bluuebunny/crossref_metadata_2025 huggingface dataset:
Foliar fungi alter reproductive timing and allocation in Arabidopsis under normal and water-stressed conditions
Authors: Zahn Geoffrey , Amend Anthony S.
Published: January 2019

Microbes influence plant phenotypes but most known examples of this are from the study of below-ground microbes and plant disease modification. To examine the potential importance of phyllosphere microbes on non-disease related plant traits, we used sterile Arabidopsis clones to test the effects of foliar fungi on flowering phenology and reproductive allocation under conditions of varying water stress. We inoculated the sterile plants with fully-factorial combinations of four fungal isolates, then measured flowering time and reproductive allocation for each treatment group under normal and water-stressed conditions. All plants inoculated with foliar fungi had significantly later flowering and greater seed mass than the sterile control groups. The magnitude of this effect depended on the specific fungi present, but individual fungal effects diminished as inoculum richness increased. Above-ground microbes likely influence other plant traits as well and should be considered in any study measuring plant phenotypes.
In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA
Authors: Ginosyan Siranush , Grabski Hovakim , Tiratsuyan Susanna
Published: January 2019

Artemisinins are secondary metabolites of the medicinal plant Artemisia annua, which has been traditionally used in Chinese medicine. Artemisinins have anti-inflammatory, anticarcinogenic, immunomodulatory, antimicrobial, anthelmintic, antiviral, antioxidant, and other properties. Our preliminary reverse virtual screening demonstrated that the ligand-binding domain of the human glucocorticoid receptor (LBD of hGR) is the optimal target for artemisinin. At the same time, the binding sites for artemisinin with the ligand-binding domain of the human glucocorticoid receptor coincide with those of dexamethasone. However, the pharmacokinetics, pharmacodynamics, and exact molecular targets and mechanisms of action of artemisinin are not well known. In this work, the interaction of artemisinin with human serum albumin (HSA) was studied both in vitro and in silico. The results indicate that artemisinin leads to a decrease in optical absorption and quenching of fluorescence by a static mechanism, which is similar to the effect of dexamethasone. Artemisinin interacts with Drug site I on HSA and forms a hydrogen bond with arginine 218. Retardation of the genomic DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. On the basis of the obtained data, we proposed a hypothetical scheme of the mechanisms of action of artemisinin.

Highlights

Artemisinin quenches the fluorescence of HSA by a static mechanism.

Artemisinin quenches fluorescence of tryptophan.

The optimized HSA structure was obtained through molecular dynamics simulations.

Artemisinin binds with HSA in Drug site I and forms a hydrogen bond with Arg218.

Dexamethasone binds with HSA in Drug site I and forms hydrogen bonds with Arg218, Arg222 and Va1343.

A hypothetical scheme of the mechanism of action of Artemisinin was proposed.

Graphical Abstract
Experimental and mathematical insights on the competition between poliovirus and a defective interfering genome
Authors: Shirogane Yuta , Rousseau Elsa , Voznica Jakub , Rouzine Igor M. , Bianco Simone , Andino Raul
Published: January 2019

During replication, RNA virus populations accumulate genome alterations, such as mutations and deletions. The interactions between individual variants within the population can determine the fitness of the virus and, thus, the outcome of infection. We developed an ordinary differential equation model to infer the effect of the interaction between defective interfering (DI) replicons and wild-type (WT) poliovirus. We measure production of RNA and viral particles during a single infection cycle, and use these data to infer model parameters. We find that DI replicates faster than WT, but an equilibrium is established when both WT and DI compete for resources needed for RNA replication and genome encapsidation. In the presence of DI, the concentration of WT virions at cell lysis is suppressed by the factor of 5. Multiple generations within a single cell infection provide opportunities for significant inhibition of WT replication by competition with the faster replicating DI genomes.
Improved state change estimation in dynamic functional connectivity using hidden semi-Markov models
Authors: Shappell Heather , Caffo Brian S. , Pekar James J. , Lindquist Martin A.
Published: January 2019

The study of functional brain networks has grown rapidly over the past decade. While most functional connectivity (FC) analyses estimate one static network structure for the entire length of the functional magnetic resonance imaging (fMRI) time series, recently there has been increased interest in studying time-varying changes in FC. Hidden Markov models (HMMs) have proven to be a useful modeling approach for discovering repeating graphs of interacting brain regions (brain states). However, a limitation lies in HMMs assuming that the sojourn time, the number of consecutive time points in a state, is geometrically distributed. This may encourage inaccurate estimation of the time spent in a state before switching to another state. We propose a hidden semi-Markov model (HSMM) approach for inferring time-varying brain networks from fMRI data, which explicitly models the sojourn distribution. Specifically, we propose using HSMMs to find each subject’s most probable series of network states and the graphs associated with each state, while properly estimating and modeling the sojourn distribution for each state. We perform a simulation study, as well as an analysis on both task-based fMRI data from an anxiety-inducing experiment and resting-state fMRI data from the Human Connectome Project. Our results demonstrate the importance of model choice when estimating sojourn times and reveal their potential for understanding healthy and diseased brain mechanisms.
The regulatory function of dIno80 correlates with its DNA binding activity
Authors: Jain S , Maini J , Narang A , Maiti S , Brahmachari V
Published: January 2019

