bluuebunny/crossref_metadata_2025 huggingface dataset:
Human CYP2E1‐dependent mutagenicity of benzene and its hydroxylated metabolites in V79‐derived cells: Suppression and enhancement by ethanol pretreatment
Authors: Hu Keqi , Cai Lu , Li Zihuan , Glatt Hansruedi , Shi Ming , Liu Yungang
Published: April 2020

Benzene is a human carcinogen that requires metabolic activation. We previously observed that benzene and its hydroxylated metabolites induce micronuclei in mammalian cells expressing human CYP2E1. This study was initially aimed to study another endpoint, the induction of gene mutations by those compounds in the same cell models. A V79‐derived cell line expressing human CYP2E1 and sulfotransferase (SULT) 1A1 (V79‐hCYP2E1‐hSULT1A1) pretreated with ethanol (a CYP2E1 stabilizer) was used in the hprt gene mutagenicity assay. Phenol, hydroquinone, catechol, and 1,2,4‐trihydroxybenzene all induced gene mutations, while they were inactive, or only weakly positive (hydroquinone), in parental V79‐Mz cells. Unexpectedly, benzene was non‐mutagenic in both cell lines, but it became positive in V79‐hCYP2E1‐hSULT1A1 cells using regimes of short exposure/long recovery without ethanol pretreatment, for both gene mutations and micronuclei formation. In silico molecular simulation showed binding energies and positions favorable for each compound to be oxidized by human CYP2E1, benzene demonstrating the highest affinity. By tunnel analysis, ethanol binding did not limit benzene to pass tunnel S, which was specifically active for benzene. However, its end product, acetic acid, decreased the occurrence of tunnel S from 5.4 to 2.2% and extended the length of its bottleneck from 5.5 to 9.0 Å. With residual ethanol molecules still being present in CYP2E1 for a period of time after benzene exposure, the acetic acid formed could limit the entrance of benzene, thus inhibit its metabolic activation. In summary, ethanol may interfere with the activation of benzene to mutagenic metabolites, at least in cultured cells.
An experimental investigation of the nonlinear gas flow and stress‐dependent permeability of shale fractures
Authors: Shen Zhonghui , Zhou Lei , Su Xiaopeng , Li Honglian , Tang Jiren , Zheng Xuelin
Published: April 2020

The fluid flow characteristics in shale fractures are of great significance for shale gas reservoir evaluation and exploitation. In this study, artificial tension fractures in shale were used to simulate the hydraulic fractures formed by fracturing, and a gas flow test under different pressure gradients was conducted. The nonlinear gas flow and stress‐dependent permeability characteristics were analyzed. The experimental results show the following: (a) CO2 flow in shale fractures exhibits strong nonlinearity. Forchheimer's law, which considers gas compressibility, satisfactorily describes the nonlinear relationship between the flow rate and the pressure gradients in shale fractures. (b) The permeability sensitivity of shale fractures under stress is very strong, and the exponential relationship better describes the pressure dependency of the permeability for the tested shale samples. The permeability of the shale fractures is similar when measured parallel or perpendicular to bedding. Furthermore, the pressure dependence of fractures in shale obeys the Walsh permeability model. (c) As the effective stress increases, the nonlinear flow behavior appears earlier. Based on the Reynolds number and the nonlinear coefficient, a friction factor model is proposed. (d) The normalized transmissivity exhibits a strong correlation with the Reynolds number. CO2 flow through shale fractures is generally dominated by transitional flow. The critical Reynolds number ranges from 1.8 to 102.88 and decreases with increasing effective stress.
The Effect of Herbicide Formulations and Herbicide–Adjuvant Mixtures on Aquatic Food Web Species of the Sacramento–San Joaquin Delta, California, USA
Authors: Stillway Marie E. , Teh Swee J.
Published: April 2020

Herbicides have recently been designated as one of the most frequently detected chemical types in aquatic systems. We evaluated the effect of the herbicide formulations Clearcast® (active ingredient imazamox) and Galleon® SC (active ingredient penoxsulam), in conjunction with the adjuvant Agri-dex®, on the diatom Thalassiosira pseudonana and the copepod Eurytemora affinis and whether their application in invasive aquatic weed control has acutely negative effects on important delta food web species. Herbicide–adjuvant mixtures were more toxic than herbicide formulations alone. For the diatom, 50% inhibition concentration (IC50) were 84.4 mg/L for Clearcast, >100 mg/L for Galleon SC, and 38.5 mg/L for Agri-dex. In the herbicide mixture diatom tests, IC50s decreased to 2.8 mg/L for Clearcast + 64 mg/L Agri-dex and to 6.6 mg/L for Galleon SC + 41 mg/L Agri-dex. In the copepod tests, 50% effect concentrations (EC50s) were 45.4 mg/L for Agri-dex, 31.2 mg/L for Galleon SC, and >100 mg/L for Clearcast. When tested together, EC50s were reduced to 24.1 for Galleon SC and 67.6 mg/L for Clearcast in the presence of 50 mg/L Agri-dex. Environmentally relevant herbicide–adjuvant mixture ratios were at the no-observed-effect level. Mixture interactions between herbicides and adjuvants indicate the potential for increased toxicity in herbicide formulations and tank mixes, especially in consideration of the unlisted, proprietary ingredients which are included in herbicide formulations, making predicting nontarget effects challenging. Environ Toxicol Chem 2020;39:1375–1381. © 2020 SETAC

