bluuebunny/crossref_metadata_2025 huggingface dataset:
Prominent efficiency in skin delivery of resveratrol by novel sucrose oleate microemulsion
Authors: Yutani Reiko , Komori Yuka , Takeuchi Atsuko , Teraoka Reiko , Kitagawa Shuji
Published: January 2016

Objectives

To achieve an efficient skin delivery of resveratrol using sucrose fatty acid ester microemulsions and to clarify the mechanism of enhanced penetration.

Methods

Skin delivery of resveratrol using different sucrose fatty acid ester microemulsions was examined in vitro. Vehicle–skin interaction was assessed by applying blank microemulsions to skin. Skin incorporation of microemulsion components was also assessed.

Key findings

The microemulsion consisting of sucrose oleate (SO), ethanol, isopropyl myristate (IPM) and water (MESO-E) showed a prominent increase in the amount of skin incorporation of resveratrol, which was more than 5-fold higher than those of all microemulsions we previously examined. Using MESO-E, resveratrol was rapidly incorporated into skin and mainly located in the dermis. When applied in the concentration range of 5–55 mm, the amount of skin incorporation of resveratrol increased with the applied concentration up to 30 mm, whereas skin incorporation efficiency was inversely proportional to the concentration. The microemulsion–skin interaction seemed to be involved in the enhanced skin delivery process of resveratrol by MESO-E. Stratum corneum modification due to the penetration of IPM, ethanol and SO is also involved in this interaction.

Conclusions

MESO-E would be a promising vehicle for the efficient skin delivery of resveratrol, especially when applied at a low concentration.
Acute lung injury induced by lipopolysaccharide is inhibited by wogonin in mice via reduction of Akt phosphorylation and RhoA activation
Authors: Yeh Yen-Cheng , Yang Ching-Ping , Lee Shiuan-Shinn , Horng Chi-Ting , Chen Hung-Yi , Cho Ta-Hsiung , Yang Ming-Ling , Lee Chien-Ying , Li Miao-Cing , Kuan Yu-Hsiang
Published: January 2016

Objectives

Neutrophil infiltration into the lung is the critical characteristic of acute lung injury (ALI), which is a clinical state with acute inflammatory syndrome. Up to now, there is no effective medicine for ALI. Wogonin has been shown to posses serval biological activities including anti-inflammation, anti-oxidant and anti-carcinoma.

Methods

Acute lung injury was induced by intratracheal injection of LPS, and wogonin at various concentrations was injected intraperitoneally 30 min prior to LPS. Contents of myeloperoxidase (MPO) and expression of chemokines and adhesion molecules were determined by commercially and ELISA assay kits, respectively. Akt phosphorylation and RhoA activation were measured by western blot and RhoA pull-down activation assay, respectively.

Key finding

Neutrophil infiltration was reduced by wogonin in a concentration-dependent manner in the LPS-induced ALI mice model. LPS-induced proinflammatory cytokines and adhesion molecules were inhibited by wogonin in bronchoalveolar lavage fluid (BALF) with LPS-induced ALI. Furthermore, wogonin suppressed Akt phosphorylation and RhoA activation in lungs in LPS-induced ALI. The similar parallel trend was observed as wogonin reduced LPS-induced neutrophils infiltration, proinflammatory cytokines generation, adhesion molecules expression, Akt phosphorylation, and RhoA activation.

These results suggested that the effects of wogonin in LPS-induced ALI were induced by inhibition of Akt phosphorylation and RhoA activation.
Preparation and evaluation of ziprasidone–phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect
Authors: Miao Yanfei , Chen Guoguang , Ren Lili , Ouyang Pingkai
Published: January 2016

Objectives

The purpose of this work was to develop ziprasidone–phospholipid complex (ZIP-PLC) in sustained-release pellets to enhance the oral bioavailability and overcome the food effect of ziprasidone.

Methods

Ziprasidone–phospholipid complex was formulated by solvent-evaporation method. The complexes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and solubility testing. The optimized ZIP-PLC was used to prepare ZIP-PLC sustained-release pellets via extrusion–spheronization method. The pellets were characterized by in vitro drug-release studies and administered to fasted and fed beagle dogs, and their pharmacokinetics were compared with commercial formulation Zeldox capsule as a control.

Key findings

The results of FTIR, SEM, DSC and PXRD studies confirmed the formation of phospholipid complex. Solubility studies showed there was a higher solubility in water for ZIP-PLC than monohydrate ziprasidoe. The in vitro release rate of ziprasidone from the ZIP-PLC sustained-release pellet exhibited controlled-release characteristics with over 95% total release in 12 h. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions, and no food effect was achieved simultaneously in ZIP-PLC sustained-release pellet compared with Zeldox capsule.

Conclusions

The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.
Conjugation of curcumin-loaded lipid nanoemulsions with cell-penetrating peptides increases their cellular uptake and enhances the anti-inflammatory effects in endothelial cells
Authors: Simion Viorel , Stan Daniela , Constantinescu Cristina Ana , Deleanu Mariana , Dragan Emanuel , Tucureanu Monica Madalina , Gan Ana-Maria , Butoi Elena , Constantin Alina , Manduteanu Ileana , Simionescu Maya , Calin Manuela
Published: January 2016

Objectives

To prepare and characterize in vitro and in vivo lipid nanoemulsions (LN) loaded with curcumin (Cm) and functionalized with a cell-penetrating peptide.

