bluuebunny/crossref_metadata_2025_split huggingface dataset:
MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy
Authors: Vafadari Behnam , Salamian Ahmad , Kaczmarek Leszek 
Published: November 2015

AbstractMatrix 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.imageMMP‐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

AbstractBackgroundCachexia 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.MethodsTwenty‐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 ResultsTumor‐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 & InferencesThere 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

Summary

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

AbstractThe 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

AbstractGVHD 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

AbstractBackgroundPsychosocial 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.MethodsIn 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.ResultsHCC 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.ConclusionsHCC 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.
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.
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.
AbstractPerinatal 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.
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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.