bluuebunny/crossref_metadata_2025 huggingface dataset:
Raclopride or high‐frequency stimulation of the subthalamic nucleus stops cocaine‐induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits
Authors: Aliane Verena , Pérez Sylvie , Deniau Jean‐Michel , Kemel Marie‐Louise
Published: July 2012

Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico‐basal ganglia circuits. Indeed, cortico‐nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high‐frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine‐induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine‐induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico‐nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N‐methyl‐d‐aspartic‐acid‐evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico‐substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine‐induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits.
Comparative proteomic analysis reveals insights into anoxic growth of Methyloversatilis universalis FAM5 on methanol and ethanol
Authors: Lu Huijie , Kalyuzhnaya Marina , Chandran Kartik
Published: July 2012

Methyloversatilis universalis FAM5 is a facultative methylotrophic bacterium that has been found in a variety of natural and engineered ecosystems. The goal of this study was to investigate M. universalis FAM5 responses to different electron/carbon donors, e.g. methanol or ethanol, during anoxic growth in chemostats with nitrate as the electron acceptor. During steady‐state anoxic growth on either methanol or ethanol, over 90% of the influent nitrate was reduced primarily to nitrite. The cell yield on methanol was lower, possibly due to high energy requirements for C1 assimilation. Label‐free proteomics further revealed that methanol‐grown cells displayed elevated concentrations of the enzymes involved in C1 metabolism (H4MPT/H4F pathways, formate oxidation and serine cycle). In contrast, C2 metabolism (glyoxylate shunt and tri‐carboxylic acid cycle) and polyhydroxy‐β‐butyrate (PHB) synthesis related proteins were overrepresented during subsequent growth on ethanol. Notably, the expression of respiratory nitrate reductase was not affected by the carbon sources applied. Furthermore, the changes in the proteome upon switching back to methanol were mostly reversible. Therefore, M. universalis displays wide‐ranging responses to adapt between growth on methanol and ethanol. Such metabolic versatility could be particularly useful in wastewater treatment systems, which need to switch between different electron donors, while still reliably meeting effluent nitrogen discharge goals.
Surgical outcomes in steroid refractory acute severe ulcerative colitis: the impact of rescue therapy
Authors: Powar M. P. , Martin P. , Croft A. R. , Walsh A. , Petersen D. , Stevenson A. R. L. , Lumley J. W. , Stitz R. W. , Radford‐Smith G. L. , Clark D. A.
Published: July 2012

Aim  The advent of rescue medical therapy (cyclosporin or infliximab) and laparoscopic surgery has shifted the paradigm in managing steroid refractory acute severe ulcerative colitis (ASUC). We investigated prospectively the impact of rescue therapy on timing and postoperative complications of urgent colectomy and subsequent restorative surgery for steroid refractory ASUC.

Method  All consecutive presentations of steroid refractory ASUC at the Royal Brisbane Hospital (1996–2009) were entered in the study. Data collated included demographics, clinical and laboratory parameters on admission, medical therapy and operative and postoperative details. Steroid refractory ASUC patients undergoing immediate colectomy were compared with those failing rescue therapy and requiring same admission colectomy.

Results  Of 108 steroid refractory ASUC presentations, 19 (18%) received intravenous steroids only and proceeded directly to colectomy. Rescue medical therapy was instituted in 89 (82%) patients with 30 (34%) failing to respond and proceeding to colectomy. There was no significant difference in the median time from admission to colectomy for rescue therapy compared with steroid‐only cases (12 vs 10 days, P = 0.70) or 30‐day complication rates (27%vs 47%, P = 0.22). The interval from colectomy to a subsequent restorative procedure was significantly longer for patients who failed rescue therapy (12 vs 5 months, P = 0.02). Furthermore 30‐day complications following pouch surgery were significantly higher in patients who failed rescue therapy (32%vs 0%, P = 0.01).

Conclusion  Rescue therapy in steroid refractory ASUC is not related to delay in urgent colectomy or increased post‐colectomy complications.
Large‐scale transcriptome characterization and mass discovery of SNPs in globe artichoke and its related taxa
Authors: Scaglione Davide , Lanteri Sergio , Acquadro Alberto , Lai Zhao , Knapp Steven J. , Rieseberg Loren , Portis Ezio
Published: July 2012

