bluuebunny/crossref_metadata_2025 huggingface dataset:
Static allometry of unicellular green algae: scaling of cellular surface area and volume in the genus Micrasterias (Desmidiales)
Authors: Neustupa J.
Published: November 2015

The surface area‐to‐volume ratio of cells is one of the key factors affecting fundamental biological processes and, thus, fitness of unicellular organisms. One of the general models for allometric increase in surface‐to‐volume scaling involves fractal‐like elaboration of cellular surfaces. However, specific data illustrating this pattern in natural populations of the unicellular organisms have not previously been available. This study shows that unicellular green algae of the genus Micrasterias (Desmidiales) have positive allometric surface‐to‐volume scaling caused by changes in morphology of individual species, especially in the degree of cell lobulation. This allometric pattern was also detected within most of the cultured and natural populations analysed. Values of the allometric S:V scaling within individual populations were closely correlated to the phylogenetic structure of the clade. In addition, they were related to species‐specific cellular morphology. Individual populations differed in their allometric patterns, and their position in the allometric space was strongly correlated with the degree of allometric S:V scaling. This result illustrates that allometric shape patterns are an important correlate of the capacity of individual populations to compensate for increases in their cell volumes by increasing the surface area. However, variation in allometric patterns was not associated with phylogenetic structure. This indicates that the position of the populations in the allometric space was not evolutionarily conserved and might be influenced by environmental factors.
Divergence in mating signals correlates with genetic distance and behavioural responses to playback
Authors: Sosa‐López J. R. , Martínez Gómez J. E. , Mennill D. J.
Published: November 2015

Animals use acoustic signals to defend resources against rivals and attract breeding partners. As with many biological traits, acoustic signals may reflect ancestry; closely related species often produce more similar signals than do distantly related species. Whether this similarity in acoustic signals is biologically relevant to animals is poorly understood. We conducted a playback experiment to measure the physical and vocal responses of male songbirds to the songs of both conspecific and allopatric‐congeneric animals that varied in their acoustic and genetic similarity. Our subjects were territorial males of four species of neotropicalTroglodyteswrens: Brown‐throatedWrens (Troglodytes brunneicollis),CozumelWrens (T. beani),ClarionWrens (T. tanneri) andSocorroWrens (T. sissonii). Our results indicate that birds respond to playback of both conspecific and allopatric‐congeneric animals; that acoustic differences increase with genetic distance; and that genetic divergence predicts the strength of behavioural responses to playback, after removing the effects of acoustic similarity between subjects’ songs and playback stimuli. Collectively, these results demonstrate that the most distantly related species have the most divergent songs; that male wrens perceive divergence in fine structural characteristics of songs; and that perceptual differences between species reflect evolutionary history. This study offers novel insight into the importance of acoustic divergence of learned signals and receiver responses in species recognition.
Physicochemical Characterization and Bioactive Value of Tropical Berry Pomaces after Spouted Bed Drying
Authors: Borges Kátia Cristina , Azevedo Juliana Chris , Medeiros Maria de Fátima , Correia Roberta Targino P.
Published: November 2015

This study addressed the physicochemical characteristics and selected bioactive compounds of tropical fruit pomaces acerola (Malpighia glabra L.), red pitanga (Eugenia uniflora) and jambolan (Syzygium cumini) obtained by spouted bed drying. The dried pomaces presented attractive colors, acidic pH, moisture between 8.3 and 9.7 g/100g, water activity lower than 0.5 and solubility around 40%. The water and ethanol extracts of these fruit powder samples showed high concentration of phenolics (10.1–30.7 mg GAE/g) with relevant DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) antioxidant activity (30.1–36.3 μmol Trolox equivalent/g). Dried jambolan also proved to be an outstanding anthocyanin‐rich product (377.0–478.7 mg cyanidin 3‐glycoside equivalent/100g). In addition, all extracts presented intermediate α‐amylase inhibitory activity (23.9–76.6%) and remarkable in vitro effect against α‐glucosidase (up to 99.3%). Overall, our results show the bioactive and technological potentials of dried acerola, red pitanga and jambolan pomaces as high quality food ingredients with functional attributes.

Practical Applications

Acerola, red pitanga and jambolan are bioactive‐rich tropical fruits. The fruit processing generates a considerable amount of low‐value fruit pomaces. The motivation for this research was to propose the spouted bed drying as an appropriate strategy to produce food ingredients using the abundant residues of these selected fruits. A relevant concentration of residual bioactive compounds, antioxidant activity and inhibitory activities against key enzymes relevant to the management of early stages of type 2 diabetes were detected in the final dried products. Overall, our results present the spouted bed drying as a promising eco‐friendly process that can be successfully applied to produce value‐added fruit co‐products with potential health benefits. The data presented here constitute the biochemical rationale for the better exploitation of these tropical fruit pomaces.
Quantifying resilience to flooding among households and local government units using system dynamics: a case study in Metro Manila
Authors: Gotangco C.K. , See J. , Dalupang J.P. , Ortiz M. , Porio E. , Narisma G. , Yulo‐Loyzaga A. , Dator‐Bercilla J.
Published: November 2015

