bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estradiol modulation of the renin–angiotensin system and the regulation of fear extinction
Authors: Parrish Jenna N. , Bertholomey Megan L. , Pang Hong W. , Speth Robert C. , Torregrossa Mary M. 
Published: January 2019

AbstractPost-traumatic stress disorder (PTSD) is more prevalent in women than men, yet much remains to be determined regarding the mechanism underlying this sex difference. Clinical and preclinical studies have shown that low estradiol levels during extinction of fear conditioning in rodents (i.e., cue exposure therapy in humans) leads to poor extinction consolidation and increased fear during extinction recall. The renin–angiotensin system (RAS) is also associated with stress-related pathologies, and RAS antagonists can enhance extinction consolidation in males. However, less is known about how estradiol and the RAS converge to alter fear extinction consolidation in females. Since estradiol downregulates the RAS, we determined the role of surgically (via ovariectomy [OVX]) and pharmacologically (via the hormonal contraceptive [HC], levonorgestrel) clamping estradiol at low levels in female rats on fear-related behavior, serum estradiol and angiotensin II (Ang II) levels, and angiotensin II type I receptor (AT1R) binding in the brain. We then tested whether the AT1R antagonist losartan would alter fear-related behavior in an estradiol-dependent manner. We found that both OVX and HC treatment produced extinction consolidation deficits relative to intact female rats in proestrus (when estradiol levels are high), and that losartan treatment mitigated these deficits and reduced freezing. OVX, but not HC, altered AT1R ligand binding, though HC reduced estradiol and increased Ang II levels in plasma. These findings have significant clinical implications, indicating that administration of an AT1R antagonist, especially if estradiol levels are low, prior to an exposure therapy session may improve treatment outcomes in females.
Urogenital schistosomiasis is associated with signatures of microbiome dysbiosis in Nigerian adolescents
Authors: Ajibola Olumide , Rowan Aislinn D. , Ogedengbe Clement O. , Mshelia Mari B. , Cabral Damien J. , Eze Anthonius A. , Obaro Stephen , Belenky Peter 
Published: January 2019

AbstractUrogenital schistosomiasis is a neglected tropical disease caused by the parasiteSchistosoma haematobium, which resides in the vasculature surrounding the urogenital system. Previous work has suggested that helminthic infections can affect the intestinal microbiome, and we hypothesized thatS.haematobiuminfection could result in an alteration of immune system-microbiota homeostasis and impact the composition of the gut microbiota. To address this question, we compared the fecal microbiomes of infected and uninfected schoolchildren from the Argungu Local Government Area of Kebbi State, Nigeria, detecting significant differences in community composition between the two groups. Most remarkably, we observed a decreased abundance of Firmicutes and increased abundance of Proteobacteria – a shift in community structure which has been previously associated with dysbiosis. More specifically, we detected a number of changes in lower taxa reminiscent of inflammation-associated dysbiosis, including decreases in Clostridiales and increases in Moraxellaceae, Veillonellaceae, Pasteurellaceae, and Desulfovibrionaceae. Functional potential analysis also revealed an enrichment in orthologs of urease, which has been linked to dysbiosis and inflammation. Overall, our analysis indicates thatS.haematobiuminfection is associated with perturbations in the gut microbiota and may point to microbiome disruption as an additional consequence of schistosome infection.
Rapid diagnosis of Mycoplasma pneumonia infection by denaturation bubble-mediated strand exchange amplification: comparison with LAMP and real-time PCR
Authors: Shi Wenqiang , Wei Manman , Wang Qing , Wang Hongwei , Ma Cuiping , Shi Chao 
Published: January 2019

