bluuebunny/crossref_metadata_2025 huggingface dataset:
N-glycosylation of immunoglobulin G predicts incident hypertension
Authors: Kifer Domagoj , Louca Panayiotis , Cvetko Ana , Deriš Helena , Cindrić Ana , Grallert Harald , Peters Annette , Polašek Ozren , Gornik Olga , Mangino Massimo , Spector Tim D. , Valdes Ana M. , Padmanabhan Sandosh , Gieger Christian , Lauc Gordan , Menni Cristina
Published: July 2021

Objectives:

Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and has been implicated in prevalent hypertension. The aim of this study is to investigate whether the IgG glycome begins to change prior to hypertension diagnosis by analysing the IgG glycome composition in a large population-based female cohort with two independent replication samples.

Methods:

We included 989 unrelated cases with incident hypertension and 1628 controls from the TwinsUK cohort (mean follow-up time of 6.3 years) with IgG measured at baseline by ultra-performance liquid chromatography and longitudinal BP measurement available. We replicated our findings in 106 individuals from the 10 001 Dalmatians and 729 from KORA S4. Cox regression mixed models were applied to identify changes in glycan traits preincident hypertension, after adjusting for age, mean arterial pressure, BMI, family relatedness and multiple testing (FDR < 0.1). Significant IgG-incident hypertension associations were replicated in the two independent cohorts by leveraging Cox regression mixed models in the 10 001 Dalmatians and logistic regression models in the KORA cohort.

Results:

We identified and replicated four glycan traits, incidence of bisecting GlcNAc, GP4, GP9 and GP21, that are predictive of incident hypertension after adjusting for confoundes and multiple testing [hazard ratio (95% CI) ranging from 0.45 (0.24–0.84) for GP21 to 2.9 (1.5–5.68) for GP4]. We then linearly combined the four replicated glycans and found that the glycan score correlated with incident hypertension, SBP and DBP.

Conclusion:

Our results suggest that the IgG glycome changes prior to the development of hypertension.
Pulse wave velocity in South African women and children: comparison between the Mobil-O-Graph and SphygmoCor XCEL devices
Authors: Kolkenbeck-Ruh Andrea , Soepnel Larske Marit , Kim Andrew Wooyoung , Naidoo Sanushka , Smith Wayne , Davies Justine , Ware Lisa Jayne
Published: July 2021

Background:

Carotid-femoral pulse wave velocity (PWV) is the gold-standard noninvasive measure of arterial stiffness. Data comparing tonometry-based devices such as the SphygmoCor XCEL to simpler brachial-cuff-based estimates of PWV, such as from the Mobil-O-Graph in African populations are sparse. We therefore aimed to compare PWV measured by the Mobil-O-Graph and the SphygmoCor XCEL device in a sample of South African women and children.

Methods:

Women (n = 85) 29 years [interquartile range (IQR): 29–69] and their children/grandchildren (n = 27) 7 years (IQR: 4–11) were recruited for PWV measurement with Mobil-O-Graph and SphygmoCor XCEL on the same day. Wilcoxon signed-rank test, regression analysis, spearman correlation and Bland–Altman plots were used for PWV comparison between devices.

Results:

For adults, the SphygmoCor XCEL device had a significantly higher PWV (7.3 m/s, IQR: 6.4–8.5) compared with the Mobil-O-Graph (5.9 m/s, IQR: 5.0–8.1, P = 0.001) with a correlation coefficient of 0.809 (P ≤ 0.001). Bland--Altman analysis indicated an acceptable level of agreement but significant bias (mean difference PWV: 0.90 ± 1.02 m/s; limits of agreement: −1.10 to 2.90). The odds of having a PWV difference more than 1 m/s decreased with a higher age [odds ratio (OR): 0.95, 95% confidence interval (95% CI) = 0.92–0.98] and increased with greater height (OR: 1.10, 95% CI = 1.01–1.21, P = 0.03) in multivariable analysis. In children, the Bland–Altman indicated an excellent level of agreement (−0.03 ± 0.63 m/s; limits of agreement: −1.26 to 1.21), but no correlation was found (r
s = 0.08, P = 0.71).

Conclusion:

Particularly in younger and taller women, the Mobil-O-Graph significantly underestimated PWV compared with the SphygmoCor. Although no correlation was found between the two devices for children, further research is required due to the small sample size. Furthermore, the clinical value of both methods in young African populations requires further investigation.
Neisseria meningitidis Serogroup Z Meningitis in a Child With Complement C8 Deficiency and Potential Cross Protection of the MenB-4C Vaccine
Authors: van den Broek Bryan , Coolen Jordy P. M. , de Jonge Marien I. , de Groot Ronald , Henriet Stefanie S. V. , Langereis Jeroen D. , van der Flier Michiel
Published: July 2021

Complement deficient patients are susceptible to rare meningococcal serogroups. A 6-year-old girl presented with serogroup Z meningitis. This led to identification of a C8 deficiency. The MenB-4C vaccine induced cross-reactive antibodies to serogroup Z and increased in vitro opsonophagocytic killing and may thus protect complement deficient patients.
Brief Report: HIV Pre-exposure Prophylaxis Prescribing in an Urban Safety-Net Health System
Authors: Agovi Afiba Manza-A. , Anikpo Ifedioranma , Cvitanovich Matthew J. , Fasanmi Esther O. , Ojha Rohit P. , Marcus Julia L.
Published: July 2021

Introduction:

Safety-net health systems are key settings for HIV pre-exposure prophylaxis (PrEP) implementation, but little evidence is available about the frequency of PrEP prescribing in safety-net settings. We assessed PrEP prescribing among people with indications for PrEP at an urban safety-net health system that serves a county designated as an Ending the HIV Epidemic priority jurisdiction.