A generic systems dynamics (SD) model template for resilience is adapted to analyse flooding impacts on household assets and local government assets of Pasig City, Metro Manila. SD simulations are used to quantify the loss of system performance due to adverse impacts, and the recovery of the system due to response measures. The simulation results reflect the decreasing levels of resilience among low‐income households, and the reliance of local government on budgeting cycles to replenish assets. The initial model needs to be expanded to include other determinants of resilience, but this exploratory study reflects the potential usefulness of SD simulations as a decision support tool for city policy makers. By quantifying changes in resilience measures over time, simulations can complement qualitative analyses and test policy and programme scenarios.
Neural stem cell transplantation decreases neuroinflammation in a transgenic mouse model of Alzheimer's disease
Authors: Zhang Qi , Wu Hua‐hui , Wang Yuan , Gu Guo‐jun , Zhang Wei , Xia Rong
Published: November 2015

Inflammatory processes are considered to play an important role in the progression of neurodegenerative changes in Alzheimer's disease (AD). A number of studies have reported that inflammatory processes are highly correlated with cognitive deficits in AD‐like mice. Transplantation of neural stem cells (NSCs) has been considered as a potential new therapy for the treatment of AD because of its effects in improving cognitive ability. However, NSCs have not been evaluated for their protective effects against inflammatory changes in AD. Here, we injected NSCs into amyloid precursor protein (APP)/PS1 transgenic mice to analyse cognitive function and to measure glial fibrillary acidic protein (GFAP), ionized calcium‐binding adaptor molecule‐1 (Iba‐1) and toll‐like receptors 4(TLR4) activation. We also quantified TLR‐4 pathway‐related agents, Aβ concentration and the levels of proinflammatory mediators. Our results showed that in NSC‐injected APP/PS1 mice, activation of GFAP, Iba‐1, TLR4 and TLR4 pathway‐related agents (MyD88, TRIF, P38 MAPK and NF‐κB P65) were significantly decreased with decreased expression of proinflammatory mediators (IL‐1, IL‐6, TNF‐α and PGE2). These changes were associated with the amelioration of cognitive deficits, but no difference was found in Aβ concentration. Our results provide novel evidence that NSC transplantation in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and TLR4‐mediated inflammatory pathway activation. Our data indicate that these pathways may potentially be important therapeutic targets to prevent or delay AD.

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This study investigated the neuroprotective effect of neural stem cell (NSC) transplantation against Alzheimer's disease (AD) inflammation. We found that NSC treatment in APP/PS1 mice significantly improved cognitive deficits and was accompanied by the attenuation of inflammatory injury via suppression of glial and toll‐like receptor 4 (TLR4) activation and its downstream signalling pathways. Our findings indicate that these pathways may be potentially important therapeutic targets to prevent or delay AD.
MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy
Authors: Vafadari Behnam , Salamian Ahmad , Kaczmarek Leszek
Published: November 2015

Matrix metalloproteinase‐9 (MMP‐9) is a member of the metzincin family of mostly extracellularly operating proteases. Despite the fact that all of these enzymes might be target promiscuous, with largely overlapping catalogs of potential substrates,MMP‐9 has recently emerged as a major and apparently unique player in brain physiology and pathology. The specificity ofMMP‐9 may arise from its very local and time‐restricted actions, even when released in the brain from cells of various types, including neurons, glia, and leukocytes. In fact, the quantity ofMMP‐9 is very low in the naive brain, but it is markedly activated at the levels of enzymatic activity, protein abundance, and gene expression following various physiological stimuli and pathological insults. NeuronalMMP‐9 participates in synaptic plasticity by controlling the shape of dendritic spines and function of excitatory synapses, thus playing a pivotal role in learning, memory, and cortical plasticity. When improperly unleashed,MMP‐9 contributes to a large variety of brain disorders, including epilepsy, schizophrenia, autism spectrum disorder, brain injury, stroke, neurodegeneration, pain, brain tumors, etc. The foremost mechanism of action ofMMP‐9 in brain disorders appears to be its involvement in immune/inflammation responses that are related to the enzyme's ability to process and activate various cytokines and chemokines, as well as its contribution to blood–brain barrier disruption, facilitating the extravasation of leukocytes into brain parenchyma. However, another emerging possibility (i.e., the control ofMMP‐9 over synaptic plasticity) should not be neglected. The translational potential ofMMP‐9 has already been recognized in both the diagnosis and treatment domains. The most striking translational aspect may be the discovery ofMMP‐9 up‐regulation in a mouse model of Fragile X syndrome, quickly followed by human studies and promising clinical trials that have sought to inhibitMMP‐9. With regard to diagnosis, suggestions have been made to useMMP‐9 alone or combined with tissue inhibitor of matrix metalloproteinase‐1 or brain‐derived neurotrophic factor as disease biomarkers.

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MMP‐9, through cleavage of specific target proteins, plays a major role in synaptic plasticity and neuroinflammation, and by those virtues contributes to brain physiology and a host of neurological and psychiatric disorders.

