bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of switching from basal insulin to once‐daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4‐week, randomized, open‐label, treat‐to‐target study
Authors: Nagai Yoshio , Nishine Ami , Hashimoto Eriko , Nakayama Taiga , Sasaki Yosuke , Murakami Mariko , Ishii Satoshi , Kato Hiroyuki , Tanaka Yasushi 
Published: September 2017

AbstractAims/IntroductionA prospective, 4‐week, single‐center, randomized, open‐label, parallel‐group, treat‐to‐target study was carried out to develop an algorithm for safe and effective switching from basal insulin to once‐daily insulin degludec/insulin aspart (IDegAsp) in patients with inadequately controlled type 2 diabetes.Materials and MethodsPatients were randomly assigned to continue their current basal insulin therapy (n = 10) or to switch to IDegAsp on a 1:1 unit basis (n = 10). The insulin dose could be titrated once weekly, targeting a self‐measured blood glucose of 80–100 mg/dL before breakfast. A mixed meal test was carried out at baseline and after 4 weeks.ResultsAfter 4 weeks, the mean daily dose of insulin was similarly increased by 60% in both groups, and there was a significant decrease of mean plasma glucose and glucose area under the glucose concentration vs time curve for 2 h in the meal test. The mean estimated treatment difference (IDegAsp group − basal insulin group) of the mean plasma glucose level was −28 mg/dL (95% confidence interval −47 to −8, P = 0.008) after 4 weeks and that of the area under the glucose concentration vs time curve for 2 h was −2,800 mg/min/dL (95% confidence interval −5,300 to −350, P = 0.028), confirming the superiority of IDegAsp to basal insulin. In the IDegAsp group, the 2‐h postprandial plasma glucose level was significantly decreased to the fasting plasma glucose range. There were no confirmed hypoglycemic episodes in either group during the 4‐week study period.ConclusionsAfter switching from basal insulin, the IDegAsp dose can be uptitrated by 60% based on fasting plasma glucose data. However, monitoring of postprandial glucose should be considered before further uptitration of IDegAsp.
Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection
Authors: Krämer Tobias , Grob Theresa , Menzel Lutz , Hirnet Tobias , Griemert Eva , Radyushkin Konstantin , Thal Serge C. , Methner Axel , Schaefer Michael K. E. 
Published: September 2017

AbstractDimethyl fumarate (DMF) is an immunomodulatory compound to treat multiple sclerosis and psoriasis with neuroprotective potential. Its mechanism of action involves activation of the antioxidant pathway regulator Nuclear factor erythroid 2‐related factor 2 thereby increasing synthesis of the cellular antioxidant glutathione (GSH). The objective of this study was to investigate whether post‐traumatic DMF treatment is beneficial after experimental traumatic brain injury (TBI). Adult C57Bl/6 mice were subjected to controlled cortical impact followed by oral administration of DMF (80 mg/kg body weight) or vehicle at 3, 24, 48, and 72 h after the inflicted TBI. At 4 days after lesion (dal), DMF‐treated mice displayed less neurological deficits than vehicle‐treated mice and reduced histopathological brain damage. At the same time, the TBI‐evoked depletion of brain GSH was prevented by DMF treatment. However, nuclear factor erythroid 2‐related factor 2 target gene mRNA expression involved in antioxidant and detoxifying pathways was increased in both treatment groups at 4 dal. Blood brain barrier leakage, as assessed by immunoglobulin G extravasation, inflammatory marker mRNA expression, and CD45+ leukocyte infiltration into the perilesional brain tissue was induced by TBI but not significantly altered by DMF treatment. Collectively, our data demonstrate that post‐traumatic DMF treatment improves neurological outcome and reduces brain tissue loss in a clinically relevant model of TBI. Our findings suggest that DMF treatment confers neuroprotection after TBI via preservation of brain GSH levels rather than by modulating neuroinflammation.
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Neuronal activity‐dependent local activation of dendritic unfolded protein response promotes expression of brain‐derived neurotrophic factor in cell soma
Authors: Saito Atsushi , Cai Longjie , Matsuhisa Koji , Ohtake Yosuke , Kaneko Masayuki , Kanemoto Soshi , Asada Rie , Imaizumi Kazunori 
Published: September 2017