The INO80 complex, including the Ino80 protein, forms a highly conserved canonical complex that remodels chromatin in the context of multiple cellular functions. TheDrosophilahomologue, dIno80, is involved in homeotic gene regulation during development as a canonical Pho-dIno80 complex. Previously, we found that dIno80 regulates homeotic genes by interacting with epigenetic regulators, such as polycomb and trithorax, suggesting the occurrence of non-canonical Ino80 complexes. Here using spectroscopic methods and gel retardation assays, we identified a set of consensus DNA sequences that DNA binding domain of dIno80 (DBINO) interacts with having differential affinity and high specificity. Testing these sequences in reporter assays, showed that this interaction can positively regulate transcription. These results suggest that, dIno80 has a sequence preference for interaction with DNA leading to transcriptional changes.

SIGNIFICANCE

The chromatin remodeling proteins control gene expression by nucleosome sliding and exchange. They are known to function as multi-subunit complexes recruited to chromatin by transcription factors or histone modification readers. Here, we report a sequence specific binding potential for the chromatin remodeler, dIno80. We have carried outin vitrostudies with DNA binding domain of dIno80 to elucidate its sequence specific DNA binding. We have also showed that this binding can regulated reporter gene expression inDrosophilacells. Our results suggest a non-canonical role of Ino80 in transcriptional regulation.
Dynamics of chromosome replication and its relationship to predatory attack lifestyles in Bdellovibrio bacteriovorus
Authors: Makowski Łukasz , Trojanowski Damian , Till Rob , Lambert Carey , Lowry Rebecca , Sockett R. Elizabeth , Zakrzewska-Czerwińska Jolanta
Published: January 2019

Bdellovibrio bacteriovorus is a small Gram-negative, an obligate predatory bacterium that is largely found in wet, aerobic environments (i.e. soil). This bacterium attacks and invades other Gram-negative bacteria, including animal and plant pathogens. The intriguing life cycle of B. bacteriovorus consists of two phases: a free-living non-replicative attack phase wherein the predatory bacterium searches for its prey, and a reproductive phase, in which B. bacteriovorus degrades a host’s macromolecules and reuses them for its own growth and chromosome replication. Although the cell biology of this predatory bacterium has gained considerable interest in recent years, we know almost nothing about the dynamics of chromosome replication in B. bacteriovorus. Here, we performed a real-time investigation into the subcellular localization of the replisome(s) in single cells of B. bacteriovorus. Our results confirm that in B. bacteriovorus chromosome replication fires only during the reproductive phase, and show for the first time that this predatory bacterium exhibits a novel spatiotemporal arrangement of chromosome replication. The replication process starts at the invasive pole of the predatory bacterium inside the prey cell and proceeds until several copies of the chromosome have been completely synthesized. This chromosome replication is not coincident with the predator-cell division, and it terminates shortly before synchronous predator-filament septation occurs. In addition, we demonstrate that if this lifecycle fails in some cells of B. bacteriovorus, they can instead use two prey cells sequentially to complete their life cycle.

Importance

New strategies are needed to combat multidrug-resistant bacterial infections. Application of the predatory bacterium, Bdellovibrio bacteriovorus, which kills other bacteria including pathogens, is considered promising for bacterial infections. The B. bacteriovorus life cycle consists of two phases, a free-living, invasive attack phase and an intracellular reproductive phase, in which this predatory bacterium degrades the host’s macromolecules and reuses them for its own growth. To understand the use of B. bacteriovorus as a ‘living antibiotic’, it is first necessary to dissect its life cycle including chromosome replication. Here, we present for the first time a real-time investigation into subcellular localization of chromosome replication in a single cells of B. bacteriovorus. This process initiates at the invasion pole of B. bacteriovorus and proceeds until several copies of the chromosome have been completely synthesized. Interestingly, we demonstrate that some cells of B. bacteriovorus require two prey cells sequentially to complete their life cycle.
Choice of birth place among antenatal clinic attendees in rural mission hospitals in Ebonyi State, South-East Nigeria
Authors: Ajah Leonard O. , Onu Fidelis A. , Ogbuinya Oliver C. , Ajah Monique I. , Ozumba Benjamin C. , Agbata Anthony T. , Onoh Robinson C. , Ekwedigwe Kenneth C.
Published: January 2019

Background

Low utilization of health facilities for delivery by pregnant women poses a public health challenge in Nigeria.

Aim

To determine the factors that influence the choice of birth place among antenatal clinic attendees.

