bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural regulation in tooth regeneration of Ambystoma mexicanum
Authors: Makanae Aki , Tajika Yuki , Nishimura Koki , Saito Nanami , Tanaka Jun-ichi , Satoh Akira 
Published: June 2020

AbstractThe presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nerve-dependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration. The presence of nerves is an important factor in successful organ regeneration in amphibians. The Mexican salamander, Ambystoma mexicanum, is able to regenerate limbs, tail, and gills when nerves are present. However, the nervedependency of tooth regeneration has not been evaluated. Here, we reevaluated tooth regeneration processes in axolotls using a three-dimensional reconstitution method called CoMBI and found that tooth regeneration is nerve-dependent although the dentary bone is independent of nerve presence. The induction and invagination of the dental lamina were delayed by denervation. Exogenous Fgf2, Fgf8, and Bmp7 expression could induce tooth placodes even in the denervated mandible. Our results suggest that the role of nerves is conserved and that Fgf+Bmp signals play key roles in axolotl organ-level regeneration.
Physiological costs of chemical defence: repeated reflex bleeding weakens the immune system and postpones reproduction in a ladybird beetle
Authors: Knapp Michal , Řeřicha Michal , Židlická Dana 
Published: June 2020

AbstractIn insects, external chemical defences, such as reflex bleeding, have been proved to be an efficient strategy against various predators. At the same time, significant costs of reflex bleeding can be expected because bled haemolymph is lost and all valuable components included have to be renewed. Interestingly, this issue has rarely been investigated for adult insects. In this study, we examined the immune and fitness costs of repeated reflex bleeding in adults of the invasive ladybird Harmonia axyridis, investigating several haemolymph parameters. Reflex bleeding induced twice a week for three weeks resulted in a significant reduction in haemocyte concentration, total protein content, and antimicrobial activity against Micrococcus luteus, and a marginally non-significant decrease in antimicrobial activity against Escherichia coli. Repeated reflex bleeding did not result in significant body mass reduction. Interestingly, resource limitation in the form of complete food absence did not significantly interact with reflex bleeding, even though starvation itself had a strong negative effect on all haemolymph parameters investigated and individual body mass. Daily reflex bleeding did not result in decreased fecundity of young ladybirds during the first 30 days of their adult life, but the start of ladybird reproduction was delayed by about two days. Moreover, ladybirds bleeding larger amounts of haemolymph started their reproduction significantly later. Overall, our results indicate that repeated reflex bleeding weakens a ladybird’s immune system and can increase their susceptibility to pathogens, but a ladybird’s reproductive potential remains almost unaffected, even by very intensive reflex bleeding.
Tandem Mass Tag (TMT)-based quantitative proteomics reveals potential targets associated with onset of Sub-clinical Mastitis in cows
Authors: Bathla Shveta , Sindhu Anil , Kumar Sudarshan , Dubey Shivam Kumar , Pattnaik Smaranika , Rawat Preeti , Chopra Alka , Dang Ajay , Kaushik Jai Kumar , Mohanty Ashok Kumar 
Published: June 2020

AbstractBovine milk is vital for infant nutrition and is a major component of the human diet. Bovine mastitis is a common inflammatory disease of mammary gland in cattle. It alters the immune profile of the animal and lowers the quality and yield of milk causing huge economic losses to dairy industry. The incidence of sub-clinical mastitis (SCM) is higher (25–65% worldwide) than clinical mastitis (CM) (>5%), and frequently progresses to clinical stage due to lack of sensitive and specific detection method. We used quantitative proteomics to identify changes in milk during sub-clinical mastitis, which may be potential biomarkers for developing rapid, non-invasive, sensitive detection methods. We performed comparative proteome analysis of the bovine milk, collected from the Indian hybrid cow Karan Fries. The differential proteome in the milk of Indian crossbred cows during sub-acute and clinical intramammary gland infection has not been investigated to date. Using high-resolution mass spectrometry-based quantitative proteomics of the bovine whey proteins, we identified a total of 1459 and 1358 proteins in biological replicates, out of which 220 and 157 proteins were differentially expressed between normal and infected samples. A total of 82 proteins were up-regulated and 27 proteins were down-regulated, having fold changes of ≥2 and ≤0.8 respectively. Among these proteins, overexpression of CHI3L1, LBP, GSN, GCLC, C4 and PIGR proteins was positively correlated with the events that elicit host defence system, triggering production of cytokines and inflammatory molecules. The appearance of these potential biomarkers in milk may be used to segregate affected cattle from the normal herd and may support mitigation measures for prevention of SCM and CM.
Outcome and toxicity analysis of single dose stereotactic radiosurgery in vestibular schwannoma based on the Koos grading system
Authors: Rueß Daniel , Pöhlmann Lea , Grau Stefan , Hamisch Christina , Hoevels Mauritius , Treuer Harald , Baues Christian , Kocher Martin , Ruge Maximillian 
Published: June 2020

