bluuebunny/crossref_metadata_2025_split huggingface dataset:
A demand model for international freight transport by road
Authors: Nuzzolo Agostino , Crisalli Umberto , Comi Antonio 
Published: December 2008

Abstract
This paper presents a system of models for the estimation of road international (import/export) freight flows by using a partial share approach. It allows to simulate generation (for export), attraction (for import) and distribution steps for the estimation of freight flows in quantities (commodity approach), from which the conversion in vehicles is made by using vehicle loading models. This modelling system has been specified according to an easy-to-use philosophy (suitable to be used for forecasting) by using aggregate variables, such as GDP. The calibration has been carried out by using a set of available data in Italy that allowed us to consider import/export flows by road for three different freight types (perishable, industrial and consumption goods).
Autophagy Plays a Role in Chloroplast Degradation during Senescence in Individually Darkened Leaves
Authors: Wada Shinya , Ishida Hiroyuki , Izumi Masanori , Yoshimoto Kohki , Ohsumi Yoshinori , Mae Tadahiko , Makino Amane 
Published: December 2008

Abstract
Chloroplasts contain approximately 80% of total leaf nitrogen and represent a major source of recycled nitrogen during leaf senescence. While bulk degradation of the cytosol and organelles in plants is mediated by autophagy, its role in chloroplast catabolism is largely unknown. We investigated the effects of autophagy disruption on the number and size of chloroplasts during senescence. When leaves were individually darkened, senescence was promoted similarly in both wild-type Arabidopsis (Arabidopsis thaliana) and in an autophagy-defective mutant, atg4a4b-1. The number and size of chloroplasts decreased in darkened leaves of wild type, while the number remained constant and the size decrease was suppressed in atg4a4b-1. When leaves of transgenic plants expressing stroma-targeted DsRed were individually darkened, a large accumulation of fluorescence in the vacuolar lumen was observed. Chloroplasts exhibiting chlorophyll fluorescence, as well as Rubisco-containing bodies, were also observed in the vacuole. No accumulation of stroma-targeted DsRed, chloroplasts, or Rubisco-containing bodies was observed in the vacuoles of the autophagy-defective mutant. We have succeeded in demonstrating chloroplast autophagy in living cells and provide direct evidence of chloroplast transportation into the vacuole.
Chronic intermittentL‐DOPA treatment induces changes in dopamine release
Authors: Lundblad Martin , Af Bjerkén Sara , Cenci M. Angela , Pomerleau Francois , Gerhardt Greg A. , Strömberg Ingrid 
Published: December 2008

Abstract3,4‐Dihydroxyphenyl‐l‐alanine(l‐DOPA)‐induced dyskinesia often develops as a side effect of chronicl‐DOPA therapy. This study was undertaken to investigate dopamine (DA) release uponl‐DOPA treatment. Chronoamperometric measurements were performed in unilaterally DA‐depleted rats, chronically treated withl‐DOPA, resulting in dyskinetic and non‐dyskinetic animals. Normal and lesionedl‐DOPA naïve animals were used as controls. Potassium‐evoked DA releases were significantly reduced in intact sides of animals undertaken chronicl‐DOPA treatment, independent on dyskinetic behavior. Acutel‐DOPA further attenuated the amplitude of the DA release in the control sides. In DA‐depleted striata, no difference was found in potassium‐evoked DA releases, and acutel‐DOPA did not affect the amplitude. While immunoreactivity to serotonin uptake transporter was higher in lesioned striata of animals displaying dyskinetic behavior, no correlation could be documented between serotonin transporter‐positive nerve fiber density and the amplitude of released DA. In conclusions, the amplitude of potassium‐evoked DA release is attenuated in intact striatum after chronic intermittentl‐DOPA treatment. No change in amplitude was found in DA‐denervated sides of either dyskinetic or non‐dyskinetic animals, while release kinetics were changed. This indicates the importance of studying DA release dynamics for the understanding of both beneficial and adverse effects ofl‐DOPA replacement therapy.
RNA editing of the serotonin 2C receptor and expression of Gαqprotein: genetic mouse models do not support a role for regulation or compensation
Authors: Canal Clinton E. , Mahautmr Kontip C. , Cao Chike , Sanders‐Bush Elaine , Airey David C. 
Published: December 2008