Cynara cardunculus (2n = 2× = 34) is a member of the Asteraceae family that contributes significantly to the agricultural economy of the Mediterranean basin. The species includes two cultivated varieties, globe artichoke and cardoon, which are grown mainly for food. Cynara cardunculus is an orphan crop species whose genome/transcriptome has been relatively unexplored, especially in comparison to other Asteraceae crops. Hence, there is a significant need to improve its genomic resources through the identification of novel genes and sequence‐based markers, to design new breeding schemes aimed at increasing quality and crop productivity. We report the outcome of cDNA sequencing and assembly for eleven accessions of C. cardunculus. Sequencing of three mapping parental genotypes using Roche 454‐Titanium technology generated 1.7 × 106 reads, which were assembled into 38 726 reference transcripts covering 32 Mbp. Putative enzyme‐encoding genes were annotated using the KEGG‐database. Transcription factors and candidate resistance genes were surveyed as well. Paired‐end sequencing was done for cDNA libraries of eight other representative C. cardunculus accessions on an Illumina Genome Analyzer IIx, generating 46 × 106 reads. Alignment of the IGA and 454 reads to reference transcripts led to the identification of 195 400 SNPs with a Bayesian probability exceeding 95%; a validation rate of 90% was obtained by Sanger‐sequencing of a subset of contigs. These results demonstrate that the integration of data from different NGS platforms enables large‐scale transcriptome characterization, along with massive SNP discovery. This information will contribute to the dissection of key agricultural traits in C. cardunculus and facilitate the implementation of marker‐assisted selection programs.
Why does vulnerability to toxic invasive cane toads vary among populations of Australian freshwater crocodiles?
Authors: Somaweera R. , Shine R. , Webb J. , Dempster T. , Letnic M.
Published: July 2012

The ecological impact of an invasive species can be heterogeneous through space and time. One such case in Australia involves native freshwater crocodiles Crocodylus johnstoni, which are highly sensitive to invasive cane toads Rhinella marina in some areas, whereas other populations experience little or no mortality from ingestion of the toxic toads. We studied the impact of toad invasion on three crocodile populations: one crashed, one showed a minor decrease and one appeared unaffected. We tested three hypotheses for the cause of this spatial variation in impact: differences among populations in toad–crocodile encounter rates (proximity of toads to crocodiles during spotlight surveys), differences in crocodile feeding responses (trials of prey preference in the laboratory) and differences in crocodile physiology (reduction of swim speed after receiving a dose of toad toxin). We found little divergence among populations in any of these traits: crocodiles from the three populations all encountered cane toads in the wild, and exhibited similar feeding responses and toxin tolerances. Thus, we cannot confidently identify causation for the impact heterogeneity. Reliance on alternative food resources and an ability to rapidly learn taste aversion may have allowed crocodiles to deal with toad arrival in Lake Argyle and the Daly River. Future work could usefully evaluate potential explanations for the failure of these adaptive mechanisms in the severely affected (Victoria River) population. We suggest that spatial variation in the availability of alternative prey (and thus the willingness of crocodiles to attack a novel toxic prey item) may have contributed to that variation in impact.
Activation of PAR2 receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint
Authors: Russell FA , Schuelert N , Veldhoen VE , Hollenberg MD , McDougall JJ
Published: July 2012

Background and Purpose

The PAR2 receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR2 activation in the rat knee joint.

Experimental Approach

PAR2 in rat knee joint dorsal root ganglia (DRG) cells at L3‐L5, retrogradely labelled with Fluoro‐gold (FG) were demonstrated immunohistochemically. Electrophysiological recordings from knee joint nerve fibres in urethane anaesthetized Wistar rats assessed the effects of stimulating joint PAR2 with its activating peptide, 2‐furoyl‐LIGRLO‐NH2 (1–100 nmol·100 μL−1, via close intra‐arterial injection). Fibre firing rate was recorded during joint rotations before and 15 min after administration of PAR2 activating peptide or control peptide. Leukocyte kinetics in the synovial vasculature upon PAR2 activation were followed by intravital microscopy for 60 min after perfusion of 2‐furoyl‐LIGRLO‐NH2 or control peptide. Roles for transient receptor potential vanilloid‐1 (TRPV1) or neurokinin‐1 (NK1) receptors in the PAR2 responses were assessed using the selective antagonists, SB366791 and RP67580 respectively.

Key Results

PAR2 were expressed in 59 ± 5% of FG‐positive DRG cells; 100 nmol 2‐furoyl‐LIGRLO‐NH2 increased joint fibre firing rate during normal and noxious rotation, maximal at 3 min (normal; 110 ± 43%, noxious; 90 ± 31%). 2‐Furoyl‐LIGRLO‐NH2 also significantly increased leukocyte rolling and adhesion over 60 min. All these effects were blocked by pre‐treatment with SB366791 and RP67580 (P < 0.05 compared with 2‐furoyl‐LIGRLO‐NH2 alone).

