bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Assessment of Food Effect on the Pharmacokinetics of Nano‐Crystallized Megestrol Acetate
Authors: Guk Jinju , Son Hankil , Chae Dong Woo , Park Kyungsoo
Published: September 2016

Megestrol acetate, an appetite stimulant with low bioavailability, shows increased bioavailability when taken together with food. However, the pharmacokinetic characteristics of megestrol acetate and its relation with food are not well understood. This study aimed to investigate the food effect on the pharmacokinetics (PK) of the recently developed nano‐crystallized megestrol acetate (NCMA), using a model‐based approach. Data were obtained from an NCMA PK study consisting of a single dose in fasting (39 individuals) and fed conditions (40 individuals). Plasma concentrations were measured up to 120 hr after dosing. With the incorporation of body‐weight via allometry, NONMEM 7.3 was used to develop a PK model, which was then used to simulate an optimal fasting dose yielding an area under concentration (AUC) and maximum concentration (Cmax) of NCMA close to those obtained with the fed dose. NCMA concentrations were best characterized by a two‐compartment model with first‐order absorption linked to a recycling compartment to account for the multiple concentration peaks observed. Food increased bioavailability 2.2 times and decreased the absorption rate constant 0.58 times. Recycling event times were estimated to be 3.56, 7.99 and 24.0 hr. The optimal fast dose was 2.0 times higher than the fed dose, and the resulting difference in drug exposure between the fasting and fed dose was 7.5%. This work suggests that the PK model developed can be applied to an optimal dosage regimen design for NCMA treatment.
Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases
Authors: Kunnumakkara Ajaikumar B , Bordoloi Devivasha , Padmavathi Ganesan , Monisha Javadi , Roy Nand Kishor , Prasad Sahdeo , Aggarwal Bharat B
Published: September 2016

Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti‐inflammatory activity through the suppression of numerous cell signalling pathways including NF‐κB, STAT3, Nrf2, ROS and COX‐2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials.

Linked Articles

This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: a pharmacological point of view
Authors: Bifari Francesco , Nisoli Enzo
Published: September 2016

Substantial evidence has been accumulated suggesting that branched‐chain amino acid (BCAA) supplementation or BCAA‐rich diets have a positive effect on the regulation of body weight, muscle protein synthesis, glucose homeostasis, the ageing process and extend healthspan. Despite these beneficial effects, epidemiological studies have shown that BCAA plasma concentrations and BCAA metabolism are altered in several metabolic disorders, including type 2 diabetes mellitus and cardiovascular diseases. In this review article, we present an overview of the current literature on the different effects of BCAAs in health and disease. We also highlight the results showing the most promising therapeutic effects of dietary BCAA supplementation and discuss how BCAAs can trigger different and even opposite effects, depending on the catabolic and anabolic states of the organisms. Moreover, we consider the effects of BCAAs when metabolism is abnormal, in the presence of a mixture of different anabolic and catabolic signals. These unique pharmacodynamic properties may partially explain some of the markedly different effects found in BCAA supplementation studies. To predict accurately these effects, the overall catabolic/anabolic status of patients should be carefully considered. In wider terms, a correct modulation of metabolic disorders would make nutraceutical interventions with BCAAs more effective.

Linked Articles

This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Carotenoids: biochemistry, pharmacology and treatment
Authors: Milani Alireza , Basirnejad Marzieh , Shahbazi Sepideh , Bolhassani Azam
Published: September 2016

Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation‐related proteins, retinoid‐like receptors, antioxidant response element, nuclear receptors, AP‐1 transcriptional complex, the Wnt/β‐catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B‐ and T‐lymphocytes, the activity of macrophages and cytotoxic T‐cells, effector T‐cell function and the production of cytokines. Recently, the beneficial effects of carotenoid‐rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β‐carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time‐ and dose‐dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action.

Linked Articles

This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
Ebola virus: A gap in drug design and discovery ‐ experimental and computational perspective
Authors: Balmith Marissa , Faya Mbuso , Soliman Mahmoud E. S.
Published: September 2016

