bluuebunny/crossref_metadata_2025 huggingface dataset:
MEMORY, PLACE, AND LANDSCAPE IN ROMAN SYRIA: THE VIEW FROM THE SANCTUARIES OF MOUNT LEBANON
Authors: NEWSON PAUL
Published: June 2019

The creation of memory and place within landscapes has received considerable critical attention in archaeology in recent years, with a focus on power relations, social cohesion, and social memory. As yet, such notions have not been fully explored within Roman contexts, generally in the Eastern Mediterranean, and particularly within the Roman province of Syria. In this region, the well-preserved Graeco-Roman temples of Lebanon have long been interpreted as powerful symbols of the Roman period. However, because of this status, study of these impressive structures has centred primarily on certain aspects, for example, the ‘Roman-ness’ of their architecture and the practical construction of their sacred landscapes. Utilizing notions of memory and power, place and performance, this paper seeks to move beyond such empirical analyses. Focusing on three case studies, it explores elements of the development of place through memory within the rural environment.
Specifically Sized Hyaluronan (35 kDa) Prevents Ethanol‐Induced Disruption of Epithelial Tight Junctions Through a layilin‐Dependent Mechanism in Caco‐2 Cells
Authors: Bellos Damien A. , Sharma Dhara , McMullen Megan R. , Wat Jeanette , Saikia Paramananda , de la Motte Carol A. , Nagy Laura E.
Published: June 2019

Background

Specific‐sized species of the carbohydrate hyaluronan elicit a variety of cellular responses mediating tissue integrity and repair, as well as regulating inflammatory responses. Orally provided hyaluronan with an average molecular weight of 35 kDa (HA35) protects mice from short‐term ethanol (EtOH)‐induced liver injury. This protection was associated with maintenance of the colocalization of zonula occludens‐1 (ZO‐1) and occludin at tight junctions in the proximal colon. However, it is not known whether HA35 also protects other regions of the intestine or whether protection is due to a direct and/or indirect interaction of HA35 with the intestinal epithelium.

Methods

Female C57BL/6J mice were fed an EtOH containing diet or pair‐fed control diet (4 days) and treated with or without HA35 via daily gavage during the last 3 days of EtOH feeding. Intestinal morphology and tight junction integrity were assessed. Differentiated Caco‐2 cells were transfected or not with scrambled siRNA or siRNA targeting layilin, a hyaluronan receptor. Caco‐2 cells were treated with or without HA35 prior to challenge with EtOH. Localization of tight junction proteins, fluorescein isothiocyanate (FITC)‐dextran permeability, and transepithelial electrical resistance (TEER) were evaluated.

Results

While short‐term EtOH did not result in any apparent changes in the gross morphology of the intestine, colocalization of ZO‐1 and occludin at tight junctions was decreased in the proximal and distal colon. HA35 prevented these effects of EtOH. In differentiated Caco‐2 cells, EtOH decreased the localization of ZO‐1 and occludin at tight junctions and increased permeability of FITC‐dextran. At higher concentrations, EtOH also decreased TEER. Pretreatment with HA35 prevented these changes. When the hyaluronan receptor layilin was knocked down in Caco‐2 cells, HA35 no longer protected cells from EtOH‐induced loss of tight junctions.

Conclusions

Taken together, these data indicate that HA35 interacts with layilin on intestinal epithelial cells and maintains intestinal tight junction integrity during short‐term EtOH exposure.
Alcohol Effects on Colon Epithelium are Time‐Dependent
Authors: Bishehsari Faraz , Zhang Lijuan , Voigt Robin M. , Maltby Natalie , Semsarieh Bita , Zorub Eyas , Shaikh Maliha , Wilber Sherry , Armstrong Andrew R. , Mirbagheri Seyed Sina , Preite Nailliw Z. , Song Peter , Stornetta Alessia , Balbo Silvia , Forsyth Christopher B. , Keshavarzian Ali
Published: June 2019

Background

Alcohol intake increases the risk of developing colon cancer. Circadian disruption promotes alcohol's effect on colon carcinogenesis through unknown mechanisms. Alcohol's metabolites induce DNA damage, an early step in carcinogenesis. We assessed the effect of time of alcohol consumption on markers of tissue damage in the colonic epithelium.

Methods

Mice were treated by alcohol or phosphate‐buffered saline (PBS), at 4‐hour intervals for 3 days, and their colons were analyzed for (i) proliferation (Ki67) and antiapoptosis (Bcl‐2) markers, (ii) DNA damage (γ‐H2AX), and (iii) the major acetaldehyde (AcH)–DNA adduct, N2‐ethylidene‐dG. To model circadian disruption, mice were shifted once weekly for 12 h and then were sacrificed at 4‐hour intervals. Samples of mice with a dysfunctional molecular clock were analyzed. The dynamics of DNA damage repair from AcH treatment as well as role of xeroderma pigmentosum, complementation group A (XPA) in their repair were studied in vitro.

Results

Proliferation and survival of colonic epithelium have daily rhythmicity. Alcohol induced colonic epithelium proliferation in a time‐dependent manner, with a stronger effect during the light/rest period. Alcohol‐associated DNA damage also occurred more when alcohol was given at light. Levels of DNA adduct did not vary by time, suggesting rather lower repair efficiency during the light versus dark. XPA gene expression, a key excision repair gene, was time‐dependent, peaking at the beginning of the dark. XPA knockout colon epithelial cells were inefficient in repair of the DNA damage induced by alcohol's metabolite.

