bluuebunny/crossref_metadata_2025 huggingface dataset:
Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus
Authors: Katahira Jun , Ishikawa Hiroki , Tsujimura Kakeru , Kurono Sadamu , Hieda Miki
Published: February 2019

A multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the HSPA1A gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked HSP70 transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for HSP70 transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of HSP70 transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the HSPA1A locus.
Distribution of emphysema and fibrosis in idiopathic pulmonary fibrosis with coexisting emphysema
Authors: Kinoshita Yoshiaki , Watanabe Kentaro , Ishii Hiroshi , Kushima Hisako , Fujita Masaki , Nabeshima Kazuki
Published: February 2019

Aims

Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome that results from tobacco smoking. Emphysema and fibrosis in CPFE patients have been considered to exist separately, with emphysema in the upper lobes and interstitial pneumonia in the lower lobes. The aim of this study was to examine the intrapulmonary distribution of fibrosis and emphysema in clinically diagnosed patients with idiopathic pulmonary fibrosis (IPF) and coexisting emphysema.

Methods and results

Among IPF patients (n = 40) who had been autopsied or pneumonectomised for lung transplantation from 1993 to 2018, we retrospectively selected patients with IPF and coexisting emphysema (n = 19) on the basis of the appearance on chest computed tomography (IPF patients with emphysema). We then histologically determined the intrapulmonary distribution of emphysema and fibrosis in the upper lobes and the lower lobes separately. In 15 of the 19 IPF patients with emphysema (79%), fibrosis and emphysema coexisted in the upper lobes and the lower lobes. No patients showed emphysema exclusively in the upper lobes and fibrosis exclusively in the lower lobes.

Conclusions

In the autopsied and pneumonectomised specimens of IPF patients with emphysema, craniocaudal separation of emphysema and fibrosis (emphysema in the upper lobes and interstitial pneumonia in the lower lobes) was histologically rare; coexistence or collision of fibrosis and emphysema in each lobe was common.
Validation of a predictive method for sunscreen formula evaluation using gene expression analysis in a Chinese reconstructed full‐thickness skin model
Authors: Liu Y. , Wang R. , He X. , Dai H. , Betts R. J. , Marionnet C. , Bernerd F. , Planel E. , Wang X. , Nocairi H. , Cai Z. , Qiu J. , Ding C.
Published: February 2019

Objective

This study aimed to establish a predictive in vitro method for assessing the photoprotective properties of sunscreens using a reconstructed full‐thickness skin model.

Materials and Methods

A full‐thickness skin model reconstructed with human fibroblasts and keratinocytes isolated from Chinese skin was exposed to daily UV radiation (DUVR). We examined the transcriptomic response, identifying genes for which expression was modulated by DUVR in a dose‐dependent manner. We then validated the methodology for efficacy evaluation of different sunscreens formulas.

Results

The reconstructed skin model was histologically consistent with human skin, and upon DUVR exposure, the constituent fibroblasts and keratinocytes exhibited transcriptomic alterations in pathways associated with oxidative stress, inflammation and extracellular matrix remodelling. When used to evaluate sunscreen protection on the model, the observed level of protection from UV‐induced gene expression was consistent with the corresponding protection factors determined clinically and allowed for statistical ranking of sunscreen efficacy.

Conclusions

Within this study we show that quantification of gene modulation within the reconstructed skin model is a biologically relevant approach with sensitivity and predictability to evaluate photoprotection products.
Nuclear receptor hormone receptor 39 is required for locust moulting by regulating the chitinase and carboxypeptidase genes
Authors: Zhao X.‐M. , Qin Z.‐Y. , Zhang J. , Yang Y. , Jia P. , Yang Q. , Ma E.‐B. , Zhang J.‐Z.
Published: February 2019

The nuclear receptor‐mediated 20‐hydroxyecdysone (20E) signalling pathway plays crucial roles in insects by initiating and regulating moulting and metamorphosis. In the present study, we identified and characterized a cDNA encoding a putative nuclear receptor protein (Locusta migratoria hormone receptor 39, LmHR39) based on L. migratoria transcriptomics data. Reverse‐transcription quantitative PCR (RT‐qPCR) revealed that LmHR39 shows low‐level expression in the early days of fifth‐instar nymphs, and peak expression occurs on day 5, which is followed by a decrease before ecdysis. LmHR39 transcription could be induced by 20E in vivo and was significantly suppressed by knocking down the expression of the L. migratoria ecdysone receptor gene and early‐late gene LmHR3. After RNA interference of LmHR39 with double‐stranded RNA (dsRNA), 85% of the insects showed abnormal morphology, with curly wings after moulting and delayed eclosion time. Haematoxylin and eosin staining indicated that apolysis of the integument and wing pad cuticle in the dsLmHR39‐treated insects was delayed compared to that in the dsRNA for green fluorescent protein‐injected control. Furthermore, RNA‐sequencing and RT‐qPCR analysis showed the expression level of carboxypeptidase genes (Carboxypeptidase A (CPA) and Carboxypeptidase M (CPM)) and chitin degrading genes (LmChitinase5 (LmCHT5) and LmChitinase10 (LmCHT10)) dramatically declined in the dsLmHR39‐treated insects, implying that the LmHR39‐mediated 20E signalling pathway is involved in the regulation of carboxypeptidase genes (CPA and CPM) and chitinase genes (LmCHT5 and LmCHT10), and participated in apolysis of the integument and wing pads during locust moulting.
Is there a role for proton pump inhibitor prophylaxis in haematology patients?
Authors: Leitinger Emma , Hui Lisa , Grigg Andrew
Published: February 2019

While proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy‐induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14‐month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.
Reply to Woltsche N. et al. Managing adverse effects by dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor vismodegib: a single‐centre experience
Authors: Scalvenzi M. , Costa C. , Cappello M. , Villani A.
Published: February 2019

Linked article: This article is commented on by N. Woltsche et al., pp. e144–e145 in this issue. To view this article visit https://doi.org/10.1111/jdv.15367.
Defining and measuring ‘eczema control’: an international qualitative study to explore the views of those living with and treating atopic eczema
Authors: Howells L. , Thomas K.S. , Sears A.V. , Nasr I. , Wollenberg A. , Schuttelaar M.L.A. , Romeijn G.L.E. , Paller A.S. , Mueller K. , Doytcheva K. , Kataoka Y. , Daguze J. , Barbarot S. , von Kobyletzki L.B. , Beckman L. , Ratib S. , Cowdell F. , Santer M. , Chalmers J.R. ,   the long‐term control of eczema working group for the HOME initiative
Published: February 2019

Background

Atopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients’ health and well‐being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that ‘long‐term control of eczema’ is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema.

Objectives

To (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term.

Methods

Online focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups.

Results

Eight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty‐two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered.

Conclusions

This study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.
Applications of reflection‐contrast microscopy, including the sensitive detection of the results ofin situhybridisation a review
Authors: PLOEM JOHAN
Published: February 2019

The observation with RCM of the reflection from reaction products produced by nonisotopicin situhybridisation and a peroxidase staining, has recently facilitated the identification of single copy genes. RCM also reveals light microscope structures in stained ultrathin (0.1 μm) epon and lowicryl sections. In such preparations no out‐of‐focus blur can be observed. Confocal optics are thus not needed to obtain high‐quality images of ultrathin sections at the highest conventional light microscope optical resolution, and with higher image‐contrast than can be obtained by classical absorption microscopy. Such RCM images provide the same type of information as confocal scanning microscope images. A sequential ultrathin section of the same microscopic specimen can be examined with electron microscopy for a simple and accurate (CLEM) procedure. For some applications RCM can replace (CLSM).

Lay Description

With reflection contrast microscopy (RCM), a microscope image can be observed if micromirror‐like reflecting substances are present in the reaction product of cytochemical stains. Using an antiflex objective for RCM, the reflected incident light from the stained microscope specimen can be observed with only a small amount of unwanted stray‐light in the image background. Stray‐light is caused by reflection of incident light from the surface of the lenses in the microscope objective and in the microscope tube (using a 50% beam splitter for epi‐illumination). Several authors who compared RCM with bright‐field and fluorescence microscopy, found RCM to be a sensitive microscope method in many applications. It has been reported that RCM, usingin situhybridisation methods, can detect DNA sequences in single copy genes. In the literature is mentioned that single copy genes have an estimated mass of less than a trillionth of a gram of DNA. From stained ultrathin microscope sections with less than 0.1 μm thickness, multicoloured images with a high image contrast, optimal resolution and no out‐of‐focus blur can be observed with RCM. To achieve this, RCM uses an antiflex microscope objective, with a quarter‐wave plate mounted on the front lens in combination with a polarising filter cube inserted in the epi‐illuminator. RCM can also make use of oblique illumination, for a further increase of the image‐contrast and the resolution of the microscope image. A central stop has then to be inserted in the aperture plane of an epi‐illuminator.
Sex hormones modulate pathogenic processes in experimental traumatic brain injury
Authors: Gölz Christina , Kirchhoff Florian Paul , Westerhorstmann Jana , Schmidt Matthias , Hirnet Tobias , Rune Gabriele M. , Bender Roland A. , Schäfer Michael K.E.
Published: February 2019

