bluuebunny/crossref_metadata_2025 huggingface dataset:
Pluronic micelles encapsulated curcumin manifests apoptotic cell death and inhibits pro‐inflammatory cytokines in human breast adenocarcinoma cells
Authors: Vaidya Foram U. , Sharma Rakesh , Shaikh Sofiya , Ray Debes , Aswal Vinod K. , Pathak Chandramani
Published: September 2018

Background

Curcumin is a natural derivative, which exhibits broad spectrum biological activities including anti‐oxidant, anti‐inflammatory, and anti‐cancer. Since ancient times, it has been used for the treatment of various diseases. Many reports highlighted its potential as a chemopreventive and chemotherapeutic agent. Despite its imperative properties, the pharmacological application had been limited due to low solubility in the aqueous medium, limited tissue absorption, and rapid degradation at physiological pH.

Aims

Cytotoxicity of drugs and their undesirable side effects are major obstacles in the regimens of cancer therapy. Therefore, natural plant derivatives‐based anti‐cancer drug delivery systems are getting more attention as they are less toxic, safer, and effective. In the present study, Pluronic block copolymer encapsulated curcumin was developed as an improved curcumin delivery system with the aim to improve its efficacy and biological response against cancer cells.

Methods and Results

Pluronic micelles encapsulated curcumin was synthesized, and its characterization was done by particle size analysis, Fourier transform infrared spectroscopy, small‐angle neutron scattering analysis, PXRD, and differential scanning calorimetry. Further, its biological activities were corroborated in cancer cells. Results indicate that Pluronic micelles encapsulated curcumin exemplify solubility and stability of curcumin in the aqueous medium. Biophysical characterization indicated that Pluronic F127 forms nanoparticle, and its micellar core radius was increased after incorporation of curcumin. Furthermore, biological studies show that Pluronic micelles encapsulated curcumin inhibits cell proliferation, improves cellular uptake of curcumin, arrests the cell cycle in G0/G1 phase, and inhibits the activation of NF‐kB and release of pro‐inflammatory cytokines to manifest apoptotic cell death rather than necrotic. This formulation was non‐toxic to normal cells.

Conclusion

This study suggests that Pluronic micelles encapsulated curcumin is stable that can effectively inhibit cell proliferation and release of pro‐inflammatory cytokines in cancer cells as compared with the free curcumin. This approach could be applied to improve the therapeutic index of anti‐cancer agents.
A case of giant complicated intraductal papilloma of breast on MRI and literature review
Authors: Wang Siqi , Lou Jianjuan
Published: September 2018

Background

With the increasing use of image‐guided biopsy, more breast intraductal papillomas are found than ever. Most intraductal papillomas are small, ranging from several milimeters to 2 cm.

Case

We described a case of giant intraductal papilloma of breast in a 19‐year‐old girl with nipple bloody discharge and rapid growth. Magnetic resonance imaging diagnostic evaluation and pathologic correlation along with review of relevant literatures are documented. The lesion was characterized by presence of mixture of cystic and solid component with cystic component occupying a large space. The solid component showed morphologic, kinetic, and diffusion weighted imaging features suggestive of malignancy. Infarction with no enhancement was noted. Cystic compartments contained hemorrhage with fluid‐fluid level formation. The patient undertook lumpectomy.

Conclusion

For a giant breast tumor with mixed solid and cystic component, intraductal papilloma should be considered in the differential diagnosis.
Leveraging MPI RMA to optimize halo‐swapping communications in MONC on Cray machines
Authors: Brown Nick , Bareford Michael , Weiland Michèle
Published: September 2018

Remote Memory Access (RMA), also known as single‐sided communications, provides a way for reading and writing directly into the memory of other processes without having to issue explicit message passing style communication calls. Previous studies have concluded that MPI RMA can provide increased communication performance over traditional MPI Point to Point (P2P), but these are based on synthetic benchmarks rather than real‐world codes. In this work, we replace the existing non‐blocking P2P communication calls in the Met Office NERC Cloud model, a mature code for modeling the atmosphere, with MPI RMA. We describe our approach in detail and discuss the options taken for correctness and performance. Experiments are performed on ARCHER, a Cray XC30, and Cirrus, an SGI ICE machine. We demonstrate on ARCHER that, by using RMA, we can obtain between a 5% and 10% reduction in communication time at each timestep on up to 32768 cores, which over the entirety of a run (with many timesteps) results in a significant improvement in performance compared to P2P on the Cray. However, RMA is not a silver bullet, and there are challenges when integrating RMA calls into existing codes: important optimizations are necessary to achieve good performance and library support is not universally mature, as is the case on Cirrus. In this paper, we discuss, in the context of a real‐world code, the lessons learned converting P2P to RMA, explore performance and scaling challenges, and contrast alternative RMA synchronization approaches in detail.
A systematic review of the clinical utility of the concept of self‐disgust
Authors: Clarke Aoife , Simpson Jane , Varese Filippo
Published: September 2018

