bluuebunny/crossref_metadata_2025 huggingface dataset:
c-FLIP is crucial for IL-7/IL-15-dependent NKp46+ ILC development and protection from intestinal inflammation in mice
Authors: Bank Ute , Deiser Katrin , Plaza-Sirvent Carlos , Osbelt Lisa , Witte Amelie , Knop Laura , Labrenz Rebecca , Jänsch Robert , Richter Felix , Biswas Aindrila , Zenclussen Ana C. , Vivier Eric , Romagnani Chiara , Kühl Anja A. , Dunay Ildiko R. , Strowig Till , Schmitz Ingo , Schüler Thomas
Published: February 2020

NKp46+ innate lymphoid cells (ILC) modulate tissue homeostasis and anti-microbial immune responses. ILC development and function are regulated by cytokines such as Interleukin (IL)−7 and IL-15. However, the ILC-intrinsic pathways translating cytokine signals into developmental programs are largely unknown. Here we show that the anti-apoptotic molecule cellular FLICE-like inhibitory protein (c-FLIP) is crucial for the generation of IL-7/IL-15-dependent NKp46+ ILC1, including conventional natural killer (cNK) cells, and ILC3. Cytokine-induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) precedes up-regulation of c-FLIP, which protects developing NKp46+ ILC from TNF-induced apoptosis. NKp46+ ILC-specific inactivation of c-FLIP leads to the loss of all IL-7/IL-15-dependent NKp46+ ILC, thereby inducing early-onset chronic colitis and subsequently microbial dysbiosis; meanwhile, the depletion of cNK, but not NKp46+ ILC1/3, aggravates experimental colitis. In summary, our data demonstrate a non-redundant function of c-FLIP for the generation of NKp46+ ILC, which protect T/B lymphocyte-sufficient mice from intestinal inflammation.
Wounding triggers MIRO-1 dependent mitochondrial fragmentation that accelerates epidermal wound closure through oxidative signaling
Authors: Fu Hongying , Zhou Hengda , Yu Xinghai , Xu Jingxiu , Zhou Jinghua , Meng Xinan , Zhao Jianzhi , Zhou Yu , Chisholm Andrew D. , Xu Suhong
Published: February 2020

Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair.
The epidermis coordinates thermoresponsive growth through the phyB-PIF4-auxin pathway
Authors: Kim Sara , Hwang Geonhee , Kim Soohwan , Thi Thom Nguyen , Kim Hanim , Jeong Jinkil , Kim Jaewook , Kim Jungmook , Choi Giltsu , Oh Eunkyoo
Published: February 2020

In plants, an elevation in ambient temperature induces adaptive morphological changes including elongated hypocotyls, which is predominantly regulated by a bHLH transcription factor, PIF4. Although PIF4 is expressed in all aerial tissues including the epidermis, mesophyll, and vascular bundle, its tissue-specific functions in thermomorphogenesis are not known. Here, we show that epidermis-specific expression of PIF4 induces constitutive long hypocotyls, while vasculature-specific expression of PIF4 has no effect on hypocotyl growth. RNA-Seq and qRT-PCR analyses reveal that auxin-responsive genes and growth-related genes are highly activated by epidermal, but not by vascular, PIF4. Additionally, inactivation of epidermal PIF4 or auxin signaling, and overexpression of epidermal phyB suppresses thermoresponsive growth, indicating that epidermal PIF4-auxin pathways are essential for the temperature responses. Further, we show that high temperatures increase both epidermal PIF4 transcription and the epidermal PIF4 DNA-binding ability. Taken together, our study demonstrates that the epidermis regulates thermoresponsive growth through the phyB-PIF4-auxin pathway.
Nanoscale triboelectrification gated transistor
Authors: Bu Tianzhao , Xu Liang , Yang Zhiwei , Yang Xiang , Liu Guoxu , Cao Yuanzhi , Zhang Chi , Wang Zhong Lin
Published: February 2020

Tribotronics has attracted great attention owing to the demonstrated triboelectrification-controlled electronics and established direct modulation mechanism by external mechanical stimuli. Here, a nanoscale triboelectrification-gated transistor has been studied with contact-mode atomic force microscopy and scanning Kevin probe microscopy. The detailed working principle was analyzed at first, in which the nanoscale triboelectrification can tune the carrier transport in the transistor. Then with the manipulated nanoscale triboelectrification, the effects of contact force, scan speed, contact cycles, contact region and charge diffusion on the transistor were investigated, respectively. Moreover, the manipulated nanoscale triboelectrification serving as a rewritable floating gate has demonstrated different modulation effects by an applied tip voltage. This work has realized the nanoscale triboelectric modulation on electronics, which could provide a deep understanding for the theoretical mechanism of tribotronics and may have great applications in nanoscale transistor, micro/nano-electronic circuit and nano-electromechanical system.
Transcriptome analysis of life stages of the house cricket, Acheta domesticus, to improve insect crop production
Authors: Oppert Brenda , Perkin Lindsey C. , Lorenzen Marcé , Dossey Aaron T.
Published: February 2020

