bluuebunny/crossref_metadata_2025 huggingface dataset:
Dapagliflozin‐lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice
Authors: Åstrand Annika , Wingren Cecilia , Benjamin Audra , Tregoning John S , Garnett James P , Groves Helen , Gill Simren , Orogo‐Wenn Maria , Lundqvist Anders J , Walters Dafydd , Smith David M , Taylor John D , Baker Emma H , Baines Deborah L
Published: February 2017

Background and Purpose

Hyperglycaemia increases glucose concentrations in airway surface liquid and increases the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction of blood and airway glucose concentrations by the anti‐diabetic drug dapagliflozin could reduce P. aeruginosa growth/survival in the lungs of diabetic mice.

Experimental Approach

The effect of dapagliflozin on blood and airway glucose concentration, the inflammatory response and infection were investigated in C57BL/6J (wild type, WT) or leptin receptor‐deficient (db/db) mice, treated orally with dapagliflozin prior to intranasal dosing with LPS or inoculation with P. aeruginosa. Pulmonary glucose transport and fluid absorption were investigated in Wistar rats using the perfused fluid‐filled lung technique.

Key Results

Fasting blood, airway glucose and lactate concentrations were elevated in the db/db mouse lung. LPS challenge increased inflammatory cells in bronchoalveolar lavage fluid from WT and db/db mice with and without dapagliflozin treatment. P. aeruginosa colony‐forming units (CFU) were increased in db/db lungs. Pretreatment with dapagliflozin reduced blood and bronchoalveolar lavage glucose concentrations and P. aeruginosa CFU in db/db mice towards those seen in WT. Dapagliflozin had no adverse effects on the inflammatory response in the mouse or pulmonary glucose transport or fluid absorption in the rat lung.

Conclusion and Implications

Pharmacological lowering of blood glucose with dapagliflozin effectively reduced P. aeruginosa infection in the lungs of diabetic mice and had no adverse pulmonary effects in the rat. Dapagliflozin has potential to reduce the use, or augment the effect, of antimicrobials in the prevention or treatment of pulmonary infection.
Effect of gonadotropin‐inhibitory hormone on luteinizing hormone secretion in humans
Authors: George J.T. , Hendrikse M. , Veldhuis J.D. , Clarke I.J. , Anderson R.A. , Millar R.P.
Published: February 2017

Background

Gonadotropin‐inhibitory hormone (GnIH, human homologue of RFRP‐3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human.

Objective

We tested the hypotheses that exogenous GnIH inhibits LH secretion (i) in postmenopausal women and (ii) in men concurrently administered exogenous kisspeptin.

Design

Following in vitro and in vivo preclinical studies to functionally characterize the GnIH peptide, a dose‐finding study (human GnIH: 1·5–150 μg/kg/h, iv for 3 h) was undertaken, and 50 μg/kg/h selected for further evaluation. Five postmenopausal women were administered 50 μg/kg/h iv infusion for 3 h or vehicle on two separate days. Four men were administered kisspeptin‐10 (0·3 μg/kg iv bolus) with simultaneous infusion of GnIH (50 μg/kg/h, iv for 3 h) or vehicle.

Participants

Healthy postmenopausal women (mean age 58 ± 2 years, LH: 30·8 ± 2·9 IU/l, FSH: 78·7 ± 6·4 IU/l, oestradiol: <50 pmol/l) and men (39·8 ± 2·1 years, mean total testosterone 12·1 ± 1·8 nmol/l, LH 2·2 ± 0·2 IU/l).

Primary outcome

Change in area under curve (AUC) of LH during GnIHvs vehicle.

Results

During GnIH administration in postmenopausal women, LH secretion decreased (ΔAUC: −9·9 ± 1·8 IU/3 h) vs vehicle (ΔAUC: −0·5 ± 1·7 IU/3 h; P = 0·02). Kisspeptin‐10‐stimulated LH responses in men were not affected by GnIH co‐administration (60‐min AUC of LH 6·2 ± 0·8 IU/h with kisspeptin‐10 alone, 6·3 ± 1·0 IU/h, kisspeptin‐10 with GnIH, P = 0·72). Exogenous GnIH was well tolerated, with no adverse events reported.

Conclusions

Gonadotropin‐inhibitory hormone decreased LH secretion in postmenopausal women in this first‐in‐human study. Kisspeptin‐stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.
Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification
Authors: Kagawa Yasuo , Hiraoka Mami , Kageyama Mitsuyo , Kontai Yoshiko , Yurimoto Mayumi , Nishijima Chiharu , Sakamoto Kaori
Published: February 2017