Clinical and animal studies have revealed sex‐specific differences in histopathological and neurological outcome after traumatic brain injury (TBI). The impact of perioperative administration of sex steroid inhibitors on TBI is still elusive. Here, we subjected male and female C57Bl/6N mice to the controlled cortical impact (CCI) model of TBI and applied pharmacological inhibitors of steroid hormone synthesis, that is, letrozole (LET, inhibiting estradiol synthesis by aromatase) and finasteride (FIN, inhibiting dihydrotestosterone synthesis by 5α‐reductase), respectively, starting 72 h prior CCI, and continuing for a further 48 h after CCI. Initial gene expression analyses showed that androgen (Ar) and estrogen receptors (Esr1) were sex‐specifically altered 72 h after CCI. When examining brain lesion size, we found larger lesions in male than in female mice, but did not observe effects of FIN or LET treatment. However, LET treatment exacerbated neurological deficits 24 and 72 h after CCI. On the molecular level, FIN administration reduced calpain‐dependent spectrin breakdown products, a proxy of excitotoxicity and disturbed Ca2+ homeostasis, specifically in males, whereas LET increased the reactive astrocyte marker glial fibrillary acid protein specifically in females. Examination of neurotrophins (brain‐derived neurotrophic factor, neuronal growth factor, NT‐3) and their receptors (p75NTR, TrkA, TrkB, TrkC) revealed CCI‐induced down‐regulation of TrkB and TrkC protein expression, which was reduced by LET in both sexes. Interestingly, FIN decreased neuronal growth factor mRNA expression and protein levels of its receptor TrkA only in males. Taken together, our data suggest a sex‐specific impact on pathogenic processes in the injured brain after TBI. Sex hormones may thus modulate pathogenic processes in experimental TBI.

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PET imaging of dopamine release in the frontal cortex of manganese‐exposed non‐human primates
Authors: Guilarte Tomas R. , Yeh Chien‐Lin , McGlothan Jennifer L. , Perez Juan , Finley Paige , Zhou Yun , Wong Dean F. , Dydak Ulrike , Schneider Jay S.
Published: February 2019

Humans and non‐human primates exposed to excess levels of manganese (Mn) exhibit deficits in working memory and attention. Frontal cortex and fronto‐striatal networks are implicated in working memory and these circuits rely on dopamine for optimal performance. Here, we aimed to determine if chronic Mn exposure alters in vivo dopamine release (DAR) in the frontal cortex of non‐human primates. We used [11C]‐FLB457 positron emission tomography with amphetamine challenge to measure DAR in Cynomolgus macaques. Animals received [11C]‐FLB457 positron emission tomography scans with and without amphetamine challenge prior to Mn exposure (baseline), at different time points during the Mn exposure period, and after 10 months of Mn exposure cessation. Four of six Mn‐exposed animals expressed significant impairment of frontal cortex in vivo DAR relative to baseline. One Mn animal had no change in DAR and another Mn animal expressed increased DAR relative to baseline. In the reversal studies, one Mn‐exposed animal exhibited complete recovery of DAR while the second animal had partial recovery. In both animals, frontal cortex Mn concentrations normalized after 10 months of exposure cessation based on T1‐weighted magnetic resonance imaging. D1‐dopamine receptor (D1R) autoradiography in frontal cortex tissue indicates that Mn animals that experienced cessation of Mn exposure expressed D1R levels that were approximately 50% lower than Mn animals that did not experience cessation of Mn exposure or control animals. The present study provides evidence of Mn‐induced alterations in frontal cortex DAR and D1R that may be associated with working memory and attention deficits observed in Mn‐exposed subjects.

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An update on clinical safety of adalimumab in treating psoriasis: A systematic review and meta‐analysis based on 20 randomized controlled trials
Authors: Guan Xin , Zhang Chun‐Lei
Published: February 2019

Purpose

The current meta‐analysis was conducted to better evaluate the role of adalimumab for patients with psoriasis in terms of its safety profile on the basis of eligible randomized controlled trials (RCTs).

Methods

The following electronic databases such as Cochrane, PubMed, and Embase database involving the index words were screened and identified for qualified studies updated to December 2018. Associated publications and sources were hand‐searched for more related details. To further analyze the main outcomes, the odds ratio (OR) and mean difference (MD) with its 95% confidence interval (95% CI) were utilized.

Results

There were a total of 20 RCTs involving respective 3795 and 3266 patients in the adalimumab and control group that met our inclusion criteria. According to the aggregated results, the adalimumab group was highly associated with significant improvement in the incidence of adverse event (AE), infection, and injection site reaction on comparison of the control group. Nevertheless, no remarkable differences were found between the two study groups in terms of the incidence of serious AE, serious infection as well as the discontinuation of study drug caused by AE.