Conclusions

Time of day of alcohol intake may be an important determinant of colon tissue damage and carcinogenicity.
Reduced sensitivity to ethanol and excessive drinking in a mouse model of neuropathic pain
Authors: Bilbao Ainhoa , Leixner Sarah , Wei Shoupeng , Cantacorps Lídia , Valverde Olga , Spanagel Rainer
Published: June 2019

The co‐occurrence of chronic pain and alcohol use disorders (AUDs) involves complex interactions between genetic and neurophysiological aspects, and the research has reported mixed findings when they both co‐occur. There is also an indication of a gender‐dependent effect; males are more likely to use alcohol to cope with chronic pain problems than females. Recently, a new conceptualization has emerged, proposing that the negative affective component of pain drives and maintains alcohol‐related behaviors. We studied in a longitudinal fashion alterations in alcohol drinking patterns and pain thresholds in a mouse model of chronic neuropathic pain in a sex‐dependent manner. Following partial denervation (spared nerve injury [SNI]), stimulus‐evoked pain responses were measured before chronic alcohol consumption, during drinking, during a deprivation phase, and following an episode of excessive drinking. During the course of alcohol drinking, we observed pronounced sex differences in pain thresholds. Male mice showed a strong increase in pain thresholds, suggesting an analgesic effect induced by alcohol over time, an effect that was not observed in female mice. SNI mice did not differ from sham‐operated controls in baseline alcohol consumption. However, following a deprivation phase and the reintroduction of ethanol, male SNI mice but not female mice showed more pronounced excessive drinking than controls. Finally, we observed decreased central ethanol sensitivity in male SNI mice but not in females. Together with our finding, that ethanol is able to decrease a pain‐induced negative affective memory we come to following conclusion. We propose that a lower sensitivity to the intoxicating effects of alcohol together with the ability of alcohol to reduce the negative affective component of pain may explain the higher co‐occurrence of AUD in male chronic pain patients.
Multiple ventricular bands and the associated trabecula septomarginalis dextra in the right ventricle of the domestic dog (Canis familiaris)
Authors: Cope Lee Anne
Published: June 2019

Ventricular bands are strand‐like intraventricular structures extending between adjacent papillary muscles; a papillary muscle and the ventricular wall or the interventricular septum and ventricular wall. Examination of the domestic dog right ventricle documented six ventricular band types. Eighty‐five of the 89 examined hearts had at least one right ventricular band. In the current study, the right ventricle of the 85 dog hearts was re‐examined for more than one ventricular band type. Seven patterns of multiple different bands were identified in the 24 dog hearts. The patterns (i.e., combinations) of different ventricular bands were grouped into three categories. Category 1 had five different patterns of bands. Each pattern had two different band types. Category 2 had one combination of three different bands. Category 3 had one combination of four different bands. The presence of right ventricular bands around the trabecula septomarginalis dextra was also documented. All 24 dog hearts with multiple ventricular bands had a trabecula septomarginalis dextra. The main goal of this study was documentation of multiple right ventricular band patterns. A secondary goal was documentation of the combined presence of these bands and a trabecula septomarginalis dextra. In the dog, the ventricular bands and trabecula are both thin, strand‐like intraventricular structures with variable branching patterns before blending into the ventricular wall. The gross similarity of these structures and lack of information on their combined presence could precipitate their misidentification.
Price Deviation Supported by Arbitrage: Evidence from Family Business Groups
Authors: Kim Woojin , Wang Shu‐Feng
Published: June 2019

This paper examines how arbitrage may contribute to, rather than remove, temporary price deviation between two related securities. Based on a unique sample of stock‐for‐stock tender offers by a member firm for another member firm within Korean family business groups, we find that arbitrage opportunity exists in more than three quarters of the sample, which is consistent with Lamont and Thaler (2003). Outside investors’ tendering decisions and institutions’ short‐selling are consistent with exploiting potential arbitrage opportunities, but not large enough to eliminate them. The prices of the two securities tend to diverge leading up to the tender offer, which may be impacted by the controlling families. This deviation, reflected in the exchange ratio of the two securities, is more likely to be sustained when there is more short‐selling during the possible arbitrage period. Our results suggest that arbitrage may support temporary deviations in the relative prices of two related securities under certain circumstances.
An extension of the dark triad and five‐factor model to three Asian societies
Authors: Arseneault Rene , Catano Victor
Published: June 2019