Methods:

We identified adults (aged 18 years or older) who engaged in primary care between January 2015 and December 2019 and had a documented indication for PrEP. PrEP indications included the presence of a behavioral or sexual risk factor of HIV acquisition or a positive bacterial sexually transmitted infection at the index visit. PrEP prescribing was defined as the proportion of patients with indications for PrEP who received a new prescription for PrEP. We estimated the cumulative incidence of PrEP prescription with corresponding 95% confidence limits (CL).

Results:

Our study population comprised 2957 individuals, of whom 58% was aged younger than 45 years, 56% was women, 67% was racial or ethnic minorities, and 60% was uninsured or provided care as part of a hospital-based managed care plan for individuals without insurance. We identified 41 individuals who were prescribed PrEP. The cumulative incidence of PrEP prescribing within 1 year of the first documented PrEP indication was 1.3% (95% CL: 0.91% to 1.7%).

Conclusions:

Our results suggest extremely low frequency of PrEP prescribing among people with indications for PrEP in an urban safety-net health system. Strategies are needed to improve PrEP implementation in high-priority populations and safety-net settings.
68Ga-PSMA Uptake Patterns of Clear Cell Renal Carcinoma Across Different Histopathological Subtypes
Authors: Oflas Melis , Ozluk Yasemin , Sanli Oner , Ozkan Zeynep Gozde , Kuyumcu Serkan
Published: July 2021

68Ga–prostate-specific membrane antigen (PSMA) PET/CT is a well-established imaging modality in patients with prostate cancer; however, PSMA expression is also reported in the tumor-associated neovasculature, including but not limited to hepatocellular carcinoma, breast cancer, and renal cell carcinoma. Herein, we present 2 patients diagnosed with different histopathological subtypes of renal cell carcinoma who underwent 68Ga-PSMA PET/CT before surgery. Both cases have different PSMA expression characteristics and are presented along with pathological findings.
Weighted gene co-expression network analysis identifies specific modules and hub genes related to Parkinson’s disease
Authors: Yang Min , Wu Xing-Quan , Ding Chuan-Bo , Zhang Guo-Feng , Li Min , Lv Li-Na , Li Yu-Hui , Sun Dong-Wen , Zhao Jian-Jun
Published: July 2021

Objective

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. This study aims to screen specific modules and key genes related to PD.

Methods

Gene expression profile data GSE6613 and GSE22491 were downloaded from the Gene Expression Omnibus database. The significantly differentially expressed genes (DEGs) in different datasets were screened, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was used to screen disease-related modules that are significantly stable across datasets. The protein–protein interaction network was constructed using the DEGs in the stable module obtained and preservation modules. Finally, the hub genes directly related to PD were screened.

Results

A total of 179 DEGs with the same significant difference direction were screened. The enrichment analysis of GO and KEGG pathways showed that 20 significantly related GO biological processes and 9 KEGG signaling pathways were screened. A total of three highly conservative modules were detected in the WGCNA network. Finally, three significant PD-related KEGG pathways screened from the Comparative Toxicogenomics Database were identified, including neuroactive ligand–receptor interaction (CRHR2, CTSG, GRIN1, GRIN2D, LPAR4 and P2RX3), amyotrophic lateral sclerosis (BCL2, GRIN1 and GRIN2D) and alcoholism (CAMKK2, GRIN1, GRIN2D and SLC18A2). Key genes, such as SLC18A2, GRIN1 and GRIN2D, may be potential candidate genes for PD progression.

Conclusions

Our findings indicate that SLC18A2, GRIN1 and GRIN2D may play an important role in the pathogenesis of PD.
Stroke injury induced by distal middle cerebral artery occlusion is resistant to N-methyl-d-aspartate receptor antagonism in FVB/NJ mice
Authors: Liu Che-Wei , Liao Kate Hsiurong , Wu Ching Mei , Chen Hsiao-Yun , Wang Eric Yuhsiang , Lai Ted Weita
Published: July 2021