Conclusion

Adalimumab was proved to be linked to higher incidence of AE, infection, and injection site reaction during the therapy process of psoriasis based on high‐quality RCTs. In addition, there was no association between adalimumab therapy and serious AE, serious infection and the discontinuation of study drug caused by AE in patients harboring psoriasis according to eligible RCTs.
Measurement properties of patient‐reported outcome measures in radiotherapy‐induced trismus
Authors: Assas Motaz , Wiriyakijja Paswach , Fedele Stefano , Porter Stephen , Ní Ríordáin Richeal
Published: February 2019

Trismus or lockjaw is the reduction in mouth opening. Radiotherapy‐induced trismus occurs when the masticatory muscles are within range of radiation treating head and neck cancer, resulting in muscular fibrosis and trismus. We aim to assess the measurement properties of available validated patient‐reported outcome measures relevant to radiotherapy‐induced trismus in head and neck cancer patients. Systematic electronic searches were performed in MEDLINE and EMBASE databases to identify studies validating radiotherapy‐induced trismus with patient‐reported outcome measures up to January 2018. Two reviewers independently rated the methodological quality of identified validation studies, using the consensus‐based standards for the selection of health status measurement instrument (COSMIN) checklist. The level of evidence for measurement properties was then summarised based upon pre‐defined criteria. Only one of the 280 retrieved studies were deemed fit for inclusion. The Gothenburg Trismus Questionnaire was assessed and found to have a good methodological quality of measurement properties except for reliability, which was poor. There was a moderate level of evidence supporting internal consistency, content validity, structural validity and hypothesis testing. The evidence for test‐retest reliability remains unknown in the population of interest. The Gothenburg Trismus Questionnaire is the only patient‐reported outcome measure in the field of showing some good measurement properties, and it may therefore represent a useful instrument for the assessment of radiotherapy‐induced trismus in head and neck cancer patients. However, further validation studies are needed especially with respect to the reliability, measurement error and the responsiveness of this instrument.
Oral submucous fibrosis: A clinicopathological study of 674 cases in China
Authors: Cai Xinjia , Yao Zhigang , Liu Gui , Cui Lin , Li Huiling , Huang Junhui
Published: February 2019

Background

Oral submucous fibrosis (OSF) has been reported frequently in India and other countries in South Asia. There are few reports on the clinicopathological features of OSF in China, where OSF is an epidemic. This study analyses the clinicopathological features of OSF in Hunan Province, China.

Methods

A total of 674 cases of OSF were collected from July 2013 to August 2018 in Xiangya Stomatological Hospital, Central South University, and gender, age, site, pathological stage, habits, symptoms and associated lesions were recorded.

Results

The male to female ratio was 32.7:1. The average age was 35.23 ± 10.08. The buccal mucosa was the most common site. A total of 99.85% of OSF cases chewed areca nut. Pale mucosa, restricted mouth opening, burning and fibrous bands were common clinical manifestations. Oral leukoplakia (OLK) was the most common associated lesion. The extended duration of chewing areca nut increased the risk of associated lesions (P < 0.05). The risk of OSF associated with OLK decreased with increasing OSF stage (P < 0.05).

Conclusion

The prevalence of OSF in males was higher than that in females, the buccal mucosa was most affected, and chewing areca nut is the most common habit of OSF patients.
Improving Polymethyl Methacrylate Resin Using a Novel Titanium Dioxide Coating
Authors: Darwish Ghaith , Huang Su , Knoernschild Kent , Sukotjo Cortino , Campbell Stephen , Bishal Arghya Kamal , Barão Valentim Adelino , Wu Christine D. , Taukodis Christos G. , Yang Bin
Published: February 2019

Purpose

The objective of this study was to improve the surface characteristics of poly (methyl methacrylate) (PMMA) by developing a novel, thin film coating process and to characterize the resulting coated surface.

Materials and Methods

An atomic layer deposition (ALD) technique was developed to deposit a titanium dioxide (TiO2) nano‐thin film on PMMA. The surface wettability for both coated and uncoated PMMA was determined by measuring water contact angle. Wear resistance was assessed using a mechanical tooth‐brushing device with a 50 g load for 6000 strokes after 5 months of water storage. A denture cleanser challenge test was performed by using sonication in 3.8% sodium perborate for 1 hour with aged specimens. X‐ray photoelectron spectroscopy (XPS) was used before and after the brushing test and challenge test to analyze the PMMA surface chemical composition. The mechanical strength of coated and uncoated PMMA was measured using a three‐point bending test. Surface microbial interactions were also evaluated by assessing Candida albicans biofilm attachment.