The aim of this study is to test the external validity of the short dark triad (SD3) and see whether the dark triad (DT) framework is replicable in Asian societies. In three independent studies involving 443 participants from South Korea, China, and the Philippines, we extend short measures of the DT and the big five framework as well as conduct confirmatory factor analysis to test various models of the SD3 in each country. We also test for measurement invariance, report intercorrelations, alpha coefficients, and gender differences within each sample. Except for Machiavellianism, all models failed configural invariance. Despite failing configural invariance across all three countries, males consistently reported higher means on all DT traits, with psychopathy the lowest, and DT constructs were significantly intercorrelated with each other across all three samples, demonstrating a pattern of consistency with previous DT literature and findings. As the DT continues to gain in popularity and is beginning to surface in cross‐cultural research, we contribute to discussions concerned with the construct's external validity. Our study's findings question what, if any, meaningful interpretations can be made from extending Western‐based personality instruments to Asian (foreign) societies. Limitations and contributions of this study are outlined, and recommendations for future research are summarized.
Complications related to peri‐operative transoesophageal echocardiography – a one‐year prospective national audit by the Association of Cardiothoracic Anaesthesia and Critical Care
Authors: Ramalingam G. , Choi S.‐W. , Agarwal S. , Kunst G. , Gill R. , Fletcher S. N. , Klein A. A. ,   on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care
Published: June 2019

Previous studies on the safety of peri‐operative transoesophageal echocardiography seem to suggest a low rate of associated morbidity and mortality. That said, there has been a paucity of prospective multicentre studies in this important area of clinical practice. We carried out a one‐year prospective study in 2017, co‐ordinated by the Association of Cardiothoracic Anaesthesia and Critical Care, to determine the rate and severity of complications associated with peri‐operative transoesophageal echocardiography in anaesthetised cardiology and cardiac surgical patients. With the help of clinicians from 28 centres across the UK and Ireland, we recorded the total number of examinations conducted in anaesthetised patients during the study period. All major complications at each centre were prospectively reported and recorded. Of the 22,314 examinations, there were 17 patients diagnosed with a major complication which caused either palatal injury or gastro‐oesophageal disruption. This corresponds to an incidence of 0.08% (95%CI 0.05–0.13%) or approximately 1:1300 examinations. There were seven deaths reported during the study period which were directly attributed to these complications, corresponding to an incidence of 0.03% (95%CI 0.01–0.07%) or approximately 1:3000. These figures are higher than previously reported and suggest a high probability of death following the development of a complication (~40%). Most complications occurred in patients without known risk factors for transoesophageal echocardiography associated gastro‐oesophageal injury. We suggest clinicians and departments review their procedural guidelines, especially in relation to probe insertion techniques, together with the information communicated to patients when the risks and benefits of such examinations are discussed.
Antimicrobial stewardship in the dairy industry: responding to the threat of antimicrobial resistance
Authors: Coombe JE , Tymms SM , Humphris M
Published: June 2019

Dairy Australia is the national service body for the Australian dairy industry. Its role is to help farmers adapt to a changing operating environment and achieve a profitable, sustainable dairy industry. Although the use of antibiotics in Australian agriculture is relatively low in global terms, Dairy Australia recognises important drivers for continuous improvement in antimicrobial stewardship (AMS). Dairy Australia’s first strategic priority is to support profitable farms. This priority has driven the development of a range of on‐farm change management programs in the animal health and welfare fields to optimise the unit cost of production and dairy cattle welfare. Dairy Australia’s third strategic priority is to further develop a ‘trusted dairy industry’. Previous and current work under these two strategies position the dairy industry favourably with respect to confronting the challenge of antimicrobial resistance (AMR) and supporting sound AMS with the guiding principle of ‘as little as possible, as much as necessary’. However, given an incomplete but ongoing threat of AMR, more work is needed. Supported by Dairy Australia, the dairy industry has developed an antimicrobial use strategy aligning with the Australian Animal Sector National AMR Plan 2018.
Robust inference for the stepped wedge design
Authors: Hughes James P. , Heagerty Patrick J. , Xia Fan , Ren Yuqi
Published: June 2019

Stepped wedge designed trials are a type of cluster‐randomized study in which the intervention is introduced to each cluster in a random order over time. This design is often used to assess the effect of a new intervention as it is rolled out across a series of clinics or communities. Based on a permutation argument, we derive a closed‐form expression for an estimate of the intervention effect, along with its standard error, for a stepped wedge design trial. We show that these estimates are robust to misspecification of both the mean and covariance structure of the underlying data‐generating mechanism, thereby providing a robust approach to inference for the intervention effect in stepped wedge designs. We use simulations to evaluate the type 1 error and power of the proposed estimate and to compare the performance of the proposed estimate to the optimal estimate when the correct model specification is known. The limitations, possible extensions, and open problems regarding the method are discussed.
SIRT3 deacetylase activity confers chemoresistance in AML via regulation of mitochondrial oxidative phosphorylation
Authors: Ma Jiao , Liu Bin , Yu Dan , Zuo Yong , Cai Rong , Yang Jianmin , Cheng Jinke
Published: June 2019