AbstractThe serotonin 2C (5‐HT2C) receptor undergoes RNA editing at five bases in a region of the pre‐mRNA encoding the second intracellular loop, generating many unique 5‐HT2Creceptor isoforms. Mechanisms regulatingin vivoexpression of different edited 5‐HT2Creceptor isoforms are poorly understood, as are the adaptive consequences of variation in editing profiles. Recent findings suggest a putative relationship between expression levels of Gαq/11protein and the degree of editing of 5‐HT2Creceptor transcripts. To elucidate the potential regulatory or adaptive role of Gαq/11protein levels, we quantified editing of 5‐HT2Creceptor RNA transcripts in Gαqnull mice and protein levels of Gαqand Gα11in transgenic male mice solely expressing either the non‐edited (INI) or the fully edited (VGV) isoforms of the 5‐HT2Creceptor. Pyrosequencing of RNA isolated from amygdaloid cortex in Gαqnull and wild‐type mice revealed no significant differences in 5‐HT2Creceptor mRNA editing profiles. Cortical tissue from INI/y, VGV/y, and wild‐type mice was assayed for expression of Gαqand Gα11subunits by Western blotting. No differences in signal density between wild‐type and INI/y or VGV/y groups were found, indicating equivalent levels of Gαqand Gα11protein. Together, these data do not support a causal or compensatory relationship between 5‐HT2Creceptor RNA editing and Gqprotein levels.
Fumarole-Supported Islands of Biodiversity within a Hyperarid, High-Elevation Landscape on Socompa Volcano, Puna de Atacama, Andes
Authors: Costello Elizabeth K. , Halloy Stephan R. P. , Reed Sasha C. , Sowell Preston , Schmidt Steven K. 
Published: December 2008

ABSTRACT

Fumarolic activity supports the growth of mat-like photoautotrophic communities near the summit (at 6,051 m) of Socompa Volcano in the arid core of the Andes mountains. These communities are isolated within a barren, high-elevation landscape where sparse vascular plants extend to only 4,600 m. Here, we combine biogeochemical and molecular-phylogenetic approaches to characterize the bacterial and eucaryotic assemblages associated with fumarolic and nonfumarolic grounds on Socompa. Small-subunit rRNA genes were PCR amplified, cloned, and sequenced from two fumarolic soil samples and two reference soil samples, including the volcanic debris that covers most of the mountain. The nonfumarolic, dry, volcanic soil was similar in nutrient status to the most extreme Antarctic Dry Valley or Atacama Desert soils, hosted relatively limited microbial communities dominated by
Actinobacteria
and
Fungi
, and contained no photoautotrophs. In contrast, modest fumarolic inputs were associated with elevated soil moisture and nutrient levels, the presence of chlorophyll
a
, and
13
C-rich soil organic carbon. Moreover, this soil hosted diverse photoautotroph-dominated assemblages that contained novel lineages and exhibited structure and composition comparable to those of a wetland near the base of Socompa (3,661-m elevation). Fumarole-associated eucaryotes were particularly diverse, with an abundance of green algal lineages and a novel clade of microarthropods. Our data suggest that volcanic degassing of water and
13
C-rich CO
2
sustains fumarole-associated primary producers, leading to a complex microbial ecosystem within this otherwise barren landscape. Finally, we found that human activities have likely impacted the fumarolic soils and that fumarole-supported photoautotrophic communities may be exceptionally sensitive to anthropogenic disturbance.
Application of Recognition of Individual Genes-Fluorescence In Situ Hybridization (RING-FISH) To Detect Nitrite Reductase Genes (nirK) of Denitrifiers in Pure Cultures and Environmental Samples
Authors: Pratscher Jennifer , Stichternoth Catrin , Fichtl Katrin , Schleifer Karl-Heinz , Braker Gesche 
Published: December 2008

