bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo genome editing of the albumin locus as a platform for protein replacement therapy
Authors: Sharma Rajiv , Anguela Xavier M. , Doyon Yannick , Wechsler Thomas , DeKelver Russell C. , Sproul Scott , Paschon David E. , Miller Jeffrey C. , Davidson Robert J. , Shivak David , Zhou Shangzhen , Rieders Julianne , Gregory Philip D. , Holmes Michael C. , Rebar Edward J. , High Katherine A. 
Published: August 2015

Key Points
AAV- and ZFN-mediated targeting of the albumin locus corrects disease phenotype in mouse models of hemophilia A and B. Robust expression from the albumin locus provides a versatile platform for liver-directed protein replacement therapy.
B-cell precursor acute lymphoblastic leukemia cells use tunneling nanotubes to orchestrate their microenvironment
Authors: Polak Roel , de Rooij Bob , Pieters Rob , den Boer Monique L. 
Published: August 2015

Key Points
Primary BCP-ALL cells use tunneling nanotubes to signal to mesenchymal stromal cells and thereby trigger cytokine secretion. Inhibiting tunneling nanotube signaling is a promising approach to induce apoptosis and sensitize BCP-ALL cells toward prednisolone.
The oldest described eurypterid: a giant Middle Ordovician (Darriwilian) megalograptid from the Winneshiek Lagerstätte of Iowa
Authors: Lamsdell James C. , Briggs Derek E. G. , Liu Huaibao P. , Witzke Brian J. , McKay Robert M. 
Published: August 2015

AbstractBackgroundEurypterids are a diverse group of chelicerates known from ~250 species with a sparse Ordovician record currently comprising 11 species; the oldest fully documented example is from the Sandbian of Avalonia. The Middle Ordovician (Darriwilian) fauna of the Winneshiek Lagerstätte includes a new eurypterid species represented by more than 150 specimens, including some juveniles, preserved as carbonaceous cuticular remains. This taxon represents the oldest described eurypterid, extending the documented range of the group back some 9 million years.ResultsThe new eurypterid species is described asPentecopterus decorahensisgen. et sp. nov.. Phylogenetic analysis placesPentecopterusat the base of the Megalograptidae, united with the two genera previously assigned to this family by the shared possession of two or more pairs of spines per podomere on prosomal appendage IV, a reduction of all spines except the pair on the penultimate podomere of appendage V, and an ornamentation of guttalate scales, including angular scales along the posterior margin of the dorsal tergites and in longitudinal rows along the tergites. The morphology ofPentecopterusreveals that the Megalograptidae are representatives of the derived carcinosomatoid clade and not basal eurypterids as previously interpreted.ConclusionsThe relatively derived position of megalograptids within the eurypterids indicates that most eurypterid clades were present by the Middle Ordovician. Eurypterids either underwent an explosive radiation soon after their origination, or earlier representatives, perhaps Cambrian in age, remain to be discovered. The available instars ofPentecopterus decorahensissuggest that eurypterids underwent extreme appendage differentiation during development, a potentially unique condition among chelicerates. The high degree of appendage specialization in eurypterids is only matched by arachnids within chelicerates, supporting a sister taxon relationship between them.
let-7b suppresses apoptosis and autophagy of human mesenchymal stem cells transplanted into ischemia/reperfusion injured heart 7by targeting caspase-3
Authors: Ham Onju , Lee Se-Yeon , Lee Chang Youn , Park Jun-Hee , Lee Jiyun , Seo Hyang-Hee , Cha Min-Ji , Choi Eunhyun , Kim Soonhag , Hwang Ki-Chul 
Published: August 2015

AbstractIntroductionMesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation.MethodsA Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCsin vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function.ResultsHere, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3.ConclusionsTaken together, these data indicate that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis and autophagy by directly targeting caspase-3 signaling.
Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats
Authors: Ammar Hania Ibrahim , Sequiera Glen Lester , Nashed Mira B. , Ammar Rasha I. , Gabr Hala M. , Elsayed Hany E. , Sareen Niketa , Rub Ejlal Abu-El , Zickri Maha B. , Dhingra Sanjiv 
Published: August 2015

Abstract
Introduction
Doxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model.