AbstractStereotactic radiosurgery (SRS) has evolved as widely accepted treatment option for small-sized (Koos I up to II) vestibular schwannoma (VS). For larger tumors (prevalent Koos VI), microsurgery or combined treatment strategies are mostly recommended. However, in patients not suited for microsurgery, SRS might also be an alternative to balance tumor control, hearing preservation and adverse effects. The purpose of this analysis was to evaluate the efficacy and toxicity of SRS for VS with regard to different Koos grades. All patients with untreated VS who received SRS at our center were included. Outcome analysis included tumor control, preservation of serviceable hearing based on median pure tone averages (PTA), and procedure-related adverse events rated by the Common Terminology Criteria for Adverse Events (CTCAE; v4.03) classification. In total, 258 patients (median age 58 years, range 21–84) were identified with a mean follow-up of 52 months (range 3–228 months). Mean tumor volume was 1.8 ml (range 0.1–18.5). The mean marginal dose was 12.3 Gy ± 0.6 (range 11–13.5). The cohort was divided into two groups: A (Koos grades I and II, n = 186) and B (Koos grades III and IV, n = 72). The actuarial tumor control rate was 98% after 2 years and 90% after 5 and 10 years. Koos grading did not show a significant impact on tumor control (p = 0.632) or hearing preservation (p = 0.231). After SRS, 18 patients (7%) had new transient or permanent symptoms classified by the CTCAE. The actuarial rate of CTCAE-free survival was not related to Koos grading (p = 0.093). Based on this selected population of Koos grade III and IV VS without or with only mild symptoms from brainstem compression, SRS can be recommended as the primary therapy with the advantage of low morbidity and satisfactory tumor control. The overall hearing preservation rate and toxicity of SRS was influenced by age and cannot be predicted by tumor volume or Koos grading alone.
Untargeted lipidomics using liquid chromatography-ion mobility-mass spectrometry reveals novel triacylglycerides in human milk
Authors: George Alexandra D. , Gay Melvin C. L. , Wlodek Mary E. , Trengove Robert D. , Murray Kevin , Geddes Donna T. 
Published: June 2020

AbstractHuman milk provides the infant with the essential nutritive and non-nutritive factors required for health, growth and development. The human milk lipidome is complex, but comprises predominantly triacylglycerides. Historically, the fatty acid profile of the entire human milk lipidome has been investigated, and many relationships have been identified between infant health and fatty acids. Most of these fatty acids are, however, delivered to the infant as triacylglycerides. Using liquid chromatography-ion mobility-mass spectrometry, the objective of this study was to characterise the triacylglyceride profile of human milk and elucidate relationships between the triacylglyceride profile and infant outcomes in a cohort of 10 exclusively breastfeeding woman-infant dyads. 205 triacylglycerides were identified, including 98 previously not reported in human milk. The dose of specific triacylglycerides differed in relation to infant health, such as lauric acid containing TAGs, which were delivered in significantly higher dose to healthy infants compared to unwell infants.
Host dependent maintenance of a blaNDM-1-encoding plasmid in clinical Escherichia coli isolates
Authors: Gama João Alves , Kloos Julia , Johnsen Pål J. , Samuelsen Ørjan 
Published: June 2020

