bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laminin alpha 5 is Necessary for Mammary Epithelial Growth and Function by Maintaining Luminal Epithelial Cell Identity
Authors: Englund Johanna I , Cojoc Hanne , Blaas Leander , Ritchie Alexandra , Pentinmikko Nalle , Döhla Julia , Munne Pauliina , Patarroyo Manuel , Klefström Juha , Ivaska Johanna , Katajisto Pekka 
Published: December 2019

ABSTRACTEpithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet the exact roles of specific BM components remain unclear. Here, we demonstrate that expression of distinct laminin α-isoforms by luminal and basal mammary epithelial cells enforces lineage identity that is necessary for normal mammary gland growth and function. Laminin α5 (LMα5) is mainly expressed by the luminal epithelial cells, and it is necessary for pubertal mammary gland growth, pregnancy induced gland remodeling, and for alveolar function. Adhesion to LMα5 containing laminin promotes luminal traits in both luminal and basal epithelial cells, and reduces progenitor activity of basal epithelial cells. Mechanistically, we show thatLama5loss interferes with differentiation of hormone receptor positive luminal cells, which results in reduced Wnt4 expression and defective crosstalk between luminal and basal epithelial cells during gland remodeling. Our results reveal a novel BM-mediated mechanism, which regulates mammary gland remodeling and function via specification of luminal epithelial cells.
Perturbation analysis of a multi-morphogen Turing Reaction-Diffusion stripe patterning system reveals key regulatory interactions
Authors: Economou Andrew D. , Monk Nicholas A.M. , Green Jeremy B.A. 
Published: December 2019

AbstractPeriodic patterning is extremely widespread in developmental biology and is broadly modelled by Reaction-Diffusion (RD) processes. However, the minimal two-component RD system is vastly simpler than the multimolecular events that current biology is now able to describe. Moreover, RD models are typically underconstrained such that it is often hard to meaningfully relate the model architecture to real interactions measured experimentally. To address both these issues, we investigated the periodic striped patterning of the rugae (transverse ridges) in the roof of the mammalian palate. We experimentally implicated a small number of major signalling pathways and established theoretical limits on the number of pathway network topologies that can account for the stable spatial phase relationships of their observed signalling outputs. We further conducted perturbation analysis both experimentally and in silico, critically to assess the effects of perturbations on established patterns. We arrived at a relatively highly-constrained number of possible networks and found that these share some common motifs. Finally, we examined the dynamics of pattern appearance and discovered a core network consisting of epithelium-specific FGF and Wnt as mutually antagonistic “activators” and Shh as the “inhibitor”, which initiates the periodicity and whose existence constrains the network topology still further. Together these studies articulate the principles of multi-morphogen RD patterning and demonstrate the utility of perturbation analysis as a tool for constraining networks in this and, in principle, any RD system.
The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction
Authors: Pan Bo , Parajuli Nirmal , Tian Zongwen , Li Jie , Wu Penglong , Lewno Megan T. , Bedford Lynn , Mayer R. John , Fang Jing , Liu Jinbao , Cui Taixing , Su Huabo , Wang Xuejun 
Published: December 2019

ABSTRACTRationaleThe ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime for example, show cardiotoxicity. Moreover, UPS and ALP defects are implicated in the pathogenesis of a large subset of heart disease. Hence, a better understanding of the cross-talk between the two catabolic pathways should help advance cardiac pathophysiology and medicine.ObjectiveSystemic pharmacological proteasome inhibition (PSMI) was shown to increase p62/SQSTM1 expression and induce myocardial macroautophagy. The present study investigates whether cardiomyocyte-restricted PSMI activates myocardial ALP and, more importantly, how proteasome malfunction activates the ALP in the heart.Methods and ResultsMyocardial macroautophagy, transcription factor EB (TFEB) expression and activity, and p62 expression were markedly increased in mice with either cardiomyocyte-restricted ablation ofPsmc1(a 19S proteasome subunit gene) or pharmacological PSMI. In cultured cardiomyocytes, PSMI-induced increases in TFEB activation and p62 expression were blunted markedly by calcineurin inhibition (cyclosporine A) and by siRNA-mediatedMolcn1silence. PSMI induced remarkable increases in myocardial autophagic flux in wild type mice but not p62 null mice. In cultured wild type, but not p62-null, mouse cardiomyocytes, PSMI induced increases in LC3-II flux and in the lysosomal removal of ubiquitinated proteins. Myocardial TFEB activation by PSMI as reflected by TFEB nuclear localization and target gene expression was strikingly less in p62 null mice compared with wild type mice.Conclusions(1) The activation of cardiac macroautophagy by proteasomal malfunction is mediated by the Mocln1-calcineurin-TFEB-p62 pathway; (2) both Mocln1 and p62 form a feed-forward loop with TFEB during TFEB activation by proteasome malfunction; and (3) targeting the Mcoln1-calcineurin-TFEB-p62 pathway may provide new means to intervene cardiac ALP activation in a proteasome malfunction setting.
Role of omega‐6 and omega‐3 fatty acids in fetal programming
Authors: Shrestha Nirajan , Sleep Simone L. , Cuffe James S.M. , Holland Olivia J. , Perkins Anthony V. , Yau Suk Yu , McAinch Andrew J. , Hryciw Deanne H. 
Published: December 2019

AbstractMaternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha‐linolenic acid (ALA) are major omega‐6 (n‐6) and n‐3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n‐6 PUFA has increased gradually worldwide, and elevated n‐6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n‐6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n‐6 PUFA in fetal programming, the importance of a balance between n‐6 and n‐3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n‐6 and n‐3 PUFA contents in diets.
Alpha‐pinene promotes osteoblast differentiation and attenuates TNFα‐induced inhibition of differentiation in MC3T3‐E1 pre‐osteoblasts
Authors: Min Hyeon‐Young , Son Hyo‐Eun , Jang Won‐Gu 
Published: December 2019

AbstractAlpha‐pinene (α‐pinene) is an organic compound, found in the oils of many species of coniferous trees, especially pine. α‐Pinene reportedly has antioxidant and anti‐inflammatory activities; however, its effects on osteoblasts are unknown. This study investigated the effects of α‐pinene on osteoblast differentiation and tumour necrosis factor‐alpha (TNFα)‐induced inhibition of osteogenesis. Culture in control or osteogenic medium containing α‐pinene increased osteogenic marker expression. Alkaline phosphatase staining and alizarin red S staining confirmed that α‐pinene enhanced osteoblast differentiation. Also, α‐pinene attenuated TNFα‐induced inhibition of Smad1/5/9 phosphorylation and extracellular matrix mineralization. Taken together, our findings suggest that α‐pinene enhances osteoblast differentiation and mineralization in MC3T3‐E1 pre‐osteoblasts.
Cancer stemness contributes to cluster formation of colon cancer cells and high metastatic potentials
Authors: Kapeleris Joanna , Zou Hong , Qi Yan , Gu Yushu , Li Jingyun , Schoning Jennifer , Monteiro Michael J. , Gu Wenyi 
Published: December 2019

AbstractThe ability of cancer cells to form clusters is a characteristic feature in the development of metastatic tumours with drug resistance. Several studies demonstrated that clusters of circulating tumour cells (CTCs) have a greater metastatic potential to establish new tumours at secondary sites than single CTCs. However, the mechanism of cluster formation is not well understood. In this study, we investigated whether cancer stemness would contribute to cluster formation. We used a tumour sphere culture method to enrich cancer stem cells (CSCs) from colon cancer cells and found that during the second generation of sphere culture, clusters (between 3 and 5 cells) formed within the first 24 hours, whereas the rest remained as single cells. The clusters were analysed for stemness and metastatic potential, including gene expressions for cancer stemness (CD133 and Lgr5), epithelial‐mesenchymal transition (E‐cadherin and TGF‐β 1‐3) and hypoxia‐induced factors (HIF‐1α and HIF‐2α). The results showed that the clusters expressed higher levels of these genes and colon CSC surface markers (including CD24, CD44 and CD133) than the single cells. Among these markers, CD24 seemed the major contributor linking the cells into the clusters. These clusters also showed a stronger ability to both form colonies and migrate. Our data collectively suggest that colon cancer stemness contributes to cluster formation and that clustered cells exhibit a great metastatic potential. Our study thus provides a method to study the CTC clusters and derive insight into oncogenesis and metastasis.
No evidence of physiological stress in an urban animal: Comparison of fecal cortisol metabolites between urban and rural Eurasian red squirrels
Authors: Shimamoto Tatsuki , Uchida Kenta , Koizumi Itsuro , Matsui Motozumi , Yanagawa Hisashi 
Published: December 2019

