bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome- and transcriptome-derived microsatellite loci in lumpfish Cyclopterus lumpus: molecular tools for aquaculture, conservation and fisheries management
Authors: Maduna Simo N. , Vivian-Smith Adam , Jónsdóttir Ólöf Dóra Bartels , Imsland Albert K. D. , Klütsch Cornelya F. C. , Nyman Tommi , Eiken Hans Geir , Hagen Snorre B.
Published: January 2020

The lumpfishCyclopterus lumpusis commercially exploited in numerous areas of its range in the North Atlantic Ocean, and is important in salmonid aquaculture as a biological agent for controlling sea lice. Despite the economic importance, few genetic resources for downstream applications, such as linkage mapping, parentage analysis, marker-assisted selection (MAS), quantitative trait loci (QTL) analysis, and assessing adaptive genetic diversity are currently available for the species. Here, we identify both genome- and transcriptome-derived microsatellites loci fromC. lumpusto facilitate such applications. Across 2,346 genomic contigs, we detected a total of 3,067 microsatellite loci, of which 723 were the most suitable ones for primer design. From 116,555 transcriptomic unigenes, we identified a total of 231,556 microsatellite loci, which may indicate a high coverage of the available STRs. Out of these, primer pairs could only be designed for 6,203 loci. Dinucleotide repeats accounted for 89 percent and 52 percent of the genome- and transcriptome-derived microsatellites, respectively. The genetic composition of the dominant repeat motif types showed differences from other investigated fish species. In the genome-derived microsatellites AC/GT (67.8 percent), followed by AG/CT (15.1 percent) and AT/AT (5.6 percent) were the major motifs. Transcriptome-derived microsatellites showed also most dominantly the AC/GT repeat motif (33 percent), followed by A/T (26.6 percent) and AG/CT (11 percent). Functional annotation of microsatellite-containing transcriptomic sequences showed that the majority of the expressed sequence tags encode proteins involved in cellular and metabolic processes, binding activity and catalytic reactions. Importantly, STRs linked to genes involved in immune system process, growth, locomotion and reproduction were discovered in the present study. The extensive genomic marker information reported here will facilitate molecular ecology studies, conservation initiatives and will benefit many aspects of the breeding programmes ofC. lumpus.
Human antibodies neutralizing diphtheria toxin in vitro and in vivo
Authors: Wenzel Esther Veronika , Bosnak Margarita , Tierney Robert , Schubert Maren , Brown Jeffrey , Dübel Stefan , Efstratiou Androulla , Sesardic Dorothea , Stickings Paul , Hust Michael
Published: January 2020

Diphtheria is an infectious disease caused by Corynebacterium diphtheriae. The bacterium primarily infects the throat and upper airways and the produced diphtheria toxin (DT), which binds to the elongation factor 2 and blocks protein synthesis, can spread through the bloodstream and affect organs, such as the heart and kidneys. For more than 125 years, the therapy against diphtheria has been based on polyclonal horse sera directed against DT (diphtheria antitoxin; DAT). Animal sera have many disadvantages including serum sickness, batch-to-batch variation in quality and the use of animals for production. In this work, 400 human recombinant antibodies were generated against DT from two different phage display panning strategies using a human immune library. A panning in microtiter plates resulted in 22 unique in vitro neutralizing antibodies and a panning in solution combined with a functional neutralization screening resulted in 268 in vitro neutralizing antibodies. 61 unique antibodies were further characterized as scFv-Fc with 35 produced as fully human IgG1. The best in vitro neutralizing antibody showed an estimated relative potency of 454 IU/mg and minimal effective dose 50% (MED50%) of 3.0 pM at a constant amount of DT (4x minimal cytopathic dose) in the IgG format. The targeted domains of the 35 antibodies were analyzed by immunoblot and by epitope mapping using phage display. All three DT domains (enzymatic domain, translocation domain and receptor binding domain) are targets for neutralizing antibodies. When toxin neutralization assays were performed at higher toxin dose levels, the neutralizing capacity of individual antibodies was markedly reduced but this was largely compensated for by using two or more antibodies in combination, resulting in a potency of 79.4 IU/mg in the in vivo intradermal challenge assay. These recombinant antibody combinations are candidates for further clinical and regulatory development to replace equine DAT.
The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis
Authors: Miyano Kanako , Eto Moeko , Hitomi Suzuro , Matsumoto Takashi , Hasegawa Seiya , Hirano Ayane , Nagabuchi Kaori , Asai Noriho , Uzu Miaki , Nonaka Miki , Omiya Yuji , Kaneko Atsushi , Ono Kentaro , Fujii Hideaki , Higami Yoshikazu , Kono Toru , Uezono Yasuhito
Published: January 2020