Results

Nano‐TiO2 coating (30 nm thick) was successfully deposited on PMMA at 65°C. After coating, water contact angle decreased from 70° to less than 5°. After brushing test, the coating remained intact. XPS analysis revealed no loss of TiO2 from coated specimens following brushing and denture cleanser sonication for 1 hour. There was no statistically significant difference in mechanical strength (MPa) (mean ± SD) between PMMA (139.4 ± 11.3) and TiO2‐PMMA (160.7 ± 37.1) (p = 0.0995). C. albicans attachment decreased by 63% to 77% on the coated PMMA surface.

Conclusions

ALD is a promising technique to modify surface properties of PMMA and resulted in a stable adherent thin film. By depositing a TiO2 coating, PMMA surface properties may lead to significantly reduced microorganism adhesion and easier pathogen removal from PMMA. For patients who wear dentures, reducing the oral microbial biofilm burden using a TiO2‐coated PMMA surface could positively impact their oral and systemic health.
Nuclear behavior and roles indicate that Codiolum phase is a sporophyte in Monostroma angicava (Ulotrichales, Ulvophyceae)
Authors: Horinouchi Yusuke , Yamaguchi Masashi , Chibana Hiroji , Togashi Tatsuya
Published: February 2019

The life‐cycle system of Ulotrichales, a major order of Ulvophyceae, remains controversial because it is unclear whether the Codiolum phase, a characteristic unicellular diploid generation in ulotrichalean algae, is a zygote or a sporophyte. This controversy inhibits the understanding of the diversified life cycles in Ulvophyceae. To distinguish between zygotes and sporophytes, we have to examine not only whether diploid generations function as sporophytes, but also whether mitosis occurs before meiosis in diploid generations. However, the nuclear behavior in the Codiolum phases is largely unknown, probably because no suitable methods are available. Using fluorescent microscopy with ethidium bromide and transmission electron microscopy of cell‐wall‐dissected specimens, we report the nuclear behavior in the Codiolum phases of an ulotrichalean alga with a representative life cycle, Monostroma angicava. Each vegetative Codiolum phase had a single polyploid nucleus due to endoreduplication, a type of mitosis without nuclear division. During zoosporogenesis, the nucleus had a structure that would be a meiosis‐specific complex. We quantitatively showed that Codiolum phases grew extremely large and produced numerous zoospores. Our results suggest that an event comparable to mitosis occurs before meiosis in the Codiolum phase of M. angicava. This nuclear behavior and the functions (growth and zoospore production abilities) correspond to those of sporophytes. Therefore, the life‐cycle system of M. angicava is a heteromorphic haplo‐diplontic cycle. This system appears to be widely adopted among other ulotrichalean algae.
MicroRNA‐30b regulates insulin sensitivity by targeting SERCA2b in non‐alcoholic fatty liver disease
Authors: Dai Li‐Li , Li Shu‐De , Ma Yi‐Cheng , Tang Jun‐Rui , Lv Jun‐Yan , Zhang Yuan‐Qing , Miao Ying‐Lei , Ma Yan‐Qiong , Li Chun‐Mei , Chu Yi‐You , Wang Kun‐Hua , Ma Lan‐Qing , Zou Cheng‐Gang
Published: February 2019

Background & Aims

Insulin resistance is strongly associated with non‐alcoholic fatty liver disease, a chronic, obesity–related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity.

Methods

We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR‐30b or inhibit miR‐30b rats were injected with lentivirus particles containing PGLV3‐miR‐30b or PGLV3‐miR‐30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects.

Results

Our data showed that miR‐30b was markedly up‐regulated in the liver of HFD–treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+‐ATPase 2b (SERCA2b), as a novel target of miR‐30b. Overexpression of miR‐30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR‐30b by miR‐30b antimiR suppressed ER stress and insulin resistance in HFD–treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR‐30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA‐IR) in human subjects.

Conclusions

Our findings suggest that miR‐30b represents not only a potential target for the treatment of insulin resistance, but also a non‐invasive disease biomarker of NAFLD.
L1 Transfer Effects in the Production of Generic Plurals in L2 Arabic
Authors: AZAZ MAHMOUD
Published: February 2019

This study examines first language (L1) English transfer in the acquisition of plural noun semantics in second language (L2) Arabic. Drawing on previous research on the L2 acquisition of plural noun interpretation, the study presents and discusses new production data of specific and generic definite plurals by English‐speaking learners of Arabic at beginning (n = 15), low‐advanced (n = 15), and high‐advanced levels (n = 11). The results from 2 meaning‐based elicitation tasks showed that the beginning group heavily transferred their L1 English generic bare plurals in the production of target‐like Arabic generic definite plurals. The low‐advanced group fluctuated between bare and definite plurals. Only the high‐advanced group, who had studied Arabic in an immersion setting combined with very structured classroom instruction, showed considerable stability in their production of target‐like definite plurals. A careful analysis of the textbook series the beginning and low‐advanced groups were taught from showed that the semantics of plural nouns, and more broadly, the semantics of the definite article, were not explicitly taught. The study concludes that the L1 effects in mapping definite and bare plural nouns to their meanings are exacerbated in the absence of explicit instruction. Further pedagogical implications for teaching form‐meaning mappings for articles are discussed.
Chloroplast ultrastructure in plants
Authors: Kirchhoff Helmut
Published: February 2019