AbstractUnfolded protein response (UPR) has roles not only in resolving the accumulation of unfolded proteins owing to endoplasmic reticulum (ER) stress, but also in regulation of cellular physiological functions. ER stress transducers providing the branches of UPR signaling are known to localize in distal dendritic ER of neurons. These reports suggest that local activation of UPR branches may produce integrated outputs for distant communication, and allow regulation of local events in highly polarized neurons. Here, we demonstrated that synaptic activity‐ and brain‐derived neurotrophic factor (BDNF)‐dependent local activation of UPR signaling could be associated with dendritic functions through retrograde signal propagation by using murine neuroblastoma cell line, Neuro‐2A and primary cultured hippocampal neurons derived from postnatal day 0 litter C57BL/6 mice. ER stress transducer, inositol‐requiring kinase 1 (IRE1), was activated at postsynapses in response to excitatory synaptic activation. Activated dendritic IRE1 accelerated accumulation of the downstream transcription factor, x‐box‐binding protein 1 (XBP1), in the nucleus. Interestingly, excitatory synaptic activation‐dependent up‐regulation of XBP1 directly facilitated transcriptional activation of BDNF. BDNF in turn drove its own expression via IRE1‐XBP1 pathway in a protein kinase A‐dependent manner. Exogenous treatment with BDNF promoted extension and branching of dendrites through the protein kinase A‐IRE1‐XBP1 cascade. Taken together, our findings indicate novel mechanisms for communication between soma and distal sites of polarized neurons that are coordinated by local activation of IRE1‐XBP1 signaling. Synaptic activity‐ and BDNF‐dependent distinct activation of dendritic IRE1‐XBP1 cascade drives BDNF expression in cell soma and may be involved in dendritic extension.Cover Image for this issue: doi. 10.1111/jnc.14159.
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Single cocaine exposure does not alter striatal pre‐synaptic dopamine function in mice: an [18F]‐FDOPA PET study
Authors: Bonsall David R , Kokkinou Michelle , Veronese Mattia , Coello Christopher , Wells Lisa A. , Howes Oliver D. 
Published: September 2017

AbstractCocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre‐synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre‐ and post‐synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre‐synaptic dopamine function remain unclear. Non‐invasive imaging techniques such as positron emission tomography have revealed impaired pre‐synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre‐synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15–20 min post treatment (p < 0.001). However, dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l‐amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre‐treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre‐synaptic dopaminergic neurons are not initiated following a single exposure to the drug.
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Growing evidence of the beneficial effects of a marine protein‐based dietary supplement for treating hair loss
Authors: Hornfeldt Carl S 
Published: September 2017

SummaryBackgroundHair loss is a common condition among women with a range of causes including nutritional deficiencies.AimsTo review the clinical data supporting the use of an oral marine supplement designed to promote hair growth.Patients/MethodsAdult women with temporary thinning hair. Following an initial pilot study, five randomized, double‐blind studies assessed the effectiveness of the oral marine supplement for promoting hair growth. Each study was approved by one or more institutional review boards.ResultsTogether, these studies demonstrated the ability of oral marine supplements to increase the growth of terminal and vellus hairs, increase the diameter of terminal and vellus hairs, and decrease hair loss. This product is beneficial for men as well as women.ConclusionsA dietary supplement containing a marine complex and other natural ingredients can safely and effectively promote hair growth and decrease hair shedding in women and men with thinning hair.
Can temperature modify the strength of density‐dependent habitat selection in ectotherms? A test with red flour beetles
Authors: Halliday W. D. , Blouin‐Demers G. 
Published: September 2017