Chemotherapy often induces oral ulcerative mucositis (OUM) in patients with cancer, characterized by severe painful inflammation. Mouth-washing with the Japanese herbal medicine hangeshashinto (HST) ameliorates chemotherapy-induced OUM in patients with colorectal cancer. Previously, we demonstrated that HST decreased interleukin 1β-induced prostaglandin E2 production in human oral keratinocytes (HOKs) and OUM-induced mechanical or spontaneous pain in rats. However, HST effects on tissue repair functions in HOKs remain unclear. Here, we examined the effects of HST on scratch-induced wound healing in vitro and in vivo. In vitro, HST enhanced wound healing mainly through scratch-induced HOK migration. Screening of the seven constituent medicinal herbs and their major components revealed that Scutellaria root, processed ginger, and Glycyrrhiza components mainly induced the scratch-induced HOK migration. Pharmacokinetic analyses indicated that the active ingredient concentrations in rat plasma following oral HST administration were below the effective doses for HOK migration, suggesting direct effects of HST in OUM. Mitogen-activated protein kinase and C-X-C chemokine receptor 4 inhibitors significantly suppressed HST-induced HOK migration. Moreover, HST enhanced tissue repair in our OUM rat model. Thus, HST likely enhanced OUM tissue repair through oral keratinocyte migration upon MAPK and CXCR4 activation and may be useful in patients with cancer-associated OUM.
Monitoring canid scent marking in space and time using a biologging and machine learning approach
Authors: Bidder Owen R. , di Virgilio Agustina , Hunter Jennifer S. , McInturff Alex , Gaynor Kaitlyn M. , Smith Alison M. , Dorcy Janelle , Rosell Frank
Published: January 2020

For canid species, scent marking plays a critical role in territoriality, social dynamics, and reproduction. However, due in part to human dependence on vision as our primary sensory modality, research on olfactory communication is hampered by a lack of tractable methods. In this study, we leverage a powerful biologging approach, using accelerometers in concert with GPS loggers to monitor and describe scent-marking events in time and space. We performed a validation experiment with domestic dogs, monitoring them by video concurrently with the novel biologging approach. We attached an accelerometer to the pelvis of 31 dogs (19 males and 12 females), detecting raised-leg and squat posture urinations by monitoring the change in device orientation. We then deployed this technique to describe the scent marking activity of 3 guardian dogs as they defend livestock from coyote depredation in California, providing an example use-case for the technique. During validation, the algorithm correctly classified 92% of accelerometer readings. High performance was partly due to the conspicuous signatures of archetypal raised-leg postures in the accelerometer data. Accuracy did not vary with the weight, age, and sex of the dogs, resulting in a method that is broadly applicable across canid species’ morphologies. We also used models trained on each individual to detect scent marking of others to emulate the use of captive surrogates for model training. We observed no relationship between the similarity in body weight between the dog pairs and the overall accuracy of predictions, although models performed best when trained and tested on the same individual. We discuss how existing methods in the field of movement ecology can be extended to use this exciting new data type. This paper represents an important first step in opening new avenues of research by leveraging the power of modern-technologies and machine-learning to this field.
5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation
Authors: Uribe-Lewis Santiago , Carroll Thomas , Menon Suraj , Nicholson Anna , Manasterski Piotr J. , Winton Douglas J. , Buczacki Simon J. A. , Murrell Adele
Published: January 2020

Cytosine hydroxymethylation (5hmC) in mammalian DNA is the product of oxidation of methylated cytosines (5mC) by Ten-Eleven-Translocation (TET) enzymes. While it has been shown that the TETs influence 5mC metabolism, pluripotency and differentiation during early embryonic development, the functional relationship between gene expression and 5hmC in adult (somatic) stem cell differentiation is still unknown. Here we report that 5hmC levels undergo highly dynamic changes during adult stem cell differentiation from intestinal progenitors to differentiated intestinal epithelium. We profiled 5hmC and gene activity in purified mouse intestinal progenitors and differentiated progeny to identify 43425 differentially hydroxymethylated regions and 5325 differentially expressed genes. These differentially marked regions showed both losses and gains of 5hmC after differentiation, despite lower global levels of 5hmC in progenitor cells. In progenitors, 5hmC did not correlate with gene transcript levels, however, upon differentiation the global increase in 5hmC content showed an overall positive correlation with gene expression level as well as prominent associations with histone modifications that typify active genes and enhancer elements. Our data support a gene regulatory role for 5hmC that is predominant over its role in controlling DNA methylation states.
Association of patient-reported outcomes and heart rate trends in heart failure: a report from the Chiron project
Authors: Monzo Luca , Schiariti Michele , Calvisi Pietro Fedele , Bonfiglio Silvio , Luštrek Mitja , Puddu Paolo E.
Published: January 2020

Patient-reported outcomes (PROs) have been previously considered “soft” end-points because of the lack of association of the reported outcome to measurable biological parameters. The present study aimed to assess whether electrocardiographic measures are associated to PROs changes. We evaluated the association between heart rate (HR), QRS and QT/QTc durations and PROs, classified as “good” or “bad” according to the patients’ overall feeling of health, in patients from the Chiron project. Twenty-four chronic heart failure (HF) patients were enrolled in the study (71% male, mean age 62.9 ± 9.4 years, 42% ischemic etiology, 15 NYHA class II and 9 class III) providing 1086 days of usable physiological recordings (4 hours/day). The mean HR was significantly higher in the “bad” than in the “good” PROs class (74.0 ± 6.4 bpm vs 68.0 ± 7.2 bpm; p < 0.001). Conversely, the ratio between movement and rest activities showed significantly higher values in “good” compared to “bad” PROs. We also found significantly longer QTc and QRS durations in patients with “bad” PROs compared to patients with “good” PROs. That in patients with mild to moderate HF, higher HR, wider QRS and longer QTc, as well as a reduced HR ratio between movement and rest, were associated with “bad” PROs is clinically noteworthy because the association of worse PROs with measurable variations of biological parameters may help physicians in evaluating PROs reliability itself and in their clinical decisions. Whether a timely intervention on these biological parameters may prevent adverse outcomes is important and deserves to be investigated in further studies.
Global vulnerability of marine mammals to global warming
Authors: Albouy Camille , Delattre Valentine , Donati Giulia , Frölicher Thomas L. , Albouy-Boyer Severine , Rufino Marta , Pellissier Loïc , Mouillot David , Leprieur Fabien
Published: January 2020

