bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of Smad4 reduces hepatic inflammation and fibrogenesis during nonalcoholic steatohepatitis progression
Authors: Qin Geng , Wang Guo Zhen , Guo Dan Dan , Bai Ru Xue , Wang Miao , Du Shi Yu 
Published: April 2018

OBJECTIVETo explore the effects of mothers against decapentaplegic homolog family member 4 (Smad4) deletion on inflammation and fibrogenesis in nonalcoholic steatohepatitis (NASH).METHODSBiopsied liver samples from NASH patients and normal liver tissue samples from patients who had received liver resection for trauma were collected. Smad4Co/Co and wild‐type (WT) mice were used to construct the NASH model using a high‐fat diet (HFD) or methionine‐ and choline‐deficient diet (MCD). HE staining and TUNEL assay were used to observe the pathological changes and cell apoptosis, respectively. Quantitative real‐time polymerase chain reaction was used to detect the expression of inflammatory, fibrogenesis and apoptosis‐related genes, and immunohistochemistry to determine the protein expression of SMAD4, MCP‐1 and α‐SMA.RESULTSSMAD4 protein expression significantly increased in NASH patients than in the control group. Compared with WT mice, HFD‐ and MCD‐fed Smad4Co/Co mice showed decreased hepatic steatosis, inflammation, liver cell apoptosis and nonalcoholic fatty liver activity score, reduced plasma glucose, triglyceride, free fatty acids, alanine aminotransferase and aspartate aminotransferase levels but increased adiponectin. Moreover, Smad4Co/Co decreased the expression of inflammatory markers (TNF‐α, MCP‐1, IFN‐γ), fibrogenetic markers (COL1A1, α‐SMA and TGF‐β1), lipogenic (Srebp1c, Fas and Acc) and proapoptotic genes (Bax and caspase‐3), but increased the expression of β‐oxidation (Ppar‐α, Cpt1 and Aco) and antiapoptotic genes (Bcl‐2).CONCLUSIONSmad4 deletion may inhibit lipogenesis, stimulate β‐oxidation, improve lipid metabolism and liver function, alleviate inflammation and fibrosis, and reduce cell apoptosis in NASH.
New lactic acid bacteria for skin health via oral intake of heat‐killed or live cells
Authors: Kimoto‐Nira Hiromi 
Published: April 2018

AbstractLactic acid bacteria play an essential role in the food industry in the manufacture of many fermented products (cheese, yogurt, fermented vegetables, etc.). Application of these organisms is now being extended to the area of health improvement, as their probiotic activities become known. Probiotics are defined as viable microorganisms that exert a beneficial effect on the health of the host when they are ingested in sufficient quantity. Lactic acid bacteria and bifidobacteria isolated from the human intestine are the most common probiotics used for human consumption. The development of new probiotics with new beneficial effects is eagerly awaited in the food industry. This review introduces Lactococcus, which are one of the genera of lactic acid bacteria and are mainly isolated from dairy products and fermented vegetables, as new probiotics, focusing especially on Lactococcus lactis H61, which improves skin status in Japanese women with oral intake of heat‐killed or live cells. The deduced mechanisms associated with the beneficial effects of strain H61 are also discussed.
Role of mechanical cues in shaping neuronal morphology and connectivity
Authors: Gangatharan Girisaran , Schneider‐Maunoury Sylvie , Breau Marie Anne 
Published: April 2018

AbstractNeuronal circuits, the functional building blocks of the nervous system, assemble during development through a series of dynamic processes including the migration of neurons to their final position, the growth and navigation of axons and their synaptic connection with target cells. While the role of chemical cues in guiding neuronal migration and axonal development has been extensively analysed, the contribution of mechanical inputs, such as forces and stiffness, has received far less attention. In this article, we review the in vitro and more recent in vivo studies supporting the notion that mechanical signals are critical for multiple aspects of neuronal circuit assembly, from the emergence of axons to the formation of functional synapses. By combining live imaging approaches with tools designed to measure and manipulate the mechanical environment of neurons, the emerging field of neuromechanics will add a new paradigm in our understanding of neuronal development and potentially inspire novel regenerative therapies.
Pulmonary vascular resistance determines mortality in end‐stage renal disease patients with pulmonary hypertension
Authors: Wolfe Jonathan D. , Hickey Gavin W. , Althouse Andrew D. , Sharbaugh Michael S. , Kliner Dustin E. , Mathier Michael A. , Wu Christine M. , Tevar Amit D. , Soman Prem 
Published: April 2018