To develop genetic resources for the improvement of insects as food, we sequenced transcripts from embryos, one-day hatchlings, three nymphal stages, and male and female adults of the house cricket, Acheta domesticus. A draft transcriptome was assembled from more than 138 million sequences combined from all life stages and sexes. The draft transcriptome assembly contained 45,866 contigs, and more than half were similar to sequences at NCBI (e value < e−3). The highest sequence identity was found in sequences from the termites Cryptotermes secundus and Zootermopsis nevadensis. Sequences with identity to Gregarina niphandrodes suggest that these crickets carry the parasite. Among all life stages, there were 5,042 genes with differential expression between life stages (significant at p < 0.05). An enrichment analysis of gene ontology terms from each life stage or sex highlighted genes that were important to biological processes in cricket development. We further characterized genes that may be important in future studies of genetically modified crickets for improved food production, including those involved in RNA interference, and those encoding prolixicin and hexamerins. The data represent an important first step in our efforts to provide genetically improved crickets for human consumption and livestock feed.
Influences of pH on transport of arsenate (As5+) through different reactive media using column experiments and transport modeling
Authors: Chotpantarat Srilert , Amasvata Chonnikarn
Published: February 2020

This research aims to evaluate the effects of pH, including both acidic and neutral conditions to simulate an acid mine environment, on the sorption and transport of As(V) in contaminated groundwater through different reactive materials by using column experiments and mathematical modeling. Six saturated columns were set up to evaluate the migration and removal efficiency of As(V) with three different materials acting as permeable reactive barrier (PRB) media under different pH conditions (pH 4 and pH 7). The reactive materials consisted of pure sand (control column), iron oxide-coated sand (IOCS) and a combination of IOCS and zero-valent iron-coated sand (ZVICS) (ZVICS + IOCS). According to the column experiments, the descending order of removal capacity (mg As/g) for ZVICS + IOCS, IOCS and sand was 0.452 > 0.062 > 0.0027 mg As/g at pH 4 and 0.117 > 0.0077 > 0.0022 mg As/g, respectively, at pH 7. The column experiments showed that the removal and retardation factor (RF) of As(V) generally increased with decreasing pH. The SEM images and the corresponding EDX spectra of acid-washed natural sand, IOCS and ZVICS + IOCS from the columns showed that the peak of As was detectable on the reactive materials. The mechanism of As(V) sorption onto sand at pH 4 and pH 7 corresponded to the uniform (equilibrium) solute transport model, whereas the IOCS and ZVICS + IOCS columns corresponded to the two-site model (TSM) with the Freundlich isotherm. The fraction of instantaneous sites (f) for As(V) sorption onto IOCS and ZVICS + IOCS appeared to decrease with increasing pH, especially for ZVICS + IOCS, which indicates that nonequilibrium sorption/desorption mainly dominated during As(V) migration.
Characterisation of HIV-1 Molecular Epidemiology in Nigeria: Origin, Diversity, Demography and Geographic Spread
Authors: Nazziwa Jamirah , Faria Nuno Rodrigues , Chaplin Beth , Rawizza Holly , Kanki Phyllis , Dakum Patrick , Abimiku Alash’le , Charurat Man , Ndembi Nicaise , Esbjörnsson Joakim
Published: February 2020

Nigeria has the highest number of AIDS-related deaths in the world. In this study, we characterised the HIV-1 molecular epidemiology by analysing 1442 HIV-1polsequences collected 1999–2014 from four geopolitical zones in Nigeria using state-of-the-art maximum-likelihood and Bayesian phylogenetic analyses. The main circulating forms were the circulating recombinant form (CRF) 02_AG (44% of the analysed sequences), CRF43_02G (16%), and subtype G (8%). Twenty-three percent of the sequences represented unique recombinant forms (URFs), whereof 37 (11%) could be grouped into seven potentially novel CRFs. Bayesian phylodynamic analysis suggested that five major Nigerian HIV-1 sub-epidemics were introduced in the 1960s and 1970s, close to the Nigerian Civil War. The analysis also indicated that the number of effective infections decreased in Nigeria after the introduction of free antiretroviral treatment in 2006. Finally, Bayesian phylogeographic analysis suggested gravity-like dynamics in which virus lineages first emerge and expand within large urban centers such as Abuja and Lagos, before migrating towards smaller rural areas. This study provides novel insight into the Nigerian HIV-1 epidemic and may have implications for future HIV-1 prevention strategies in Nigeria and other severely affected countries.
p38 MAPK signalling regulates cytokine production in IL-33 stimulated Type 2 Innate Lymphoid cells
Authors: Petrova Tsvetana , Pesic Jelena , Pardali Katerina , Gaestel Matthias , Arthur J. Simon C.
Published: February 2020

Type 2 Innate lymphoid cells (ILC2s) are implicated in helminth infections and asthma where they play a role in the production of Th2-type cytokines. ILC2s express the IL-33 receptor and are a major cell type thought to mediate the effects of this cytokinein vivo. To study the signalling pathways that mediate IL-33 induced cytokine production, a culture system was set up to obtain pure populations of ILC2s from mice. Inhibitors of the p38α/β and ERK1/2 MAPK pathways reduced the production of IL-5, IL-6, IL-9, IL-13 and GM-CSF by ILC2 in response to IL-33, with inhibition of p38 having the greatest effect. MK2 and 3 are kinases activated by p38α; MK2/3 inhibitors or knockout of MK2/3 in mice reduced the production of IL-6 and IL-13 (two cytokines implicated in asthma) but not IL-5, IL-9 or GM-CSF in response to IL-33. MK2/3 inhibition also suppressed IL-6 and IL-13 production by human ILC2s. MK2/3 were required for maximal S6 phosphorylation, suggesting an input from the p38α-MK2/3 pathway to mTOR1 activation in ILC2s. The mTORC1 inhibitor rapamycin also reduced IL-6 and IL-13 production, which would be consistent with a model in which MK2/3 regulate IL-6 and IL-13 via mTORC1 activation in ILC2s.
Modern precipitation of hydrogenetic ferromanganese minerals during on-site 15-year exposure tests
Authors: Usui A. , Hino H. , Suzushima D. , Tomioka N. , Suzuki Y. , Sunamura M. , Kato S. , Kashiwabara T. , Kikuchi S. , Uramoto G.-I. , Suzuki K. , Yamaoka K.
Published: February 2020