Acute myeloid leukaemia (AML) cells possess metabolism profiles, such as higher rates of oxidative phosphorylation and dependence on fatty acid oxidation for survival, and are dependent on the sophisticated regulation of reactive oxygen species (ROS) generation for survival, drug resistance and stemness maintenance. We found that sensitivity of primary AML cells to cytarabine correlated with SOD2 acetylation and the ability of the drug to induce mitochondrial ROS. The SOD2 deacetylase, SIRT3, protected AML cells from chemotherapy as shown by inhibited apoptosis via inhibited drug‐induced production of mitochondrial ROS. SIRT3 significantly decreased nicotinamide adenine dinucleotide phosphate (NADP)/reduced NADP ratio and increased reduced glutathione/oxidized glutathione ratio. Furthermore, SIRT3 enhanced oxidative phosphorylation (OxPhos) in AML cells under both basic and cytarabine‐treated conditions. A xenograft mouse model showed that SIRT3 overexpressing AML cells and patient‐derived xenograft mice bearing high SIRT3 deacetylase activity were more resistant to chemotherapy in vivo. SIRT3 inhibitor displayed synergy with cytarabine to ablate AML cells in vitro and in mouse models. Taken together, our study showed that SIRT3 is capable of reprograming mitochondrial metabolism towards OxPhos and downregulating ROS generation, which contribute to the chemoresistance of AML cells. SIRT3 can be utilized as a potential therapeutic target to improve the anti‐leukaemic efficacy of standard chemotherapeutic agents for AML.
Inhibitors of class I histone deacetylases attenuate thioacetamide‐induced liver fibrosis in mice by suppressing hepatic type 2 inflammation
Authors: Loh Zhixuan , Fitzsimmons Rebecca L. , Reid Robert C. , Ramnath Divya , Clouston Andrew , Gupta Praveer K. , Irvine Katharine M. , Powell Elizabeth E. , Schroder Kate , Stow Jennifer L. , Sweet Matthew J. , Fairlie David P. , Iyer Abishek
Published: June 2019

Background and Purpose

Chronic liver diseases feature excessive collagen and matrix protein deposition or crosslinking that characterises fibrosis, leads to scar tissue, and disrupts liver functions. There is no effective treatment. This study investigated whether treatment with selective histone deacetylase (HDAC) inhibitors might specifically reduce type 2 inflammation in the injured liver, thereby attenuating fibrogenesis in mice.

Experimental Approach

Thioacetamide (TAA) was used to induce hepatic inflammation, fibrosis, and liver damage in female C57BL/6 mice, similar to the clinical features of chronic human liver disease. We used eight inhibitors of different human HDAC enzymes to probe histological (IHC and TUNEL), biochemical and immunological changes (flow cytometry, qPCR, Legendplex, and ELISA) in pathology, fibrosis, hepatic immune cell flux, and inflammatory cytokine expression.

Key Results

Inhibitors of class I, but not class II, HDAC enzymes potently suppressed chronic hepatic inflammation and fibrosis in mice, attenuating accumulation and activation of IL‐33‐dependent, but not IL‐25‐dependent, group 2 innate lymphoid cells (ILC2) and inhibiting type 2 inflammation that drives hepatic stellate cells to secrete excessive collagen and matrix proteins.

Conclusions and Implications

The results show that potent and selective inhibitors of class I only HDAC enzymes profoundly inhibit hepatocyte death and type 2 inflammation to prevent TAA‐induced liver fibrosis in mice. The specific HDAC enzymes identified here may be key promoters of inflammation in chronic liver fibrosis.
Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T‐cell leukemia/lymphoma
Authors: Morichika Kazuho , Karube Kennosuke , Kayo Hirona , Uchino Shuta , Nishi Yukiko , Nakachi Sawako , Okamoto Shiki , Morishima Satoko , Ohshiro Kazuiku , Nakazato Iwao , Fukushima Takuya , Masuzaki Hiroaki
Published: June 2019

Adult T‐cell leukemia/lymphoma (ATLL) is a mature T‐cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. Based on previous integrated molecular analyses suggesting the importance of the JAK‐STAT pathway in ATLL, we attempted to clarify the clinicopathological significance of this pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6 were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Expression of pSTAT3 was observed in 43% (50/116) of ATLL cases, whereas pSTAT5 and pSTAT6 were largely undetected. Cases with the lymphoma type showed significantly less frequent pSTAT3 expression (8/45, 18%) than those with the other subtypes (41/66, 62%; P < .001). STAT3 mutations were detected in 36% (10/28) and 19% (12/64) of cases with the smoldering and aggressive types of ATLL, respectively. The correlation between STAT3 mutation and pSTAT3 expression was not significant (P = .07). Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression‐free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data show that only the lymphoma type showed a low prevalence of tumor cells positive for pSTAT3 expression, and raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.
Humanitarian aid and local power structures: lessons from Haiti's ‘shadow disaster’
Authors: Hsu Kaiting Jessica , Schuller Mark
Published: June 2019

This paper investigates the confluence of humanitarian aid, centralisation, and politics. The 7.0 magnitude earthquake in Haiti on 12 January 2010 led to more than USD 16 billion in pledges. By contrast, Hurricane Matthew, which made landfall in Haiti on 4 October 2016, stayed in the shadows, attracting about one per cent of the amount. While the earthquake exhibited one face of centralisation, the Category 4 storm laid bare rural vulnerabilities shaped by postcolonial state neglect, and reinforced by the influx of non‐governmental organisations in the ‘Republic of Port‐au‐Prince’. The study draws on data from four case studies in two departments to illuminate the legacies of hyper‐centralisation in Haiti. Compounding matters, Matthew struck in the middle of an extended election that the international community attempted to control again. The paper argues that disaster assistance and politics are uncomfortably close, while reflecting on the momentary decentralisation of aid after the hurricane and its effectiveness.
Agreement among equine veterinarians and between equine veterinarians and inertial sensor system during clinical examination of hindlimb lameness in horses
Authors: Leelamankong P. , Estrada R. , Mählmann K. , Rungsri P. , Lischer C.
Published: June 2019

Background

Hindlimb lameness evaluation is known to be challenging. Experience is essential for the ability of equine veterinarians to detect lameness. Nevertheless, even an experienced veterinarian is still subject to bias. Objective lameness detecting methods have been established to aid veterinarians.