AbstractThe multifactorial etiology of pulmonary hypertension (PH) in end‐stage renal disease (ESRD) includes patients with and without elevated pulmonary vascular resistance (PVR). We explored the prognostic implication of this distinction by evaluating pretransplant ESRD patients who underwent right heart catheterization and echocardiography. Demographics, clinical data, and test results were analyzed. All‐cause mortality data were obtained. Median follow‐up was 4 years. Of the 150 patients evaluated, echocardiography identified 99 patients (66%) with estimated pulmonary artery (PA) systolic pressure > 36 mm Hg, which correlated poorly with mortality (HR = 1.28, 95% CI 0.72‐2.27, P = .387). Right heart catheterization identified 88 (59%) patients with mean PA pressure ≥ 25 mm Hg. Of these, 70 had PVR ≤ 3 Wood units and 18 had PVR > 3 Wood units. Survival analysis demonstrated a significant prognostic effect of an elevated PVR in patients with high mean PA pressures (HR = 2.26, 95% CI 1.07‐4.77, P = .03), while patients with high mean PA pressure and normal PVR had equivalent survival to those with normal PA pressure. Despite the high prevalence of PH in ESRD patients, elevated PVR is uncommon and is a determinant of prognosis in patients with PH. Patients with normal PVR had survival equivalent to those with normal PA pressures.
Biotic homogeneity of putative biogeographic units in the Neotropics: A test with Sapotaceae
Authors: Serrano Julieth , Richardson James E. , Pennington Terence D. , Cortes‐B Rocio , Cardenas Dairon , Elliott Alan , Jimenez Ivan 
Published: April 2018

AbstractAimTo evaluate Morrone's (2001, Biogeografia de America Latina y el Caribe. Zaragoza, Spain: CYTED, ORCYT‐UNESCO, Sociedad Entomológica Aragonesa (SEA)) Neotropical regionalization by testing the prediction that biotas are more homogeneous within than among biogeographic units.LocationNeotropics.MethodsWe conducted pairwise comparisons of beta diversity of Sapotaceae species within and between biogeographic units in the hierarchical regionalization proposed by Morrone (2001, Biogeografia de America Latina y el Caribe. Zaragoza, Spain: CYTED, ORCYT‐UNESCO, Sociedad Entomológica Aragonesa (SEA)), at a spatial resolution of 1‐degree cells. We used a null model to control differences in sampling effort across 1‐degree cells and performed beta‐diversity comparisons conditional on geographic distance to control for distance decay of biotic similarity.ResultsNone of the biogeographic units proposed by Morrone (2001, Biogeografia de America Latina y el Caribe. Zaragoza, Spain: CYTED, ORCYT‐UNESCO, Sociedad Entomológica Aragonesa (SEA)) was biotically homogeneous with respect to all other units at the same hierarchical level. This was the case even for units commonly reported to be isolated and to host distinctive taxa like “Choco.” However, five of 45 biogeographic units were biotically homogenous relative to several other units. These units were “Cuba,” “Chaco,” “Varzea,” “Cauca” and “Costa Pacífica Mexicana.” Also, beta diversity within units was often lower than beta diversity between units at relatively short geographic distances.Main conclusionsThe distribution of Sapotaceae species showed generally low biotic homogeneity within Morrone's (2001, Biogeografia de America Latina y el Caribe. Zaragoza, Spain: CYTED, ORCYT‐UNESCO, Sociedad Entomológica Aragonesa (SEA)) biogeographic units and did not support his biogeographic regionalization. This result suggests a strong role for dispersal and biotic interchange among biogeographic units and across barriers like the Andes. It also casts doubt on the usefulness of Morrone's (2001, Biogeografia de America Latina y el Caribe. Zaragoza, Spain: CYTED, ORCYT‐UNESCO, Sociedad Entomológica Aragonesa (SEA)) biogeographic units as tools for the identification of priority areas for the conservation of biodiversity. However, relatively high biotic homogeneity within some biogeographic units suggests that they capture significant spatial patterns. In particular, noteworthy biotic homogeneity within “Cuba,” “Cauca” and “Costa Pacifica Mexicana” could be explained by isolation. Also, in “Costa Pacifica Mexicana,” patterns of biotic homogeneity could reflect closer affinities to humid lowland montane forest in Central America than to lowland rain forest in South America. Finally, substantial biotic homogeneity within “Varzea” could result from common adaptation to edaphic environments near the Amazon River.
Technology transfer via foreign patents in Germany, 1843–77
Authors: Donges Alexander , Selgert Felix 
Published: April 2018