Methods
Diabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD.

Results
Glucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups.

Conclusions
In conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.
Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice
Authors: Trevino Michelle B. , Mazur-Hart David , Machida Yui , King Timothy , Nadler Joseph , Galkina Elena V. , Poddar Arjun , Dutta Sucharita , Imai Yumi 
Published: August 2015

Abstract
Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-α was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.
A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides
Authors: Voelz Kerstin , Gratacap Remi L. , Wheeler Robert T. 
Published: August 2015

Mucormycosis is an emerging fungal infection that is clinically difficult to manage, with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity and traumatic injury are at increased risk of developing disease. These patients often present with defects in phagocytic effector cell function. Research utilising mammalian models and phagocytic effector cell lines has attempted to decipher the importance of the innate immune system in host defence against mucormycosis. However, these model systems have not been satisfactory to directly analyse the interaction between innate immune effector cells and infectious sporangiospores in vivo.
Here, we report the first real-time in vivo analysis of the early innate immune response to mucormycete infection using a whole animal zebrafish larval model system. We identified differential host susceptibility, dependent on the site of infection (hindbrain ventricle and swimbladder), as well as differential functions of the two major phagocyte effector cell types in response to viable and non-viable spores. Larval susceptibility to mucormycete spore infection was increased upon immunosuppressant treatment. We show for the first time that macrophages and neutrophils were readily recruited in vivo to the site of infection in an intact host and spore phagocytosis can be observed in real-time in vivo. Whilst exploring innate immune effector recruitment dynamics, we discovered the formation of phagocyte clusters in response to fungal spores that potentially play a role in fungal spore dissemination. Spores failed to activate pro-inflammatory gene expression by six hours post infection in both infection models. After 24 hours, induction of a pro-inflammatory response was only observed in hindbrain ventricle infections. Only a weak pro-inflammatory response was initiated after spore injection into the swimbladder during the same time frame.
In the future, the zebrafish larva as a live whole animal model system will contribute greatly to the study of molecular mechanisms involved in the interaction of the host innate immune system with fungal spores during mucormycosis.
Phylogenetic aspects of the concept of intelligent life design
Authors: Krajewski Zbigniew 
Published: August 2015

AbstractThis paper presents a new treatment of molecular evolutionary model as a product of intelligent changes. The aim of this paper is to obtain a life design system, drawing on processes occurring in nature regardless of explanations of the origins of life. The idea of intelligent design and molecular relationship is considered as a basic concept of the intelligent life design system, using some analogies taken from molecular evolutionary models. Three steps of life design system are outlined; however, the main subject is an attempt to find certain similar effects of the design system processes and the processes simulated with basic evolutionary substitution models: Jukes-Cantor; Felsenstein; and Hasegawa, Kishino, and Yano (HKY). An idea of gene reduction has been applied, from more complex (taking into account information density) biological systems to less complex, specialised biological systems. Two steps have been taken into consideration: a test stage in the virtual world and an adaptation finishing process after running the systems in the real world. Two algorithms have been applied. The first one has applied similarity related to an accommodation process to required conditions in the virtual and the real world. The second algorithm has applied accommodation to required conditions separately (expressed as amino acid substitution) in the first step, using a convenient criterion, and further (similar to observable) accommodation in the real world. A phylogenetic tree, similar to a real one, has been calculated using the above method for mammals, for mtDNA, with the maximum likelihood method, and with the aid of PhyML for the HKY model. This paper is an introduction showing an aspect of the life design system, related to phylogenetic relationships.
Nanoporous copper from dual-phase alloy families and its technology application in lithium ion batteries
Authors: Liu Wenbo , Chen Long , Yan Jiazhen , Li Ning , Shi Sanqiang , Zhang Shichao 
Published: August 2015

