bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential effects of pollution on adult and recruits of a canopy-forming alga: implications for population viability under low pollutant levels
Authors: de Caralt Sònia , Verdura Jana , Vergés Alba , Ballesteros Enric , Cebrian Emma
Published: October 2020

Marine macroalgal forests are highly productive and iconic ecosystems, which are seriously threatened by number of factors such as habitat destruction, overgrazing, ocean warming, and pollution. The effect of chronic, but low levels of pollutants on the long-term survival of the canopy-forming algae is not well understood. Here we test the effects of low concentrations (found in good quality water-bodies) of nitrates, heavy metals copper (Cu) and lead (Pb), and herbicides (glyphosate) on both adults and recruits of Carpodesmia crinita, a Mediterranean canopy forming macroalga. We show that although adult biomass, height and photosynthetic yield remain almost unaffected in all the assays, low Cu levels of 30 µg/L completely suppress adult fertility.
In addition, all the assays have a strong and negative impact on the survival and growth of recruits; in particular, glyphosate concentrations above 1 µg/L almost totally inhibit their survival. These results suggest that the long-term viability of C. crinita may be severely compromised by low pollutant levels that are not affecting adult specimens. Our results provide important data for a better understanding of the present-day threats to marine canopy-forming macroalgae and for the design of future management actions aimed at preserving macroalgal forests.
Synthesis of bio-oil from waste Trichosanthes cucumerina seeds: a substitute for conventional fuel
Authors: Manimaran Rajayokkiam , Murugu Mohan Kumar Kandasamy , Sathiya Narayanan Nagarajan
Published: October 2020

The present study explores the methodology for the synthesis of bio-oil from waste trichosanthes cucumerina seeds by the solvent extraction method. It investigates the yield percentage, concentration of free fatty acids and acid contents in the extracted bio-oil. Effects of size of the crushed seeds, moisture content, extraction time, solvent to seed ratio and extraction temperatures were examined. The non-polar hexane solvent resulted in a higher percentage of oil yield (28.4 ± 0.4%) for the crushed seed size of 0.21 mm, 6% moisture content, 270 min extraction time, 68 °C temperature and 6:1(ml/g) of solvent to seed ratio. The synthesized bio-oil was characterized using Fourier Transform Infra-Red spectrum and Gas Chromatography–Mass Spectroscopy analysis. The properties of the bio-oil and biodiesel were assessed according to the American Society for Testing and Materials and the Association of Official Analytical Chemists standards. The obtained methyl-ester by trans-esterification process results in the fuel properties closer to the conventional fuel. Thus, Trichosanthes cucumerina bio-diesel can be used as a potential substitute.
The potential roles of NAD(P)H:quinone oxidoreductase 1 in the development of diabetic nephropathy and actin polymerization
Authors: Moon Sung-Je , Jeong Jin Young , Kim Jae-Hoon , Choi Dong-Hee , Choi Hyunsu , Chang Yoon-Kyung , Na Ki Ryang , Lee Kang Wook , Lee Chul-Ho , Choi Dae Eun , Hwang Jung Hwan
Published: October 2020

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that has been involved in the progression of several kidney injuries. However, the roles of NQO1 in DN are still unclear. We investigated the effects of NQO1 deficiency in streptozotocin (STZ)-induced DN mice. NQO1 was upregulated in the glomerulus and podocytes under hyperglycemic conditions. NQO1 knockout (NKO) mice showed more severe changes in blood glucose and body weight than WT mice after STZ treatment. Furthermore, STZ-mediated pathological parameters including glomerular injury, blood urea nitrogen levels, and foot process width were more severe in NKO mice than WT mice. Importantly, urine albumin-to-creatinine ratio (ACR) was higher in healthy, non-treated NKO mice than WT mice. ACR response to STZ or LPS was dramatically increased in the urine of NKO mice compared to vehicle controls, while it maintained a normal range following treatment of WT mice. More importantly, we found that NQO1 can stimulate actin polymerization in an in vitro biochemical assay without directly the accumulation on F-actin. In summary, NQO1 has an important role against the development of DN pathogenesis and is a novel contributor in actin reorganization via stimulating actin polymerization.
A national database analysis for factors associated with thyroid cancer occurrence
Authors: Lee Joon-Hyop , Youn Sora , Jung Sohee , Kim Kwangsoo , Chai Young Jun , Chung Yoo Seung , Park Won Seo , Lee Kyu Eun , Yi Ka Hee
Published: October 2020