Methods

Curcumin-loaded lipid nanoemulsions (CmLN) functionalized with a nona-arginine peptide (R9-CmLN) have been obtained, characterized and optimized for size, entrapment efficiency and in vitro Cm release. The interaction of R9-CmLN with human endothelial cells (HEC) was investigated using cultured EA.hy926 cells, and in vivo biodistribution studies were performed using C57BL6 mice.

Key findings

When used in therapeutically relevant concentration, R9-CmLN have low haemolytic activity, low cytotoxicity on HEC, and show anti-inflammatory effects by reducing the monocytes adhesion to TNF-α activated HEC. Moreover, HEC uptake and internalization of R9-CmLN was significantly higher compared to the non-functionalized CmLN. In vivo biodistribution studies in mice revealed a higher accumulation of R9-CmLN in the liver and the lungs compared to CmLN and the body clearance of the both nanoformulations after 72 h.

Conclusions

Cell-penetrating peptides-functionalized CmLN have superior characteristics compared to their non-functionalized counterparts: are more efficiently internalized by the cells, produces anti-inflammatory effects in HEC and when administrated intravenously in mice exhibit increased accumulation in the liver and the lungs, suggesting their potential therapeutic applications in different inflammatory pathologies localized in the liver or the lungs.
A supermatrix approach provides a comprehensive genus‐level phylogeny for Gentianales
Authors: Yang Lei‐Lei , Li Hong‐Lei , Wei Lei , Yang Tuo , Kuang Dai‐Yong , Li Ming‐Hong , Liao Yi‐Ying , Chen Zhi‐Duan , Wu Hong , Zhang Shou‐Zhou
Published: January 2016

Gentianales consist of Apocynaceae, Gelsemiaceae, Gentianaceae, Loganiaceae, and Rubiaceae, of which the majority are woody plants in tropical and subtropical areas. Despite extensive efforts in reconstructing the phylogeny of Gentianales based on molecular data, some interfamily and intrafamily relationships remain uncertain. We reconstructed the genus‐level phylogeny of Gentianales based on the supermatrix of eight plastid markers (rbcL, matK, atpB, ndhF, rpl16, rps16, the trnL‐trnF region, and atpB‐rbcL spacer) and one mitochondrial gene (matR) using maximum likelihood. The major clades and their relationships retrieved in the present study concur with those of previous studies. All of the five families of Gentianales are monophyletic with strong support. We resolved Rubiaceae as sister to the remaining families in Gentianales and showed support for the sister relationship between Loganiaceae and Apocynaceae. Our results provide new insights into relationships among intrafamilial clades. For example, within Rubiaceae we found that Craterispermeae were sister to Morindeae + (Palicoureeae + Psychotrieae) and that Theligoneae were sister to Putorieae. Within Gentianaceae, our phylogeny revealed that Gentianeae were sister to Helieae and Potalieae, and subtribe Lisianthiinae were sister to Potaliinae and Faroinae. Within Loganiaceae, we found Neuburgia as sister to Spigelieae. Within Apocynaceae, our results supported Amsonieae as sister to Melodineae, and Hunterieae as sister to a clade comprising Plumerieae + (Carisseae + APSA). We also confirmed the monophyly of Perplocoideae and the relationships among Baisseeae + (Secamonoideae + Asclepiadoideae).
Reduced evoked motor and sensory potential amplitudes in obstructive sleep apnea patients
Authors: Mihalj Mario , Lušić Linda , Đogaš Zoran
Published: January 2016

It is unknown to what extent chronic intermittent hypoxaemia in obstructive sleep apnea causes damage to the motor and sensory peripheral nerves. It was hypothesized that patients with obstructive sleep apnea would have bilaterally significantly impaired amplitudes of both motor and sensory peripheral nerve‐evoked potentials of both lower and upper limbs. An observational study was conducted on 43 patients with obstructive sleep apnea confirmed by the whole‐night polysomnography, and 40 controls to assess the relationship between obstructive sleep apnea and peripheral neuropathy. All obstructive sleep apnea subjects underwent standardized electroneurographic testing, with full assessment of amplitudes of evoked compound muscle action potentials, sensory neural action potentials, motor and sensory nerve conduction velocities, and distal motor and sensory latencies of the median, ulnar, peroneal and sural nerves, bilaterally. All nerve measurements were compared with reference values, as well as between the untreated patients with obstructive sleep apnea and control subjects. Averaged compound muscle action potential and sensory nerve action potential amplitudes were significantly reduced in the nerves of both upper and lower limbs in patients with obstructive sleep apnea compared with controls (P < 0.001). These results confirmed that patients with obstructive sleep apnea had significantly lower amplitudes of evoked action potentials of both motor and sensory peripheral nerves. Clinical/subclinical axonal damage exists in patients with obstructive sleep apnea to a greater extent than previously thought.
How many hours do people sleep in Bangladesh? A country‐representative survey
Authors: Yunus Fakir M. , Khan Safayet , Akter Tahera , Jhohura Fatema T. , Reja Saifur , Islam Akramul , Rahman Mahfuzar
Published: January 2016