Methodology

This was a cross-sectional study of the eligible antenatal clinic attendees at Mater Misericordiae Hospital, Afikpo and Saint Vincent Hospital, Ndubia in Ebonyi State from February 1, 2016 to June 30, 2016. Analysis was done using EPI Info 7.21 software (CDC Atlanta Georgia).

Results

A total of 397(99.3%) completely filled questionnaires were collated and analysed. Approximately 71% of the health facilities closest to the respondents had maternity services. It took at least 1 hour for 80.9% of the respondents to access health facilities with maternity services. Most (60.2%) of the respondents had antenatal care attendance and majority of them did so at public hospitals. Approximately 43.8% of the respondents were delivered by the skilled birth attendants. The common determinants of birth place were nearness of the health facilities, familiarity of healthcare providers, improved services, sudden labour onset and cost. Also 61.7% of the respondents chose to deliver in public health facilities due to favourable reasons but this could be hampered by the rudeness of some healthcare providers at such facilities. A significant proportion of private health facilities had unskilled manpower and shortage of drugs.

Conclusion

A greater proportion of women will prefer to deliver in health facilities. However there are barriers to utilization of these facilities hence the need for reversal of this ugly trend.
A pilot study to evaluate the effect of a novel calcium and vitamin D-containing oral bolus on serum calcium levels in Holstein dairy cows following parturition
Authors: Shock Daniel A. , Roche Steven M. , Genore Rachel , Olson Merle E.
Published: January 2019

The initiation of lactation challenges the ability of the modern lactating cow to maintain calcium homeostasis, and typically results in a drop in blood calcium levels; leading to mobilization of calcium reserves from skeletal stores. As such, the recommendation to provide supplemental calcium at parturition to older cows has become an industry-standard practice. Mature cows were treated at calving and 12 hours later with either the novel calcium bolus (NB), or a commercially available calcium bolus (CB). Blood was collected from animals at 0, 1, 6, 12, 13, and 24 hours following calving, and the resulting serum samples were analyzed. Overall, there was no statistical difference between the NB and CB groups for blood calcium levels within the first 24 hours following parturition (P = 0.50). Cows in both groups experienced a significant increase in serum calcium by 1 hour after parturition; however, this increase was not sustained through subsequent sampling times. This pilot study demonstrates that both boluses have a similar effect in the elevation of blood calcium.
Surviving in the digital era – business models of digital enterprises in a developing economy
Authors: Ansong Eric , Boateng Richard
Published: January 2019

Purpose

This study aims to explore the business models and strategies of digital enterprises in a developing economy context to understand the nature of their operations, as well as their survival tactics.

Design/methodology/approach

A review of literature on digital enterprise models led to the adaptation of a 16 business model archetype for analyzing digital enterprises in Ghana. Using a critical realism perspective, survey data from a sample of 91 digital enterprises were used for the study.

Findings

The findings suggest that among human, physical and intangible assets, financial assets were the least used assets in the operations of the digital enterprises. This stems from the fact that the online financial business sector is still in its nascent stages in most developing economies. The findings further suggest that all digital enterprises leverage on accessible and low-cost social networking services as part of their operations and use them as an avenue to engage with their target customers.

Research limitations/implications

The findings from this study provide guidelines to entrepreneurs who wish to venture into the digital ecosystem of Ghana, particularly with regard to the economic, financial and technological factors that enable digital enterprises to survive in the competitive digital economy.

Practical implications

The findings suggest that it is important for governments to realize that there is an increasing rise in digital enterprises in the developing economies and these enterprises are creating jobs and providing business solutions locally that would hitherto be sought from developed economies. There is therefore the need for the requisite legal infrastructure and financial support that will cushion these enterprises from the fierce competitions that stagnate their growth.

Originality/value

The study provides a mapping of the digital business models of Ghanaian digital enterprises. This knowledge is arguably the first of its kind in the context of a developing economy. Hence, it serves as a stepping-stone for future studies to explore other areas in the digital economy, especially from a developing economy perspective.
Role of team transformational leadership and workplace spirituality in facilitating team viability: an optimal distinctiveness of identities’ theory-based perspective
Authors: K.P. Nandan Prabhu , Rodrigus L.R. Lewlyn , K.P.V. Ramana Kumar , Pai Yogesh P.
Published: January 2019

Purpose

The purpose of this paper is to investigate the moderating role of workplace spirituality (WS) in the relationship between team transformational leadership (TTL) and team viability (TV) under the theoretical lens of the theory of optimal distinctiveness of identities.

Design/methodology/approach

This study adopted quantitative, cross-sectional research design at the team level of analysis among 141 software development project teams that belonged to 22 information technology (IT) organizations in the Indian IT sector to evaluate the effect of TTL behavior on TV under the conditional presence of WS.

Findings

This research has found empirical evidence to show that TTL is positively associated with TV or the team members’ desire to be a part of future performance episodes of their team. However, this research has shown that the relative effect of WS on the relationship between TTL and TV is weaker in those teams that experience higher levels of WS than those teams that experience lower levels of WS.