Although N-methyl-d-aspartate receptor (NMDAR) antagonism has been shown to have a neuroprotective effect in many preclinical stroke models, the efficacy of this antiexcitotoxicity strategy in clinical trials in stroke patients has been disappointing. Interestingly, it has been reported that NMDAR antagonism is not neuroprotective in C57BL/6 mice subjected to distal middle cerebral artery occlusion (dMCAO), supporting the notion that whether these treatments are neuroprotective depends on the type of cerebral ischemia. However, because C57BL/6 mice are inherently resistant to excitotoxicity, the reported lack of neuroprotection could also be explained by the difference in the mouse strain studied rather than the stroke model used. Here we examined the neuroprotective efficacy of NMDAR antagonism in FVB/NJ mice, an excitotoxicity-prone mouse strain, subjected to dMCAO. Although C57BL/6 mice are known to have an excitotoxicity-resistant genetic background and FVB/NJ mice are known to have an excitotoxicity-prone genetic background, the infarct volume and density of neurodegenerating neurons were similar in the two mouse strains following dMCAO. In addition, none of the antiexcitotoxicity agents studied, including the canonical NMDAR antagonist MK801 and the therapeutic peptides Tat-NR2B9c and L-JNKI-1, protected the FVB/NJ mouse brain against ischemic damage induced by dMCAO. In conclusion, our data demonstrated that FVB/NJ mice are no more susceptible to cerebral ischemia than C57BL/6 mice and that NMDAR antagonism is ineffective in mice, even in an excitotoxicity-prone strain, subjected to dMCAO.
Chronic food restriction enhances dopamine-mediated intracranial self-stimulation
Authors: Gnazzo Federico G. , Mourra Devry , Guevara Christopher A. , Beeler Jeff A.
Published: July 2021

Dopamine-mediated reinforcement and behavioral adaptation is essential to survival. Here, we test the effects of food restriction on dopamine-mediated learning and reinforcement using optical intracranial self-stimulation (oICSS), an optogenetic version of conventional electrical ICSS (also known as brain stimulation reward, BSR). Using mouse genetic lines to express channelrhodopsin selectively in midbrain dopamine neurons, we demonstrate that genetically expressed channelrhodopsin can mediate optically evoked dopamine release and support self-stimulation in a lever-pressing paradigm. Using this midbrain dopamine oICSS preparation, we compare acquisition and rate of pressing in ad libitum versus food restricted mice. Food restriction facilitated both more rapid acquisition of self-stimulation behavior and higher rates of responding; reversing food status after acquisition modulated response vigor in already established behavior. These data suggest that food restriction enhances both the acquisition and expression of dopamine-reinforced self-stimulation responding. These data demonstrate the utility of oICSS for examining changes in reinforcement learning concomitant to neuroadaptations induced in dopamine signaling by experimental manipulations such as food restriction.
Numerical simulation study on the crack propagation of conglomerate
Authors: Luo Senlin , Ge Hongkui , Wang Jianbo , Zhou Wei , Shen Yinghao , Liu Pengyu , Liu Jiantong
Published: July 2021

The conglomerate reservoir is rich in oil and gas reserves; however, the gravel's mechanical properties and laws are difficult to gain through laboratory experiments, which furthermore constrain the hydraulic fracturing design. To analyse the failure law of conglomerate, we simulated the uniaxial compression test based on discrete element software PFC2D and analysed the effect of different cementation strength, gravel content and gravel geometry on the rock deformation and failure characteristics. Results show that (i) as the cementation strength decreases, the compressive strength and elasticity modulus both reduce clearly, while the crack shapes get more complex and the critical value is 0.3; (ii) as the gravel content increases, the conglomerate strength first decreases then increases under the influences of cracks bypassing gravels; cementation strength and gravel content of the conglomerate both contribute to the increase in local additional stress, which leads to a series of changes in crack shapes and mechanical properties of the conglomerate. Based on the above research, the conglomerate strength and crack shapes after failure are relatively complex due to the common influence of cementation strength and gravel content. The gravel edge crack caused by stress concentration is the micro-mechanism that affects the conglomerate mechanical properties.
Amycolatopsis dendrobii sp. nov., an endophytic actinomycete isolated from Dendrobium heterocarpum Lindl.
Authors: Tedsree Nisachon , Tanasupawat Somboon , Sritularak Boonchoo , Kuncharoen Nattakorn , Likhitwitayawuid Kittisak
Published: July 2021

Three novel actinomycete strains, designated as DR6-1T, DR6-2 and DR6-4, isolated from the roots of Dendrobium heterocarpum Lindl in Thailand were studied using a polyphasic taxonomic approach. The strains grew at 20–37 °C, at pH 5–10 and with 5 % (w/v) NaCl. They contained meso-diaminopimelic acid in the cell-wall peptidoglycan and MK-9(H4) was a major menaquinone. Arabinose and galactose were the major sugars in the cell wall. The predominant cellular fatty acids were iso-C16 : 0 and iso-C15 : 0. The detected polar lipids were diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylglycerol. Strains DR6-1T, DR6-2 and DR6-4 shared 99.9–100 % 16S rRNA gene sequence similarity and were closely related to

Amycolatopsis echigonensis

JCM 21831T (98.7-98.8%). The approximate genome size of strain DR6-1T was 9.6 Mb with a G+C content of 69.6 mol%. The ANIb and dDDH values between genomic sequences of strain DR6-1T and

Amycolatopsis echigonensis

JCM21831T,

Amycolatopsis rubida

JCM 10871T and

Amycolatopsis nivea

KCTC 39515T were 90.55, 92.25, 92.60%, and 47.20, 52.10 and 52.50%, respectively. Based on the phenotypic, chemotaxonomic and genotypic characteristics, it has been concluded that strains DR6-1T, DR6-2 and DR6-4 represent a novel species of the genus