This article is part of the60th Anniversary special issue.
Walker 256 tumor‐bearing rats demonstrate altered interstitial cells of Cajal. Effects on ICC in the Walker 256 tumor model
Authors: Fracaro L. , Frez F. C. V. , Silva B. C. , Vicentini G. E. , de Souza S. R. G. , Martins H. A. , Linden D. R. , Guarnier F. A. , Zanoni J. N.
Published: November 2015

Background

Cachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied.

Methods

Twenty‐eight male Wistar rats were divided into four groups: control (C), control supplemented with L‐glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L‐glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis.

Key Results

Tumor‐bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake.

Conclusions & Inferences

There are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L‐glutamine has differential and complex effects of ICC, it reduces tumor size and tumor‐associated cachexia, which supports its beneficial therapeutic role in cancer.
Ectomycorrhizal fungi decompose soil organic matter using oxidative mechanisms adapted from saprotrophic ancestors
Authors: Shah Firoz , Nicolás César , Bentzer Johan , Ellström Magnus , Smits Mark , Rineau Francois , Canbäck Björn , Floudas Dimitrios , Carleer Robert , Lackner Gerald , Braesel Jana , Hoffmeister Dirk , Henrissat Bernard , Ahrén Dag , Johansson Tomas , Hibbett David S. , Martin Francis , Persson Per , Tunlid Anders
Published: November 2015

Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter (SOM). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocellulose‐degrading enzymes that are present in their saprotrophic ancestors.

Spectroscopic analyses and transcriptome profiling were used to examine the mechanisms by which five species of ectomycorrhizal fungi, representing at least four origins of symbiosis, decompose SOM extracted from forest soils.

In the presence of glucose and when acquiring nitrogen, all species converted the organic matter in the SOM extract using oxidative mechanisms. The transcriptome expressed during oxidative decomposition has diverged over evolutionary time. Each species expressed a different set of transcripts encoding proteins associated with oxidation of lignocellulose by saprotrophic fungi. The decomposition ‘toolbox’ has diverged through differences in the regulation of orthologous genes, the formation of new genes by gene duplications, and the recruitment of genes from diverse but functionally similar enzyme families.

The capacity to oxidize SOM appears to be common among ectomycorrhizal fungi. We propose that the ancestral decay mechanisms used primarily to obtain carbon have been adapted in symbiosis to scavenge nutrients instead.
Non‐factualism Versus Nominalism
Authors: Plebani Matteo
Published: November 2015

The platonism/nominalism debate in the philosophy of mathematics concerns the question whether numbers and other mathematical objects exist. Platonists believe the answer to be in the positive, nominalists in the negative. According to non‐factualists (about mathematical objects), the question is ‘moot’, in the sense that it lacks a correct answer. Elaborating on ideas from Stephen Yablo, this article articulates a non‐factualist position in the philosophy of mathematics and shows how the case for non‐factualism entails that standard arguments for rival positions fail. In particular, showing how and why non‐factualists reject nominalism illuminates the originality and interest of their position.
Graft‐versus‐host disease (GVHD) prophylaxis by using methotrexate decreases pre‐engraftment syndrome and severe acute GVHD, and accelerates engraftment after cord blood transplantation
Authors: Iguchi Akihiro , Terashita Yukayo , Sugiyama Minako , Ohshima Junjiro , Sato Tomonobu Z. , Cho Yuko , Kobayashi Ryoji , Ariga Tadashi
Published: November 2015

GVHD and graft failure are serious problems in CBT. PES after CBT also occurs frequently and is associated with transplantation‐related complications such as acute GVHD. We reviewed medical records for 70 consecutive child CBT recipients between December 1997 and April 2015. Forty‐nine patients received prophylaxis against GVHD with CsA or Tac in combination with mPSL from day +7 (mPSL group), and 21 patients received CsA or Tac with MTX on day +1 and day +3 (MTX group). Neutrophil engraftment was detected in 59 patients (84.3%). Neutrophil engraftment rate in the MTX group was significantly higher than that in the mPSL group (21/21 (100%) and 38/49 (77.6%), respectively, p = 0.027). PES developed in 35 patients, and the incidence of PES in the mPSL group was significantly higher than that in the MTX group (p = 0.036). The incidence of severe acute GVHD (grade III or IV) in the MTX group was significantly lower than that in the mPSL group (p = 0.049). Although this study was a small‐scale study, the results showed that increase in the rate of engraftment and decrease in the incidence of early immune reactions such as PES and severe acute GVHD could be achieved by early commencement of immunosuppression using MTX.
The Association of Hair Cortisol with Self‐Reported Chronic Psychosocial Stress and Symptoms of Anxiety and Depression in Women Shortly after Delivery
Authors: Braig Stefanie , Grabher Felix , Ntomchukwu Clarissa , Reister Frank , Stalder Tobias , Kirschbaum Clemens , Rothenbacher Dietrich , Genuneit Jon
Published: November 2015

Background

Psychosocial stress during pregnancy including anxiety and depression is known to have adverse health effects on newborns. However, measuring these psychological constructs is complex with psychological, endocrinological, and physiological systems being affected. Hair cortisol concentrations (HCC), assumed to reflect long‐term endocrine consequences of stress exposure, represent a promising instrument for epidemiological research. However, the association between HCC and questionnaire‐based instruments is unclear.