AbstractOver the last few decades, urban environments have been regarded as alternative habitats for wildlife. Given the continuous anthropogenic disturbance, however, it remains largely unknown whether urban environments are truly beneficial to some animals or whether the animals are merely just surviving. Glucocorticoids, which play an important role in coping with environmental challenges, are often measured as primary biomarkers of physiological stress. Chronic secretions of these hormones can have deleterious effects on animal health. Some urban stressors are constantly present and may increase the risk of chronic stress. In this study, we compared fecal cortisol metabolite (FCM) levels to evaluate stress levels between an urban and rural population of Eurasian red squirrels Sciurus vulgaris. We hypothesized that if squirrels suffer from greater stress in urban environments, their FCM levels would be significantly higher than that of rural squirrels. Our results showed that FCM levels were not significantly different between the urban and rural squirrel populations, and urban squirrels did not weigh less than rural squirrels. We conclude that the urban squirrels were not subjected to greater stress than their rural counterparts. Urban environments may be preferable for red squirrels, possibly because of release from predators and increased food availability through artificial feeding.
Amino acids levels in early pregnancy predict subsequent gestational diabetes
Authors: Jiang Rong , Wu Shuhua , Fang Chen , Wang Chang , Yang Ya , Liu Chao , Hu Ji , Huang Yun 
Published: December 2019

AbstractBackgroundWe aimed to estimate the performance of amino acids levels in predicting the risk of subsequent gestational diabetes mellitus (GDM).MethodsA total of 431 women at 12 to 16 weeks of gestation in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Soochow University were recruited. High‐performance liquid chromatography electrospray tandem mass spectrometry was used to measure amino acids levels in maternal blood at 12 to 16 weeks of gestation. At 24 to 28 weeks of gestation, all participants were administered 75‐g oral glucose tolerance tests for the diagnosis of GDM.ResultsAlanine, isoleucine, and tyrosine levels in early pregnancy were significantly different between women who developed GDM and those who remained normal glucose tolerant. Logistic regressions showed that after adjustments for age, parity, body mass index, family history of diabetes, γ‐glutamyltranspeptidase, triglycerides, fasting glucose and fasting insulin levels, alanine (odds ratio [OR], 1.46; 95% CI, 1.05‐2.04; P = .027), isoleucine (OR, 1.48; 95% CI, 1.12‐1.96; P = .0062), and tyrosine (OR, 1.46; 95% CI, 1.07‐2.03; P = .020) levels in early pregnancy were independently associated with subsequent GDM. The addition of isoleucine and tyrosine into the conventional model improved the area under curve from 0.692 to 0.737 (P = .036) and significantly increased the net reclassification improvement (+13.7%, P = .0025).ConclusionsThe present study suggests that elevated isoleucine, tyrosine, and alanine levels are independently and significantly associated with subsequent incidence of GDM. New models including conventional risk factors, isoleucine and tyrosine levels in early pregnancy might help physicians identify high‐risk population of GDM.
Close relatives in population samples: Evaluation of the consequences for genetic stock identification
Authors: Östergren Johan , Palm Stefan , Gilbey John , Dannewitz Johan 
Published: December 2019

AbstractDetermining the origin of individuals in mixed population samples is key in many ecological, conservation and management contexts. Genetic data can be analyzed using genetic stock identification (GSI), where the origin of single individuals is determined using Individual Assignment (IA) and population proportions are estimated with Mixed Stock Analysis (MSA). In such analyses, allele frequencies in a reference baseline are required. Unknown individuals or mixture proportions are assigned to source populations based on the likelihood that their multilocus genotypes occur in a particular baseline sample. Representative sampling of populations included in a baseline is important when designing and performing GSI. Here, we investigate the effects of family sampling on GSI, using both simulated and empirical genotypes for Atlantic salmon (Salmo salar). We show that nonrepresentative sampling leading to inclusion of close relatives in a reference baseline may introduce bias in estimated proportions of contributing populations in a mixed sample, and increases the amount of incorrectly assigned individual fish. Simulated data further show that the induced bias increases with increasing family structure, but that it can be partly mitigated by increased baseline population sample sizes. Results from standard accuracy tests of GSI (using only a reference baseline and/or self‐assignment) gave a false and elevated indication of the baseline power and accuracy to identify stock proportions and individuals. These findings suggest that family structure in baseline population samples should be quantified and its consequences evaluated, before carrying out GSI.
Aberrant expansion of circulating CD4+CXCR5+CCR7loPD1hi Tfh precursor cells in idiopathic inflammatory myopathy
Authors: Zhang Lu , Li Wenli , Cai Ying , Liu Xia , Peng Qinglin , Liang Lin 
Published: December 2019