In order to analyze the associations between thyroid cancer and environmental factors, we analyzed the national sample cohort representative of the entire population provided by the Korean National Health Insurance Service database record from 2006 to 2015. The cohort was categorized according to age, body mass index, income, residential areas, frequency of exercise, frequency of alcohol drinking, diet, presence or absence of hyperthyroidism, presence or absence of hypothyroidism, and smoking data. Age ≥ 55 years (HR 0.68, 95% CI 0.53–0.88), lower income (0.57, 0.40–0.80), and current smoking (0.69, 0.55–0.85) were associated with lower thyroid cancer occurrence among men. Body mass index (BMI) ≥ 25 kg/m2 (1.51, 1.26–1.82), higher income (1.44, 1.19–1.76), urban residence (1.24, 1.03–1.49), and presence of hypothyroidism (3.31, 2.38–4.61) or hyperthyroidism (2.46, 1.75–3.46) were associated with higher thyroid cancer occurrence among men. Age ≥ 55 years (0.63, 0.56–0.71), moderate alcohol drinking (0.87, 0.77–0.99), and current smoking (0.56, 0.37–0.85) were associated with lower thyroid cancer occurrence among women. BMI ≥ 25 kg/m2 (1.41, 1.26–1.57), frequent exercise (1.21, 1.07–1.36), higher income (1.18, 1.06–1.32), urban residence (1.17, 1.06–1.29), and presence of hypothyroidism (1.60, 1.40–1.82) or hyperthyroidism (1.38, 1.19–1.61) were associated with higher thyroid cancer occurrence among women. In conclusion, age ≥ 55 years and current smoking were associated with lower thyroid cancer occurrence, while BMI ≥ 25 kg/m2, higher income, urban residence, hypothyroidism, and hyperthyroidism were associated with higher occurrence in both men and women.
Response guided therapy for reducing duration of direct acting antivirals in chronic hepatitis C infected patients: a Pilot study
Authors: Etzion Ohad , Dahari Harel , Yardeni David , Issachar Assaf , Nevo-Shor Anat , Cohen-Naftaly Michal , Ashur Yaffa , Uprichard Susan L. , Arbib Orly Sneh , Munteanu Daniela , Braun Marius , Cotler Scott J. , Abufreha Naim , Keren-Naus Ayelet , Shemer-Avni Yonat , Mor Orna , Murad Jayanah , Novack Victor , Shlomai Amir
Published: October 2020

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.
Neuron type-specific expression of a mutant KRAS impairs hippocampal-dependent learning and memory
Authors: Ryu Hyun-Hee , Kang Minkyung , Hwang Kyoung-Doo , Jang Han Byul , Kim Sang Jeong , Lee Yong-Seok
Published: October 2020

KRAS mutations are associated with rare cases of neurodevelopmental disorders that can cause intellectual disabilities. Previous studies showed that mice expressing a mutant KRAS have impaired the development and function of GABAergic inhibitory neurons, which may contribute to behavioural deficits in the mutant mice. However, the underlying cellular mechanisms and the role of excitatory neurons in these behavioural deficits in adults are not fully understood. Herein, we report that neuron type-specific expression of a constitutively active mutant KRASG12V in either excitatory or inhibitory neurons resulted in spatial memory deficits in adult mice. In inhibitory neurons, KRASG12V induced ERK activation and enhanced GABAergic synaptic transmission. Expressing KRASG12V in inhibitory neurons also impaired long-term potentiation in the hippocampal Shaffer-collateral pathway, which could be rescued by picrotoxin treatment. In contrast, KRASG12V induced ERK activation and neuronal cell death in excitatory neurons, which might have contributed to the severe behavioural deficits. Our results showed that both excitatory and inhibitory neurons are involved in mutant KRAS-associated learning deficits in adults via distinct cellular mechanisms.
Unveiling the effect of dietary essential oils supplementation in Sparus aurata gills and its efficiency against the infestation by Sparicotyle chrysophrii
Authors: Firmino Joana P. , Vallejos-Vidal Eva , Sarasquete Carmen , Ortiz-Delgado Juan B. , Balasch Joan Carles , Tort Lluis , Estevez Alicia , Reyes-López Felipe E. , Gisbert Enric
Published: October 2020

A microencapsulated feed additive composed by garlic, carvacrol and thymol essential oils (EOs) was evaluated regarding its protective effect in gills parasitized by Sparicotyle chrysophrii in Sparus aurata. A nutritional trial (65 days) followed by a cohabitation challenge with parasitized fish (39 days) were performed. Transcriptomic analysis by microarrays of gills of fish fed the EOs diet showed an up-regulation of genes related to biogenesis, vesicular transport and exocytosis, leukocyte-mediated immunity, oxidation–reduction and overall metabolism processes. The functional network obtained indicates a tissue-specific pro-inflammatory immune response arbitrated by degranulating acidophilic granulocytes, sustained by antioxidant and anti-inflammatory responses. The histochemical study of gills also showed an increase of carboxylate glycoproteins containing sialic acid in mucous and epithelial cells of fish fed the EOs diet, suggesting a mucosal defence mechanism through the modulation of mucin secretions. The outcomes of the in vivo challenge supported the transcriptomic results obtained from the nutritional trial, where a significant reduction of 78% in the abundance of S. chrysophrii total parasitation and a decrease in the prevalence of most parasitic developmental stages evaluated were observed in fish fed the EOs diet. These results suggest that the microencapsulation of garlic, carvacrol and thymol EOs could be considered an effective natural dietary strategy with antiparasitic properties against the ectoparasite S. chrysophrii.
Porcine circovirus 2 (PCV2) population study in experimentally infected pigs developing PCV2-systemic disease or a subclinical infection
Authors: Correa-Fiz Florencia , Franzo Giovanni , Llorens Anna , Huerta Eva , Sibila Marina , Kekarainen Tuija , Segalés Joaquim
Published: October 2020