ABSTRACTDenitrification is an alternative type of anaerobic respiration in which nitrate is reduced to gaseous products via nitrite. The key step in this process is the reduction of nitrite to nitric oxide, which is catalyzed by two structurally different but functionally equivalent forms of nitrite reductase encoded by thenirKandnirSgenes. Cultivation-independent studies based on these functional marker genes showed that in the environment there was a dominance of organisms withnirKandnirSgenes presumably derived from organisms that have not been cultured yet. However, the phylogenetic affiliation of these organisms has not been resolved since the ability to denitrify is widespread in phylogenetically unrelated organisms. To unravel the phylogeny of the organisms from which the nitrite reductase (nirK) genes originated, one option is to use a special variant of whole-cell hybridization termed recognition of individual genes-fluorescence in situ hybridization (RING-FISH). In RING-FISH a multiply labeled transcript polynucleotide probe is used to detect a single gene on the bacterial chromosome during FISH. Here, RING-FISH was used with laboratory cultures and environmental samples, such as activated sludge. Furthermore, probe-based cell sorting using magnetic beads could also be carried out with mixtures of pure cultures, which led to effective depletion of thenirK-negative organism but capture of thenirK-positive organism, which was demonstrated by terminal restriction fragment length polymorphism analysis based on 16S rRNA genes. The results indicate that RING-FISH coupled with probe-based cell sorting could be used with environmental samples, which could provide a means for phylogenetic classification ofnirK-type denitrifiers. Thus, the results of RING-FISH could increase our understanding of the phylogeny and function of denitrifying microorganisms in the environment.
Functional Differentiation of
tbf1
Orthologues in Fission and Budding Yeasts
Authors: Cockell Moira M. , Lo Presti Libera , Cerutti Lorenzo , Cano Del Rosario Elena , Hauser Philippe M. , Simanis Viesturs 
Published: December 2008

ABSTRACT

In
Saccharomyces cerevisiae
,
TBF1
, an essential gene, influences telomere function but also has other roles in the global regulation of transcription. We have identified a new member of the
tbf1
gene family in the mammalian pathogen
Pneumocystis carinii
. We demonstrate by transspecies complementation that its ectopic expression can provide the essential functions of
Schizosaccharomyces pombe tbf1
but that there is no rescue between fission and budding yeast orthologues. Our findings indicate that an essential function of this family of proteins has diverged in the budding and fission yeasts and suggest that effects on telomere length or structure are not the primary cause of inviability in
S. pombe tbf1
null strains.
The White Cell Response to Pheromone Is a General Characteristic of
Candida albicans
Strains
Authors: Sahni Nidhi , Yi Song , Pujol Claude , Soll David R. 
Published: December 2008

ABSTRACT

For
Candida albicans
, evidence has suggested that the mating pheromones activate not only the mating response in mating-competent opaque cells but also a unique response in mating-incompetent white cells that includes increased cohesion and adhesion, enhanced biofilm formation, and expression of select mating-related and white cell-specific genes. On the basis of a recent microarray analysis comparing changes in the global expression patterns of white cells in two strains in response to α-pheromone, however, skepticism concerning the validity and generality of the white cell response has been voiced. Here, we present evidence that the response occurs in all tested media (Lee's, RPMI, SpiderM, yeast extract-peptone-dextrose, and a synthetic medium) and in all of the 27 tested strains, including
a
/
a
and α/α strains, derivatives of the common laboratory strain SC5314, and representatives from all of the five major clades. The white cell response to pheromone is therefore a general characteristic of
MTL
-homozygous strains of
C. albicans
.
Crystal Structures of Cytochrome P450 105P1 fromStreptomyces avermitilis: Conformational Flexibility and Histidine Ligation State
Authors: Xu Lian-Hua , Fushinobu Shinya , Ikeda Haruo , Wakagi Takayoshi , Shoun Hirofumi 
Published: December 2008

ABSTRACTThe polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway ofStreptomyces avermitiliscontains two position-specific hydroxylases, C26-specific CYP105P1 and C1′-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-bound wild-type (WT-4PI), and ligand-free H72A mutant (H72A-free) forms. The BC loop region in the WT-free structure has a unique feature; the side chain of His72 within this region is ligated to the heme iron. On the other hand, this region is highly disordered and widely open in WT-4PI and H72A-free structures, respectively. Histidine ligation of wild-type CYP105P1 was not detectable in solution, and a type II spectral change was clearly observed when 4-phenylimidazole was titrated. The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein. In the H72A-free structure, there is a large pocket that is of the same size as the filipin molecule. The highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate.
Roles of ExoI and SbcCD Nucleases in “Reckless” DNA Degradation inrecAMutants ofEscherichia coli
Authors: Zahradka Ksenija , Buljubašić Maja , Petranović Mirjana , Zahradka Davor 
Published: December 2008