AbstractNanoporous metals have recently attracted considerable interest in a wide variety of applications, including catalysis, sensors, actuators, fuel cells, microfluidic flow controllers, and so forth. Their inherent special morphology and characteristic is expected to have superior performances, such as the open porosity, high surface area, good electron conductivity, extremely clean metal surface, and high structural stability with no agglomeration in comparison with other nanostructures. Here, we mainly review our group’s systematical studies related to nanoporous copper (NPC) from dual-phase alloy families, aiming at giving a comprehensive summary about our step-by-step progress in its fabrication, microstructure evolution, dealloying behavior, and one-step strategies to special 3-D bicontinuous porous architectures in the last 5 years. Meanwhile, some encouraging test findings on the original application of NPC in lithium ion batteries have also been covered briefly in the last part of this review, which would open a window toward their other technology applications in high-performance electrochemical devices within the green, new energy industry.
Process Modelling, Thermodynamic Analysis and Optimization of Dry Reforming, Partial Oxidation and Auto-Thermal Methane Reforming for Hydrogen and Syngas production
Authors: Ayodele Bamidele V. , Cheng Chin Kui 
Published: August 2015

Abstract
In this work, process modelling, thermodynamic analysis and optimization of stand-alone dry and partial oxidation reforming of methane as well as, the auto-thermal reforming processes were investigated. Firstly, flowsheet models were developed for both the stand-alone systems and auto-thermal reforming process using ASPEN HYSYS®. Furthermore, thermodynamic studies were conducted for the stand-alone and auto-thermal reforming processes for temperatures range of 200–1000°C and pressure range of 1–3 bar using Gibbs free energy minimization methods which was also performed using ASPEN HYSYS®. The simulation of the auto-thermal reforming process was also performed at 20 bar to mimic industrial process. Process parameters were optimized in the combined reforming process for hydrogen production using desirability function. The simulation results show that 84.60 kg/h, 62.08 kg/h and 154.7 kg/h of syngas were produced from 144 kg/h, 113 kg/h and 211 kg/h of the gas fed into the Gibbs reactor at CH4/CO2/O2 ratio 1:1:1 for the stand-alone dry reforming, partial oxidation reforming and auto-thermal processes respectively. Equilibrium conversion of CH4, CO2, O2 were thermodynamically favoured between 400 and 800°C with highest conversions of 100%, 95.9% and 86.7% for O2, CO2 and CH4 respectively. Highest yield of 99% for H2 and 40% for CO at 800°C was obtained. The optimum conditions for hydrogen production were obtained at CH4/CO2, CH4/O2 ratios of 0.634, 0.454 and temperature of 800°C respectively. The results obtained in this study corroborate experimental studies conducted on auto-thermal reforming of methane for hydrogen and syngas production.
The role of proteotoxic stress in vascular dysfunction in the pathogenesis of Alzheimer’s disease
Authors: Fonseca Ana Catarina R.G. , Resende Rosa , Cardoso Sandra M. , Pereira Cláudia F. 
Published: August 2015

AbstractAlzheimer’s disease (AD) is the principal cause of dementia in the elderly; however, its prevalence is increasing due to the fact that current pharmaceuticals used to manage the symptoms are not capable of preventing, halting, or reversing disease progression. In the last decade, evidence has accumulated to support the hypothesis that a primary cerebral vascular dysfunction initiates the cascade of events that leads to neuronal injury and the subsequent cognitive decline observed in AD. The mechanisms underlying these vascular defects and their relationship with neurodegeneration are still poorly understood however. It is pathologically known that cerebrovascular dysfunctions can induce the deposition of amyloid-β (Aβ), an amyloidogenic and toxic peptide that in turn causes cerebrovascular degeneration. Mammalian cells regulate proteostasis and the functioning of intracellular organelles through diverse mechanisms such as the Unfolded Protein Response, the Ubiquitin-Proteasome System and autophagy; however, when these mechanisms cannot compensate for perturbations in homeostasis, the cell undergoes programmed death via apoptosis. This review summarizes recent studies that together correlate the deregulation of protein quality control pathways with dysfunction of vascular endothelial cells of the brain in AD, thus supporting the hypothesis that it is the vicious, progressive failure of the proteostatic network and endothelial activation that underlies the cerebrovascular changes that symptomize AD.
Parenthood linked to new onset overweight or obesity among Chilean adolescents
Authors: Lee July , East Patricia , Blanco Estela , Kang-Sim Eastern , Castillo Marcela , Lozoff Betsy , Gahagan Sheila 
Published: August 2015

Abstract

Objective: To determine whether early parenthood is associated with the onset of overweight/obesity during adolescence.