Methods

In the Ulm SPATZ Health Study, mothers were recruited shortly after delivery in the University Medical Centre Ulm, Germany between April 2012 and May 2013. HCC of 768 participants were determined in scalp‐near 3 cm maternal hair segments, assumed to reflect cortisol exposure over the last trimester of pregnancy. Chronic stress, anxiety, and depressive symptomatology were self‐reported in questionnaire‐based instruments. Spearman correlation coefficients between HCC and these instruments as well as means of HCC in highly and low stressed subgroups were calculated.

Results

HCC were not correlated with self‐reported chronic stress, anxiety, or depressive symptomatology. Furthermore, the investigation of sub‐populations did not reveal substantial differences of HCC across highly and low stressed women.

Conclusions

HCC were not found to correlate with self‐reports of chronic stress, anxiety, or depressive symptomatology. Among other things, these findings could reflect problems with questionnaire‐based assessments obtained shortly after delivery such as recall bias and/or suggest that associations between cortisol secretion and psychosocial stress are difficult to detect due to, e.g. a strong physiological increase of cortisol in the last trimester.
Inclusion of Consumption into the EU ETS: The Legal Basis under European Union Law
Authors: Ismer Roland , Haussner Manuel
Published: November 2015

Traditionally discussed measures to prevent carbon leakage under the European Union (EU) emissions trading system, such as the free allocation of allowances or border carbon adjustments, either suffer from significant economic drawbacks or have seen their political, legal and administrative feasibility questioned. Recently, a novel approach has been proposed in the form of the inclusion of consumption into emissions trading schemes. Under this approach, a charge would be imposed on carbon‐intensive products at the time of their release for consumption within the EU. After sketching this proposal, this article discusses the correct legal basis under EU law. It develops the argument that the inclusion of consumption may be based on Article 192.1 of the Treaty on the Functioning of the EU and thus be adopted without unanimity voting in the Council of the EU.
Presence of nucleotide substitutions in the ABO promoter in individuals with phenotypes A3 and B3
Authors: Isa K. , Yamamuro Y. , Ogasawara K. , Yabe R. , Ogiyama Y. , Ito S. , Takahashi Y. , Kominato Y. , Sano R. , Uchikawa M.
Published: November 2015

Recently, the involvement of mutation and deletion of transcription regulatory elements in the Bm, Am, A3 and B3 phenotypes has been reported. In the present study, we carried out genetic analysis of individuals with A3 and B3 using peptide nucleic acid‐clamping PCR to exclude amplification of O alleles. Two single‐point mutations, −76G>C and −68G>T, were found in the ABO promoter on the A‐allele in three A3 individuals and on the B allele in a B3 individual, respectively. Transient transfection of luciferase reporter plasmids carrying the same mutations into K562 cells revealed decreased luciferase activity in comparison with that carrying the wild‐type promoter. These observations suggest that the mutations downregulate the promoter activity, leading to reduction in A‐ or B‐antigen expression on red blood cells in individuals with the A3 and B3 phenotypes.
Mitogenomics of Vetigastropoda: insights into the evolution of pallial symmetry
Authors: Uribe Juan E. , Kano Yasunori , Templado José , Zardoya Rafael
Published: November 2015

The nucleotide sequences of the complete or nearly complete mitochondrial (mt) genomes of seven vetigastropods were determined:Angaria neglecta(Angarioidea),Phasianella solida(Phasianelloidea),Granata lyrata(Seguenzioidea),Tegula lividomaculataandBolma rugosa(Trochoidea),Diodora graeca(Fissurelloidea) andLepetodrilus schrolli(Lepetodriloidea). While the mt genomes of the superfamilies Angarioidea, Phasianelloidea, Seguenzioidea and Trochoidea conform generally to the ancestral gene order of Vetigastropoda and Gastropoda, those of the superfamilies Fissurelloidea and Lepetodriloidea have suffered important rearrangements. The gene order of the mtDNAofChrysomallon squamiferum, a representative of Neomphalina, was also analysed since it has been proposed to be closely related to Vetigastropoda, and showed a distinct arrangement. The reconstructed phylogenies recovered Neomphalina as a distinct gastropod lineage that is the sister group (only with moderate bootstrap support) of a clade including Vetigastropoda and Neritimorpha + Caeno‐gastropoda while the relative position of Heterobranchia and Patellogastropoda in the gastropod tree could not be determined definitively due to their long branches. Within the monophyletic Vetigastropoda, the superfamily Fissurelloidea was recovered as the sister group of two lineages, one including Lepetodriloidea as the sister group of Seguenzioidea + Halitoidea, the other including Phasianelloidea, Angarioidea and Trochoidea without resolved relationships. The long branches of Fissurelloidea were found to introduce significant tree instability in phylogenetic reconstruction. The new phylogeny supports that the loss of the right pallial gill occurred multiple times in vetigastropod evolution as previously suggested and that Phasianelloidea, Angarioidea and Trochoidea radiated from a common asymmetric (single‐gilled) ancestor that lived in the middle Palaeozoic.
On the relationship between depth and cohomological dimension
Authors: Dao Hailong , Takagi Shunsuke
Published: November 2015