Objectives

1) To estimate the effect of experience on the interobserver agreement and the agreement between a body‐mounted inertial sensor system (BMISS) and veterinarians on detecting hindlimb lameness, and 2) to estimate the agreement between the BMISS and highly experienced veterinarians on change in lameness after diagnostic analgesia.

Study design

Cross‐sectional study.

Methods

Twenty‐six horses with hindlimb lameness were evaluated in clinical conditions by clinicians and simultaneously measured by the BMISS. Videos of their lameness examination were recorded and shown to 13 veterinarians from three groups of varying experience for evaluation. The interobserver agreement and the agreement between veterinarians and the BMISS were calculated.

Results

Interobserver agreement from all three groups was recorded as ‘fair’. The strength of agreement between veterinarians and BMISS was ‘fair’ for the highly experienced group, ‘slight to fair’ for the moderately experienced group and ‘slight’ in the inexperienced group. The BMISS and the highly experienced veterinarians declared a ‘strong’ agreement in assigning an improvement in lameness after diagnostic analgesia.

Main limitations

Lameness evaluation through video viewing might be more challenging for some evaluators than live situations.

Conclusions

Given the task of evaluating videos of horses trotting in a straight line, the more experienced veterinarians did not show more reliability than those with less experience. Due to 1) the moderate agreement between the BMISS and clinicians (highly experienced and moderately experienced) in the live clinical evaluation in determining hindlimb lameness, and 2) the strong association between the BMISS and highly experienced veterinarians in determining improvement of lameness after anaesthesia, therefore the use of the BMISS as a supporting tool for veterinarians is encouraged.
Evaluation of antitumor effects of aspirin and LGK974 drugs on cellular signaling pathways, cell cycle and apoptosis in colorectal cancer cell lines compared to oxaliplatin drug
Authors: Bagheri Malihe , Tabatabae Far Mohamad Amin , Mirzaei Hamed , Ghasemi Faezeh
Published: June 2019

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Despite recent advances in the treatment for CRC, resistance to chemotherapy drugs and recurrence of the tumor are among the main problems for treatment in this cancer. The MTT assay was performed to assess the cytotoxic effects of drugs on CRC cell lines (SW742 and SW480) and normal colon cells. Three‐dimensional culture (spheroid) was also used to evaluate the effect of drugs on tumor cell masses. The rate of expression of genes was also evaluated using Real‐Time PCR. The analysis of the results demonstrated that aspirin and LGK974 have cytotoxic effects on CRC cell lines, and in the IC50 dose, they disintegrate the cancerous cell masses. These drugs reduce the invasion and increase apoptosis in SW742 and SW480 cell lines. A decrease in the expression of WNT, AXIN, TCF and APC genes and an increase in the expression of β‐catenin gene in the WNT signaling pathway were revealed. The genes involved in the MAPK signaling pathway such as ERK, JNK, KRAS and MEK showed a decrease in expression and a increase in expression of RAF gene. In the apoptotic pathway, increased expression of BAX and decreased expression of BCL‐2 were reported. Also, decreased expression of P53, cyclin D1 and COX‐2 was observed. This study demonstrates that aspirin and LGK974 could be effective in inhibiting the signaling pathways of WNT and MAPK, arresting cell cycle and inducing apoptosis in CRC cell lines.
Specific basic patch‐dependent multimerization of Saccharomyces cerevisiae ORC on single‐stranded DNA promotes ATP hydrolysis
Authors: Kawakami Hironori , Muraoka Ryuya , Ohashi Eiji , Kawabata Kenta , Kanamoto Shota , Chichibu Takeaki , Tsurimoto Toshiki , Katayama Tsutomu
Published: June 2019

Replication initiation at specific genomic loci dictates precise duplication and inheritance of genetic information. In eukaryotic cells, ATP‐bound origin recognition complexes (ORCs) stably bind to double‐stranded (ds) DNA origins to recruit the replicative helicase onto the origin DNA. To achieve these processes, an essential region of the origin DNA must be recognized by the eukaryotic origin sensor (EOS) basic patch within the disordered domain of the largest ORC subunit, Orc1. Although ORC also binds single‐stranded (ss) DNA in an EOS‐independent manner, it is unknown whether EOS regulates ORC on ssDNA. We found that, in budding yeast, ORC multimerizes on ssDNA in vitro independently of adenine nucleotides. We also found that the ORC multimers form in an EOS‐dependent manner and stimulate the ORC ATPase activity. An analysis of genomics data supported the idea that ORC‐ssDNA binding occurs in vivo at specific genomic loci outside of replication origins. These results suggest that EOS function is differentiated by ORC‐bound ssDNA, which promotes ORC self‐assembly and ATP hydrolysis. These mechanisms could modulate ORC activity at specific genomic loci and could be conserved among eukaryotes.
Profiles and characteristics of clinical subtypes of perinatal depressive symptoms: A latent class analysis
Authors: Sun Ji‐Wei , Cao Dan‐Feng , Li Jia‐Huan , Zhang Xuan , Wang Ying , Bai Hua‐Yu , Lin Ping‐Zhen , Zhang Hui‐Hui , Cao Feng‐Lin
Published: June 2019

Aims

To investigate clinically relevant subtypes of perinatal depressive symptoms.