Conclusions and Implications

PAR2 receptors play an acute inflammatory role in the knee joint via TRPV1‐ and NK1‐dependent mechanisms involving both PAR2‐mediated neuronal sensitization and leukocyte trafficking.
Transient Sulcal Hyperintensities on Fluid‐Attenuated Inversion Recovery in Migraine With Aura
Authors: Kang Kyung‐Wook , Kim Joon‐Tae , Chang Jane , Choi Won‐Ho , Lim Daekeon , Bang Dong‐Ho , Choi Yun Ju
Published: July 2012

Migraine has been found to be associated with patent foramen ovale. However, in practice, it is difficult to show that microemboli via patent foramen ovale can induce a migraine attack. Our patient showed transient sulcal hyperintensities on fluid‐attenuated inversion recovery images during a migraine attack. This supports the hypothesis that microemboli via right‐to‐left shunt may induce migraine attacks through transient occlusion of microcirculation.
Comparative in vitro analysis of different hematopoietic cell populations from human cord blood: in search of the best option for clinically oriented ex vivo cell expansion
Authors: Flores‐Guzman Patricia , Fernandez‐Sanchez Veronica , Valencia‐Plata Ignacio , Arriaga‐Pizano Lourdes , Alarcon‐Santos Guadalupe , Mayani Hector
Published: July 2012

BACKGROUND: Ex vivo expansion of hematopoietic stem and progenitor cells has become a priority in the experimental hematology arena. In this study we have obtained different hematopoietic cell populations from umbilical cord blood and simultaneously assessed their proliferation and expansion kinetics. Our main goal was to determine which one of these cell populations would be more suitable for clinical‐grade ex vivo expansion.

STUDY DESIGN AND METHODS: By using immunomagnetic‐negative selection and cell sorting, five cell populations were obtained: unseparated mononuclear cells (MNCs; I); two lineage‐negative cell populations, one enriched for CD34+ CD38+ cells (II) and the other enriched for CD34+ CD38− cells (III); and two CD34+ cell fractions purified by fluorescence‐activated cell sorting, one containing CD34+ CD38+ cells (IV) and the other containing CD34+ CD38− cells (V). The kinetics of such populations were analyzed in both relative and absolute terms.

RESULTS: No expansion was observed in Population I; in contrast, significant increments in the numbers of both progenitor and stem cells were observed in cultures of Populations II to V. Population V (reaching 12,800‐fold increase in total cells; 1280‐fold increase in CD34+ cells; 490‐fold increase in colony‐forming cells; and 12‐fold increase in long‐term culture–initiating cells) showed the highest proliferation and expansion potentials.

CONCLUSION: Our study suggests that the cell fraction containing greater than 98% CD34+ CD38− cells would be the ideal one for large‐scale ex vivo expansion; however, based on our data, it seems that, except for MNCs, all other cell populations could also be used as input cell fractions.
Evaluating the 4‐hour and 30‐minute rules: effects of room temperature exposure on red blood cell quality and bacterial growth
Authors: Ramirez‐Arcos Sandra , Mastronardi Cherie , Perkins Heather , Kou Yuntong , Turner Tracey , Mastronardi Emily , Hansen Adele , Yi Qi‐Long , McLaughlin Natasha , Kahwash Eiad , Lin Yulia , Acker Jason
Published: July 2012

BACKGROUND: A 30‐minute rule was established to limit red blood cell (RBC) exposure to uncontrolled temperatures during storage and transportation. Also, RBC units issued for transfusion should not remain at room temperature (RT) for more than 4 hours (4‐hour rule). This study was aimed at determining if single or multiple RT exposures affect RBC quality and/or promote bacterial growth.

STUDY DESIGN AND METHODS: Growth and RT exposure experiments were performed in RBCs inoculated with Serratia liquefaciens and Serratia marcescens. RBCs were exposed once to RT for 5 hours (S. liquefaciens) or five times to RT for 30 minutes (S. marcescens) with periodic sampling for bacterial counts. Noncontaminated units were exposed to RT once (5 hr) or five times (30 min each) and sampled to measure in vitro quality variables. RBC core temperature was monitored using mock units with temperature loggers. Growth and RT exposure experiments were repeated three and at least six times, respectively. Statistical analysis was done using mixed‐model analysis.

RESULTS: RBC core temperature ranged from 7.3 to 11.6°C during 30‐minute RT exposures and the time to reach 10°C varied from 22 to 55 minutes during 5‐hour RT exposures. RBC quality was preserved after single or multiple RT exposures. Increased growth of S. liquefaciens was only observed after 2 hours of continuous RT exposure. S. marcescens concentration increased significantly in multiple‐exposed units compared to the controls but did not reach clinically important levels.