Let $(S,\mathfrak{m})$ be an $n$-dimensional regular local ring essentially of finite type over a field and let $\mathfrak{a}$ be an ideal of $S$. We prove that if $\text{depth}\,S/\mathfrak{a}\geqslant 3$, then the cohomological dimension $\text{cd}(S,\mathfrak{a})$ of $\mathfrak{a}$ is less than or equal to $n-3$. This settles a conjecture of Varbaro for such an $S$. We also show, under the assumption that $S$ has an algebraically closed residue field of characteristic zero, that if $\text{depth}\,S/\mathfrak{a}\geqslant 4$, then $\text{cd}(S,\mathfrak{a})\leqslant n-4$ if and only if the local Picard group of the completion $\widehat{S/\mathfrak{a}}$ is torsion. We give a number of applications, including a vanishing result on Lyubeznik’s numbers, and sharp bounds on the cohomological dimension of ideals whose quotients satisfy good depth conditions such as Serre’s conditions $(S_{i})$.
Cord blood mononuclear cells prevent neuronal apoptosis in response to perinatal asphyxia in the newborn lamb
Authors: Aridas James D. S. , McDonald Courtney A. , Paton Madison C. B. , Yawno Tamara , Sutherland Amy E. , Nitsos Ilias , Pham Yen , Ditchfield Michael , Fahey Michael C. , Wong Flora , Malhotra Atul , Castillo‐Melendez Margie , Bhakoo Kishore , Wallace Euan M. , Jenkin Graham , Miller Suzanne L.
Published: November 2015

Key points

Asphyxia at the time of birth is a significant cause of death or disability in newborns. There is very limited treatment available for these newborns.

Autologous umbilical cord blood (UBC) mononuclear cells reduce clinical markers of brain damage following perinatal asphyxia.

Autologous UBC mononuclear cells reduce neuroinflammation and neuronal apoptosis within the brain following perinatal asphyxia.

Autologous UBC mononuclear cells administered 12 h after perinatal asphyxia are neuroprotective, and a well‐tolerated and feasible treatment for infants following hypoxic ischaemic encephalopathy.

Perinatal asphyxia is a significant cause of death or long‐term neurodevelopmental impairment. Hypothermia, currently the only effective treatment, leads to modest improvements, but new therapeutic strategies are required. Umbilical cord blood (UCB) mononuclear cells have potent anti‐inflammatory properties and may reduce neuropathology. This study examined whether autologous UCB mononuclear cells were neuroprotective when administered to newborn lambs at 12 h after birth asphyxia. At caesarean section, birth asphyxia was induced by clamping the umbilical cord until mean arterial blood pressure decreased to 18–20 mmHg. Asphyxia (n = 20) or control (n = 11) lambs were resuscitated and maintained, with magnetic resonance spectroscropy (MRS) performed at 12 and 72 h, and were then killed at 72 h. Cord blood was collected once the cord was clamped, and mononuclear cells were isolated and labelled fluorescently and administered to control (n = 3) or asphyxia (n = 8) lambs. Asphyxia induced a significant increase in cellular apoptosis (caspase‐3 immunopositive) within all brain regions examined, including cortex, hippocampus, thalamus, striatum and subcortical white matter (P < 0.01 vs. control). Additionally, asphyxia induced significant and widespread astrogliosis and increased inflammatory cells (activated microglia and macrophages). The administration of UCB mononuclear cells (asphyxia+UCB) significantly decreased neuronal apoptosis, astrogliosis and inflammation (P < 0.05 vs. asphyxia alone). Asphyxia+UCB lambs also demonstrated decreased brain metabolites lactate:choline (P = 0.01) and lactate:N‐acetylaspartate (P < 0.01) from 12 to 72 h, detected using MRS. Autologous UCB mononuclear cell treatment restores normal brain metabolism following perinatal asphyxia, and reduces brain inflammation, astrogliosis and neuronal apoptosis, supporting its use as a neuroprotective therapy following asphyxia.
Charge control in N-polar InAlN high-electron-mobility transistors grown by plasma-assisted molecular beam epitaxy
Authors: Hardy Matthew T. , Storm David F. , Downey Brian P. , Katzer D. Scott , Meyer David J. , McConkie Thomas O. , Smith David J.
Published: November 2015

N-polar InAlN-based high-electron-mobility transistors (HEMTs) have fundamental advantages relative to conventional Ga-polar AlGaN HEMTs for high frequency devices. An understanding of the epitaxial design space for controlling sheet carrier density (ns) and mobility (μ) is desirable to maximize power and frequency performance by improving breakdown voltage and reducing parasitic access resistance. In this work, the authors show that In0.17Al0.83N barrier thickness has a minimal impact on ns and μ, and an AlGaN cap layer decreases both ns and μ. Optimization of AlN and GaN interlayers can be used to maximize μ and set ns in the range of 1–3 × 1013 cm−2. The authors use this approach to demonstrate N-polar HEMTs grown on freestanding GaN substrates with sheet resistance Rs = 190 Ω/◻ and μ = 1400 cm2/V·s, leading to a maximum drain current density of 1.5 A/mm for HEMTs with a 5-μm source–drain spacing and Pt-based Schottky gates.
Asymmetric interaural generalization of learning gains in a speech-in-noise identification task
Authors: Ari-Even Roth Daphne , Karni Avi , Hildesheimer Minka , Kishon-Rabin Liat
Published: November 2015