The introduction of mandatory fortification of grains with folate in 1998 in the United States resulted in 767 fewer spina bifida cases annually and a cost saving of $603 million per year. However, far more significant medical cost savings result from preventing common diseases, including myocardial infarction, stroke, dementia and osteoporosis. A cost‐effectiveness analysis showed a gain of 266 649 quality‐adjusted life‐years and $3.6 billion saved annually, mainly due to the reduction of cardiac infarction. The recommended folate intake in Japan is 240 μg/day whereas it is 400 μg/day internationally. Our Sakado Folate Project targeted individuals with genetic polymorphism of methylenetetrahydrofolate reductase or with hyperhomocysteinemia. Using, for example, folate‐fortified rice, resulted in an increase in serum folate and a decrease in serum homocysteine in the participants, and reduced medical costs were achieved by decreasing myocardial infarction, stroke, dementia and fracture. Due to the small population of Sakado City (approximately 101 000) and small number of births (693) in 2015, a decrease in spina bifida could not be confirmed but there was a significant decrease in the number of very low birthweight infants. The genome notification of subjects was effective in motivating intake of folate, but the increase in serum folate (from 17.4 to 22.5 nmol/L, 129%) was less than that observed following compulsory folic acid fortification of cereals in the USA (from 12.1 to 30.2 nmol/L, 149.6%). Mandatory folic acid fortification is cheap in decreasing medical costs and is thus recommended in Japan.
Short‐ and long‐term outcomes with renin–angiotensin–aldosterone inhibitors in renal transplant recipients: A meta‐analysis of randomized controlled trials
Authors: Liao Ruo‐xi , Lyu Xia‐fei , Tang Wen‐jiao , Gao Kai
Published: February 2017

Background

Angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) are often prescribed for renal transplant recipients (RTRs), but the outcomes of these medications in RTRs remain controversial.

Methods

The PubMed, Embase, and Cochrane Library databases were systematically searched. Randomized controlled trials investigating the outcomes of ACEI/ARBs in RTRs were included for meta‐analysis.

Results

Twenty‐two trials with 2242 patients were identified. After treatment for at least 12 months, ACEI/ARBs were associated with a decline in glomerular filtration rate (GFR) (weighed mean differences [WMD] −5.76 mL/min; 95% confidence intervals [CI]: −9.31 to −2.20) and a decrease in hemoglobin (WMD −9.81 g/L; 95% CI: −14.98 to −4.64). There were no significant differences in mortality between ACEI/ARB and non‐ACEI/ARB groups (risk ratio [RR] 0.98, 95% CI: 0.58 to 1.76), nor in graft failure (RR 0.68, 95% CI: 0.38 to 1.32). After short‐term treatment (less than 1 year), significant differences were found in changes of 24‐hour proteinuria (WMD−0.57 g/d; 95% CI: −0.72 to −0.42) and serum potassium (WMD 0.25 mEq/L; 95% CI: 0.14 to 0.37) in ACEI/ARB groups compared to control arm, while these differences were not confirmed in the long run.

Conclusion

This meta‐analysis indicates ACEI/ARBs may be prescribed to RTRs with GFR and hemoglobin being carefully monitored.
Cognitive function after heart transplantation: Comparing everolimus‐based and calcineurin inhibitor‐based regimens
Authors: Bürker Britta S. , Gullestad Lars , Gude Einar , Relbo Authen Anne , Grov Ingelin , Hol Per K. , Andreassen Arne K. , Arora Satish , Dew Mary Amanda , Fiane Arnt E. , Haraldsen Ira R. , Malt Ulrik F. , Andersson Stein
Published: February 2017

Background

Studies have shown conflicting results concerning the occurrence of cognitive impairment after successful heart transplantation (HTx). Another unresolved issue is the possible differential impact of immunosuppressants on cognitive function. In this study, we describe cognitive function in a cohort of HTx recipients and subsequently compare cognitive function between subjects on either everolimus‐ or calcineurin inhibitor (CNI)‐based immunosuppression.

Methods

Cognitive function, covering attention, processing speed, executive functions, memory, and language functions, was assessed with a neuropsychological test battery. Thirty‐seven subjects were included (everolimus group: n=20; CNI group: n=17). The extent of cerebrovascular pathology was assessed with magnetic resonance imaging.

Results

About 40% of subjects had cognitive impairment, defined as performance at least 1.5 standard deviations below normative mean in one or several cognitive domains. Cerebrovascular pathology was present in 33.3%. There were no statistically significant differences between treatment groups across cognitive domains.

Conclusions

Given the high prevalence of cognitive impairment in the sample, plus the known negative impact of cognitive impairment on clinical outcome, our results indicate that cognitive assessment should be an integrated part of routine clinical follow‐up after HTx. However, everolimus‐ and CNI‐based immunosuppressive regimens did not show differential impacts on cognitive function.
Radiocesium contamination of aquatic organisms in the estuary of the Abukuma River flowing through Fukushima
Authors: Shigenobu Yuya , Ambe Daisuke , Ono Tsuneo , Fujimoto Ken , Morita Takami , Ichikawa Tadafumi , Watanabe Tomowo
Published: February 2017

In the summer of 2013, we measured the radiocesium (134Cs and 137Cs) concentrations in aquatic organisms inhabiting the estuary of the Abukuma River, which flows through the Fukushima and Miyagi Prefectures. Radiocesium concentrations in four muscle‐tissue samples of blackhead seabream (Acanthopagrus schlegeli) [1240, 914, 202 and 106 Bq kg−1 wet weight (w.w.)] and two whole‐body samples deriving from multiple individuals of flathead grey mullet (Mugil cephalus) (129 and 110 Bq kg−1 w.w.) exceeded the Japanese standard limit for radiocesium levels in foods (100 Bq kg−1 w.w.). However, radiocesium concentrations in the other fish samples were lower than the Japanese standard limit. In addition, radiocesium concentrations in crustaceans, major prey items of omnivorous and carnivorous fish species in the Abukuma River estuary, were generally low (0.444–15.1 Bq kg−1 w.w.). Stable isotope analysis indicated that the feeding habit of the three heavily contaminated blackhead seabream, which the radiocesium concentrations were about several times or more higher than the Japanese standard limit, were similar to those of other individuals collected from the same sampling site. Therefore, the difference in the radiocesium level between the three heavily contaminated individuals and the less‐contaminated individuals of blackhead seabream was not because of a recent feeding habit in the Abukuma River estuary. Environmental conditions in the Abukuma River estuary in the summer of 2013 would not have had the potential to increase radiocesium concentrations in the muscle tissues of fish inhabiting the estuary to levels greater than 100 Bq kg−1 w.w.
Pathologic Investigation of Cutaneous Stretch
Authors: Wechsler Harry L. , Fisher Edwin R.
Published: February 2017