CONCLUSION: Single or multiple RT exposures did not affect RBC quality but slightly promoted bacterial growth in contaminated units. The clinical significance of these results remains unclear and needs further investigation.
Semaphorin 7A protein variants differentially regulate T‐cell activity
Authors: Gras Christiane , Eiz‐Vesper Britta , Seltsam Axel , Immenschuh Stephan , Blasczyk Rainer , Figueiredo Constança
Published: July 2012

BACKGROUND: Semaphorin 7A (Sema7A) carries the John‐Milton‐Hagen human blood group antigen on red blood cells and shows molecular diversity. It is known that Sema7A has immunomodulatory functions, but its regulatory effects on T‐cell activation are not completely understood. In this study, the functional role of the R461C Sema7A polymorphism on T‐cell responses was investigated.

STUDY DESIGN AND METHODS: Soluble recombinant wild‐type Sema7A (Sema7A_wt) and its R461C variant (Sema7A_R461C) were produced in human embryonic kidney cells. Specific assays were performed to determine the effects of Sema7A_wt and Sema7A_R461C on T‐cell activation in terms of proliferation, phenotypic alterations, granzyme B transcript levels, and secretion of proinflammatory cytokines.

RESULTS: Sema7A_wt did not affect T‐cell activity, but Sema7A_R461C led to marked antigen‐independent activation of T cells. In the presence of antigen stimulation, Sema7A_R461C had a major costimulatory effect on T‐cell response. Upon Sema7A_R461C stimulation, CD4+ T cells strongly proliferated and exhibited a cytotoxic phenotype with significant up regulation of granzyme B transcripts (up to 220‐fold), even in the absence of antigen stimulation. Antibody blocking studies indicated that Sema7A_R461C‐mediated T‐cell activation is largely β1 integrin dependent.

CONCLUSION: These data demonstrate that Sema7A_R461C, unlike wild‐type Sema7A, causes differential regulation of T‐cell responses. Since Sema7A has important immunomodulatory functions in inflammatory responses, it might play a key role in autoimmune diseases and other major disorders. Further studies are needed to elucidate the regulatory role of Sema7A and its variants.
Routine use of a rapid test to detect bacteria at the time of issue for nonleukoreduced, whole blood–derived platelets
Authors: Harm Sarah K. , Delaney Meghan , Charapata Michael , AuBuchon James P. , Triulzi Darrell J. , Yazer Mark H.
Published: July 2012

BACKGROUND: The Pan Genera detection (PGD) test is used to screen platelet (PLT) products for bacterial contamination. We report the experience of using the PGD test on whole blood–derived PLTs (WBPs) at two large centralized transfusion services (CTS).

STUDY DESIGN AND METHODS: Records of PGD test results were retrospectively reviewed. The PGD test was performed on individual WBP units or pools of WBPs ranging in size from 2 to 6 units at the time of issue. Bacterial culture was performed on PLT products with positive PGD tests, and at one CTS, the available cocomponents.

RESULTS: A total of 70,561 WBP pools were screened with the PGD test. There were seven true‐positive PGD tests and 242 false‐positive tests (positive predictive value of PGD test, 2.81%). The overall contamination rate was 99 per 106 WBP pools (1:10,080; 95% confidence interval [CI], 40‐204), and the false‐positive rate was 3430 per 106 WBP pools (1:292; 95% CI, 3011‐3890). All seven bacterial isolates were Gram positive. The median age of the individual WBP units in the seven contaminated pools was 5 days (range, 3‐5 days) compared to 4 days (range, 1‐5 days) in the false‐positive pools (p = 0.0012). The same bacteria isolated from a positive PLT pool also grew in one red blood cell cocomponent.

CONCLUSION: After testing more than 70,000 WBP pools at two large CTSs, the rate of contaminated WBP pools detected by the PGD test was 99 per 106 pools (1:10,080).
Synthesis and Luminescence Properties of Mg–Si Co‐doped Tb3Al5O12:Ce3+ Phosphors with Blue Excitation for White LEDs
Authors: Luo Hongde , Liu Jie , Zheng Xiao , Xu Bo , Lu Yiming , Han Lixian , Ren Kuaixia , Yu Xibin
Published: July 2012