The pattern of generalization of learning gains to untrained conditions in adult human perceptual skill learning has been used as an effective behavioral probe for studying the functional organization of the learning system. Learning gains were previously reported to generalize symmetrically between the ears for tonal stimuli. However, given the open question concerning the specialization of the hemispheres in the processing of speech sounds, it is not clear whether symmetrical interaural generalization will follow training on such stimuli. Here the effect of monaural single-session training on the identification of consonant-vowel stimuli in noise was examined. Participants showed similar robust gains in performance at 24 h post-training in both trained ears. There was, however, an asymmetrical generalization of the learning gains from the trained to the untrained ear, with more transfer from the right-trained to the left-untrained ear than vice versa. Training and transfer gains were retained for both ears over an interval of several months, although for the untrained ear a brief exposure was necessary to relearn the task. These results provide first-time evidence for an asymmetry in interaural generalization for speech sounds following training and provide further support to the lateralization of speech sounds along the auditory system.
To What Extent Can the Use of a Mobility Assistance Dog Reduce Upper Limb Efforts When Manual Wheelchair Users Ascend a Ramp?
Authors: Martin-Lemoyne Valérie , Gagnon Dany H. , Routhier François , Poissant Lise , Tousignant Michel , Corriveau Hélène , Vincent Claude
Published: November 2015

Biomechanical evidence is needed to determine to what extent the use of a mobility assistance dog (ADMob) may minimize mechanical loads and muscular demands at the upper limbs among manual wheelchair users. This study quantified and compared upper limb efforts when propelling up a ramp with and without an ADMob among manual wheelchair users. Ten manual wheelchair users with a spinal cord injury who own an ADMob ascended a ramp with and without their ADMob. The movements of the wheelchair and upper limbs were captured and the forces applied at the pushrims were recorded to compute shoulder mechanical loading. Muscular demand of the pectoralis major, anterior deltoid, biceps, and the triceps was normalized against the maximum electromyographic values. The traction provided by the ADMob significantly reduced the total force applied at the pushrim and its tangential component while the mechanical effectiveness remained similar. The traction provided by the ADMob also resulted in a significant reduction in shoulder flexion, internal rotation, and adduction moments. The muscular demands of the anterior deltoid, pectoralis major, biceps, and triceps were significantly reduced by the traction provided by the ADMob. The use of ADMob represents a promising mobility assistive technology alternative to minimize upper limb mechanical loads and muscular demands and optimize performance during wheelchair ramp ascent.
Biomechanical Testing of Distal Radius Fracture Treatments: Boundary Conditions Significantly Affect the Outcome of In Vitro Experiments
Authors: Synek Alexander , Chevalier Yan , Schröder Christian , Pahr Dieter H. , Baumbach Sebastian F.
Published: November 2015

The variety of experimental setups used during in vitro testing of distal radius fracture treatments impairs interstudy comparison and might lead to contradictory results. Setups particularly differ with respect to their boundary conditions, but the influence on the experimental outcome is unknown. The aim of this biomechanical study was to investigate the effects of 2 common boundary conditions on the biomechanical properties of an extra-articular distal radius fracture treated using volar plate osteosynthesis. Uniaxial compression tests were performed on 10 synthetic radii that were randomized into a proximally constrained group (ProxConst) or proximally movable group (ProxMove). The load was applied distally through a ball joint to enable distal fragment rotation. A significantly larger (ProxConst vs ProxMove) stiffness (671.6 ± 118.9 N·mm−1 vs 259.6 ± 49.4 N·mm−1), elastic limit (186.2 ± 24.4 N vs 75.4 ± 20.2 N), and failure load (504.9 ± 142.5 N vs 200.7 ± 49.0 N) were found for the ProxConst group. The residual tilt did not differ significantly between the 2 groups. We concluded that the boundary conditions have a profound impact on the experimental outcome and should be considered more carefully in both study design and interstudy comparison.
Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake
Authors: Haskins Jonathan W. , Zhang Shannon , Means Robert E. , Kelleher Joanne K. , Cline Gary W. , Canfrán-Duque Alberto , Suárez Yajaira , Stern David F.
Published: November 2015

The epidermal growth factor receptor family member ERBB4 stimulates cholesterol biosynthesis in breast epithelial cells.
The benefits of
Escherichia coli
Authors: Ash Caroline
Published: November 2015

Gut bacteria stimulate signaling pathways that promote tolerance to infection and limit physiological damage.
Repurposing drugs for glioblastoma
Authors: Ferrarelli Leslie K.
Published: November 2015