Originality/value

This research’s originality exists in its team-level conceptualization of WS, a gap in prior research addressed by this paper, in order to evaluate the interactive effects of team-level conceptualizations of transformational leadership and WS on TV. Further, this paper’s originality stems from the explanation of TV as the result of desirable balance between team members’ needs for within-team inclusion and within-team differentiation.
The employee engagement and OCB as mediating on employee performance
Authors: Ayu Putu Widani Sugianingrat Ida , Rini Widyawati Sapta , Alexandra de Jesus da Costa Carla , Ximenes Mateus , Dos Reis Piedade Salustiano , Gede Sarmawa Wayan
Published: January 2019

Purpose

The purpose of this paper is to examine the effect of ethical leadership on employee performance, with the employee engagement and organizational citizenship behavior (OCB) as mediating variables.

Design/methodology/approach

The design of this study was to ascertain the predictive generalizations truth of the theory. The population in this study was all employees of non-star hotels in Sarbagita area of Bali.

Findings

First, ethical leadership does not have a significant effect on employee performance, where the increase in leadership value is not able to provide a significant improvement in the performance of non-star hotel employees in the Sarbagita area of Bali. Second, employee engagement is able to mediate ethical leadership in improving employee performance. Third, the OCB will be able to play a role in mediating the influence of ethical leadership on employee performance if it passes the mediating role of employee engagement first.

Originality/value

The inconsistencies of the previous study results provide evidence and opportunities for this study to review by including mediating variables on ethical leadership and employee performance relationship. The studied variable as a mediating variable is employee engagement. In addition to employee engagement, this study also included the OCB variable as a mediating variable. Several previous studies have identified the influence of ethical leadership, employee engagement and OCB in improving employee performance in separate research models, so there is still a gap for further research.
Labour-only procurement
Authors: Awodele Oluwaseyi Alabi , Aghimien Douglas Omoregie , Akinkunmi Olutayo Gabriel , Aigbavboa Clinton Ohis
Published: January 2019

Purpose

Due to its cost savings nature and ability to ensure constant jobs for contractors, this study aims to assess the capability of the labour-only procurement system to serve as a surviving strategy for construction contractors in a challenging economy.

Design/methodology/approach

The study adopted a mixed-methods design. An interview and questionnaire were used to harness information from 98 construction participants who have been involved in labour-only procured projects. These respondents were identified through snowballing. Frequency, percentage, mean item score, Mann–Whitney u-test and content analysis were used in analysing the data gathered.

Findings

Result revealed that participants are willing to execute more projects through this system because it gives considerable cost savings for clients and provides reduction in contractor’s risk and allows them to maintain healthy cash flow. The main factors influencing its usage are the client’s decision to procure materials, need for job at hand for contractors and the need for referrals from clients for subsequent jobs.

Practical implications

Findings of this study will assist contractors to understand the potential of this procurement system as a surviving option in a harsh economy. Small and medium contractors can make use of this available opportunity of having projects at hand at reduced risk to ensure continuous cash flow to keep their organisations afloat.

Originality/value

The contribution of this study to the body of knowledge lies in its provision of a reasonable insight on the inherent nature of a procurement system as a surviving strategy for contractors unlike the usual assessment of the generic survival strategies adopted in other studies.
How far have we come with the study of knowledge risks?
Authors: Durst Susanne
Published: January 2019

Purpose

This paper aims to review research on the topic of knowledge risks to establish the current body of knowledge and, on this basis, to suggest some promising avenues for future research.

Design/methodology/approach

This study consists of a systematic review of 52 refereed articles on knowledge risks.

Findings

The findings contribute to a more holistic view of the topic and related aspects and, thus, complement the study of knowledge management. Additionally, a number of research questions are proposed, aimed at guiding and informing future research activities.

Research limitations/implications

This study may not have enabled a complete coverage of all articles in the field of knowledge risks. Yet, based on the chosen research methodology, it seems reasonable to assume that the review process covered a large share of studies available.

Originality/value

To the best of the author’s knowledge, no systematic literature review on knowledge risks and related issues has previously been published in academic journals.
Neutrophil‐lymphocyte ratio as a predictor of kidney function decline among individuals with diabetes and prediabetes: A 3‐year follow‐up study
Authors: Li Jia , Li Tong , Wang Haibin , Yan Wenhua , Mu Yiming
Published: January 2019

Highlights

This study is the first study to confirm that the neutrophil–lymphocyte ratio (NLR) is an independent predictive factor for kidney function decline among individuals with diabetes and prediabetes.

