efficiency and resource consumption for planting, forestry, animal husbandry, and fishery in various regions of China. Using the super-efficiency Slacks-Based Measure (SBM) analysis method, the main agricultural pollution emissions (Chemical Oxygen Demand, ammonia nitrogen, and agricultural carbon emissions) were proposed as environmental constraints for the first time. The threshold regression model was used to measure the impact of agricultural water use efficiency on agricultural water consumption by constructing seven different explanatory variables. The results show that the overall utilization efficiency of agricultural water resources in China presents a fluctuating downward trend, and the regional differences are significant. A single threshold effect on agricultural water consumption was found in five variables: per capita water resources, disposable income, dependence on foreign trade, industrial structure, and Gross Domestic Product. The increase in each parameter will have a positive effect on agricultural water consumption. The relationship between agricultural water use efficiency and agricultural water use was non-linear when the government's attention and the rural labor force were used as threshold variables.
Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India
Authors: Das Sabyasachi , Kar Amrita , Manna Subhankar , Mandal Samaresh , Mandal Sayantani , Das Subhasis , Saha Bhaskar , Hati Amiya Kumar
Published: May 2021

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015–January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P < 0.005) along with significantly higher RSA (2.2%) than cured patients (0.4%). None of day-3 positive isolates contained the pfkelch13 mutation implicated in artemisinin resistance. Parasite recrudescence was observed in 5.6% patients, which was associated with triple dhfr–dhps (A16I51R59N108I164–S436G437K540G581T613) combination mutation. Emergence of reduced sensitivity to artesunate-sulfadoxine-pyrimethamine, in central India highlighted the risk toward spread of resistant parasite across different parts of India. Day-3 positive parasite, featuring the phenotype of artemisinin-resistance without pfkelch13 mutation, suggested kelch13-independent artemisinin-resistance.
Distinguishing active from quiescent disease in ANCA-associated vasculitis using attenuated total reflection Fourier-transform infrared spectroscopy
Authors: Morris Adam D. , Morais Camilo L. M. , Lima Kássio M. G. , Freitas Daniel L. D. , Brady Mark E. , Dhaygude Ajay P. , Rowbottom Anthony W. , Martin Francis L.
Published: May 2021

The current lack of a reliable biomarker of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis poses a significant clinical unmet need when determining relapsing or persisting disease. In this study, we demonstrate for the first time that attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy offers a novel and functional candidate biomarker, distinguishing active from quiescent disease with a high degree of accuracy. Paired blood and urine samples were collected within a single UK centre from patients with active disease, disease remission, disease controls and healthy controls. Three key biofluids were evaluated; plasma, serum and urine, with subsequent chemometric analysis and blind predictive model validation. Spectrochemical interrogation proved plasma to be the most conducive biofluid, with excellent separation between the two categories on PC2 direction (AUC 0.901) and 100% sensitivity (F-score 92.3%) for disease remission and 85.7% specificity (F-score 92.3%) for active disease on blind predictive modelling. This was independent of organ system involvement and current ANCA status, with similar findings observed on comparative analysis following successful remission-induction therapy (AUC > 0.9, 100% sensitivity for disease remission, F-score 75%). This promising technique is clinically translatable and warrants future larger study with longitudinal data, potentially aiding earlier intervention and individualisation of treatment.
Blocking facial mimicry during binocular rivalry modulates visual awareness of faces with a neutral expression
Authors: Quettier Thomas , Gambarota Filippo , Tsuchiya Naotsugu , Sessa Paola
Published: May 2021

Several previous studies have interfered with the observer’s facial mimicry during a variety of facial expression recognition tasks providing evidence in favor of the role of facial mimicry and sensorimotor activity in emotion processing. In this theoretical context, a particularly intriguing facet has been neglected, namely whether blocking facial mimicry modulates conscious perception of facial expressions of emotions. To address this issue, we used a binocular rivalry paradigm, in which two dissimilar stimuli presented to the two eyes alternatingly dominate conscious perception. On each trial, female participants (N = 32) were exposed to a rivalrous pair of a neutral and a happy expression of the same individual through anaglyph glasses in two conditions: in one, they could freely use their facial mimicry, in the other they had to keep a chopstick between their lips, constraining the mobility of the zygomatic muscle and producing ‘noise’ for sensorimotor simulation. We found that blocking facial mimicry affected the perceptual dominance in terms of cumulative time favoring neutral faces, but it did not change the time before the first dominance was established. Taken together, our results open a door to future investigation of the intersection between sensorimotor simulation models and conscious perception of emotional facial expressions.
Thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones in conscious dogs
Authors: Nakazawa Nobuhiro , Sohda Makoto , Ogata Kyoichi , Baatar Seded , Ubukata Yasunari , Kuriyama Kengo , Hara Keigo , Suzuki Masaki , Yanoma Toru , Kimura Akiharu , Kogure Norimichi , Sano Akihiko , Sakai Makoto , Yokobori Takehiko , Oue Atsushi , Mochiki Erito , Kuwano Hiroyuki , Shirabe Ken , Koibuchi Noriyuki , Saeki Hiroshi
Published: May 2021