Tb2.94MgxAl5−2xSixO12:Ce3+0.06 (TMASG: Ce) were synthesized by high temperature Solid‐State Reaction (SSR) at different temperatures from 1650°C to 1550°C. Samples with x = 0.1, 0.2, 0.3, 0.6 were fabricated and characterized using powder X‐ray diffraction (XRD) and room‐temperature photoluminescence spectroscopy. In this work, the excitation and emission spectra indicate that the phosphor can be excited effectively by the blue light (450–550 nm) and exhibit a satisfactory orange–yellow emission from 550 to 575 nm. The reasons of the red‐shift of the phosphor have been discussed. A crystal field analysis of the Ce3+ 5d energy levels is conducted to explain the correlation between the TMASG:Ce lattice expansion and the Ce3+ energy level changes. The chromaticity coordinates of the phosphors are tuned from (0.465, 0.527) to (0.512, 0.483). This indicates a prospective for application of this novel phosphor in white light emitting diodes (LEDs).
Critical size defect regeneration using PEG‐mediated BMP‐2 gene delivery and the use of cell occlusive barrier membranes – the osteopromotive principle revisited
Authors: Wehrhan Falk , Amann Kerstin , Molenberg Aart , Lutz Rainer , Neukam Friedrich W. , Schlegel Karl A.
Published: July 2012

Objective

The objective of this study was to investigate if osseous regeneration can be accelerated by involvement of periosteal tissue. Bone defect regeneration could be accelerated by the involvement of periosteal tissue if osteogenic cell signalling is maintained within the defect. It was questioned if local cell‐mediated BMP‐2 gene delivery makes a cell occlusive membrane dispensable during bone critical size defect regeneration.

Methods

PEG matrix (degradation time 10 days) and PEG membrane (degradation time 120 days) were used in the pig calvarial model. Cylindrical (1 × 1 cm) critical size defects (CSD) (9 per animal; 20 animals) were filled with: (i) particulated autologous bone, covered with PEG membrane (group 1); (ii) HA/TCP, covered with PEG membrane (group 2); (iii) HA/TCP, mixed with PEG matrix (group 3); and (iv) HA/TCP mixed with BMP‐2‐transfected osteoblasts and PEG matrix (group 4). BMP‐2/4 gene transfer: liposomal in vitro transfection of BMP‐2/V5‐tag fusion‐protein. Quantitative histomorphometry (toluidine blue staining) after 2, 4 and 12 weeks assessed bone formation. Semiquantitative immunohistochemistry estimated the expression of BMP‐2, V5‐tag, Runx‐2 and Sox9.

Results

PEG matrix embedded BMP‐2 expressing cells presented higher bone formation (P < 0.05) than HA/TCP + PEG matrix defect filling or PEG membrane covering (HA/TCP filling) after 12 weeks. Highest expression of BMP‐2, Runx‐2 and lowest expression of fibrous tissue marker Sox9 was seen in the BMP‐2 group.

Conclusion

PEG matrix embedded BMP‐2 expressing cells are capable to maintain osteogenic signalling and to accelerate osseous defect regeneration in absence of a cell occlusive membrane.
The impact of hospitalization on dental plaque accumulation: an observational study
Authors: Needleman Ian , Hyun‐Ryu Jung , Brealey David , Sachdev Mishal , Moskal‐Fitzpatrick Donna , Bercades Georgia , Nagle Janette , Lewis Katherine , Agudo Elisa , Petrie Aviva , Suvan Jean , Donos Nikos , Singer Mervyn
Published: July 2012

Aim

To investigate the effect of hospitalization on oral health as assessed by dental plaque.

Materials and Methods

Observational study in a critical care unit (CCU). Participants were recruited within 24 h of admission. Dental plaque amount was assessed at baseline, 1 and 2 weeks using the Debris index‐soft deposits (Greene & Vermillion 1960).

Results

Fifty participants were recruited with 36 available for outcome assessment at 1 week and 10 at 2 weeks. The principal reason for losses was early discharge with no evidence of a difference between patients present only at baseline and those present at 1 week. The median value for dental plaque at baseline was 4 (95% CI: 4, 6). The median dental plaque increase from baseline to week 1 was 1.5 (95% CI: −1, 4), and this was statistically significant (p = 0.04). The median increase from week 1 to week 2 was 1.0 (95% CI −8, 6) and not statistically significant (p = 0.68).

Conclusions

Oral health as assessed by dental plaque deteriorates following hospitalization in CCU. Such change could lead to impairment of quality of life and well‐being as well as to increasing the risk of important healthcare‐associated infections such as nosocomial pneumonia.
Effects of different manual periodontal probes on periodontal measurements
Authors: Holtfreter Birte , Alte Dietrich , Schwahn Christian , Desvarieux Moïse , Kocher Thomas
Published: July 2012

Aim

To quantify the digit preference effect for three manual periodontal probes and to calculate correction values to enable comparison of studies with equal recording protocols, but different periodontal probes.

Material and Methods

A prospective in vivo crossover study was conducted with a six‐sequence three‐period design. Six examiners assessed attachment loss (AL), probing pocket depth (PD) and gingiva height (GH) at four surfaces, full‐mouth, in six generally healthy subjects using three manual probes: PCP11 (3‐3‐3‐2 mm increments), PCP2 (2 mm increments), and PCPUNC15 (1 mm increments).