Calculating the NLR is easy and inexpensive, so we believe that with more research support the NLR will be used as an effective indicator in the clinical management of individuals with diabetes and prediabetes.
Pilot Trial of an Emergency Department–based Intervention to Promote Child Passenger Safety Best Practices
Authors: Macy Michelle L. , Kandasamy Deepika , Resnicow Ken , Cunningham Rebecca M.
Published: January 2019

Background

Despite demonstrated effectiveness of child restraint systems (CRSs), use remains suboptimal. In this randomized pilot trial, we sought to determine the feasibility, acceptability, and potential efficacy of “Tiny Cargo, Big Deal” an ED‐based intervention to promote guideline‐concordant size‐appropriate CRS use.

Methods

Parents of children < 11 years old were recruited in two EDs and randomized in a 2 × 2 factorial design to four conditions: 1) generic information sheet, 2) tailored brochure mailed after the ED visit, 3) a single motivational interviewing‐based counseling session in the ED, and 4) full intervention (counseling session plus tailored brochure). We assessed feasibility (recruitment, completion, follow‐up rates) and acceptability (parent attitudes, uptake of information) in the ED, at 1 month and at 6 months. We obtained preliminary estimates of effect sizes of the intervention components on appropriate CRS use at 6‐month follow‐up.

Results

Of the 514 parents assessed for eligibility, 456 met inclusion criteria and 347 consented to participate. Enrolled parents were mostly mothers (88.1%); 48.7% were 18 to 29 years old; 52.5% were non‐Hispanic, white; and 65.2% reported size‐appropriate CRS use. Completion rates were 97.7% for baseline survey, 81.6% for counseling, 51.9% for 1‐month follow‐up, and 59.3% for 6‐month follow‐up. In the ED, 70.5% rated thinking about child passenger safety in the ED as very helpful. At 1 month, 70.0% expressed positive attitudes toward the study. Of 132 parents who reported receiving study mailings, 78.9% reviewed the information. Parents randomized to the full intervention demonstrated an increase (+6.12 percentage points) and other groups a decrease (–1.69 to –9.3 percentage points) in the proportion of children reported to use a size‐appropriate CRS at 6‐month follow‐up.

Conclusions

Suboptimal CRS use can be identified and intervened upon during a child's ED visit. A combined approach with ED‐based counseling and mailed tailored brochures shows promise to improve size‐appropriate CRS use.
Two climate‐sensitive tree‐ring chronologies from Arnhem Land, monsoonal Australia
Authors: Allen Kathryn J. , Brookhouse Matthew , French Ben J. , Nichols Scott C. , Dahl Brittany , Norrie Declan , Prior Lynda D. , Palmer Jonathan G. , Bowman David J. M. S.
Published: January 2019

The ecology of the Australian monsoon tropics is fundamentally shaped by dry conditions between May and October followed by highly variable rainfall over the months of November to April. Due to its crucial ecological importance, a better understanding of past hydroclimate variability in the region is of great interest to land managers and custodians in this region. Short instrumental records also make highly resolved terrestrial palaeoclimate records for northern Australia prior to 1900 CE of considerable scientific importance. Here, we present two new well‐replicated Callitris intratropica ring‐width chronologies from Arnhem Land in northern Australia, one of which extends the tree‐ring record in the region by another 86 years, back to 1761. Both chronologies have clearly defined regional patterns of correlations with temperature, precipitation, potential evapotranspiration and two drought indices (the self‐calibrating Palmer Drought Severity Index (PDSI) and the Standardised Precipitation Evapotranspiration Index (SPEI)) across the lower latitudes of the Northern Territory. Results indicate considerable scope for hydroclimatic reconstructions based on C. intratropica for transitional periods into and out of the wettest time of the year. This suggests that such reconstructions would reflect variability in the duration of the wet period. While precipitation or streamflow reconstructions may be possible for both these transitional periods, drought reconstructions will be best focused on the months of March–May at the end of the wet period. Hydroclimate reconstructions would provide important baseline information for understanding the rate and magnitude of current regional climate change for these ecologically and culturally important transitional periods.
Urban Systems of Accumulation: Half a Century of Chilean Neoliberal Urban Policies
Authors: Navarrete‐Hernandez Pablo , Toro Fernando
Published: January 2019