Abstract

Herbicide formulations and herbicide–adjuvant mixtures were added to individual test replicates containing either the copepod Eurytemora affinis (top row) or the diatom Thalassiosira pseudonana (bottom row). Test treatments were conducted in quadruplicate, and species were tested separately.
Effect of feeding regimen on meat quality, MyHC isoforms, AMPK, and PGC‐1α genes expression in the biceps femoris muscle of Mongolia sheep
Authors: Hou Yanru , Su Lin , Su Rina , Luo Yulong , Wang Bohui , Yao Duo , Zhao Lihua , Jin Ye
Published: April 2020

The effects of two feeding regimens on meat quality, myosin heavy chain (MyHC) types, and key factors regulating muscle fiber type (AMP‐activated protein kinase [AMPK] and peroxisome proliferator‐activated receptor‐coactivator‐1α [PGC‐1α]) in the biceps femoris muscle of Mongolia sheep were investigated. A total of 20 Mongolia sheep were weaning for 90 days and divided into two groups (pasture group (P) and confinement group (C)) at 10.36 ± 0.35 kg of weaning weight. After weaning, sheep were pasture fed or confinement fed for 9 months. The results showed that live weights, carcass weight, intramuscular fat (IMF), and Warner–Bratzler shear force (WBSF) in P group were significantly lower (p < .05) than that in C group. Compared with P group, color evaluations with respect to L* and b* values were significantly higher (p < .05) in C group. Expression of the MyHC I gene in the P group was significantly higher, while MyHC IIa and MyHC IIb genes expression was significantly lower (p < .05) than that in C group. Also, AMPK activity and expression of AMPKα2 and PGC‐1α genes were significantly higher (p < .05) in P group compared with C group. The present study indicated that muscle fiber composition was one of the key differences leading to the differences of meat quality in different feeding regimens. AMPK, particularly AMPKα2, and PGC‐1α were considered to be two key factors regulating muscle fiber types in Mongolia sheep. The results support that AMPK activity and the expression of AMPKα2 and PGC‐1α genes may affect the composition of muscle fibers; thus, AMPK activity and the expression of AMPKα2 and PGC‐1α genes had an effect on meat quality by changed composition of muscle fibers.
Comparative study of the nutritional composition of local brown rice, maize (obaatanpa), and millet—A baseline research for varietal complementary feeding
Authors: Yankah Nancy , Intiful Freda Dzifa , Tette Edem M. A.
Published: April 2020

Introduction

Childhood malnutrition remains a major public health issue of concern particularly in sub‐Saharan Africa, and inadequate complementary feeding is a common cause. Promoting dietary diversity is one way of tackling this problem. High dependence on maize has its limitations; modifying other local staples into complementary foods can be a feasible alternative to promote optimum nutrition.

Objectives

Comparing the nutritional composition of brown rice to millet and maize to determine its beneficial value as complementary food.

Methods

Experimental study was carried out at the Department of Nutrition and Food Science of University of Ghana. Samples of maize, millet, and brown rice were obtained from the Ministry of Agriculture, Accra and nutritional contents analyzed. Statistical Package for Social Sciences version 20.0 and ANOVA were used to assess differences.

Results

Results showed brown rice contained the highest content of carbohydrates (77.94 ± 0.32) % and zinc (12.15 ± 0.21) mg while millet had the highest protein (10.49 ± 0E‐7) mg and fat (4.99 ± 0.46) % content. Maize contained highest amount of calcium (21.24 ± 0.14) mg. Iron was only found in millet (10.72 ± 0.15) mg. The zinc content per 100 g of all three (3) cereals was above RDA. All three (3) cereals contributed significantly <10% to the RDA of calcium. Iron content of millet contributed more than 90% to RDA.

Conclusions

Locally produced brown rice is rich in zinc and carbohydrates compared to millet and maize. Thus, can be used for complementary feed but, given the low protein and iron content, it may need to be fortified or diversified and used as a cereal blend.
Assessment of aflatoxin in milk and feed samples and impact of seasonal variations in the Punjab, Pakistan
Authors: Akbar Naveed , Nasir Muhammad , Naeem Naureen , Ahmad Mansur‐ud‐Din , Saeed Farhan , Anjum Faqir Muhammad , Iqbal Sanaullah , Imran Muhammad , Tufail Tabussam , Shah Faiz‐ul‐Hassan , Atif Muhammad
Published: April 2020