Porcine circovirus 2 (PCV2) is a single stranded DNA virus with one of the highest mutation rates among DNA viruses. This ability allows it to generate a cloud of mutants constantly providing new opportunities to adapt and evade the immune system. This pig pathogen is associated to many diseases, globally called porcine circovirus diseases (PCVD) and has been a threat to pig industry since its discovery in the early 90’s. Although 11 ORFs have been predicted from its genome, only two main proteins have been deeply characterized, i.e. Rep and Cap. The structural Cap protein possesses the majority of the epitopic determinants of this non-enveloped virus. The evolution of PCV2 is affected by both natural and vaccine-induced immune responses, which enhances the genetic variability, especially in the most immunogenic Cap region. Intra-host variability has been also demonstrated in infected animals where long-lasting infections can take place. However, the association between this intra-host variability and pathogenesis has never been studied for this virus. Here, the within-host PCV2 variability was monitored over time by next generation sequencing during an experimental infection, demonstrating the presence of large heterogeneity. Remarkably, the level of quasispecies diversity, affecting particularly the Cap coding region, was statistically different depending on viremia levels and clinical signs detected after infection. Moreover, we proved the existence of hyper mutant subjects harboring a remarkably higher number of genetic variants. Altogether, these results suggest an interaction between genetic diversity, host immune system and disease severity.
Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells
Authors: Calizo R. C. , Bell M. K. , Ron A. , Hu M. , Bhattacharya S. , Wong N. J. , Janssen W. G. M. , Perumal G. , Pederson P. , Scarlata S. , Hone J. , Azeloglu E. U. , Rangamani P. , Iyengar R.
Published: October 2020

The shape of the cell is connected to its function; however, we do not fully understand underlying mechanisms by which global shape regulates a cell’s functional capabilities. Using theory, experiments and simulation, we investigated how physiologically relevant cell shape changes affect subcellular organization, and consequently intracellular signaling, to control information flow needed for phenotypic function. Vascular smooth muscle cells going from a proliferative and motile circular shape to a contractile fusiform shape show changes in the location of the sarcoplasmic reticulum, inter-organelle distances, and differential distribution of receptors in the plasma membrane. These factors together lead to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCβ pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm, and the nucleus resulting in phenotypic changes, as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell shape affects subcellular organization to modulate signaling that enables phenotypic changes.
Effects of physical activity and stress on the relationship between social capital and quality of life among breast cancer survivors
Authors: Zhao Jie , Ma Yong , Tanimoto Tetsuya , Ozaki Akihiko , Chen Wan-Li , Wang Jing-Ya , Zhang Yu-Xin , Chen Lin-Li , Wang Ji-Wei , Yu Jin-Ming
Published: October 2020

This study aims to investigate the serial multiple mediation of physical activity and perceived stress in the relationship between individual social capital and quality of life (QOL) in breast cancer survivors (BCSs). This study was conducted among 520 BCSs between March and April 2017 in Shanghai, China. Data were collected using the Individual Social Capital Scale, the Health-Promoting Lifestyle Profile-II, the Perceived Stress Scale-14 and the EORTC QLQ-C30. Ordinary least-squares regression and the bootstrap method was used to test the significance of the serial multiple mediation model. The serial-multiple mediations of physical activity and perceived stress were found significant in the relationship of QOL with all five dimensions of individual social capital. The separate mediations of two single mediating variables were found significant in the relationship of QOL with control over life and feeling about the community. In the relationship of QOL with social participation, social network and social support, the separate mediation of physical activity was significant, while the separate mediation of perceived stress was not significant. A multidisciplinary team approach and a variety of delivery systems are needed to address the social, physical and psychological issues for improving QOL among BCSs.
Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma
Authors: Areeb Zammam , Stuart Sarah F. , West Alice J. , Gomez Juliana , Nguyen Hong P. T. , Paradiso Lucia , Zulkifli Ahmad , Jones Jordan , Kaye Andrew H. , Morokoff Andrew P. , Luwor Rodney B.
Published: October 2020

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.
Abrogation of HLA surface expression using CRISPR/Cas9 genome editing: a step toward universal T cell therapy
Authors: Lee Jeewon , Sheen Joong Hyuk , Lim Okjae , Lee Yunjung , Ryu Jihye , Shin Duckhyang , Kim Yu Young , Kim Munkyung
Published: October 2020