Unevenly stretched skin of the back of rats resulted in macroscopic as well as light microscopic features of wounding with subsequent repair as a result of the trauma due to this type of stretch. In skin evenly stretched, dermal collagen was markedly thickened and homogeneous as compared to controls. The increased thickness of evenly stretched skin despite its increase in surface area is consonant with views indicating that stretch may increase the synthesis ordiminish the degradation of dermal collagen. The validity of this conclusion, however, is dependent upon the premise that the evenly stretched skin is also “wounded” since this latter would be required to account for the rapid turnover of collagen in these rather acute experiments. This implies a defect at a molecular or biochemical level since no qualitative structural alterations were detected by the conventional techniques employed.
Social comparisons in consumption, international capital flows and tax competition
Authors: Chang Juin‐Jen , Cheng Yi‐Ling , Peng Shin‐Kun
Published: February 2017

This paper explores the implications of consumption externalities for capital mobility, the distribution of firms and tax competition. In the absence of tax competition, the country with higher consumption externality attracts more capital/firms. In contrast, under tax competition, because the country with higher consumption externality will impose a higher tax rate on capital, due to the strong negative effect of taxation, the country with lower externality attracts more capital. Besides, as trade openness increases, capital agglomerates in the country with lower consumption externality. We also show that there may exist an efficiency‐enhancing role for tax competition.
Atrophic bladder in long‐term dialysis patients increases the risk for urological complications after kidney transplantation
Authors: Hotta Kiyohiko , Miura Masayoshi , Wada Yoshiki , Fukuzawa Nobuyuki , Iwami Daiki , Sasaki Hajime , Seki Toshimori , Harada Hiroshi
Published: February 2017

Objectives

To evaluate the risk for urological complications after kidney transplantation at a single medical center in Japan.

Methods

In the present study, 408 kidney recipients (255 men, 153 women) were enrolled. There were 349 living and 59 deceased donors. The average age of the recipients was 42.5 ± 13.5 years, and the average pretransplant dialysis period was 71.8 ± 88.2 months. Ureteroneocystostomy was carried out on 347 patients, and ureteroureterostomy on 61 patients. We investigated the relationship between pretransplant duration of dialysis and bladder capacity, and examined the risk factors for urological complication. We also evaluated the incidence of vesicoureteral reflux in 191 recipients who underwent ureteroneocystostomy during transplantation.

Results

The preoperative duration of dialysis therapy showed a significant negative correlation with bladder capacity (R2 = 0.33, P < 0.001). The overall urological complication rate was 3.4% (14 patients), including urinary leakage (12 patients) and ureteral stricture (two patients). Univariate analysis showed that atrophic bladder, long‐term dialysis therapy, deceased donor and ureteroureterostomy were associated with a higher incidence of urological complications (odds ratio 8.05, 4.43, 3.42 and 3.35; P < 0.01, P = 0.01, P = 0.04 and P = 0.04, respectively). Furthermore, multivariate analysis showed that atrophic bladder was the only significant factor associated with urological complications (odds ratio 10.37; P = 0.01). Among 191 recipients, vesicoureteral reflux was observed in 32 (16.8%). The incidence of vesicoureteral reflux was significantly higher in patients with atrophic bladder.

Conclusions

Bladder atrophy in renal transplant recipients after long‐term dialysis therapy is associated with a higher risk of urological complications.
Individual consistency of long‐distance migration in a songbird: significant repeatability of autumn route, stopovers and wintering sites but not in timing of migration
Authors: Hasselquist Dennis , Montràs‐Janer Teresa , Tarka Maja , Hansson Bengt
Published: February 2017

Through new tracking techniques, data on timing and routes of migration in long‐distance migrant birds are accumulating. However, studies of the consistency of migration of the same individuals between years are still rare in small‐sized passerine birds. This type of information is important to understand decisions and migration abilities at the individual level, but also for life history theory, for understanding carry over effects between different annual cycle stages and for conservation. We analysed individual repeatability of migration between years in great reed warblers Acrocephalus arundinaceus; a medium‐sized European songbird migrating to sub‐Saharan Africa. In seven males, with geolocator data from 2–4 yr per bird, we found low to moderate (non significant) repeatability in timing of migration parameters (R ≤ 0.41), but high (and significant) repeatability for most spatial parameters, i.e. autumn route (R = 0.64) and stopover sites (R = 0.59–0.87) in Europe, and wintering sites (R = 0.77–0.99) in sub‐Saharan Africa. This pattern of high spatial but low temporal within‐individual repeatability of migration between years contrasts other tracking studies of migrating birds that generally have found consistency in timing but flexibility in routes. High spatial consistency of migration in the great reed warbler may be due to it being a specialist in wetlands, an unevenly distributed habitat, favouring a strategy of recurrence at previously visited sites. Low temporal repeatability may be caused by large between‐year variation in carry‐over effects from the breeding season, high flexibility in decision rules during migration or high sensitivity to environmental factors (weather, wind) during migration.
Eggs brought in from afar: Svalbard‐breeding pink‐footed geese can fly their eggs across the Barents Sea
Authors: Klaassen Marcel , Hahn Steffen , Korthals Harry , Madsen Jesper
Published: February 2017

