bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafine particles altered gut microbial population and metabolic profiles in a sex-specific manner in an obese mouse model
Authors: Yang Kundi , Xu Mengyang , Cao Jingyi , Zhu Qi , Rahman Monica , Holmén Britt A. , Fukagawa Naomi K. , Zhu Jiangjiang
Published: March 2021

Emerging evidence has highlighted the connection between exposure to air pollution and the increased risk of obesity, metabolic syndrome, and comorbidities. Given the recent interest in studying the effects of ultrafine particle (UFP) on the health of obese individuals, this study examined the effects of gastrointestinal UFP exposure on gut microbial composition and metabolic function using an in vivo murine model of obesity in both sexes. UFPs generated from light-duty diesel engine combustion of petrodiesel (B0) and a petrodiesel/biodiesel fuel blend (80:20 v/v, B20) were administered orally. Multi-omics approaches, including liquid chromatography–mass spectrometry (LC–MS) based targeted metabolomics and 16S rRNA gene sequence analysis, semi-quantitatively compared the effects of 10-day UFP exposures on obese C57B6 mouse gut microbial population, changes in diversity and community function compared to a phosphate buffer solution (PBS) control group. Our results show that sex-specific differences in the gut microbial population in response to UFP exposure can be observed, as UFPs appear to have a differential impact on several bacterial families in males and females. Meanwhile, the alteration of seventy-five metabolites from the gut microbial metabolome varied significantly (ANOVA p < 0.05) across the PBS control, B0, and B20 groups. Multivariate analyses revealed that the fuel-type specific disruption to the microbial metabolome was observed in both sexes, with stronger disruptive effects found in females in comparison to male obese mice. Metabolic signatures of bacterial cellular oxidative stress, such as the decreased concentration of nucleotides and lipids and increased concentrations of carbohydrate, energy, and vitamin metabolites were detected. Furthermore, blood metabolites from the obese mice were differentially affected by the fuel types used to generate the UFPs (B0 vs. B20).
Studies on the mitochondrial, immunological and inflammatory effects of solvent fractions of Diospyros mespiliformis Hochst in Plasmodium berghei-infected mice
Authors: David Oluwole Moses , Olanlokun John Oludele , Owoniyi Bisola Evelyn , Ayeni MoyinOluwa , Ebenezer Oluwakemi , Koorbanally Neil Anthony
Published: March 2021

The use of medicinal plants in the treatment of malaria is gaining global attention due to their efficacy and cost effectiveness. This study evaluated the bioactivity-guided antiplasmodial efficacy and immunomodulatory effects of solvent fractions of Diospyros mespiliformis in mice infected with a susceptible strain of Plasmodium berghei (NK 65). The crude methanol extract of the stem of D. mespiliformis (DM) was partitioned between n-hexane, dichloromethane, ethyl acetate and methanol. Male Swiss mice (20 ± 2 g) infected with P. berghei were grouped and treated with vehicle (10 mL/kg, control), Artemether lumefantrine (10 mg/kg), 100, 200 and 400 mg/kg of n-hexane, dichloromethane, ethyl acetate and methanol fractions of D. mespiliformis for seven days. Blood was obtained for heme and hemozoin contents while serum was obtained for inflammatory cytokines and immunoglobulins G and M assessments. Liver mitochondria were isolated for mitochondrial permeability transition (mPT), mitochondrial F1F0 ATPase (mATPase) and lipid peroxidation (mLPO) assays. The GC–MS was used to identify the compounds present in the most potent fraction. The dichloromethane fraction had the highest parasite clearance and improved hematological indices relative to the drug control. The heme values increased, while the hemozoin content significantly (P < 0.05) decreased compared with the drug control. The highest dose of HF and MF opened the mPT pore while the reversal effects of DF on mPT, mATPase and mLPO were dose-dependent. The levels of IgG, IgM and TNFα in the DF group were significantly higher than the drug control, while the IL-1β and IL-6 values did not vary linearly with the dose. Lupeol and Stigmastan-3,5-diene were the most abundant phytochemicals in the DF. The outcome of this study showed that the DF has immunomodulatory effects in infected mice, reduced proliferation of the malaria parasite and thus protect liver cells.
Factors influencing exclusive breastfeeding rates until 6 months postpartum: the Japan Environment and Children’s Study
Authors: Inano Hitomi , Kameya Mariko , Sasano Kyoko , Matsumura Kenta , Tsuchida Akiko , Hamazaki Kei , Inadera Hidekuni , Hasegawa Tomomi ,   The Japan Environment and Children’s Study (JECS) Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Kusuhara Koichi , Katoh Takahiko
Published: March 2021