This study investigated total sleep time in the Bangladeshi population and identified the proportion of the population at greater risk of developing chronic diseases due to inadequate sleep. Using a cross‐sectional survey, total sleep time was captured and analysed in 3968 respondents aged between 6 and 106 years in 24 (of 64) districts in Bangladesh. Total sleep time was defined as the hours of total sleep in the previous 24 h. We used National Sleep Foundation (2015) guidelines to determine the recommended sleep hours in different age categories. Less or more than the recommended total sleep time (in hours) was considered ‘shorter’ and ‘longer’ sleep time, respectively. Linear and multinomial logistic regression models were used to determine the relationship between demographic variables and estimated risk of shorter and longer total sleep time. The mean (±standard deviation) total sleep time of children (6–13 years), teenagers (14–17 years), young adults and adults (18–64 years) and older adults (≥65 years) were 8.6 (±1.1), 8.1 (±1.0), 7.7 (±0.9) and 7.8 (±1.4) h, respectively, which were significantly different (P < 0.01). More than half of school‐age children (55%) slept less than, and 28.2% of older adults slept longer than, recommended. Residents in all divisions (except Chittagong) in Bangladesh were less likely to sleep longer than in the Dhaka division. Rural populations had a 3.96× greater chance of sleeping for a shorter time than urban residents. The Bangladeshi population tends to sleep for longer and/or shorter times than their respective recommended sleep hours, which is detrimental to health.
Rheological and Thermal Properties of Selected Brazilian Honeys from Various Floral Origins
Authors: Silva Vanelle Maria Da , Carvalho Larissa Andrade De , Oliveira Natália Leite De , Torres Filho Robledo De Almeida , Resende Jaime Vilela De
Published: January 2016

The rheological and thermal properties of honeys have a practical importance for beekeepers and industries, as their determination allows their proper processing and quality control. However, few studies have been carried out in this area with Brazilian honeys. Therefore, physicochemical, rheological and thermal properties of 40 Brazilian honeys of different floral origins were determined in this study. All the physicochemical properties indicated that the analyzed honey samples met the criteria for honeys established by Codex Alimentarius. The honeys showed non‐Newtonian behavior from 10C to 15C and Newtonian behavior from 20C to 30C with the influence of temperature on viscosity and on the viscous modulus (G″) described by the Arrhenius models. Oscillatory rheological data revealed a liquid‐like behavior (G″> elastic modulus (G′)) of the honeys. The glass transition temperature (Tg) of the honeys varied between −46.7C and −43.7C. By the principal component analysis (PCA), the first component explained 70.0% of the variation of the data, forming two groups described by moisture content, aw, viscosity (10C to 30C), G″ and Tg. This analysis confirms the important influence of the moisture content and of aw in the rheological and thermal properties of honeys and provide useful information for the industrialization of honey and honey‐based products.

Practical Application

Determining the honey rheological and thermal properties allows its proper processing and quality control, preventing the waste of economic resources. Conclusions for beekeepers and industries are: the honey physicochemical properties are in conformity with the Brazilian legislation and the Codex Alimentarius, which could be used by consumers and the food industry; rheological and thermal properties are inversely correlated with the moisture content and with aw, and could be used to distinguish Brazilian honeys; Brazilian honeys behave as diluted materials, and their viscosity is temperature‐ and floral origin‐dependent. Determining their viscosity helps in the performance, sizing and selection of equipment such as pumps, mixers, filters, centrifuges and heat exchangers; temperature fluctuations induce physical and chemical alterations in the honey, and temperature control during its processing and storage is important for maintaining its quality. All of these parameters provide useful information for the development of new products, optimization of industrial processes and control of quality and authenticity of honeys.
Potential of Microbubbles as Fat Replacer: Effect on Rheological, Tribological and Sensorial Properties of Model Food Systems
Authors: Rovers Tijs A.M. , Sala Guido , Van der Linden Erik , Meinders Marcel B.J.
Published: January 2016

The potential of microbubbles as fat replacers and texture modifiers was assessed by comparison of the rheological and tribological properties of model food systems that contained (1) microbubbles, (2) emulsion droplets or (3) no added colloidal structures. We used (a) liquids with thickener, (b) liquids without thickener and (c) gels as model food systems. A sensory test was performed in which we investigated whether panellists could discriminate between the different samples. It was found that the food system containing emulsion droplets had better lubrication properties than the dispersions containing microbubbles and solutions without any colloidal structures. The systems with emulsion droplets could be well discriminated sensorially from those with microbubbles or those without an added colloidal structures. Samples containing a mixture of emulsion droplets and microbubbles were comparable to those of samples containing only emulsion droplets. We conclude that at the studied volume fraction of 5% the measured friction and perceived mouthfeel of systems containing microbubbles is rather different from those of systems containing emulsion droplets, while both have a diameter of about 1 μm. At this volume fraction microbubbles cannot simply replace emulsion droplets.