As recent advancements in the chimeric antigen receptor-T cells have revolutionized the way blood cancers are handled, potential benefits from producing off-the-shelf, standardized immune cells entail the need for development of allogeneic immune cell therapy. However, host rejection driven by HLA disparity in adoptively transferred allogeneic T cells remains a key obstacle to the universal donor T cell therapy. To evade donor HLA-mediated immune rejection, we attempted to eliminate T cell’s HLA through the CRISPR/Cas9 gene editing system. First, we screened 60 gRNAs targeting B2M and multiple sets of gRNA each targeting α chains of HLA-II (DPA, DQA and DRA, respectively) using web-based design tools, and identified specific gRNA sequences highly efficient for target deletion without carrying off-target effects. Multiplex genome editing of primary human T cells achieved by the newly discovered gRNAs yielded HLA-I- or HLA-I/II-deficient T cells that were phenotypically unaltered and functionally intact. The overnight mixed lymphocyte reactions demonstrated the HLA-I-negative cells induced decreased production of IFN-γ and TNF-α in alloreactive T cells, and deficiency of HLA-I/II in T cells further dampened the inflammatory responses. Taken together, our approach will provide an efficacious pathway toward the universal donor cell generation by manipulating HLA expression in therapeutic T cells.
Improvement of glucose metabolism in pregnant women through probiotic supplementation depends on gestational diabetes status: meta-analysis
Authors: Łagowska Karolina , Malinowska Anna M. , Zawieja Bogna , Zawieja Emilia
Published: October 2020

The aim of this study was to assess the effects of probiotic and synbiotic supplementation on glucose metabolism in pregnant women using data from randomized controlled trials. Furthermore, this meta-analysis examines whether the observed effects depend on the presence or absence of gestational diabetes mellitus (GDM), and if the effect is dependent on the type of supplement used (probiotic or synbiotic). We performed a literature search of databases (Medline, Scopus, Web of Knowledge, and Cochrane Library) and identified all relevant randomized controlled trials (RCTs) published prior to May 2019. We compared the effects of probiotic supplementation with the administration of placebos in pregnant women with and without GDM. The systematic review and meta-analysis protocol were registered in the International Prospective Register of Systematic Reviews as number CRD 42019111467. 1119 study participants from 15 selected studies were included. The participants in four studies did not have GDM (being recruited to the study before week 20 of pregnancy) and the participants in the rest of the studies were diagnosed with GDM between weeks 24 and 28 of gestation. The meta-analysis showed that supplementation lowers serum glucose, insulin levels, and HOMA-IR index, but only in pregnant women with GDM. Moreover, both probiotics and synbiotics lower serum insulin level and HOMA-IR index, but the glucose lowering effect is specific only to probiotics and not synbiotics. Probiotic supplementation may improve glucose metabolism in pregnant women with GDM. There is a need for more RCT studies with larger groups to better estimate this effect.
Diagnosis of Subungual Glomus Tumors with 18 MHz Ultrasound and CDFI
Authors: Chen Li , Gao Yi-Hui , Chen Jie , Yao Yi-Jing , Wang Rui , Yu Qian , Hu Bing , Jiang Li-Xin
Published: October 2020

To evaluate the imaging features of subungual glomus tumors using 18 MHz high-frequency ultrasound with CDFI (Color Doppler Flow Imaging). 20 patients treated by surgical resection and examined by ultrasound between January 2008 and December 2019. All eligible cases are divided into two groups: Group A used the probe frequency of 9–14 MHz from January 2008 to December 2014, and Group B used the probe frequency of 18 MHz from January 2015 to December 2019. Patient demographics, clinical records, pathologic specimens and sonography features were reviewed. 50% of tumors in Group A and 100% of tumors in Group B showed clear boundary and regular shape. Blood flow signals were identified inside 50% tumors in Group A (3 in 6), all 14 cases with blood flow signals detected in Group B (14 in 14,100%). 2 cases were misdiagnosed and 1 case escaped diagnosis in Group A, no case was misdiagnosed in Group B. The accuracy of diagnosis rate of Group B is significantly higher than that of Group A. 18-MHz ultrasound combined with CDFI may be a practical useful tool for detecting subungual glomus tumors. More importantly 18-MHz ultrasound can obviously improve the diagnostic accuracy.
A digital reconstruction of the 1630–1631 large plague outbreak in Venice
Authors: Lazzari Gianrocco , Colavizza Giovanni , Bortoluzzi Fabio , Drago Davide , Erboso Andrea , Zugno Francesca , Kaplan Frédéric , Salathé Marcel
Published: October 2020