This research aimed to examine the efficacy of the early initiation of breastfeeding within 1 h of birth, early skin-to-skin contact, and rooming-in for the continuation of exclusive breastfeeding until 6 months postpartum. The research used data from the Japan Environment and Children’s Study (JECS), a nationwide government-funded birth cohort study. A total of 80,491 mothers in Japan between January 2011 and March 2014 who succeeded or failed to exclusively breastfeed to 6 months were surveyed in JECS. Multiple logistic regression model was used to analyse the data. The percentage of mothers who succeeded in exclusively breastfeeding to 6 months is 37.4%. Adjusted odds ratios were analysed for all 35 variables. Early initiation of breastfeeding (adjusted odds ratio [AOR]: 1.455 [1.401–1.512]), early skin-to-skin contact (AOR: 1.233 [1.165–1.304]), and rooming-in (AOR: 1.567 [1.454–1.690]) affected continuation of exclusive breastfeeding. Regional social capital (AOR: 1.133 [1.061–1.210]) was also discovered to support the continuation of breastfeeding. In contrast, the most influential inhibiting factors were starting childcare (AOR: 0.126 [0.113–0.141]), smoking during pregnancy (AOR: 0.557 [0.496–0.627]), and obese body type during early pregnancy (AOR: 0.667 [0.627–0.710]).
Comparative proteomic profiling of newly acquired, virulent and attenuated Neoparamoeba perurans proteins associated with amoebic gill disease
Authors: Dhufaigh Kerrie Ní , Dillon Eugene , Botwright Natasha , Birlanga Victor , Talbot Anita , O’Connor Ian , MacCarthy Eugene , Slattery Orla
Published: March 2021

The causative agent of amoebic gill disease, Neoparamoeba perurans is reported to lose virulence during prolonged in vitro maintenance. In this study, the impact of prolonged culture on N. perurans virulence and its proteome was investigated. Two isolates, attenuated and virulent, had their virulence assessed in an experimental trial using Atlantic salmon smolts and their bacterial community composition was evaluated by 16S rRNA Illumina MiSeq sequencing. Soluble proteins were isolated from three isolates: a newly acquired, virulent and attenuated N. perurans culture. Proteins were analysed using two-dimensional electrophoresis coupled with liquid chromatography tandem mass spectrometry (LC–MS/MS). The challenge trial using naïve smolts confirmed a loss in virulence in the attenuated N. perurans culture. A greater diversity of bacterial communities was found in the microbiome of the virulent isolate in contrast to a reduction in microbial community richness in the attenuated microbiome. A collated proteome database of N. perurans, Amoebozoa and four bacterial genera resulted in 24 proteins differentially expressed between the three cultures. The present LC–MS/MS results indicate protein synthesis, oxidative stress and immunomodulation are upregulated in a newly acquired N. perurans culture and future studies may exploit these protein identifications for therapeutic purposes in infected farmed fish.
Stochastic modelling of the effects of human-mobility restriction and viral infection characteristics on the spread of COVID-19
Authors: Ando Shiho , Matsuzawa Yuki , Tsurui Hiromichi , Mizutani Tetsuya , Hall Damien , Kuroda Yutaka
Published: March 2021

After several months of "lockdown" as the sole answer to the COVID-19 pandemic, balancing the re-opening of society against the implementation of non-pharmaceutical measures needed for minimizing interpersonal contacts has become important. Here, we present a stochastic model that examines this problem. In our model, people are allowed to move between discrete positions on a one-dimensional grid with viral infection possible when two people are collocated at the same site. Our model features three sets of adjustable parameters, which characterize (i) viral transmission, (ii) viral detection, and (iii) degree of personal mobility, and as such, it is able to provide a qualitative assessment of the potential for second-wave infection outbreaks based on the timing, extent, and pattern of the lockdown relaxation strategies. Our results suggest that a full lockdown will yield the lowest number of infections (as anticipated) but we also found that when personal mobility exceeded a critical level, infections increased, quickly reaching a plateau that depended solely on the population density. Confinement was not effective if not accompanied by a detection/quarantine capacity surpassing 40% of the symptomatic patients. Finally, taking action to ensure a viral transmission probability of less than 0.4, which, in real life, may mean actions such as social distancing or mask-wearing, could be as effective as a soft lockdown.
Impact of home-based squat training with two-depths on lower limb muscle parameters and physical functional tests in older adults
Authors: Yoshiko Akito , Watanabe Kohei
Published: March 2021

This study investigated the effect of home-based shallow and deep squat trainings on knee extension peak torque, muscle thickness, one-repetition maximum (1RM) leg press, and physical function in older individuals. Sixteen participants were randomly assigned to the shallow squat group (SS group; age, 71.0  ±  4.0 years) or deep squat group (DS group, age; 68.6  ± 3.6 years). Chairs of 40-cm height and chairs with a cushion of 20-cm height (60-cm in total) were used as the depth targets for squats, with participants instructed to sink until their hip touched the chair and cushion. Participants performed four sets of squats per day (35 repetitions per set), three days per week, for 12 weeks at their home. Knee extension peak torque, muscle thickness of quadriceps femoris (e.g., vastus lateralis, rectus femoris, and vastus intermedius), and physical function were measured at weeks 0 (baseline), 4, 8, and 12. Maximal isometric knee extension peak torque, muscle thickness, and walking speed did not change significantly over the 12-week training period in either group (P > 0.05). However, compared with the baseline, there was significant improvement in the results of 30-s sit-to-stand repetition tests after weeks 8 and 12 in both groups (P < 0.05). Additionally, 1RM leg press results were significantly improved after weeks 4 and 12 in the DS group, and weeks 4, 8, and 12 in the SS group (P < 0.05). Results indicate that home-based weight-bearing squat training improves lower limb function in older adults, as well as performance in physical functional tests related to activities of daily living. Moreover, such training benefits older adults regardless of whether squats are shallow or deep.
Successful extraction of insect DNA from recent copal inclusions: limits and perspectives
Authors: Modi Alessandra , Vergata Chiara , Zilli Cristina , Vischioni Chiara , Vai Stefania , Tagliazucchi Guidantonio Malagoli , Lari Martina , Caramelli David , Taccioli Cristian
Published: March 2021