The present study was designed to assess the incidence of aflatoxin contamination in animal feed and raw milk samples (total 240 each) collected from dairy farms during the complete year of 2015. These samples were collected through a cluster random sampling technique by dividing the province of Punjab, Pakistan into five clusters (north, south, east, west and central). Factors (environmental & physical) affecting aflatoxin contamination in milk and animal feed at farms were also studied. The AFM1 levels in raw milk & AFB1 levels in feed samples were analyzed by using the ELISA technique. Results demonstrated that overall about 53% raw milk samples from dairy farms were contaminated beyond the US MRL (0.50 µg/L) for AFM1 with than average level of 0.59 µg/L, while the 95% farm feed samples were exceeding the FDA MRL (20 µg/kg) of AFB1 with average level of 43 µg/kg. During winter season, the concentration of AFM1 was higher in all clusters with avg 0.68 µg/L, while the AFB1 contamination was highest in the spring season with avg 54 µg/kg. Market feed prices had negative correlation with AFB1 contamilevels, which were further supported by the positive correlation between quantity of feed at farms with AFM1 and AFB1 contamination. Results exhibited significantly positive impact of environmental factors on milk and feed aflatoxin contamination levels, whereas temperature showed an inverse relationship with AFM1 and AFB1 levels. The study recommends need of synergistic extension work to support dairy farms and highlight the contamination levels for regulatory bodies to introduce strategic policies for control measures.
Climate change shapes the future evolution of plant metabolism
Authors: Xu Sophia Y. , Weng Jing‐Ke
Published: April 2020

Planet Earth has experienced many dramatic atmospheric and climatic changes throughout its 4.5‐billion‐year history that have profoundly impacted the evolution of life as we know it. Photosynthetic organisms, and specifically plants, have played a paramount role in shaping the Earth's atmosphere through oxygen production and carbon sequestration. In turn, the diversity of plants has been shaped by historical atmospheric and climatic changes: plants rose to this challenge by evolving new developmental and metabolic traits. These adaptive traits help plants to thrive in diverse growth conditions, while benefiting humanity through the production of food, raw materials, and medicines. However, the current rapid rate of climate change caused by human activities presents unprecedented new challenges to the future of plants. Here, we discuss the potential effects of modern climate change on plants, with specific attention to plant specialized metabolism. We explore potential avenues of future scientific investigations, powered by cutting‐edge methods such as synthetic biology and genome engineering, to better understand and mitigate the consequences of rapid climate change on plant fitness and plant usage by humans.
Unravelling selection signatures in a single dog breed suggests recent selection for morphological and behavioral traits
Authors: Friedrich Juliane , Talenti Andrea , Arvelius Per , Strandberg Erling , Haskell Marie J. , Wiener Pamela
Published: April 2020

Strong selection has resulted in substantial morphological and behavioral diversity across modern dog breeds, which makes dogs interesting model animals to study the underlying genetic architecture of these traits. However, results from between‐breed analyses may confound selection signatures for behavior and morphological features that were coselected during breed development. In this study, we assess population genetic differences in a unique resource of dogs of the same breed but with systematic behavioral selection in only one population. We exploit these different breeding backgrounds to identify signatures of recent selection. Selection signatures within populations were found on chromosomes 4 and 19, with the strongest signals in behavior‐related genes. Regions showing strong signals of divergent selection were located on chromosomes 1, 24, and 32, and include candidate genes for both physical features and behavior. Some of the selection signatures appear to be driven by loci associated with coat color (Chr 24; ASIP) and length (Chr 32; FGF5), while others showed evidence of association with behavior. Our findings suggest that signatures of selection within dog breeds have been driven by selection for morphology and behavior. Furthermore, we demonstrate that combining selection scans with association analyses is effective for dissecting the traits under selection.
Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval, and combining them attenuates the acquisition rate of spatial reference memory
Authors: Hauser Jonas , Llano López Luis H. , Feldon Joram , Gargiulo Pascual A. , Yee Benjamin K.
Published: April 2020

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over‐generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.
Numerical and experimental investigation on capture of CO2 and other pollutants from an SI engine using the physical adsorption technique
Authors: Subramaniam Mohankumar , Satish S. , Solomon Jenoris Muthiya , Sathyamurthy Ravishankar
Published: April 2020

Carbon dioxide (CO2) is considered as a major contributor to global warming. Automobile contributes to around 65% of total carbon dioxide emissions globally when compared with other sources. On considering the upcoming stringent emission norms, this problem needs to be addressed properly. In this proposed study, an attempt is made to capture CO2 and other emissions from spark ignition engines using activated carbon as an adsorbent. In the initial part of this study, a numerical investigation on backpressure was carried out by varying the porosity factor of activated carbon. Computational analysis is carried out by placing activated carbon at three different variations. It is done by varying three different porosity percentages 30, 35, and 45 by placing activated carbon at three different locations. The final study reveals that activated carbon placed at the PC 35‐3 layout shows optimum backpressure and high filtration efficiency when compared with the other two layouts. Then, the PC35‐3 layout is fabricated and tested on a three‐cylinder, carburetted, variable speed, water‐cooled petrol engine at various load conditions (0%, 25%, 50%, 75%, and 100%.). Final results show that considerable amount of hydrocarbon, carbon monoxide, and CO2 gets reduced while operating the engine at idle and part load conditions and reduced exhaust gas temperature.
One‐carbon metabolism‐related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study
Authors: Antwi Samuel O. , Petrick Jessica L. , Campbell Peter T. , Norez Daniel A. , Stevens Victoria L. , Liao Linda M. , Roberts Lewis R. , Patel Tushar , McGlynn Katherine A.
Published: April 2020