The Ebola virus, formally known as the Ebola hemorrhagic fever, is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the Ebola virus been developed, including Zmapp and peptides. In addition, existing drugs which have been repurposed toward anti‐Ebola virus activity have been re‐examined and are seen to be promising candidates toward combating Ebola. Drug development involving computational tools has been widely employed toward target‐based drug design. Screening large libraries have greatly stimulated research toward effective anti‐Ebola virus drug regimens. Current emphasis has been placed on the investigation of host proteins and druggable viral targets. There is a huge gap in the literature regarding guidelines in the discovery of Ebola virus inhibitors, which may be due to the lack of information on the Ebola drug targets, binding sites, and mechanism of action of the virus. This review focuses on Ebola virus inhibitors, drugs which could be repurposed to combat the Ebola virus, computational methods which study drug–target interactions as well as providing further insight into the mode of action of the Ebola virus.
Telling the Tale and Living Well: Adolescent Narrative Identity, Personality Traits, and Well‐Being Across Cultures
Authors: Reese Elaine , Myftari Ella , McAnally Helena M. , Chen Yan , Neha Tia , Wang Qi , Jack Fiona , Robertson Sarah‐Jane
Published: September 2016

This study explored links between narrative identity, personality traits, and well‐being for 263 adolescents (age 12–21) from three New Zealand cultures: Māori, Chinese, and European. Turning‐point narratives were assessed for autobiographical reasoning (causal coherence), local thematic coherence, emotional expressivity, and topic. Across cultures, older adolescents with higher causal coherence reported better well‐being. Younger adolescents with higher causal coherence instead reported poorer well‐being. Personal development topics were positively linked to well‐being for New Zealand European adolescents only, and thematic coherence was positively linked to well‐being for Māori adolescents only. Negative expressivity, neuroticism, conscientiousness, and openness were also linked to well‐being. Implications of these cultural similarities and differences are considered for theories of narrative identity, personality, and adolescent well‐being.
Cohort‐specific variation in juvenile coho salmon habitat use
Authors: Bradley Catherine , Sethi Suresh Andrew , Ashline Joshua , Gerken Jonathon
Published: September 2016

In this study, we examined summer and fall freshwater rearing habitat use by juvenile coho salmon (Oncorhynchus kisutch) in the quickly urbanising Big Lake drainage in south‐central Alaska. Habitat use was assessed by regressing fish count data against habitat survey information across thirty study sites using generalised linear mixed models. Habitat associations were examined by age‐0 and age‐1+ cohorts separately, providing an opportunity to compare habitat use across different juvenile coho salmon life stages during freshwater rearing. Regression results indicated that the age‐0 cohorts were strongly associated with shallow, wide stream reaches with in‐stream vegetation, whereas age‐1+ cohorts were associated with deeper stream reaches. Furthermore, associations between fork length and habitat characteristics suggest cohort‐specific habitat use patterns are distinct from those attributable to fish size. Habitat use information generated from this study is being used to guide optimal fish passage restoration planning in the Big Lake drainage. Evidence for habitat use partitioning by age cohort during freshwater juvenile rearing indicates that pooling age cohorts into a single “juvenile” stage for the purposes of watershed management may mask important habitat use dynamics.
Reproductive resilience: a paradigm shift in understanding spawner‐recruit systems in exploited marine fish
Authors: Lowerre‐Barbieri Susan , DeCelles Greg , Pepin Pierre , Catalán Ignacio A , Muhling Barbara , Erisman Brad , Cadrin Steven X , Alós Josep , Ospina‐Alvarez Andres , Stachura Megan M , Tringali Michael D , Burnsed Sarah Walters , Paris Claire B
Published: September 2016

A close relationship between adult abundance and stock productivity may not exist for many marine fish stocks, resulting in concern that the management goal of maximum sustainable yield is either inefficient or risky. Although reproductive success is tightly coupled with adult abundance and fecundity in many terrestrial animals, in exploited marine fish where and when fish spawn and consequent dispersal dynamics may have a greater impact. Here, we propose an eco‐evolutionary perspective, reproductive resilience, to understand connectivity and productivity in marine fish. Reproductive resilience is the capacity of a population to maintain the reproductive success needed to result in long‐term population stability despite disturbances. A stock's reproductive resilience is driven by the underlying traits in its spawner‐recruit system, selected for over evolutionary timescales, and the ecological context within which it is operating. Spawner‐recruit systems are species specific, have both density‐dependent and fitness feedback loops and are made up of fixed, behavioural and ecologically variable traits. They operate over multiple temporal, spatial and biological scales, with trait diversity affecting reproductive resilience at both the population and individual (i.e. portfolio) scales. Models of spawner‐recruit systems fall within three categories: (i) two‐dimensional models (i.e. spawner and recruit); (ii) process‐based biophysical dispersal models which integrate physical and environmental processes into understanding recruitment; and (iii) complex spatially explicit integrated life cycle models. We review these models and their underlying assumptions about reproductive success vs. our emerging mechanistic understanding. We conclude with practical guidelines for integrating reproductive resilience into assessments of population connectivity and stock productivity.
Acidity and organic matter promote abiotic nitric oxide production in drying soils
Authors: Homyak Peter M. , Kamiyama Matthew , Sickman James O. , Schimel Joshua P.
Published: September 2016