Insects entombed in copal, the sub-fossilized resin precursor of amber, represent a potential source of genetic data for extinct and extant, but endangered or elusive, species. Despite several studies demonstrated that it is not possible to recover endogenous DNA from insect inclusions, the preservation of biomolecules in fossilized resins samples is still under debate. In this study, we tested the possibility of obtaining endogenous ancient DNA (aDNA) molecules from insects preserved in copal, applying experimental protocols specifically designed for aDNA recovery. We were able to extract endogenous DNA molecules from one of the two samples analyzed, and to identify the taxonomic status of the specimen. Even if the sample was found well protected from external contaminants, the recovered DNA was low concentrated and extremely degraded, compared to the sample age. We conclude that it is possible to obtain genomic data from resin-entombed organisms, although we discourage aDNA analysis because of the destructive method of extraction protocols and the non-reproducibility of the results.
Fine scale infectious disease modeling using satellite-derived data
Authors: Randhawa Nistara , Mailhot Hugo , Lang Duncan Temple , Martínez-López Beatriz , Gilardi Kirsten , Mazet Jonna A. K.
Published: March 2021

Innovative tools for modeling infectious agents are essential for better understanding disease spread given the inherent complexity of changing and interacting ecological, environmental, and demographic factors. We leveraged fine-scale satellite data on urban areas to build a road-connected geospatial network upon which to model disease spread. This model was tested by simulating the spread of the 2009 pandemic influenza in Rwanda and also used to determine the effects of vaccination regimens on outbreak spread and impact. Our results were comparable to data collected during the actual pandemic in Rwanda, determining the initial places affected after outbreak introduction in Kigali. They also highlighted the effectiveness of preventing outbreaks by targeting mitigation efforts at points of outbreak origin. This modeling approach can be valuable for planning and control purposes in real-time disease situations, providing helpful baseline scenarios during initial phases of outbreaks, and can be applied to other infectious diseases where high population mobility promotes rapid disease propagation.
Heating performance of a laboratory pilot-plant combining heat exchanger and air scrubber for animal houses
Authors: Krommweh Manuel S. , Büscher Wolfgang
Published: March 2021

Exhaust air treatment systems (EATS) are used in animal husbandry to reduce emissions. However, EATS are associated with high acquisition and operating costs. Therefore, a plant technology is being developed that integrates a recuperative heat exchanger into a biological air scrubber. The overall aim is to reduce total costs of livestock buildings with EATS by saving heating costs and to improve animal environment. In this study, a special pilot-plant on a small-scale, using clean exhaust air, was constructed to evaluate the heating performance on laboratory scale. Three assembly situations of the heat exchanger into trickle-bed reactor were part of a trial with two different defined air flow rates. In all three assembly situations, preheating of cold outside air was observed. The heating performance of the assembly situation with the sprayed heat exchanger arranged below showed an average of 4.4 kW at 1800 m3 h−1 (outside air temperature range 0.0–7.9 °C). This is up to 18% higher than the other two experimental setups. The heating performance of the pilot-plant is particularly influenced by the outside air temperature. Further research on the pilot-plant is required to test the system under field conditions.
Quantitative comparison of corneal surface areas in keratoconus and normal eyes
Authors: Crahay François-Xavier , Debellemanière Guillaume , Tobalem Stephan , Ghazal Wassim , Moran Sarah , Gatinel Damien
Published: March 2021

Keratoconus is a highly prevalent corneal disorder characterized by progressive corneal thinning, steepening and irregular astigmatism. To date, pathophysiology of keratoconus development and progression remains debated. In this study, we retrospectively analysed topographic elevation maps from 3227 eyes of 3227 patients (969 keratoconus and 2258 normal eyes) to calculate anterior and posterior corneal surface area. We compared results from normal eyes and keratoconus eyes using the Mann–Whitney U test. The Kruskal–Wallis test was used to compare keratoconus stages according to the Amsler–Krumeich classification. Keratoconus eyes were shown to have statistically significantly larger corneal surface areas, measured at the central 4.0 mm and 8.0 mm, and total corneal diameter. However, no significant increase in corneal surface area was seen with increasing severity of keratoconus. We suggest that these results indicate redistribution, rather than increase, of the corneal surface area with keratoconus severity.
Pharmacokinetics and metabolomics investigation of an orally modified formula of standardized Centella asiatica extract in healthy volunteers
Authors: Songvut Phanit , Chariyavilaskul Pajaree , Khemawoot Phisit , Tansawat Rossarin
Published: March 2021