AbstractHabitat selection is an important aspect of the ecology of animals and models predict that density dependence is a strong force shaping patterns of habitat selection. In ectotherms, however, density dependence of fitness tends to weaken as temperature deviates from the species’ optimal temperature (To). This may have important implications for density‐dependent habitat selection because the underlying mechanism for density‐dependent habitat selection is density dependence in fitness. We examine how temperature can modify the predictions from isodar theory and obtain temperature‐dependent predictions for density‐dependent habitat selection. We specifically predict that the isodar's intercept will be furthest from zero and the slope will be steepest at the optimal temperature. As temperature deviates from the optimal temperature, we predict that the intercept will approach zero and the slope will approach one. We then test these predictions with experiments on habitat selection based on food abundance by red flour beetles in the laboratory. We also confirm that fitness decreases as density increases and that density dependence weakens as temperature deviates from To. In agreement with our predictions, preference for habitats with more food weakened as density dependence weakened. Our results have implications for habitat selection by ectotherms because we demonstrate that variation in environmental temperature can weaken markedly the effect of density on both fitness and habitat selection. High density may entail no fitness costs for ectotherms that cannot maintain their optimal temperature.
The three‐component system EsrISR regulates a cell envelope stress response in Corynebacterium glutamicum
Authors: Kleine Britta , Chattopadhyay Ava , Polen Tino , Pinto Daniela , Mascher Thorsten , Bott Michael , Brocker Melanie , Freudl Roland 
Published: September 2017

SummaryWhen the cell envelope integrity is compromised, bacteria trigger signaling cascades resulting in the production of proteins that counteract these extracytoplasmic stresses. Here, we show that the two‐component system EsrSR regulates a cell envelope stress response in the Actinobacterium Corynebacterium glutamicum. The sensor kinase EsrS possesses an amino‐terminal phage shock protein C (PspC) domain, a property that sets EsrSR apart from all other two‐component systems characterized so far. An integral membrane protein, EsrI, whose gene is divergently transcribed to the esrSR gene locus and which interestingly also possesses a PspC domain, acts as an inhibitor of EsrSR under non‐stress conditions. The resulting EsrISR three‐component system is activated among others by antibiotics inhibiting the lipid II cycle, such as bacitracin and vancomycin, and it orchestrates a broad regulon including the esrI‐esrSR gene locus itself, genes encoding heat shock proteins, ABC transporters, and several putative membrane‐associated or secreted proteins of unknown function. Among those, the ABC transporter encoded by cg3322‐3320 was shown to be directly involved in bacitracin resistance of C. glutamicum. Since similar esrI‐esrSR loci are present in a large number of actinobacterial genomes, EsrISR represents a novel type of stress‐responsive system whose components are highly conserved in the phylum Actinobacteria.
Homozygous mutation in the NPHP3 gene causing foetal nephronophthisis
Authors: Abdullah Uzma , Farooq Muhammad , Fatima Ambrin , Tauseef Wasima , Sarwar Yasra , Nuri Mmh , Tommerup Niels , Baig Shahid M. 
Published: September 2017

AbstractWe present a case of a foetal sonographic finding of hyper‐echogenic kidneys, which led to a strategic series of genetic tests and identified a homozygous mutation (c.424C > T, p. R142*) in the NPHP3 gene. Our study provides a rare presentation of NPHP3‐related ciliopathy and adds to the mutation spectrum of the gene, being the first one from Pakistani population. With a thorough literature review, it also advocates for molecular assessment of ciliopathies to improve risk estimate for future pregnancies, and identify predisposed asymptomatic carriers.
Sympatric parallel diversification of major oak clades in the Americas and the origins of Mexican species diversity
Authors: Hipp Andrew L. , Manos Paul S. , González‐Rodríguez Antonio , Hahn Marlene , Kaproth Matthew , McVay John D. , Avalos Susana Valencia , Cavender‐Bares Jeannine 
Published: September 2017

Summary

Oaks (Quercus, Fagaceae) are the dominant tree genus of North America in species number and biomass, and Mexico is a global center of oak diversity. Understanding the origins of oak diversity is key to understanding biodiversity of northern temperate forests.

A phylogenetic study of biogeography, niche evolution and diversification patterns in Quercus was performed using 300 samples, 146 species. Next‐generation sequencing data were generated using the restriction‐site associated DNA (RAD‐seq) method. A time‐calibrated maximum likelihood phylogeny was inferred and analyzed with bioclimatic, soils, and leaf habit data to reconstruct the biogeographic and evolutionary history of the American oaks.