Although extinctions due to climate change are still uncommon, they might surpass those caused by habitat loss or overexploitation over the next few decades. Among marine megafauna, mammals fulfill key and irreplaceable ecological roles in the ocean, and the collapse of their populations may therefore have irreversible consequences for ecosystem functioning and services. Using a trait-based approach, we assessed the vulnerability of all marine mammals to global warming under high and low greenhouse gas emission scenarios for the middle and the end of the 21stcentury. We showed that the North Pacific Ocean, the Greenland Sea and the Barents Sea host the species that are most vulnerable to global warming. Future conservation plans should therefore focus on these regions, where there are long histories of overexploitation and there are high levels of current threats to marine mammals. Among the most vulnerable marine mammals were several threatened species, such as the North Pacific right whale (Eubalaena japonica) and the dugong (Dugong dugon), that displayed unique combinations of functional traits. Beyond species loss, we showed that the potential extinctions of the marine mammals that were most vulnerable to global warming might induce a disproportionate loss of functional diversity, which may have profound impacts on the future functioning of marine ecosystems worldwide.
Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta
Authors: Natale Bryony V. , Gustin Katarina N. , Lee Kendrick , Holloway Alison C. , Laviolette Steven R. , Natale David R. C. , Hardy Daniel B.
Published: January 2020

1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9–tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC (3 mg/kg) from embryonic (E)6.5 through 22. Dams were allowed to deliver normally to measure pregnancy and neonatal outcomes, with a subset sacrificed at E19.5 for placenta assessment via immunohistochemistry and qPCR. Gestational Δ9-THC exposure resulted in pups born with symmetrical fetal growth restriction, with catch up growth by post-natal day (PND)21. During pregnancy there were no changes to maternal food intake, maternal weight gain, litter size, or gestational length. E19.5 placentas from Δ9-THC-exposed pregnancies exhibited a phenotype characterized by increased labyrinth area, reduced Epcam expression (marker of labyrinth trophoblast progenitors), altered maternal blood space, decreased fetal capillary area and an increased recruitment of pericytes with greater collagen deposition, when compared to vehicle controls. Further, at E19.5 labyrinth trophoblast had reduced glucose transporter 1 (GLUT1) and glucocorticoid receptor (GR) expression in response to Δ9-THC exposure. In conclusion, maternal exposure to Δ9-THC effectively compromised fetal growth, which may be a result of the adversely affected labyrinth zone development. These findings implicate GLUT1 as a Δ9-THC target and provide a potential mechanism for the fetal growth restriction observed in women who use cannabis during pregnancy.
Statin use, HMGCR expression, and breast cancer survival – The Malmö Diet and Cancer Study
Authors: Bjarnadottir Olöf , Feldt Maria , Inasu Maria , Bendahl Pär-Ola , Elebro Karin , Kimbung Siker , Borgquist Signe
Published: January 2020

Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), which is inhibited by statins, might serve as such a marker. Thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and Cancer Study breast cancer cohort. Statin use and cause of death data were retrieved from the Swedish Prescribed Drug Register and Swedish Death Registry, respectively. Breast cancer-specific mortality (BCM) according to statin use and HMGCR expression were analyzed using Cox regression models. Three-hundred-twelve of 910 breast cancer patients were prescribed statins; 74 patients before and 238 after their breast cancer diagnosis. HMGCR expression was assessable for 656 patients; 119 showed negative, 354 weak, and 184 moderate/strong expressions. HMGCR moderate/strong expression was associated with prognostically adverse tumor characteristics as higher histological grade, high Ki67, and ER negativity. HMGCR expression was not associated with BCM. Neither was statin use associated with BCM in our study. Among breast cancer patients on statins, no or weak HMGCR expression predicted favorable clinical outcome. These suggested associations need further testing in larger cohorts.
Better brain connectivity is associated with higher total fat mass and lower visceral adipose tissue in military pilots
Authors: Cárdenas David , Madinabeitia Iker , Vera Jesús , de Teresa Carlos , Alarcón Francisco , Jiménez Raimundo , Catena Andrés
Published: January 2020