AbstractM. pneumoniae infection is often ignored due to its similar clinical symptom with respiratory tract infections caused by bacteria or viruses, and thus leading to misdiagnosis and delayed treatment. It is critical to develop a rapid, sensitive and specific diagnosis method. Denaturation Bubble-mediated Strand Exchange Amplification (SEA) was established, which is an isothermal method with only a primer pair and one Bst DNA polymerase. Notably, colorimetric SEA assay was developed with simple visual readout, making instrument-independent in detection step. The method could detect as low as 1.0 × 104 copies/mL genomic DNA within 60 min. Considering that more than 80% infected patients have 1.0 × 105−1.0 × 107 copies/mL M. pneumonia DNA, SEA is available for the practical diagnosis of M. pneumoniae in clinical specimens. Through comparing 224 sputum specimens, excellent performance of SEA assay with 90.48% sensitivity and 100% specificity relative to real-time PCR was observed. Compared with LAMP, a comparable sensitivity and low false positive rate was observed for SEA method. Therefore, SEA is a promising method for detecting M. pneumoniae directly from clinical specimens, which is especially suitable for point-of-care testing in primary care facilities and resource-limited settings with minimal equipment and technological expertises.
Novel benzofuran derivative DK-1014 attenuates lung inflammation via blocking of MAPK/AP-1 and AKT/mTOR signaling in vitro and in vivo
Authors: Xu Xuezhen , Kwon Ok-Kyoung , Shin In-Sik , Mali Jyotirling R. , Harmalkar Dipesh S. , Lim Yourim , Lee Gilhye , Lu Qili , Oh Sei-Ryang , Ahn Kyung-Seop , Jeong Hye-Gwang , Lee Kyeong 
Published: January 2019

AbstractBenzofuran derivatives have wide range of biological activities as anti-oxidant, anti-inflammatory and anticonvulsant agent. In this study, we investigated whether the novel benzofuran derivative, DK-1014 has the anti-inflammatory effects on macrophage and lung epithelial cells and anti-asthmatic effects on ovalbumin-treated mice. A series of 2-arylbenzofuran analogues were synthesized and evaluated for NO and interleukin-6 (IL-6) inhibition in LPS-stimulated Raw264.7 cells. Of these analogues, compounds 8, 22a, 22d, and 22 f (DK-1014) exhibited notable inhibitory activity with respect to IL-6 and NO production. In particular, compound DK-1014 strongly reduced IL-6, IL-8, and MMP-9 mRNA expression and IL-6, IL-8, and MCP-1 production in phorbol myristate acetate stimulated A549 cells, reduced MAPKs phosphorylation and c-fos translocation, and attenuated AKT, p70S6K and GSK phosphorylation. In vivo experiments were also performed on ovalbumin-sensitized and challenged BALB/c mice. DK-1014 reduced the airway hyperresponsiveness, inflammatory cell counts and cytokine levels (IL-4, 5, 13) in bronchial alveolar lavage fluid (BALF) and immunoglobulin E in serum, and attenuated inflammatory cell infiltration and mucus hypersecretion in lung tissue. These findings indicate that DK-1014 can protect against allergic airway inflammation through the AP-1 and AKT/mTOR pathways and could be useful source for the development of a therapeutic agent for asthma.
Exposure to environmental radionuclides associates with tissue-specific impacts on telomerase expression and telomere length
Authors: Kesäniemi Jenni , Lavrinienko Anton , Tukalenko Eugene , Boratyński Zbyszek , Kivisaari Kati , Mappes Tapio , Milinevsky Gennadi , Møller Anders Pape , Mousseau Timothy A. , Watts Phillip C. 
Published: January 2019

AbstractTelomeres, the protective structures at the ends of chromosomes, can be shortened when individuals are exposed to stress. In some species, the enzyme telomerase is expressed in adult somatic tissues, and potentially protects or lengthens telomeres. Telomeres can be damaged by ionizing radiation and oxidative stress, although the effect of chronic exposure to elevated levels of radiation on telomere maintenance is unknown for natural populations. We quantified telomerase expression and telomere length (TL) in different tissues of the bank vole Myodes glareolus, collected from the Chernobyl Exclusion Zone, an environment heterogeneously contaminated with radionuclides, and from uncontaminated control sites elsewhere in Ukraine. Inhabiting the Chernobyl Exclusion Zone was associated with reduced TL in the liver and testis, and upregulation of telomerase in brain and liver. Thus upregulation of telomerase does not appear to associate with longer telomeres but may reflect protective functions other than telomere maintenance or an attempt to maintain shorter telomeres in a stressful environment. Tissue specific differences in the rate of telomere attrition and apparent radiosensitivity weaken the intra-individual correlation in telomere length among tissues in voles exposed to radionuclides. Our data show that ionizing radiation alters telomere homeostasis in wild animal populations in tissue specific ways.
The increase of photosynthetic carbon assimilation as a mechanism of adaptation to low temperature in Lotus japonicus
Authors: Calzadilla Pablo Ignacio , Vilas Juan Manuel , Escaray Francisco José , Unrein Fernando , Carrasco Pedro , Ruiz Oscar Adolfo 
Published: January 2019