Design

Cross‐sectional study.

Methods

A sample of 2,783 women at different prenatal and postnatal periods was recruited between August 2015 – August 2017. The Patient Health Questionnaire–9 (PHQ‐9) was used to assess depressive symptoms. Data analyses consisted of latent class analysis (LCA), analysis of variance and multinomial logistic regression.

Results

(a) Five latent subtypes (Classes 5/4/3/1/2) were identified: ‘no symptoms’, ‘mild physio‐somatic symptoms’, ‘severe physio‐somatic symptoms and moderate anhedonia’, ‘moderate‐to‐severe symptoms’ and ‘severe symptoms’; (b) Postpartum women were more likely to belong to the severe depressive symptoms group, whereas pregnant women were likely to report severe physio‐somatic symptoms; and (c) History of abortion and perinatal complications increased the likelihood of belonging to all moderate‐to‐severe classes. Lower levels of education increased the probability of belonging to Class 2. Younger women were more likely to be categorized into Classes 1 and 2.

Conclusions

This is the first study to examine heterogeneity of perinatal depressive symptoms and delineate the characteristics of subtypes at different prenatal and postnatal periods via the PHQ‐9, using LCA in a Chinese general population.

Impact

This research details the heterogeneity of perinatal depressive symptoms and delineates the characteristics of subtypes at different prenatal and postnatal periods in a Chinese general population.
Cost‐benefit analysis of clinical pharmacist intervention in preventing adverse drug events in the general chronic diseases outpatients
Authors: Al‐Qudah Rajaa A. , Al‐Badriyeh Daoud , Al‐Ali Farah M. , Altawalbeh Shoroq M. , Basheti Iman A.
Published: June 2019

Rationale, aims, and objectives

Clinical pharmacy services are vital in the prevention of adverse drug events (ADEs) in clinical practice, extending beyond the hospital to chronic disease management in outpatient settings. This study sought to evaluate the cost benefit of a clinical pharmacy intervention in resolving treatment‐related problems (TRPs) among hospital outpatients with chronic diseases.

Methods

From the hospital system perspective, the cost‐benefit analysis was based on a randomized clinical trial in the general outpatients of the major hospital in Jordan. Eligible patients were randomly assigned to either an intervention or a control group. TRPs were identified in both study groups, but interventions were delivered only to the intervention group via a home medication management review (HMMR) by a clinical pharmacist. A follow‐up in both groups took place 3 months after recruitment. The total economic benefit was the sum of (a) cost savings due to intervention and (b) cost avoidance associated with preventable ADEs. The primary outcome measures were the net benefit and benefit‐to‐cost ratio with the clinical pharmacist‐based HMMR.

Results

In both groups, 158 TRPs were identified, and 79 interventions were provided in the study group. The monthly cost of intervention was JD764 (US $1078), and the total monthly benefit was JD4570 (US $6444), leading to a benefit‐to‐cost ratio of 5.98 and an annual net benefit of JD45 669 (US $64 393). Sensitivity analyses confirmed the robustness of results.

Conclusion

The RCT‐based cost‐benefit evaluation provided evidence‐based insight into the economic benefit of a clinical pharmacist‐provided HMMR for preventing ADEs in the general chronic diseases outpatients. This intervention method against the TRPs among outpatients is cost beneficial and offers substantial cost savings to the health care hospital payer in Jordan.
Neuronal Ca2+‐dependent activator protein 1 (NCDAP1) induces neuronal cell death by activating p53 pathway following traumatic brain injury
Authors: Arai Masaaki , Imamura Osamu , Kondoh Nobuo , Dateki Minori , Takishima Kunio
Published: June 2019

Overactivation of N‐methyl‐d‐aspartate glutamate receptors (NMDARs) after traumatic brain injury (TBI) contributes to excitotoxic cell death. The hyperactivation of NMDARs results in toxic levels of intracellular Ca2+ and in the activation of p53‐mediated apoptosis pathway. Neuronal Ca2+‐dependent activator protein 1 (NCDAP1) was identified as an epileptogenic gene of unknown function in our laboratory. In this study, we investigated the expression and cellular localization of NCDAP1 in rat models of fluid percussion‐induced TBI. NCDAP1 expression increased in the ipsilateral cortex and hippocampus adjacent to the lesion of the TBI rats compared with that in the sham‐operated controls. In addition, NCDAP1 was co‐expressed with neuronal marker (NeuN), and the results of terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling (TUNEL) staining suggest that NCDAP1 is involved in neuronal apoptosis that occurs after brain injury. In addition, the expression levels of p53, Bax, and active caspase‐3 correlated with those of NCDAP1. To further investigate the function of NCDAP1, primary cultured neurons were employed to establish an apoptosis model. The expression of NCDAP1 was induced by NMDA‐induced Ca2+ influx, and the knockdown of NCDAP1 by siRNA decreased apoptosis caused by treatment with NMDA. Silencing of NCDAP1 also reduced p53 expression, whereas the over‐expression of NCDAP1 induced cell death and up‐regulated the expression of p53. The inhibition of p53 with pifithrin alpha or siRNA counteracted the effects of NCDAP1. Based on our data, we suggest that NCDAP1 plays an important role in p53‐mediated neuronal apoptosis following TBI.