Practical Applications

Microbubbles may have practical applications in food products as texture modifiers and fat replacers, and can be therefore considered as new colloidal structures with a potential in the development of healthier food products. Combining rheological, tribological, and sensorial experiments is a useful tool to test the application of new ingredients in food products and to understand their working mechanisms. This study represents an example of this approach to assess the potential of new colloidal structures as food ingredients. The combination of rheology and tribology with limited sensory experiments allows to estimate this potential without the need of extensive sensory studies that would require large amounts of samples, which in the case of systems containing microbubbles would be also extremely expensive.
Long‐legged caracaras: terrestrial habitat and hindlimb morphology
Authors: Mosto M. C. , Picasso M. B. J. , Biondi L. M.
Published: January 2016

The hindlimb of the Polyborinae has always been characterized as long when it was compared with other diurnal raptors; however, no empirical work has been done to support such a traditional well‐known fact. The objective of this work is to analyze the femur, tibiotarsus and tarsometatarsus of this group to corroborate whether this assumption has a significant statistical support. The proportions of these bones were analyzed with a one‐way Kruskal–Wallis test and Dunn's test as post hoc comparisons. The allometric relationships between the long bones and body mass or the total length of the hindlimb were carried out with the reduced major axis method. In addition, the osteological study is complemented with a myological dissection of the hindlimb of Milvago chimachima and Caracara plancus. The three long bones of the limb of Polyborinae show significant differences with those from Falconinae. The presence of a long tarsometatarsus is a typical feature of terrestrial birds, it produces an increase in length stride allowing an effective locomotion on land. Among the myological differences, the most prominent are the presence of the musculus flexor cruris lateralis (absent in other Falconidae) and a well‐developed musculus fibularis longus. These osseous and myological features are related to the terrestrial locomotion present in this subfamily.
Progression of fibrosis in patients with chronic viral hepatitis is associated with IL‐17+ neutrophils
Authors: Macek Jilkova Zuzana , Afzal Samia , Marche Hélène , Decaens Thomas , Sturm Nathalie , Jouvin‐Marche Evelyne , Huard Bertrand , Marche Patrice N.
Published: January 2016

Background & Aims

The pro‐inflammatory cytokine IL‐17 plays a crucial role in liver diseases associated with hepatic fibrosis and increased risk of cancer development. Nevertheless, the cellular source of this cytokine has never been characterized in patients with liver fibrosis.

Methods

In this study, we investigated liver biopsies from 49 patients with chronic viral hepatitis at different stages of liver fibrosis. We monitored IL‐17 production by intracellular flow cytometry, immunofluorescence and immunohistochemical in situ stainings, allowing a precise quantification, characterization and localization of IL‐17+ cells.

Results

Density of IL‐17+ cells increased with the stage of liver fibrosis specifically in fibrotic septa and portal areas (correlation coefficient r = 0.7373; P < 0.0001). Data clearly show that the frequency of intrahepatic IL‐17+ lymphocytes (including T, NKT and NK cells) was independent on stage of liver fibrosis, and we observed no statistical differences in number of IL‐17+ macrophages during progression of fibrosis. On the other hand, the number of IL‐17+ neutrophils in fibrotic septa and portal areas strongly correlated with the stages of fibrosis (correlation coefficient r = 0.6986; P < 0.0001), contributing significantly to total IL‐17 production in liver tissue.

Conclusions

Our data indicate that neutrophils represent an important source of IL‐17 in the human liver, especially in late fibrosis stages. Inhibition of this specific harmful subset of neutrophils may offer therapeutic opportunities in fibrotic liver.
Space weathering of silicates simulated by successive laser irradiation: In situ reflectance measurements of Fo90, Fo99+, and SiO2
Authors: Loeffler M. J. , Dukes C. A. , Christoffersen R. , Baragiola R. A.
Published: January 2016

Pulsed‐laser irradiation causes the visible‐near‐infrared spectral slope of olivine (Fo90 and Fo99+) and SiO2 to increase (redden), while the olivine samples darken and the SiO2 samples brighten slightly. XPS analysis shows that irradiation of Fo90 produces metallic Fe. Analytical SEM and TEM measurements confirm that reddening in the Fo90 olivine samples correlates with the production of “nanophase” metallic Fe (npFe0) grains, 20–50 nm in size. The reddening observed in the SiO2 sample is consistent with the formation of SiO or other SiOx species that absorb in the visible. The weak spectral brightening induced by laser irradiation of SiO2 is consistent with a change in surface topography of the sample. The darkening observed in the olivine samples is likely caused by the formation of larger npFe0 particles, such as the 100–400 nm diameter npFe0 identified during our TEM analysis of Fo90 samples. The Fo90 reflectance spectra are qualitatively similar to those in previous experiments suggesting that in all cases formation of npFe0 is causing the spectral alteration. Finally, we find that the accumulation of successive laser pulses cause continued sample darkening in the Vis‐NIR, which suggests that repeated surface impacts are an efficient way to darken airless body surfaces.
Microchondrules in three unequilibrated ordinary chondrites
Authors: Bigolski John N. , Weisberg Michael K. , Connolly Harold C. , Ebel Denton S.
Published: January 2016