AbstractLow temperature is one of the most important factors affecting plant growth, it causes an stress that directly alters the photosynthetic process and leads to photoinhibition when severe enough. In order to address the photosynthetic acclimation response of Lotus japonicus to cold stress, two ecotypes with contrasting tolerance (MG-1 and MG-20) were studied. Their chloroplast responses were addressed after 7 days under low temperature through different strategies. Proteomic analysis showed changes in photosynthetic and carbon metabolism proteins due to stress, but differentially between ecotypes. In the sensitive MG-1 ecotype acclimation seems to be related to energy dissipation in photosystems, while an increase in photosynthetic carbon assimilation as an electron sink, seems to be preponderant in the tolerant MG-20 ecotype. Chloroplast ROS generation was higher under low temperature conditions only in the MG-1 ecotype. These data are consistent with alterations in the thylakoid membranes in the sensitive ecotype. However, the accumulation of starch granules observed in the tolerant MG-20 ecotype indicates the maintenance of sugar metabolism under cold conditions. Altogether, our data suggest that different acclimation strategies and contrasting chloroplast redox imbalance could account for the differential cold stress response of both L. japonicus ecotypes.
In silico comparison of protein-bound uremic toxin removal by hemodialysis, hemodiafiltration, membrane adsorption, and binding competition
Authors: Maheshwari Vaibhav , Thijssen Stephan , Tao Xia , Fuertinger Doris H. , Kappel Franz , Kotanko Peter 
Published: January 2019

AbstractProtein-bound uremic toxins (PBUTs) are poorly removed during hemodialysis (HD) due to their low free (dialyzable) plasma concentration. We compared PBUT removal between HD, hemodiafiltration (HDF), membrane adsorption, and PBUT displacement in HD. The latter involves infusing a binding competitor pre-dialyzer, which competes with PBUTs for their albumin binding sites and increases their free fraction. We used a mathematical model of PBUT/displacer kinetics in dialysis comprising a three-compartment patient model, an arterial/venous tube segment model, and a dialyzer model. Compared to HD, improvements in removal of prototypical PBUTs indoxyl sulfate (initial concentration 100 µM, 7% free) and p-cresyl sulfate (150 µM, 5% free) were: 5.5% and 6.4%, respectively, for pre-dilution HDF with 20 L replacement fluid; 8.1% and 9.1% for post-dilution HDF 20 L; 15.6% and 18.3% for pre-dilution HDF 60 L; 19.4% and 22.2% for complete membrane adsorption; 35.0% and 41.9% for displacement with tryptophan (2000 mg in 500 mL saline); 26.7% and 32.4% for displacement with ibuprofen (800 mg in 200 mL saline). Prolonged (one-month) use of tryptophan reduces the IS and pCS time-averaged concentration by 28.1% and 29.9%, respectively, compared to conventional HD. We conclude that competitive binding can be a pragmatic approach for improving PBUT removal.
Microbiome Alteration in Type 2 Diabetes Mellitus Model of Zebrafish
Authors: Okazaki Fumiyoshi , Zang Liqing , Nakayama Hiroko , Chen Zhen , Gao Zi-Jun , Chiba Hitoshi , Hui Shu-Ping , Aoki Takahiko , Nishimura Norihiro , Shimada Yasuhito 
Published: January 2019

AbstractUnderstanding the gut microbiota in metabolic disorders, including type 2 diabetes mellitus (T2DM), is now gaining importance due to its potential role in disease risk and progression. We previously established a zebrafish model of T2DM, which shows glucose intolerance with insulin resistance and responds to anti-diabetic drugs. In this study, we analysed the gut microbiota of T2DM zebrafish by deep sequencing the 16S rRNA V3-V4 hypervariable regions, and imputed a functional profile using predictive metagenomic tools. While control and T2DM zebrafish were fed with the same kind of feed, the gut microbiota in T2DM group was less diverse than that of the control. Predictive metagenomics profiling using PICRUSt revealed functional alternation of the KEGG pathways in T2DM zebrafish. Several amino acid metabolism pathways (arginine, proline, and phenylalanine) were downregulated in the T2DM group, similar to what has been previously reported in humans. In summary, we profiled the gut microbiome in T2DM zebrafish, which revealed functional similarities in gut bacterial environments between these zebrafish and T2DM affected humans. T2DM zebrafish can become an alternative model organism to study host-bacterial interactions in human obesity and related diseases.
Multi-omics dataset to decipher the complexity of drug resistance in diffuse large B-cell lymphoma
Authors: Fornecker Luc-Matthieu , Muller Leslie , Bertrand Frédéric , Paul Nicodème , Pichot Angélique , Herbrecht Raoul , Chenard Marie-Pierre , Mauvieux Laurent , Vallat Laurent , Bahram Seiamak , Cianférani Sarah , Carapito Raphaël , Carapito Christine 
Published: January 2019