Soils are an important source of NO, particularly in dry lands because of trade‐offs that develop between biotic and abiotic NO‐producing processes when soils dry out. Understanding how drier climates may offset the balance of these trade‐offs as soils transition toward more arid states is, therefore, critical to estimating global NO budgets, especially because drylands are expected to increase in size. We measured NO emission pulses after wetting soils from similar lithologies along an altitudinal gradient in the Sierra Nevada, CA, where mean annual precipitation varied from 670 to 1500 mm. Along the gradient, we measured field NO emissions, and used chloroform in the laboratory to reduce microbial activity and partition between biotic and abiotic NO‐producing processes (i.e., chemodenitrification). Field NO emission pulses were lowest in the acidic and SOM‐rich soils (4–72 ng NO‐N m−2 s−1), but were highest in the high‐elevation barren site (~560 ng NO‐N m−2 s−1). In the laboratory, NO emission pulses were up to 19× greater in chloroform‐treated soils than in the controls, and these abiotic pulses increased with elevation as pH decreased (6.2–4.4) and soil organic matter (SOM) increased (18–157 mg C g−1). Drought can shift the balance between the biotic and abiotic processes that produce NO, favoring chemodenitrification during periods when biological processes become stressed. Acidic and SOM‐rich soils, which typically develop under mesic conditions, are most vulnerable to N loss via NO as interactions between pH, SOM, and drought stimulate chemodenitrification.
Inhibition of MicroRNA‐21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis
Authors: Jafarinejad‐Farsangi Saeideh , Farazmand Ali , Gharibdoost Farhad , Karimizadeh Elham , Noorbakhsh Farshid , Faridani Habibeh , Mahmoudi Mahdi , Jamshidi Ahmad Reza
Published: September 2016

Background

Prolonged activation of dermal fibroblasts is the main cause of progressive fibrosis in systemic sclerosis (SSc). It seems that inhibition of apoptosis in SSc fibroblasts deregulates fibrosis. MicroRNA‐21 (miR‐21) is a pro‐fibrotic factor with high expression in lesional areas of SSc skin and fibroblasts.

Methods

The effects of miR‐21 on expression of Bcl‐2 and Bax, two apoptotic genes, in dermal fibroblasts of SSc patients were evaluated using real‐time polymerase chain reaction and Western blot analysis. Apoptotic cells were detected using flow cytometry and Hoechst 33258 staining assays.

Results

Overexpression of miR‐21 using synthetic miR‐21 RNA increased expression of Bcl‐2, an inhibitor of apoptosis, and decreased the Bax : Bcl‐2 expression ratio, a cell fate determinant, in SSc fibroblasts. Antisense inhibition of miR‐21 induced a high rate of apoptosis in SSc fibroblasts. We propose that this may be associated with a decrease in Bcl‐2 expression and a shift in the Bax : Bcl‐2 ratio.

Conclusions

Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR‐21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.
Maternal allocation in eggs when counting on helpers in a cooperatively breeding bird
Authors: Valencia Juliana , Mateos Concha , de la Cruz Carlos , Carranza Juan
Published: September 2016

For cooperatively breeding birds, it has been proposed that breeders should reduce their investment in eggs when they count on helpers, because this can be compensated for by helpers provisioning of nestlings. Data from some species have supported this prediction, but this is not the case in others. It has also been proposed that mothers should not reduce but rather increase investment if the presence of helpers enhances the reproductive value of offspring, a pattern that might also influence egg production as long as helpers are predictable for laying females. Here, we studied maternal expenditure in eggs and clutches in the Iberian magpie, to see whether mothers reduce their expenditure at the egg stage in the presence of helpers. Our results show that investment in clutches varied depending on the year, date in the season and age of the mother, but there were no reductions in maternal expenditure per individual egg when they counted on helpers. On the contrary, a pattern emerged in the opposite direction of more investment in eggs associated with the future presence of helpers at the nestling stage. Our data suggest that the predictability of helpers, along with the type of benefits accrued from the contribution of helpers, may be crucial to understanding the reaction of mothers at egg production.
A Comparison of the Discoloration Potential for EndoSequence Bioceramic Root Repair Material Fast Set Putty and ProRoot MTA in Human Teeth: An In Vitro Study
Authors: Alsubait S. , Al‐Haidar S. , Al‐Sharyan N.
Published: September 2016

Objective

To compare the discoloration potential of Endosequence Bioceramic Root Repair Material fast set putty (ERRMF) and ProRoot MTA (PMTA) when placed coronally in human extracted teeth over a 4‐month period.