AbstractObjectiveTo determine circulating follicular T helper (Tfh) cell precursor and its relationship with clinical characteristics in idiopathic inflammatory myopathy (IIM).MethodsThe study population included 47 patients with IIM and 30 healthy controls. Circulating CD4+CXCR5+CCR7loPD‐1hi T cells and intracellular interleukin (IL)‐21 were assessed by flow cytometry. Serum IL‐21 levels were measured by enzyme‐linked immunosorbent assay. The disease activity was evaluated using myositis disease activity assessment visual analog scales (VAS) as well as muscle and physician global assessment (PGA).ResultsThe percentage of the CCR7loPD‐1hi subset cells within CD4+CXCR5+ T cells was significantly increased in patients with IIM compared to that in healthy controls (14.3 ± 6.5 vs 11.4 ± 2.6, P = .009). Patients with higher percentages of CCR7loPD‐1hi subsets presented with higher PGA VAS (P = .000), muscle VAS (P = .000), as well as serum creatinine kinase (CK) levels (P = .000) than those with lower percentages of CCR7loPD‐1hi subsets. IL‐21 expression significantly increased in CD4+CXCR5+CCR7loPD‐1hi T cells in patients with IIM compared to that in healthy controls (26.07 ± 7.38 vs 19.25 ± 5.67, P = .001). Meanwhile, both the CCR7loPD‐1hi subset and intracellular IL‐21 expression in IIM patients showed significantly positive correlation with PGA VAS, muscle VAS and serum CK levels. Circulating CD4+CXCR5+CCR7loPD‐1hi T cells and intracellular IL‐21 decreased significantly when disease was improved (P = .018; P = .028).ConclusionThe percentage of circulating CCR7loPD‐1hi subset among total CD4+CXCR5+ T cells and intracellular IL‐21 expression expanded and showed significant correlation with disease activity in IIM. The circulating follicular helper T cell precursor may be involved in the pathogenesis, especially muscle injury in IIM.
Routine management of postoperative delirium outside the ICU: Results of an international survey among anaesthesiologists
Authors: Bilotta Federico , Weiss Bjoern , Neuner Bruno , Kramer Sylvia , Aldecoa César , Bettelli Gabriella , Sanders Robert D. , Delp Simon M. , Spies Claudia D. 
Published: December 2019

BackgroundPostoperative delirium (POD) is a severe brain dysfunction. Although data indicate a high relevance, no survey has investigated the routine practice to monitor delirium outside the ICU setting after surgery. Prior to publishing of the new European Society of Anaesthesiology (ESA) guidelines on POD, an international survey was conducted to assess current practice.MethodsEuropean Society of Anaesthesiology‐endorsed online survey; Trial Registration: NCT‐identifier: 02513537.ResultsIn total, 566 respondents from 62 countries accessed, and 564 (99.6%) completed the survey (completion rate). Overall, 385 (68%) of the respondents reported that delirium is either “very relevant” or “relevant” for their daily clinical practice. In all, 38 (7%) of the respondents routinely monitor for delirium in >50% of all patients. Asked on the monitoring time point, more than half (n = 308, 55%) indicated to screen before or at recovery room discharge, 235 (42%) up to the first postoperative day, 143 (25%) up to 3 days, and 77 (14%) up to 5 postoperative days. Although there is a lack of long‐term monitoring, nearly all respondents (n = 530, 94%) reported to treat delirium. Availability of EEG/EMG‐based monitoring to assess the depth of anaesthesia was high in the study group (n = 547, 97%) and was used by more than one‐third of the respondents to reduce risk of burst suppression (n = 189, 34%).ConclusionAlthough delirium is perceived as a relevant condition among anaesthesiologists, there is a high demand for implementing monitoring strategies after publishing of the POD Guideline. The survey shows that tools necessary for POD Guideline implementation are available in the centres represented by the respondents.
Social capital and access to informal finance – evidence from Chinese private firms
Authors: Deng Lu , Jiang Ping , Li Sifei , Liao Mingqing 
Published: December 2019