The chloroplast organelle in mesophyll cells of higher plants represents a sunlight‐driven metabolic factory that eventually fuels life on our planet. Knowledge of the ultrastructure and the dynamics of this unique organelle is essential to understanding its function in an ever‐changing and challenging environment. Recent technological developments promise unprecedented insights into chloroplast architecture and its functionality. The review highlights these new methodical approaches and provides structural models based on recent findings about the plasticity of the thylakoid membrane system in response to different light regimes. Furthermore, the potential role of the lipid droplets plastoglobuli is discussed. It is emphasized that detailed structural insights are necessary on different levels ranging from molecules to entire membrane systems for a holistic understanding of chloroplast function.
Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease
Authors: Gao Li‐Wei , Yin Qing‐Qin , Tong Yue‐Juan , Gui Jin‐Gang , Liu Xiu‐yun , Feng Xue‐li , Yin Ju , Liu Jun , Guo Yan , Yao Yao , Xu Bao‐Ping , He Jian‐Xin , Shen Kun‐Ling , Lau Yu‐Lung , Jiang Zai‐Fang
Published: February 2019

Background

Chronic granulomatous disease (CGD) is a rare disease in China, and very little large‐scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients.

Methods

Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016.

Results

A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X‐linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment.

Conclusions

Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL‐CGD are higher than AR‐CGD.
Salvage Therapy With Burst Spinal Cord Stimulation for Chronic Pancreatitis: A Case Report
Authors: Delange Segura Laureano , Rodríguez Padilla Marisa , Palomino Jiménez Maria Teresa , Fernández Baena Mariano , Rodríguez Staff José Felipe
Published: February 2019

Introduction

Pain associated with chronic pancreatitis is often difficult to treat. On many occasions, interventional techniques may be necessary. In recent years, spinal cord stimulation techniques have been used successfully in the treatment of these patients. However, only the use of traditional tonic stimulation based on paresthesias has been published for this purpose. Spinal cord burst stimulation has been shown to be more effective than tonic stimulation, especially in failed back surgery syndrome.

Case description

We present the case of an 82‐year‐old patient with incoercible pain related to chronic pancreatitis for the preceding 5 years. She had shown good short‐term results with lidocaine‐cortisone blocks and celiac plexus radiofrequency. After a failed trial period with low‐frequency conventional tonic stimulation, she was successfully treated with burst stimulation.

Results

A sustained pain score reduction of over 50% on the visual analogue scale was seen, as were a decrease in opioid consumption and a high degree of satisfaction with the therapy by our patient.
Are the Questions of Metaphysics More Fundamental Than Those of Science?
Authors: Ney Alyssa
Published: February 2019

When pursued naturalistically, metaphysics may seem forced to navigate a narrow path. So that it may be a worthwhile enterprise, it must have claim to discovery of a distinctive set of objective truths. Yet it must also avoid potential competition or conflict with the results of scientific theories. In response to this problem, some naturalistic metaphysicians have argued that properly understood, metaphysics is aimed at a set of truths distinct from those of science. Metaphysicians investigate a realm of truths more fundamental than those of even fundamental science. This paper examines what is required both in science and metaphysics for a theory to count as a fundamental theory. Several criteria are presented which suggest that metaphysics does not investigate a realm more fundamental than that of science.
A case of high‐grade pancreatic intraepithelial neoplasia concomitant with type 1 autoimmune pancreatitis: The process underlying both conditions
Authors: Sugiyama Tomoko , Tajiri Takuma , Hiraiwa Shinichiro , Machida Tomohisa , Ito Hiroyuki , Yoshii Hisanori , Izumi Hideki , Nomura Eiji , Mukai Masaya , Nakamura Naoya
Published: February 2019