Methodology

Forty‐eight premolars were sectioned 2 mm below the cementoenamel junction. The pulp chambers were cleaned chemo‐mechanically. The specimens were randomly assigned to three groups: PMTA, ERRMF, and no fill (control). Tooth color was measured spectrophotometrically at six time points: after material placement, after 2, 4, 8, 12, and 16 weeks. Data were transformed into Commission Internationale de l'éclairage (CIE) L*a*b* system and color difference values (ΔΕ) were calculated. Specimen images were recorded for each time point. Three random specimens from experimental groups were sectioned longitudinally and examined under a stereomicroscope. For data analyses, we used one‐way analysis of variance with repeated measurements and Tukey's test (α = 0.05).

Results

At 2 weeks, the ΔE means did not differ significantly between the groups. At 4, 8, 12, and 16 weeks, PMTA group exhibited a significantly higher ΔE compared with the ERRMF and control groups. The ΔE did not differ significantly between the ERRMF and control groups. Teeth restored using PMTA exhibited a visually progressive dark discoloration. The control and ERRMF group specimens exhibited color stability. Sections of PMTA specimens revealed grayish discoloration of the material with dark dentinal staining that was not visible in the ERRMF specimens.

Conclusion

Teeth restored using PMTA exhibited progressive discoloration, whereas teeth restored with ERRMF maintained color stability over a 4‐month period.

Clinical Significance

The results found in the present study suggest that PMTA produces tooth discoloration over time, whereas ERRMF does not induce tooth discoloration. Therefore, ERRMF might be an alternative to PMTA, especially for coronal restoration in aesthetic zone teeth. (J Esthet Restor Dent 29:59–67, 2017)
Standard and double‐dose intravenous proton pump inhibitor injections for prevention of bleeding after endoscopic resection
Authors: Jung Sung Woo , Kim Seung Young , Choe Jung Wan , Hyun Jong Jin , Jung Young Kul , Koo Ja Seol , Yim Hyung Joon , Lee Sang Woo
Published: September 2016

Background and Aim

Endoscopic resection is commonly used to remove gastric neoplasms. However, effective dosing or scheduling of proton pump inhibitors for the prevention of delayed bleeding after endoscopic resection remains unclear.

Methods

One hundred sixty‐six patients with gastric adenoma or early gastric cancer were enrolled. After an endoscopic procedure, each subject was randomly assigned to 40 mg every 24 h (standard dose group) or 40 mg every 12 h (double‐dose group) of intravenous pantoprazole for 48 h. Second‐look endoscopy was performed on day 2 after endoscopic resection to compare signs of rebleeding and ulcer status between the two groups.

Result

Eighty‐one patients of the standard dose group and 81 of the double‐dose group were analyzed. There were no significant differences in the incidence of delayed bleeding events (1.3% vs 6.2%, P = 0.21) and bleeding ulcer at the second‐look endoscopy (6.2% vs 3.9%, P = 0.69) between standard and double‐dose groups. There were no other significant variables associated with delayed bleeding or bleeding ulcer on second‐look endoscopy.

Conclusions

Intravenous pantoprazole 40 mg every 24 h or 12 h for 2 days after endoscopic resection was equally effective for the prevention of delayed bleeding.
A case of dysphagia following botulinum toxin injection for neck rejuvenation
Authors: Phothong Weeranut , Wanitphakdeedecha Rungsima , Keskool Phawin , Manuskiatti Woraphong
Published: September 2016

Botulinum toxin type A (BTX‐A) is now extensively employed for cosmetic concerns. Upper face rejuvenation, including glabella frown lines and crow's feet lines, received FDA approval for cosmetic uses. However, other off‐label uses for lower face conditions have been employed for texture and contouring purposes, including masseter hypertrophy and vertical banding of the neck. BTX‐A for rejuvenation of the aging neck is an effective and popular treatment with high patient satisfaction rates. Alleviating the aging appearance of the neck by BTX‐A is the result of denervation of hyperkinetic platysma. Concerning an extensive area of treatment and the relationship of treated muscles with other nearby muscles, dermatologists should be aware of potential adverse effects of the BTX‐A injection. We herein present a case of dysphagia following botulinum toxin injection for the treatment of platysma bands.
Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses
Authors: Uney K. , Altan F. , Altan S. , Erol H. , Arican M. , Elmas M.
Published: September 2016