Amycolatopsis

for which the name Amycolatopsis dendrobii sp. nov. is proposed. The type strain is DR6-1T (=JCM 33742T=KCTC 49546T=TISTR 2840T).
Description of Novosphingopyxis iocasae sp. nov., isolated from deep sea sediment from the Mariana Trench, and emended description of the genus Novosphingopyxis
Authors: Zhou Hai-zhen , Zhang Jian , Sun Qing-lei
Published: July 2021

In this study, we reported a Gram-stain-negative, orange-coloured, rod-shaped, motile and faculatively anaerobic bacterium named strain PB63T, which was isolated from the deep-sea sediment from the Mariana Trench. Growth of PB63Toccurred at 10–35 °C (optimum, 28 °C), pH 5.0–8.0 (optimum, 5.0–6.0) and with 0–7 % (w/v) NaCl (optimum, 2–3 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that PB63Trepresented a member of the genusNovosphingopyxisand was closely related toNovosphingopyxis baekryungensisDSM 16222T(97.9 % sequence similarity). PB63Tshowed tolerance to a variety of heavy metals, including Co2+, Zn2+, Mn2+and Cu2+. The complete genome of PB63Twas obtained, and many genes involved in heavy metal resistance were found. The genomic DNA G+C content of PB63Twas 62.8 mol%. The predominant respiratory quinone of PB63Twas ubiquinone-10 (Q-10). The polar lipids of PB63Tcontained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, glycolipid, phosphatidylcholines and three unidentified lipids. The major fatty acids of PB63Tincluded summed feature 8 (C18 : 1ω7cor/and C18 : 1ω6c), C14 : 02-OH, 11-methyl C18 : 1ω7c, C16 : 0, summed feature 3 (C16 : 1ω7cand/or C16 : 1ω6c) and C17 : 1ω6c. The results of phylogenetic, physiological, biochemical and morphological analyses indicated that strain PB63Trepresents a novel species of the genusNovosphingopyxis, and the nameNovosphingopyxis iocasaesp. nov. is proposed with the type species PB63T(=CCTCC AB 2019195T=JCM 34178T).
Comparative analysis of proximate composition, amino acid and fatty
acid content, and antioxidant activities in fresh cuts of Korean native goat
(Capra hircus coreanae) meat
Authors: Moon Sang-Ho , Kim Na Yeon , Seong Hye-Jin , Chung Sang Uk , Tang Yujiao , Oh Mirae , Kim Eun-Kyung
Published: July 2021

The aim of this study was to evaluate the chemical compositions and antioxidant
activities of different cuts of Korean native goat (Capra
hircus
coreanae) meat. Five wethers were used in this experiment.
Samples were divided into four cuts: loin, leg, neck and rib. The proximate
compositions and antioxidant activities of these cuts were determined using
in vitro human digestion model. Results showed that dry
matter content (27.25±0.26%) of the leg was higher than others
(p<0.05). The contents of crude protein (65.31±1.44%) and ash
(3.74±0.17%) from loin were significantly higher than the others
(p<0.05), while crude fat (43.55±0.97%) content of rib was higher
than the others (p<0.05). Total contents of amino acid and fatty acid
from leg were higher than the others (p<0.05). The antioxidant activity
of rib, based on oxygen radical absorbance capacity, was higher than the others
(p<0.05). Ferric reducing antioxidant power activity of neck was
significantly higher than the others (p<0.05). This study provides the
basic data on the chemical compositions and antioxidant activities of four cuts
of Korean native goat meat.
Effect of application time of 1-methylcyclopropene treatment on fruit quality attributes in ‘Fuji’ apples during simulated marketing period
Authors: Yoo Jingi , Kang In-Kyu
Published: July 2021

This study was evaluated the effect of 1-methylcyclopropene (1-MCP) treatment on fruit quality of ‘Fuji’ apples during shelf life condition at room temperature (RT) after cold storage. Fruits were treated with 1-MCP at 0, 1st, and 2nd day after harvest, stored at 0°C cold storage for 3 months and assessed after 10, 20, and 30 days in RT shelf life condition after cold storage. After 30 days in RT, flesh firmness of untreated fruits was decreased to 45.8 Newton (N), while all of 1-MCP-treated fruits were maintained at 61.8-64.3 N. Internal ethylene concentration was sharply increased to 177.93 μL/L in untreated fruits, while it was inhibited by all of 1-MCP treatments at 0.74-3.06 μL/L. Titratable acidity (TA) was decreased to 0.19% in untreated fruits and all of 1-MCP treatments slowed the decrease of TA at 0.24-0.28%. The soluble solids content / titratable acidity (SSC/TA) ratio was gradually increased in untreated fruits, but it was not significantly changed in 1-MCP treatments. In addition, lightness of fruit peel color was maintained greater by 1-MCP treatments. Therefore, the results suggested the storability of untreated fruits was limited to 10 days in RT, but 1-MCP treatment extended the storability of ‘Fuji’ apples up to 30 days in shelf life condition at RT after cold storage.
Quality characteristics of hot-air dried ‘Darae’
(Actinidia arguta) with different sugar osmotic
dehydration pretreatment
Authors: Choi Ji-Young , Kim Jiyoon , Kim Jungsoo , Jeong Saeul , Yun Kyeom Ju , Kim Jihye , Moon Jong Tae , Moon Kwang-Deog
Published: July 2021