Redox-sensitive metallic elements, Mn and Fe, are oxidized in deep sea waters and form abundant ferromanganese crusts and nodules on the world’s ocean floors at ultraslow rates of growth. This process of oxidation and the mechanism of precipitation are yet unknown. In this paper, the results of the first successful, long-term, on-site experiment of mineral precipitation that ascertains modern, ongoing hydrogenetic deposition of oxide materials from normal seawaters at water depths of 900–4500 m of geologically active and inactive environments are presented. We succeeded in the in-situ precipitation experiment on the sea floor and characterized the precipitates using high-resolution and submicron-scale chemical, mineralogical, and structural analyses. The installed artificial plates of glass, ceramics, and plastic yielded spread-out particles of sizes varying from one to a few micrometers in diameter, of coccoid-like irregular shapes, with a maximum of 1,000–10,000 individual particles/mm2/year after 12–15 years of exposure. The results indicated a continuous substantial growth of the hydrogenetic minerals if both Mn and Fe are supplied to the bottom waters. The mineralogical, chemical, and structural properties of the precipitates are similar to those of the natural precipitates on the seabed that are made up of hydrogenetic ferromanganese crusts and nodules, together with settling sediments, suspended hydrothermal particles, or microbial precipitates from cultivated Mn-oxidizing bacteria. Our work presents new realistic insight into proposed genetic models of marine hydrogenetic ferromanganese deposits in modern diverse ocean environments.
Alterations of estrous cycle, 3β hydroxysteroid dehydrogenase activity and progesterone synthesis in female rats after exposure to hypobaric hypoxia
Authors: Shaw Snigdha , Kumar Utkarsha , Bhaumik Gopinath , Reddy M. Prasanna Kumar , Kumar Bhuvnesh , Ghosh Dishari
Published: February 2020

The underlying mechanism regulating hypoxia induced alteration in female steroid hormones is first time explored in this study. To understand the mechanistic approach, female Sprague- Dawley rats were exposed to acute and chronic hypobaric hypoxia (282 mm-Hg, ~7620 m, 6 hours, 3 and 7 days). Estrous cycle, body weight, plasma progesterone and estradiol levels, morphology, histology and two key steroidogenic enzymes: 3ß hydroxysteroid dehydrogenase (HSD) and 17ß HSD activity of ovary and adrenal gland were studied. A persistent diestrous phase and a significant decrease in body weight were found in chronic hypoxia groups. Histological study suggested degenerative changes in ovarian corpus luteum of 7 days chronic hypobaric hypoxia (7CHH) group and a declined percentage of adrenocortical cells in 3 days chronic hypobaric hypoxia (3CHH) and 7CHH groups. Plasma estradiol level was unaltered, but progesterone level was decreased significantly in all hypoxic groups. Ovarian 3ß HSD activity was decreased significantly with increasing days of hypoxic treatment along with a significantly low adrenal 3ß HSD activity in 7CHH. In conclusion, hypobaric hypoxia causes a state of low circulatory progesterone level in females likely due to the degenerative changes in the female ovarian and adrenal tissues together with low steroidogenic 3ß HSD enzyme activity.
Intra- and extra-hospital improvement in ischemic stroke patients: influence of reperfusion therapy and molecular mechanisms
Authors: Hervella Pablo , Rodríguez-Castro Emilio , Rodríguez-Yáñez Manuel , Arias Susana , Santamaría-Cadavid María , López-Dequidt Iria , Estany-Gestal Ana , Maqueda Elena , López-Loureiro Ignacio , Sobrino Tomás , Campos Francisco , Castillo José , Iglesias-Rey Ramón
Published: February 2020