The formula of a standardized extract ofCentella asiatica(ECa 233) was modified to improve its dissolution, with implications for pharmacokinetics and metabolomic profile. This study aimed to understand the resultant changes in disposition kinetics of ECa 233 and alterations to human metabolome after oral administration. This study was a two-sequence of dosages (250 and 500 mg), with an open-label phase I clinical trial. The modified formula was administered in single and multiple doses to twelve healthy Thai volunteers. The major parent compounds, madecassoside and asiaticoside, were rarely absorbed, instead undergoing biotransformation into active metabolites, madecassic acid and asiatic acid with possibility to be eliminated via fecal route. Increasing the dose of ECa 233 resulted in significantly greater plasma levels of those active metabolites, with accumulation of asiatic acid after multiple oral administration for seven days. Examining the impacts of accumulation behavior on metabolomics, the study traced changes in levels pre- and post-dose of five relevant human metabolites. Administration of ECa 233 was found to be significantly associated with an increase of choline, an endogenous metabolite with documented benefits for learning and memory. Therefore, ECa 233 may be useful in mitigating cognitive impairment, through its role in modulating human metabolites.
Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation
Authors: Enomoto Nobuko , Anraku Ayako , Tomita Goji , Iwase Aiko , Sato Takashi , Shoji Nobuyuki , Shiba Tomoaki , Nakazawa Toru , Sugiyama Kazuhisa , Nitta Koji , Araie Makoto
Published: March 2021

To characterize laser speckle flowgraphy (LSFG) pulse waveform parameters for ocular circulation evaluation, a multicenter, prospective, cross-sectional study was conducted in 111 eyes of 86 healthy Japanese individuals. Optic nerve head (ONH) tissue-area, vessel-area mean blur rate (MT and MV, respectively), and MT and MV pulse waveform parameters were obtained using LSFG and ONH structural parameters using planimetry. Multivariate linear mixed-effects modeled regression analysis identified factors contributing to MT- or MV-waveforms using age, gender, smoking history, body mass index, systolic and diastolic blood pressure, heart rate, intraocular pressure, axial length, disc, rim, and β-peripapillary atrophy areas, MT or MV, central retinal artery, and vein equivalents (CRAE and CRVE) as explanatory variables. MT- and MV-waveforms significantly correlated with one or more systemic factors, consistent with previous studies. Following confounding factor adjustment, MT-Skew significantly negatively correlated with β-PPA area (P = 0.026); MT- and MV-flow acceleration index positively correlated with CRAE, MT, and MV (P = 0.041–< 0.001), compatible with these parameters’ observed correlations to systemic factors. Significantly negative correlations of the blowout score and acceleration time index to CRAE partly conflicted with their correlations to systemic factors, and other waveform parameters showed little correlation to ocular factors. Thus, Skew and flow acceleration index assisted the in vivo ocular circulation characterization.
Exploring traditional medicine utilisation during antenatal care among women in Bulilima District of Plumtree in Zimbabwe
Authors: Mudonhi Nicholas , Nunu Wilfred Njabulo , Sibanda Nomathemba , Khumalo Nkosana
Published: March 2021

Traditional medicine utilisation during antenatal care has been on the increase in several countries. Therefore, addressing and reinforcing the Sustainable Development Goal of maternal mortality reduction, there is a need to take traditional medicine utilisation during pregnancy into consideration. This paper explores traditional medicine utilisation during antenatal care among women in Bulilima District of Plumtree in Zimbabwe. A cross-sectional survey was conducted on 177 randomly selected women using a semi-structured questionnaire. Fisher's Exact Test, Odds Ratios, and Multiple Logistic Regression were utilised to determine any associations between different demographic characteristics and traditional medicine utilisation patterns using STATA SE Version 13. The prevalence of Traditional Medicine utilisation among pregnant women was estimated to be 28%. Most traditional remedies were used in the third trimester to quicken delivery. The majority of women used holy water and unknown Traditional Medicine during pregnancy. There was a strong association between age and Traditional Medicine utilisation as older women are 13 times more likely to use Traditional Medicine than younger ones. Women use traditional medicine for different purposes during pregnancy, and older women's likelihood to use Traditional Medicine is higher than their counterparts. The traditional system plays an essential role in antenatal care; therefore, there is a need to conduct further studies on the efficacy and safety of utilising Traditional Medicines.
Tunneling-induced Talbot effect
Authors: Azizi Babak , Amini Sabegh Zahra , Mahmoudi Mohammad , Rasouli Saifollah
Published: March 2021