In this study, various osmosis pretreatments were performed and the quality
characteristics were compared in order to develop the optimal hot-air dried
‘Darae’ product. Treatment groups were osmoticized with sugar
(SUC) and sorbitol (SOR), and were divided according to the presence or absence
of ascorbic acid treatment at 30 and 55, respectively. The SOR groups showed
high weight reduction (%) and low moisture content. Among the SUC groups the
treatments added with ascorbic acid added at 55 showed high drying efficiency.
The browning of fruits was more severe in the SOR, and as a result of the
physical property analysis, the SUC tended to have a lower hardness and the
flesh was soft. The total flavonoid contents and DPPH scavenging activity were
high in the SUC groups, and especially the ascorbic acid treatment groups showed
significantly higher antioxidant activity. Sensory evaluation showed that, there
was no significant difference in sweetness or sourness, and in terms of
appearance, SUC groups scored high. Therefore, it is appropriate to use an
osmotic-dried solution of a 55 sugar osmosis solution added with ascorbic acid
for manufacturing the optimal dried sputum with both palatability,
functionality, and drying efficiency.
Antioxidant and α-glucosidase inhibitory effects of
Pethorum chinense Purch seed extracts
Authors: Kim JunHyeok , Im Jin Hyun , Park Chung Youl , Lee Da Hyun , Lee Mi Hyun , Jung Young Ho , Park Cho Hee , Na Chae Sun
Published: July 2021

Penthorum chinense Pursh is a plant belonging to the
Crassulaceae family and is a representative perennial herb that grows nationwide
in watersides and wetlands. This study was conducted to enhance the
competitiveness of wild plant seeds and contribute to the conservation of
species diversity through the evaluation of antioxidant and antidiabetic
activities of P. chinense seed extracts based on extraction
solvents. The total phenolics content was 19.83 mg GAE/g seeds in the 75%
ethanol extract, whereas the flavonoid content was the highest (10.89 mg QE/g
seeds) in the 75% methanol extract. Total phenolicss content was higher in the
organic solvent extract than in the water extract. The DPPH radical scavenging
activity was the highest (IC50 27.60 μg/mL) in the 75%
methanol extract, and the ABTS radical scavenging activity was the highest
(IC50 53.54 μg/mL) in the 75% methanol extract. Total
antioxidant capacity was the highest (30.87 μmol AAE/g) in the 75%
ethanol extract. The α-glucosidase-inhibitory activity was the highest
(IC50 46.47 μg/mL) in the 75% ethanol extract. From the
results of this study, it was confirmed that P. chinense seed
extracts, which possess high phenolics content, exhibit antioxidant and
antidiabetic effects, and could be used as an effective health functional food
material and natural medicine.
Inhibitory effects of Tunisian plants extracts on oxidative stress
and lipid accumulation in HepG2 cells
Authors: Kim SukJin , Kim Gun-Hee
Published: July 2021

This study was undertaken to evaluate the antioxidative and lipid accumulation
inhibitory effects in HepG2 cell of 11 Tunisian plants extracts. Total phenolics
contents (TPC), and total flavonoid contents (TFC) of 11 plants extracts were
measured, and antioxidative activities was analyzed using DPPH, ABTS, FRAP, ORAC
and TBA assay. Inhibitory effect of oxidative stress was evaluated by cell
viability and lipid peroxidation level in H2O2-treated
HepG2 cells. Lipid accumulation inhibitory effect was determined by Oil-Red-O
staining and intracellular triglyceride assay in HepG2 cell. M.
communis L. (156.73 mgGAE/g) and N. glauca Graham
(108.81 mgNAE/g) were the highest TPC and TFC, respectively, among 11 plants.
M. communis L. were the highest antioxidant activity in
DPPH and ABTS. FRAP and ORAC results revealed that antioxidant activity in 10
species were higher than the positive control. Among the 11 species, 5 species
with the lowest malondialdehyde level were selected and HPLC analysis revealed
that plants contain caffeic acid, quercetin, and rutin. 5 plants treatment
inhibited lipid peroxidation level and protected HepG2 cells from oxidative
stress. Moreover 5 plants significantly inhibited the lipid accumulation and
triglyceride content. These results imply scientific evidence for the
development of functional foods using 11 plants from Tunisia which has oxidative
stress and lipid accumulation reduction effects.
Binocular integrated visual field deficits are associated with changes in local network function in primary open-angle glaucoma: a resting-state fMRI study
Authors: Demaria Giorgia , Invernizzi Azzurra , Ombelet Daniel , Carvalho Joana C. , Renken Remco J. , Cornelissen Frans W.
Published: July 2021

Recent brain imaging studies have shown that the degenerative eye damage generally observed in the clinical setting, also extends intracranially. Both structural and functional brain changes have been observed in glaucoma participants, but we still lack an understanding of whether these changes also affect the integrity of cortical functional networks. This is relevant, as functional network integrity may affect the applicability of future treatments, as well as the options for rehabilitation or training. Here, we compare global and local functional connectivity between glaucoma and controls. Moreover, we study the relationship between functional connectivity and visual field (VF) loss.