Neuroprotective treatments in ischemic stroke are focused to reduce the pernicious effect of excitotoxicity, oxidative stress and inflammation. However, those cellular and molecular mechanisms may also have beneficial effects, especially during the late stages of the ischemic stroke. The objective of this study was to investigate the relationship between the clinical improvement of ischemic stroke patients and the time-dependent excitotoxicity and inflammation. We included 4295 ischemic stroke patients in a retrospective study. The main outcomes were intra and extra-hospital improvement. High glutamate and IL-6 levels at 24 hours were associated with a worse intra-hospital improvement (OR:0.993, 95%CI: 0.990–0.996 and OR:0.990, 95%CI: 0.985–0.995). High glutamate and IL-6 levels at 24 hours were associated with better extra-hospital improvement (OR:1.13 95%CI, 1.07–1.12 and OR:1.14, 95%CI, 1.09–1.18). Effective reperfusion after recanalization showed the best clinical outcome. However, the long term recovery is less marked in patients with an effective reperfusion. The variations of glutamate and IL6 levels in the first 24 hours clearly showed a relationship between the molecular components of the ischemic cascade and the clinical outcome of patients. Our findings suggest that the rapid reperfusion after recanalization treatment blocks the molecular response to ischemia that is associated with restorative processes.
One maternal lineage leads the expansion of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae) in the New and Old Worlds
Authors: Machado Dayanna do N. , Costa Ervandil C. , Guedes Jerson V. C. , Barbosa Leonardo R. , Martínez Gonzalo , Mayorga Sandra I. , Ramos Sergio O. , Branco Manuela , Garcia André , Vanegas-Rico Juan Manuel , Jiménez-Quiroz Eduardo , Laudonia Stefania , Novoselsky Tania , Hodel Donald R. , Arakelian Gevork , Silva Horacio , Perini Clérison R. , Valmorbida Ivair , Ugalde Gustavo A. , Arnemann Jonas A.
Published: February 2020

The bronze bug,Thaumastocoris peregrinus, an Australian native insect, has become a nearly worldwide invasive pest in the last 16 years and has been causing significant damage to eucalypts (Myrtaceae), includingEucalyptusspp. andCorymbiaspp. Its rapid expansion leads to new questions about pathways and routes thatT. peregrinusused to invade other continents and countries. We used mtDNA to characterize specimens ofT. peregrinuscollected from 10 countries where this species has become established, including six recently invaded countries: Chile, Israel, Mexico, Paraguay, Portugal, and the United States of America. We then combined our mtDNA data with previous data available from South Africa, Australia, and Europe to construct a world mtDNA network of haplotypes. Haplotype A was the most common present in all specimens of sites sampled in the New World, Europe, and Israel, however from Australia second more frequently. Haplotype D was the most common one from native populations in Australia. Haplotype A differs from the two major haplotypes found in South Africa (D and G), confirming that at least two independent invasions occurred, one from Australia to South Africa, and the other one from Australia to South America (A). In conclusion, Haplotype A has an invasion success over many countries in the World. Additionally, analyzing data from our work and previous reports, it is possible to suggest some invasive routes ofT. peregrinusto predict such events and support preventive control measures.
In Vitro CRISPR/Cas9-Directed Gene Editing to Model LRRK2 G2019S Parkinson’s Disease in Common Marmosets
Authors: Vermilyea Scott C. , Babinski Alexander , Tran Nina , To Samantha , Guthrie Scott , Kluss Jillian H. , Schmidt Jenna Kropp , Wiepz Gregory J. , Meyer Michael G. , Murphy Megan E. , Cookson Mark R. , Emborg Marina E. , Golos Thaddeus G.
Published: February 2020

Leucine-rich repeat kinase 2 (LRRK2) G2019S is a relatively common mutation, associated with 1–3% of Parkinson’s disease (PD) cases worldwide. G2019S is hypothesized to increase LRRK2 kinase activity. Dopaminergic neurons derived from induced pluripotent stem cells of PD patients carrying LRRK2 G2019S are reported to have several phenotypes compared to wild type controls, including increased activated caspase-3 and reactive oxygen species (ROS), autophagy dysfunction, and simplification of neurites. The common marmoset is envisioned as a candidate nonhuman primate species for comprehensive modeling of genetic mutations. Here, we report our successful use of CRISPR/Cas9 with repair template-mediated homology directed repair to introduce the LRRK2 G2019S mutation, as well as a truncation of the LRRK2 kinase domain, into marmoset embryonic and induced pluripotent stem cells. We found that, similar to humans, marmoset LRRK2 G2019S resulted in elevated kinase activity. Phenotypic evaluation after dopaminergic differentiation demonstrated LRRK2 G2019S-mediated increased intracellular ROS, decreased neuronal viability, and reduced neurite complexity. Importantly, these phenotypes were not observed in clones with LRRK2 truncation. These results demonstrate the feasibility of inducing monogenic mutations in common marmosets and support the use of this species for generating a novel genetic-based model of PD that expresses physiological levels of LRRK2 G2019S.
Nature more than nurture affects the growth rate of mussels
Authors: Prieto D. , Tamayo D. , Urrutxurtu I. , Navarro E. , Ibarrola I. , Urrutia M. B.
Published: February 2020

We tested the hypothesis that environmental trophic conditions prominent during the growing period (nurture conditions) can modify the differing physiological profiles between fast (F)- and slow (S)-growing juveniles of the mussel Mytilus galloprovincialis. Approximately 200 individuals were fed a high organic content diet dosed below the pseudofaeces threshold (BP), whereas another 200 were fed a low organic content diet dosed above the pseudofaeces threshold (AP), forcing them to maintain a continuous production of pseudofaeces. After 3 months, F and S individuals in each rearing condition were selected and used in feeding experiments. We measured the physiological parameters of the energy balance of selected F and S mussels fed on 4 different diets and tested the effects of the rearing condition (BP vs AP) and growth condition (F vs S) upon the physiological variables. Irrespective of the rearing condition, F-mussels attained higher values of scope for growth with the four experimental diets due to their capacity to display higher clearance rates and preingestive selection efficiencies. F-individuals also had higher gill-surface areas than S individuals. We discussed the role of the gills in determining inter-individual growth rate differences in the mussel.
Co-appearance of superconductivity and ferromagnetism in a Ca2RuO4 nanofilm crystal
Authors: Nobukane Hiroyoshi , Yanagihara Kosei , Kunisada Yuji , Ogasawara Yunito , Isono Kakeru , Nomura Kazushige , Tanahashi Keita , Nomura Takahiro , Akiyama Tomohiro , Tanda Satoshi
Published: February 2020