We report on a suite of microchondrules from three unequilibrated ordinary chondrites (UOCs). Microchondrules, a subset of chondrules that are ubiquitous components of UOCs, commonly occur in fine‐grained chondrule rims, although may also occur within matrix. Microchondrules have a variety of textures: cryptocrystalline, microporphyritic, radial, glassy. In some cases, their textures, and in many cases, their compositions, are similar to their larger host chondrules. Bulk compositions for both chondrule populations frequently overlap. The primary material that composes many of the microchondrules has compositions that are pyroxene‐normative and is similar to low‐Ca‐pyroxene phenocrysts from host chondrules; primary material rarely resembles olivine or plagioclase. Some microchondrules are composed of FeO‐rich material that has compositions similar to the bulk submicron fine‐grained rim material. These microchondrules, however, are not a common compositional type and probably represent secondary FeO‐enrichment. Microchondrules may also be porous, suggestive of degasing to form vesicles. Our work shows that the occurrence of microchondrules in chondrule rims is an important constraint that needs to be considered when evaluating chondrule‐forming mechanisms. We propose that microchondrules represent melted portions of the chondrule surfaces and/or the melt products of coagulated dust in the immediate vicinity of the larger chondrules. We suggest that, through recycling events, the outer surfaces of chondrules were heated enough to allow microchondrules to bud off as protuberances and become entrained in the surrounding dusty environment as chondrules were accreting fine‐grained rims. Microchondrules are thus byproducts of cyclic processing of chondrules in localized environments. Their occurrence in fine‐grained rims represents a snapshot of the chondrule‐forming environment. We evaluate mechanisms for microchondrule formation and hypothesize a potential link between the emergence of type II chondrules in the early solar system and the microchondrule‐bearing fine‐grained rims surrounding type I chondrules.
High crustal diversity preserved in the lunar meteorite Mount DeWitt 12007 (Victoria Land, Antarctica)
Authors: Collareta Alberto , D'Orazio Massimo , Gemelli Maurizio , Pack Andreas , Folco Luigi
Published: January 2016

The meteorite Mount DeWitt (DEW) 12007 is a polymict regolith breccia mainly consisting of glassy impact‐melt breccia particles, gabbroic clasts, feldspathic clasts, impact and volcanic glass beads, basaltic clasts, and mingled breccia clasts embedded in a matrix dominated by fine‐grained crystals; vesicular glassy veins and rare agglutinates are also present. Main minerals are plagioclase (typically An>85) and clinopyroxene (pigeonites and augites, sometimes interspersed). The presence of tranquillityite, coupled with the petrophysical data, the O‐isotope data (Δ17O = −0.075), and the FeOtot/MnO ratios in olivine (91), pyroxene (65), and bulk rock (77) indicate a lunar origin for DEW 12007. Impactites consist of Al‐rich impact‐melt splashes and plagioclase‐rich meta‐melt clasts. The volcanic products belong to the very low titanium (VLT) or low titanium (LT) suites; an unusual subophitic fragment could be cryptomare‐related. Gabbroic clasts could represent part of a shallow intrusion within a volcanic complex with prevailing VLT affinity. DEW 12007 has a mingled bulk composition with relatively high incompatible element abundances and shows a high crustal diversity comprising clasts from the Moon's major terranes and rare lithologies. First‐order petrographic and chemical features suggest that DEW 12007 could be launch‐paired with other meteorites including Y 793274/981031, QUE 94281, EET 87521/96008, and NWA 4884.
Transcriptome profiling of immune tissues reveals habitat‐specific gene expression between lake and river sticklebacks
Authors: Huang Yun , Chain Frédéric J. J. , Panchal Mahesh , Eizaguirre Christophe , Kalbe Martin , Lenz Tobias L. , Samonte Irene E. , Stoll Monika , Bornberg‐Bauer Erich , Reusch Thorsten B. H. , Milinski Manfred , Feulner Philine G. D.
Published: January 2016

The observation of habitat‐specific phenotypes suggests the action of natural selection. The three‐spined stickleback (Gasterosteus aculeatus) has repeatedly colonized and adapted to diverse freshwater habitats across the northern hemisphere since the last glaciation, while giving rise to recurring phenotypes associated with specific habitats. Parapatric lake and river populations of sticklebacks harbour distinct parasite communities, a factor proposed to contribute to adaptive differentiation between these ecotypes. However, little is known about the transcriptional response to the distinct parasite pressure of those fish in a natural setting. Here, we sampled wild‐caught sticklebacks across four geographical locations from lake and river habitats differing in their parasite load. We compared gene expression profiles between lake and river populations using 77 whole‐transcriptome libraries from two immune‐relevant tissues, the head kidney and the spleen. Differential expression analyses revealed 139 genes with habitat‐specific expression patterns across the sampled population pairs. Among the 139 differentially expressed genes, eight are annotated with an immune function and 42 have been identified as differentially expressed in previous experimental studies in which fish have been immune challenged. Together, these findings reinforce the hypothesis that parasites contribute to adaptation of sticklebacks in lake and river habitats.
Disruptive selection without genome‐wide evolution across a migratory divide
Authors: von Rönn Jan A.C. , Shafer Aaron B.A. , Wolf Jochen B.W.
Published: January 2016