Results

Distributions of AL, PD and GH differed between probes (p < 0.001). Compared with PCPUNC15, periodontal measurements coinciding with probe markings of PCP11 and PCP2, respectively, were preferentially named by examiners. Digit preference was most pronounced for PD, but less for AL and GH. In multilevel models, PD differed significantly between all three probes (p < 0.05); probe‐ and examiner‐related effects were also observed for AL and GH. Correction values for pairwise combinations of probes were determined.

Conclusions

We provided empirical evidence and quantified the effect of probe type on periodontal measurements. Differences in probe type should be considered when comparing periodontal data within and between epidemiological studies and appropriate corrections, provided here, should be applied.
Arbuscular mycorrhizal fungi in a wetland constructed for benzene‐, methyl tert‐butyl ether‐ and ammonia‐contaminated groundwater bioremediation
Authors: Fester Thomas
Published: July 2012

Arbuscular mycorrhizal fungi (AMF), which are present in most natural environments, have demonstrated capacity to promote biodegradation of organic pollutants in the greenhouse. However, it is not certain whether AMF can spontaneously establish in phytoremediation systems constructed to decontaminate groundwater, because of the unusual conditions during the construction and operation of such systems. To assess this possibility, root samples from a wetland constructed for the phytoremediation of groundwater contaminated with benzene, methyl tert‐butyl ether and ammonia were analysed. Substantial AMF colonization was observed in plant roots sampled close to the inlet of a basin filled with fine gravel and planted with Phragmites australis. In addition, analysis of a fragment of the nuclear large ribosomal subunit, amplified by nested PCR, revealed the presence of AMF molecular operational taxonomic units closely related to Funneliformis mosseae and Rhizophagus irregularis in the samples. These findings demonstrate the capacity of generalist AMF strains to establish spontaneously, rapidly and extensively in groundwater bioremediation technical installations.
Commensal Escherichia coli strains in Guiana reveal a high genetic diversity with host‐dependant population structure
Authors: Lescat Mathilde , Clermont Olivier , Woerther Paul Louis , Glodt Jérémy , Dion Sara , Skurnik David , Djossou Felix , Dupont Claire , Perroz Gilles , Picard Bertrand , Catzeflis François , Andremont Antoine , Denamur Erick
Published: July 2012

We undertook a large‐scale epidemiological survey of commensal Escherichia coli in Trois‐Sauts, an isolated village located in the south of French Guiana where human population exchanges are restricted and source of antibiotics controlled. Stools from 162 Wayampi Amerindians and rectal swabs from 33 human associated and 198 wild animals were collected in the close proximity of the village. The prevalence of E. coli was decreasing from humans (100%) to human associated (64%) and wild (45%) animals. A clear genetic structure between these three E. coli populations was observed with human strains belonging very rarely to B2 phylogroup (3.7%), exhibiting few virulence genes and bacteriocins but being antibiotic resistant whereas wild animal strains were characterized by 46.1% of B2 phylogroup belonging, with very unique and infrequent sequence types, numerous extraintestinal genes and bacteriocins but no antibiotic resistance; the human‐associated animal strains being intermediate. Furthermore, an unexpected genetic diversity was observed among the strains, as the housekeeping gene nucleotide diversity per site of the Trois‐Sauts's strains was higher than the one of reference strains representative of the known species diversity. The existence of such E. coli structured phylogenetic diversity within various hosts of a single localization has never been reported.
Lunar meteorites from Oman
Authors: KOROTEV Randy L.
Published: July 2012

Abstract– Sixty named lunar meteorite stones representing about 24 falls have been found in Oman. In an area of 10.7 × 103 km2 in southern Oman, lunar meteorite areal densities average 1 g km−2. All lunar meteorites from Oman are breccias, although two are dominated by large igneous clasts (a mare basalt and a crystalline impact‐melt breccia). Among the meteorites, the range of compositions is large: 9–32% Al2O3, 2.5–21.1% FeO, 0.3–38 μg g−1 Sm, and <1 to 22.5 ng g−1 Ir. The proportion of nonmare lunar meteorites is higher among those from Oman than those from Antarctica or Africa. Omani lunar meteorites extend the compositional range of lunar rocks as known from the Apollo collection and from lunar meteorites from other continents. Some of the feldspathic meteorites are highly magnesian (high MgO/[MgO + FeO]) compared with most similarly feldspathic Apollo rocks. Two have greater concentrations of incompatible trace elements than all but a few Apollo samples. A few have moderately high abundances of siderophile elements from impacts of iron meteorites on the Moon. All lunar meteorites from Oman are contaminated, to various degrees, with terrestrial Na, K, P, Zn, As, Se, Br, Sr, Sb, Ba, U, carbonates, or sulfates. The contamination is not so great, however, that it seriously compromises the scientific usefulness of the meteorites as samples from randomly distributed locations on the Moon.
A global rain of micrometeorites following breakup of the L‐chondrite parent body—Evidence from solar wind‐implanted Ne in fossil extraterrestrial chromite grains from China
Authors: ALWMARK C. , SCHMITZ B. , MEIER M. M. M. , BAUR H. , WIELER R.
Published: July 2012

