bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of hypergravity stimulus on global gene expression during reproductive growth in Arabidopsis
Authors: Tamaoki D. , Karahara I. , Nishiuchi T. , Wakasugi T. , Yamada K. , Kamisaka S. 
Published: December 2013

AbstractThe life cycle of higher plants consists of successive vegetative and reproductive growth phases. Understanding effects of altered gravity conditions on the reproductive growth is essential, not only to elucidate how higher plants evolved under gravitational condition on Earth but also to approach toward realization of agriculture in space. In the present study, a comprehensive analysis of global gene expression of floral buds under hypergravity was carried out to understand effects of altered gravity on reproductive growth at molecular level. Arabidopsis plants grown for 20–26 days were exposed to hypergravity of 300 g for 24 h. Total RNA was extracted from flower buds and microarray (44 K) analysis performed. As a result, hypergravity up‐regulated expression of a gene related to β‐1,3‐glucanase involved in pectin modification, and down‐regulated β‐galactosidase and amino acid transport, which supports a previous study reporting inhibition of pollen development and germination under hypergravity. With regard to genes related to seed storage accumulation, hypergravity up‐regulated expression of genes of aspartate aminotransferase, and down‐regulated those related to cell wall invertase and sugar transporter, supporting a previous study reporting promotion of protein body development and inhibition of starch accumulation under hypergravity, respectively. In addition, hypergravity up‐regulated expression of G6PDH and GPGDH, which supports a previous study reporting promotion of lipid deposition under hypergravity. In addition, analysis of the metabolic pathway revealed that hypergravity substantially changed expression of genes involved in the biosynthesis of phytohormones such as abscisic acid and auxin.
Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots
Authors: Aubry‐Hivet D. , Nziengui H. , Rapp K. , Oliveira O. , Paponov I. A. , Li Y. , Hauslage J. , Vagt N. , Braun M. , Ditengou F. A. , Dovzhenko A. , Palme K. 
Published: December 2013

AbstractPlant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1−g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation‐related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella‐located PIN3 were stronger than in those deprived of the epidermis and cortex cell‐specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up‐regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis.
A Comprehensive Framework for Intrinsic OpenStreetMap Quality Analysis
Authors: Barron Christopher , Neis Pascal , Zipf Alexander 
Published: December 2013

AbstractOpenStreetMap (OSM) is one of the most popular examples of a Volunteered Geographic Information (VGI) project. In the past years it has become a serious alternative source for geodata. Since the quality of OSM data can vary strongly, different aspects have been investigated in several scientific studies. In most cases the data is compared with commercial or administrative datasets which, however, are not always accessible due to the lack of availability, contradictory licensing restrictions or high procurement costs. In this investigation a framework containing more than 25 methods and indicators is presented, allowing OSM quality assessments based solely on the data's history. Without the usage of a reference data set, approximate statements on OSM data quality are possible. For this purpose existing methods are taken up, developed further, and integrated into an extensible open source framework. This enables arbitrarily repeatable intrinsic OSM quality analyses for any part of the world.
Changes in blood transfusion practices in the UK role 3 medical treatment facility in Afghanistan, 2008–2011
Authors: Jansen J. O. , Morrison J. J. , Midwinter M. J. , Doughty H. 
Published: December 2013

SUMMARYObjectiveTo document blood component usage in the UK medical treatment facility, Afghanistan, over a period of 4 years; and to examine the relationship with transfusion capability, injury pattern and survival.BackgroundHaemostatic resuscitation is now firmly established in military medical practice, despite the challenges of providing such therapy in austere settings.Materials and MethodsRetrospective study of blood component use in service personnel admitted for trauma. Data were extracted from the UK Joint Theatre Trauma Registry.ResultsA total of 2618 patients were identified. Survival increased from 76 to 84% despite no change in injury severity. The proportion of patients receiving blood components increased from 13 to 32% per annum; 417 casualties received massive transfusion (≥10 units of RCC), the proportion increasing from 40 to 62%. Use of all blood components increased significantly in severely injured casualties, to a median (IQR) of 16 (9–25) units of red cell concentrate (P = 0·006), 15 (8–24) of plasma (P = 0·002), 2 (0–5) of platelets (P < 0·001) and 1 (0–3) of cryoprecipitate (P < 0·001). Cryoprecipitate (P = 0·009) and platelet use (P = 0·005) also increased in moderately injured casualties.ConclusionsThe number of blood components transfused to individual combat casualties increased during the 4‐year period, despite no change in injury severity or injury pattern. Survival also increased. Combat casualties requiring massive transfusion have a significantly higher chance of survival than civilian patients. Survival is the product of the entire system of care. However, we propose that the changes in military transfusion practice and capability have contributed to increased combat trauma survival.
Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study
Authors: Rigas Andreas Stribolt , Sørensen Cecilie Juul , Pedersen Ole Birger , Petersen Mikkel Steen , Thørner Lise Wegner , Kotzé Sebastian , Sørensen Erik , Magnussen Karin , Rostgaard Klaus , Erikstrup Christian , Ullum Henrik 
Published: December 2013

BackgroundDietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood.Study Design and MethodsIn the Danish Blood Donor Study, we assessed the effect of blood donation frequency, physiologic factors, lifestyle and supplemental factors, and dietary factors on ferritin levels. We used multiple linear and logistic regression analyses stratified by sex and menopausal status.ResultsAmong high‐frequency donors (more than nine donations in the past 3 years), we found iron deficiency (ferritin below 15 ng/mL) in 9, 39, and 22% of men, premenopausal women, and postmenopausal women, respectively. The strongest predictors of iron deficiency were sex, menopausal status, the number of blood donations in a 3‐year period, and the time since last donation. Other significant factors included weight, age, intensity of menstruation, iron tablets, vitamin pills, and consumption of meat and wine.ConclusionThe study confirms iron deficiency as an important problem, especially among menstruating women donating frequently. The risk of iron depletion was largely explained by sex, menopausal status, and donation frequency. Other factors, including dietary and supplemental iron intake, had a much weaker effect on the risk of iron depletion.
Monocytic suppressor cells derived from human peripheral blood suppress xenogenic immune reactions
Authors: Maeda Akira , Kawamura Takuji , Ueno Takehisa , Usui Noriaki , Miyagawa Shuji 
Published: December 2013

AbstractBackgroundMyeloid‐derived suppressor cells (MDSC) were initially found to contribute to the immunosuppression in tumor patients and have recently been recognized as a subset of innate immune cells that are capable of regulating adaptive immunity. A variety of innate immune stimuli such as Lipopolysaccharide (LPS), which act as a double‐edged sword, induce both the maturation of dendritic cells (DC) and the expansion of MDSCs.MethodsIn this study, we isolated MDSCs from peripheral blood mononuclear cells and examined the suppressive effect of MDSCs against cytotoxic T lymphocyte (CTL)‐mediated xenocytotoxicity.ResultsPeripheral blood monocytes cultured in the presence of GM‐CSF and IL‐4 were stimulated with polyiosinic‐polycytidylic acid [poly (I:C)] or LPS. Flow cytometric analyses revealed that LPS and poly I:C stimulation allows the CD33+ CD14+ HLA‐DR− subset to be significantly increased. To assess the suppressive capacity of MDSCs in xenotoxicity, CTL assay was performed. Poly (I:C)‐activated MDSCs dramatically suppressed the CTL xenocytotoxicity. Phagocytosis assays revealed that activated MDSCs aggressively phagocytose the xenogenic CTLs. Characterization of MDSCs by real‐time PCR revealed that poly (I:C) and LPS‐stimulated MDSCs expressed significant amounts of mRNA for indolamine 2,3‐dioxygenase (IDO) compared to untreated MDSCs. Furthermore, when MDSCs were incubated with the IDO inhibitor, the MDSC‐induced suppression of xenocytotoxicity was abolished. Taken together, the possibility that activated MDSCs could induce apoptosis in xenogenic CTLs via an IDO‐dependent manner and aggressively phagocytose apoptotic CTLs cannot be excluded.ConclusionThese findings indicate that MDSCs have a great deal of potential as a therapeutic strategy for dealing with xenograft rejection. Further investigations of the underlying mechanisms will facilitate the development of this therapeutic strategy.
Looping circuit: a novel mechanism for prolonged spontaneous [Ca2+]i increases in developing embryonic mouse brainstem
Authors: Watari Hirofumi , Tose Amanda J. , Bosma Martha M. 
Published: December 2013