We investigate the reforming of a plane wave into a periodic waveform in its propagation through a structural asymmetry four-level quantum dot molecule (QDM) system that is induced by an inter-dot tunneling process and present the resulting tunneling-induced Talbot effect. The tunneling process between two neighborhood dots is provided with the aid of a gate voltage. Using a periodic coupling field the response of the medium to the propagating plane probe beam becomes periodic. The needed periodic coupling field is generated with the interference of two coherent plane waves having a small angle and propagating almost parallel to the probe beam direction. In the presence of the tunneling effect of an electron between two adjacent QDs, for the probe beam propagating through the QDM system, the medium becomes transparent where the coupling fields interfere constructively. As a result, the spatial periodicity of the coupling field modulates the passing plane probe beam. We determine the minimum length of the QDM system to generate a periodic intensity profile with a visibility value equal to 1 for the probe field at the exit plane of the medium. It is also shown that by increasing the propagation length of the probe beam through the QDM medium, the profile of the maximum intensity areas becomes sharper. This feature is quantified by considering a sharpness factor for the intensity profile of the probe beam at the transverse plane. Finally, we investigate free space propagation of the induced periodic field and present the Talbot images of the tunneling-induced periodic patterns at different propagation distances for different values of the QDM medium lengths. The presented dynamically designing method of the periodic coherent intensity patterns might find applications in science and technology. For instance, in optical lithography, the need to use micro/nanofabricated physical transmission diffraction gratings, in which preparation of them is expensive and time-consuming, can be eliminated.
Exposure to low doses of pesticides induces an immune response and the production of nitric oxide in honeybees
Authors: Bartling Merle T. , Thümecke Susanne , Russert José Herrera , Vilcinskas Andreas , Lee Kwang-Zin
Published: March 2021

Honeybees are essential pollinators of many agricultural crops and wild plants. However, the number of managed bee colonies has declined in some regions of the world over the last few decades, probably caused by a combination of factors including parasites, pathogens and pesticides. Exposure to these diverse biotic and abiotic stressors is likely to trigger immune responses and stress pathways that affect the health of individual honeybees and hence their contribution to colony survival. We therefore investigated the effects of an orally administered bacterial pathogen (Pseudomonas entomophila) and low-dose xenobiotic pesticides on honeybee survival and intestinal immune responses. We observed stressor-dependent effects on the mean lifespan, along with the induction of genes encoding the antimicrobial peptide abaecin and the detoxification factor cytochrome P450 monooxygenase CYP9E2. The pesticides also triggered the immediate induction of a nitric oxide synthase gene followed by the delayed upregulation of catalase, which was not observed in response to the pathogen. Honeybees therefore appear to produce nitric oxide as a specific defense response when exposed to xenobiotic stimuli. The immunity-related and stress-response genes we tested may provide useful stressor-dependent markers for ecotoxicological assessment in honeybee colonies.
Efficacy of Texture and Color Enhancement Imaging in visualizing gastric mucosal atrophy and gastric neoplasms
Authors: Ishikawa Tsubasa , Matsumura Tomoaki , Okimoto Kenichiro , Nagashima Ariki , Shiratori Wataru , Kaneko Tatsuya , Oura Hirotaka , Tokunaga Mamoru , Akizue Naoki , Ohta Yuki , Saito Keiko , Arai Makoto , Kato Jun , Kato Naoya
Published: March 2021

In 2020, Olympus Medical Systems Corporation introduced the Texture and Color Enhancement Imaging (TXI) as a new image-enhanced endoscopy. This study aimed to evaluate the visibility of neoplasms and mucosal atrophy in the upper gastrointestinal tract through TXI. We evaluated 72 and 60 images of 12 gastric neoplasms and 20 gastric atrophic/nonatrophic mucosa, respectively. The visibility of gastric mucosal atrophy and gastric neoplasm was assessed by six endoscopists using a previously reported visibility scale (1 = poor to 4 = excellent). Color differences between gastric mucosal atrophy and nonatrophic mucosa and between gastric neoplasm and adjacent areas were assessed using the International Commission on Illumination L*a*b* color space system. The visibility of mucosal atrophy and gastric neoplasm was significantly improved in TXI mode 1 compared with that in white-light imaging (WLI) (visibility score: 3.8 ± 0.5 vs. 2.8 ± 0.9, p < 0.01 for mucosal atrophy; visibility score: 2.8 ± 1.0 vs. 2.0 ± 0.9, p < 0.01 for gastric neoplasm). Regarding gastric atrophic and nonatrophic mucosae, TXI mode 1 had a significantly greater color difference than WLI (color differences: 14.2 ± 8.0 vs. 8.7 ± 4.2, respectively, p < 0.01). TXI may be a useful observation modality in the endoscopic screening of the upper gastrointestinal tract.
Transcriptome-based analysis of resistance mechanism to black point caused by Bipolaris sorokiniana in wheat
Authors: Li Qiaoyun , Gao Chuang , Xu Kaige , Jiang Yumei , Niu Jishan , Yin Guihong , Wang Chenyang
Published: March 2021