We analyse a half‐century of Chilean urban reforms to explain the introduction of a system of urban accumulation by dispossession of public resources and opportunities. Three stages have been conceptualised in the imposition of a neoliberal creative‐destructive process: proto‐neoliberalism, roll‐back and roll‐out periods. Empirical studies have traditionally analysed this process by examining a single urban policy's evolution over time. In this paper, we go beyond these types of studies by performing a systemic analysis of multiple urban policy reforms in Santiago, Chile. We use a genealogical thematic analysis to track changes in laws, government programmes and planning documents from between 1952 and 2014. Our analysis identifies different “urban systems of accumulation” by looking at the interplay of four urban policies: (1) urban planning deregulation; (2) social housing privatisation; (3) devolution of territorial taxes; and (4) decreased public service provision. Moreover, our multidimensional policy analysis in Santiago characterises a more radical, fourth expression in the creative destruction process of “accumulation by dismantling”. Consequently, we advocate for more multidimensional urban policy research that goes beyond a three‐period analysis in order to gain a deeper understanding of contemporary neoliberal creative‐destructive processes in variegated geographies.
Mesenchymal stromal cells for acute graft‐versus‐host disease: response at 1 week predicts probability of survival
Authors: Galleu Antonio , Milojkovic Dragana , Deplano Simona , Szydlo Richard , Loaiza Sandra , Wynn Robert , Marks David I. , Richardson Deborah , Orchard Kim , Kanfer Edward , Tholouli Eleni , Saif Muhammad , Sivaprakasam Ponni , Lawson Sarah , Bloor Adrian , Pagliuca Antonio , Potter Victoria , Mehra Varun , Snowden John A. , Vora Ajay , Kishore Bhuvan , Hunter Hannah , Apperley Jane F. , Dazzi Francesco
Published: January 2019

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid‐resistant graft‐versus‐host‐disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients’ overall survival. In our cohort, cell dose, patients’ age and type of organ involvement are crucial factors associated with clinical responses.
Androgen deprivation therapy for prostate cancer and risk of dementia
Authors: Robinson David , Garmo Hans , Van Hemelrijck Mieke , Damber Jan‐Erik , Bratt Ola , Holmberg Lars , Wahlund Lars‐Olof , Stattin Pär , Adolfsson Jan
Published: January 2019

Objectives

To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.

Methods

Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer‐free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non‐Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW.

Results

A total of 25 967 men with prostate cancer and 121 018 prostate cancer‐free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin‐releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07–1.23) and orchiectomy (HR 1.60, 95% CI 1.32–1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer‐free men; however, this increase in risk was only observed for non‐Alzheimer's dementia and occurred from year 1–4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW.

Conclusion

This population‐based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non‐Alzheimer's dementia.
Shortcuts to intestinal carcinogenesis by genetic engineering in organoids
Authors: Maru Yoshiaki , Onuma Kunishige , Ochiai Masako , Imai Toshio , Hippo Yoshitaka
Published: January 2019

Inactivation of the Adenomatous polyposis coli (APC) gene is an initiating and the most relevant event in most sporadic cases of colorectal cancer, providing a rationale for using Apc‐mutant mice as the disease model. Whereas carcinogenesis has been observed only at the organism level, the recent development of the organoid culture technique has enabled long‐term propagation of intestinal stem cells in a physiological setting, raising the possibility that organoids could serve as an alternative platform for modeling colon carcinogenesis. Indeed, it is demonstrated in the present study that lentivirus‐based RNAi‐mediated knockdown of Apc in intestinal organoids gave rise to subcutaneous tumors upon inoculation in immunodeficient mice. Reconstitution of common genetic aberrations in organoids resulted in development of various lesions, ranging from aberrant crypt foci to full‐blown cancer, recapitulating multi‐step colorectal tumorigenesis. Due to its simplicity and utility, similar organoid‐based approaches have been applied to both murine and human cells in many investigations, to gain mechanistic insight into tumorigenesis, to validate putative tumor suppressor genes or oncogenes, and to establish preclinical models for drug discovery. In this review article, we provide a multifaceted overview of these types of approaches that will likely accelerate and advance research on colon cancer.
Ligand‐binding affinity of alternative conformers of human β2‐adrenergic receptor in the presence of intracellular loop 3 (ICL3) and their potential use in virtual screening studies
Authors: Dilcan Gonca , Doruker Pemra , Akten Ebru Demet
Published: January 2019

This study investigates the structural distinctiveness of orthosteric ligand‐binding sites of several human β2 adrenergic receptor (β2‐AR) conformations that have been obtained from a set of independent molecular dynamics (MD) simulations in the presence of intracellular loop 3 (ICL3). A docking protocol was established in order to classify each receptor conformation via its binding affinity to selected ligands with known efficacy. This work's main goal was to reveal many subtle features of the ligand‐binding site, presenting alternative conformations, which might be considered as either active‐ or inactive‐like but mostly specific for that ligand. Agonists, inverse agonists, and antagonists were docked to each MD conformer with distinct binding pockets, using different docking tools and scoring functions. Mostly favored receptor conformation persistently observed in all docking/scoring evaluations was classified as active or inactive based on the type of ligand's biological effect. Classified MD conformers were further tested for their ability to discriminate agonists from inverse agonists/antagonists, and several conformers were proposed as important targets to be used in virtual screening experiments that were often limited to a single X‐ray structure.
Perceived health of patients with common variable immunodeficiency – a cluster analysis
Authors: Bayrhuber M , Tinsel I , Goldacker S , Kindle G , Warnatz K , Farin E , Nieters A
Published: January 2019