Key points
Calcium concentration is kept at extremely low levels inside brain cells; each episode of calcium entry is cleared within seconds.
Changes in calcium entry are mediated by spontaneous activity in embryonic mouse brainstem from embryonic day 11.5 to 13.5.
Transiently, at embryonic day 12.5, spontaneous events occur frequently such that calcium concentration stays above baseline levels for minutes.
This unusual phenomenon, which we termed ‘bash bursts’, is caused by an event that propagates by looping along a defined path; the path gets modified a day later, ending it.
The results help us to understand how prolonged increases in calcium concentration can occur in development and how the increases may influence the development of serotonin and dopamine circuits that are related to neurological diseases later in life, such as depression and Parkinson's disease.
AbstractMost cells maintain [Ca2+]i at extremely low levels; calcium entry usually occurs briefly, and within seconds it is cleared. However, at embryonic day 12.5 in the mouse brainstem, trains of spontaneous events occur with [Ca2+]i staying close to peak value, well above baseline, for minutes; we termed this ‘bash bursts’. Here, we investigate the mechanism of this unusual activity using calcium imaging and electrophysiology. Bash bursts are triggered by an event originating at the mid‐line of the rostral hindbrain and are usually the result of that event propagating repeatedly along a defined circular path. The looping circuit can either encompass both the midbrain and hindbrain or remain in the hindbrain only, and the type of loop determines the duration of a single lap time, 5 or 3 s, respectively. Bash bursts are supported by high membrane excitability of mid‐line cells and are regulated by persistent inward ‘window current’ at rest, contributing to spontaneous activity. This looping circuit is an effective means for increasing [Ca2+]i at brief, regular intervals. Bash bursts disappear by embryonic day 13.5 via alteration of the looping circuit, curtailing the short epoch of bash bursts. The resulting sustained [Ca2+]i may influence development of raphe serotonergic and ventral tegmental dopaminergic neurons by modulating gene expression.
Huntingtin‐associated protein 1 regulates exocytosis, vesicle docking, readily releasable pool size and fusion pore stability in mouse chromaffin cells
Authors: Mackenzie Kimberly D. , Duffield Michael D. , Peiris Heshan , Phillips Lucy , Zanin Mark P. , Teo Ee Hiok , Zhou Xin‐Fu , Keating Damien J. 
Published: December 2013

Key points
Huntingtin‐associated protein 1 (HAP1) is expressed in neurons and endocrine cells, in which it is thought to regulate vesicle trafficking.
HAP1 is a binding partner of the Huntington's disease (HD)‐causing protein huntingtin, and binding is stronger in HD.
Whether HAP1 regulates a significant end‐point of vesicle transport, exocytosis, and what stage of exocytosis HAP1 may regulate, is unknown.
We use mouse chromaffin cells to demonstrate that HAP1 regulates exocytosis via two potentially interlinked mechanisms: control of vesicle docking and the readily releasable vesicle pool, and regulation of fusion pore stabilization.
These results establish HAP1 as a significant player in exocytosis control with potential relevance for HD and for a number of neuronal and homeostatic pathways.
AbstractHuntingtin‐associated protein 1 (HAP1) was initially established as a neuronal binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking and cell signalling. In this study, we establish that HAP1 is important in several steps of exocytosis in adrenal chromaffin cells. Using carbon‐fibre amperometry, we measured single vesicle exocytosis in chromaffin cells obtained from HAP1−/− and HAP1+/+ littermate mice. Numbers of Ca2+‐dependent and Ca2+‐independent full fusion events in HAP1−/− cells are significantly decreased compared with those in HAP1+/+ cells. We observed no change in the frequency of ‘kiss‐and‐run’ fusion events or in Ca2+ entry. Whereas release per full fusion event is unchanged in HAP1−/− cells, early fusion pore duration is prolonged, as indicated by the increased duration of pre‐spike foot signals. Kiss‐and‐run events have a shorter duration, indicating opposing roles for HAP1 in the stabilization of the fusion pore during full fusion and transient fusion, respectively. We use electron microscopy to demonstrate a reduction in the number of vesicles docked at the plasma membrane of HAP1−/− cells, where membrane capacitance measurements reveal the readily releasable pool of vesicles to be reduced in size. Our study therefore illustrates that HAP1 regulates exocytosis by influencing the morphological docking of vesicles at the plasma membrane, the ability of vesicles to be released rapidly upon stimulation, and the early stages of fusion pore formation.
Reduced Antimony Accumulation in
ARM58
-Overexpressing Leishmania infantum
Authors: Schäfer Carola , Tejera Nevado Paloma , Zander Dorothea , Clos Joachim 
Published: December 2013