We report a case of high‐grade pancreatic intraepithelial neoplasia (PanIN) concomitant with lymphoplasmacytic sclerosing pancreatitis. The patient was an 82‐year‐old man in whom narrowing of the main pancreatic duct was detected incidentally by abdominal ultrasonography. Magnetic resonance cholangiopancreatography further revealed abrupt narrowing plus distal dilatation of the duct, from the pancreatic body to the tail. Distal pancreatectomy was performed under a preoperative diagnosis of intraductal papillary‐mucinous neoplasm. Macroscopic examination of the surgical specimen showed an ill‐demarcated, white‐gray area and prominent pancreatic atrophy, while histological analysis detected small (<5 mm in diameter) cystic dilatations of the main pancreatic duct and some branch ducts plus pancreatic atrophy with fibrosis and fatty replacement of acinar cells. We also detected variously sized papillary projections, fused glands, and scattered focal papillary proliferation of columnar ductal epithelium comprising cells with elongated, mildly hyperchromatic nuclei, consistent with high‐grade PanIN. In addition, we observed marked lymphoplasmacytic infiltration, periductal storiform fibrosis, and obliterative phlebitis. Immunohistochemical staining revealed abundant immunogloblin G4‐positive plasma cells, indicative of type 1 autoimmune pancreatitis (AIP). The coexistence of high‐grade PanIN and marked lymphoplasmacytic infiltration, typical of AIP, point to a close association between the former, as a carcinogenic process, and the latter, as an immune response.
Selling Assortments of Used Products to Third‐Party Remanufacturers
Authors: Mutha Akshay , Bansal Saurabh , Guide V. Daniel R.
Published: February 2019

This paper analyzes the business‐to‐business transactions in which a supplier sells assortments of used products to third‐party remanufacturers. The supplier offers used products in different quality conditions, called grades. We model this buyer–supplier transaction as a Stackelberg game in which the buyer chooses his optimal purchase quantity of various grades, and the supplier chooses the optimal assortment and the prices of the grades in the assortment anticipating buyer’s behavior. We first develop an analytically tractable solution to the buyer’s and supplier’s problems. Subsequently, we show several structural properties of the optimal assortment offered by the supplier, including (i) the optimal prices set by the supplier are such that high quality grades have a higher profit margin for the buyer; and (ii) the grades in the optimal assortment constitute a convex hull of the remanufacturing and acquisition costs. We also extend the results to the case when the supplier’s acquisition costs are marginally increasing in the quantity acquired.
Small‐sphere distributions for directional data with application to medical imaging
Authors: Kim Byungwon , Huckemann Stephan , Schulz Jörn , Jung Sungkyu
Published: February 2019

We propose novel parametric concentric multi‐unimodal small‐subsphere families of densities forp − 1 ≥ 2‐dimensional spherical data. Their parameters describe a common axis forKsmall hypersubspheres, an array ofKdirectional modes, one mode for each subsphere, andKpairs of concentrations parameters, each pair governing horizontal (within the subsphere) and vertical (orthogonal to the subsphere) concentrations. We introduce two kinds of distributions. In its one‐subsphere version, the first kind coincides with a special case of the Fisher–Bingham distribution, and the second kind is a novel adaption that models independent horizontal and vertical variations. In its multisubsphere version, the second kind allows for a correlation of horizontal variation over different subspheres. In medical imaging, the situation ofp − 1 = 2 occurs precisely in modeling the variation of a skeletally represented organ shape due to rotation, twisting, and bending. For both kinds, we provide new computationally feasible algorithms for simulation and estimation and propose several tests. To the best knowledge of the authors, our proposed models are the first to treat the variation of directional data along several concentric small hypersubspheres, concentrated near modes on each subsphere, let alone horizontal dependence. Using several simulations, we show that our methods are more powerful than a recent nonparametric method and ad hoc methods. Using data from medical imaging, we demonstrate the advantage of our method and infer on the dominating axis of rotation of the human knee joint at different walking phases.
Armor for Ethnographers
Authors: Katz Jack
Published: February 2019

As its public readership has vastly increased, ethnography has entered a new world of social interaction, at once rewarding and dangerous. Among social researchers, ethnographic fieldworkers are unusually exposed to pressures to both make and break promises of confidentiality to subjects because they work to expose subjects to readers in a relatively transparent way. By showing individuals in their individuality, ethnographers draw the attention of nonacademic readers, which can be motivating but also terrifying because sources might be questioned and subjects sought out in ways the ethnographer may not be able to control. Tracking the schizophrenia that now threatens to pervade ethnographic work, I describe overlooked risks that all practitioners face and point to an as‐yet unexplored collective strategy for resisting pressures to breach promises of confidentiality. I then switch from a collective to an individual focus and review ethnography as a multiphased research act, suggesting ways to minimize personal and ethical risks at each stage.
Effects of land use change and seasonal variation in the hydrophysical properties in Vertisols in northeastern Mexico
Authors: Yáñez‐Díaz María I. , Cantú‐Silva Israel , González‐Rodríguez Humberto , Sánchez‐Castillo Laura
Published: February 2019