Abstract– Previous studies of limestone beds of mid‐Ordovician age from both Sweden and China show that the Earth saw an at least two orders of magnitude increase in the influx of extraterrestrial material approximately 470 Ma, following the disruption of an L‐chondrite parent body in the asteroid belt. Recovered extraterrestrial material consists of fossil meteorites and sediment‐dispersed extraterrestrial chromite (SEC) grains, both with L‐chondritic origin. Ne isotope analysis of SEC grains from one of the Swedish limestone sections revealed that the vast majority of the grains were delivered to Earth as micrometeorites. In this study, we extend the previous work, both in time and geographically, by measuring concentrations and isotopic ratios of Ne in individual SEC grains (60–120 μm in diameter) from three different beds from a contemporary Middle Ordovician limestone section in China. All of the Chinese SEC grains, 44 in total, contain surface‐implanted Ne of fractionated solar wind composition, implying that these grains were, as in the case of the Swedish SEC grains, delivered to Earth as micrometeorites. This gives further compelling evidence that the two to three orders of magnitude increase in the influx of micrometeoritic material following the breakup of the L‐chondrite parent body was indeed a global event. The rain of micrometeorites prevailed for at least 2 Myr (the estimated time of the deposition of the topmost Chinese bed) after the breakup event.
Nuclear factor‐κB signalling and transcriptional regulation in skeletal muscle atrophy
Authors: Jackman Robert W. , Cornwell Evangeline W. , Wu Chia‐Ling , Kandarian Susan C.
Published: July 2012

New findings

What is the topic for this review?

An up‐to‐date analysis on the role of nuclear factor‐κB signaling and transcriptional control in adult skeletal muscle atrophy.

What advances does it highlight?

Our analysis of the literature and research in our laboratory has allowed us to propose interpretations that have not previously been published. We believe these interpretations will be of interest to scientists studying the cellular control of adult skeletal muscle atrophy.

The nuclear factor‐κB (NF‐κB) signalling pathway is a necessary component of adult skeletal muscle atrophy resulting from systemic illnesses or disuse. Studies showing a role for the NF‐κB pathway in muscle disuse include unloading, denervation and immobilization, and studies showing a role for NF‐κB in systemic illnesses include cancer, chronic heart failure and acute septic lung injury. Muscle atrophy due to most of these triggers is associated with activation of NF‐κB transcriptional activity. With the exception of muscle unloading, however, there is a paucity of data on the NF‐κB transcription factors that regulate muscle atrophy, and little is known about which genes are targeted by NF‐κB transcription factors during atrophy. Interestingly, in some cases it appears that the amelioration of muscle atrophy by genetic inhibition of NF‐κB signalling proteins is due to effects that are independent of the downstream NF‐κB transcription factors. These questions are prime areas for investigation if we are to understand a key component of muscle wasting in adult skeletal muscle.
Cigarette smoke induces endoplasmic reticulum stress response and proteasomal dysfunction in human alveolar epithelial cells
Authors: Somborac‐Bačura Anita , van der Toorn Marco , Franciosi Lorenza , Slebos Dirk‐Jan , Žanić‐Grubišić Tihana , Bischoff Rainer , van Oosterhout Antoon J. M.
Published: July 2012

New findings

What is the central question of this study?

The endoplasmic reticulum stress response caused by cigarette smoke may lead to excessive apoptosis with disruption of the epithelial barrier, thus contributing to chronic obstructive pulmonary disease. One way of promoting cell survival is to facilitate degradation of cigarette smoke‐induced protein damage through the ubiquitin–proteasome pathway. Direct effects of gas‐phase cigarette smoke on proteasomal activities have not been demonstrated previously.

What is the main finding and what is its importance?

We show that cigarette smoke induces protein damage and triggers the endoplasmic reticulum stress response in human alveolar epithelial cells. A significant reduction of all three proteasomal activities was found. Ineffective degradation of damaged proteins could lead to a sustained epithelial stress response and development of chronic obstructive pulmonary disease.