This systematic literature review examined the clinical utility of the construct of self‐disgust in understanding mental distress. Specifically, the review assessed whether there is a shared conceptual definition of self‐disgust, the face and construct validity of the quantitative assessment measures of self‐disgust, and the predictive validity of self‐disgust in formulating the development of a range of psychological difficulties. A systematic database search supplemented by manual searches of references and citations identified 31 relevant papers (27 quantitative, 3 qualitative, and 1 mixed). Analysis of qualitative papers indicated a number of shared features in the definition of self‐disgust, including a visceral sense of self‐elicited nausea accompanied by social withdrawal and attempts at cleansing or suppressing aspects of the self. Quantitative assessment measures appeared to capture these dimensions and evidenced good psychometric properties, although some measures may have only partially captured the full self‐disgust construct. Strong relationships were observed between self‐disgust and a range of mental health presentations, in particular, depression, body‐image difficulties, and trauma‐related difficulties. However, these relationships are smaller when the effects of other negative self‐referential emotions were controlled, and stronger conclusions about the predictive validity of self‐disgust are limited by the cross‐sectional nature of many of the studies.
A Water‐Soluble NaCMC/NaPAA Binder for Exceptional Improvement of Sodium‐Ion Batteries with an SnO2‐Ordered Mesoporous Carbon Anode
Authors: Patra Jagabandhu , Rath Purna Chandra , Li Chi , Kao Hsien‐Ming , Wang Fu‐Ming , Li Ju , Chang Jeng‐Kuei
Published: September 2018

SnO2@CMK‐8 composite, a highly promising anode for Na‐ion batteries (NIBs), was incorporated with polyvinylidene difluoride (PVDF), sodium carboxymethylcellulose (NaCMC), sodium polyacrylate (NaPAA), and NaCMC/NaPAA mixed binders to optimize the electrode sodiation/desodiation properties. Synergistic effects between NaCMC and NaPAA led to the formation of an effective protective film on the electrode. This coating layer not only increased the charge–discharge Coulombic efficiency, suppressing the accumulation of solid–electrolyte interphases, but also kept the SnO2 nanoparticles in the CMK‐8 matrix, preventing the agglomeration and removal of oxide upon cycling. The adhesion strength and stability towards the electrolyte of the binders were evaluated. In addition, the charge–transfer resistance and apparent Na+ diffusion of the SnO2@CMK‐8 electrodes with various binders were examined and post‐mortem analyses were conducted. With NaCMC/NaPAA binder, exceptional electrode capacities of 850 and 425 mAh g−1 were obtained at charge–discharge rates of 20 and 2000 mA g−1, respectively. After 300 cycles, 90 % capacity retention was achieved. The thermal reactivity of the sodiated electrodes was studied by using differential scanning calorimetry. The binder effects on NIB safety, in terms of thermal runaway, are discussed.
Sulfophenylated Terphenylene Copolymer Membranes and Ionomers
Authors: Skalski Thomas J. G. , Adamski Michael , Britton Benjamin , Schibli Eric M. , Peckham Timothy J. , Weissbach Thomas , Moshisuki Takashi , Lyonnard Sandrine , Frisken Barbara J. , Holdcroft Steven
Published: September 2018

The copolymerization of a prefunctionalized, tetrasulfonated oligophenylene monomer was investigated. The corresponding physical and electrochemical properties of the polymers were tuned by varying the ratio of hydrophobic to hydrophilic units within the polymers. Membranes prepared from these polymers possessed ion exchange capacities ranging from 1.86 to 3.50 meq g−1 and exhibited proton conductivities of up to 338 mS cm−1 (80 °C, 95 % relative humidity). Small‐angle X‐ray scattering and small‐angle neutron scattering were used to elucidate the effect of the monomer ratios on the polymer morphology. The utility of these materials as low gas crossover, highly conductive membranes was demonstrated in fuel cell devices. Gas crossover currents through the membranes of as low as 4 % (0.16±0.03 mA cm−2) for a perfluorosulfonic acid reference membrane were demonstrated. As ionomers in the catalyst layer, the copolymers yielded highly active porous electrodes and overcame kinetic losses typically observed for hydrocarbon‐based catalyst layers. Fully hydrocarbon, nonfluorous, solid polymer electrolyte fuel cells are demonstrated with peak power densities of 770 mW cm−2 with oxygen and 456 mW cm−2 with air.
High‐Performance Flexible Perovskite Solar Cells with Effective Interfacial Optimization Processed at Low Temperatures
Authors: Jiang Jun , Jia Xuguang , Wang Shubo , Chen Yiqi , Liu Wei , Ding Jianning , Yuan Ningyi
Published: September 2018

Exploration of low‐temperature solution‐processing methodologies for fabricating planar perovskite solar cells (PSCs) is important for industrial mass production and helps simplify the manufacture and design of flexible perovskite solar cells. However, the interface between electron‐transport layers (ETLs) and perovskite layers is crucial for the development of highly efficient flexible PSCs. We report a drastically improved solar cell efficiency through surface optimization of TiO2 ETLs by using a simple and inexpensive ionic compound that shows high optical transparency and superior electron mobility. Solution‐derived TiO2 nanocrystalline films are employed at low temperatures as ETLs through solution processing. The modification of TiO2 with NH4Cl can increase the interactions between the surface and organic–inorganic hybrid perovskites; Cl anions lead to a stronger interfacial coupling between TiO2 and perovskite. Ammonium cations tend to combine with perovskite. Due to this strong combined effect of the ionic compound, the efficiency of PSC from low‐temperature solution processing reaches 18.71 % on rigid glass/indium tin oxide (ITO) for an improvement of 12.6 % over a control device using bare TiO2. Furthermore, the power conversion efficiency (PCE) can reach an efficiency of 17.69 % for the ITO/PEN substrates. This work contributes to the evolution of flexible PSCs with simple fabrication and high device performance.
Bias in meta‐analyses using Hedges’ d
Authors: Hamman Elizabeth A. , Pappalardo Paula , Bence James R. , Peacor Scott D. , Osenberg Craig W.
Published: September 2018