For our study, 20 subjects with primary open-angle glaucoma (POAG) and 24 age-similar healthy participants were recruited to undergo a complete ophthalmic assessment followed by two resting-state (RS) (f)MRI scans. For each scan and for each group, the ROIs with EC values higher than the 95th percentile were considered the most central brain regions (“hubs”). Hubs for which we found a significant difference in EC in both scans between glaucoma and healthy were considered to provide evidence for network changes. In addition, for each participant, behavioural scores were derived based on the notion that a brain region’s hub function might relate to the: 1) sensitivity of the worse eye – indicating disease severity, 2) sensitivity of both eyes combined – with one eye potentially compensating for loss in the other, or 3) difference in eye sensitivity – requiring additional network interactions. By correlating each of these VF scores and the EC values, we assessed whether VF defects could be associated with centrality alterations in POAG. Our results show that no functional connectivity disruptions were found at the global brain level in POAG participants. This indicates that in glaucoma global brain network communication is preserved. Furthermore, a positive correlation was found between the EC value of the Lingual Gyrus, identified as a brain hub, and the behavioural score for the VF sensitivity of both eyes combined. The fact that reduced local network functioning is associated with reduced sensitivity of the binocular VF suggests the presence of local brain reorganisation that has a bearing on functional visual abilities.
Genetic, structural and clinical analysis of spastic paraplegia 4
Authors: Varghaei Parizad , Estiar Mehrdad A , Ashtiani Setareh , Veyron Simon , Mufti Kheireddin , Leveille Etienne , Yu Eric , Spiegelman Dan , Rioux Marie-France , Yoon Grace , Tarnopolsky Mark , Boycott Kym M. , Dupre Nicolas , Suchowersky Oksana , Trempe Jean-François , Rouleau Guy A. , Gan-Or Ziv
Published: July 2021

Introduction

Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). We aimed to study genetic and clinical characteristics of SPG4 across Canada.

Methods

The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations.

Results

We identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and clinically isolated syndrome, and novel or rarely reported signs and symptoms seen in SPG4 patients.

Conclusion

Our study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered.
Measuring fingerpad deformation during active object manipulation
Authors: Delhaye Benoit P. , Schiltz Félicien , Barrea Allan , Thonnard Jean-Louis , Lefèvre Philippe
Published: July 2021

Abstract

During active object manipulation, the finger-object interactions give rise to complex fingertip skin deformations. These deformations are in turn encoded by the local tactile afferents and provide rich and behaviorally relevant information to the central nervous system. Most of the work studying the mechanical response of the finger to dynamic loading has been performed under a passive setup, thereby precisely controlling the kinematics or the dynamics of the loading. However, to identify aspects of the deformations that are relevant to online control during object manipulation, it is desirable to measure the skin response in an active setup. To that end, we developed a device that allows us to monitor finger forces, skin deformations, and kinematics during fine manipulation. We describe the device in detail and test it to precisely describe how the fingertip skin in contact with the object deforms during a simple vertical oscillation task. We show that the level of grip force directly influences the fingerpad skin strains and that the strain rates are substantial during active manipulation (norm up to 100%/s). The developed setup will enable us to causally relate sensory information, i.e. skin deformation, to online control, i.e. grip force adjustment, in future studies.
BashTheBug: a crowd of volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates
Authors: Fowler Philip W , Wright Carla , Spiers Helen , Zhu Tingting , Baeten Elisabeth ML , Hoosdally Sarah W , Cruz Ana Luíza Gibertoni , Roohi Aysha , Kouchaki Samaneh , Walker Timothy M , Peto Timothy EA , Miller Grant , Lintott Chris , Clifton David , Crook Derrick W , Walker A Sarah ,   The Zooniverse Volunteer Community,   The CRyPTIC Consortium
Published: July 2021

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, thereby determining the minimum inhibitory concentration (MIC) of each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing.
ENGINEERING, DECODING AND SYSTEMS-LEVEL CHARACTERIZATION OF CHIMPANZEE CYTOMEGALOVIRUS
Authors: Phan Quang Vinh , Bogdanow Boris , Wyler Emanuel , Landthaler Markus , Liu Fan , Hagemeier Christian , Wiebusch Lueder
Published: July 2021

The chimpanzee cytomegalovirus (CCMV) is the closest relative of human CMV (HCMV). Because of the high conservation between these two species and the ability of human cells to fully support CCMV replication, CCMV holds great potential as a model system for HCMV. To make the CCMV genome available for precise and rapid gene manipulation techniques, we captured the genomic DNA of CCMV strain Heberling as a bacterial artificial chromosome (BAC). Selected BAC clones were reconstituted to infectious viruses, growing to similar high titers as parental CCMV. DNA sequencing confirmed the integrity of our clones and led to the identification of two polymorphic loci within the CCMV genome. To re-evaluate the CCMV coding potential, we analyzed the transcriptome and proteome of infected cells and identified several novel ORFs, splice variants, and regulatory RNAs. We further characterized the dynamics of CCMV gene expression and found that viral proteins cluster into five distinct temporal classes. In addition, our datasets revealed that the host response to CCMV infection and the de-regulation of cellular pathways are in line with known hallmarks of HCMV infection. In a first functional experiment, we investigated a proposed frameshift mutation in UL128 that was suspected to restrict CCMV's cell tropism. In fact, repair of this frameshift re-established productive CCMV infection in endothelial and epithelial cells, expanding the options of CCMV as an infection model. Thus, BAC-cloned CCMV can serve as a powerful tool for systematic approaches in comparative functional genomics, exploiting the close phylogenetic relationship between CCMV and HCMV.
The efficacy of antimicrobial agents is decreased in a polymicrobial environment
Authors: O’Brien Thomas James , Figueroa Wendy , Welch Martin
Published: July 2021