This study was conducted to clarify the relationship between thyroid function and gastrointestinal motility. We established an experimental configuration in which the feedback of thyroid function was completely removed using conscious dogs. With hypothyroidism, time of phase I of interdigestive migrating contractions (IMC) was longer, time of phase II and phase III was significantly shortened, and both the continuous time of strong tetanic contraction at antrum and 10-h frequency of phase III counted from the first IMC after meal significantly decreased. Whereas, hyperthyroidism caused the opposite events to those with hypothyroidism. Furthermore, We found giant migrating contractions (GMC) occurred from the upper gastrointestinal tract when we administrated high dose of thyroid hormone. One GMC occurred from anal sides propagated to cardiac, and this propagation was similar to the emesis-like interdigestive motor activity, the other GMC occurred from oral sides propagated to anal sides and this was similar to the diarrhea-like interdigestive motor activity. We examined the relationship between thyroid function and gastrointestinal hormones including of ghrelin, GLP-1, and cholecystokinin (CCK). However, we could not find significant differences under different thyroid hormone status. This is the first report that thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones.
Treatment strategy to maximize the treatment outcome of spinal dural arteriovenous fistula after initial endovascular embolization attempt at diagnostic angiography
Authors: Lee Heui Seung , Kang Hyun-Seung , Kim Sung Min , Kim Chi Heon , Yang Seung Heon , Han Moon Hee , Chung Chun Kee
Published: May 2021

Initial attempt of endovascular treatment (EVT) for spinal dural arteriovenous fistula (SDAVF) is preferred because of concurrent diagnosis and treatment. However, outcomes following further treatment with initial EVT are not well studied. We retrospectively reviewed 71 patients with SDAVF to evaluate treatment outcomes of SDAVF after an initial EVT attempt. Pretreatment and posttreatment functional states were assessed by the Aminoff-Logue scale (ALS). In the case of incomplete occlusion or recurrence, overall outcomes after further treatments were compared. Of the 71 patients, 56 underwent initial EVT. Complete occlusion was achieved by initial EVT in 37 of 56 patients (66.1%). Multiple feeders were more frequently observed in patients with incomplete occlusion than complete occlusion after initial EVT (73.7% vs. 27%, P < 0.001). Among 19 patients with incomplete occlusion upon initial EVT, 14 underwent additional surgery, 13 of whom (92.9%) obtained improved or stationary functional outcomes. Functional improvement was not observed in patients who had repeated EVT or follow-up without further treatment. Recurrence was observed in 8 of 37 patients with complete occlusion upon initial EVT. Additional surgery achieved improved functional outcomes in cases of incomplete occlusion of SDAVF after the initial EVT attempt or recurrence rather than repeated EVT or follow-up.
Reference values and factors associated with hand grip strength among older adults living in southeastern Poland
Authors: Wiśniowska-Szurlej Agnieszka , Ćwirlej-Sozańska Agnieszka , Kilian Justyna , Wołoszyn Natalia , Sozański Bernard , Wilmowska-Pietruszyńska Anna
Published: May 2021

Handgrip strength (HGS) is used as a biomarker for the state of health of older people, but the number of research publications containing the normative values of HGS in older adult populations is limited. The aim of the study was to define reference values and factors associated with HGS in older adults living in southeastern Poland. A cross-sectional study including 405 participants aged 65 and older was conducted. Handgrip strength for the dominant hand was assessed by the average of three trials using a JAMAR dynamometer. The sample was categorized into the following age groups: 65–69 years, 70–74 years, 75–79 years, 80–84 years, 85 and over. The average HGS was 19.98 kg (16.91 kg for women and 26.19 kg for men). There was a decrease in handgrip strength across the age range in both sexes. The average handgrip strength of the older people was 17.97 kg (14.47 kg for women and 25.66 kg for men) for those aged 80–85 and 16.68 kg (13.51 kg for women and 21.77 kg for men) in the group over 85 years old. In both sexes, marital status was an independent factor associated with reduced handgrip strength. In conclusion, this study described, for the first time, handgrip strength values for the southeastern Polish population aged ≥ 65 years according to age and gender.
Identification of a methylomics-associated nomogram for predicting overall survival of stage I–II lung adenocarcinoma
Authors: Wang Heng , Wei Chuangye , Pan Peng , Yuan Fengfeng , Cheng Jiancheng
Published: May 2021