By tuning the physical and chemical pressures of layered perovskite materials we can realize the quantum states of both superconductors and insulators. By reducing the thickness of a layered crystal to a nanometer level, a nanofilm crystal can provide novel quantum states that have not previously been found in bulk crystals. Here we report the realization of high-temperature superconductivity in Ca2RuO4 nanofilm single crystals. Ca2RuO4 thin film with the highest transition temperature Tc (midpoint) of 64 K exhibits zero resistance in electric transport measurements. The superconducting critical current exhibited a logarithmic dependence on temperature and was enhanced by an external magnetic field. Magnetic measurements revealed a ferromagnetic transition at 180 K and diamagnetic magnetization due to superconductivity. Our results suggest the co-appearance of superconductivity and ferromagnetism in Ca2RuO4 nanofilm crystals. We also found that the induced bias current and the tuned film thickness caused a superconductor-insulator transition. The fabrication of micro-nanocrystals made of layered material enables us to discuss rich superconducting phenomena in ruthenates.
Extracting the Jugular Venous Pulse from Anterior Neck Contact Photoplethysmography
Authors: García-López Irene , Rodriguez-Villegas Esther
Published: February 2020

The jugular venous pulse (JVP) is the reference physiological signal used to detect right atrial and central venous pressure (CVP) abnormalities in cardio-vascular diseases (CVDs) diagnosis. Invasive central venous line catheterization has always been the gold standard method to extract it reliably. However, due to all the risks it entails, novel non-invasive approaches, exploiting distance cameras and lasers, have recently arisen to measure the JVP at the external and internal jugular veins. These remote options however, constraint patients to very specific body positions in front of the imaging system, making it inadequate for long term monitoring. In this study, we demonstrate, for the first time, that reflectance photoplethysmography (PPG) can be an alternative for extracting the JVP from the anterior jugular veins, in a contact manner. Neck JVP-PPG signals were recorded from 20 healthy participants, together with reference ECG and arterial finger PPG signals for validation. B-mode ultrasound imaging of the internal jugular vein also proved the validity of the proposed method. The results show that is possible to identify the characteristic a, c, v pressure waves in the novel signals, and confirm their cardiac-cycle timings in consistency with established cardiac physiology. Wavelet coherence values (close to 1 and phase shifts of ±180°) corroborated that neck contact JVP-PPG pulses were negatively correlated with arterial finger PPG. Average JVP waveforms for each subject showed typical JVP pulses contours except for the singularity of an unknown "u" wave occurring after the c wave, in half of the cohort. This work is of great significance for the future of CVDs diagnosis, as it has the potential to reduce the risks associated with conventional catheterization and enable continuous non-invasive point-of-care monitoring of CVP, without restricting patients to limited postures.
Ganoderma lucidum cultivation affect microbial community structure of soil, wood segments and tree roots
Authors: Ren Fei , Zhang Yuguang , Yu Hai , Zhang Yong An
Published: February 2020

The popular medicinal mushroom Ganoderma lucidum (Fr.) Karst. [Ling Zhi] has been widely used for the general promotion of health and longevity in Asian countries. Continuous cultivation may affect soil microbe and soil properties. However, the effect of G. lucidum cultivation on related wood segments, soil and tree roots microbial communities and soil properties is remain unknown. In our study, the microbial communities of soils, wood segments, and tree roots before and after G. lucidum cultivation were investigated by Illumina Miseq sequencing of both ITS and 16S rDNA, and taxonomic composition of eukaryotic and prokaryotic microorganisms were observed. Indices of microbial richness, diversity and evenness significantly differed between before and after G. lucidum cultivation. Each of the investigated sampling type harbored a distinctive microbial community and differed remarkably before and after G. lucidum cultivation. Ascomycota and Basidiomycota (fungi), Proteobacteria and Actinobacteria (bacteria) showed significant differences after Ling Zhi cultivation. The soil property values also changed after cultivation. The redundancy analysis (RDA) showed that both the fungal and bacterial community structure significantly correlated with soil humus, pH, nitrogen, carbon and trace elements (Fe, Zn, Mn, Cu) contents. The results indicated that G. lucidum cultivation may have significant differed the associated microbial community structures and soil properties. The study will provide useful information for G. lucidum cultivation and under-forest economic development.
Factors influencing the accuracy for tissue classification in multi spectral in-vivo endoscopy for the upper gastro-internal tract
Authors: Hohmann Martin , Albrecht Heinz , Lengenfelder Benjamin , Klämpfl Florian , Schmidt Michael
Published: February 2020