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Contribution of Chinese and French ear acupuncture for the management of chronic back pain: A randomised controlled trial
Authors: Moura Caroline de Castro , Chaves Erika de Cássia Lopes , Chianca Tânia Couto Machado , Ruginsk Silvia Graciela , Nogueira Denismar Alves , Souza Valéria Helena Salgado , Iunes Denise Hollanda
Published: June 2019

Aims and objectives

To compare the efficacy of Chinese and French ear acupuncture in people with chronic back pain.

Background

Chronic back pain is a common public health problem worldwide. An intervention for this condition is ear acupuncture. Several approaches are used for ear acupuncture, particularly the Chinese and French guidelines.

Methods

An open, randomised and controlled clinical trial, followed the recommendations of the CONSORT Checklist. One hundred and eleven people were selected and randomised into three groups: Chinese ear acupuncture, French ear acupuncture and Control. Evaluations were performed before the first intervention session (initial), 1 week after the fifth session (final) and after a fifteen‐day follow‐up period (follow‐up), using the Brief Pain Inventory, Rolland Morris Disability Questionnaire, and a thermal imaging camera. For data analysis, the Generalized Estimating Equation Model was applied, with significance level set at 5%.

Results

Pain severity was significantly decreased by Chinese ear acupuncture throughout intervention period. Both types of ear acupuncture affected pain interference with daily activities. However, in the comparison between initial and final evaluations, only Chinese ear acupuncture produced statistically significant results. A reduction in physical disability was observed in both ear acupuncture‐treated groups during the intervention period and, although Chinese ear acupuncture failed to induce significant changes in tissular temperature at individual time points, a significant increase in cutaneous temperature was detected after the follow‐up period in the dorsal region of individuals treated with Chinese ear acupuncture. Importantly, at this time point, the mean difference between Chinese and French ear acupuncture revealed a more benefic effect of Chinese procedure on this parameter.

Conclusions

The individualised treatment based on the Chinese precepts showed, in an overall evaluation, better results for management of chronic back pain in the present study.

Relevance to clinical practice

Ear acupuncture can be implemented in the nurse's clinical practice to assist the treatment of people with chronic back pain.
Summer precipitation limits plant species richness but not overall productivity in a temperate mesic old‐field meadow
Authors: Serafini John , Grogan Paul , Aarssen Lonnie
Published: June 2019

Question

Water availability is a primary regulator of plant productivity and species richness in arid and semi‐arid ecosystems, but its influence in other habitats is much less clear partly because experimental manipulations of water are relatively rare. How important is soil moisture availability relative to other key environmental factors in determining plant species biomass and diversity in temperate mesic grasslands?

Location

An old‐field meadow in southeastern Ontario, Canada.

Methods

We established a long‐term factorial field experiment to investigate how variation in soil water (achieved by rainout shelters and water additions), nutrients (NPK fertilizer additions), and above‐ground herbivory (deer fence exclosures), interact as regulators of plant production, species richness, and species composition. Above‐ground biomass for each species was determined in replicate plots (1 m2, n = 10) after five years of treatment applications.

Results

The rainout shelters reduced community shoot biomass by 35% relative to ambient (control) plots, with no influence of the fertiliser. To our surprise, however, the fertiliser enhanced community biomass in the ambient and water addition plots to a similar extent. Species richness and Shannon diversity were increased by water addition, but reduced by the rainout shelters and by fertilisation. Total species richness across all replicate plots was 60% higher in the water addition treatment, and almost halved in the water‐reduced treatment. In contrast to the above, the exclosures had negligible impacts on these community variables.

Conclusions

Together, these results suggest that in old‐field meadow grasslands: (a) shoot productivity is primarily limited by soil nutrient supply except under drought conditions when water availability becomes the primary constraint; (b) the two main soil resources for plants — water and nutrients — affect productivity and species richness/composition in fundamentally different ways; and (c) future increases in summer soil aridity and anthropogenic nitrogen deposition may interact to reduce vegetation productivity and diversity in temperate mesic ecosystems.
Early childhood development and stunting: Findings from the MAL‐ED birth cohort study in Bangladesh
Authors: Nahar Baitun , Hossain Muttaquina , Mahfuz Mustafa , Islam M. Munirul , Hossain Md Iqbal , Murray‐Kolb Laura E. , Seidman Jessica C. , Ahmed Tahmeed
Published: June 2019