Transcontinental migration is a fascinating example of how animals can respond to climatic oscillation. Yet, quantitative data on fitness components are scarce, and the resulting population genetic consequences are poorly understood. Migratory divides, hybrid zones with a transition in migratory behaviour, provide a natural setting to investigate the micro‐evolutionary dynamics induced by migration under sympatric conditions. Here, we studied the effects of migratory programme on survival, trait evolution and genome‐wide patterns of population differentiation in a migratory divide of European barn swallows. We sampled a total of 824 individuals from both allopatric European populations wintering in central and southern Africa, respectively, along with two mixed populations from within the migratory divide. While most morphological characters varied by latitude consistent with Bergmann's rule, wing length co‐varied with distance to wintering grounds. Survival data collected during a 5‐year period provided strong evidence that this covariance is repeatedly generated by disruptive selection against intermediate phenotypes. Yet, selection‐induced divergence did not translate into genome‐wide genetic differentiation as assessed by microsatellites, mtDNAand >20 000 genome‐wideSNPmarkers; nor did we find evidence of local genomic selection between migratory types. Among breeding populations, a single outlier locus mapped to theBUB1 gene with a role in mitotic and meiotic organization. Overall, this study provides evidence for an adaptive response to variation in migration behaviour continuously eroded by gene flow under current conditions of nonassortative mating. It supports the theoretical prediction that population differentiation is difficult to achieve under conditions of gene flow despite measurable disruptive selection.
Hyperglycemia‐Mediated Oxidative Stress Increases Pulmonary Vascular Permeability
Authors: Clemmer John S. , Xiang Lusha , Lu Silu , Mittwede Peter N. , Hester Robert L.
Published: January 2016

Objective

Hyperglycemia in diabetes mellitus is associated with endothelial dysfunction as evidenced by increased oxidative stress and vascular permeability. Whether impaired glucose control in metabolic syndrome impacts pulmonary vascular permeability is unknown. We hypothesized that in metabolic syndrome, hyperglycemia increases lung vascular permeability through superoxide.

Methods

Lung capillary Kf and vascular superoxide were measured in the isolated lungs of LZ and OZ rats. OZ were subjected to 4 weeks of metformin treatment (300 mg/kg/day orally) to improve insulin sensitivity. In a separate experiment, lung vascular permeability and vascular superoxide were measured in LZ exposed to acute hyperglycemia (30 mM).

Results

As compared to LZ, OZ had impaired glucose and insulin tolerance and elevated vascular superoxide which was associated with an elevated lung Kf. Chronic metformin treatment in OZ improved glucose control and insulin sensitivity which was associated with decreased vascular oxidative stress and lung Kf. Acute hyperglycemia in isolated lungs from LZ increased lung Kf, which was blocked with the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin (3 mM). Apocynin also decreased baseline Kf in OZ.

Conclusions

These data suggest that hyperglycemia in metabolic syndrome exacerbates lung vascular permeability through increases in vascular superoxide, possibly through NADPH oxidase.
Graph‐Based Modeling of Information Flow Evolution and Propagation under V2V Communications‐Based Advanced Traveler Information Systems
Authors: Kim Yong Hoon , Peeta Srinivas
Published: January 2016

A vehicle equipped with a vehicle‐to‐vehicle (V2V) communications capability can continuously update its knowledge on traffic conditions using its own experience and anonymously obtained travel experience data from other such equipped vehicles without any central coordination. In such a V2V communications‐based advanced traveler information system (ATIS), the dynamics of traffic flow and intervehicle communication lead to the time‐dependent vehicle knowledge on the traffic network conditions. In this context, this study proposes a graph‐based multilayer network framework to model the V2V‐based ATIS as a complex system which is composed of three coupled network layers: a physical traffic flow network, and virtual intervehicle communication and information flow networks. To determine the occurrence of V2V communication, the intervehicle communication layer is first constructed using the time‐dependent locations of vehicles in the traffic flow layer and intervehicle communication‐related constraints. Then an information flow network is constructed based on events in the traffic and intervehicle communication networks. The graph structure of this information flow network enables the efficient tracking of the time‐dependent vehicle knowledge of the traffic network conditions using a simple graph‐based reverse search algorithm and the storage of the information flow network as a single graph database. Further, the proposed framework provides a retrospective modeling capability to articulate explicitly how information flow evolves and propagates. These capabilities are critical to develop strategies for the rapid flow of useful information and traffic routing to enhance network performance. It also serves as a basic building block for the design of V2V‐based route guidance strategies to manage traffic conditions in congested networks. Synthetic experiments are used to compare the graph‐based approach to a simulation‐based approach, and illustrate both memory usage and computational time efficiencies.
Regulation of cell reversal frequency in Myxococcus xanthus requires the balanced activity of CheY‐like domains inFrzEandFrzZ
Authors: Kaimer Christine , Zusman David R.
Published: January 2016

The Frz pathway of Myxococcus xanthus controls cell reversal frequency to support directional motility during swarming and fruiting body formation. Previously, we showed that phosphorylation of the response regulator FrzZ correlates with reversal frequencies, suggesting that this activity represents the output of the Frz pathway. Here, we tested the effect of different expression levels of FrzZ and its cognate kinase FrzE on M. xanthus motility. FrzZ overexpression caused a slight increase in phosphorylation and reversals. By contrast, FrzE overexpression abolished phosphorylation of FrzZ; this inhibition required the response regulator domain of FrzE. FrzZ phosphorylation was restored when both FrzE and FrzZ were overexpressed together. Our results show that the response regulator domain of FrzE is a negative regulator of FrzE kinase activity. This inhibition can be modulated by FrzZ, which acts as a positive regulator. Interestingly, fluorescence microscopy revealed that FrzZ and FrzE localize differently: FrzE colocalizes with the FrzCD receptor and the nucleoid, while FrzZ shows dispersed and polar localization. However, FrzZ binds tightly to the truncated variant FrzEΔCheY. This indicates that the response regulator domain of FrzE is required for the interaction between FrzE and FrzZ to be transient, providing an unexpected regulatory output to the Frz pathway.
Calcium signalling in malaria parasites
Authors: Brochet Mathieu , Billker Oliver
Published: January 2016