The type of metric and weighting method used in meta‐analysis can create bias and alter coverage of confidence intervals when the estimated effect size and its weight are correlated. Here, we investigate bias associated with the common metric, Hedges’ d, under conditions common in ecological meta‐analyses. We simulated data from experiments, computed effect sizes and their variances, and performed meta‐analyses applying three weighting schemes (inverse variance, sample size, and unweighted) for varying levels of effect size, within‐study replication, number of studies in the meta‐analysis, and among‐study variance. Unweighted analyses, and those using weights based on sample size, were close to unbiased and yielded coverages close to the nominal level of 0.95. In contrast, the inverse‐variance weighting scheme led to bias and low coverage, especially for meta‐analyses based on studies with low replication. This bias arose because of a correlation between the estimated effect and its weight when using the inverse‐variance method. In many cases, the sample size weighting scheme was most efficient, and, when not, the differences in efficiency among the three methods were relatively minor. Thus, if using Hedges’ d, we recommend using weights based upon sample size that do not involve individual study estimates of the effect size.
Interlacing roles of bottom‐up, top‐down, endogenous, and anthropogenic factors in population oscillations
Authors: Moreau Gaétan , Ostaff Don P. , Bauce Éric , Eveleigh Eldon S. , Lucarotti Christopher J. , Morin Benoit , Quiring Dan T.
Published: September 2018

The relative importance of bottom‐up, top‐down, and endogenous factors in population oscillations has been vigorously debated, yet few longer‐term studies of population dynamics have considered their potential nonadditive interactions. This study tests the hypothesis that oscillations can arise from the combined effects of bottom‐up, top‐down, and endogenous factors, with some of these factors being sensitive to anthropogenic modifications of habitats. Populations of Neodiprion abietis, a univoltine sawfly whose oscillations have strong first‐ and second‐order components, were monitored over six to eight generations in a natural and an adjacent managed (precommercially thinned) balsam fir (Abies balsamea) stand at each of three sites in Newfoundland, Canada. Endogenous and exogenous factors affecting N. abietis were evaluated to identify the factors contributing to first‐ and second‐order density dependence and uncover any differences in dynamics attributable to forest management. In both natural and managed stands, N. abietis populations remained at high densities for 2–4 yr before collapsing. At the beginning of outbreaks, immigration, high fecundity, female‐biased sex ratios, and high survival in later larval instars and during the cocoon stage allowed N. abietis populations to increase rapidly. After this increasing phase, top‐down (mortality by the baculovirus Neodiprion abietis nucleopolyhedrovirus [NeabNPV] and, under some circumstances, parasitism by Mesopolobus verditer) and bottom‐up (host‐plant) exogenous factors combined with endogenous factors associated with recruitment to initiate the localized collapse of N. abietis populations. Because first‐order density dependence was attributable to NeabNPV (and sometimes M. verditer) and second‐order density dependence was attributable to host‐plant effects and endogenous factors associated with recruitment, these factors are inferred to cause the periodic behavior of this species. Host‐plant effects, but not top‐down mortality factors, were more pronounced in natural than thinned stands, suggesting that recent increases in N. abietis outbreak severity and range are best explained by a management‐induced reduction of host‐plant effects. By considering nonadditive interactions between trophic forces, this study reveals the intricate relationships between the factors responsible for population oscillations that would otherwise remain hidden.
Context‐dependent mutualisms in the Joshua tree–yucca moth system shift along a climate gradient
Authors: Harrower Jennifer , Gilbert Gregory S.
Published: September 2018

Changing climate patterns can affect the geographic distribution of species through effects on species interactions. Iconic Joshua trees are limited to a narrow range of climate conditions, and climate change is expected to shift suitable habitat to higher elevations and latitudes than their current geographic distribution. As such, the survival of the species requires colonization of new habitats. However, Joshua trees form an obligate mutualistic relationship with yucca moths that pollinate the flowers but whose offspring then consume a portion of the developing seeds. It is not known whether the yucca moths will move in synchrony with Joshua trees, or how changing environmental conditions may affect the net benefits and costs of the yucca moth–Joshua tree interaction. To evaluate the spectrum of conditional outcomes of the interaction, we examined a range of performance measures and abiotic factors across the elevation range that spans the distribution of Joshua trees in Joshua Tree National Park. We found a strong concordance between tree size, moth and tree abundance, and reproductive success, with peak performance of both partners at intermediate elevation. Within sites, larger trees produced more flowers, attracted more pollinators, and had greater seed set. We found that the conditional outcomes of the interaction varied predictably along the gradient: Seed set, as well as seed predation, was greatest at intermediate elevations where trees and pollinators were both at high abundance. At range margins, the proportion of infertile seeds increased, possibly because low pollinator abundance led to pollen limitation. The reproductive success of Joshua trees is tightly linked to pollinator abundance, and the conditional outcomes (magnitude of the fitness benefit) of the mutualism change depending on where it occurs on the elevation gradient.
Omalizumab dampens type 2 inflammation in a group of long‐term treated asthma patients and detaches IgE from FcεRI
Authors: Maggi Laura , Rossettini Beatrice , Montaini Gianni , Matucci Andrea , Vultaggio Alessandra , Mazzoni Alessio , Palterer Boaz , Parronchi Paola , Maggi Enrico , Liotta Francesco , Annunziato Francesco , Cosmi Lorenzo
Published: September 2018