ABSTRACTExponentially growingrecAmutant cells ofEscherichia colidisplay pronounced DNA degradation that starts at the sites of DNA damage and depends on RecBCD nuclease (ExoV) activity. As a consequence of this “reckless” DNA degradation, populations ofrecAmutants contain a large proportion of anucleate cells. We have found that both DNA degradation and anucleate-cell production are efficiently suppressed by mutations in thexonA(sbcB) andsbcDgenes. The suppressive effects of these mutations were observed in normally grown, as well as in UV-irradiated,recAcells. The products of thexonAandsbcDgenes are known to code for the ExoI and SbcCD nucleases, respectively. Since bothxonAandsbcDmutations are required for strong suppression of DNA degradation while individual mutations have only a weak suppressive effect, we infer that ExoI and SbcCD play partially redundant roles in regulating DNA degradation inrecAcells. We suggest that their roles might be in processing (blunting) DNA ends, thereby producing suitable substrates for RecBCD binding.
Paroxetine-induced increase in LDL cholesterol levels
Authors: Le Melledo JM , Mailo K , Lara N , Abadia MC , Gil L , Van Ameringen M , Baker G , Perez-Parada J 
Published: December 2008

Abstract Paroxetine is widely prescribed because it has the indication for multiple psychiatric disorders. Our objective was to assess the effect of short-term administration of paroxetine on low-density lipoprotein cholesterol (LDL-C) levels in both healthy controls (HCs) and in patients with panic disorder (PD). Blood samples for measurement of LDL-C were collected atbaseline, after 8 weeks of paroxetine administration and post-discontinuation in 24 male HCs and nine male patients suffering from PD, for a total of 33 subjects. Paroxetine treatment, both in HCs and PD patients, induced a mean 9% increase per subject in LDL-C that normalized post-discontinuation, suggesting causality. The National Cholesterol Education Program (NCEP) guidelines suggest that this paroxetine-induced increase in LDL-C is clinically significant but would not warrant therapeutic intervention in this population selected to be at low cardiovascular risk. However, the increase in LDL-C levels raised above the threshold of 2.7 mmol/L (100 mg/dL) in 36% of our low-risk subjects. The LDL-C increase in this subgroup would be associated with a minor increase in coronary heart disease (CHD) risk. A similar 9% paroxetine-induced increase in LDL-C observed in the large number of psychiatric patients suffering from comorbid established CHD would be detrimental from a cardiovascular perspective and would oppose the new NCEP therapeutic goals of decreasing LDL-C levels by 30–40% in high and moderately high-risk patients. It is possible that longer treatment duration and use of higher doses of paroxetine would lead to a greater increase in LDL-C.
Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients
Authors: Fontana Raffaella , Bregni Marco , Cipponi Arcadi , Raccosta Laura , Rainelli Cristina , Maggioni Daniela , Lunghi Francesca , Ciceri Fabio , Mukenge Sylvain , Doglioni Claudio , Colau Didier , Coulie Pierre G. , Bordignon Claudio , Traversari Catia , Russo Vincenzo 
Published: December 2008

AbstractDendritic cell (DC) targeting in vivo has recently been shown to confer strong and protective cytotoxic T lymphocyte (CTL)–based immunity in tumor murine models. Our group has recently demonstrated in preclinical models that the infusion of genetically modified lymphocytes (GMLs) expressing the self/tumor antigen TRP-2 is able to elicit functional TRP-2–specific effectors with antitumor activity by targeting DCs in vivo. Here we have analyzed vaccine- and tumor-specific immune responses of 10 melanoma patients treated with autologous GMLs expressing the cancer germline gene MAGE-A3. Three of 10 patients treated with MAGE-A3–GML showed an increase of circulating anti–MAGE-A3 T cells, and developed skin delayed-type hypersensitivity to MAGE-A3. Interestingly, in 2 of these patients, with progressive and measurable tumors at study entry, anti–MAGE-A3 T cells were detected not only in the blood but also within tumors resected after vaccination. These results demonstrate that the infusion of MAGE-A3–GML elicits antitumor T cells, which are capable of trafficking to inflamed tissues and of infiltrating tumors. Clinical studies on a larger group of patients are needed to evaluate the clinical efficacy of such a strategy.
Cotreatment with BCL-2 antagonist sensitizes cutaneous T-cell lymphoma to lethal action of HDAC7-Nur77–based mechanism
Authors: Chen Jianguang , Fiskus Warren , Eaton Kelly , Fernandez Pravina , Wang Yongchao , Rao Rekha , Lee Pearl , Joshi Rajeshree , Yang Yonghua , Kolhe Ravindra , Balusu Ramesh , Chappa Prasanthi , Natarajan Kavita , Jillella Anand , Atadja Peter , Bhalla Kapil N. 
Published: December 2008