Many Arctic‐breeding waterbirds are thought to bring nutrients for egg production from southern latitudes to allow early breeding. It has proved problematic to quantify the extent of such capital breeding and identify whether nutrients for egg production are brought in from nearby or from afar. Before reaching their breeding grounds on Svalbard, pink‐footed geese Anser brachyrhynchus fly ∼ 1100 km across the Barents Sea from Norway. Using abdominal profile indexing (API) we scored body stores in individually marked geese just prior to migration from the northernmost staging area in Norway to Svalbard, followed by their breeding success on their non‐breeding grounds in autumn. In productive breeding years leading to a high (> 13.8%) proportion of juveniles in the autumn population, there was a positive relationship between female API and number of young produced, suggesting that the geese are at least partial capital breeders. Moreover, focusing on the geographic origin of proteins used in egg synthesis and measuring nitrogen stable isotope ratios in pink‐footed geese's eggs and food sources in Norway and Svalbard, we identified that capital breeding in this species is ∼ 50% on average but may potentially amount to as much as 100%, notably in females laying early. About 60% of this protein capital is carried in well‐developed follicles across the Barents Sea, the remainder likely being stored in muscle tissues. Conditions on the wintering grounds and migratory stopover sites can have profound effects on an individual's fitness but the here presented link between the use of migratory stopover sites and breeding performance is particularly noteworthy. Apparently, some individuals accept the putative costs of carrying body stores over large distances to the breeding grounds. The data also highlights considerable variation in the reliance on capital for breeding, suggesting substantial individual scope to adjust breeding strategy to changing environmental conditions.
The ‘Oops!’ of EU Engagement Abroad: Analyzing Unintended Consequences of EU External Action
Authors: Burlyuk Olga
Published: February 2017

The mainstream scholarship assessing EU external action frames the subject in terms of success or failure to achieve the intended effects, the latter generally defined against the EU's own stated objectives. Resting on a tacit assumption that EU engagement in third states is a good thing, these analyses are framed as ‘positive impact or no impact’ and tend to neglect the wider effects of EU policies. This article maintains that EU external action may and often does have unintended consequences, thus expanding the study of EU impact beyond the sheer study of EU effectiveness. Drawing on broader literature on unintended consequences, the article proposes a framework for analyzing unintended consequences of EU external action. It synthesizes and adapts to the EU context a classification of unintended consequences and, in order to illustrate its utility, applies the proposed framework to three empirical examples derived from EU neighbourhood, migration and trade policies.
Research Review: Language problems in children with Attention‐Deficit Hyperactivity Disorder – a systematic meta‐analytic review
Authors: Korrel Hannah , Mueller Kathryn L. , Silk Tim , Anderson Vicki , Sciberras Emma
Published: February 2017

Background

Children with Attention‐Deficit Hyperactivity Disorder (ADHD) appear to have a higher risk of language problems compared with typically developing children, although the types of language problems experienced are less clear. This review aims to establish the types of language problems experienced by children with ADHD according to systematically reviewed literature and determine the empirical evidence for language problems in children with ADHD compared with non‐ADHD controls.

Methods

A standardized search protocol was used on databases: CINAHL, Medline, and PsychINFO. We identified studies with the following inclusion criteria: (a) confirmed ADHD status at the time of the study, (b) inclusion of a non‐ADHD control group, (c) use of a validated language measure, and (d) age ≤ 18. t‐Tests, Pearson's r, and Hedges g effect sizes (ES) were calculated using summary statistics. Random effects meta‐analyses were conducted for the language domain suitable for analysis. Publication bias was investigated using both the trim and fill and p‐curve techniques.

Results

Twenty‐one studies were included in the systematic review (ADHD = 1,209; Control = 1,101), within which 60 of 68 separate analyses found significant differences between the ADHD and control group on the language measures (p < .05). Follow‐up meta‐analyses found evidence for large deficits in the ADHD groups overall (10/11 studies met p < .05; weighted mean ES [WMES]: 1.04); expressive (10/10 met p < .05; WMES: 1.23); receptive (12/14 met p < .05; WMES: 0.97), and pragmatic language (4/4 studies met p < .05; WMES: 0.98) compared with controls.

Conclusions

This study demonstrates that children with ADHD have poorer performance on measures of overall, expressive, receptive, and pragmatic language compared with controls. A screening of language functioning may be a valuable addition to the assessment of ADHD.
A model to predict the onset of non‐alcoholic fatty liver disease within 2 years in elderly adults
Authors: Lin Ya‐Jie , Gao Xi‐Mei , Pan Wei‐Wei , Gao Shuai , Yu Zhen‐Zhen , Xu Ping , Fan Xiao‐Peng
Published: February 2017

Background and Aim

Non‐alcoholic fatty liver disease (NAFLD) is a common cause of chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. However, it is difficult to identify subjects at high risk for NAFLD onset. This study aims to construct a model to predict the onset of NAFLD within 2 years in elderly adults.