The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2‐amino‐5‐thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high‐performance liquid chromatography assay. The data were evaluated using noncompartmental pharmacokinetic analyses. The estimated plasma pharmacokinetic parameters were compared with the hypothetical minimum inhibitory concentration (MIC) values (0.125–2 μg/mL). The plasma and synovial fluid concentrations and area under the concentration–time curves (AUC) of cefquinome showed a dose‐dependent increase. After a first dose of cefquinome, the ranges for the mean plasma half‐life values (2.30–2.41 h), the mean residence time (1.77–2.25 h), the systemic clearance (158–241 mL/h/kg), and the volume of distribution at steady‐state (355–431 mL/kg) were consistent across dose levels and similar to those observed after multiple doses. Cefquinome did not accumulate after multiple doses. Cefquinome penetrated the synovial fluid with AUCsynovial fluid/AUCplasma ratios ranging from 0.57 to 1.37 after first and thirteenth doses, respectively. Cefquinome is well tolerated, with no adverse effects. The percentage of time for which the plasma concentrations were above the MIC was >45% for bacteria, with MIC values of ≤0.25, ≤0.5, and ≤1 μg/mL after the administration of 1, 2, and 4 or 6 mg/kg doses of CFQ at 12‐h intervals, respectively. Further studies are needed to determine the optimal dosage regimes in critically ill patients.
Interactive effects of disturbance and dispersal on community assembly
Authors: Ojima Miriam N. , Jiang Lin
Published: September 2016

The traditional debate on alternative community states has been over whether or not they exist. Studies of community assembly have examined the role of assembly history in driving community divergence, but the context in which assembly history becomes important is a continued topic of interest. In this study, we created communities of bacterivorous ciliated protists in laboratory microcosms and manipulated assembly history, disturbance frequency, and the presence of dispersal among local communities to investigate the mechanisms behind community divergence. Specifically, we sought to understand how the role of assembly history changed in response to disturbance, dispersal, and the combination of the two. Assembly history influenced the identity of the dominant species through priority effects, and dispersal and disturbance showed interactive effects on both alpha and beta diversity. Dispersal substantially increased alpha diversity, but only in the absence of disturbance, and it reduced beta diversity, but not in the presence of low or mixed disturbance. These results demonstrate that the role of assembly history and the strength of priority effects depend on community context, suggesting that understanding the interactions between various factors shaping community assembly is important for understanding how ecological communities are structured.
Ectopic expression of a cyanobacterial flavodoxin in creeping bentgrass impacts plant development and confers broad abiotic stress tolerance
Authors: Li Zhigang , Yuan Shuangrong , Jia Haiyan , Gao Fangyuan , Zhou Man , Yuan Ning , Wu Peipei , Hu Qian , Sun Dongfa , Luo Hong
Published: September 2016

Flavodoxin (Fld) plays a pivotal role in photosynthetic microorganisms as an alternative electron carrier flavoprotein under adverse environmental conditions. Cyanobacterial Fld has been demonstrated to be able to substitute ferredoxin of higher plants in most electron transfer processes under stressful conditions. We have explored the potential of Fld for use in improving plant stress response in creeping bentgrass (Agrostis stolonifera L.). Overexpression of Fld altered plant growth and development. Most significantly, transgenic plants exhibited drastically enhanced performance under oxidative, drought and heat stress as well as nitrogen (N) starvation, which was associated with higher water retention and cell membrane integrity than wild‐type controls, modified expression of heat‐shock protein genes, production of more reduced thioredoxin, elevated N accumulation and total chlorophyll content as well as up‐regulated expression of nitrite reductase and N transporter genes. Further analysis revealed that the expression of other stress‐related genes was also impacted in Fld‐expressing transgenics. Our data establish a key role of Fld in modulating plant growth and development and plant response to multiple sources of adverse environmental conditions in crop species. This demonstrates the feasibility of manipulating Fld in crop species for genetic engineering of plant stress tolerance.
Optimal plant water economy
Authors: Buckley Thomas N , Sack Lawren , Farquhar Graham D
Published: September 2016