ABSTRACT

Antimony-based drugs are still the mainstay of chemotherapy against
Leishmania
infections in many countries where the parasites are endemic. The efficacy of antimonials has been compromised by increasing numbers of resistant infections, the basis of which is not fully understood and likely involves multiple factors. By using a functional cloning strategy, we recently identified a novel antimony resistance marker,
ARM58
, from the parasite
Leishmania braziliensis
that protects the parasites against antimony-based antileishmanial compounds. Here we show that the
Leishmania infantum
homologue also confers resistance against antimony but not against other antileishmanial drugs and that its function depends critically on one of four conserved domains of unknown function. This critical domain requires at least two hydrophobic amino acids and is predicted to form a transmembrane structure. Overexpression of ARM58 in antimony-exposed parasites reduces the intracellular Sb accumulation by over 70%, indicating a role for ARM58 in Sb extrusion pathways, but without involvement of energy-dependent transporter proteins.
KAI407, a Potent Non-8-Aminoquinoline Compound That Kills Plasmodium cynomolgi Early Dormant Liver Stage ParasitesIn Vitro
Authors: Zeeman Anne-Marie , van Amsterdam Sandra M. , McNamara Case W. , Voorberg-van der Wel Annemarie , Klooster Els J. , van den Berg Alexander , Remarque Edmond J. , Plouffe David M. , van Gemert Geert-Jan , Luty Adrian , Sauerwein Robert , Gagaring Kerstin , Borboa Rachel , Chen Zhong , Kuhen Kelli , Glynne Richard J. , Chatterjee Arnab K. , Nagle Advait , Roland Jason , Winzeler Elizabeth A. , Leroy Didier , Campo Brice , Diagana Thierry T. , Yeung Bryan K. S. , Thomas Alan W. , Kocken Clemens H. M. 
Published: December 2013

ABSTRACTPreventing relapses ofPlasmodium vivaxmalaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay ofin vitro-cultured hypnozoite forms ofPlasmodium cynomolgi(an excellent and accessible model forPlasmodium vivax). In this assay, primary rhesus hepatocytes are infected withP. cynomolgisporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class forP. vivaxmalaria prophylaxis and potentially a radical cure.
Green Fluorescent Diamidines as Diagnostic Probes for Trypanosomes
Authors: Giordani Federica , Munde Manoj , Wilson W. David , Ismail Mohamed A. , Kumar Arvind , Boykin David W. , Barrett Michael P. 
Published: December 2013

ABSTRACT
Light-emitting diode (LED) fluorescence microscopy offers potential benefits in the diagnosis of human African trypanosomiasis and in other aspects of diseases management, such as detection of drug-resistant strains. To advance such approaches, reliable and specific fluorescent markers to stain parasites in human fluids are needed. Here we describe a series of novel green fluorescent diamidines and their suitability as probes with which to stain trypanosomes.
Molecular Identification and Antifungal Susceptibility of Yeast Isolates Causing Fungemia Collected in a Population-Based Study in Spain in 2010 and 2011
Authors: Guinea Jesús , Zaragoza Óscar , Escribano Pilar , Martín-Mazuelos Estrella , Pemán Javier , Sánchez-Reus Ferrán , Cuenca-Estrella Manuel 
Published: December 2013

ABSTRACT

We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were
Candida albicans
(44.6%),
Candida parapsilosis
(24.5%),
Candida glabrata
(13.2%),
Candida tropicalis
(7.6%),
Candida krusei
(1.9%),
Candida guilliermondii
(1.7%), and
Candida lusitaniae
(1.3%). Other
Candida
and non-
Candida
species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of
C. glabrata
has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of
C. glabrata
. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole
in vitro
resistance was low (<2%). In the case of
C. tropicalis
, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from
FKS1
or
FKS2
genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.
In Vitro
Activity of Nemonoxacin, a Novel Nonfluorinated Quinolone Antibiotic, against Chlamydia trachomatis and Chlamydia pneumoniae
Authors: Chotikanatis Kobkul , Kohlhoff Stephan A. , Hammerschlag Margaret R. 
Published: December 2013

ABSTRACT

The
in vitro
activities of nemonoxacin, levofloxacin, azithromycin, and doxycycline were tested against 10 isolates each of
Chlamydia trachomatis
and
Chlamydia pneumoniae
. The MICs at which 90% of the isolates of both
C. trachomatis
and
C. pneumoniae
were inhibited (MIC
90
s) were 0.06 μg/ml (range, 0.03 to 0.13 μg/ml). The minimal bactericidal concentrations at which 90% of the isolates were killed by nemonoxacin (MBC
90
s) were 0.06 μg/ml for
C. trachomatis
(range, 0.03 to 0.125 μg/ml) and 0.25 for
C. pneumoniae
(range, 0.015 to 0.5 μg/ml).