AbstractThis article analyses the spread of innovation in mid‐nineteenth‐century Germany using foreign patents as an indicator for technology transfer. It introduces a new dataset of over 1,400 patents granted in the Grand Duchy of Baden between 1843 and 1877. The data show that Baden's technology import via foreign patents from German and non‐German inventors was important. This technology transfer was broadly based, although technologies related to the textile and machine‐building industries are prominent in the data. The decision to file a patent in Baden was driven by competition and the risk of imitation. Using a gravity model with city‐level data, we find evidence that technology transfer through patents reflected existing trade links. The strong correlation between technologies filed by foreigners and domestic inventors provides further evidence that the risk of imitation fostered patent‐based technology transfer during the mid‐nineteenth century. Furthermore, we show that foreigners filed patents predominantly in industries that accounted for a high share of the workforce in Baden.
Individualistic cultures and crash risk
Authors: Dang Tung Lam , Faff Robert , Luong Hoang , Nguyen Lily 
Published: April 2018

AbstractThis study examines whether individualistic national culture is associated with stock price crash risk (‘crash risk’) for a sample of firms from 36 countries over the period of 1990–2015. We find robust evidence that firms in more individualistic cultural settings exhibit higher future crash risk. Digging deeper, we find that earnings management, excessive managerial risk‐taking, and investors’ difference of opinion and overconfidence are all possible explanations for the positive effect of individualism on crash risk. Overall, our findings suggest that individualism, as a key cultural dimension, has an important impact on investor welfare, manifested through crash risk.
Fitness costs of key point mutations that underlie acaricide target‐site resistance in the two‐spotted spider miteTetranychus urticae
Authors: Bajda Sabina , Riga Maria , Wybouw Nicky , Papadaki Stavrini , Ouranou Eleni , Fotoukkiaii Seyedeh Masoumeh , Vontas John , Van Leeuwen Thomas 
Published: April 2018

AbstractThe frequency of insecticide/acaricide target‐site resistance is increasing in arthropod pest populations and is typically underpinned by single point mutations that affect the binding strength between the insecticide/acaricide and its target‐site. Theory predicts that although resistance mutations clearly have advantageous effects under the selection pressure of the insecticide/acaricide, they might convey negative pleiotropic effects on other aspects of fitness. If such fitness costs are in place, target‐site resistance is thus likely to disappear in the absence of insecticide/acaricide treatment, a process that would counteract the spread of resistance in agricultural crops. Hence, there is a great need to reliably quantify the various potential pleiotropic effects of target‐site resistance point mutations on arthropod fitness. Here, we used near‐isogenic lines of the spider mite pestTetranychus urticaethat carry well‐characterized acaricide target‐site resistance mutations to quantify potential fitness costs. Specifically, we analyzed P262T in the mitochondrial cytochrome b, the combined G314D and G326E substitutions in the glutamate‐gated chloride channels, L1024V in the voltage‐gated sodium channel, and I1017F in chitin synthase 1. Five fertility life table parameters and nine single‐generation life‐history traits were quantified and compared across a total of 15 mite lines. In addition, we monitored the temporal resistance level dynamics of populations with different starting frequency levels of the chitin synthase resistant allele to further support our findings. Three target‐site resistance mutations, I1017F and the co‐occurring G314D and G326E mutations, were shown to significantly and consistently alter certain fitness parameters inT. urticae. The other two mutations (P262T and L1024V) did not result in any consistent change in a fitness parameter analyzed in our study. Our findings are discussed in the context of the global spread ofT. urticaepesticide resistance and integrated pest management.
Progress in melanoma modelling in vitro
Authors: Marconi Alessandra , Quadri Marika , Saltari Annalisa , Pincelli Carlo 
Published: April 2018