Information on the association between stunting and child development is limited from low‐income settings including Bangladesh where 36% of children under‐ 5 are stunted. This study aimed to explore differences in early childhood development (ECD) between stunted (length‐for‐age z‐score [LAZ] < −2) and nonstunted (LAZ ≥ −2) children in Bangladesh. Children (n = 265) aged 6–24 months who participated in the MAL‐ED birth cohort study were evaluated by trained psychologists at 6, 15, and 24 months of age using the Bayley Scales of Infant and Toddler Development‐III; child length and weight were measured using standard procedures. ECD scores (z‐scores derived from cognitive, motor, language and socio‐emotional skills) were compared between stunted, underweight (weight‐for‐age z‐score < −2), and wasted (weight‐for‐length z‐score < −2) children, controlling for child age and sex and maternal age, education, body mass index (BMI), and depressive symptoms. Stunted children had significantly lower ECD scores than their nonstunted peers on cognitive (P = .049), motor (P < .001), language (P < .001) and social–emotional (P = .038) scales where boys had significantly lower fine motor skills compared with girls (P = .027). Mother's schooling and BMI were significant predictors of ECD. Similar to stunting, underweight children had developmental deficits in all domains (cognitive: P = .001; fine motor: P = .039, and P < .001 for both gross motor and total motor; expressive communication: P = .032; total language: P = .013; social–emotional development: P = .017). Wasted children had poor motor skills (P = .006 for the fine motor; P < .001 for both gross motor and total motor development) compared with the nonwasted peers. Early childhood stunting and underweight were associated with poor developmental outcomes in Bangladesh.
Linking plant genes to insect communities: Identifying the genetic bases of plant traits and community composition
Authors: Barker Hilary L. , Riehl Jennifer F. , Bernhardsson Carolina , Rubert‐Nason Kennedy F. , Holeski Liza M. , Ingvarsson Pär K. , Lindroth Richard L.
Published: June 2019

Community genetics aims to understand the effects of intraspecific genetic variation on community composition and diversity, thereby connecting community ecology with evolutionary biology. Thus far, research has shown that plant genetics can underlie variation in the composition of associated communities (e.g., insects, lichen and endophytes), and those communities can therefore be considered as extended phenotypes. This work, however, has been conducted primarily at the plantgenotypelevel and has not identified the key underlying genes. To address this gap, we used genome‐wide association mapping with a population of 445 aspen (Populus tremuloides) genets to identify the genes governing variation in plant traits (defence chemistry, bud phenology, leaf morphology, growth) and insect community composition. We found 49 significant SNP associations in 13Populusgenes that are correlated with chemical defence compounds and insect community traits. Most notably, we identified an early nodulin‐like protein that was associated with insect community diversity and the abundance of interacting foundation species (ants and aphids). These findings support the concept that particular plant traits are the mechanistic link between plant genes and the composition of associated insect communities. In putting the “genes” into “genes to ecosystems ecology”, this work enhances understanding of the molecular genetic mechanisms that underlie plant–insect associations and the consequences thereof for the structure of ecological communities.
Impacts of long‐term elevated atmospheric CO2 concentrations on communities of arbuscular mycorrhizal fungi
Authors: Maček Irena , Clark Dave R. , Šibanc Nataša , Moser Gerald , Vodnik Dominik , Müller Christoph , Dumbrell Alex J.
Published: June 2019

The ecological impacts of long‐term elevated atmospheric CO2 (eCO2) levels on soil microbiota remain largely unknown. This is particularly true for the arbuscular mycorrhizal (AM) fungi, which form mutualistic associations with over two‐thirds of terrestrial plant species and are entirely dependent on their plant hosts for carbon. Here, we use high‐resolution amplicon sequencing (Illumina, HiSeq) to quantify the response of AM fungal communities to the longest running (>15 years) free‐air carbon dioxide enrichment (FACE) experiment in the Northern Hemisphere (GiFACE); providing the first evaluation of these responses from old‐growth (>100 years) semi‐natural grasslands subjected to a 20% increase in atmospheric CO2. eCO2 significantly increased AM fungal richness but had a less‐pronounced impact on the composition of their communities. However, while broader changes in community composition were not observed, more subtle responses of specific AM fungal taxa were with populations both increasing and decreasing in abundance in response to eCO2. Most population‐level responses to eCO2 were not consistent through time, with a significant interaction between sampling time and eCO2 treatment being observed. This suggests that the temporal dynamics of AM fungal populations may be disturbed by anthropogenic stressors. As AM fungi are functionally differentiated, with different taxa providing different benefits to host plants, changes in population densities in response to eCO2 may significantly impact terrestrial plant communities and their productivity. Thus, predictions regarding future terrestrial ecosystems must consider changes both aboveground and belowground, but avoid relying on broad‐scale community‐level responses of soil microbes observed on single occasions.
Speech rhythm and language acquisition: an amplitude modulation phase hierarchy perspective
Authors: Goswami Usha
Published: June 2019

Language lies at the heart of our experience as humans and disorders of language acquisition carry severe developmental costs. Rhythmic processing lies at the heart of language acquisition. Here, I review our understanding of the perceptual and neural mechanisms that support language acquisition, from a novel amplitude modulation perspective. Amplitude modulation patterns in infant‐ and child‐directed speech support the perceptual experience of rhythm, and the brain encodes these rhythm patterns in part via neuroelectric oscillations. When brain rhythms align themselves with (entrain to) acoustic rhythms, speech intelligibility improves. Recent advances in the auditory neuroscience of speech processing enable studies of neuronal oscillatory entrainment in children and infants. The “amplitude modulation phase hierarchy” theoretical perspective on language acquisition is applicable across languages, and cross‐language investigations adopting this novel perspective would be valuable for the field.