The plague, an infectious disease caused by the bacterium Yersinia pestis, is widely considered to be responsible for the most devastating and deadly pandemics in human history. Starting with the infamous Black Death, plague outbreaks are estimated to have killed around 100 million people over multiple centuries, with local mortality rates as high as 60%. However, detailed pictures of the disease dynamics of these outbreaks centuries ago remain scarce, mainly due to the lack of high-quality historical data in digital form. Here, we present an analysis of the 1630–1631 plague outbreak in the city of Venice, using newly collected daily death records. We identify the presence of a two-peak pattern, for which we present two possible explanations based on computational models of disease dynamics. Systematically digitized historical records like the ones presented here promise to enrich our understanding of historical phenomena of enduring importance. This work contributes to the recently renewed interdisciplinary foray into the epidemiological and societal impact of pre-modern epidemics.
Author Correction: Biomarkers of myocardial injury in rats after cantharidin poisoning: Application for postmortem diagnosis and estimation of postmortem interval
Authors: Zhang Youyou , Yu Yalei , Zhang Jie , Guan Chuhuai , Liu Liang , Ren Liang
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Low expression of Talin1 is associated with advanced pathological features in colorectal cancer patients
Authors: Vafaei Somayeh , Saeednejad Zanjani Leili , Habibi Shams Zohreh , Naseri Marzieh , Fattahi Fahimeh , Gheytanchi Elmira , Alemrajabi Mahdi , Ebrahimi Marzieh , Madjd Zahra
Published: October 2020

To explore the proper prognostic markers for the likelihood of metastasis in CRC patients. Seventy-seven fresh CRC samples were collected to evaluate the mRNA level of the selected marker using Real-time PCR. Moreover, 648 formalin-fixed paraffin-embedded CRC tissues were gathered to evaluate protein expression by immunohistochemistry (IHC) on tissue microarrays. The results of Real-Time PCR showed that low expression of Talin1 was significantly associated with advanced TNM stage (p = 0.034) as well as gender (p = 0.029) in mRNA levels. Similarly, IHC results indicated that a low level of cytoplasmic expression of Talin1 was significantly associated with advanced TNM stage (p = 0.028) as well as gender (p = 0.009) in CRC patients. Moreover, decreased expression of cytoplasmic Talin1 protein was found to be a significant predictor of worse disease-specific survival (DSS) (p = 0.011) in the univariate analysis. In addition, a significant difference was achieved (p = 0.039) in 5-year survival rates of DSS: 65% for low, 72% for moderate, and 88% for high Talin1 protein expression. Observations showed that lower expression of Talin1 at both the gene and protein level may drive the disparity of CRC patients’ outcomes via worse DSS and provide new insights into the development of progression indicators because of its correlation with increased tumor aggressiveness.
Reference transcriptomes and comparative analyses of six species in the threatened rosewood genus Dalbergia
Authors: Hung Tin Hang , So Thea , Sreng Syneath , Thammavong Bansa , Boounithiphonh Chaloun , Boshier David H. , MacKay John J.
Published: October 2020

Dalbergiais a pantropical genus with more than 250 species, many of which are highly threatened due to overexploitation for their rosewood timber, along with general deforestation. ManyDalbergiaspecies have received international attention for conservation, but the lack of genomic resources forDalbergiahinders evolutionary studies and conservation applications, which are important for adaptive management. This study produced the first reference transcriptomes for 6Dalbergiaspecies with different geographical origins and predicted ~ 32 to 49 K unique genes. We showed the utility of these transcriptomes by phylogenomic analyses with other Fabaceae species, estimating the divergence time of extantDalbergiaspecies to ~ 14.78 MYA. We detected over-representation in 13 Pfam terms including HSP, ALDH and ubiquitin families inDalbergia. We also compared the gene families of geographically co-occurringD. cochinchinensisandD. oliveriand observed that more genes underwent positive selection and there were more diverged disease resistance proteins in the more widely distributedD. oliveri, consistent with reports that it occupies a wider ecological niche and has higher genetic diversity. We anticipate that the reference transcriptomes will facilitate future population genomics and gene-environment association studies onDalbergia, as well as contributing to the genomic database where plants, particularly threatened ones, are currently underrepresented.
Inhibition of ecto-5′-nucleotidase and adenosine deaminase is able to reverse long-term behavioural effects of early ethanol exposure in zebrafish (Danio rerio)
Authors: Lutte Aline Haab , Majolo Julia Huppes , Da Silva Rosane Souza
Published: October 2020