A lack of exercise leads to being overweight or obese affecting regional brain structure and functional connectivity associated with impaired cognitive function and dementia. In recent decades, several studies of healthy individuals suggest that adiposity may also produce negative independent effects on the brain. We aimed to investigate the relationship between body composition – total fat mass (TFM) and visceral adipose tissue (VAT) – with white matter (WM) integrity using a whole-brain approach in military pilots. Twenty-three military helicopter pilots (Mage = 36.79; SD = 8.00; MBMI = 25.48; SD = 2.49) took part in the study. Brain volumes were studied using diffusion tensor imaging technique by means of a 3T Magnetom Tim Trio. Measurements of body mass index (BMI), TFM and VAT were obtained using Dual-energy X-ray Absorptiometry (DXA). The results showed that, on one hand, higher TFM was associated with higher white matter fractional anisotropy (FA) and, on the other hand, higher VAT was associated with lower FA. Data showed that TFM and VAT are the critical factors underlying WM integrity in combat helicopter pilots. The authors suggest that fat presence enhance brain connectivity while there is no excess, specifically in VAT.
The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis
Authors: Pascual-Itoiz Miguel Angel , Peña-Cearra Ainize , Martín-Ruiz Itziar , Lavín José Luis , Simó Carolina , Rodríguez Héctor , Atondo Estibaliz , Flores Juana María , Carreras-González Ana , Tomás-Cortázar Julen , Barriales Diego , Palacios Ainhoa , García-Cañas Virginia , Pellón Aize , Fullaondo Asier , Aransay Ana Mª , Prados-Rosales Rafael , Martín Rebeca , Anguita Juan , Abecia Leticia
Published: January 2020

Recent evidences indicate that mitochondrial genes and function are decreased in active ulcerative colitis (UC) patients, in particular, the activity of Complex I of the electron transport chain is heavily compromised. MCJ is a mitochondrial inner membrane protein identified as a natural inhibitor of respiratory chain Complex I. The induction of experimental colitis in MCJ-deficient mice leads to the upregulation ofTimp3expression resulting in the inhibition of TACE activity that likely inhibitsTnfandTnfr1shedding from the cell membrane in the colon. MCJ-deficient mice also show higher expression ofMyd88andTlr9, proinflammatory genes and disease severity. Interestingly, the absence of MCJ resulted in distinct microbiota metabolism and composition, including a member of the gut community in UC patients,Ruminococcus gnavus. These changes provoked an effect on IgA levels. Gene expression analyses in UC patients showed decreased levels ofMCJand higher expression ofTIMP3, suggesting a relevant role of mitochondrial genes and function among active UC. The MCJ deficiency disturbs the regulatory relationship between the host mitochondria and microbiota affecting disease severity. Our results indicate that mitochondria function may be an important factor in the pathogenesis. All together support the importance of MCJ regulation during UC.
20% of US electricity from wind will have limited impacts on system efficiency and regional climate
Authors: Pryor S. C. , Barthelmie R. J. , Shepherd T. J.
Published: January 2020

Impacts from current and future wind turbine (WT) deployments necessary to achieve 20% electricity from wind are analyzed using high resolution numerical simulations over the eastern USA. Theoretical scenarios for future deployments are based on repowering (i.e. replacing with higher capacity WTs) thus avoiding competition for land. Simulations for the contemporary climate and current WT deployments exhibit good agreement with observed electricity generation efficiency (gross capacity factors (CF) from simulations = 45–48%, while net CF for WT installed in 2016 = 42.5%). Under the scenario of quadrupled installed capacity there is a small decrease in system-wide efficiency as indicated by annual mean CF. This difference is approximately equal to that from the two simulation years and may reflect saturation of the wind resource in some areas. WT modify the local near-surface climate in the grid cells where they are deployed. The simulated impact on near-surface climate properties at both the regional and local scales does not increase with increasing WT installed capacity. Climate impacts from WT are modest compared to regional changes induced by historical changes in land cover and to the global temperature perturbation induced by use of coal to generate an equivalent amount of electricity.
Female Reproductive Performance and Maternal Birth Month: A Comprehensive Meta-Analysis Exploring Multiple Seasonal Mechanisms
Authors: Boland Mary Regina , Fieder Martin , John Luis H. , Rijnbeek Peter R. , Huber Susanne
Published: January 2020

Globally, maternal birth season affects fertility later in life. The purpose of this systematic literature review is to comprehensively investigate the birth season and female fertility relationship. Using PubMed, we identified a set of 282 relevant fertility/birth season papers published between 1972 and 2018. We screened all 282 studies and removed 131 non-mammalian species studies on fertility and 122 studies that were on non-human mammals. Our meta-analysis focused on the remaining 29 human studies, including twelve human datasets from around the world (USA, Europe, Asia). The main outcome was change in female fertility as observed by maternal birth month and whether this change was correlated with either temperature or rainfall. We found that temperature was either strongly correlated or anti-correlated in studies, indicating that another factor closely tied to temperature may be the culprit exposure. We found that rainfall only increases fertility in higher altitude locations (New Zealand, Romania, and Northern Vietnam). This suggests the possibility of a combined or multi-factorial mechanism underlying the female fertility – birth season relationship. We discuss other environmental and sociological factors on the birth season – female fertility relationship. Future research should focus on the role of birth season and female fertility adjusting for additional factors that modulate female fertility as discussed in this comprehensive review.
Arginyltransferase knockdown attenuates cardiac hypertrophy and fibrosis through TAK1-JNK1/2 pathway
Authors: Singh Kanika , Gupta Ankit , Sarkar Ashish , Gupta Ishita , Rana Santanu , Sarkar Sagartirtha , Khan Sameena
Published: January 2020