Common variable immunodeficiency (CVID) is a complex disease with various influences on perceived health, which correlate with different outcomes, including new morbidity and mortality. Our hypothesis was that CVID patients fall into distinct clusters of perceived health which can inform care. Ward hierarchical cluster analysis and K-means cluster analysis were performed on data of 209 CVID patients to identify subgroups regarding their self-reported physical and mental health status, assessed by the physical (PCS) and mental component scores (MCS) of the Short Form-12 (SF-12). Four clusters of CVID-patients were identified. Cluster 1 was the largest cluster, characterized by a relatively high physical and mental health status (44·0%). In contrast, cluster 2 (21·1%) included patients with low physical and mental health status. Clusters 3 and 4 were mixed groups with high mental and low physical health (15·8%) and vice versa (19·1%). Significant differences between the clusters were found for patient-reported outcomes such as work ability and health literacy, but not for CVID-associated complications such as enteropathy, interstitial lung disease, granulomatosis, lymphadenopathy and autoimmune cytopenia or laboratory parameters such as immunoglobulin levels or B cell-based classification. The results suggest different subgroups of CVID patients with contrasting individual needs which, surprisingly, did not differ in clinical or laboratory characteristics. The main finding of this study is that patients with CVID fall into four distinct clusters according to perceived health, which are largely independent of CVID complications.
Arthropod communities in fungal fruitbodies are weakly structured by climate and biogeography across European beech forests
Authors: Friess Nicolas , Müller Jörg C. , Aramendi Pablo , Bässler Claus , Brändle Martin , Bouget Christophe , Brin Antoine , Bussler Heinz , Georgiev Kostadin B. , Gil Radosław , Gossner Martin M. , Heilmann‐Clausen Jacob , Isacsson Gunnar , Krištín Anton , Lachat Thibault , Larrieu Laurent , Magnanou Elodie , Maringer Alexander , Mergner Ulrich , Mikoláš Martin , Opgenoorth Lars , Schmidl Jürgen , Svoboda Miroslav , Thorn Simon , Vandekerkhove Kris , Vrezec Al , Wagner Thomas , Winter Maria‐Barbara , Zapponi Livia , Brandl Roland , Seibold Sebastian
Published: January 2019

Aim

The tinder fungusFomes fomentariusis a pivotal wood decomposer in European beechFagus sylvaticaforests. The fungus, however, has regionally declined due to centuries of logging. To unravel biogeographical drivers of arthropod communities associated with this fungus, we investigated how space, climate and habitat amount structure alpha and beta diversity of arthropod communities in fruitbodies ofF. fomentarius.

Location

Temperate zone of Europe.

Taxon

Arthropods.

Methods

We reared arthropods from fruitbodies sampled from 61 sites throughout the range of European beech and identified 13 orders taxonomically or by metabarcoding. We estimated the total number of species occurring in fruitbodies ofF. fomentariusin European beech forests using the Chao2 estimator and determined the relative importance of space, climate and habitat amount by hierarchical partitioning for alpha diversity and generalized dissimilarity models for beta diversity. A subset of fungi samples was sequenced for identification of the fungus’ genetic structure.

Results

The total number of arthropod species occurring in fruitbodies ofF. fomentariusacross European beech forests was estimated to be 600. Alpha diversity increased with increasing fruitbody biomass; it decreased with increasing longitude, temperature and latitude. Beta diversity was mainly composed by turnover. Patterns of beta diversity were only weakly linked to space and the overall explanatory power was low. We could distinguish two genotypes ofF. fomentarius,which showed no spatial structuring.

Main conclusion

Fomes fomentariushosts a large number of arthropods in European beech forests. The low biogeographical and climatic structure of the communities suggests that fruitbodies represent a habitat that offers similar conditions across large gradients of climate and space, but are characterized by high local variability in community composition and colonized by species with high dispersal ability. For European beech forests, retention of trees withF. fomentariusand promoting its recolonization where it had declined seems a promising conservation strategy.
Regional Financial Arrangements in the Global Financial Safety Net: The Arab Monetary Fund and the Eurasian Fund for Stabilization and Development
Authors: Fritz Barbara , Mühlich Laurissa
Published: January 2019

The so‐called global financial safety net provides backstop insurance during financial crises. The three elements of the global safety net — the IMF, regional financial arrangements (RFAs) and bilateral swap agreements — underwent substantial changes after the global financial crisis. How have these changes influenced their use? What role do RFAs have in the safety net? This contribution addresses these questions by examining the timeliness, volume and policy conditionality of liquidity provision of each of the three elements, using a data set of 50 RFA member countries from the period 1976–2015. The article presents case studies of the Arab Monetary Fund (AMF) and the Eurasian Fund for Stabilization and Development (EFSD) to create a deeper institutional understanding of the governance mechanisms of regional funds. The authors find that today's global financial safety net produces inequalities in emergency liquidity provision. In terms of volume, RFAs improve the safety net only for small member countries — about one‐third of the countries in the sample can access sufficient liquidity regionally. The experiences of AMF and EFSD demonstrate that intra‐regional asymmetries of RFAs play a contradictory role: while the participation of large economies leverages liquidity provision, it simultaneously creates difficulties for the governance of the regional body.
Regime Complexity and the Institutions of Crisis and Development Finance
Authors: Henning C. Randall
Published: January 2019