Methods

This study included and followed 3378 initial NAFLD‐free subjects aged 60 years or over for 2 years, which were randomly divided into a training set and a validation set. NAFLD was diagnosed on ultrasound. Clinical and laboratory data were recorded at baseline. A model was constructed in the training set to predict the onset of NAFLD and validated in the validation set.

Results

Body mass index, hemoglobin, fasting blood glucose, and triglycerides were identified as predictors for the onset of NAFLD. A risk score (R) was calculated by them. It classified the subjects into low‐risk group (R ≤ −2.88), moderate‐risk group (−2.88 < R ≤ −1.26), and high‐risk group (R > −1.26). In the training set, 4.68% of the participants in the low‐risk group, 11.59% of the participants in the moderate‐risk group, and 31.02% of the participants in the high‐risk group developed NAFLD. In the validation set, 5.84% of the participants in the low‐risk group, 10.57% of the participants in the moderate‐risk group, and 29.44% of the participants in the high‐risk group developed NAFLD.

Conclusions

This study developed a model to predict the onset of NAFLD in elderly adults, which might provide indications for intervention to these subjects.
Rana Plaza Fieldwork and Academic Anxiety: Some Reflections
Authors: Chowdhury Rashedur
Published: February 2017

The Rana Plaza collapse, which took place in Bangladesh in 2013, killed and injured at least 1135 and 2500 people respectively. Although the structural fault with the building had been identified before the collapse, the owner of the building and five garment factories housed in Rana Plaza had forced workers to continue production for 31 Western multinational corporations (MNCs). It was the deadliest structural failure in modern history, and resulted in a horrific rescue operation. First, the fire brigade did not have the necessary training and equipment to rescue the victims, and so the general public also participated in the rescue operation. Second, when victims were rescued, it was found that many of them had lost their limbs or suffered severe internal injuries, including internal organ failure, due to several days without water. After the completion of the rescue, the victims received neither appropriate compensation nor rehabilitation to overcome their psychological trauma and physical disabilities.
Is chronic ulcerative stomatitis a variant of lichen planus, or a distinct disease?
Authors: Feller Liviu , Khammissa Razia A.G. , Lemmer Johan
Published: February 2017

Chronic ulcerative stomatitis is an immune‐mediated mucocutaneous disorder characterized clinically by erosions or ulcers. Most cases are limited to the mouth. The histopathological features are non‐specific or mimic those of oral lichen planus, and studies by immunofluorescent microscopy are essential for definitive diagnosis. The defining immunopathogenic mechanism is the binding of IgG to the nuclear protein deltaNp63alpha of keratinocytes in the basal and parabasal cell layers of the oral stratified epithelium. DeltaNp63alpha functions as a regulator of epithelial stem cell activity and as an antiapoptotic agent and regulates the expression of cell‐to‐cell and cell‐to‐basement membrane adhesion molecules. The autoimmune IgG‐deltaNp63alpha interaction is thought to result in damage to the structural attachment of keratinocytes to one another and to the epithelial basement membrane zone and in dysregulation of the cell cycle and apoptosis of basal keratinocytes with the development of erosions or ulcers. The aims of treatment are to suppress the pathogenic immunoinflammatory responses, to prevent local infection and to promote healing. The purpose of this article is to provide a succinct review of the diagnostic, clinical and etiopathogenic features of, and treatment guidelines for chronic ulcerative stomatitis, and to argue that this disease should be regarded as a variant of oral lichen planus, rather than as a distinct entity.
Structural modeling and functional analysis of the essential ribosomal processing protease Prp from Staphylococcus aureus
Authors: Wall Erin A. , Johnson Adam L. , Peterson Darrell L. , Christie Gail E.
Published: February 2017

In Firmicutes and related bacteria, ribosomal large subunit protein L27 is encoded with a conserved N‐terminal extension that is removed to expose residues critical for ribosome function. Bacteria encoding L27 with this N‐terminal extension also encode a sequence‐specific cysteine protease, Prp, which carries out this cleavage. In this work, we demonstrate that L27 variants with an un‐cleavable N‐terminal extension, or lacking the extension (pre‐cleaved), are unable to complement an L27 deletion in Staphylococcus aureus. This indicates that N‐terminal processing of L27 is not only essential but possibly has a regulatory role. Prp represents a new clade of previously uncharacterized cysteine proteases, and the dependence of S. aureus on L27 cleavage by Prp validates the enzyme as a target for potential antibiotic development. To better understand the mechanism of Prp activity, we analyzed Prp enzyme kinetics and substrate preference using a fluorogenic peptide cleavage assay. Molecular modeling and site‐directed mutagenesis implicate several residues around the active site in catalysis and substrate binding, and support a structural model in which rearrangement of a flexible loop upon binding of the correct peptide substrate is required for the active site to assume the proper conformation. These findings lay the foundation for the development of antimicrobials that target this novel, essential pathway.
DNA methylation and gene expression regulation associated with vascularization in Sorghum bicolor
Authors: Turco Gina M. , Kajala Kaisa , Kunde‐Ramamoorthy Govindarajan , Ngan Chew‐Yee , Olson Andrew , Deshphande Shweta , Tolkunov Denis , Waring Barbara , Stelpflug Scott , Klein Patricia , Schmutz Jeremy , Kaeppler Shawn , Ware Doreen , Wei Chia‐Lin , Etchells J. Peter , Brady Siobhan M.
Published: February 2017

Plant secondary cell walls constitute the majority of plant biomass. They are predominantly found in xylem cells, which are derived from vascular initials during vascularization. Little is known about these processes in grass species despite their emerging importance as biomass feedstocks. The targeted biofuel crop Sorghum bicolor has a sequenced and well‐annotated genome, making it an ideal monocot model for addressing vascularization and biomass deposition.