Myocardial hypertrophy, an inflammatory condition of cardiac muscles is a maladaptive response of the heart to biomechanical stress, hemodynamic or neurohormonal stimuli. Previous studies indicated that knockout of Arginyltransferase (ATE1) gene in mice and embryos leads to contractile dysfunction, defective cardiovascular development, and impaired angiogenesis. Here we found that in adult rat model, downregulation of ATE1 mitigates cardiac hypertrophic, cardiac fibrosis as well as apoptosis responses in the presence of cardiac stress i.e. renal artery ligation. On contrary, in wild type cells responding to renal artery ligation, there is an increase of cellular ATE1 protein level. Further, we have shown the cardioprotective role of ATE1 silencing is mediated by the interruption of TAK1 activity-dependent JNK1/2 signaling pathway. We propose that ATE1 knockdown in presence of cardiac stress performs a cardioprotective action and the inhibition of its activity may provide a novel approach for the treatment of cardiac hypertrophy.
Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis
Authors: Lee Hwaryeon , Park Sohyun , Kang Ji Eun , Lee Hee Min , Kim Sun Ah , Rhie Sandy Jeong
Published: January 2020

The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69–3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07–3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62–0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54–0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC.
Ultrasensitive nano-aptasensor for monitoring retinol binding protein 4 as a biomarker for diabetes prognosis at early stages
Authors: Torabi Raheleh , Ghourchian Hedayatollah
Published: January 2020

Prognosis of diabetes risk at early stages has become an important challenge due to the prevalence of this disease. Retinol binding protein 4 (RBP4), a recently identified adipokine, has been introduced as a predictor for the onset of diabetes type 2 in coming future. In the present report a sensitive aptasensor for detection of RBP4 is introduced. The immune sandwich was prepared by immobilizing biotinylated RBP4 aptamers on streptavidin coated polystyrene micro-wells and then incubation of RBP4 as target and finally addition of luminol-antibody bearing intercross-linked gold nanoparticles as reporter. The chemiluminescence intensity was recorded in the presence of hydrogen peroxide as oxidant agent and Au3+ as an efficient catalyst for luminol oxidation. The aptasensor responded to RBP4 in the linear concentration range from 0.001 to 2 ng/mL and detection limit was slightly less than 1 pg/mL. The proposed method has successfully applied to determine the RBP4 in patient real serums. By using the intercross-linked gold nanoparticles, it is possible to provide more accessible surface for immobilizing luminol and enhance the chemiluminescence signal. Therefore, the analytical parameters such as sensitivity, specificity, detection limit and linear range were improved in compare to the biosensors reported in the literature.
Hard plant tissues do not contribute meaningfully to dental microwear: evolutionary implications
Authors: van Casteren Adam , Strait David S. , Swain Michael V. , Michael Shaji , Thai Lidia A. , Philip Swapna M. , Saji Sreeja , Al-Fadhalah Khaled , Almusallam Abdulwahab S. , Shekeban Ali , McGraw W. Scott , Kane Erin E. , Wright Barth W. , Lucas Peter W.
Published: January 2020

Reconstructing diet is critical to understanding hominin adaptations. Isotopic and functional morphological analyses of early hominins are compatible with consumption of hard foods, such as mechanically-protected seeds, but dental microwear analyses are not. The protective shells surrounding seeds are thought to induce complex enamel surface textures characterized by heavy pitting, but these are absent on the teeth of most early hominins. Here we report nanowear experiments showing that the hardest woody shells – the hardest tissues made by dicotyledonous plants – cause very minor damage to enamel but are themselves heavily abraded (worn) in the process. Thus, hard plant tissues do not regularly create pits on enamel surfaces despite high forces clearly being associated with their oral processing. We conclude that hard plant tissues barely influence microwear textures and the exploitation of seeds from graminoid plants such as grasses and sedges could have formed a critical element in the dietary ecology of hominins.
Design and Molecular dynamic Investigations of 7,8-Dihydroxyflavone Derivatives as Potential Neuroprotective Agents Against Alpha-synuclein
Authors: Mohankumar Thangavel , Chandramohan Vivek , Lalithamba Haralur Shankaraiah , Jayaraj Richard L. , Kumaradhas Poomani , Sivanandam Magudeeswaran , Hunday Govindasamy , Vijayakumar Rajendran , Balakrishnan Rangasamy , Manimaran Dharmar , Elangovan Namasivayam
Published: January 2020