Our highly resolved phylogeny demonstrates sympatric parallel diversification in climatic niche, leaf habit, and diversification rates. The two major American oak clades arose in what is now the boreal zone and radiated, in parallel, from eastern North America into Mexico and Central America.

Oaks adapted rapidly to niche transitions. The Mexican oaks are particularly numerous, not because Mexico is a center of origin, but because of high rates of lineage diversification associated with high rates of evolution along moisture gradients and between the evergreen and deciduous leaf habits. Sympatric parallel diversification in the oaks has shaped the diversity of North American forests.
Cogency, Warrant Transmission‐Increase and non‐Ideal Thinkers
Authors: Pérez Otero Manuel 
Published: September 2017

AbstractContemporary debates concerning warrant transmission take for granted this thesis: when warrant transmission fails the argument fails. I challenge this thesis. An argument with conclusion C, addressed to subject S, can be cogent in the sense that recognition that the premises entail (or make highly likely) C can rationally foster in S the belief in C, without the warrant for C necessarily being gained (or reinforced) by such recognition. A key idea is to accept that some arguments should be understood in a way that involves the abandonment of two characteristic idealizations imposed on rational thinkers by Bayesian modelling.
Increased risk organ transplantation in the pediatric population
Authors: Wrenn Sean M. , Callas Peter W. , Kapoor Trishul , Aunchman Alia F. , Paine Adam N. , Pineda Jaime A. , Marroquin Carlos E. 
Published: September 2017

AbstractIRD organs are classified by the Public Health Service to be at above‐average risk for harboring human immunodeficiency virus, hepatitis C, and hepatitis B. Traditionally underutilized, there exists even greater reluctance for their use in pediatric patients. We performed a retrospective analysis via the United Network for Organ Sharing database of all pediatric renal and hepatic transplants performed from 2004 to 2008 in the United States. Primary outcomes were patient and graft survival. Proportional hazards regression was performed to control for potentially confounding factors. Waitlist time, organ acceptance rates, and infectious transmissions were analyzed. There were 1830 SRD renal, 92 IRD renal, 1695 SRD hepatic, and 59 IRD hepatic transplants. There were no statistically significant differences in allograft or patient survival in either group. Acceptance rates of IRD organs were lower for kidney (1.5% IRD vs 4.82% SRD) and liver (1.99% IRD vs 4.51% SRD). One transmission of a bloodborne pathogen involving a pediatric recipient out of 7797 unique transplants was reported from 2008 to 2015. IRD organs appear to have equivalent outcomes. Increasing their utilization may improve access to transplant while decreasing wait times and circumventing waitlist morbidity and mortality.
PEGylation of cationic liposomes encapsulating soluble Leishmania antigens reduces the adjuvant efficacy of liposomes in murine model
Authors: Naseri H. , Eskandari F. , Jaafari M. R. , Khamesipour A. , Abbasi A. , Badiee A. 
Published: September 2017

SummaryAlthough there have been several attempts to develop a vaccine against leishmaniasis, no vaccine in human has been developed yet. Liposomes consisting of 1, 2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP) encapsulating soluble Leishmania antigens (SLA) enhance protective immunity of SLA against Leishmania major infection in mice. However, they immobilized at the injection site because of their positive charge. To overcome the problem, shielding the surface charge with polyethylene glycol (PEGylation) was chosen in this study. Liposomal SLA consisting different concentrations of PEG (1.9%‐15% mol) were prepared. BALB/c mice were immunized three times in 3 weeks intervals with different formulations. Lesion development and parasite burden in footpad and spleen were evaluated to specify the type of generated immune response and extent of protection. Th1/Th2 cytokine profiles and IgG isotypes were also analysed. The maximum protection was observed in mice immunized with Lip‐SLA or pLip‐SLA (1.9%) due to smaller footpad swelling, reduction in parasite load, an increase in IgG2a and IFN‐γ production. Our results showed that immunization of mice with a high level of PEG (>7.5%) did not improve protective immunity of liposomal SLA. The presence of PEG, particularly more than 3.75%, is not recommended for protection against leishmaniasis.
Local pre‐adaptation to disturbance and inbreeding–environment interactions affect colonisation abilities of diploid and tetraploid Centaurea stoebe
Authors: Rosche C. , Hensen I. , Lachmuth S. 
Published: September 2017