Here we generated tissue‐specific transcriptome and DNA methylome data from sorghum shoots, roots and developing root vascular and nonvascular tissues.

Many genes associated with vascular development in other species show enriched expression in developing vasculature. However, several transcription factor families varied in vascular expression in sorghum compared with Arabidopsis and maize. Furthermore, differential expression of genes associated with DNA methylation were identified between vascular and nonvascular tissues, implying that changes in DNA methylation are a feature of sorghum root vascularization, which we confirmed using tissue‐specific DNA methylome data. Roots treated with a DNA methylation inhibitor also showed a significant decrease in root length.

Tissues and organs can be discriminated based on their genomic methylation patterns and methylation context. Consequently, tissue‐specific changes in DNA methylation are part of the normal developmental process.
Variation in seed size is structured by dispersal syndrome and cone morphology in conifers and other nonflowering seed plants
Authors: Leslie Andrew B. , Beaulieu Jeremy M. , Mathews Sarah
Published: February 2017

Seed size varies tremendously in plants and its evolution is influenced by multiple ecological and biological factors that are difficult to disentangle. In this study, we focus on understanding the role of seed dispersal by animals in the evolution of seed size in conifers, the most diverse extant nonflowering seed plant group.

Relationships among seed size, dispersal syndrome, climate and cone morphology were analyzed across conifers using quantitative models of character evolution and phylogenetic regression techniques.

Dispersal syndrome is a more consistent predictor of seed size within major extant conifer clades than climate. Seeds are generally larger in animal‐dispersed than wind‐dispersed species, and particular cone morphologies are consistently associated with specific ranges in seed size.

Seed size and cone morphology evolve in a correlated manner in many animal‐dispersed conifers, following a trade‐off that minimizes the total size of the dispersal unit. These relationships are also present in other nonflowering seed plant groups, and have been important in the evolution of seeds and cones at least over the Cenozoic and perhaps over much of the later Mesozoic.
Evolutionary asymmetry in the arbuscular mycorrhizal symbiosis: conservatism in fungal morphology does not predict host plant growth
Authors: Koch Alexander M. , Antunes Pedro M. , Maherali Hafiz , Hart Miranda M. , Klironomos John N.
Published: February 2017

Although arbuscular mycorrhizal (AM) fungi are obligate symbionts that can influence plant growth, the magnitude and direction of these effects are highly variable within fungal genera and even among isolates within species, as well as among plant taxa.

To determine whether variability in AM fungal morphology and growth is correlated with AM fungal effects on plant growth, we established a common garden experiment with 56 AM fungal isolates comprising 17 genera and six families growing with three plant host species.

Arbuscular mycorrhizal fungal morphology and growth was highly conserved among isolates of the same species and among species within a family. By contrast, plant growth response to fungal inoculation was highly variable, with the majority of variation occurring among different isolates of the same AM fungal species.

Our findings show that host performance cannot be predicted from AM fungal morphology and growth traits. Divergent effects on plant growth among isolates within an AM fungal species may be caused by coevolution between co‐occurring fungal and plant populations.
A meta‐analysis of overall effects of weight loss interventions delivered via mobile phones and effect size differences according to delivery mode, personal contact, and intervention intensity and duration
Authors: Schippers M. , Adam P. C. G. , Smolenski D. J. , Wong H. T. H. , de Wit J. B. F.
Published: February 2017

Weight loss interventions are delivered through various mediums including, increasingly, mobile phones. This systematic review and meta‐analysis assesses whether interventions delivered via mobile phones reduce body weight and which intervention characteristics are associated with efficacy. The study included randomised controlled trials assessing the efficacy of weight loss interventions delivered via mobile phones. A meta‐analysis to test intervention efficacy was performed, and subgroup analyses were conducted to determine whether interventions' delivery mode(s), inclusion of personal contact, duration and interaction frequency improve efficacy. Pooled body weight reduction (d = −0.23; 95% confidence interval = −0.38, −0.08) was significant. Interventions delivered via other modes in addition to the mobile phone were associated with weight reduction. Personal contact and more frequent interactions in interventions were also associated with greater weight reduction. In conclusion, the current body of evidence shows that interventions delivered via mobile phones produce a modest reduction in body weight when combined with other delivery modes. Delivering interventions with frequent and personal interactions may in particular benefit weight loss results.
Methodological considerations and impact of school‐based interventions on objectively measured physical activity in adolescents: a systematic review and meta‐analysis
Authors: Borde R. , Smith J. J. , Sutherland R. , Nathan N. , Lubans D. R.
Published: February 2017

Objective

The aims of this systematic review and meta‐analysis are (i) to determine the impact of school‐based interventions on objectively measured physical activity among adolescents and (ii) to examine accelerometer methods and decision rule reporting in previous interventions.