Parkinson’s disease (PD) is the second most common neurodegenerative disorder caused due to loss of dopaminergic neurons in substantia nigra pars compacta, which occurs the presence of Lewy bodies made up of Alpha-synuclein (ASN) aggregation resulting in neuronal death. This study aims to identify potent 7,8-Dihydroxyflavone (DHF) derivatives to inhibit the ASN aggregation from in silico analysis. Molecular docking study reveals that carbamic ester derivatives of DHF [DHF-BAHPC (8q), DHF-BAHPEC (8s), DHF-BAHEC (8p), DHF-BDOPC (8c), DHF-BAPEC (8n) and DHF-BAMC (8h)] have good binding affinity towards ASN, when compared with DHF and L-DOPA; their docking score values are −16.3120, −16.1875, −15.2223, −14.3118, −14.2893, –14.2810, −14.0383, and −9.1560 kcal/mol respectively. The in silico pharmacological evaluation shows that these molecules exhibit the drug-likeness and ADMET properties. Molecular dynamics simulation confirms the stability of the molecules with ASN. The intermolecular interaction analyzed under the dynamic condition, allows to identify the candidate which potentially inhibits ASN aggregation. Hence, we propose that DHF derivatives are the potential lead drug molecules and preclinical studies are needed to confirm the promising therapeutic ability against PD.
Colossal heating efficiency via eddy currents in amorphous microwires with nearly zero magnetostriction
Authors: Morales Irene , Archilla Diego , de la Presa Patricia , Hernando Antonio , Marin Pilar
Published: January 2020

It is well stablished that heating efficiency of magnetic nanoparticles under radiofrequency fields is due to the hysteresis power losses. In the case of microwires (MWs), it is not clear at all since they undergo non-coherent reversal mechanisms that decrease the coercive field and, consequently, the heating efficiency should be much smaller than the nanoparticles. However, colossal heating efficiency has been observed in MWs with values ranging from 1000 to 2800 W/g, depending on length and number of microwires, at field as low as H = 36 Oe at f = 625 kHz. It is inferred that this colossal heating is due to the Joule effect originated by the eddy currents induced by the induction field B = M + χH parallel to longitudinal axis. This effect is observed in MWs with nearly zero magnetostrictive constant as Fe2.25Co72.75Si10B15 of 30 μm magnetic diameter and 5 mm length, a length for which the inner core domain of the MWs becomes axial. This colossal heating is reached with only 24 W of power supplied making these MWs very promising for inductive heating applications at a very low energy cost.
A twin study of body mass index and dental caries in childhood
Authors: Silva M. J. , Kilpatrick N. M. , Craig J. M. , Manton D. J. , Leong P. , Ho H. , Saffery R. , Burgner D. P. , Scurrah K. J.
Published: January 2020

Sub-optimal nutrition and dental caries are both common with significant short and long-term implications for child health and development. We applied twin statistical methods to explore the relationship between body mass index (BMI) and dental caries. We measured BMI at 18 months and six years of age and cumulative dental caries experience at six years in 344 twin children. Dental caries in primary teeth was categorised into ‘any’ or ‘advanced’ and BMI was analysed as both a continuous and categorical variable. Statistical analyses included multiple logistic regression using generalized estimating equations and within/between-pair analyses. There was no association between BMI and ‘any’ dental caries experience at either time-point, neither overall nor in within/between pair analyses. However, ‘advanced’ dental caries at six years was associated with a within-pair difference in BMI of −0.55 kg/m2 (95% CI −1.00, −0.11, p = 0.015). A within-pair increase of 1 kg/m2 in BMI was associated with a lower within-pair risk of advanced dental caries (OR 0.68, 95% CI 0.52, 0.90, p = 0.007). These findings reveal a possible causal relationship between lower BMI and dental caries. As dental outcomes were only measured at one time point, the direction of this potentially causal relationship is unclear.
The relationship between consumption of nitrite or nitrate and risk of non-Hodgkin lymphoma
Authors: Yu Mengxia , Li Chenying , Hu Chao , Jin Jingrui , Qian Shenxian , Jin Jie
Published: January 2020

Epidemiologic studies of the relationship between nitrite or nitrate consumption and risk of non-Hodgkin lymphoma (NHL) remain controversial. The current meta-analysis aimed to reexamine the evidence and quantitatively evaluate that relationship. Manuscripts were retrieved from the Web of Science, Chinese National Knowledge Infrastructure and PubMed databases up to May 2019. From the studies included in the review, results were combined and presented as odds ratios (OR). To conduct a dose-response (DR) analysis, studies presenting risk estimates over a series of categories of exposure were selected. Our data indicate that the consumption of nitrite was linked to a significantly increased hazard of NHL (OR: 1.37; 95% CI: 1.14–1.65), rather than nitrate (OR: 1.02; 95% CI: 0.94–1.10). According to Egger’s and Begg’s tests (P > 0.05), there was no evidence of significant publication bias. Moreover, our DR analysis indicated that the risk of NHL grew by 26% for each additional microgram of nitrite consumed in the diet per day (OR: 1.26; 95% CI: 1.09–1.42). Through subset analysis of the nitrite studies, data from the high-quality studies indicated that consumption was positively associated with carcinogenicity, leading to NHL (OR: 1.44; 95% CI: 1.17–1.77) and positively correlated with the development of diffuse large B-cell lymphoma (OR: 1.55; 95% CI: 1.07–2.26), but not other NHL subtypes. In addition, the data suggested that females (OR: 1.50; 95% CI: 1.15–1.95) and high levels of nitrite intake (OR: 1.64; 95% CI: 1.28–2.09) had a higher risk of NHL. Our meta-analysis supports the hypothesis that nitrite intake, but not that of nitrate, raises the risk of developing NHL. In the future, better designed prospective research studies should be conducted to confirm our findings, clarify potential biological mechanisms and instruct clinicians about NHL prophylaxis.
Rejection of the genetic implications of the “Abundant Centre Hypothesis” in marine mussels
Authors: Ntuli Noxolo N. , Nicastro Katy R. , Zardi Gerardo I. , Assis Jorge , McQuaid Christopher D. , Teske Peter R.
Published: January 2020