Black point is a cereal disease caused by complex pathogens, of which the pathogenicity of Bipolaris sorokiniana is the most serious in wheat. Resistance to black point is quantitative in nature, and thus the mechanism is poorly understood. We conducted a comparative transcriptome analysis to identify differentially expressed genes (DEGs) in black point-slightly susceptible and -highly susceptible wheat lines at different timepoints following B. sorokiniana inoculation. DEGs associated with photosynthesis were upregulated in black point-slightly susceptible lines. The top Gene Ontology enrichment terms for biological processes were oxidation–reduction, response to cold, salt stress, oxidative stress, and cadmium ion; terms for cellular component genes were mainly involved in plasma membrane and cytoplasmic membrane-bounded vesicle, whereas those for molecular function were heme binding and peroxidase activity. Moreover, activities of antioxidant enzymes superoxide dismutase, catalase, and peroxidase were higher in slightly susceptible lines than those in highly susceptible lines (except peroxidase 12–24 days post-inoculation). Thus, resistance to B. sorokiniana-caused black point in wheat was mainly related to counteracting oxidative stress, although the specific metabolic pathways require further study. This study presents new insights for understanding resistance mechanisms of selected wheat lines to black point.
Characterization of a novel sn1,3 lipase from Ricinus communis L. suitable for production of oleic acid-palmitic acid-glycerol oleate
Authors: Li Yue , Li Guorui , Sun Huajun , Chen Yongsheng
Published: March 2021

The hydrolysis properties of lipase in castor was evaluated using two different substrate forms (tripalmitic glycerides and trioleic glycerides) to catalyze the reaction under different operational conditions. RcLipase was obtained from castor seeds and results show that RcLipase is a conservative serine lipase with a conserved catalytic center (SDH) and a conserved pentapeptide (GXSXG). This enzyme exhibited the greatest activity and tolerance to chloroform and toluene when it was expressed in Pichia pastoris GS115 at 40 ℃ and pH 8.0. Zn and Cu ions exerted obvious inhibitory effects on the enzyme, and displayed good hydrolytic activity for long-chain natural and synthetic lipids. HPLC analysis showed that this enzyme has 1,3 regioselectivity when glycerol tripalmitate and oleic acid are used as substrates. The fatty acid composition in the reaction product was 21.3% oleic acid and 79.1% sn-2 palmitic acid.
Prediction of disease flare by biomarkers after discontinuing biologics in patients with rheumatoid arthritis achieving stringent remission
Authors: Kameda Hideto , Hirata Ayako , Katagiri Takaharu , Takakura Yuto , Inoue Yuki , Takenaka Sayaka , Ito Hideki , Mizushina Kennosuke , Ogura Takehisa
Published: March 2021

To elucidate the disease-flare process in rheumatoid arthritis (RA) after discontinuing biological disease-modifying antirheumatic drugs (bDMARDs), we first focused on RA-flare prediction after achieving stringent remission criteria. Patients with RA who maintained a simplified disease activity index ≤ 3.3 for ≥ 3 months during November 2014–January 2018 in our medical centre in Tokyo, Japan, were eligible. The primary endpoint was flare (disease activity score 28—erythrocyte sedimentation rate ≥ 3.2 with increase from baseline > 0.6) within 2 years after bDMARD discontinuation. Comprehensive clinical assessments, ultrasonographic evaluation of 40 joints, and blood sampling for 12 biomarkers were performed every 2–3 months for 2 years unless patients experienced flare. Flare-positive and flare-negative patients were compared using univariate and Kaplan–Meier analyses. Thirty-six patients (80.6% female, median disease duration, 5.2 years; median treatment period with discontinued bDMARD, 2 years; median remission duration, 18 months) were enrolled. Twenty patients (55.6%) experienced RA flare 43–651 (median, 115) days after the first skipped date of bDMARDs. Two patients who withdrew without disease flare were excluded from the comparison. Clinical and ultrasonographic evaluations did not show significant between-group differences; Kaplan–Meier analysis showed that higher baseline soluble tumour necrosis factor receptor 1 (sTNFR1) concentration impacted subsequent disease flare (p = 0.0041); higher baseline interleukin (IL)-2 concentration was exclusively beneficial to patients with lower sTNFR1 (p = 0.0058), resulting in remission maintenance in 83.3% of patients with lower sTNFR1 and higher IL-2. We demonstrated the usefulness of combined biomarker evaluation for predicting sustained remission after bDMARD discontinuation in RA.
Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment
Authors: Muiño Elena , Maisterra Olga , Jiménez-Balado Joan , Cullell Natalia , Carrera Caty , Torres-Aguila Nuria P. , Cárcel-Márquez Jara , Gallego-Fabrega Cristina , Lledós Miquel , González-Sánchez Jonathan , Olmos-Alpiste Ferran , Espejo Eva , March Álvaro , Pujol Ramón , Rodríguez-Campello Ana , Romeral Gemma , Krupinski Jurek , Martí-Fàbregas Joan , Montaner Joan , Roquer Jaume , Fernández-Cadenas Israel
Published: March 2021