Ca2+ is a ubiquitous intracellular messenger in malaria parasites with important functions in asexual blood stages responsible for malaria symptoms, the preceding liver‐stage infection and transmission through the mosquito. Intracellular messengers amplify signals by binding to effector molecules that trigger physiological changes. The characterisation of some Ca2+ effector proteins has begun to provide insights into the vast range of biological processes controlled by Ca2+ signalling in malaria parasites, including host cell egress and invasion, protein secretion, motility and cell cycle regulation. Despite the importance of Ca2+ signalling during the life cycle of malaria parasites, little is known about Ca2+ homeostasis. Recent findings highlighted that upstream of stage‐specific Ca2+ effectors is a conserved interplay between second messengers to control critical intracellular Ca2+ signals throughout the life cycle. The identification of the molecular mechanisms integrating stage‐transcending mechanisms of Ca2+ homeostasis in a network of stage‐specific regulator and effector pathways now represents a major challenge for a meaningful understanding of Ca2+ signalling in malaria parasites.
Mitochondrial pyruvate carrier in Trypanosoma brucei
Authors: Štáfková Jitka , Mach Jan , Biran Marc , Verner Zdeněk , Bringaud Frédéric , Tachezy Jan
Published: January 2016

Pyruvate is a key product of glycolysis that regulates the energy metabolism of cells. In Trypanosoma brucei, the causative agent of sleeping sickness, the fate of pyruvate varies dramatically during the parasite life cycle. In bloodstream forms, pyruvate is mainly excreted, whereas in tsetse fly forms, pyruvate is metabolized in mitochondria yielding additional ATP molecules. The character of the molecular machinery that mediates pyruvate transport across mitochondrial membrane was elusive until the recent discovery of mitochondrial pyruvate carrier (MPC) in yeast and mammals. Here, we characterized pyruvate import into mitochondrion of T. brucei. We identified mpc1 and mpc2 homologs in the T. brucei genome with attributes of MPC protein family and we demonstrated that both proteins are present in the mitochondrial membrane of the parasite. Investigations of mpc1 or mpc2 gene knock‐out cells proved that T. brucei MPC1/2 proteins facilitate mitochondrial pyruvate transport. Interestingly, MPC is expressed not only in procyclic trypanosomes with fully activated mitochondria but also in bloodstream trypanosomes in which most of pyruvate is excreted. Moreover, MPC appears to be essential for bloodstream forms, supporting the recently emerging picture that the functions of mitochondria in bloodstream forms are more diverse than it was originally thought.
Signalling mucin Msb2 Regulates adaptation to thermal stress in Candida albicans
Authors: Saraswat Darpan , Kumar Rohitashw , Pande Tanaya , Edgerton Mira , Cullen Paul J.
Published: January 2016

Temperature is a potent inducer of fungal dimorphism. Multiple signalling pathways control the response to growth at high temperature, but the sensors that regulate these pathways are poorly defined. We show here that the signalling mucin Msb2 is a global regulator of temperature stress in the fungal pathogen Candida albicans. Msb2 was required for survival and hyphae formation at 42°C. The cytoplasmic signalling domain of Msb2 regulated temperature‐dependent activation of the CEK mitogen activated proteins kinase (MAPK) pathway. The extracellular glycosylated domain of Msb2 (100‐900 amino acid residues) had a new and unexpected role in regulating the protein kinase C (PKC) pathway. Msb2 also regulated temperature‐dependent induction of genes encoding regulators and targets of the unfolded protein response (UPR), which is a protein quality control (QC) pathway in the endoplasmic reticulum that controls protein folding/degradation in response to high temperature and other stresses. The heat shock protein and cell wall component Ssa1 was also required for hyphae formation and survival at 42°C and regulated the CEK and PKC pathways.
The AP‐2 complex is required for proper temporal and spatial dynamics of endocytic patches in fission yeast
Authors: de León Nagore , Hoya Marta , Curto M.‐Angeles , Moro Sandra , Yanguas Francisco , Doncel Cristina , Valdivieso M.‐Henar
Published: January 2016

In metazoans the AP‐2 complex has a well‐defined role in clathrin‐mediated endocytosis. By contrast, its direct role in endocytosis in unicellular eukaryotes has been questioned. Here, we report co‐ immunoprecipitation between the fission yeast AP‐2 component Apl3p and clathrin, as well as the genetic interactions between apl3Δ and clc1 and sla2Δ/end4Δ mutants. Furthermore, a double clc1 apl3Δ mutant was found to be defective in FM4‐64 uptake. In an otherwise wild‐type strain, apl3Δ cells exhibit altered dynamics of the endocytic sites, with a heterogeneous and extended lifetime of early and late markers at the patches. Additionally, around 50% of the endocytic patches exhibit abnormal spatial dynamics, with immobile patches and patches that bounce backwards to the cell surface, showing a pervasive effect of the absence of AP‐2. These alterations in the endocytic machinery result in abnormal cell wall synthesis and morphogenesis. Our results complement those found in budding yeast and confirm that a direct role of AP‐2 in endocytosis has been conserved throughout evolution.
Seasonal movements of river dolphins (Inia geoffrensis) in a protected Amazonian floodplain
Authors: Mintzer Vanessa J. , Lorenzen Kai , Frazer Thomas K. , da Silva Vera M. F. , Martin Anthony R.
Published: January 2016