The theory of regime complexity offers a useful lens through which to analyse the increasing density of international institutions and the patterns of conflict and cooperation among them. Scholarship on crisis and development finance would benefit from more fully employing this approach to explain the emergence of overlapping institutions and offer recommendations for designing regime complexes. The theory advanced here emphasizes the strategies of key states to use institutional overlap to limit agency ‘drift’ away from their preferences. Prioritizing control often comes at the cost of conflict among the institutions, however, and can thus impede the achievement of financial stability and development goals. The regime complexity approach is distinct from the rational design of institutions, institutional experimentalism and theoretical realism. Drawing on lessons from the euro crisis, this article offers informed conjectures on financial arrangements in the regions of Latin America and East Asia and their interaction with global multilateral institutions, such as the International Monetary Fund.
The (Ineffective) Financial Statecraft of China's Bilateral Swap Agreements
Authors: McDowell Daniel
Published: January 2019

Since 2008, the People's Bank of China has signed bilateral swap agreements (BSAs) with 35 foreign central banks. Collectively, these deals amount to nearly US$ 500 billion in Chinese renminbi (RMB) available to Beijing's foreign partners. What has led China to be so aggressive in its efforts to sign so many swap agreements? What are the political economic implications of the swap programme for the US‐centric global economic order? China's BSAs can be understood as a form of financial statecraft: the use of national financial and monetary capabilities to achieve foreign policy ends. China has deployed BSAs for both defensive and offensive reasons. Defensively, Beijing has sought to use BSAs to promote trade settlement in RMB thereby reducing China's vulnerability to the dollar's structural dominance in trade. Yet, as explained in this article, they have been ineffective in this regard. Offensively, Beijing has used BSAs as a short‐term liquidity backstop outside of the Bretton Woods institutions for partner countries in need. Here, there is greater potential for BSAs to impact the status quo economic order by enhancing Chinese economic influence. However, their potential is dependent on Beijing's willingness to act as a unilateral crisis lender and its ability to further internationalize the RMB.
The relationship between attaining formal qualifications at older ages and outcomes related to active ageing
Authors: Desjardins Richard
Published: January 2019

Active ageing has become a policy concept that serves as an important response to the ageing of many societies, primarily because it is thought to lead to positive outcomes such as increased employment, productivity, health and other well‐being into older ages. This article presents results of an analysis of the relationship between attaining qualifications at older ages and active ageing in later life. The analysis is based on data made available by the Programme for the International Assessment of Adult Competencies (PIAAC). Results of the analysis show that adults who attain higher levels of qualifications in mid to later life are associated with an increased probability of, being employed, participating in continued learning, and scoring higher on the PIAAC literacy scale when they are older. The findings suggest that open and flexible formal education structures at all levels is good for activating the population to be employed, to engage in continued learning and to develop and maintain literacy skills into older ages.
Barriers to hybridisation and their conservation implications for a highly threatened Australian fish species
Authors: Moy Karl G. , Unmack Peter J. , Lintermans Mark , Duncan Richard P. , Brown Culum
Published: January 2019

Hybridisation and introgression are natural phenomena that may lead to the transfer of adaptive alleles from one species to another and increased species diversity. At the same time, hybridisation and subsequent introgression threaten many species world‐wide through the loss of genetic and species diversity. In Australia, introgressive hybridisation between native and alien species has not typically been considered a significant threat to native biodiversity because of the taxonomic distance between native and alien biota. However, many native fish have been introduced outside their natural range. Recently, four taxa in the genus Melanotaenia have been nationally listed as threatened due to introgressive hybridisation with introduced Melanotaenia splendida. We examined pre‐ and post‐zygotic barriers to hybridisation between M. splendida and one of these threatened taxa—Running River rainbowfish (RRR)—to assess the potential for hybridisation to occur. We used dichotomous mate choice experiments to examine pre‐zygotic barriers and mating experiments to examine post‐zygotic barriers. Size was not a significant predictor of the proportion of time subjects spent with a potential mate, nor was there any significant difference in the amount of time subjects spent with potential mates of their own or the opposite species. Eggs from hybrid pairings with female RRR had a slightly higher hatching rate than those from hybrid pairings with female M. splendida, but neither were significantly different from intraspecies crosses. We could not identify any definite barriers to hybridisation, demonstrating that the introduction of “native” fish species outside their natural range poses a higher risk of hybridisation than previously thought. We call for better education around the consequences of moving “native” fish and the development of rapid response plans to deal with recently established alien populations of Australian fish species in order to prevent future extinctions due to introgressive hybridisation.