CADASIL is a small vessel disease caused by mutations inNOTCH3that lead to an odd number of cysteines in the EGF-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, being executive function characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further. A genome-wide transcriptome study (four cases paired with three healthy siblings) was carried out, in addition to a qRT-PCR for validation purposes (ten new cases and eight new controls). To study the expression profile by cell type of the significant mRNAs found, we performed an in situ hybridization (ISH) (nine cases and eight controls) and a research in the Single-nuclei Brain RNA-seq expression browser (SNBREB). Pathway analysis enrichment was carried out with Gene Ontology and Reactome. Neuropsychological tests were performed in five of the qRT-PCR cases. The two most significant differentially expressed mRNAs (BANP,p-value = 7.23 × 10–4andPDCD6IP,p-value = 8.36 × 10–4) were selected for the validation study by qRT-PCR. Additionally, we selected two more mRNAs (CAMK2G,p-value = 4.52 × 10–3andE2F4,p-value = 4.77 × 10–3) due to their association with ischemic neuronal death.E2F4showed differential expression in the genome-wide transcriptome study and in the qRT-PCR (p = 1.23 × 10–3), and it was upregulated in CADASIL cases. Furthermore, higherE2F4expression was associated with worse executive function (p = 2.04 × 10–2) and attention and information processing speed (IPS) (p = 8.73 × 10–2). In situ hibridization showedE2F4expression in endothelial and vascular smooth vessel cells. In silico studies indicated thatE2F4is also expressed in brain endothelial cells. Among the most significant pathways analyzed, there was an enrichment of vascular development, cell adhesion and vesicular machinery terms and autophagy process. E2F4 is more highly expressed in the skin biopsy of CADASIL patients compared to controls, and its expression is present in endothelial cells and VSMCs. Further studies are needed to understand whether E2F4 could be useful as a biomarker, to monitor the disease or be used as a therapeutic target.
Ground state and stability of the fractional plateau phase in metallic Shastry–Sutherland system TmB4
Authors: Orendáč Matúš , Gabáni Slavomír , Farkašovský Pavol , Gažo Emil , Kačmarčík Jozef , Marcin Miroslav , Pristáš Gabriel , Siemensmeyer Konrad , Shitsevalova Natalya , Flachbart Karol
Published: March 2021

We present a study of the ground state and stability of the fractional plateau phase (FPP) with M/Msat = 1/8 in the metallic Shastry–Sutherland system TmB4. Magnetization (M) measurements show that the FPP states are thermodynamically stable when the sample is cooled in constant magnetic field from the paramagnetic phase to the ordered one at 2 K. On the other hand, after zero-field cooling and subsequent magnetization these states appear to be of dynamic origin. In this case the FPP states are closely associated with the half plateau phase (HPP, M/Msat = ½), mediate the HPP to the low-field antiferromagnetic (AF) phase and depend on the thermodynamic history. Thus, in the same place of the phase diagram both, the stable and the metastable (dynamic) fractional plateau (FP) states, can be observed, depending on the way they are reached. In case of metastable FP states thermodynamic paths are identified that lead to very flat fractional plateaus in the FPP. Moreover, with a further decrease of magnetic field also the low-field AF phase becomes influenced and exhibits a plateau of the order of 1/1000 Msat.
Increased RNA virus population diversity improves adaptability
Authors: Mattenberger Florian , Vila-Nistal Marina , Geller Ron
Published: March 2021

The replication machinery of most RNA viruses lacks proofreading mechanisms. As a result, RNA virus populations harbor a large amount of genetic diversity that confers them the ability to rapidly adapt to changes in their environment. In this work, we investigate whether further increasing the initial population diversity of a model RNA virus can improve adaptation to a single selection pressure, thermal inactivation. For this, we experimentally increased the diversity of coxsackievirus B3 (CVB3) populations across the capsid region. We then compared the ability of these high diversity CVB3 populations to achieve resistance to thermal inactivation relative to standard CVB3 populations in an experimental evolution setting. We find that viral populations with high diversity are better able to achieve resistance to thermal inactivation at both the temperature employed during experimental evolution as well as at a more extreme temperature. Moreover, we identify mutations in the CVB3 capsid that confer resistance to thermal inactivation, finding significant mutational epistasis. Our results indicate that even naturally diverse RNA virus populations can benefit from experimental augmentation of population diversity for optimal adaptation and support the use of such viral populations in directed evolution efforts that aim to select viruses with desired characteristics.
Distinct expression profiles of regulatory RNAs in the response to biocides in Staphylococcus aureus and Enterococcus faecium
Authors: Dejoies Loren , Le Neindre Killian , Reissier Sophie , Felden Brice , Cattoir Vincent
Published: March 2021

The aim of the study was to characterize the antimicrobial activity of clinically-relevant biocides (chlorhexidine digluconate, benzalkonium chloride, PVP-iodine and triclosan) and to determine the sRNA expression profiles under biocide exposure in two major bacterial opportunistic pathogens, Enterococcus faecium and Staphylococcus aureus. In vitro activities were evaluated against S. aureus HG003 and E. faecium Aus0004. We determined MIC, MBC, sub-inhibitory concentrations (SIC) and growth curves under SIC conditions. sRNA expression study under SIC exposure of biocides was performed by RT-qPCR on 3 sRNAs expressed in S. aureus (RNAIII, SprD and SprX) and the first 9 sRNAs identified as expressed in E. faecium. MICs were higher against E. faecium than for S. aureus. Growth curves under increasing biocide concentrations highlighted two types of bactericidal activity: “on/off” effect for chlorhexidine, benzalkonium chloride, PVP-iodine and a “concentration-dependent” activity for triclosan. Exposure to biocide SICs led to an alteration of several sRNA expression profiles, mostly repressed. The distinct biocide activity profiles must be evaluated with other compounds and bacterial species to enrich the prediction of resistance risks associated with biocide usage. Biocide exposure induces various sRNA-mediated responses in both S. aureus and E. faecium, and further investigations are needed to decipher sRNA-driven regulatory networks.
Position sensitive measurement of trace lithium in the brain with NIK (neutron-induced coincidence method) in suicide
Authors: Schoepfer J. , Gernhäuser R. , Lichtinger S. , Stöver A. , Bendel M. , Delbridge C. , Widmann T. , Winkler S. , Graw M.
Published: March 2021