AbstractDissemination of bacterial clones carrying plasmid-mediated resistance genes is a major factor contributing to the increasing prevalence of antibiotic resistance. Understanding the evolution of successful clones and the association to mobile resistance elements are therefore crucial. In this study, we determined the sequence of a 145 kb IncC multi-drug resistance plasmid (pK71-77-1-NDM), harbouring resistance genes to last-resort antibiotics including carbapenems. We show that the plasmid is able to transfer into a range of genetically diverse clinical Escherichia coli strains and that the fitness cost imposed on the host is often low. Moreover, the plasmid is stably maintained under non-selective conditions across different genetic backgrounds. However, we also observed a lower conjugation frequency and higher fitness cost in the E. coli sequence type (ST) 73 background, which could partially explain why this clone is associated with a lower level of antibiotic resistance than other E. coli clones. This is supported by a bioinformatical analysis showing that the ST73 background harbours plasmids less frequently than the other studied E. coli STs. Studying the evolution of antibiotic resistance in a clinical context and in diverse genetic backgrounds improves our understanding of the variability in plasmid-host associations.
Antenatal corticosteroids and preterm offspring outcomes in hypertensive disorders of pregnancy: A Japanese cohort study
Authors: Ushida Takafumi , Kotani Tomomi , Hayakawa Masahiro , Hirakawa Akihiro , Sadachi Ryo , Nakamura Noriyuki , Moriyama Yoshinori , Imai Kenji , Nakano-Kobayashi Tomoko , Kikkawa Fumitaka 
Published: June 2020

AbstractTo estimate whether antenatal corticosteroids (ACS) improve short- and long-term preterm offspring outcomes in singleton pregnancies complicated by hypertensive disorders of pregnancy (HDP) similar to pregnancies without HDP. This population-based retrospective study was conducted based on an analysis of data collected by the Neonatal Research Network of Japan on 21,014 singleton neonates weighing ≤1,500 g between 24 and 31 weeks’ gestation during 2003–2016. Logistic regression analyses were performed to compare short- and long-term offspring outcomes between mothers receiving ACS treatment and those who did not among pregnancies with HDP and without HDP. Of 21,014 neonates, 4,806 (22.9%) were born to mothers with HDP. ACS treatment was associated with significant decreases in short-term adverse outcomes in the both HDP and non-HDP groups, with similar reduced odds of neonatal death, respiratory distress syndrome, and intraventricular haemorrhage (IVH). However, ACS treatment did not significantly decrease severe IVH (aOR 0.76; 95% CI 0.51–1.13) and periventricular leukomalacia (1.14; 0.78–1.66) in the HDP group. In addition, ACS treatment in mothers without HDP significantly decreased cerebral palsy (aOR 0.70; 95% CI 0.58–084), developmental quotient scores <85 (0.79; 0.69–0.90), and composite adverse outcomes (0.85; 0.75–0.96) at 3 years of age, whereas ACS treatment in mothers with HDP did not significantly improve these outcomes (1.04; 0.69–1.57, 1.11; 0.88–1.39, 0.96; 0.75–1.22, respectively). ACS treatment was associated with significantly decreased major short-term morbidities and mortality among extremely and very preterm neonates of mothers with HDP, with ACS treatment having a decreased effect compared to that observed in neonates of mothers without HDP. Although ACS treatment has no additional effects on offspring outcomes at 3 years of age, our results did not suggest that ACS treatment should be withheld from mothers with HDP.
An anticonvulsive drug, valproic acid (valproate), has effects on the biosynthesis of fatty acids and polyketides in microorganisms
Authors: Poolchanuan Prapassorn , Unagul Panida , Thongnest Sanit , Wiyakrutta Suthep , Ngamrojanavanich Nattaya , Mahidol Chulabhorn , Ruchirawat Somsak , Kittakoop Prasat 
Published: June 2020

AbstractValproic acid or valproate (VPA) is an anticonvulsive drug used for treatments of epilepsy, bipolar disorder, and migraine headaches. VPA is also an epigenetic modulator, inhibiting histone deacetylase, and it has been subjected to clinical study for cancer treatment. During the investigation of VPA on a metabolite profile in a fungus, we found that VPA has significant effects on the production of some fatty acids. Further exploration of VPA on fatty acid profiles of microorganisms, fungi, yeast, and bacteria, as well as representative gut microbiome, revealed that VPA could enhance or reduce the production of some fatty acids. VPA was found to induce the production of trans-9-elaidic acid, a fatty acid that was previously reported to have cellular effects in human macrophages. VPA could also inhibit the production of some polyketides produced by a model fungus. The present work suggests that the induction or inhibition of fatty acid biosynthesis by VPA (100 µM) in gut microbiome could give effects to patients treated with VPA because high doses of VPA oral administration (up to 600 mg to 900 mg) are used by patients; the concentration of VPA in the human gut may reach a concentration of 100 µM, which may give effects to gut microorganisms.
Neuroanatomy of the spinosaurid Irritator challengeri (Dinosauria: Theropoda) indicates potential adaptations for piscivory
Authors: Schade Marco , Rauhut Oliver W. M. , Evers Serjoscha W. 
Published: June 2020