The behavioural impacts of prenatal exposure to ethanol include a lower IQ, learning problems, anxiety and conduct disorders. Several components of the neurochemical network could contribute to the long-lasting effects of ethanol embryonic exposure. Adenosine is an important neuromodulator, that has been indicated to be affected by acute and chronic exposure to ethanol. Here, embryos of zebrafish exposed to 1% ethanol during the developmental stages of gastrula/segmentation or pharyngula exhibited anxiolytic effect, increased aggressiveness, and decreased social interaction. The exposure during pharyngula stage was able to affect all behavioural parameters analysed at 3 months-post fertilization (mpf), while the treatment during gastrula stage affected the anxiety and social interaction parameters. The aggressiveness was the only behavioural effect of early ethanol exposure that lasted to 12 mpf. The use of a specific inhibitor of adenosine production, the inhibitor of ecto-5′-nucleotidase (AMPCP/150 mg/kg), and the specific inhibitor of adenosine degradation, the inhibitor of adenosine deaminase, EHNA (100 mg/kg) did not affect the effects over anxiety. However, AMPCP at 3 mpf, but not EHNA, reversed aggressive parameters. AMPCP also recovered the social interaction parameter at 3 mpf in animals treated in both stages, while EHNA recovered this parameter just in those animals treated with ethanol during the gastrula stage. These results suggest that long-lasting behavioural effects of ethanol can be modulated by intervention on ecto-5′-nucleotidase and adenosine deaminase activities.
Valproic acid inhibits interferon-γ production by NK cells and increases susceptibility to Listeria monocytogenes infection
Authors: Soria-Castro Rodolfo , Chávez-Blanco Alma D. , García-Pérez Blanca Estela , Wong-Baeza Isabel , Flores-Mejía Raúl , Flores-Borja Fabián , Estrada-Parra Sergio , Estrada-García Iris , Serafín-López Jeanet , Chacón-Salinas Rommel
Published: October 2020

Valproic acid (VPA) is a drug commonly used for epileptic seizure control. Recently, it has been shown that VPA alters the activation of several immune cells, including Natural Killer (NK) cells, which play an important role in the containment of viruses and intracellular bacteria. Although VPA can increase susceptibility to extracellular pathogens, it is unknown whether the suppressor effect of VPA could affect the course of intracellular bacterial infection. This study aimed to evaluate the role of VPA duringListeria monocytogenes(L.m) infection, and whether NK cell activation was affected. We found that VPA significantly augmented mortality in L.m infected mice. This effect was associated with increased bacterial load in the spleen, liver, and blood. Concurrently, decreased levels of IFN-γ in serum and lower splenic indexes were observed. Moreover, in vitro analysis showed that VPA treatment decreased the frequency of IFN-γ-producing NK cells within L.m infected splenocytes. Similarly, VPA inhibited the production of IFN-γ by NK cells stimulated with IL-12 and IL-18, which is a crucial system for early IFN-γ production in listeriosis. Finally, VPA decreased the phosphorylation of STAT4, p65, and p38, without affecting the expression of IL-12 and IL-18 receptors. Altogether, our results indicate that VPA increases the susceptibility toListeria monocytogenesinfection and suggest that NK cell is one of the main targets of VPA, but further work is needed to ascertain this effect.
Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses
Authors: Kosuge Masato , Furusawa-Nishii Emi , Ito Koyu , Saito Yoshiro , Ogasawara Kouetsu
Published: October 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces severe pneumonia and is the cause of a worldwide pandemic. Coronaviruses, including SARS-CoV-2, have RNA proofreading enzymes in their genomes, resulting in fewer gene mutations than other RNA viruses. Nevertheless, variants of SARS-CoV-2 exist and may induce different symptoms; however, the factors and the impacts of these mutations are not well understood. We found that there is a bias to the mutations occurring in SARS-CoV-2 variants, with disproportionate mutation to uracil (U). These point mutations to U are mainly derived from cytosine (C), which is consistent with the substrate specificity of host RNA editing enzymes, APOBECs. We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of cytokines, such as TNF-α and IL-6, in cell lines when compared with stimulation by the ssRNA sequence of the isolated virus in Wuhan. Therefore, RNA editing is a factor for mutation bias in SARS-CoV-2 variants, which affects host inflammatory cytokines production.
Fibers-based temporal super-resolved imaging
Authors: Asraf Sagie , Fridman Moti , Zalevsky Zeev
Published: October 2020

In this paper we present a new technique for a fiber-based temporal super resolving system allowing to improve the resolution of a temporal imaging system. The proposed super resolving concept is based upon translating the field of view multiplexing method that is used to increase resolution in spatial imaging systems from the spatial domain to the temporal domain. In this paper, an optical realization of our proposed system is presented, using optical fibers and electro-optic modulators. In addition, we show how one can apply this method using low-rate electronics for the required modulation. We also show simulation results that demonstrate the high resolution accepted in our method compares to the basic temporal imaging system. Experimental results which demonstrate resolution improvement by a factor of 1.5 based on the proposed method are presented together with an additional experiment that shows the ability to generate the desired modulation with low rate electronics.
1H NMR serum metabolomic profiling of patients at risk of cardiovascular diseases performing stress test
Authors: Lema Camila , Andrés Mireia , Aguadé-Bruix Santiago , Consegal Marta , Rodriguez-Sinovas Antonio , Benito Begoña , Ferreira-Gonzalez Ignacio , Barba Ignasi
Published: October 2020