Mood disorder is the leading intrinsic risk factor for suicidal ideation. Questioning any potency of mood-stabilizers, the monovalent cation lithium still holds the throne in medical psychiatric treatment. Furthermore, lithium`s anti-aggressive and suicide-preventive capacity in clinical practice is well established. But little is still known about trace lithium distribution and any associated metabolic effects in the human body. We applied a new technique (neutron-induced coincidence method “NIK”) utilizing the 6Li(n,α)3H reaction for the position sensitive, 3D spatially resolved detection of lithium traces in post-mortem human brain tissue in suicide versus control. NIK allowed, for the first time in lithium research, to collect a three dimensional high resolution map of the regional trace lithium content in the non lithium-medicated human brain. The results show an anisotropic distribution of lithium, thus indicating a homeostatic regulation under physiological conditions as a remarkable link to essentiality. In contrast to suicide we could empirically prove significantly higher endogenous lithium concentrations in white compared to gray matter as a general trend in non-suicidal individuals and lower lithium concentrations in emotion-modulating regions in suicide.
Reactive transport modelling of an intra-basalt sandstone reservoir, Rosebank, UK
Authors: Sætre C. , Hellevang H. , Dennehy C. , Dypvik H.
Published: March 2021

The Rosebank field, located in the Faroe-Shetland Basin, contains producible hydrocarbons in intra-basaltic siliciclastic reservoirs. The volcanic-reservoir interface is poorly studied and the geochemical system, as a function of distance from the basalt, is largely unknown. The current paper applies a geochemical model coupling mineral dissolution and precipitation with element diffusion to investigate the geochemical system in time and space from the basalt-sandstone interface. Earlier studies indicate few negative effects on reservoir properties despite the proximity to a reactive volcanic lithology. The causes of this minimal impact have not been studied. The numerical simulations in this study expand on the knowledge demonstrating that precipitation of authigenic phases at the basalt-sandstone interface buffer the formation water solution for key elements, which hamper the transport of solutes and subsequent precipitation of secondary minerals within the reservoir. Saturation index values over the simulated period indicate that precipitation of authigenic phases should not extend beyond the basalt-sandstone interface. This shows that diffusion alone is not enough to reduce the reservoir quality due to increased precipitation of secondary phases. The basalt dissolution rate varies according to the silica concentration. The combined effects on silica concentration by diffusional fluxes, mineral precipitation and dissolution, control the basalt dissolution rate, and there are no differences in the results between high and low basalt reactive surface area.
Symptoms and syndromes associated with SARS-CoV-2 infection and severity in pregnant women from two community cohorts
Authors: Molteni Erika , Astley Christina M. , Ma Wenjie , Sudre Carole H. , Magee Laura A. , Murray Benjamin , Fall Tove , Gomez Maria F. , Tsereteli Neli , Franks Paul W. , Brownstein John S. , Davies Richard , Wolf Jonathan , Spector Tim D. , Ourselin Sebastien , Steves Claire J. , Chan Andrew T. , Modat Marc
Published: March 2021

We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18–44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.
Molecular typing and antimicrobial resistance profiling of 33 mastitis-related Staphylococcus aureus isolates from cows in the Comarca Lagunera region of Mexico
Authors: Mora-Hernández Y. , Vera Murguía E. , Stinenbosch J. , Hernández Jauregui P. , van Dijl Jan Maarten , Buist G.
Published: March 2021

Mastitis in cows is a major cause of economic losses and it is commonly associated with Staphylococcus aureus. Little is known about the S. aureus lineages causing mastitis in Mexican cattle. The aim of this study was to type S. aureus isolates causing mastitis in cows from the Comarca Lagunera region in Mexico in 2015–2016. Multi-locus variable number tandem repeat fingerprinting (MLVF) of 33 S. aureus isolates obtained from 210 milk samples revealed the MLVF clusters A (n = 1), B (n = 26), C (n = 5) and D (n = 1). Spa-typing showed that clusters A and B represent the spa-type t224, cluster C includes spa-types t3196 and t416, and cluster D represents spa-type t114. The different spa-types were mirrored by the masses of protein A bands as detected by Western blotting. Antimicrobial susceptibility testing showed that one isolate was susceptible to all antimicrobials tested, whereas all other strains were resistant only to benzylpenicillin. These findings show that only four S. aureus lineages, susceptible to most antimicrobials, were responsible for causing mastitis at the time of sampling. Lastly, many isolates carried the same small plasmid, designated pSAM1. The high prevalence of pSAM1 amongst the antimicrobial-susceptible isolates suggests an association with bovine colonization or mastitis rather than antimicrobial resistance.