AbstractThe prognosis of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains unsatisfactory and, despite major advances in genomic studies, the biological mechanisms underlying chemoresistance are still poorly understood. We conducted for the first time a large-scale differential multi-omics investigation on DLBCL patient’s samples in order to identify new biomarkers that could early identify patients at risk of R/R disease and to identify new targets that could determine chemorefractoriness. We compared a well-characterized cohort of R/R versus chemosensitive DLBCL patients by combining label-free quantitative proteomics and targeted RNA sequencing performed on the same tissues samples. The cross-section of both data levels allowed extracting a sub-list of 22 transcripts/proteins pairs whose expression levels significantly differed between the two groups of patients. In particular, we identified significant targets related to tumor metabolism (Hexokinase 3), microenvironment (IDO1, CXCL13), cancer cells proliferation, migration and invasion (S100 proteins) or BCR signaling pathway (CD79B). Overall, this study revealed several extremely promising biomarker candidates related to DLBCL chemorefractoriness and highlighted some new potential therapeutic drug targets. The complete datasets have been made publically available and should constitute a valuable resource for the future research.
Comparative analysis of cognitive impairment prevalence and its etiological subtypes in a rural area of northern China between 2010 and 2015
Authors: Lu Hui , Wang Xiao-Dan , Shi Zhihong , Yue Wei , Zhang Ying , Liu Shuai , Liu Shuling , Zhao Lei , Xiang Lei , Zhang Yajing , Guan Yalin , Su Wenhua , Li Zhiyong , Wang Jinhuan , Wisniewski Thomas , Ji Yong 
Published: January 2019

AbstractThe purpose of this study was to evaluate changes in the prevalence and risk factors of cognitive impairment (CI) by analyzing and comparing two cross-sectional epidemiological surveys of CI and its subtypes were performed in a rural area of northern China between 2010 and 2015. Residents aged ≥60 years were drawn in northern China. The Mini Mental State Examination (MMSE) is recommended to test for CI. Dementia was further categorised into Alzheimer’s disease (AD), vascular dementia (VaD), and dementia caused by other diseases (ODs). Mild cognitive impairment (MCI) was classified into MCI caused by AD (MCI-A), MCI caused by VaD (MCI-VD), and MCI caused by ODs (MCI-O). The prevalence of CI increased in China. The prevalence of all-cause CI was 30·5% (22.9% MCI and 7.6% dementia) in 2010. The prevalence of all-cause CI was 38.3% (27.8% MCI and 10.5% dementia) in 2015. Similar increases were observed for the prevalence of subtypes of dementia and MCI. These findings suggest an increasing prevalence of CI and its subtypes in China, which may be related to alterations in sociodemographic factors, vascular risk factors and lifestyle changes over time in these cohorts.
Imaging study of midface growth with bone-borne trans-sutural distraction osteogenesis therapy in growing cleft lip and palate patients
Authors: Tong Haizhou , Song Tao , Sun Xiaomei , Yin Ningbei , Liu Lei , Wang Xingang , Zhao Zhenmin 
Published: January 2019

AbstractTrans-sutural distraction osteogenesis (TSDO) promotes midface growth in growing cleft lip and palate (CLP) patients with midfacial hypoplasia. The superficial skeletal changes after therapy revealed rotation advancement of the midfacial skeleton associated with differential displacement in each segment, but reports rarely focus on the changes of internal structures, including circummaxillary sutures, the maxillary tuberosity and the maxillary sinus, which may play a crucial role during this process. This study evaluated the computed tomographic (CT) images of 26 growing CLP patients who received bone-borne TSDO therapy. The results revealed that the most prominent new bone formation occurred in the pterygomaxillary suture and pushed the P-point forward. The maxillary first molar exhibited significantly greater advancement compared with the P-point due to the growth of the maxillary tuberosity. The contribution ratio values of the advancement of the maxillary tuberosity and P-point to the maxillary first molar were 26% and 74%, respectively, in UCLP and 25% and 75%, respectively, in BCLP. Furthermore, the maxillary sinus volume was also significantly increased. In conclusion, midface growth with bone-borne TSDO therapy depends on both secondary displacement promoted by sutural bone formation mainly in the pterygomaxillary suture and primary displacement by growth of the maxillary tuberosity and maxillary sinus volume.
Improved Cd, Zn and Mn tolerance and reduced Cd accumulation in grains with wheat-based cell number regulator TaCNR2
Authors: Qiao Kun , Wang Fanhong , Liang Shuang , Wang Hong , Hu Zhangli , Chai Tuanyao 
Published: January 2019