The aim of this paper was to identify DNA methylation based biomarkers for predicting overall survival (OS) of stage I–II lung adenocarcinoma (LUAD) patients. Methylation profile data of patients with stage I–II LUAD from The Cancer Genome Atlas (TCGA) database was used to determine methylation sites-based hallmark for stage I–II LUAD patients’ OS. The patients were separated into training and validation datasets by using median risk score as cutoff. Univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to develop a DNA methylation signature for OS of patients with stage I–II LUAD. As a result, an 11-DNA methylation signature was determined to be critically associated with the OS of patients with stage I–II LUAD. Analysis of receiver operating characteristics (ROC) suggested a high prognostic effectiveness of the 11-DNA methylation signature in patients with stage I–II LUAD (AUC at 1, 3, 5 years in training set were (0.849, 0.879, 0.831, respectively), validation set (0.742, 0.807, 0.904, respectively), entire TCGA dataset (0.747, 0.818, 0.870, respectively). Kaplan–Meier survival analyses exhibited that survival was significantly longer in the low-risk cohort compared to the high-risk cohort in the training dataset (P = 7e − 07), in the validation dataset (P = 1e − 08), and in the all-cohort dataset (P = 6e − 14). In addition, a nomogram was developed based on molecular factor (methylation risk score) as well as clinical factors (age and cancer status) (AUC at 1, 3, 5 years entire TCGA dataset were 0.770, 0.849, 0.979, respectively). The result verified that our methylomics-associated nomogram had a strong robustness for predicting stage I–II LUAD patients’ OS. Furthermore, the nomogram combined clinical and molecular factors to determine an individualized probability of recurrence for patients with stage I–II LUAD, which stood for a major advance in the field of personalized medicine for pulmonary oncology. Collectively, we successfully identified a DNA methylation biomarker and a DNA methylation-based nomogram to predict the OS of patients with stage I–II LUAD.
A novel automatic cough frequency monitoring system combining a triaxial accelerometer and a stretchable strain sensor
Authors: Otoshi Takehiro , Nagano Tatsuya , Izumi Shintaro , Hazama Daisuke , Katsurada Naoko , Yamamoto Masatsugu , Tachihara Motoko , Kobayashi Kazuyuki , Nishimura Yoshihiro
Published: May 2021

Objective evaluations of cough frequency are considered important for assessing the clinical state of patients with respiratory diseases. However, cough monitors with audio recordings are rarely used in clinical settings. Issues regarding privacy and background noise with audio recordings are barriers to the wide use of these monitors; to solve these problems, we developed a novel automatic cough frequency monitoring system combining a triaxial accelerator and a stretchable strain sensor. Eleven healthy adult volunteers and 10 adult patients with cough were enrolled. The participants wore two devices for 30 min for the cough measurements. An accelerator was attached to the epigastric region, and a stretchable strain sensor was worn around their neck. When the subjects coughed, these devices displayed specific waveforms. The data from all the participants were categorized into a training dataset and a test dataset. Using a variational autoencoder, a machine learning algorithm with deep learning, the components of the test dataset were automatically judged as being a “cough unit” or “non-cough unit”. The sensitivity and specificity in detecting coughs were 92% and 96%, respectively. Our cough monitoring system has the potential to be widely used in clinical settings without any concerns regarding privacy or background noise.
A systematic review and meta-analysis of angiotensin-converting enzyme inhibitor use and psoriasis incidence
Authors: Song Gonjin , Kim Ji Yea , Yoon Ha Young , Yee Jeong , Gwak Hye Sun
Published: May 2021