It was shown over 40 years ago that plants maximize carbon gain for a given rate of water loss if stomatal conductance,gs, varies in response to external and internal conditions such that the marginal carbon revenue of water, ∂A/∂E, remains constant over time. This theory has long held promise for understanding the physiological ecology of water use and for informing models of plant‐atmosphere interactions. Full realization of this potential hinges on three questions: (i) Are analytical approximations adequate for applying the theory at diurnal time scales? (ii) At what time scale is it realistic and appropriate to apply the theory? (iii) How shouldgsvary to maximize growth over long time scales? We review the current state of understanding for each of these questions and describe future research frontiers. In particular, we show that analytical solutions represent the theory quite poorly, especially when boundary layer or mesophyll resistances are significant; that diurnal variations in hydraulic conductance may help or hinder maintenance of ∂A/∂E, and the matter requires further study; and that optimal diurnal responses are distinct from optimal long‐term variations ings, which emerge from optimal shifts in carbon partitioning at the whole‐plant scale.
Household siblings and nasal and fecal microbiota in infants
Authors: Hasegawa Kohei , Linnemann Rachel W , Mansbach Jonathan M , Ajami Nadim J , Espinola Janice A , Fiechtner Lauren G , Petrosino Joseph F , Camargo Carlos A
Published: September 2016

Background

Early‐life exposure to older siblings is associated with a lower risk of asthma. To date, no study has addressed the impact of having siblings on both the airway and fecal microbiota during infancy. The aim of this study was therefore to profile the nasal airway and fecal microbiota in infants, and to examine the association between having siblings and microbiota profile.

Methods

We conducted a cross‐sectional study of 105 healthy infants (aged <1 year). Using 16S rRNA gene sequencing and an unbiased clustering approach to the nasal airway and fecal samples, we identified microbiota profiles and then determined the association between having siblings and microbiome profile.

Results

Overall, the median age was 3.4 months (IQR, 2.0–4.7 months); 43% had siblings in the household. Unbiased clustering of nasal airway microbiota identified three profiles: Moraxella dominant (43%), Corynebacterium/Dolosigranulum dominant (36%), and mixed (21%). Infants with siblings were more likely to have a Moraxella‐dominant profile than Corynebacterium/Dolosigranulum‐dominant profile (76% vs 18%), while those without siblings had the opposite pattern (18% vs 50%; P < 0.001, multivariable‐adjusted). Fecal microbiota consisted of three profiles: Bifidobacterium dominant (39%), Escherichia dominant (31%), and Enterobacter dominant (30%). Infants with siblings were more likely to have a Bifidobacterium‐dominant profile than Escherichia‐dominant profile (49% vs 24%) while those without siblings had the opposite pattern (32% vs 37%; P = 0.04, multivariable‐adjusted).

Conclusions

In this cross‐sectional study, infants with siblings were more likely to have a Moraxella‐dominant nasal microbiota profile and Bifidobacterium‐dominant fecal microbiota profile. These findings should facilitate further investigation of the interplay between early‐life environmental exposure, the microbiome, and childhood asthma.
A Network Analysis of the Volatility of High Dimensional Financial Series
Authors: Barigozzi Matteo , Hallin Marc
Published: September 2016

Interconnectedness between stocks and firms plays a crucial role in the volatility contagion phenomena that characterize financial crises, and graphs are a natural tool in their analysis. We propose graphical methods for an analysis of volatility interconnections in the Standard & Poor's 100 data set during the period 2000–2013, which contains the 2007–2008 Great Financial Crisis. The challenges are twofold: first, volatilities are not directly observed and must be extracted from time series of stock returns; second, the observed series, with about 100 stocks, is high dimensional, and curse-of-dimensionality problems are to be faced. To overcome this double challenge, we propose a dynamic factor model methodology, decomposing the panel into a factor-driven and an idiosyncratic component modelled as a sparse vector auto-regressive model. The inversion of this auto-regression, along with suitable identification constraints, produces networks in which, for a given horizon h, the weight associated with edge (i, j) represents the h-step-ahead forecast error variance of variable i accounted for by variable j's innovations. Then, we show how those graphs yield an assessment of how systemic each firm is. They also demonstrate the prominent role of financial firms as sources of contagion during the 2007–2008 crisis.
A Bayesian Hidden Markov Mixture Model to Detect Overexpressed Chromosome Regions
Authors: Mayrink Vinícius Diniz , Gonçalves Flávio Bambirra
Published: September 2016

We propose a hidden Markov mixture model for the analysis of gene expression measurements mapped to chromosome locations. These expression values represent preprocessed light intensities observed in each probe of Affymetrix oligonucleotide arrays. Here, the algorithm BLAT is used to align thousands of probe sequences to each chromosome. The main goal is to identify genome regions associated with high expression values which define clusters composed of consecutive observations. The model proposed assumes a mixture distribution in which one of the components (the one with the highest expected value) is supposed to accommodate the overexpressed clusters. The model takes advantage of the serial structure of the data and uses the distance information between neighbours to infer about the existence of a Markov dependence. This dependence is crucially important in the detection of overexpressed regions. We propose and discuss a Markov chain Monte Carlo algorithm to fit the model. Finally, the methodology proposed is used to analyse five data sets representing three types of cancer (breast, ovarian and brain).
Comparison of two series of non‐invasive instruments used for the skin physiological properties measurements: the DermaLab® from Cortex Technology vs. the series of detectors from Courage & Khazaka
Authors: Hua W. , Fan L.‐M. , Dai R. , Luan M. , Xie H. , Li A.‐Q. , Li L.
Published: September 2016