Deliberate killing for use as bait in a regional catfish (Calophysus macropterus) fishery is the primary threat affecting the survival of the Amazon river dolphin, or boto (Inia geoffrensis). Establishing and improving freshwater protected areas has been suggested as a possible course of action to protect the species. However, the ecology of the boto is poorly understood and more information is needed on the species’ habitat use and movement patterns to ensure that spatial protection initiatives meet conservation needs. In this study, mark‐recapture/resight data collected in and near the Mamirauá Sustainable Development Reserve, a várzea in the Brazilian Amazon, was used to examine transition probabilities of botos between various habitat types. Our findings suggest that it is imperative that spatial protection initiatives focused on the boto take into account the importance of várzea habitat and bay systems for individuals in early life stages. Moreover, because botos frequently occupy the main rivers, particularly during the low water period, protecting areas of the main river waters adjacent to várzeas could aid in the protection of hunted populations.
Seasonality of Antarctic minke whale (Balaenoptera bonaerensis) calls off the western Antarctic Peninsula
Authors: Dominello Talia , Širović Ana
Published: January 2016

The Antarctic minke whale (Balaenoptera bonaerensis) is a difficult species to study because of its low visual detectability and preference for living within the sea ice habitat, accessible only by ice‐strengthened vessels. Recent identification of the Antarctic minke whale as the source of the seasonally ubiquitous bio‐duck call has allowed the use of this sound, as well as downsweeps, to investigate seasonality trends and diel patterns in Antarctic minke whale call production, and their relationship to sea ice cover. Passive acoustic data were collected using an autonomous Acoustic Recording Package (ARP) off the western Antarctic Peninsula. Bio‐duck calls were classified into four distinct call variants, with one variant having two subtypes. Bio‐duck calls were detected between April and November, with increasing call duration during the austral winter, indicating a strong seasonality in call production. Downsweeps, which were also attributed to Antarctic minke whales, were present throughout most months during the recording period, with a peak in July, and an absence in March and April. Both bio‐duck and downsweeps were significantly correlated with sea ice cover. No diel patterns were observed in bio‐duck calls or in downsweep call production at this site.
The effects of proton pump inhibitors on autonomic tone in patients with erosive and non‐erosive esophagitis
Authors: Jones E. L. , Perring S. , Khattab A. , Allenby‐Smith O.
Published: January 2016

Background

Reduction in autonomic tone as measured by heart rate variability (HRV) has been associated with various inflammatory conditions including reflux disease. The nature of and permanence of this damage have not been fully assessed.

Methods

Fourteen individuals with non‐erosive reflux disease (NERD) and 10 individuals with erosive reflux disease (ERD) as identified on endoscopy were assessed for HRV prior to starting a course of proton pump inhibitor (PPI) therapy and 8 weeks from the start of PPI therapy.

Key Results

Reflux symptoms were significantly improved by PPI therapy (p = 0.001), with no significant difference in reflux symptoms between the NERD and ERD groups either before (p = 0.45) or following therapy (p = 0.17). The ERD group displayed reduced HRV prior to PPI therapy as compared with a non‐symptomatic group. There was significant improvement of HRV resulting from PPI therapy in the ERD group as measured by inspiration/expiration ratio on forced breathing (p = 0.02), Valsalva ratio (p = 0.03), and extended metronome‐guided breathing at 6 breaths per minute (p = 0.03). While a similar pattern was seen in the NERD group, the effects were not as strong and did not reach statistical significance.

Conclusions & Inferences

The results are consistent with a growing body of evidence that cardiac autonomic neuropathy as measured by HRV is associated with gastro‐esophageal reflux disease and also suggest that successful treatment of the inflammation can lead to reversal of the deterioration of autonomic tone associated with that inflammation.
Converting cell fates: generating hematopoietic stem cells de novo via transcription factor reprogramming
Authors: Daniel Michael G. , Lemischka Ihor R. , Moore Kateri
Published: January 2016

Even though all paradigms of stem cell therapy and regenerative medicine emerged from the study of hematopoietic stem cells (HSCs), the inability to generate these cells de novo or expand them in vitro persists. Initial efforts to obtain these cells began with the use of embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technologies, but these strategies have yet to yield fully functional cells. Subsequently, more recent approaches involve transcription factor (TF) overexpression to reprogram PSCs and various somatic cells. The induction of pluripotency with just four TFs by Yamanaka informs our ability to convert cell fates and demonstrates the feasibility of utilizing terminally differentiated cells to generate cells with multilineage potential. In this review, we discuss the recent efforts undertaken using TF‐based reprogramming strategies to convert several cell types into HSCs.