AbstractThis study investigates how firms’ social capital affects their access to informal finance. We argue that social capital helps reduce information asymmetry, increase trust between related parties and enforce lending contracts, so it has positive effects on firms’ access to informal finance. Using novel survey data of Chinese private firms, we find that firms with more social capital have more access to informal finance with lower costs. Further tests show that the effect of social capital is more significant when firms are located in regions with less developed market and lower community’s social capital and during the 2008 financial crisis.
Concordance between health administrative data and survey‐derived diagnoses for mood and anxiety disorders
Authors: Edwards J. , Thind A. , Stranges S. , Chiu M. , Anderson K. K. 
Published: December 2019

ObjectiveTo assess whether estimates of survey structured interview diagnoses of mood and anxiety disorders were concordant with diagnoses of these disorders obtained from health administrative data.MethodsAll Ontario respondents to the 2012 Canadian Community Health Survey‐Mental Health (CCHS‐MH) were linked to health administrative databases at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Survey structured interview diagnoses were compared with health administrative data diagnoses obtained using a standardized algorithm. We used modified Poisson regression analyses to assess whether socio‐demographic factors were associated with concordance between the two measures.ResultsOf the 4157 Ontarians included in our sample, 20.4% had either a structured interview diagnosis (13.9%) or health administrative diagnosis (10.4%) of a mood or anxiety disorder. There was high discordance between measures, with only 19.4% agreement. Migrant status, age, employment, and income were associated with discordance between measures.ConclusionsOur findings indicate that previous estimates of the 12‐month prevalence of mood and anxiety disorders in Ontario may be underestimating the true prevalence, and that population‐based surveys and health administrative data may be capturing different groups of people. Understanding the limitations of data commonly used in epidemiologic studies is a key foundation for improving population‐based estimates of mental disorders.
The effect of maternal body mass index on duration of induced labor
Authors: Carlhäll Sara , Källén Karin , Blomberg Marie 
Published: December 2019

AbstractIntroductionObese primiparous women with induction of labor are at high risk for a cesarean section. There are contradictory results regarding time in induced labor in relation to maternal body mass index (BMI). It is important to characterize the course of induced labor to prevent unnecessary cesarean section. We aimed to evaluate whether the duration of labor was associated with maternal BMI in primiparous women with induction of labor.Material and methodsA national retrospective cohort study, including 15 259 primiparae with a single term pregnancy, admitted for induction of labor from January 2014 to August 2017. Data were obtained from the Swedish Pregnancy Registry. Cox regression analyses were used to illustrate the association between BMI and active labor and between BMI and time from admission until start of active labor.ResultsDuration of active labor was shorter in underweight women and prolonged in women with BMI ≥40 kg/m2 compared with women in other BMI classes, illustrated by Cox regression graphs (P < .001). The median durations of active labor in underweight women were 6.1 and 7.4 hours in women with BMI ≥40 kg/m2. The time from admission until start of active labor increased with maternal BMI, illustrated by Cox regression graphs (P < .001) and the median duration increased from 12.9 hours in underweight women to 22.6 hours in women with BMI ≥40 kg/m2. The cesarean section rate in active labor increased significantly with BMI (P < .001) from 7.4% in underweight women to 22.0% in women with BMI ≥40 kg/m2. Obese and normal weight women had similar rates of spontaneous vaginal delivery (69.9% in the total study population).ConclusionsThe duration of active labor was associated with maternal BMI for underweight women and women with BMI ≥40 kg/m2. Although women with BMI ≥40 kg/m2 who reached the active phase of labor had the same chance for a spontaneous vaginal delivery as normal weight women, the duration of active labor and the cesarean section rate were increased. The time from admission until start of active labor increased successively with maternal BMI.