Background/purpose

The detectors from Courage & Khazaka and DermaLab® from Cortex Technology were two series of the most commonly used non‐invasive instruments for the skin physiological properties measurements. The aim of this study is to reveal the differences and correlations in measuring skin color, hydration, transepidermal water loss (TEWL), sebum and elasticity on the forearm or faces between two commercially available series of instruments.

Methods

30 subjects were enrolled to be measured by the two series of instruments. The measurements by each series were performed on the left/right side of the body randomly. The hydration, sebum, elasticity and TEWL measurements were performed on different sites.

Results

Positive correlations were found in the values of skin color, hydration, TEWL, sebum and visco‐elasticity detected by the two series. The values related to skin firmness measured by the two instruments were statistically negative correlated. Contrary to the results in measuring the skin color, the detectors from Courage & Khazaka presented lower values of variation in measuring skin hydration and TEWL than those from DermaLab®.

Conclusion

The two series have significant correlations.The differences of the two series can be due either to differences in the design of the probe or left/right part of the body.
Megafan formation driven by explosive volcanism and active tectonic processes in a humid tropical environment
Authors: Galve Jorge P. , Alvarado Guillermo E. , Pérez‐Peña José Vicente , Mora Mauricio M. , Booth‐Rea Guillermo , Azañón José Miguel
Published: September 2016

Quaternary volcanism in the Central Cordillera of Costa Rica has created an orographic barrier that concentrates rainfall on its northern side. This humid climate produces weathered bedrock prone to landsliding. Ash fall from explosive eruptions kills the vegetation cover and intensifies erosion processes. These eruptions, hydrothermal activity and associated earthquakes destabilize the slopes of river valleys, and even the volcanic edifices, producing landslides and large debris avalanches. All these processes mobilize an extra sediment input that is deposited in the piedmont lowlands forming the Santa Clara megafan. The megafans described in the literature mainly grow according to climatic fluctuations; however, sedimentation in the Santa Clara megafan is also controlled by endogenic processes with longer recurrence periods. Analysis of this megafan provides new insight into the origin and evolution of these landforms. In volcanic regions, active volcanism should be considered when investigating the formation of some megafans.
Multicenter evaluation of efficacy and safety of low‐dose versus high‐dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients
Authors: Heldenbrand Seth , Li Chenghui , Cross Rosemary P. , DePiero Kelly A. , Dick Travis B. , Ferguson Kara , Kim Miae , Newkirk Erin , Park Jeong M. , Sudaria‐Kerr Janice , Tichy Eric M. , Ueda Kimi R. , Weng Renee , Wisniewski Jesse , Gabardi Steven
Published: September 2016

Background

The cytomegalovirus (CMV) donor‐positive/recipient‐positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate‐risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head‐to‐head analysis, to our knowledge, comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs 900 mg/day for 3 months in D+/R+ RTR.

Methods

A multicenter, retrospective analysis evaluated 478 adult RTR between January 2008 and October 2011. Study participants received VGCV 450 mg/day (Group 1; n=398) or 900 mg/day (Group 2; n=89)×3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study‐approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months.

Results

The rates of graft loss, patient survival, T‐cell and/or antibody‐mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups.

Conclusion

The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs 3.4%; P=1.000). Log‐rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P=.939).
Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial
Authors: Sarmiento Elizabeth , Diez Pablo , Arraya Mauricio , Jaramillo Maria , Calahorra Leticia , Fernandez‐Yañez Juan , Palomo Jesus , Sousa Iago , Hortal Javier , Barrio Jose , Alonso Roberto , Muñoz Patricia , Navarro Joaquin , Vicario Jose , Fernandez‐Cruz Eduardo , Carbone Javier
Published: September 2016

Background

Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post‐transplant IgG HGG.

Methods

Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited. Patients received IVIG (Flebogamma 5%), as follows: 2 doses of 200 mg/kg followed by up to 5 additional doses of 300 mg/kg to maintain IgG >750 mg/dL. IgG and specific antibody titers to distinct microorganisms were tested during follow‐up. The primary outcome measure was development of severe infection during the study period. Data on the primary outcome were matched with those of 13 recipients with post‐transplant HGG who were not included in the clinical trial and with those of 11 recipients who did not develop HGG during the same study period.