Although a considerable volume of data supporting induction or aggravation of psoriasis because of angiotensin-converting enzyme (ACE) inhibitor use exists, it remains insufficient for definitive conclusions. Therefore, we aimed to evaluate the association between ACE inhibitor use and psoriasis incidence through a systematic literature review and meta-analysis. We searched for qualifying studies across PubMed, Web of Science, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association between ACE inhibitor use and psoriasis incidence. Eight studies with a total of 54,509 patients with a psoriasis diagnosis were included in this meta-analysis. The pooled OR for psoriasis incidence among ACE inhibitor users was 1.52 (95% CI, 1.16–2.00) compared to that among non-users. From subgroup analysis by continent, the OR for ACE inhibitor users versus non-users was 2.37 (95% CI 1.28–4.37) in Asia. Per the subgroup analysis by climate, the OR for ACE inhibitor users vs non-users in dry climate was 3.45 (95% CI: 2.05–5.79) vs 1.32 (95% CI 1.01–1.73) in temperate climate. Our results reveal a significant association between ACE inhibitor use and psoriasis incidence.
Work-related risk factors for ulnar nerve entrapment in the Northern Finland Birth Cohort of 1966
Authors: Miettinen Laura , Ryhänen Jorma , Shiri Rahman , Karppinen Jaro , Miettunen Jouko , Auvinen Juha , Hulkkonen Sina
Published: May 2021

Ulnar nerve entrapment (UNE) is the second most common entrapment neuropathy in the upper extremity. The aetiology of UNE is multifactorial and is still not fully understood. The aim of the study was to identify occupational risk factors for UNE and to determine whether smoking modifies the effects of work-related factors on UNE. The study population consisted of the Northern Finland Birth Cohort of 1966 (NFBC1966). In total, 6325 individuals active in working life participated at baseline in 1997. Occupational risk factors were evaluated by a questionnaire at baseline. The data on hospitalizations due to UNE were obtained from the Care Register for Health Care between 1997 and 2018. The incidence rate of hospitalization due to UNE was 47.6 cases per 100,000 person-years. After adjusting for confounders, entrepreneurs (Hazard ratio (HR) = 3.68, 95% CI 1.20–11.27), smokers (HR = 2.51, 95% CI 1.43–4.41), workers exposed to temperature changes (HR = 1.72, 95% CI 1.00–2.93), workers with physically demanding jobs (HR = 3.02, 95% CI 1.39–6.58), and workers exposed to hand vibration (HR = 1.94, 95% CI 1.00–3.77) were at an increased risk of hospitalization for UNE. Exposure to work requiring arm elevation increased the risk of hospitalization due to UNE among smokers (HR = 2.62, 95% CI 1.13–6.07), but not among non-smokers. Work-related exposure to vibration and temperature changes, and physically demanding work increase the risk of hospitalization for UNE. Smoking may potentiate the adverse effects of work-related factors on UNE.
Functional characterization and related evolutionary implications of invertebrate gonadotropin-releasing hormone/corazonin in a well-established model species
Authors: Fodor István , Svigruha Réka , Bozsó Zsolt , Tóth Gábor K. , Osugi Tomohiro , Yamamoto Tatsuya , Satake Honoo , Pirger Zsolt
Published: May 2021

In vertebrates, gonadotropin-releasing hormone (GnRH) peptide is the central mediator of reproduction. Homologous peptides have previously also been identified in molluscan species. However, emerging evidence suggests that these molecules might serve diverse regulatory functions and proposes to consider them as corazonin (CRZ). We previously isolated the full-length cDNA of the invGnRH/CRZ peptide (termed ly-GnRH/CRZ) in the well-established invertebrate model species, the great pond snail Lymnaea stagnalis; however, its predicted functions remain to be verified. In this study, we first confirmed the presence of the deduced active peptide from the central nervous system of L. stagnalis. Further, we performed in vivo and in vitro studies to explore the functions of ly-GnRH/CRZ. Injection of sexually mature specimens with synthetic active peptide had an inhibitory effect on locomotion and an acceleratory effect on egg-laying, but had no effect on feeding. The previously predicted modulatory effect of ly-GnRH/CRZ was supported by its identified co-localization with serotonin on the surface of the heart atria. Lastly, we demonstrated not only the presence of ly-GnRH/CRZ in the penial complex but also that ly-GnRH/CRZ-containing neurons project to the efferent penis nerve, suggesting ly-GnRH/CRZ may directly modulate the motor output of this peripheral tissue. Overall, our findings strongly support that ly-GnRH/CRZ is a multifunctional neuropeptide. These results contribute to the understanding of the GnRH superfamily and, more broadly, disciplines such as comparative endocrinology and neurobiology.