Even if omalizumab is broadly used in the treatment of severe, allergic asthma, the immunological effects in long‐term treated patients have not been fully elucidated. To this aim, a cohort of 15 allergic asthmatic patients treated with omalizumab for at least three years was compared with 12 allergic asthma patients treated with standard therapy. Omalizumab treated asthmatic patients showed lower frequencies of circulating plasmacytoid DCs, and lower CD154 expression on CD4 T‐helper cells than the control group. Moreover, basophils and DCs from omalizumab‐treated patients had lower surface expression of IgE compared to the control group. In a longitudinal evaluation of two patients that started omalizumab treatment, we show that FcεRI free of IgE were evident on basophils just after four weeks of drug administration. Finally, in vitro experiments with basophils obtained from healthy donors confirm that omalizumab is able to detach IgE from high affinity IgE receptors.

Collectively these data indicate that long‐term omalizumab treatment dampens type 2 inflammation acting on different cell types that play a pivotal role in the pathogenesis of allergic asthma. Moreover, we have identified a further mechanism of action of omalizumab, such as the ability to detach IgE from its receptor.
Photocatalytic Solar Light H2 Production by Aqueous Glucose Reforming
Authors: Bellardita Marianna , García‐López Elisa Isabel , Marcì Giuseppe , Nasillo Giorgio , Palmisano Leonardo
Published: September 2018

A series of tungsten and nitrogen doped Pt‐TiO2 samples were prepared with the aim to extend the TiO2 absorption to the visible light region and to enhance the separation efficiency of the photogenerated electron/hole pairs. The physicochemical features of the powders were characterized by X‐ray diffraction (XRD), UV/Vis reflectance spectra, specific surface area (SSA) determinations, and transmission electron microscopy (TEM) analyses. The influence of the presence of different doping agents was evaluated, under anaerobic conditions, in the aqueous photo‐reforming of glucose to form H2 at ambient pressure and temperature under a halogen lamp or natural solar light irradiation. Arabinose, erythrose, and formic acid were the main glucose partial oxidation products observed in the liquid phase, whilst H2 and CO2 were measured in the gaseous phase. The highest H2 production was observed in the presence of the Pt‐TiO2‐W0.25 sample.
A single seizure selectively impairs hippocampal‐dependent memory and is associated with alterations in PI3K/Akt/mTOR and FMRP signaling
Authors: Holley Andrew J. , Hodges Samantha L. , Nolan Suzanne O. , Binder Matthew , Okoh James T. , Ackerman Kaylin , Tomac Lindsey A. , Lugo Joaquin N.
Published: September 2018

Objective

A single brief seizure before learning leads to spatial and contextual memory impairment in rodents without chronic epilepsy. These results suggest that memory can be impacted by seizure activity in the absence of epilepsy pathology. In this study, we investigated the types of memory affected by a seizure and the time course of impairment. We also examined alterations to mammalian target of rapamycin (mTOR) and fragile X mental retardation protein (FMRP) signaling, which modulate elements of the synapse and may underlie impairment.

Methods

We induced a single seizure and investigated hippocampal and nonhippocampal memory using trace fear conditioning, novel object recognition (NOR), and accelerating rotarod to determine the specificity of impairment in mice. We used western blot analysis to examine for changes to cellular signaling and synaptic proteins 1 h, 24 h, and 1 week after a seizure. We also included a histologic examination to determine if cell loss or gross lesions might alternatively explain memory deficits.

Results

Behavioral results indicated that a seizure before learning leads to impairment of trace fear memory that worsens over time. In contrast, nonhippocampal memory was unaffected by a seizure in the NOR and rotarod tasks. Western analysis indicated increased hippocampal phospho‐S6 and total FMRP 1 h following a seizure. Tissue taken 24 h after a seizure indicated increased hippocampal GluA1, suggesting increased α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor expression. Histologic analysis indicated that neither cell loss nor lesions are present after a single seizure.