Hyper spectral imaging is a possible way for disease detection. However, for carcinoma detection most of the results are ex-vivo. However, in-vivo results of endoscopic studies still show fairly low accuracies in contrast to the good results of many ex-vivo studies. To overcome this problem and to provide a reasonable explanation, Monte-Carlo simulations of photon trajectories are proposed as a tool to generate multi spectral images including inter patient variations to simulate 40 patients. Furthermore, these simulations have the huge advantage that the position of the carcinoma is known. Due to this, the effect of mislabelled data can be studied. As shown in this study, a percentage of 30–35% of mislabelled data might lead to significant decrease of the accuracy from around 90% to around 70–75%. Therefore, the main focus of hyper spectral imaging has to be the exact characterization of the training data in the future.
Subtypes of anterior circulation large artery occlusions with acute brain ischemic stroke
Authors: Zhang Kun , Li Tong , Tian Jing , Li Peifang , Fu Baosheng , Yang Xiaoli , Liu Luji , Zhao Yanying , Lu Honglin , Zhao Pandi , Bu Kailin , Li Zhongzhong , Yuan Si , Wang Qisong , Zhang Yingzhen , Guo Li , Liu Xiaoyun
Published: February 2020

Anterior circulation large artery occlusion (AC-LAO) related acute ischemic stroke (AIS) is particularly common in clinics in China. We retrospectively analyzed 787 consecutively hospitalized AIS patients with AC-LAO in Hebei Province, China. AC-LAO was defined as a complete occlusion of at least one intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) based on computed tomography or magnetic resonance angiography. Among eight subtypes of AC-LAO, unilateral MCA occlusion is the most common one (49.8%, n = 392), while bilateral ICA/unilateral MCA occlusion is the least (0.3%, n = 2). Compared with unilateral MCA and unilateral ICA occlusion, patients with tandem ICA/MCA and bilateral ICA/MCA occlusion had poor outcomes after suffering AIS. Age (OR 1.022; 95%CI, 1.007 to 1.036) was an independent risk factor for single artery progressed to multiple artery occlusion, while ApoA1 (OR 0.453; 95% CI, 0.235 to 0.953) was a protective factor. Patients with unilateral MCA occlusion were prone to artery-to-artery embolism infarction subtype, unilateral ICA occlusion group were the most vulnerable to hypoperfusion/impaired emboli clearance subtype. Our results suggested various AC-LAO subtypes have different clinical characteristics and prognosis and were prone to different subtypes of infarction. Customized preventive measures based on AC-LAO subtypes may be more targeted preventions of stroke recurrences for AIS patients and could improve their prognoses.
Data-driven prediction of diamond-like infrared nonlinear optical crystals with targeting performances
Authors: Wang Rui , Liang Fei , Lin Zheshuai
Published: February 2020

Combining high-throughput screening and machine learning models is a rapidly developed direction for the exploration of novel optoelectronic functional materials. Here, we employ random forests regression (RFR) model to investigate the second harmonic generation (SHG) coefficients of nonlinear optical crystals with distinct diamond-like (DL) structures. 61 DL structures in Inorganic Crystallographic Structure Database (ICSD) are selected, and four distinctive descriptors, including band gap, electronegativity, group volume and bond flexibility, are used to model and predict second-order nonlinearity. It is demonstrated that the RFR model has reached the first-principles calculation accuracy, and gives validated predictions for a variety of representative DL crystals. Additionally, this model shows promising applications to explore new crystal materials of quaternary DL system with superior mid-IR NLO performances. Two new potential NLO crystals, Li2CuPS4 with ultrawide bandgap and Cu2CdSnTe4 with giant SHG response, are identified by this model.
Cyclic Digestion and Ligation-Mediated PCR Used for Flanking Sequence Walking
Authors: Yu Dong , Zhou Tianshun , Sun Xuewu , Sun Zhizhong , Sheng Xiabing , Tan Yanning , Liu Ling , Ouyang Ning , Xu Ke , Shi Kaibing , Yuan Guilong , Ding Jia , Duan Meijuan , Yuan Dingyang
Published: February 2020

Ligation-mediated PCR (LM-PCR) is a classical method for isolating flanking sequences; however, it has a common limitation of reduced success rate owing to the circularization or multimerization of target restriction fragments including the known sequence. To address this limitation, we developed a novel LM-PCR method, termed Cyclic Digestion and Ligation-Mediated PCR (CDL-PCR). The novelty of this approach involves the design of new adapters that cannot be digested after being ligated with the restriction fragment, and cyclic digestion and ligation may be manipulated to block the circularization or multimerization of the target restriction fragments. Moreover, to improve the generality and flexibility of CDL-PCR, an adapter precursor sequence was designed, which could be digested to prepare 12 different adapters at low cost. Using this method, the flanking sequences of T-DNA insertions were obtained from transgenic rice and Arabidopsis thaliana. The experimental results demonstrated that CDL-PCR is an efficient and flexible method for identifying the flanking sequences in transgenic rice and Arabidopsis thaliana.
Graphene quantum dots as cysteine protease nanocarriers against stored grain insect pests
Authors: Batool Muazzama , Hussain Dilshad , Akrem Ahmed , Najam-ul-Haq Muhammad , Saeed Shafqat , Zaka Syed Muhammad , Nawaz Muhammad Shoib , Buck Friedrich , Saeed Qamar
Published: February 2020