The ‘Abundant-Centre Hypothesis’ is a well-established but controversial hypothesis stating that the abundance of a species is highest at the centre of its range and decreases towards the edges, where conditions are unfavourable. As genetic diversity depends on population size, edge populations are expected to show lower intra-population genetic diversity than core populations, while showing high inter-population genetic divergence. Here, the genetic implications of the Abundant-Centre Hypothesis were tested on two coastal mussels from South Africa that disperse by means of planktonic larvae, the native Perna perna and the invasive Mytilus galloprovincialis. Genetic structure was found within P. perna, which, together with evidence from Lagrangian particle simulations, points to significant reductions in gene flow between sites. Despite this, the expected diversity pattern between centre and edge populations was not found for either species. We conclude that the genetic predictions of the Abundant-Centre Hypothesis are unlikely to be met by high-dispersal species with large population sizes, and may only become evident in species with much lower levels of connectivity.
Variation among S-locus haplotypes and among stylar RNases in almond
Authors: Goonetilleke Shashi N. , Croxford Adam E. , March Timothy J. , Wirthensohn Michelle G. , Hrmova Maria , Mather Diane E.
Published: January 2020

In many plant species, self-incompatibility systems limit self-pollination and mating among relatives. This helps maintain genetic diversity in natural populations but imposes constraints in agriculture and plant breeding. In almond [Prunus dulcis (Mill.) D.A. Webb], the specificity of self-incompatibility is mainly determined by stylar ribonuclease (S-RNase) and S-haplotype-specific F-box (SFB) proteins, both encoded within a complex locus, S. Prior to this research, a nearly complete sequence was available for one S-locus haplotype. Here, we report complete sequences for four haplotypes and partial sequences for 11 haplotypes. Haplotypes vary in sequences of genes (particularly S-RNase and SFB), distances between genes and numbers and positions of long terminal repeat transposons. Haplotype variation outside of the S-RNase and SFB genes may help maintain functionally important associations between S-RNase and SFB alleles. Fluorescence-based assays were developed to distinguish among some S-RNase alleles. With three-dimensional modelling of five S-RNase proteins, conserved active sites were identified and variation was observed in electrostatic potential and in the numbers, characteristics and positions of secondary structural elements, loop anchoring points and glycosylation sites. A hypervariable region on the protein surface and differences in the number, location and types of glycosylation sites may contribute to determining S-RNase specificity.
Zebrafish C-reactive protein isoforms inhibit SVCV replication by blocking autophagy through interactions with cell membrane cholesterol
Authors: Bello-Perez Melissa , Pereiro Patricia , Coll Julio , Novoa Beatriz , Perez Luis , Falco Alberto
Published: January 2020

In the present work, the mechanisms involved in the recently reported antiviral activity of zebrafish C-reactive protein-like protein (CRP1-7) against the spring viraemia of carp rhabdovirus (SVCV) in fish are explored. The results neither indicate blocking of the attachment or the binding step of the viral replication cycle nor suggest the direct inhibition of G protein fusion activity or the stimulation of the host’s interferon system. However, an antiviral state in the host is induced. Further results showed that the antiviral protection conferred by CRP1-7 was mainly due to the inhibition of autophagic processes. Thus, given the high affinity of CRPs for cholesterol and the recently described influence of the cholesterol balance in lipid rafts on autophagy, both methyl-β-cyclodextrin (a cholesterol-complexing agent) and 25-hydroxycholesterol (a cholesterol molecule with antiviral properties) were used to further describe CRP activity. All the tested compounds exerted antiviral activity by affecting autophagy in a similar manner. Further assays indicate that CRP reduces autophagy activity by initially disturbing the cholesterol ratios in the host cellular membranes, which in turn negatively affects the intracellular regulation of reactive oxygen species (ROS) and increases lysosomal pH as a consequence. Ultimately, here we propose that such pH changes exert an inhibitory direct effect on SVCV replication by disrupting the pH-dependent membrane-fusogenic ability of the viral glycoprotein G, which allows the release of the virus from endosomes into cytoplasm during its entry phase.
Impact of anticancer chemotherapy on the extension of beta-lactamase spectrum: an example with KPC-type carbapenemase activity towards ceftazidime-avibactam
Authors: Hobson Claire Amaris , Bonacorsi Stéphane , Hocquet Didier , Baruchel André , Fahd Mony , Storme Thomas , Tang Raksamy , Doit Catherine , Tenaillon Olivier , Birgy André
Published: January 2020