Significance

The presence of memory impairment in the absence of damage suggests that memory impairment caused by seizure activity differs from general memory impairment in epilepsy. Instead, memory impairment after a single seizure is associated with alterations to mTOR and FMRP signaling, which leads to a disruption of synaptic proteins involved in consolidation of long‐term memory. These results have implications for understanding memory impairment in epilepsy.
Adaptive MBSFN subframe allocation scheme for VBR video streaming over LTE‐A networks
Authors: Ghandri Abdennaceur , Boujelben Yassine , Ben Jemaa Maher
Published: September 2018

Meeting the growing demand for multimedia services is still the main challenge for the current mobile network technologies. The 3rd Generation Partnership Project has proposed an emerging technology called multimedia broadcast/multicast service (MBMS). This service is gaining traction as a method of efficiently using the scarce wireless resources for multicasting the same content to a large number of users belonging to the same area. In the multicast broadcast single frequency network (MBSFN) context, the conventional approach specified by the 3rd Generation Partnership Project standard adopts a semistatic resource allocation mechanism for MBMS services according to their quality‐of‐service parameters. More precisely, the resources assigned to all MBMS service flows remain unchanged along the transmission period and reallocation may take place only when a new multicast session is admitted for transmission or a current session ends. This approach is inefficient and not suitable, especially for services with variable bit rate such as live video streaming. In this paper, we propose a proactive resource allocation algorithm that can dynamically adjust the subframe allocation within an MBSFN area in order to keep pace with the variable bit rate traffics' fluctuations. The basic idea of the proposed solution is to periodically reallocate the MBSFN subframes, in case of persistent over or under allocations, based on a linear prediction model of the resources actually consumed and the traffic behavior. The simulation results show that our proposed algorithm can reduce the waste of MBSFN resources, which could be used for other multicast or unicast transmissions, without violating the quality‐of‐service and fairness constraints.
Competitive species interactions constrain abiotic adaptation in a bacterial soil community
Authors: Hall James P. J. , Harrison Ellie , Brockhurst Michael A.
Published: September 2018

Studies of abiotic adaptation often consider single species in isolation, yet natural communities contain many coexisting species which could limit or promote abiotic adaptation. Here we show, using soil bacterial communities, that evolving in the presence of a competitor constrained abiotic adaptation. Specifically, Pseudomonas fluorescens evolved alone was fitter than P. fluorescens evolved alongside Pseudomonas putida, when P. putida was absent. Genome analyses indicated this was due to mutation of the acetate scavenger actP, which occurred exclusively, and almost universally, in single-species-evolved clones. actP disruption was associated with increased growth in soil compared with wild-type actP, but this benefit was abolished when P. putida was present, suggesting a role for carbon scavenging transporters in species interactions, possibly through nutrient competition. Our results show that competitive species interactions can limit the evolutionary response to abiotic selection, because the fitness benefits of abiotic adaptive mutations were negated in more complex communities.
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome‐wide association studies
Authors: Lee James J. , McGue Matt , Iacono William G. , Chow Carson C.
Published: September 2018

To infer that a single‐nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP‐phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this study, we study the properties of linkage disequilibrium (LD) Score regression, a recently developed method for using summary statistics from genome‐wide association studies to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method. We demonstrate that LD Score regression can produce estimates of confounding at null SNPs that are unbiased or conservative under fairly general conditions. This robustness holds in the case of the parent genotype affecting the offspring phenotype through some environmental mechanism, despite the resulting correlation over SNPs between LD Scores and the degree of confounding. Additionally, we demonstrate that LD Score regression can produce reasonably robust estimates of the genetic correlation, even when its estimates of the genetic covariance and the two univariate heritabilities are substantially biased.
Embryonic macrophages and microglia ablation alter the development of dorsal root ganglion sensory neurons in mouse embryos
Authors: Angelim Monara Kaélle Sérvulo Cruz , Maia Luciana Maria Silva de Seixas , Mouffle Christine , Ginhoux Florent , Low Donovan , Amancio‐Dos‐Santos Angela , Makhoul Jennifer , Le Corronc Hervé , Mangin Jean‐Marie , Legendre Pascal
Published: September 2018

Microglia are known to regulate several aspects of the development of the central nervous system. When microglia colonize the spinal cord, from E11.5 in the mouse embryo, they interact with growing central axons of dorsal root ganglion sensory neurons (SNs), which suggests that they may have some functions in SN development. To address this issue, we analyzed the effects of embryonic macrophage ablation on the early development of SNs using mouse embryo lacking embryonic macrophages (PU.1 knock‐out mice) and immune cell ablation. We discovered that, in addition to microglia, embryonic macrophages contact tropomyosin receptor kinase (Trk) C+ SN, TrkB+ SN, and TrkA+ SN peripheral neurites from E11.5. Deprivation of immune cells resulted in an initial reduction of TrkC+ SN and TrkB+ SN populations at E11.5 that was unlikely to be related to an alteration in their developmental cell death (DCD), followed by a transitory increase in their number at E12.5. It also resulted in a reduction of TrkA+ SN number during the developmental period analyzed (E11.5–E15.5), although we did not observe any change in their DCD. Proliferation of cells negative for brain fatty acid‐binding protein (BFABP−), which likely correspond to neuronal progenitors, was increased at E11.5, while their proliferation was decreased at E12.5, which could partly explain the alterations of SN subtype production observed from E11.5. In addition, we observed alterations in the proliferation of glial cell progenitors (BFABP+ cells) in the absence of embryonic macrophages. Our data indicate that embryonic macrophages and microglia ablation alter the development of SNs.
Understanding the quality of life of family carers of people with dementia: Development of a new conceptual framework
Authors: Daley Stephanie , Murray Joanna , Farina Nicolas , Page Thomas E. , Brown Anna , Basset Thurstine , Livingston Gill , Bowling Ann , Knapp Martin , Banerjee Sube
Published: September 2018

Background

Dementia is a major global health and social care challenge, and family carers are a vital determinant of positive outcomes for people with dementia. This study's aim was to develop a conceptual framework for the Quality of Life (QOL) of family carers of people with dementia.