The airways of people with cystic fibrosis (CF) often harbour diverse polymicrobial communities. These airway infections can be impossible to resolve though antibiotic intervention, even though isolates of the individual species present are susceptible to the treatment when tested in vitro. This suggests that susceptibility to antimicrobial agents may be altered in the presence of other microbial species. In this work, we investigate how polymicrobial cultures of key CF-associated species respond to challenge with species-specific antimicrobial agents; colistin (targets Pseudomonas aeruginosa), fusidic acid (targets Staphylococcus aureus) and fluconazole (targets Candida albicans). We found that, compared with growth in axenic cultures, the target organism was protected (sometimes by several orders of magnitude) from the effect(s) of the antimicrobial agent when grown in a polymicrobial culture. This decreased antimicrobial efficacy in polymicrobial cultures was found to have both phenotypic and inherited components. Whole genome sequencing of the colistin-resistant P. aeruginosa isolates revealed single nucleotide polymorphisms and indels in genes encoding lipopolysaccharide (LPS) biosynthesis or pilus biogenesis. Colistin resistance associated with loss-of-function mutations in the LPS biosynthetic gene, wzy, could be complemented by expression of the wild-type wzy gene in trans. Our findings indicate that the polymicrobial nature of the CF airways is likely to have a significant impact on the clinical response to antimicrobial therapy.
CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage
Authors: Conners Rebecca , McLaren Mathew , Łapińska Urszula , Sanders Kelly , Stone M. Rhia L. , Blaskovich Mark A. T. , Pagliara Stefano , Daum Bertram , Rakonjac Jasna , Gold Vicki A. M.
Published: July 2021

The Ff family of filamentous bacteriophages infect gram-negative bacteria, but do not cause lysis of their host cell. Instead, new virions are extruded via the phage-encoded pIV protein, which has homology with bacterial secretins. Here, we determine the structure of pIV from the f1 filamentous bacteriophage at 2.7 Å resolution by cryo-electron microscopy, the first near-atomic structure of a phage secretin. Fifteen f1 pIV subunits assemble to form a gated channel in the bacterial outer membrane, with associated soluble domains projecting into the periplasm. We model channel opening and propose a mechanism for phage egress. By single-cell microfluidics experiments, we demonstrate the potential for secretins such as pIV to be used as adjuvants to increase the uptake and efficacy of antibiotics in bacteria. Finally, we compare the f1 pIV structure to its homologues to reveal similarities and differences between phage and bacterial secretins.
Single-cell genomics reveals region-specific developmental trajectories underlying neuronal diversity in the human hypothalamus
Authors: Herb Brian R. , Glover Hannah J. , Bhaduri Aparna , Colantuoni Carlo , Bale Tracy L. , Siletti Kimberly , Linnarsson Sten , Hodge Rebecca , Lein Ed , Kriegstein Arnold R. , Doege Claudia A. , Ament Seth A.
Published: July 2021

The development and diversity of neuronal subtypes in the human hypothalamus has been insufficiently characterized. We sequenced the transcriptomes of 40,927 cells from the prenatal human hypothalamus spanning from 6 to 25 gestational weeks and 25,424 mature neurons in regions of the adult human hypothalamus, revealing a temporal trajectory from proliferative stem cell populations to mature neurons and glia. Developing hypothalamic neurons followed branching trajectories leading to 170 transcriptionally distinct neuronal subtypes in ten hypothalamic nuclei in the adult. The uniqueness of hypothalamic neuronal lineages was examined developmentally by comparing excitatory lineages present in cortex and inhibitory lineages in ganglionic eminence from the same individuals, revealing both distinct and shared drivers of neuronal maturation across the human forebrain. Cross-species comparisons to the mouse hypothalamus identified human-specificPOMCpopulations expressing unique combinations of transcription factors and neuropeptides. These results provide the first comprehensive transcriptomic view of human hypothalamus development at cellular resolution.

One-Sentence Summary

Using single-cell genomics, we reconstructed the developmental lineages by which precursor populations give rise to 170 distinct neuronal subtypes in the human hypothalamus.
Emerald – a 16-rotor multicopter for stereo imaging
Authors: Zabunov Svetoslav , Mardirossian Garo , Strelnitski Katia
Published: July 2021

Purpose

The current manuscript aims to propose a novel multirotor design.

Design/methodology/approach

This paper presents a novel 16-rotor multicopter design named Emerald. The novel design innovations and benefits are disclosed. Comparison to existing 16-rotor designs is carried out. Implementation areas where the novel idea shall yield benefit are discussed. A prototype of the presented design is described.