AbstractSpinosauridae, a theropod group characterized by elongated snouts, conical teeth, enlarged forelimbs, and often elongated neural spines, show evidence for semiaquatic adaptations and piscivory. It is currently debated if these animals represent terrestrial carnivores with adaptations for a piscivorous diet, or if they largely lived and foraged in aquatic habitats. The holotype of Irritator challengeri, a nearly complete skull from the late Early Cretaceous Santana Formation of northeastern Brazil, includes one of the few preserved spinosaurid braincases and can provide insights into neuroanatomical structures that might be expected to reflect ecological affinities. We generated digital models of the neuroanatomical cavities within the braincase, using computer tomography (CT) data. The cranial endocast of Irritator is generally similar to that of other non-maniraptoriform theropods, with weakly developed distinctions of hindbrain and midbrain features, relatively pronounced cranial flexures and relatively long olfactory tracts. The endosseous labyrinth has a long anterior semicircular canal, a posteriorly inclined common crus and a very large floccular recess fills the area between the semicircular canals. These features indicate that Irritator had the ability for fast and well-controlled pitch-down head movements. The skull table and lateral semicircular canal plane are strongly angled to one another, suggesting a downward angling of approximately 45° of the snout, which reduces interference of the snout with the field of vision of Irritator. These neuroanatomical features are consistent with fast, downward snatching movements in the act of predation, such as are needed for piscivory.
Periostin and tenascin-C interaction promotes angiogenesis in ischemic proliferative retinopathy
Authors: Kubo Yuki , Ishikawa Keijiro , Mori Kenichiro , Kobayashi Yoshiyuki , Nakama Takahito , Arima Mitsuru , Nakao Shintaro , Hisatomi Toshio , Haruta Masatoshi , Sonoda Koh-Hei , Yoshida Shigeo 
Published: June 2020

AbstractIschemic proliferative retinopathy (IPR), such as proliferative diabetic retinopathy (PDR), retinal vein occlusion and retinopathy of prematurity is a major cause of vision loss. Our previous studies demonstrated that periostin (PN) and tenascin-C (TNC) are involved in the pathogenesis of IPR. However, the interactive role of PN and TNC in angiogenesis associated with IPR remain unknown. We found significant correlation between concentrations of PN and TNC in PDR vitreous humor. mRNA and protein expression of PN and TNC were found in pre-retinal fibrovascular membranes excised from PDR patients. Interleukin-13 (IL-13) promoted mRNA and protein expression of PN and TNC, and co-immunoprecipitation assay revealed binding between PN and TNC in human microvascular endothelial cells (HRECs). IL-13 promoted angiogenic functions of HRECs. Single inhibition of PN or TNC and their dual inhibition by siRNA suppressed the up-regulated angiogenic functions. Pathological pre-retinal neovessels of oxygen-induced retinopathy (OIR) mice were attenuated in PN knock-out, TNC knock-out and dual knock-out mice compared to wild-type mice. Both in vitro and in vivo, PN inhibition had a stronger inhibitory effect on angiogenesis compared to TNC inhibition, and had a similar effect to dual inhibition of PN and TNC. Furthermore, PN knock-out mice showed scant TNC expression in pre-retinal neovessels of OIR retinas. Our findings suggest that interaction of PN and TNC facilitates pre-retinal angiogenesis, and PN is an effective therapeutic target for IPR such as PDR.
Estimation of the soil hydraulic properties from field data by solving an inverse problem
Authors: Guellouz Lamia , Askri Brahim , Jaffré Jérome , Bouhlila Rachida 
Published: June 2020