Storing grains remain vulnerable to insect pest attack. The present study developed a biopesticide using biomolecules and their encapsulation in nanoparticles. A 25 kDa cysteine protease extracted from seeds of Albizia procera (ApCP) was encapsulated in graphene quantum dots (GQDs). The insecticidal activity of ApCP, with or without GQDs, against two stored grain insect pests, Tribolium castaneum (Herbst) and Rhyzopertha dominica (Fabricius) was explored. Insects were exposed to three concentrations 7.0, 3.5 and 1.7 mg of ApCP per a gram of wheat flour and grains. The insecticidal activity of ApCP encapsulated with GQDs was improved compared to that of ApCP without GQDs for both insect pests. The number of eggs and larvae of T. castaneum was reduced by 49% and 86%, respectively. Larval mortality was increased to 72%, and adult eclosion of T. castaneum was reduced by 98% at a 7.0 mg/g concentration of ApCP with GQDs compared to that of ApCP without GQDs. Exposure to 7.0 mg/g ApCP with GQDs, the number of R. dominica eggs and larvae was reduced by 72% and 92% respectively, larval mortality was increased by 90%, and eclosion was reduced by 97%. The extraction, purification, characterization, quantification and encapsulation of ApCP with GQDs were also studied. Cysteine protease nanocarriers have the potential to control stored grain insect pests.
Leishmania donovani infection induce differential miRNA expression in CD4+ T cells
Authors: Kumar Vinod , Das Sushmita , Kumar Ajay , Tiwari Neeraj , Kumar Ashish , Abhishek Kumar , Mandal Abhishek , Kumar Manjay , Shafi Taj , Bamra Tanvir , Singh Rakesh Kumar , Vijayakumar Saravanan , Sen Abhik , Das Pradeep
Published: February 2020

Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host uponLeishmaniainfection. However, the regulatory mechanism for Th1/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells withLeishmania donovaniinfected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p < 0.05), which were validated by qPCR. Further, usinginsilcoapproach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1/2 dichotomy uponLeishmania donovaniinfection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role inLeishmania donovaniinfection.
Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis
Authors: Tan Shing Cheng , Lim Poh Ying , Fang Jie , Mokhtar Mira Farzana Mohamad , Hanif Ezanee Azlina Mohamad , Jamal Rahman
Published: February 2020

Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03–1.71, P = 0.03; heterozygous, OR = 1.08, 95% CI = 1.00–1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02–1.30; P = 0.03; recessive, OR = 1.35, 95% CI = 1.06–1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00–1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.
Improving emulsion stability based on ovalbumin-carboxymethyl cellulose complexes with thermal treatment near ovalbumin isoelectric point
Authors: Li Zhenshun , Kuang Hairui , Yang Jinchu , Hu Jie , Ding Baomiao , Sun Weiqing , Luo Yangchao
Published: February 2020

Ovalbumin (OVA) is an important protein emulsifier. However, it is unstable near the isoelectric point pH, which limits its applications in the food industry. Polysaccharides may be explored to tackle this challenge by improving its pH-dependent instability. In this work, carboxymethyl cellulose (CMC) was used as a model polysaccharide to mix with OVA near its isoelectric point (pH 4.7) with subsequent mild heating at 60 °C for 30 min. The molecular interactions between OVA and CMC were comprehensively studied via a series of characterizations, including turbidity, zeta potential, intrinsic fluorescence, surface hydrophobicity, circular dichroism (CD) spectra and Fourier transform infrared spectroscopy (FTIR). The droplet sizes of the emulsions prepared by OVA-CMC were measured to analyze emulsifying property and stability. The results indicated that free OVA was easily aggregated due to loss of surface charges, while complexing with CMC significantly inhibited OVA aggregation before and after heating owing to the strong electrostatic repulsion. In addition, OVA exposed more hydrophobic clusters after heating, which resulted in the growth of surface hydrophobicity. Altogether, the heated OVA-CMC complexes presented the best emulsifying property and stability. Our study demonstrated that complexing OVA with CMC not only greatly improved its physicochemical properties but also significantly enhanced its functionality as a food-grade emulsifying agent, expanding its applications in the food industry, as development of emulsion-based acidic food products.
Detection of mutations associated with artemisinin resistance at k13-propeller gene and a near complete return of chloroquine susceptible falciparum malaria in Southeast of Tanzania
Authors: Bwire George M. , Ngasala Billy , Mikomangwa Wigilya P. , Kilonzi Manase , Kamuhabwa Appolinary A. R.
Published: February 2020

In Tanzania, chloroquine was replaced by sulphadoxine- pyrimethamine (SP) as a first-line for treatment of uncomplicated malaria. Due to high resistance in malaria parasites, SP lasted for only 5 years and by the end of 2006 it was replaced with the current artemisinin combination therapy. We therefore, set a study to determine the current genotypic mutations associated with Plasmodium falciparum resistance to artemisinin, partner drugs and chloroquine. Parasites DNA were extracted from dried blood spots collected by finger-prick from Tanzanian malaria infected patients. DNA were sequenced using MiSeq then genotypes were translated into drug resistance haplotypes at Wellcome Sanger Institute, UK. About 422 samples were successful sequenced for K13 gene (marker for artemisinin resistance), the wild type (WT) was found in 391 samples (92.7%) whereby 31 samples (7.3%) had mutations in K13 gene. Of 31 samples with mutations, one sample had R561H, a mutation that has been associated with delayed parasite clearance in Southeast Asia, another sample had A578S, a mutation not associated with artemisinin whilst 29 samples had K13 novel mutations. There were no mutations in PGB, EXO, P23_BP and PfMDR1 at position 86 and 1246 (markers for resistance in artemisinin partner drugs) but 270 samples (60.4%) had mutations at PfMDR1 Y184F. Additionally, genotyped PfCRT at positions 72–76 (major predictors for chroquine resistance), found WT gene in 443 out of 444 samples (99.8%). In conclusion, this study found mutations in K13-propeller gene and high prevalence of chloroquine susceptible P. falciparum in Southeast of Tanzania.
Liver function monitoring: a prospective nested case-control study of Salvia miltiorrhiza polyphenol injection
Authors: Cheng Jin-quan , Shi Qing-ping , Ding Feng , Kong Ling-ti , Yu Mei-ling , Wang Can
Published: February 2020