Cardiovascular diseases are the leading cause of death worldwide. Changes in lifestyle and/or pharmacological treatment are able to reduce the burden of coronary artery diseases (CAD) and early diagnosis is crucial for the timely and optimal management of the disease. Stress testing is a good method to measure the burden of CAD but it is time consuming and pharmacological testing may not fully mimic exercise test. The objectives of the present project were to characterize the metabolic profile of the population undergoing pharmacological and exercise stress testing to evaluate possible differences between them, and to assess the capacity of 1H NMR spectroscopy to predict positive stress testing. Pattern recognition was applied to 1H NMR spectra from serum of patients undergoing stress test and metabolites were quantified. The effects of the stress test, confounding variables and the ability to predict ischemia were evaluated using OPLS-DA. There was an increase in lactate and alanine concentrations in post-test samples in patients undergoing exercise test, but not in those submitted to pharmacological testing. However, when considering only pharmacological patients, those with a positive test result, showed increased serum lactate, that was masked by the much larger amount of lactate associated to exercise testing. In conclusion, we have established that pharmacological stress test does not reproduce the dynamic changes observed in exercise stress. Although there is promising evidence suggesting that 1H NMR based metabolomics could predict stress test results, further studies with much larger populations will be required in order to obtain a definitive answer.
Picosecond Yb-doped tapered fiber laser system with 1.26 MW peak power and 200 W average output power
Authors: Petrov Andrey , Odnoblyudov Maxim , Gumenyuk Regina , Minyonok Lidiya , Chumachenko Andrey , Filippov Valery
Published: October 2020

We demonstrate a compact picosecond master-oscillator power-amplifier (MOPA) system based on an Yb-doped polarization-maintaining double-clad tapered fiber (T-DCF) delivering pulses with over 1.26 MW peak power and average output power up to 200 W preserving near diffraction limited beam quality. The unique properties of an active tapered fiber enable to amplify the seed pulses directly with no need for applying of additional stretching technique. This simplified laser system can find the practical implementation in industrial micromachining.
Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis
Authors: Wang Ji-gan , Cui Hai-rong , Tang Hua-bo , Deng Xiu-li
Published: October 2020

In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. The results of fecal nucleic acid detection were analyzed systematically. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). However, the prevalence of gastrointestinal symptoms in other countries (21.1%, 95% CI 16.5–25.7%) was higher compared to China (12.9%, 95% CI 8–17.7%). In Wuhan, the pooled prevalence was much higher (41.3%, 95% CI 3.2–79.4%) compared to areas outside Wuhan in China (7.1%, 95% CI 4.0–10.3%). The positive rate of fecal nucleic acid testing in COVID-19 children was relatively high at 85.8% (91/106). Additionally, 71.2% (52/73) were still positive for fecal nucleic acid after respiratory tract specimens turned negative. One and two weeks after the respiratory tract specimens turned nucleic acid-negative, 45.2% (33/73) and 34.2% (25/73) patients, respectively, remained fecal nucleic acid-positive. The longest interval between the respiratory tract specimens turning negative and fecal specimens turning negative exceeded 70 days. Conclusions and relevance: gastrointestinal symptoms in pediatric COVID-19 are relatively common. Attention should be paid to the detection of fecal nucleic acids in children. Fecal nucleic acid-negative status should be considered as one of the desegregation standards.
Reduction behavior of chromium(VI) with oxalic acid in aqueous solution
Authors: Peng Hao , Guo Jing
Published: October 2020

The direct Cr(VI) reduction process by oxalic acid was conducted. The existence of Cr(VI) in the reaction medium was measured by software Visual MINTEQ and the concentration of Cr(VI) was measured by ICP-OES. The results showed that the Cr(VI) was efficiently reduced by oxalic acid at high reaction temperature and high dosage of oxalic acid. The reduced product, Cr(III), was easily generated stable complex compounds (Cr(HC2O4)3) with oxalate, which displayed a negative effect on the reduction process. The high reaction temperature and high acidic medium could destroy the stable structure of a complex compound to release oxalate, and facilitate the reduction of Cr(VI). Generally, the results showed in this paper provided a versatile strategy for Cr(VI) reduction and exhibited a bright application future for real wastewater treatment.
Interleukin-11 is important for vascular smooth muscle phenotypic switching and aortic inflammation, fibrosis and remodeling in mouse models
Authors: Lim Wei-Wen , Corden Ben , Ng Benjamin , Vanezis Konstantinos , D’Agostino Giuseppe , Widjaja Anissa A. , Song Wei-Hua , Xie Chen , Su Liping , Kwek Xiu-Yi , Tee Nicole G. Z. , Dong Jinrui , Ko Nicole S. J. , Wang Mao , Pua Chee Jian , Jamal Muhammad H. , Soh Beeyong , Viswanathan Sivakumar , Schafer Sebastian , Cook Stuart A.
Published: October 2020