AbstractEstimating unsaturated soil hydraulic properties to predict water dynamics through a vertical soil profile under the effects of irrigation, drainage and evapotranspiration is imperative for managing soils in the arid regions. The aim of this work was to determine the soil water retention curve and the hydraulic permeability function of a bare soil profile in a Tunisian oasis threatened by salinization. The developed model combines a numerical inversion of the unsaturated flow equation with the BOBYQA optimisation algorithm. The direct model solved the Richards equation using a cell-centred finite difference model. Hydraulic properties were described by van Genuchten-Mualem models. Input data for the inverse problem are the infiltration flow, soil water contents and pressure heads measured during ponded infiltration and internal drainage tests. Numerical simulations of these two tests were performed considering a homogeneous single-layer soil profile but a better fitting between measured and simulated water contents was obtained when the soil profile was divided into five sub-layers. The hysteresis phenomenon was highlighted from the soil water retention and the relative permeability curves corresponding to the ponded infiltration and internal drainage tests.
Exposure to Endocrine Disrupting Chemicals in the Dutch general population is associated with adiposity-related traits
Authors: van der Meer Thomas P. , van Faassen Martijn , van Beek André P. , Snieder Harold , Kema Ido P. , Wolffenbuttel Bruce H. R. , van Vliet-Ostaptchouk Jana V. 
Published: June 2020

AbstractEndocrine Disrupting Chemicals (EDCs) have been linked to a variety of cardiometabolic diseases. Yet, few studies have investigated the exposure to EDCs and cardiometabolic health taking lifestyle into account. We aimed to assess exposure to five parabens, three bisphenols and thirteen metabolites of in total eight phthalates in a general Dutch population and to investigate their association with cardiometabolic traits. In 662 adult subjects from the population-based Lifelines cohort, 21 EDC analytes were measured in 24-hour urine collected in 2012, using LC-MS/MS. Association analyses between cardiometabolic traits and EDC concentrations were performed using multivariate linear models adjusting for age, sex, education, smoking, diabetes, physical activity and caloric intake. Quartile analyses were performed to assess linearity. Bisphenol A, four parabens and eight phthalate metabolites were detected in 84-100% of the samples. Adjusted associations for MiBP and MBzP and adiposity-related traits were robust for multiple testing (Beta’s, BMI: 1.12, 2.52; waist circumference: 0.64, 1.56, respectively; FDR < 0.009). Associations for triglyceride, HDL-cholesterol, glucose and blood pressure were not. Linearity was confirmed for significant associations. Exposure to EDCs in the Dutch population is ubiquitous. We found direct associations between phthalates and adiposity-related traits. Prospective studies are needed to confirm these findings.
Development of 177Lu-scFvD2B as a Potential Immunotheranostic Agent for Tumors Overexpressing the Prostate Specific Membrane Antigen
Authors: Carpanese Debora , Ferro-Flores Guillermina , Ocampo-Garcia Blanca , Santos-Cuevas Clara , Salvarese Nicola , Figini Mariangela , Fracasso Giulio , De Nardo Laura , Bolzati Cristina , Rosato Antonio , Meléndez-Alafort Laura 
Published: June 2020

AbstractThe clinical translation of theranostic 177Lu-radiopharmaceuticals based on inhibitors of the prostate-specific membrane antigen (PSMA) has demonstrated positive clinical responses in patients with advanced prostate cancer (PCa). However, challenges still remain, particularly regarding their pharmacokinetic and dosimetric properties. We developed a potential PSMA-immunotheranostic agent by conjugation of a single-chain variable fragment of the IgGD2B antibody (scFvD2B) to DOTA, to obtain a 177Lu-labelled agent with a better pharmacokinetic profile than those previously reported. The labelled conjugated 177Lu-scFvD2B was obtained in high yield and stability. In vitro, 177Lu-scFvD2B disclosed a higher binding and internalization in LNCaP (PSMA-positive) compared to PC3 (negative control) human PCa cells. In vivo studies in healthy nude mice revealed that 177Lu-scFvD2B present a favorable biokinetic profile, characterized by a rapid clearance from non-target tissues and minimal liver accumulation, but a slow wash-out from kidneys. Micro-SPECT/CT imaging of mice bearing pulmonary microtumors evidenced a slow uptake by LNCaP tumors, which steadily rose up to a maximum value of 3.6 SUV at 192 h. This high and prolonged tumor uptake suggests that 177Lu-scFvD2B has great potential in delivering ablative radiation doses to PSMA-expressing tumors, and warrants further studies to evaluate its preclinical therapeutic efficacy.