Antidepressants plus anticoagulants trigger self-destruction in glioma cells.
Influence of Colistin Dose on Global Cure in Patients with Bacteremia Due to Carbapenem-Resistant Gram-Negative Bacilli
Authors: Gibson Gabrielle A. , Bauer Seth R. , Neuner Elizabeth A. , Bass Stephanie N. , Lam Simon W.
Published: November 2015

The increasing prevalence of multidrug-resistant (MDR) nosocomial infections accounts for increased morbidity and mortality of such infections. Infections with MDR Gram-negative isolates are frequently treated with colistin. Based on recent pharmacokinetic studies, current colistin dosing regimens may result in a prolonged time to therapeutic concentrations, leading to suboptimal and delayed effective treatment. In addition, studies have demonstrated an association between an increased colistin dose and improved clinical outcomes. However, the specific dose at which these outcomes are observed is unknown and warrants further investigation. This retrospective study utilized classification and regression tree (CART) analysis to determine the dose of colistin most predictive of global cure at day 7 of therapy. Patients were assigned to high- and low-dose cohorts based on the CART-established breakpoint. The secondary outcomes included microbiologic outcomes, clinical cure, global cure, lengths of intensive care unit (ICU) and hospital stays, and 7- and 28-day mortalities. Additionally, safety outcomes focused on the incidence of nephrotoxicity associated with high-dose colistin therapy. The CART-established breakpoint for high-dose colistin was determined to be >4.4 mg/kg of body weight/day, based on ideal body weight. This study evaluated 127 patients; 45 (35%) received high-dose colistin, and 82 (65%) received low-dose colistin. High-dose colistin was associated with day 7 global cure (40% versus 19.5%;
P
= 0.013) in bivariate and multivariate analyses (odds ratio [OR] = 3.40; 95% confidence interval [CI], 1.37 to 8.45;
P
= 0.008). High-dose colistin therapy was also associated with day 7 clinical cure, microbiologic success, and mortality but not with the development of acute kidney injury. We concluded that high-dose colistin (>4.4 mg/kg/day) is independently associated with day 7 global cure.
Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027
Authors: Wieczorkiewicz Jeffrey T. , Lopansri Bert K. , Cheknis Adam , Osmolski James R. , Hecht David W. , Gerding Dale N. , Johnson Stuart
Published: November 2015

Antibiotics have been shown to influence the risk of infection with specific
Clostridium difficile
strains as well as the risk of
C. difficile
infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by
C. difficile
toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (
P
< 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0;
P
= 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4;
P
= 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI,
P
= 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI,
P
= 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI,
P
= 0.0001). Fluoroquinolone use, macrolide use, and
C. difficile
resistance to these antibiotic classes were associated with infection by the epidemic BI strain of
C. difficile
in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain.
Double Copies of
bla
KPC-3
::Tn
4401a
on an IncX3 Plasmid in Klebsiella pneumoniae Successful Clone ST512 from Italy
Authors: Fortini Daniela , Villa Laura , Feudi Claudia , Pires João , Bonura Celestino , Mammina Caterina , Endimiani Andrea , Carattoli Alessandra
Published: November 2015

A carbapenem-resistant sequence type 512 (ST512)
Klebsiella pneumoniae
carbapenemase 3 (KPC-3)-producing
K. pneumoniae
strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of
bla
KPC
genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the
bla
KPC-3
gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of
bla
KPC-3
::Tn
4401a
caused by intramolecular transposition events were detected in the plasmid.
Analysis of the Structure and Function of FOX-4 Cephamycinase
Authors: Lefurgy S. T. , Malashkevich V. N. , Aguilan J. T. , Nieves E. , Mundorff E. C. , Biju B. , Noel M. A. , Toro R. , Baiwir D. , Papp-Wallace K. M. , Almo S. C. , Frere J.-M. , Bou G. , Bonomo R. A.
Published: November 2015

Class C β-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC β-lactamases conferring resistance to cefoxitin, the FOX family, has grown to include nine unique members descended from the
Aeromonas caviae
chromosomal AmpC. To understand the basis for the unique cephamycinase activity in the FOX family, we determined the first X-ray crystal structures of FOX-4, apo enzyme and the acyl-enzyme with its namesake compound, cefoxitin, using the Y150F deacylation-deficient variant. Notably, recombinant expression of N-terminally tagged FOX-4 also yielded an inactive adenylylated enzyme form not previously observed in β-lactamases. The posttranslational modification (PTM), which occurs on the active site Ser64, would not seem to provide a selective advantage, yet might present an opportunity for the design of novel antibacterial drugs. Substantial ligand-induced changes in the enzyme are seen in the acyl-enzyme complex, particularly the R2 loop and helix H10 (P289 to N297), with movement of F293 by 10.3 Å. Taken together, this study provides the first picture of this highly proficient class C cephamycinase, uncovers a novel PTM, and suggests a possible cephamycin resistance mechanism involving repositioning of the substrate due to the presence of S153P, N289P, and N346I substitutions in the ligand binding pocket.
Penicillin Binding Protein 1 Is Important in the Compensatory Response of Staphylococcus aureus to Daptomycin-Induced Membrane Damage and Is a Potential Target for β-Lactam–Daptomycin Synergy
Authors: Berti Andrew D. , Theisen Erin , Sauer John-Demian , Nonejuie Poochit , Olson Joshua , Pogliano Joseph , Sakoulas George , Nizet Victor , Proctor Richard A. , Rose Warren E.
Published: November 2015