Methods

A systematic search was performed to identify randomized controlled trials targeting adolescents (age: ≥10 years), conducted in the school setting, and reporting objectively measured physical activity. Random effects meta‐analyses were conducted to determine the pooled effects of previous interventions on total and moderate‐to‐vigorous physical activity. Potential moderators of intervention effects were also explored.

Results

Thirteen articles met the inclusion criteria, and twelve were included in the meta‐analysis. The pooled effects were small and non‐significant for both total physical activity (standardized mean difference = 0.02 [95% confidence interval = −0.13 to 0.18]) and moderate‐to‐vigorous physical activity (standardized mean difference = 0.24 [95% confidence interval = −0.08 to 0.56]). Sample age and accelerometer compliance were significant moderators for total physical activity, with a younger sample and higher compliance associated with larger effects.

Conclusion

Previous school‐based physical activity interventions targeting adolescents have been largely unsuccessful, particularly for older adolescents. There is a need for more high‐quality research using objective monitoring in this population. Future interventions should comply with best‐practice recommendations regarding physical activity monitoring protocols.
Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review
Authors: Montanari T. , Pošćić N. , Colitti M.
Published: February 2017

Obesity is the result of energy intake chronically exceeding energy expenditure. Classical treatments against obesity do not provide a satisfactory long‐term outcome for the majority of patients. After the demonstration of functional brown adipose tissue in human adults, great effort is being devoted to develop therapies based on the adipose tissue itself, through the conversion of fat‐accumulating white adipose tissue into energy‐dissipating brown adipose tissue. Anti‐obesity treatments that exploit endogenous, pharmacological and nutritional factors to drive such conversion are especially in demand. In the present review, we summarize the current knowledge about the various molecules that can be applied in promoting white‐to‐brown adipose tissue conversion and energy expenditure and the cellular mechanisms involved.
The Compatibility of the Structure‐and‐Dynamics Argument and Phenomenal Functionalism about Space
Authors: Roelofs Luke
Published: February 2017

Chalmers argues against physicalism using the premise that no truth about consciousness is deducible a priori from purely structural truths, and later defines what it is for a truth to be structural, which turns out to include spatiotemporal truths. But Chalmers then defines spatiotemporal terms by reference to their role in causing spatiotemporal experiences. Stoljar and Ebbers argue that these definitions allow for the trivial falsification of Chalmers premise about structure and consciousness. I show that this result can be avoided by tweaking the relevant premise, and that this tweak is not ad hoc.
Photomorphogenic responses to ultraviolet‐B light
Authors: Jenkins Gareth I.
Published: February 2017

Exposure to ultraviolet B (UV‐B) light regulates numerous aspects of plant metabolism, morphology and physiology through the differential expression of hundreds of genes. Photomorphogenic responses to UV‐B are mediated by the photoreceptor UV RESISTANCE LOCUS8 (UVR8). Considerable progress has been made in understanding UVR8 action: the structural basis of photoreceptor function, how interaction with CONSTITUTIVELY PHOTOMORPHOGENIC 1 initiates signaling and how REPRESSOR OF UV‐B PHOTOMORPHOGENESIS proteins negatively regulate UVR8 action. In addition, recent research shows that UVR8 mediates several responses through interaction with other signaling pathways, in particular auxin signaling. Nevertheless, many aspects of UVR8 action remain poorly understood. Most research to date has been undertaken with Arabidopsis, and it is important to explore the functions and regulation of UVR8 in diverse plant species. Furthermore, it is essential to understand how UVR8, and UV‐B signaling in general, regulates processes under natural growth conditions. Ultraviolet B regulates the expression of many genes through UVR8‐independent pathways, but the activity and importance of these pathways in plants growing in sunlight are poorly understood.
Enhancement of the Efficacy of Photodynamic Inactivation of Candida albicans with the Use of Biogenic Gold Nanoparticles
Authors: Maliszewska Irena , Lisiak Barbara , Popko Katarzyna , Matczyszyn Katarzyna
Published: February 2017

This study reports on successful photodynamic inactivation of planktonic and biofilm cells of Candida albicans using Rose Bengal (RB) in combination with biogenic gold nanoparticles synthesized by the cell‐free filtrate of Penicillium funiculosum BL1 strain. Monodispersed colloidal gold nanoparticles coated with proteins were characterized by a number of techniques including SEM–EDS, TEM, UV–Vis absorption and fluorescence spectroscopy, as well as Fourier transform infrared spectroscopy to be 24 ± 3 nm spheres. A Xe lamp (output power of 20mW, delivering intensity of 53 mW cm−2) was used as a light source to study the effects of RB alone, the gold nanoparticles alone and the RB‐gold nanoparticle mixture on the viability of C. albicans cells. The most effective reduction in the number of planktonic cells was found after 30 min of Xe lamp light irradiation (95.4 J cm−2) and was 4.89 log10 that is 99.99% kill for the mixture of RB with gold nanoparticles compared with 2.19 log10 or 99.37% for RB alone. The biofilm cells were more resistant to photodynamic inactivation, and the highest effective reduction in the number of cells was found after 30 min of irradiation in the presence of the RB–gold nanoparticles mixture and was 1.53 log10, that is 97.04% kill compared with 0.6 log10 or 74.73% for RB. The probable mechanism of enhancement of RB‐mediated photodynamic fungicidal efficacy against C. albicans in the presence of biogenic gold nanoparticles is discussed leading to the conclusion that this process may have a multifaceted character.
Attempting to restore mountain big sagebrush (Artemisia tridentata ssp. vaseyana) four years after fire
Authors: Davies Kirk W. , Bates Jon D. , Hulet April
Published: February 2017