AbstractMelanoma is one of the most studied neoplasia, although laboratory techniques used for investigating this tumor are not fully reliable. Animal models may not predict the human response due to differences in skin physiology and immunity. In addition, international guidelines recommend to develop processes that contribute to the reduction, refinement and replacement of animals for experiments (3Rs). Adherent cell culture has been widely used for the study of melanoma to obtain important information regarding melanoma biology. Nonetheless, these cells grow in adhesion on the culture substrate which differs considerably from the situation in vivo. Melanoma grows in a 3D spatial conformation where cells are subjected to a heterogeneous exposure to oxygen and nutrient. In addition, cell‐cell and cell‐matrix interaction play a crucial role in the pathobiology of the tumor as well as in the response to therapeutic agents. To better study, melanoma new techniques, including spherical models, tumorospheres and melanoma skin equivalents, have been developed. These 3D models allow to study tumors in a microenvironment that is more close to the in vivo situation and are less expensive and time‐consuming than animal studies. This review will also describe the new technologies applied to skin reconstructs such as organ‐on‐a‐chip that allows skin perfusion through microfluidic platforms. 3D in vitro models, based on the new technologies, are becoming more sophisticated, representing at a great extent the in vivo situation, the “perfect” model that will allow less involvement of animals up to their complete replacement, is still far from being achieved.
The effects of vitamin K1 and vitamin K2 on the proliferation, cytokine production and regulatory T‐cell frequency in peripheral blood mononuclear cells of paediatric atopic dermatitis patients
Authors: Meng Kehan , Xu Wencheng , Miura Taro , Suzuki Shunsuke , Chiyotanda Masako , Tanaka Sachiko , Sugiyama Kentaro , Kawashima Hisashi , Hirano Toshihiko 
Published: April 2018

AbstractWe estimated the pharmacological efficacy of vitamin K1 (VK1) and VK2 on the mitogen‐activated peripheral blood mononuclear cells (PBMCs) of paediatric atopic dermatitis (AD) patients. VK2 suppressed the in vitro proliferation of T‐cell mitogen‐activated PBMCs of AD patients. In contrast, VK1 had little effect on the PBMC proliferation. The IL‐2 production from the activated PBMCs of AD patients significantly increased (P < .05), while the production significantly decreased by 100 μmol L−1 VK2 (P < .01). In addition, 100 μmol L−1 VK2 reduced the percentage of CD4+ and CD4+CD25+ cells in PBMCs. These results suggest that VK2 can modulate T‐cell function in PBMCs of AD patients.
Oxygen isotope analysis of bacterial and fungal manganese oxidation
Authors: Sutherland K. M. , Wankel S. D. , Hansel C. M. 
Published: April 2018