AbstractSoil microelement deficiency and heavy metal contamination affects plant growth and development, but improving trace element uptake and reducing heavy metal accumulation by genetic breeding can help alleviate this. Cell number regulator 2 (TaCNR2) from common wheat (Triticum aestivum) are similar to plant cadmium resistance proteins, involved with regulating heavy metal translocation. Our aim was to understand the effect of TaCNR2 on heavy metal tolerance and translocation. In this study, real-time quantitative PCR indicated TaCNR2 expression in the wheat seedlings increased under Cd, Zn and Mn treatment. Overexpression of TaCNR2 in Arabidopsis and rice enhanced its stress tolerance to Cd, Zn and Mn, and overexpression in rice improved Cd, Zn and Mn translocation from roots to shoots. The grain husks in overexpressed rice had higher Cd, Zn and Mn concentrations, but the brown rice accumulated less Cd but higher Mn than wild rice. The results showed that TaCNR2 can transport heavy metal ions. Thus, this study provides a novel gene resource for increasing nutrition uptake and reducing toxic metal accumulation in crops.
Towards reconstructing intelligible speech from the human auditory cortex
Authors: Akbari Hassan , Khalighinejad Bahar , Herrero Jose L. , Mehta Ashesh D. , Mesgarani Nima 
Published: January 2019

AbstractAuditory stimulus reconstruction is a technique that finds the best approximation of the acoustic stimulus from the population of evoked neural activity. Reconstructing speech from the human auditory cortex creates the possibility of a speech neuroprosthetic to establish a direct communication with the brain and has been shown to be possible in both overt and covert conditions. However, the low quality of the reconstructed speech has severely limited the utility of this method for brain-computer interface (BCI) applications. To advance the state-of-the-art in speech neuroprosthesis, we combined the recent advances in deep learning with the latest innovations in speech synthesis technologies to reconstruct closed-set intelligible speech from the human auditory cortex. We investigated the dependence of reconstruction accuracy on linear and nonlinear (deep neural network) regression methods and the acoustic representation that is used as the target of reconstruction, including auditory spectrogram and speech synthesis parameters. In addition, we compared the reconstruction accuracy from low and high neural frequency ranges. Our results show that a deep neural network model that directly estimates the parameters of a speech synthesizer from all neural frequencies achieves the highest subjective and objective scores on a digit recognition task, improving the intelligibility by 65% over the baseline method which used linear regression to reconstruct the auditory spectrogram. These results demonstrate the efficacy of deep learning and speech synthesis algorithms for designing the next generation of speech BCI systems, which not only can restore communications for paralyzed patients but also have the potential to transform human-computer interaction technologies.
Novel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly properties
Authors: Cochet Florent , Facchini Fabio A. , Zaffaroni Lenny , Billod Jean-Marc , Coelho Helena , Holgado Aurora , Braun Harald , Beyaert Rudi , Jerala Roman , Jimenez-Barbero Jesus , Martin-Santamaria Sonsoles , Peri Francesco 
Published: January 2019

AbstractNew monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. A panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized with the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding of the synthetic compounds to purified, functional recombinant human MD-2 was studied by four independent methods. All compounds bound to MD-2 with similar affinities and inhibited in a concentration-dependent manner the LPS-stimulated TLR4 signaling in human and murine cells, while being inactive as TLR4 agonists when provided alone. A compound of the panel was testedin vivoand was not able to inhibit the production of proinflammatory cytokines in animals. This lack of activity is probably due to strong binding to serum albumin, as suggested by cell experiments in the presence of the serum. The interesting self-assembly property in solution of this type of compounds was investigated by computational methods and microscopy, and formation of large vesicles was observed by cryo-TEM microscopy.