Methods

We studied family carers of people with dementia and staff working in dementia services iteratively using in‐depth individual qualitative interviews and focus groups discussions. Analysis used constant comparison techniques underpinned by a collaborative approach with a study‐specific advisory group of family carers.

Results

We completed 41 individual interviews with 32 family carers and nine staff and two focus groups with six family carers and five staff. From the analysis, we identified 12 themes that influenced carer QOL. These were organised into three categories focussing on person with dementia, carer, and external environment.

Conclusions

For carers of people with dementia, the QOL construct was found to include condition‐specific domains which are not routinely considered in generic assessment of QOL. This has implications for researchers, policy makers, and service providers in addressing and measuring QOL in family carers of people with dementia.
Cortical and subcortical areas involved in the regulation of reach movement speed in the human brain: An fMRI study
Authors: Shirinbayan Seyyed Iman , Dreyer Alexander M. , Rieger Jochem W.
Published: September 2018

Reach movements are characterized by multiple kinematic variables that can change with age or due to medical conditions such as movement disorders. While the neural control of reach direction is well investigated, the elements of the neural network regulating speed (the nondirectional component of velocity) remain uncertain. Here, we used a custom made magnetic resonance (MR)‐compatible arm movement tracking system to capture the real kinematics of the arm movements while measuring brain activation with functional magnetic resonance imaging to reveal areas in the human brain in which BOLD‐activation covaries with the speed of arm movements. We found significant activation in multiple cortical and subcortical brain regions positively correlated with endpoint (wrist) speed (speed‐related activation), including contralateral premotor cortex (PMC), supplementary motor area (SMA), thalamus (putative VL/VA nuclei), and bilateral putamen. The hand and arm regions of primary sensorimotor cortex (SMC) and a posterior region of thalamus were significantly activated by reach movements but showed a more binary response characteristics (movement present or absent) than with continuously varying speed. Moreover, a subregion of contralateral SMA also showed binary movement activation but no speed‐related BOLD‐activation. Effect size analysis revealed bilateral putamen as the most speed‐specific region among the speed‐related clusters whereas primary SMC showed the strongest specificity for movement versus non‐movement discrimination, independent of speed variations. The results reveal a network of multiple cortical and subcortical brain regions that are involved in speed regulation among which putamen, anterior thalamus, and PMC show highest specificity to speed, suggesting a basal‐ganglia‐thalamo‐cortical loop for speed regulation.
Reward‐related regions form a preferentially coupled system at rest
Authors: Huckins Jeremy F. , Adeyemo Babatunde , Miezin Fran M. , Power Jonathan D. , Gordon Evan M. , Laumann Timothy O. , Heatherton Todd F. , Petersen Steven E. , Kelley William M.
Published: September 2018

Neuroimaging studies have implicated a set of striatal and orbitofrontal cortex (OFC) regions that are commonly activated during reward processing tasks. Resting‐state functional connectivity (RSFC) studies have demonstrated that the human brain is organized into several functional systems that show strong temporal coherence in the absence of goal‐directed tasks. Here we use seed‐based and graph‐theory RSFC approaches to characterize the systems‐level organization of putative reward regions of at rest. Peaks of connectivity from seed‐based RSFC patterns for the nucleus accumbens (NAcc) and orbitofrontal cortex (OFC) were used to identify candidate reward regions which were merged with a previously used set of regions (Power et al., 2011). Graph‐theory was then used to determine system‐level membership for all regions. Several regions previously implicated in reward‐processing (NAcc, lateral and medial OFC, and ventromedial prefrontal cortex) comprised a distinct, preferentially coupled system. This RSFC system is stable across a range of connectivity thresholds and shares strong overlap with meta‐analyses of task‐based reward studies. This reward system shares between‐system connectivity with systems implicated in cognitive control and self‐regulation, including the fronto‐parietal, cingulo‐opercular, and default systems. Differences may exist in the pathways through which control systems interact with reward system components. Whereas NAcc is functionally connected to cingulo‐opercular and default systems, OFC regions show stronger connectivity with the fronto‐parietal system. We propose that future work may be able to interrogate group or individual differences in connectivity profiles using the regions delineated in this work to explore potential relationships to appetitive behaviors, self‐regulation failure, and addiction.
Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances
Authors: Sirica Alphonse E. , Gores Gregory J. , Groopman John D. , Selaru Florin M. , Strazzabosco Mario , Wei Wang Xin , Zhu Andrew X.
Published: September 2018