AbstractThe ability of micro‐organisms to oxidize manganese (Mn) from Mn(II) to Mn(III/IV) oxides transcends boundaries of biological clade or domain. Many bacteria and fungi oxidize Mn(II) to Mn(III/IV) oxides directly through enzymatic activity or indirectly through the production of reactive oxygen species. Here, we determine the oxygen isotope fractionation factors associated with Mn(II) oxidation via various biotic (bacteria and fungi) and abiotic Mn(II) reaction pathways. As oxygen in Mn(III/IV) oxides may be derived from precursor water and molecular oxygen, we use a twofold approach to determine the isotope fractionation with respect to each oxygen source. Using both 18O‐labeled water and closed‐system Rayleigh distillation approaches, we constrain the kinetic isotope fractionation factors associated with O atom incorporation during Mn(II) oxidation to −17.3‰ to −25.9‰ for O2 and −1.9‰ to +1.8‰ for water. Results demonstrate that stable oxygen isotopes of Mn(III/IV) oxides have potential to distinguish between two main classes of biotic Mn(II) oxidation: direct enzymatic oxidation in which O2 is the oxidant and indirect enzymatic oxidation in which superoxide is the oxidant. The fraction of Mn(III/IV) oxide‐associated oxygen derived from water varies significantly (38%–62%) among these bio‐oxides with only weak relationship to Mn oxidation state, suggesting Mn(III) disproportionation may account for differences in the fraction of mineral‐bound oxygen from water and O2. Additionally, direct incorporation of molecular O2 suggests that Mn(III/IV) oxides contain a yet untapped proxy of of environmental O2, a parameter reflecting the integrated influence of global respiration, photorespiration, and several other biogeochemical reactions of global significance.
Treatment of single maxillary gingival recession associated with non‐carious cervical lesion: Randomized clinical trial comparing connective tissue graft alone to graft plus partial restoration
Authors: Santamaria Mauro Pedrine , Silveira Camila Augusto , Mathias Ingrid Fernandes , Neves Felipe Lucas da Silva , dos Santos Lúcio Murilo , Jardini Maria Aparecida Neves , Tatakis Dimitris N. , Sallum Enilson Antônio , Bresciani Eduardo 
Published: April 2018

AbstractBackgroundGingival recession (GR) is frequently associated with non‐carious cervical lesion (NCCL) forming a combined defect (CD). The aim of this study was to evaluate a new multidisciplinary protocol for CDs.MethodsForty patients presenting 40 Miller's Class I or II GR defects associated with B+ tooth cervical defect were randomly allocated to one of the following treatments: test group (n = 20), partial restoration (PR) of the NCCL, in which the apical border of the restoration was placed 1 mm beyond the cement–enamel junction estimation, and connective tissue graft (CTG + PR) and Control Group (n = 20), odontoplasty of the NCCL and connective tissue graft (CTG). Clinical, aesthetic and patient‐centred outcomes were evaluated.ResultsAfter 12 months, CD coverage rates were 75.3% (2.5 ± 1.0 mm) for CTG + PR and 74.6% (2.4 ± 1.1 mm) for CTG (p > 0.05). The estimated complete root coverage was 60% (n = 12) for CTG + PR and 70% (n = 14) for CTG. CTG + PR resulted in significantly better dentin hypersensitivity (DH) reduction (p = 0.034). Both groups resulted in aesthetic improvements; however, the CTG + PR group showed better gingival contour results.ConclusionsCTG and CTG + PR were effective to treat CD. Use of PR resulted in better gingival margin contour and DH reduction, without effect on CD coverage by CTG. (NCT02817763).
Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia
Authors: Bekele A. , Gebreselassie N. , Ashenafi S. , Kassa E. , Aseffa G. , Amogne W. , Getachew M. , Aseffa A. , Worku A. , Raqib R. , Agerberth B. , Hammar U. , Bergman P. , Aderaye G. , Andersson J. , Brighenti S. 
Published: April 2018

AbstractObjectiveImmunotherapy using vitamin D (vitD3) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB).MethodsA randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear‐positive or smear‐negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6‐month chemotherapy. Primary end‐point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention‐to‐treat (mITT, n = 348) and per‐protocol (n = 296) analyses. Secondary end‐points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations.ResultsMost subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L−1). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (−0.52, 95% CI −0.93, −0.10; P = 0.015) while the modified TB score was reduced at week 8 (−0.58, 95% CI −1.02, −0.14; P = 0.01) and 16 (−0.34, 95% CI −0.64, −0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum‐smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%).ConclusionDaily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease‐specific complications, while the intervention had no effect on bacterial clearance in sputum.