Deficient intake of micronutrients involved in one‐carbon metabolism (eg, choline, methionine, vitamin B12 and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but is under‐investigated in humans. We investigated the association between one‐carbon metabolism‐related micronutrient intake and HCC risk in a prospective cohort of 494 860 participants with 16 years of follow‐up in the NIH‐AARP study. Dietary intakes and supplement use were ascertained at baseline using a food‐frequency questionnaire. Total intake (diet plus supplements) of the following one‐carbon metabolism‐related micronutrients were calculated: folate, methionine and vitamins B2 (riboflavin), B3 (niacin), B6 and B12. These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16‐year follow‐up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B3 intake was associated with a lower HCC risk (HRQ5 vs Q1 = 0.60; 95% CI = 0.42‐0.85; Ptrend = .008), and the association remained significant when all six micronutrients were examined simultaneously (HRQ5 vs Q1 = 0.32; 95% CI = 0.18‐0.55; Ptrend < .0001). Among participants with >3 years of follow‐up, higher total vitamin B3 intake was again associated with lower risk (HRQ5 vs Q1 = 0.37; 95% CI = 0.20‐0.68; Ptrend = .001), whereas higher total vitamin B6 intake was associated with higher risk (HRQ5 vs Q1 = 2.04; 95% CI = 1.02‐4.07; Ptrend = .04). Restricted cubic spline analyses showed a dose‐response inverse association between total vitamin B3 intake and HCC risk, and dose‐response positive association between total vitamin B6 intake and HCC risk. The study suggests that higher vitamin B3 intake is associated with lower HCC risk, whereas higher vitamin B6 intake is associated with increased risk.
Development and validation of a stromal immune phenotype classifier for predicting immune activity and prognosis in triple‐negative breast cancer
Authors: Zheng Shaoquan , Zou Yutian , Xie Xinhua , Liang Jie‐ying , Yang Anli , Yu Kai , Wang Jian , Tang Hailin , Xie Xiaoming
Published: April 2020

Our study aims to construct a prognosis‐related immune phenotype classifier for predicting clinical prognosis and immune activity in triple‐negative breast cancer (TNBC). A total of 237 patients with TNBC from Sun Yat‐sen University Cancer Center (SYSUCC) and 533 patients with TNBC from public datasets were included in our study. A stromal immune quantified index was generated with a LASSO Cox regression model based on five prognosis‐related immune cells evaluated by CIBERSORT or IHC and was used to determine immune phenotypes. Immune features were evaluated in the samples before chemotherapy. A total of 119 patients in the SYSUCC training cohort were classified into immune Phenotypes A and B according to the density of stromal CD4+ T cells, γδ T cells, monocytes, M1 macrophages and M2 macrophages. Phenotype A predicted better survival than Phenotype B, and the classification was further validated in the testing cohort of 118 patients and the validation cohort of 533 patients. In the combined cohort, significant differences were found in Phenotype A compared to Phenotype B for the 5‐year overall survival (83.5% vs 65.8%, respectively, P < .01) and the 5‐year disease‐free survival (87.3% vs 76.0%, respectively, P < .01). In Phenotype A, immune‐related pathways were significantly enriched, and a higher level of immune checkpoint molecules, including PD‐L1, PD‐1 and CTLA‐4, could be observed. The immune phenotype classification was an independent prognostic indicator for TNBC and might serve as a potential predictor for immune activity within the tumor microenvironment.
General and reproductive health among women after an episode of severe maternal morbidity: Results from the COMMAG study
Authors: Ferreira Elton C. , Costa Maria L. , Pacagnella Rodolfo C. , Silveira Carla , Andreucci Carla B. , Zanardi Dulce M. , Santos Juliana P. , Angelini Carina R. , Souza Renato T. , Parpinelli Mary A. , Sousa Maria H. , Cecatti Jose G.
Published: April 2020

Objective

To assess general and reproductive health in women after severe maternal morbidity (SMM).

Methods

A retrospective cohort study was performed at a tertiary maternity hospital. Women with SMM criteria who delivered during 2008–2012 were included in the SMM group. The control group included a random sample of women without SMM delivering in the same year of cases. Both groups were compared regarding sociodemographic/obstetric characteristics, general and reproductive health, using χ2, Yates χ2, Fisher exact, and Mann‐Whitney tests.

Results

There were 315 women in the SMM group and 323 women in the control group. The SMM group was older and had a history of more medical conditions (hypertension, diabetes, obesity), cesarean deliveries, preterm births, and perinatal deaths. Breastfeeding was negatively affected in these women, as was fertility. The SMM group had a non‐significant trend of fewer children after index pregnancy, had new complications in subsequent pregnancies, and required specialized medical care, besides higher risk of death.