The activity of daptomycin (DAP) against methicillin-resistant
Staphylococcus aureus
(MRSA) is enhanced in the presence of β-lactam antibiotics. This effect is more pronounced with β-lactam antibiotics that exhibit avid binding to penicillin binding protein 1 (PBP1). Here, we present evidence that PBP1 has a significant role in responding to DAP-induced stress on the cell. Expression of the
pbpA
transcript, encoding PBP1, was specifically induced by DAP exposure whereas expression of
pbpB
,
pbpC
, and
pbpD
, encoding PBP2, PBP3, and PBP4, respectively, remained unchanged. Using a MRSA COL strain with
pbpA
under an inducible promoter, increased
pbpA
transcription was accompanied by reduced susceptibility to, and killing by, DAP
in vitro
. Exposure to β-lactams that preferentially inactivate PBP1 was not associated with increased DAP binding, suggesting that synergy in the setting of anti-PBP1 pharmacotherapy results from increased DAP potency on a per-molecule basis. Combination exposure in an
in vitro
pharmacokinetic/pharmacodynamic model system with β-lactams that preferentially inactivate PBP1 (DAP-meropenem [MEM] or DAP-imipenem [IPM]) resulted in more-rapid killing than did combination exposure with DAP-nafcillin (NAF) (nonselective), DAP-ceftriaxone (CRO) or DAP-cefotaxime (CTX) (PBP2 selective), DAP-cefaclor (CEC) (PBP3 selective), or DAP-cefoxitin (FOX) (PBP4 selective). Compared to β-lactams with poor PBP1 binding specificity, exposure of
S. aureus
to DAP plus PBP1-selective β-lactams resulted in an increased frequency of septation and cell wall abnormalities. These data suggest that PBP1 activity may contribute to survival during DAP-induced metabolic stress. Therefore, targeted inactivation of PBP1 may enhance the antimicrobial efficiency of DAP, supporting the use of DAP–β-lactam combination therapy for serious MRSA infections, particularly when the β-lactam undermines the PBP1-mediated compensatory response.
Quantitative Analysis of Single-Nucleotide Polymorphism for Rapid Detection of TR
34
/L98H- and TR
46
/Y121F/T289A-Positive Aspergillus fumigatus Isolates Obtained from Patients in Iran from 2010 to 2014
Authors: Mohammadi Faezeh , Hashemi Seyed Jamal , Zoll Jan , Melchers Willem J. G. , Rafati Haleh , Dehghan Parvin , Rezaie Sasan , Tolooe Ali , Tamadon Yalda , van der Lee Henrich A. , Verweij Paul E. , Seyedmousavi Seyedmojtaba
Published: November 2015

We employed an endpoint genotyping method to update the prevalence rate of positivity for the TR
34
/L98H mutation (a 34-bp tandem repeat mutation in the promoter region of the
cyp51A
gene in combination with a substitution at codon L98) and the TR
46
/Y121F/T289A mutation (a 46-bp tandem repeat mutation in the promoter region of the
cyp51A
gene in combination with substitutions at codons Y121 and T289) among clinical
Aspergillus fumigatus
isolates obtained from different regions of Iran over a recent 5-year period (2010 to 2014). The antifungal activities of itraconazole, voriconazole, and posaconazole against 172 clinical
A. fumigatus
isolates were investigated using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. For the isolates with an azole resistance phenotype, the
cyp51A
gene and its promoter were amplified and sequenced. In addition, using a LightCycler 480 real-time PCR system, a novel endpoint genotyping analysis method targeting single-nucleotide polymorphisms was evaluated to detect the L98H and Y121F mutations in the
cyp51A
gene of all isolates. Of the 172
A. fumigatus
isolates tested, the MIC values of itraconazole (≥16 mg/liter) and voriconazole (>4 mg/liter) were high for 6 (3.5%). Quantitative analysis of single-nucleotide polymorphisms showed the TR
34
/L98H mutation in the
cyp51A
genes of six isolates. No isolates harboring the TR
46
/Y121F/T289A mutation were detected. DNA sequencing of the
cyp51A
gene confirmed the results of the novel endpoint genotyping method. By microsatellite typing, all of the azole-resistant isolates had genotypes different from those previously recovered from Iran and from the Dutch TR
34
/L98H controls. In conclusion, there was not a significant increase in the prevalence of azole-resistant
A. fumigatus
isolates harboring the TR
34
/L98H resistance mechanism among isolates recovered over a recent 5-year period (2010 to 2014) in Iran. A quantitative assay detecting a single-nucleotide polymorphism in the
cyp51A
gene of
A. fumigatus
is a reliable tool for the rapid screening and monitoring of TR
34
/L98H- and TR
46
/Y121F/T289A-positive isolates and can easily be incorporated into clinical mycology algorithms.