Findings

The herein proposed 16-rotor design has a number of benefits over existing 16-rotor multicopters. The paper elaborates on those advantages.

Research limitations/implications

The research was limited to prototype testing, as the presented design is a novel concept.

Practical implications

The motivation to research and develop this novel design is implementing the vehicle for stereoscopic photography and reconnaissance. The design is also applicable to carrying payloads while flying indoors.
Advanced debonding detection technique for aerospace composite structures
Authors: Sorrentino Assunta , Romano Fulvio , De Fenza Angelo
Published: July 2021

Purpose

The purpose of this paper is to introduce a methodology aimed to detect debonding induced by low impacts energies in typical aeronautical structures. The methodology is based on high frequency sensors/actuators system simulation and the application of elliptical triangulation (ET) and probability ellipse (PE) methods as damage detector. Numerical and experimental results on small-scale stiffened panels made of carbon fiber-reinforced plastic material are discussed.

Design/methodology/approach

The damage detection methodology is based on high frequency sensors/actuators piezoceramics system enabling the ET and the PE methods. The approach is based on ultrasonic guided waves propagation measurement and simulation within the structure and perturbations induced by debonding or impact damage that affect the signal characteristics.

Findings

The work is focused on debonding detection via test and simulations and calculation of damage indexes (DIs). The ET and PE methodologies have demonstrated the link between the DIs and debonding enabling the identification of position and growth of the damage.

Originality/value

The debonding between two structural elements caused in manufacturing or in-service is very difficult to detect, especially when the components are in low accessibility areas. This criticality, together with the uncertainty of long-term adhesive performance and the inability to continuously assess the debonding condition, induces the aircrafts’ manufacturers to pursuit ultraconservative design approach, with in turn an increment in final weight of these parts. The aim of this research’s activity is to demonstrate the effectiveness of the proposed methodology and the robustness of the structural health monitoring system to detect debonding in a typical aeronautical structural joint.
Antecedents and consequences of fast-food restaurant customers' perception of price fairness
Authors: Singh Gurmeet , Slack Neale J. , Sharma Shavneet , Aiyub Asheefa Shaheen , Ferraris Alberto
Published: July 2021

Purpose

This study examines the influence of service quality dimensions (food quality, physical environment quality and employee service quality) and brand image of fast-food restaurants on price fairness and its consequence on customer retention.

Design/methodology/approach

This survey collected 331 responses using the public intercept method. Data analysis involved performing confirmatory factor analysis (CFA) on the measurement model, followed by structural equation modeling. Moderation analysis was performed using SPSS (model1 in process macro), while mediation was performed using model 4 in process macro.

Findings

Empirical results of this study revealed the positive effect of restaurant service quality dimensions on price fairness and price fairness on customer retention. It also revealed that brand image strengthened the restaurant service-quality/price fairness interrelationship, and that customer satisfaction partially mediated the price fairness/customer retention interrelationship.

Research limitations/implications

Findings of this study are useful to marketers and fast-food restaurateurs in establishing the right combination of service quality dimensions and brand image that increase perceptions of price fairness and increase customer satisfaction and retention.

Originality/value

This study contributes to advancing the theoretical foundations of customers' perceived price fairness and retention research, specifically in the understudied fast-food sector of emerging economies. It extends the application of the equity theory to expose the direct and indirect influences on customer perceived price fairness and customer retention. The findings provide a better understanding of price fairness perceptions.
Destination brand equity and tourist's revisit intention towards health tourism: an empirical study
Authors: Rahman Muhammad Sabbir , Bag Surajit , Hassan Hasliza , Hossain Md Afnan , Singh Rajesh Kumar
Published: July 2021

Purpose

This paper aims to investigate the relationship between destination brand equity and tourist's revisit intention towards health tourism destinations. The study also examines the mediating effect of destination brand association between destination-based brand equity and travellers' revisit intention for health tourism destinations.

Design/methodology/approach

A survey instrument is used to examine the relationships in the proposed model using the co-variance-based structural equation modelling (SEM) technique. The collected primary data from two hundred forty-six respondents (n = 246) are analysed to test the relationship amongst exogenous, mediating, moderating and endogenous constructs articulated in the proposed structural model.

Findings

Empirical findings reveal that destination brand equity influences the revisit intention of a traveller for health tourism via destination brand association. The perceived trust, reliability and soft issues of a traveller moderate the relationship between destination brand equity and destination brand association. Enduring travel involvement also proves a significant moderation effect on the relationship between destination brand association and the revisit intention of a traveller for a health tourism destination.

Practical implications

This paper is an initial attempt to develop and empirically examine a conceptual model of the intention of a traveller to revisit a health tourism destination in a dynamic process of information search using the data collected from current travellers after medical tourism-related trips. Results suggest that stakeholders must focus on hedonic and utilitarian factors of the destination that are recognised by travellers to encourage revisit for medical tourism.

Originality/value

Although there have been numerous studies on health tourism. However, to the best of the authors' knowledge, this research is a pioneer in the healthcare tourism literature that links destination brand equity, brand association and revisit intention of a traveller for health tourism. These findings extend the knowledge of how healthcare tourism that is embedded with destination brand equity and destination brand association. The study findings potentially benefit the marketers for gaining competitive advantages through considering the experience of a traveller.