Abstract
Pan-histone deacetylase inhibitors, for example, vorinostat and panobinostat (LBH589; Novartis Pharmaceuticals, East Hanover, NJ), have shown clinical efficacy against advanced cutaneous T-cell lymphoma (CTCL). However, the molecular basis of this activity remains unclear. HDAC7, a class IIA histone deacetylase (HDAC), is overexpressed in thymocytes, where it represses expression of the proapoptotic nuclear orphan receptor Nur77. Here, we demonstrate that treatment with panobinostat rapidly inhibits the in vitro and intracellular activity, as well as the mRNA and protein levels of HDAC7, and induces expression and translocation of Nur77 to the mitochondria. There, Nur77 converts death resistance protein Bcl-2 into a killer protein, promoting cell death of cultured and patient-derived human CTCL cells. Treatment with panobinostat improved survival of athymic nude mice implanted with human CTCL cells. Ectopic expression of Nur77 induced apoptosis and sensitized HH cells to panobinostat, whereas combined knockdown of Nur77 and its family member Nor1 was necessary to inhibit panobinostat-induced apoptosis of CTCL cells. Cotreatment with the Bcl-2/Bcl-xL antagonist ABT-737 decreased resistance and synergistically induced apoptosis of human CTCL cells. These findings mechanistically implicate HDAC7 and Nur77 in sensitizing human CTCL cells to panobinostat as well as suggest that cotreatment with an anti–Bcl-2 agent would augment the anti-CTCL activity of panobinostat.
microRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia
Authors: Roccaro Aldo M. , Sacco Antonio , Chen Changzhong , Runnels Judith , Leleu Xavier , Azab Feda , Azab Abdel Kareem , Jia Xiaoying , Ngo Hai T. , Melhem Molly R. , Burwick Nicholas , Varticovski Lyuba , Novina Carl D. , Rollins Barrett J. , Anderson Kenneth C. , Ghobrial Irene M. 
Published: December 2008

AbstractMultilevel genetic characterization of Waldenström macroglobulinemia (WM) is required to improve our understanding of the underlying molecular changes that lead to the initiation and progression of this disease. We performed microRNA-expression profiling of bone marrow–derived CD19+ WM cells, compared with their normal cellular counterparts and validated data by quantitative reverse-transcription–polymerase chain reaction (qRT-PCR). We identified a WM-specific microRNA signature characterized by increased expression of microRNA-363*/-206/-494/-155/-184/-542-3p, and decreased expression of microRNA-9* (ANOVA; P < .01). We found that microRNA-155 regulates proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways. Potential microRNA-155 target genes were identified using gene-expression profiling and included genes involved in cell-cycle progression, adhesion, and migration. Importantly, increased expression of the 6 miRNAs significantly correlated with a poorer outcome predicted by the International Prognostic Staging System for WM. We further demonstrated that therapeutic agents commonly used in WM alter the levels of the major miRNAs identified, by inducing downmodulation of 5 increased miRNAs and up-modulation of patient-downexpressed miRNA-9*. These data indicate that microRNAs play a pivotal role in the biology of WM; represent important prognostic marker; and provide the basis for the development of new microRNA-based targeted therapies in WM.
Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice
Authors: Yamaza Takayoshi , Miura Yasuo , Akiyama Kentaro , Bi Yanming , Sonoyama Wataru , Gronthos Stan , Chen WanJun , Le Anh , Shi Songtao 
Published: December 2008

Abstract
Subcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age-related degeneration in multiple organs and benefited an increase in life span extension compared with control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor/signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.