Restoration of shrubs is needed throughout the world because of altered fire regimes, anthropogenic disturbance, and overutilization. The native shrub mountain big sagebrush (Artemisia tridentata Nutt. ssp. vaseyana (Rydb.) Beetle) is a restoration priority because of its value to wildlife in western North America. One of the principal threats to mountain big sagebrush is encroachment by western juniper (Juniperus occidentalis ssp. occidentalis Hook) and other conifers. Fire is frequently applied to control juniper; however, sagebrush recovery after fire can be variable. Seeding sagebrush postfire can hasten sagebrush recovery; however, seeding is not always necessary. Therefore, it may be advantageous to monitor postfire recovery to determine if seeding is needed. The effect of seeding sagebrush several years after fire is unknown. We evaluated the efficiency of seeding mountain big sagebrush four years after fire‐controlled junipers at five sites. Sagebrush cover (<0.5%) and density (<0.07 plants/m2) was low in seeded plots and did not differ from unseeded controls in the three postseeding years. We conclude that seeding sagebrush four years after fire did not accelerate sagebrush recovery. We speculate that seeded sagebrush failed to establish because of competition from herbaceous vegetation that had four years to recover after fire. Although it would be beneficial to seed sagebrush only when needed, our results suggest postponing seeding until monitoring has determined that recovery is inadequate may not be advisable. We suggest researchers investigate methods to improve predicting sagebrush recovery to allow for seeding, when needed, before the first postfire growing season.
Intersecting Contexts: Understanding Rural Utah Veterans’ Experiences with Accessing VA Health Care
Authors: Ward Carol , Stearmer Matthew , Cope Michael R.
Published: February 2017

Since the passage of the Rural Veterans Care Act of 2006 research has focused on health care provider issues with less attention given to individual and contextual factors that contribute to the remaining service gap. Adopting the health care user's viewpoint, we focus on two questions: How do health care users perceive access to health care, and which contextual factors are relevant to explaining the failure of recent efforts to increase access by rural veterans? We collected detailed data through focus groups and individual interviews involving veterans and knowledgeable community members in four rural areas of Utah. Framing the analysis of interview data using the sociospatial approach reveals key dimensions of several contexts that affect rural veterans’ access to health care: the historical period of military service that influences attitudes toward use of Veterans Administration health care and access to specialists, regulations of regionally and locally organized insurance coverage that affects access to and coordination of health care, and local social aspects of rural communities that inform use of specific health care sources. These dimensions provide new insights into the conditions that contribute to variations in the vulnerability of rural Utah veterans.
Do perceptions of the Red‐tailed Hawk indicate a human‐wildlife conflict on the island of La Gonave, Haiti?
Authors: White Justin , Kennedy Lisa M. , Christie Maria Elisa
Published: February 2017

The Caribbean subspecies of the Red‐tailed Hawk (Buteo jamaicensis solitudinus or B.j. jamaicensis) is the largest native carnivore on the island of La Gonave, Haiti, and the island's apex predator. On other Caribbean islands, raptors have been persecuted by local people typically because of their depredation of livestock. In addition to possible persecution from humans, Red‐tailed Hawks on La Gonave face challenges from island‐wide timber overharvest and rapid land‐cover changes. To better understand the human‐apex predator relationship on La Gonave, we surveyed islanders about their perceptions of, and interactions with, the Red‐tailed Hawk. According to 121 respondents from 10 villages, La Gonavans do not hunt, kill, or consume Red‐tailed Hawks. Our study revealed a notable absence of negative perceptions of the hawk by respondents despite intense hawk depredation of domestic chickens. While the chicken depredation may lead outside observers to consider the human‐hawk relationship on La Gonave as representative of a human‐wildlife conflict, our interview data do not support that conception. Our findings reflect an important conversation in related contemporary scientific literature about what constitutes human‐wildlife conflicts across various cultures. Despite tolerance by residents, Red‐tailed Hawks on La Gonave remain threatened by habitat degradation.
Filial Norms, Co‐Residence, and Intergenerational Exchange in Japan
Authors: Taniguchi Hiromi , Kaufman Gayle
Published: February 2017

Objective

We examine the effects of filial norms and co‐residence as well as patterns of social exchange on support that adult children give to their parents and in‐laws in Japan.

Methods

We estimate ordered logit models with data from the Japanese General Social Survey.

Results

Children who receive money from their parents are more likely than those who receive no such support to give their parents nonmonetary support, while children who receive nonmonetary support from their parents are more likely to assist their parents financially. Receiving money from in‐laws is reciprocated with nonmonetary and monetary support. Filial norms increase the level of monetary support to parents and in‐laws, especially for men. Co‐residence increases monetary and nonmonetary support from children to parents and in‐laws, while the positive effect of co‐residence on nonmonetary support from children to in‐laws is limited to women.

Conclusion

Notions of social exchange as well as filial norms and co‐residence encourage intergenerational support in Japan.