Methods: Weight status changes between ages 16 and 21 years were measured in 270 Chilean youths. Parenthood by age 21 was assessed by interview.

Results: Sixty-three youths became overweight/obese between ages 16 and 21 years (23%), and 24% (n=65) of the total sample were parents by age 21. Bearing a child by age 21 was associated with a two-fold risk of becoming newly overweight or obese (OR=2.6, CI: 1.1, 5.9, p<0.05). Earlier internalizing problems were also associated with the development of overweight/obesity in young mothers.

Conclusion: Weight status changes from normal to overweight or obese were more likely to occur among young parents than non-parents. This has implications for adolescents’ future health given their likelihood of having subsequent pregnancies and the known risks of increased weight at each pregnancy.
Sildenafil, a phosphodiesterase type 5 inhibitor, attenuates diabetic nephropathy in STZ-induced diabetic rats
Authors: Tripathi Alok Shiomurti , Mazumder Papiya Mitra , Chandewar Anil Vilasrao 
Published: August 2015

Abstract

Background: The present study evaluates the possible mechanism of sildenafil citrate (SIL) for the attenuation of renal failure in diabetic nephropathic (DN) animals.

Methods: Diabetic nephropathy was induced by a single dose of streptozotocin (STZ) (60 mg/kg, i.p.) and confirmed by assessing the blood and urine biochemical parameters on the 28th day of its induction. The selected DN animals were treated with glimepiride (0.5 mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) for a period of 6 weeks. Biochemical parameters in blood and urine were estimated after the 29th and 70th day of the protocol for the estimation of the effect of SIL.

Result: There were significant alterations in the blood and urine biochemical parameters in STZ-treated groups which confirmed DN. There was a significant decrease in the triglyceride level in the SIL-only-treated group on the 70th day of the protocol. The histopathology study also suggested that SIL treatment results in the improvement in the podocyte count in DN animals.

Conclusions: The present study concludes that SIL improves the renal function by decreasing the triglyceride level and improving the podocyte count in DN animals.
Ethics and the Reach of Actually Existing Capitalist Markets
Authors: Sherman David 
Published: August 2015

Abstract
Although philosophers tend to differ in terms of the criteria that they offer for determining when market transactions should be morally prohibited, they tend to converge with respect to a certain methodological bias: they fail to reflexively consider how the existing politico-economic context bears on the way in which they formulate these criteria. After discussing the nature of actually existing, rather than idealized, markets, I consider four such offerings, which are either liberal egalitarian or communitarian, and I articulate how this failure is manifested in their respective positions. I conclude by pointing toward an alternative approach to the question of marketization, one that is both methodologically and substantively more faithful to the scope of the underlying problems that this question raises.
Damage detection of three-dimensional braided composite materials using carbon nanotube thread
Authors: Wan Zhenkai , Guo Jianmin , Jia Minrui 
Published: August 2015

AbstractStructural health monitoring (SHM) takes advantage of the recent advances in structural behavior monitoring to assess the performance of a structure, identifying the damage in the early stage. In this study, a carbon nanotube thread strain sensor was fabricated into a three-dimensional (3D) braided composite preform for the strain sensing of SHM. We present the results of an investigation on a carbon nanotube thread network in 3D composites for damage detection, in which the variation of the electrical resistance of the carbon nanotube thread embedded into 3D composites was recorded. Based on the variation of the electrical resistance, the location and size of damages were estimated by the response surface method, providing an effective solution for the estimation of the location and size of damages in 3D composites.