Abstract

Primary colonisation in invasive ranges most commonly occurs in disturbed habitats, where anthropogenic disturbance may cause physical damage to plants. The tolerance to such damage may differ between cytotypes and among populations as a result of differing population histories (adaptive differentiation between ruderal verus natural habitats). Moreover, founder populations often experience inbreeding depression, the effects of which may increase through physical damage due to inbreeding–environment interactions. We aimed to understand how such colonisation processes differ between diploid and tetraploid Centaurea stoebe populations, with a view to understanding why only tetraploids are invasive.

We conducted a clipping experiment (frequency: zero, once or twice in the growing season) on inbred versus outbred offspring originating from 37 C. stoebe populations of varying cytotype, range and habitat type (natural versus ruderal). Aboveground biomass was harvested at the end of the vegetation period, while re‐sprouting success was recorded in the following spring.

Clipping reduced re‐sprouting success and biomass, which was significantly more pronounced in natural than in ruderal populations. Inbreeding depression was not detected under benign conditions, but became increasingly apparent in biomass when plants were clipped. The effects of clipping and inbreeding did not differ between cytotypes.

Adaptive differentiation in disturbance tolerance was higher among populations than between cytotypes, which highlights the potential of pre‐adaptation in ruderal populations during early colonisation on anthropogenically disturbed sites. While the consequences of inbreeding increased through clipping‐mediated stress, they were comparable between cytotypes, and consequently do not contribute to understanding the cytotype shift in the invasive range.
Measurement of urinary concentrations of the mycotoxins zearalenone and sterigmatocystin as biomarkers of exposure in mares
Authors: Takagi M , Uno S , Kokushi E , Sato F , Wijayagunawardane MMP , Fink‐Gremmels J 
Published: September 2017

ContentsMycotoxins may affect animal health, including reproduction. Little is known about the clinical relevance of exposure of horses to contaminated feed. This study aimed at (i) monitoring the levels of the mycotoxins zearalenone (ZEN), with its metabolites α‐ and β‐zearalenol (α‐ and β‐ZOL), and sterigmatocystin (STC) in urine samples from thoroughbred mares in Japan and (ii) relating these findings to the potential effects on reproductive efficacy of breeding mares. Sixty‐three urine samples of breeding mares from 59 breeding farms were used. Urine samples and reproductive records were collected from each mare when it was presented to the stallion station. Urinary concentrations of ZEN, α‐ and β‐ZOL, and STC were measured using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). ZEN, α‐ and β‐ZOL were measurable in the urine of all examined mares, indicating the prevalence of ZEN in equine feeds. In seven of the 63 samples, STC was also detected at levels ranging from 1.3 to 18.0 pg/mg creatinine. No significant correlation between the concentrations of mycotoxins and pregnancy status was observed. In conclusion, measurement of mycotoxins in urine samples is a useful non‐invasive method for monitoring the systemic exposure of mares to multiple mycotoxins.
How Homeric is the Aristotelian Conception of Courage?
Authors: Zavaliy Andrei G. 
Published: September 2017

AbtractWhen Aristotle limits the manifestation of true courage to the military context only, his primary target is an overly inclusive conception of courage presented by Plato in the Laches. At the same time, Aristotle explicitly tries to demarcate his ideal of genuine courage from the paradigmatic examples of courageous actions derived from the Homeric epics. It remains questionable, though, whether Aristotle is truly earnest in his efforts to distance himself from Homer. It will be argued that Aristotle's attempt to associate with Homer the two forms of specious courage—courage of the citizen troops and spirit‐caused courage—fails to provide sufficient criteria for the demarcation in question. All the essential elements of the Aristotelian account of courage, such as a voluntary choice, a noble goal, and a thumos‐driven reaction guided by reason are exemplified by a number of Homeric characters as well. It is thus likely that the philosopher's account of courage largely incorporates the poetic tradition at a new level, rather than supersedes it.