Results

Mean time to detection of HGG was 15 days. IgG and specific antibody reconstitution (anti‐cytomegalovirus, anti‐Haemophilus influenza, and anti‐hepatitis B surface antigen antibodies) was observed in IVIG‐treated patients. Severe infection was detected in 3 of 12 (25%) IVIG‐treated recipients, in 10 of 13 (77%) HGG non‐IVIG patients, and in 2 of 11 (18%) non‐HGG patients (log‐rank, 15.31; P=.0005). No severe IVIG‐related side effects were recorded.

Conclusion

Data from this study demonstrate that prophylactic IVIG replacement therapy safely modulates HGG and specific antimicrobial antibodies. Our data also preliminarily suggest that IVIG replacement therapy might decrease the incidence of severe infection in heart recipients with HGG.
Is pregnancy a teachable moment to promote handwashing with soap among primiparous women in rural Bangladesh? Follow‐up of a randomised controlled trial
Authors: Kamm Kelly B. , Vujcic Jelena , Nasreen Sharifa , Luby Stephen P. , Zaman K. , El Arifeen Shams , Ram Pavani K.
Published: September 2016

Objective

Promoting handwashing with soap to mothers of young children can significantly reduce diarrhoea and pneumonia morbidity among children, but studies that measured long‐term behaviour after interventions rarely found improvements in handwashing habits. Expecting mothers may experience emotional and social changes that create a unique environment that may encourage adoption of improved handwashing habits. The objective of this study was to determine whether exposure to an intensive handwashing intervention in the perinatal period (perinatal arm) was associated with improved maternal handwashing behaviour vs. exposure to the same intervention after the end of the perinatal period (post‐neonatal arm).

Methods

We identified primiparous women previously enrolled a randomised controlled handwashing intervention trial (November 2010–December 2011) and observed handwashing behaviours at the home 1–14 months after completion of the RCT (January–May 2012). We observed maternal handwashing and estimated the prevalence ratio (PR) of maternal handwashing using log‐binomial regression.

Results

We enrolled 107 mothers in the perinatal arm and 105 mothers in the post‐neonatal arm. Handwashing with soap at recommended times was low overall (4.6%) and comparable between arms (PR = 0.9, 95% CI 0.5, 1.5).

Conclusions

This handwashing intervention was unable to develop and establish improved handwashing practices in primiparous women in rural Bangladesh. While pregnancy may present an opportunity and motivation to do so, further studies should assess whether social, individual and environmental influences overcome this motivation and prevent handwashing with soap among new mothers.
Comparative proteomics of cucurbit phloem indicates both unique and shared sets of proteins
Authors: Lopez‐Cobollo Rosa M. , Filippis Ioannis , Bennett Mark H. , Turnbull Colin G.N.
Published: September 2016

Cucurbits are well‐studied models for phloem biology but unusually possess both fascicular phloem (FP) within vascular bundles and additional extrafascicular phloem (EFP). Although the functional differences between the two systems are not yet clear, sugar analysis and limited protein profiling have established that FP and EFP have divergent compositions. Here we report a detailed comparative proteomics study of FP and EFP in two cucurbits, pumpkin and cucumber. We re‐examined the sites of exudation by video microscopy, and confirmed that in both species, the spontaneous exudate following tissue cutting derives almost exclusively from EFP. Comparative gel electrophoresis and mass spectrometry‐based proteomics of exudates, sieve element contents and microdissected stem tissues established that EFP and FP profiles are highly dissimilar, and that there are also species differences. Searches against cucurbit databases enabled identification of more than 300 FP proteins from each species. Few of the detected proteins (about 10%) were shared between the sieve element contents of FP and EFP, and enriched Gene Ontology categories also differed. To explore quantitative differences in the proteomes, we developed multiple reaction monitoring methods for cucumber proteins that are representative markers for FP or EFP and assessed exudate composition at different times after tissue cutting. Based on failure to detect FP markers in exudate samples, we conclude that FP is blocked very rapidly and therefore makes a minimal contribution to the exudates. Overall, the highly divergent contents of FP and EFP indicate that they are substantially independent vascular compartments.
Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis
Authors: Tartaglio Virginia , Rennie Emilie A. , Cahoon Rebecca , Wang George , Baidoo Edward , Mortimer Jennifer C. , Cahoon Edgar B. , Scheller Henrik V.
Published: September 2016

Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss‐of‐function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen‐specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid‐mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short‐chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. This study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important roles for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.