Conclusion

Women experiencing SMM are at higher risk of general and reproductive health problems after pregnancy, including risk of death. Therefore, their surveillance and follow‐up should continue beyond 42 days postpartum, highlighting the importance of more specialized health care.
Introduction to the special section: The development of infant mental health home visiting in Michigan state government
Authors: Tableman Betty , Ludtke Mary
Published: April 2020

This issue of the Infant Mental Health Journal presents the first papers from a tripartite evaluation study of state‐sponsored infant mental health home visiting program in Michigan, United States. This series of studies has been led by Kate Rosenblum PhD and Maria Muzik MD, Department of Psychiatry, the University of Michigan and faculty from the Michigan Collaborative for Infant Mental Health Research for the State of Michigan, Department of Health and Human Services, Mental Health Services for Children, to fulfill the requirements of state legislation (State of Michigan Act No. 291, Public Acts of 2013) that required that all home visiting programs meet certain requirements to be established as an evidence‐based practice. In this introduction, we provide a historical context for the delivery of infant mental health home visiting through the community mental health system in the state of Michigan.
Is deflation costly after all? The perils of erroneous historical classifications
Authors: Kaufmann Daniel
Published: April 2020

I estimate average economic activity during periods of inflation and deflation while accounting for measurement errors in 19th century prices. These measurement errors lead to underestimation (overestimation) of economic activity during periods of inflation (deflation). By exploiting multiple deflation indicators, it is possible to recover the true relationship; the shortfall of US industrial production growth during periods of deflation ranges from −4.5 pp to −7.6 pp, instead of −2 pp. I also find a negative relationship between deflation and real activity in the UK. I then examine the cross‐country variation in the estimates for eleven countries. The patterns are consistent with stronger biases for countries with more serious measurement errors in prices.
Spatial autocorrelation analysis on two‐dimensional images of Mueller matrix for diagnosis and differentiation of cervical precancer
Authors: Zaffar Mohammad , Pradhan Asima
Published: April 2020

The spatial autocorrelation and correlation map of amplitude and phase anisotropy along with depolarization parameter from the stroma of uterine cervix utilizing their Mueller matrix (MM) images have been reported for early diagnosis of cervical cancer and differentiation of precancerous stages. The comparative results of the evaluation of the spatial autocorrelation over MM images of optically anisotropic collagen structures from normal and various grades of cervical precancer reflect significant alterations which are correlated with the pathological changes. The spatially varying polarizance from different region of anisotropic stromal region gets correlated within a given spatial lag during the precancerous changes. The diattenuation governing elements M12, M13 and M14 clearly discriminate normal and various grades of precancerous cervical tissue through their autocorrelation profile and correlation map. Evaluation of autocorrelation of spatially varying linear birefringence and linear‐45 birefringence characterized by MM elements M34 and M43 and M24 and M42 are not found to differ between the precancer grades, indicating that these changes may be arising from highly directional collagen network while the changes displayed by MM elements M23 and M32 faithfully represent that the chirality of the stromal region is compromised as the cervical cancer evolves and only one type of nature dominates.
FAK Promotes Early Osteoprogenitor Cell Proliferation by Enhancing mTORC1 Signaling
Authors: Qi Shuqun , Sun Xiumei , Choi Han Kyoung , Yao Jinfeng , Wang Li , Wu Guomin , He Yun , Pan Jian , Guan Jun-Lin , Liu Fei
Published: April 2020

Focal adhesion kinase (FAK) has important functions in bone homeostasis but its role in early osteoprogenitor cells is unknown. We show herein that mice lacking FAK in Dermo1-expressing cells exhibited low bone mass and decreased osteoblast number. Mechanistically, FAK-deficient early osteoprogenitor cells had decreased proliferation and significantly reduced mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling, a central regulator of cell growth and proliferation. Furthermore, our data showed that the pharmacological inhibition of FAK kinase-dependent function alone was sufficient to decrease the proliferation and compromise the mineralization of early osteoprogenitor cells. In contrast to the Fak deletion in early osteoprogenitor cells, FAK loss in Col3.6 Cre-targeted osteoblasts did not cause bone loss, and Fak deletion in osteoblasts did not affect proliferation, differentiation, and mTORC1 signaling but increased the level of active proline-rich tyrosine kinase 2 (PYK2), which belongs to the same non–receptor tyrosine kinase family as FAK. Importantly, mTORC1 signaling in bone marrow stromal cells (BMSCs) was reduced if FAK kinase was inhibited at the early osteogenic differentiation stage. In contrast, mTORC1 signaling in BMSCs was not affected if FAK kinase was inhibited at a later osteogenic differentiation stage, in which, however, the concomitant inhibition of both FAK kinase and PYK2 kinase reduced mTORC1 signaling. In summary, our data suggest that FAK promotes early osteoprogenitor cell proliferation by enhancing mTORC1 signaling via its kinase-dependent function and the loss of FAK in osteoblasts can be compensated by the upregulated active PYK2. © 2020 American Society for Bone and Mineral Research.