Intrahepatic cholangiocarcinoma (iCCA) has over the last 10‐20 years become the focus of increasing concern, largely due to its rising incidence and high mortality rates worldwide. The significant increase in mortality rates from this primary hepatobiliary cancer, particularly over the past decade, has coincided with a rapidly growing interest among clinicians, investigators, and patient advocates to seek greater mechanistic insights and more effective biomarker‐driven targeted approaches for managing and/or preventing this challenging liver cancer. In addition to discussing challenges posed by this aggressive cancer, this review will emphasize recent epidemiological, basic, and translational research findings for iCCA. In particular, we will highlight emerging demographic changes and evolving risk factors, the critical role of the tumor microenvironment, extracellular vesicle biomarkers and therapeutics, intertumoral and intratumoral heterogeneity, and current and emerging targeted therapies regarding iCCA. Specifically, recent evidence linking non–bile duct medical conditions, such as nonalcoholic fatty liver disease and nonspecific cirrhosis, to intrahepatic cholangiocarcinogenesis together with geographic and ethnic variation will be assessed. Recent developments concerning the roles played by transforming growth factor‐β and platelet‐derived growth factor D in driving the recruitment and expansion of cancer‐associated myofibroblasts within cholangiocarcinoma (CCA) stroma as well as their therapeutic implications will also be discussed. In addition, the potential significance of extracellular vesicles as bile and serum biomarkers and therapeutic delivery systems for iCCA will be described. An integrated systems approach to classifying heterogeneous iCCA subtypes will be further highlighted, and recent clinical trials and emerging targeted therapies will be reviewed, along with recommendations for future translational research opportunities. Established international CCA networks are now facilitating collaborations aimed at advancing iCCA translational and clinical research.
Sialylation of vasorin by ST3Gal1 facilitates TGF‐β1‐mediated tumor angiogenesis and progression
Authors: Yeo Hui Ling , Fan Tan‐Chi , Lin Ruey‐Jen , Yu Jyh‐Cherng , Liao Guo‐Shiou , Chen Eric Sheng‐Wen , Ho Ming‐Yi , Lin Wen‐Der , Chen Kowa , Chen Chein‐Hung , Hung Jung‐Tung , Wu Jen‐Chine , Chang Nai‐Chuan , Chang Margaret Dah‐Tsyr , Yu John , Yu Alice Lin‐Tsing
Published: September 2018

ST3Gal1 is a key sialyltransferase which adds α2,3‐linked sialic acid to substrates and generates core 1 O‐glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1‐silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF‐β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC‐MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O‐glycans are sialyl‐3T and disialyl‐T. ST3GAL1‐silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF‐β1 by 2‐ to 3‐fold and thereby dampening TGF‐β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse‐free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14–7.67). Since TGF‐β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF‐β1 upregulates ST3Gal1 to circumvent the negative impact of VASN.
Association of IL‐1β, IL‐1RN, and ESR1 genes polymorphism with risk of infection and response to sofosbuvir plus daclatasvir combination therapy in hepatitis C virus genotype‐4 patients
Authors: Khairy Rasha M. , Abdulghany Hend M. , Abdel‐Raheim Salama , Zenhom Nagwa M. , Abd Elfatah Aliaa S , Abdalla Nilly H.
Published: September 2018

Sofosbuvir (SOF) and daclatasvir combination with or without ribavirin proved to be effective and safe in the treatment of hepatitis C virus infection. The study aimed to assess the efficacy of (SOF plus daclatasvir) combination + ribavirin in the treatment of treatment‐experienced HCV genotype 4 Egyptian patients and to investigate the impact of IL‐1β _31, IL‐1β _511, and IL‐1RN and T29C of ESR1 genes polymorphisms on treatment outcome. The study also aimed to assess the effect of the treatment on liver fibrosis. The sustained virologic response was assessed at 0, 4, 12, and 24 weeks from the beginning of treatment by RT‐PCR. IL‐1β _31, IL‐1β _511, IL‐1RN, and T29C genes polymorphisms were examined by PCR‐based techniques in two groups of patients (responders and non‐responders) and a control group of healthy subjects. A significant association between IL‐1β_511 gene polymorphism and SOF/DAV‐induced response was observed, where the “CC” genotype was the most frequent in responders while the “CT” genotype was the most frequent among non‐responders (P = 0.0001, OR = 39; 95% CI = 4.7–316). IL‐1RN gene polymorphism also showed significant associations with response to treatment, genotypes that include allele “1” were the most frequent in responders, particularly the homozygous genotype “1/1” (P = 0.0001, OR = 2.3; 95% CI = 1.57–3.2). However, the genotypes “4/4” and “2/4” were the most frequent in non‐responders; (P = 0.0001). At least 71% of the responders carry allele “1” while 54% of non‐responders were allele “4” carriers (P value = 0.0001. OR = 2.8; 95% CI = 6.4–134.2). Liver fibrosis is significantly improved regardless of the response. © 2018 IUBMB Life, 70(11):1156–1163, 2018
Limulus and heart rhythm
Authors: Kodirov Sodikdjon A. , Psyrakis Dimitrios , Brachmann Johannes , Zhuravlev Vladimir L.
Published: September 2018