Instructions for Salvia miltiorrhiza polyphenol injections indicate abnormal liver function as an occasional adverse reaction, but the incidence of this adverse drug reaction (ADR) has increased in recent years. We assessed S. miltiorrhiza polyphenol ADRs by performing a nested case-control study(NCCS) and meta-analysis. In the NCCS, 2633 patients receiving this treatment in the First Affiliated Hospital of Bengbu Medical College were enrolled. Logistic regression models found that in 58 (2.2%) patients experiencing abnormal liver function, the risk for liver dysfunction was associated with sulfa drug allergy (OR = 7.874, 95%CI (1.280, 48.447), P = 0.026), payment methods (OR = 0.106, 95%CI (0.012, 0.934), P = 0.043), duration of administration (OR = 0.922, 95%CI (0.862, 0.986), P = 0.017), cefathiamidine (OR = 0.441, 95%CI (0.216, 0.900), P = 0.025), human serum albumin (OR = 1.958, 95%CI (1.011, 3.789), P = 0.046), Dazhu Rhodiola injection (OR = 2.599, 95%CI (1.112, 6.070), P = 0.027), or reduced glutathione (OR = 0.394, 95%CI (0.188, 0.826), P = 0.014). Meta-analysis of reports on S. miltiorrhiza polyphenol ADRs in controlled trials and other observational studies included 676 patients, of which 17 (2.17%; 95%CI (0.0105, 0.0358)) presented with liver dysfunction; associated ADR risk factors included co-administration of other drugs. Our NCCS and meta-analysis had similar ADR incidence rates, which were higher than the rate in the drug instructions. This study provides guidance for assessing liver dysfunction risks associated with S. miltiorrhiza polyphenol injections.
Development and validation of UPLC-MS/MS method for studying the pharmacokinetic interaction of dasabuvir and tamoxifen, 4-hydroxytamoxifen in Wistar rats
Authors: Almomen Aliyah , Maher Hadir M. , Alzoman Nourah Z. , Shehata Shereen M. , Al-taweel Shorog M. , Alanazi Ashwaq A.
Published: February 2020

Hepatitis C virus (HCV) is the main cause of chronic hepatitis and probably liver cirrhosis. Dasabuvir (DSV) is a direct-acting antiviral agent with efficiency in managing HCV. The anti-viral activity of the anti-estrogen drug tamoxifen (TAM) suggested the synergistic effect of DSV and TAM for blocking the replication of HCV. However, being substrates and inhibitors of efflux transporters (TAM inhibits P-gp, DSV inhibits P-gp and BCRP), there is a possibility for a pharmacokinetic (PK) drug-drug interaction. In this work, a new UPLC-MS/MS method was developed and validated for the simultaneous determination of TAM, its active metabolite 4-hydroxy tamoxifen (TOH), and DSV in rat plasma. The method was applied to investigate the PK interaction between DSV and TAM/TOH following the co-administration of DSV and TAM to Wistar rats. Chromatographic analysis was performed on Waters BEHTM C18 column using a mobile phase of acetonitrile/water containing 0.1% formic acid (80: 20, v/v). The method allowed the determination of concentration ranges 20–1000, 0.1–500, 0.5–500 ng/mL for DSV, TAM, and TOH, respectively. Unexpectedly, results revealed the absence of PK interactions between DSV and TAM/TOH, compared with their single administration, suggesting the safety of co-administering DSV/TAM as an anti-viral combination without the need of dosage adjustment.
Energy metabolism of the equine cumulus oocyte complex during in vitro maturation
Authors: Lewis N. , Hinrichs K. , Leese H. J. , McG. Argo C. , Brison D. R. , Sturmey R.
Published: February 2020

Horses are one of the few species, beside humans, in which assisted reproductive technology has important clinical applications. Furthermore, the horse can serve as a valuable model for the study of comparative reproductive biology. Here we present the first comprehensive characterisation of energy metabolism and mitochondrial efficiency in equine cumulus-oocyte complexes (COCs) during in vitro maturation (IVM), as determined using a combination of non-invasive consumption and release assays and mitochondrial function analysis. These data reveal notable species-specific differences in the rate and kinetics of glucose consumption and glycolysis throughout IVM. Approximately 95% of glucose consumed was accounted for by lactate production; however, high concurrent oxygen consumption indicated a comparatively increased role for non-glycolytic oxidative phosphorylation. Up to 38% of equine COC oxygen consumption could be attributed to non-mitochondrial activities and there was a significant loss of spare respiratory capacity over the course of IVM. Notably, our data also revealed that current IVM protocols may be failing to satisfy the metabolic demands of the equine COC. Our findings constitute the first report on mitochondrial efficiency in the equine COC and provide new insight into comparative gamete biology as well as metabolism of the COC during in vitro maturation.