Transforming growth factor beta-1 (TGFβ1) is a major driver of vascular smooth muscle cell (VSMC) phenotypic switching, an important pathobiology in arterial disease. We performed RNA-sequencing of TGFβ1-stimulated human aortic or arterial VSMCs which revealed large and consistent upregulation of Interleukin 11(IL11). IL11 has an unknown function in VSMCs, which highly express the IL11 receptor alpha, suggestive of an autocrine loop. In vitro, IL11 activated ERK signaling, but inhibited STAT3 activity, and caused VSMC phenotypic switching to a similar extent as TGFβ1 or angiotensin II (ANGII) stimulation. Genetic or therapeutic inhibition of IL11 signaling reduced TGFβ1- or ANGII-induced VSMC phenotypic switching, placing IL11 activity downstream of these factors. Aortas of mice withMyh11-driven IL11 expression were remodeled and had reduced contractile but increased matrix and inflammatory genes expression. In two models of arterial pressure loading, IL11 was upregulated in the aorta and neutralizing IL11 antibodies reduced remodeling along with matrix and pro-inflammatory gene expression. These data show that IL11 plays an important role in VSMC phenotype switching, vascular inflammation and aortic pathobiology.
Microbial community dynamics during alfalfa silage with or without clostridial fermentation
Authors: Li Rongrong , Jiang Di , Zheng Mingli , Tian Pengjiao , Zheng Menghu , Xu Chuncheng
Published: October 2020

This study was conducted to examine the effects of Lactobacillus plantarum (LP) and sucrose (S) on clostridial community dynamics and correlation between clostridia and other bacteria in alfalfa silage during ensiling. Fresh alfalfa was directly ensiled without (CK) or with additives (LP, S, LP + S) for 7, 14, 28 and 56 days. Clostridial and bacterial communities were evaluated by next-generation sequencing. Severe clostridial fermentation occurred in CK, as evidenced by the high contents of butyric acid, ammonia nitrogen, and clostridia counts, whereas all additives, particularly LP + S, decreased silage pH and restrained clostridial fermentation. Clostridium perfringens and Clostridium butyricum might act as the main initiators of clostridial fermentation, with Clostridium tyrobutyricum functioning as the promoters of fermentation until the end of ensiling. Clostridium tyrobutyricum (33.5 to 98.0%) dominated the clostridial community in CK from 14 to 56 days, whereas it was below 17.7% in LP + S. Clostridium was negatively correlated with the genus Lactobacillus, but positively correlated with the genera Enterococcus, Lactococcus and Leuconostoc. Insufficient acidification promoted the vigorous growth of C. tyrobutyricum of silage in later stages, which was mainly responsible for the clostridial fermentation of alfalfa silage.
Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery
Authors: Kothiyal Prachi , Schulkers Keriann , Liu Xinyue , Hazrati Sahel , Vilboux Thierry , Gomez Luis M. , Huddleston Kathi , Wong Wendy S. W. , Niederhuber John E. , Conrads Thomas P. , Maxwell G. Larry , Hourigan Suchitra K.
Published: October 2020

Cesarean section (CS) is recognized as being a shared environmental risk factor associated with chronic immune disease. A study of maternal gene expression changes between different delivery modes can add to our understanding of how CS contributes to disease patterns later in life. We evaluated the association of delivery mode with postpartum gene expression using a cross-sectional study of 324 mothers who delivered full-term (≥ 37 weeks) singletons. Of these, 181 mothers had a vaginal delivery and 143 had a CS delivery (60 with and 83 without labor). Antimicrobial peptides (AMP) were upregulated in vaginal delivery compared to CS with or without labor. Peptidase inhibitor 3 (PI3), a gene in the antimicrobial peptide pathway and known to be involved in antimicrobial and anti-inflammatory activities, showed a twofold increase in vaginal delivery compared to CS with or without labor (adjusted p-value 1.57 × 10–11 and 3.70 × 10–13, respectively). This study evaluates differences in gene expression by delivery mode and provides evidence of antimicrobial peptide upregulation in vaginal delivery compared to CS with or without labor. Further exploration is needed to determine if AMP upregulation provides protection against CS-associated diseases later in life.
Deep learning for identifying corneal diseases from ocular surface slit-lamp photographs
Authors: Gu Hao , Guo Youwen , Gu Lei , Wei Anji , Xie Shirong , Ye Zhengqiang , Xu Jianjiang , Zhou Xingtao , Lu Yi , Liu Xiaoqing , Hong Jiaxu
Published: October 2020

To demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm’s performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis.
Crucial transcripts predict response to initial immunoglobulin treatment in acute Kawasaki disease
Authors: Geng Zhimin , Liu Jingjing , Hu Jian , Wang Ying , Tao Yijing , Zheng Fenglei , Wang Yujia , Fu Songling , Wang Wei , Xie Chunhong , Zhang Yiying , Gong Fangqi
Published: October 2020

Although intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.