Through their action on DNA replication, anticancer chemotherapies could increase the basal mutation rate in bacteria and increase the risk of selecting antibiotic resistant mutants. We investigated the impact of several drugs on a beta-lactamase model using KPC-type carbapenemase-producing Enterobacteriaceae. We studied the impact of anticancer chemotherapies used in pediatric hematologic malignancies on 7 clinical isolates of Enterobacteriaceae producing KPC-type carbapenemases. We compared the mutation rates from cultures with/without chemotherapy on ceftazidime-avibactam, rifampicin and ceftazidime-avibactam combined with meropenem media. Mechanisms of ceftazidime-avibactam resistance were explored on a subset of mutants. After exposure to some cytotoxic molecules, the bacterial mutation rates leading to ceftazidime-avibactam and to rifampicin resistance increased up to 104-fold while we observed no emergence of resistant mutants (frequency of <10−10) on a meropenem combined with ceftazidime-avibactam media. Compared to the parental strains, an increased susceptibility to meropenem was observed in the ceftazidime-avibactam resistant mutants. The blaKPC genes of ceftazidime-avibactam mutants harbored either mutations, deletions or insertions, especially in the region encoding the Ω-loop of the KPC-type carbapenemase. Anticancer chemotherapy can increase the mutation rates of bacteria accelerating the extension of KPC-type carbapenemases towards ceftazidime-avibactam, one of the last resort antimicrobial chemotherapy.
Chemical production of acidified activated carbon and its influences on soil fertility comparative to thermo-pyrolyzed biochar
Authors: Sultan Haider , Ahmed Niaz , Mubashir Muhammad , Danish Subhan
Published: January 2020

Biochar (BC) is gaining attention day by day due to its potential benefits for the improvement in degraded soil health. During its production by pyrolysis, carbon sequestration is an important aspect that makes it environment-friendly amendment. However, 100% anaerobic combustion of waste at such a high temperature decreases its adaptability to produce BC at commercial scale. On the other hand, the alkaline nature of BC also causes adverse effects on soil health when used in alkaline soils. Keeping in mind the problem of BC production and its high pH, current experiment was conducted to introduce chemical production of acidified activated carbon (AAC) and its effects on soil nutrients status comparative to high temperature pyrolyzed BC. As compared to thermal pyrolysis, sulphuric acid produce acidified activated carbon in minimum time and large in quantity. Sulphuric acid produces acidified activated carbon, fix higher carbon as compared to thermal pyrolyzed BC. Results also showed that application of 2% AAC was far better for decreasing alkaline soil pHs(3.52 and 4.71%) and ECe(45.2 and 71.4%) as compared to control in clay and sandy clay loam. A significant maximum increase in available P (117.5 and 25.9%), extractable Zn (42.0 and 52.2%), B (111.4 and 46.2%) and Fe (59.5 and 34.4%) in clay and sandy clay texture soils also validated the efficacious functioning of AAC over BC and control. It is concluded that sulphuric acid use is an easier and adaptable method to produce activated carbon at commercial scale. As compared to thermal pyrolyzed BC, application of AAC could be more effective in the improvement of soil health and fertility status.
Author Correction: Lipid normalization and stable isotope discrimination in Pacific walrus tissues
Authors: Clark Casey T. , Horstmann Lara , Misarti Nicole
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Definitive evidence of the presence of 24-methylenecycloartanyl ferulate and 24-methylenecycloartanyl caffeate in barley
Authors: Ito Junya , Sawada Kazue , Ogura Yusuke , Xinyi Fan , Rahmania Halida , Mohri Tomoyo , Kohyama Noriko , Kwon Eunsang , Eitsuka Takahiro , Hashimoto Hiroyuki , Kuwahara Shigefumi , Miyazawa Teruo , Nakagawa Kiyotaka
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Seasonality of Taylor’s law of fluctuation scaling in all-India daily rainfall
Authors: Tippett Michael K. , Cohen Joel E.
Published: January 2020

Here we show that the variance over time of all-India daily rainfall (AIR) can be related to the mean over time of AIR by a seasonally varying power law. Outside of the peak monsoon months of July and August, AIR variance increases in proportion to a positive power of mean daily rainfall. During July and August, monthly averages of AIR show little association with the corresponding variances. This power-law relationship of temporal variance to temporal mean is known in biological sciences as Taylor’s law (TL) and in physical sciences as fluctuation scaling. We explain the seasonal variation in TL qualitatively by independent and identically distributed random sampling. Accounting for day-to-day correlation in AIR is sufficient to match quantitatively the observed power-law behavior. Our findings provide a quantitative month-specific assessment of the variability of AIR that could prove useful for the design of crop insurance and social safety nets for the large fraction of the population of the Indian subcontinent that depends on rainfed agriculture.
Colorimetric chiral discrimination of lysine enantiomers and configurable logic gate operation based on fluorescein-functionalized polydiacetylene vesicles
Authors: Yang Guang , Ji Jie , Zhang Siyu , Li Guangyao , Li Bin
Published: January 2020

This study describes a sensitive sensor for based on fluorescein-functionalized diacetylene (F-DA) chromatic conjugated vesicle which allows colorimetric visualization for the chiral recognition of lysine by the naked-eye.
Vacancy and interstitial atom evolution with the separation of the nanoscale phase in Fe–Cr alloys: phase-field simulations
Authors: Yan Zhengwei , Shi Shujing , Li Yongsheng , Chen Jing , Maqbool Shahid
Published: January 2020

Vacancies and interstitial atoms accumulate in a loop around the nanoscale phase and promote phase separation.