Abstract

Schematic model of the differential roles of FAK in the cells of osteoblast lineage. The model depicts the mechanisms of FAK action at three distinct stages of osteoblast lineage in which the roles of FAK have been addressed by genetic and pharmacological approaches as well as the respective Cre transgenes used to target Fak, including Dermo1-Cre (this study), Osterix-Cre,(10)Col3.6-Cre (this study), and Col2.3-Cre.(9) Red ↔ indicates that the loss of FAK in osteoblasts can be compensated by the upregulated active PYK2.
Complete active space analysis of a reaction pathway: Investigation of the oxygen–oxygen bond formation
Authors: Han Ruocheng , Luber Sandra
Published: April 2020

Water nucleophilic attack is an important step in water oxidation reactions, which have been widely studied using density functional theory (DFT). Nevertheless, a single‐determinant DFT picture may be insufficient for a deeper insight into the process, in particular during the oxygen–oxygen bond formation. In this work, we use complete active space self‐consistent field calculations and describe an approach for a complete active space analysis along a reaction pathway. This is applied to the water nucleophilic attack at a Ru‐based catalyst, which has successfully been used for efficient water oxidation and in silico design of new water oxidation catalysts recently.
Synthesis of dehydroepiandrosterone by co‐immobilization of keto reductase and glucose dehydrogenase
Authors: Zhang Junliang , Pu Tian , Xu Ying , Huang Junhai , Chen Daijie , Shao Lei
Published: April 2020

BACKGROUND

Dehydroepiandrosterone (DHEA), a steroid hormone drug and a precursor of other steroid hormone drugs, is industrially important. We aimed to establish the co‐immobilization of keto reductase and glucose dehydrogenase by a crosslinked enzyme aggregate (co‐CLEA) and to determine whether co‐CLEAs can improve DHEA yield compared with crude enzymes.

RESULTS

Heterologous expression plasmids containing genes coding for keto reductase or glucose dehydrogenase were constructed. The size of each of these proteins was determined using SDS‐PAGE and purification on a nickel column. After optimizing the expression conditions for these two enzymes, the co‐CLEAs were prepared with 80% acetone as a precipitant and 0.005% glutaraldehyde as a crosslinking agent. Compared with the crude enzyme solutions, the co‐CLEAs showed better thermal stability and pH stability. After six cycles of use, the co‐CLEAs still showed 70% (keto reductase) and 46% (glucose dehydrogenase) of their initial activities. After four reaction cycles, the accumulated production of DHEA using the co‐CLEAs reached 183 g L–1.

CONCLUSIONS

This research provides a possible strategy for the production of clinically useful DHEA through co‐immobilization. © 2020 Society of Chemical Industry
Arc‐disjoint strong spanning subdigraphs of semicomplete compositions
Authors: Bang‐Jensen Jørgen , Gutin Gregory , Yeo Anders
Published: April 2020

A strong arc decomposition of a digraph is a decomposition of its arc set into two disjoint subsets and such that both of the spanning subdigraphs and are strong. Let be a digraph with vertices and let be digraphs such that has vertices . Then the composition is a digraph with vertex set and arc set
We obtain a characterization of digraph compositions which have a strong arc decomposition when is a semicomplete digraph and each is an arbitrary digraph. Our characterization generalizes a characterization by Bang‐Jensen and Yeo (2003) of semicomplete digraphs with a strong arc decomposition and solves an open problem by Sun, Gutin, and Ai (2019) on strong arc decompositions of digraph compositions in which is semicomplete and each is arbitrary. Our proofs are constructive and imply the existence of a polynomial algorithm for constructing a strong arc decomposition of a digraph , with semicomplete, whenever such a decomposition exists.
Topologically 4‐chromatic graphs and signatures of odd cycles
Authors: Simons Gord , Tardif Claude , Wehlau David
Published: April 2020

We investigate group‐theoretic “signatures” of odd cycles of a graph, and their connections to topological obstructions to 3‐colourability. In the case of signatures derived from free groups, we prove that the existence of an odd cycle with trivial signature is equivalent to having the coindex of the hom‐complex at least 2 (which implies that the chromatic number is at least 4). In the case of signatures derived from elementary abelian 2‐groups we prove that the existence of an odd cycle with trivial signature is a sufficient condition for having the index of the hom‐complex at least 2 (which again implies that the chromatic number is at least 4).
Hospital‐acquired rotavirus acute gastroenteritis in 10 consecutive seasons in Umbria (Italy)
Authors: Camilloni Barbara , Alunno Anna , Nunzi Emilia , Sarnari Laura , Ianiro Giovanni , Monini Marina
Published: April 2020

Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young (aged <5 years) children. Several studies showed that RVA is one of the main cause of nosocomial gastroenteritis in hospitalized pediatric population worldwide, with an incidence ranging from 8 to 33 cases per 100 hospitalized children. Nosocomial infections, in which AGE symptoms develop at least 2 days after admission, may severely affect children already admitted to hospital for other causes. This study aimed to define the trends of the RVA genotypes through statistical analysis of the data obtained by the rotavirus surveillance in Umbria in 10 consecutive seasons, from 2007‐2008 to 2016‐2017, with update information on hospital‐acquired RVA AGE. During RVA gastroenteritis surveillance in Umbria (Italy) in 2007 to 2017, a total of 741 RVA positive faecal samples were collected from children hospitalized with AGE, and RVA strains were genotyped following standard EuroRotaNet protocols. Of the 741 analyzed samples, 75 (10%) were reported to be hospital‐acquired. Comparing the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections, we observed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community except in 2010 to 2011, 2011 to 2012, and 2012 to 2013 when G1P[8], G4P[8] and the novel strain G12P[8] caused a large community‐ and hospital‐acquired outbreak. Of the 741 analyzed samples, 75 (10%) were reported to be hospital‐acquired. Comparing the distributions of the RVA genotypes circulating in the community or associated with nosocomial infections, we observed a different distribution of genotypes circulating inside the hospital wards, with respect to those observed in the community except in 2010 to 2011, 2011 to 2012, and 2012 to 2013 when G1P[8], G4P[8], and the novel strain G12P[8] caused a large community‐ and hospital‐acquired outbreak. The information from this study will be useful to implement guidelines for preventing nosocomial RVA AGE, which should include an improved management of the hospitalized patients and an increase in vaccination coverage.
Determination of potential biotin interference on accuracy of results of serologic assays for various viral hepatitis markers
Authors: Kodani Maja , Poe Amanda , Drobeniuc Jan , Mixson‐Hayden Tonya
Published: April 2020

Biotin taken orally can interfere with some diagnostic immunoassays, including those for thyroid hormones, ferritin, and markers of infectious disease. Assays affected are ones that use streptavidin‐biotin in their design. The goal of our study was to examine the effect of biotin concentrations of up to 1200 ng/mL on three serological assays performed on VITROS 3600 system, Immunoglobulin M (IgM) antibodies to hepatitis A virus (anti‐HAV), total anti‐HAV, and IgM antibodies to hepatitis B virus core antigen (anti‐HBc), by spiking serum samples with variable amounts of biotin. No false‐negative results were generated with either concentration of biotin for total anti‐HAV (65/65). Likewise, biotin caused no false‐positive IgM anti‐HAV results (59/59) with either concentration of biotin; however, 6.7% false negativity was found for IgM anti‐HAV when samples were spiked with 1200 ng/mL of biotin. Conversely, 100% false positivity (30/30) was produced by biotin interference in total anti‐HAV negative specimens with both concentrations of biotin. False negativity rate was 87.5% in IgM anti‐HBc positive samples when biotin levels were at 1200 ng/mL. These data show that individuals taking biotin‐containing supplements may test false‐positive in some serologic assays using streptavidin‐biotin chemistries. Further studies are warranted to determine the extent of biotin interference resulting in false‐positive and negative results and their impact, if any, on surveillance and diagnostic settings.
The passion bug: How and when do leaders inspire work passion?
Authors: Ho Violet T. , Astakhova Marina N.
Published: April 2020

Drawing from signaling theory, we propose a work passion transfer model where leaders' passion is transmitted to employees through the former's leadership style and is contingent on employees' perceived importance of performance to self‐esteem (IPSE). Data from 201 supervisor–employee dyads from the health‐care industry show that leaders' harmonious passion led to employees' harmonious passion through charismatic leadership, whereas contingent reward leadership accounted for the transfer of obsessive passion; IPSE did not play a moderating role for either form of passion. Results from a supplementary study further reveal that the link between leadership and employee passion operated through employees' perception of leader passion and that employees' IPSE accentuated for the relationship between perceived leader obsessive passion and employees' obsessive passion. This study advances research in work passion, leadership, and signaling theory and provides important implications for managerial practice.
Expression of alarmins in a murine rotator cuff tendinopathy model
Authors: Zhang Ying , Deng Xiang‐Hua , Lebaschi Amir H. , Wada Susumu , Carballo Camila B. , Croen Brett , Ying Liang , Rodeo Scott A.
Published: April 2020

The aim of this study was to investigate the presence of alarmins in a novel murine rotator cuff tendinopathy model. Alarmins have been described as essential early activators of an immune response to tissue damage. Subacromial impingement was induced in both shoulders of 37 male C57Bl/6 mice by placement of a small metal clip in the subacromial space. Animals were allocated to different time points up to 6 weeks. The morphology and cellularity of the supraspinatus tendon were evaluated by hematoxylin‐eosin staining, alcian blue, and picrosirius red. The expression and localization of alarmins interleukin‐33 (IL‐33), c (HMGB1), hypoxia‐inducible factor‐1 subunit α (HIF1α), and S100A9 were evaluated by immunohistochemical staining and quantitative polymerase chain reaction. The percentage of positively stained cells with HMGB1 and IL‐33 was significantly increased in the impingement group at 1w, 4w, and 6w. HIF1α staining was higher in the impingement group at 1w and 6w compared with the control group. HMGB1 gene expression was higher in the 5d impingement group and 6w impingement group. The gene expression of HIF1α was upregulated at all‐time points in the impingement group (5d, 2w, 4w, and 6w). The expression of the S100A9 gene was also upregulated in the 5d impingement group. This is the first study to demonstrate the involvement of alarmins in the early phase of tendinopathy using a reproducible animal model. Alarmins may play an important role in the early phases of the development of tendinopathy They may represent potential therapeutic targets for treatment of tendinopathy.
Evaluation of mental health training for community pharmacy staff members and consumers
Authors: Shams Sara , Hattingh Hendrika Laetitia
Published: April 2020

Background

Community pharmacy staff in rural and remote areas need to have the skills to recognise mental health signs and symptoms, provide support and appropriate advice.