The impact of the use of natural resources associated with anthropogenic activities has increased evidently, mainly through land use changes which have altered hydrophysical properties of soils. We hypothesized that, in the same soil type (Vertisol), four types of land use system (grassland, agricultural, Eucalyptus plantation and thornscrub) and seasonal variation can modify the soil hydrophysical properties. Results showed significant differences between land use systems and seasons for hydraulic conductivity (K), infiltration capacity (fp) and cumulative infiltration (fc). There were no seasonal differences in soil penetration resistance (SPR), bulk density (ρd) and total porosity (φP). Grassland presented higher values for ρd (1.2 g cm−3) and SPR (5.3 kg cm−2) and lower for K (0.8 × 10−5 cm s−1) and φP (53%), unlike thornscrub. Agriculture presented lower SPR (0.4 kg cm−2), while plantation showed similar values when compared to the thornscrub. Kostiakov infiltration model was fitted to land use infiltration curves, showing differences between land use and season. The values for fp oscillated between 53.6 and 548.8 mm hr−1 and fc ranged from 105.3 to 1,061 mm. The order of the infiltration values goes as follows: agriculture > plantation > thornscrub > grassland. Land use changes in Vertisols induced modification of soil physical properties affecting processes like permeability, soil compaction and water availability.
Synchronous Periadriatic magmatism in the Western and Central Alps in the absence of slab breakoff
Authors: Ji Wei‐Qiang , Malusà Marco G. , Tiepolo Massimo , Langone Antonio , Zhao Liang , Wu Fu‐Yuan
Published: February 2019

Periadriatic Alpine magmatism has long been attributed to slab breakoff after Adria–Europe continental collision, but this interpretation is challenged by geophysical data suggesting the existence of a continuous slab. Here, we shed light on this issue based on a comprehensive dataset of zircon U–Pb ages and Hf isotopic compositions from the main western Periadriatic intrusives (from Traversella to Adamello). Our zircon U–Pb data provide the first evidence of Eocene magmatism in the Western Alps (42–41 Ma in Traversella), and demonstrate that magmatism started synchronously in different segments of the Alpine belt, when subduction was still active. Zircon U–Pb ages define younging trends perpendicular to the strike of the European slab, suggesting a progressive Eocene–Oligocene slab steepening. We propose that slab steepening enhanced the corner flow. This process was more effective near the torn edge of the European slab, and triggered Periadriatic magmatism in the absence of slab breakoff.
A gradual transition to plate tectonics on Earth between 3.2 to 2.7 billion years ago
Authors: Hartnady Michael I. H. , Kirkland Christopher L.
Published: February 2019

Zircon crystals precipitated from granitoid magmas contain a robust record of the age and chemistry of continental magmatism spanning some 4.375 Ga of Earth history, a record that charts initiation of plate tectonics. However, constraining when exactly plate tectonics began to dominate crustal growth processes is challenging as the geochemical signatures of individual rocks may reflect local subduction processes rather than global plate tectonics. Here we apply counting statistics to a global database of coupled U–Pb and Hf isotope analyses on magmatic zircon grains from continental igneous and sedimentary rocks to quantify changes in the compositions of their source rocks. The analysis reveals a globally significant change in the sources of granitoid magmas between 3.2 and 2.7 Ga. These secular changes in zircon chemistry are driven by a coupling of the deep (depleted mantle) and shallow (crustal) Earth reservoirs, consistent with a geodynamic regime dominated by Wilson cycle style plate tectonics.
Commoning mobility: Towards a new politics of mobility transitions
Authors: Nikolaeva Anna , Adey Peter , Cresswell Tim , Lee Jane Yeonjae , Nóvoa Andre , Temenos Cristina
Published: February 2019

Scholars have argued that transitions to more sustainable and just mobilities require moving beyond technocentrism to rethink the very meaning of mobility in cities, communities, and societies. This paper demonstrates that such rethinking is inherently political. In particular, we focus on recent theorisations of commoning practices that have gained traction in geographic literatures. Drawing on our global comparative research of low‐carbon mobility transitions, we argue that critical mobilities scholars can rethink and expand the understanding of mobility through engagement with commons–enclosure thinking. We present a new concept, “commoning mobility,” a theorisation that both envisions and shapes practices that develop fairer and greener mobilities and more inclusive, collaboratively governed societies. Our analysis introduces three “logics” of mobility transition projects. First, the paper discusses how a logic of scarcity has been a driver for mobility planning as the scarcity of oil, finance, space, and time are invoked across the world as stimuli for aspiring to greener, “smarter,” and cheaper mobilities. The paper then identifies two responses to the logic of scarcity: the logics of austerity and the logics of commoning. Austere mobilities are examined to problematise the distribution of responsibility for emissions and ensuing injustices and exclusion in low‐carbon transitions. The logics of commoning shows a potential to reassess mobility not only as an individual freedom but also as a collective good, paving the way for fairer mobility transitions and a collaborative tackling of sustainable mobility challenges.