Great interest in the comparative physiology of hearts and their functions in Animalia has emerged with classic papers on Limulus polyphemus and mollusks. The recurrent cardiac activity—heart rate—is the most important physiological parameter and when present the
kardia (Greek) is vital to the development of entire organs of the organisms in the animal kingdom. Extensive studies devoted to the regulation of cardiac rhythm in invertebrates have revealed that the basics of heart physiology are comparable to mammals. The hearts of invertebrates also beat spontaneously and are supplied with regulatory nerves: either excitatory or inhibitory or both. The distinct nerves and the source of excitation/inhibition at the level of single neurons are described for many invertebrate genera. The vertebrates and a majority of invertebrates have myogenic hearts, whereas the horseshoe crab
L. polyphemus and a few other animals have a neurogenic cardiac rhythm. Nevertheless, the myogenic nature of heartbeat is precursor, because the contraction of native and stem‐cell‐derived cardiomyocytes does occur in the absence of any neural elements. Even in
L. polyphemus, the heart rhythm is myogenic at embryonic stages.
Recent Synthetic Approaches Towards Biologically Potent Derivatives/Analogues of Theophylline
Authors: Yousaf Muhammad , Zahoor Ameer Fawad , Faiz Sadia , Javed Sadia , Irfan Muhammad
Published: September 2018

Theophylline, also known as 1,3‐dimethylxanthine, belongs to class of purine‐based drugs, which are used in the treatment of air ways disorders such as asthma and chronic obstructive pulmonary disease. Its derivatives play a significant role in the variety of biological applications of medicinal interest as it exhibits numerous activities such as anticancer, anti‐inflammatory, bronchodilator activity, antibacterial, and antifungal activities. This review article summarizes the recent advances in the synthesis of theophylline derivatives, which were reported during 2008–2017, and also describes the detailed biological studies of synthesized analogues.
Synthesis and Urease Inhibition Study of Some New Quinazolinone Derivatives Bearing Triazole, Thiadiazole, and Piperazine Moiety
Authors: Karaali Nesrin , Menteşe Meltem , Baltas Nimet , Menteşe Emre
Published: September 2018

A new series of 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives bearing triazole and thiadiazole nucleus has been synthesized and then screened for their urease inhibition properties. All synthesized compounds showed outstanding urease inhibitory potentials with IC50 values ranging between 0.25 ± 0.01 and 18.00 ± 0.64 μg/mL when compared with standard inhibitors thiourea (IC50 = 15.08 ± 0.71 μg/mL) and acetohydroxamic acid (IC50 = 21.05 ± 0.96 μg/mL). All new molecules were characterized by 1H NMR, 13C NMR, and MS.
Simultaneous Evaluation of Lung Anatomy and Ventilation Using 4D Respiratory‐Motion‐Resolved Ultrashort Echo Time Sparse MRI
Authors: Feng Li , Delacoste Jean , Smith David , Weissbrot Joseph , Flagg Eric , Moore William H , Girvin Francis , Raad Roy , Bhattacharji Priya , Stoffel David , Piccini Davide , Stuber Matthias , Sodickson Daniel K , Otazo Ricardo , Chandarana Hersh
Published: September 2018

Background

Computed tomography (CT) and spirometry are the current standard methods for assessing lung anatomy and pulmonary ventilation, respectively. However, CT provides limited ventilation information and spirometry only provides global measures of lung ventilation. Thus, a method that can enable simultaneous examination of lung anatomy and ventilation is of clinical interest.

Purpose

To develop and test a 4D respiratory‐resolved sparse lung MRI (XD‐UTE: eXtra‐Dimensional Ultrashort TE imaging) approach for simultaneous evaluation of lung anatomy and pulmonary ventilation.

Study Type

Prospective.

Population

In all, 23 subjects (11 volunteers and 12 patients, mean age = 63.6 ± 8.4).

Field Strength/Sequence

3T MR; a prototype 3D golden‐angle radial UTE sequence, a Cartesian breath‐hold volumetric‐interpolated examination (BH‐VIBE) sequence.

Assessment

All subjects were scanned using the 3D golden‐angle radial UTE sequence during normal breathing. Ten subjects underwent an additional scan during alternating normal and deep breathing. Respiratory‐motion‐resolved sparse reconstruction was performed for all the acquired data to generate dynamic normal‐breathing or deep‐breathing image series. For comparison, BH‐VIBE was performed in 12 subjects. Lung images were visually scored by three experienced chest radiologists and were analyzed by two observers who segmented the left and right lung to derive ventilation parameters in comparison with spirometry.

Statistical Tests

Nonparametric paired two‐tailed Wilcoxon signed‐rank test; intraclass correlation coefficient, Pearson correlation coefficient.

Results

XD‐UTE achieved significantly improved image quality compared both with Cartesian BH‐VIBE and radial reconstruction without motion compensation (P < 0.05). The global ventilation parameters (a sum of the left and right lung measures) were in good correlation with spirometry in the same subjects (correlation coefficient = 0.724). There were excellent correlations between the results obtained by two observers (intraclass correlation coefficient ranged from 0.8855–0.9995).

Data Conclusion

Simultaneous evaluation of lung anatomy and ventilation using XD‐UTE is demonstrated, which have shown good potential for improved diagnosis and management of patients with heterogeneous lung diseases.

Level of Evidence: 2

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;49:411–422.