Aims

To evaluate the impact of Mental Health First Aid (MHFA) training through collaborative sessions attended by pharmacy staff and community members.

Methods

Pharmacy staff, alongside members of the local farming community, attended collaborative MHFA training in four Queensland towns. This study evaluated the training through pre‐ and post‐training questionnaires and email feedback following practice application of skills.

Results

Thirty‐two pharmacy staff and 14 community members participated in both pre‐ and post‐ questionnaires; 10 males and 36 females varying in age between 18 and 65 with the majority (26, 72.2%) aged 30–49 years. Participants’ understanding of the need to ask a person directly about suicide changed significantly through the training. The pre‐and post‐course surveys demonstrated a difference in knowledge of both the consumers and pharmacy staff members. Community members’ perception about how pharmacy staff can assist with mental health issues changed significantly and pharmacy staff reported an increase in confidence to approach consumers regarding their mental health. Qualitative feedback from consumers and pharmacy staff 8–12 weeks following the training was positive.

Conclusion

Pharmacy staff members are well placed to provide mental health support to farming communities. A collaborative mental health training approach in rural and remote areas that involved pharmacy staff and local community members showed improved knowledge, skills and collaboration between staff and consumers. This approach could easily be adapted to other contexts.
Climate control on stacked paleosols in the Pleistocene of the Po Basin (northern Italy)
Authors: Bruno Luigi , Marchi Michela , Bertolini Ilaria , Gottardi Guido , Amorosi Alessandro
Published: April 2020

Paleosols are recurrent features in alluvial successions and provide information about past sedimentary dynamics and climate change. Through sedimentological analysis on six sediment cores, the mud‐dominated succession beneath the medieval ‘Two Towers’ of Bologna was investigated down to 100 m depth. A succession of weakly developed paleosols (Inceptisols) was identified. Four paleosols (P1, P2, P3 and PH) were radiocarbon‐dated to 40–10 cal ka bp. Organic matter and CaCO3 determinations indicate low groundwater levels during soil development, which spanned periods < 5 ka. The development and burial of soils, which occurred synchronously in the Bologna region and in other sectors of the Po Plain, are interpreted to reflect climatic and eustatic variations. Climatic oscillations, at the scale of the Bond cycles, controlled soil development and burial during Marine Isotope Stage (MIS) 3 (P1 and P2). Rapid sea‐level oscillations probably induced soil development at the MIS 3/2 transition (P3) and favored burial of PH after 10 ka bp. Weakly developed paleosols in alluvial successions can provide clues to millennial‐scale climatic and environmental variations. In particular, the paleosol‐bearing succession of the Po Plain represents an unprecedent record of environmental changes across the Late Pleistocene (MIS 3 and 2) in the Mediterranean region.
Raman spectroscopic analysis and imaging in two cases of benign cementoma: Comparison with dental and bone tissues
Authors: Chappard Daniel , Guillaume Bernard , Teman Gil , Kün‐Darbois Jean‐Daniel
Published: April 2020

Benign cementoma is a rare tumor of the jaws whose origin is still debating. The tumor may derive from the dental cementum or the bone surrounding the socket. We have studied the profiles of enamel, dentine, and cementum from normal teeth and alveolar and cortical bone of the mandible. Raman spectroscopy was used to compare the spectra of these tissues embedded in poly(methylmethacrylate) from 300 to 3,100 cm−1. The degree of mineralization, carbonate‐to‐phosphate ratio, and crystallinity were derived. Tissue hydration was determined by measuring the ratio of the 813 cm−1 band of methacrylate to the 960 cm−1 band of phosphate. Raman spectroscopic imaging was obtained on large tissue areas with a bandwidth from 500 to 1,620 cm−1. Maps of the different peak ratio were obtained to analyze the mineral and organic phases (crystallinity, carbonate‐to‐phosphate, degree of mineralization) together with tissue hydration. Cementomas appeared highly heterogeneous, and their matrix possessed histological and spectroscopic characteristics that resemble highly calcified woven bone with a poor organization of the hydroxyapatite crystals.
A Concise Review on Nano‐emulsion Formation by the Phase Inversion Composition (PIC) Method
Authors: Feng Jin , Rodríguez‐Abreu Carlos , Esquena Jordi , Solans Conxita
Published: April 2020

Nano‐emulsion formation by the phase inversion composition method is reviewed. The relationship between phase behavior and nano‐emulsion formation is revised with emphasis on the key role of phase transitions involving changes in the sign of the curvature of the surfactant layer (inversion) via zero‐average‐curvature structures such as bicontinuous microemulsions or lamellar liquid crystalline phases. The different low‐energy methods that can be involved in a nano‐emulsification process at constant temperature are also discussed.