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease. Cigarette smoke (CS) causes oxidative stress and severe damage to proteins in the lungs. One of the main systems to protect cells from the accumulation of damaged proteins is the ubiquitin–proteasome pathway. In the present study, we aimed to find out whether exposure of alveolar epithelial cells to CS induces an endoplasmic reticulum (ER) stress response by accumulation of damaged proteins that are inefficiently degraded by the proteasomes. The hypothesis was tested in a human alveolar epithelial cell line (A549) exposed to gas‐phase CS. Exposure to gas‐phase CS for 5 min caused an increase in the amount of ubiquitin–protein conjugates within 4 h. Cigarette smoke exposure also induced the ER stress response marker eIF2α, followed by a significant reduction of nascent protein synthesis and increase in the level of free intracellular amino acids. Moreover, CS exposure significantly reduced all three proteasomal activities (caspase‐, trypsin‐ and chymotrypsin‐like activity) within 4 h, which was still present after 24 h. It can be concluded that gas‐phase CS induces ER stress in A549 alveolar epithelial cells, leading to inadequate protein turnover caused by an accumulation of damaged proteins, reduction in nascent protein synthesis and inhibition of the proteasome. We suggest that prolonged ER stress may lead to excessive cell death with disruption of the epithelial barrier, contributing to development of chronic obstructive pulmonary disease.
A characterization of robust radiation therapy treatment planning methods—from expected value to worst case optimization
Authors: Fredriksson Albin
Published: July 2012

Purpose:

To characterize a class of optimization formulations used to handle systematic and random errors in radiation therapy, and to study the differences between the methods within this class.

Methods:

The class of robust methods that can be formulated as minimax stochastic programs is studied. This class generalizes many previously used methods, ranging between optimization of the expected and the worst case objective value. The robust methods are used to plan intensity‐modulated proton therapy (IMPT) treatments for a case subject to systematic setup and range errors, random setup errors with and without uncertain probability distribution, and combinations thereof. As reference, plans resulting from a conventional method that uses a margin to account for errors are shown.

Results:

For all types of errors, target coverage robustness increased with the conservativeness of the method. For systematic errors, best case organ at risk (OAR) doses increased and worst case doses decreased with the conservativeness. Accounting for random errors of fixed probability distribution resulted in heterogeneous dose. The heterogeneities were reduced when uncertainty in the probability distribution was accounted for. Doing so, the OAR doses decreased with the conservativeness. All robust methods studied resulted in more robust target coverage and lower OAR doses than the conventional method.

Conclusions:

Accounting for uncertainties is essential to ensure plan quality in complex radiation therapy such as IMPT. The utilization of more information than conventional in the optimization can lead to robust target coverage and low OAR doses. Increased target coverage robustness can be achieved by more conservative methods.
Tyrosine Kinases EnAbling Adaptor Molecules for Chemokine-Induced Rap1 Activation in T Cells
Authors: Malherbe Laurent P. , Wang Demin
Published: July 2012

T cell migration requires phosphorylation of an adaptor protein by Abl family kinases to activate guanosine triphosphatase Rap1.
Focus Issue: Regulation of Lymphocyte Function
Authors: Andrianantoandro Ernesto , Foley John F.
Published: July 2012

Similar modes of regulation across different cell types promote effective innate and adaptive immunity.
Anchors Away
Authors: Gough Nancy R.
Published: July 2012

Monomeric Homer isoforms release receptors from multimeric Homer scaffolds to mediate synaptic modulation.
Effect of Systemic Infection Induced by Pseudomonas aeruginosa on the Brain Uptake of Colistin in Mice
Authors: Jin Liang , Li Jian , Nation Roger L. , Nicolazzo Joseph A.
Published: July 2012

In view of reports of colistin-induced neurotoxicity in infected patients, the aim of this study was to assess whether the integrity of the blood-brain barrier (BBB) and the brain uptake of colistin are altered in the presence of systemic
Pseudomonas aeruginosa
infection. Bacteremia was confirmed 8 h after intramuscular administration of
P. aeruginosa
ATCC 27853 to Swiss Outbred mice, at which time a single subcutaneous dose of colistin sulfate (40 mg/kg of body weight) or an intravenous dose of [
14
C]sucrose (2 μCi) was administered. Despite a substantial elevation in plasma levels of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β, and interleukin-6 during bacterial infection, the brain uptake of colistin was similar between infected and noninfected mice with AUC
brain
/AUC
plasma
(where AUC
brain
is the area under the brain concentration-time curve and AUC
plasma
is the area under the plasma concentration-time curve) ratios of 0.023 and 0.024, respectively. Similarly, the brain-to-plasma ratios of [
14
C]sucrose were no different between infected and noninfected mice, consistent with a lack of effect of bacteremia on BBB integrity. To further correlate any relationship between BBB disruption and plasma levels of proinflammatory cytokines, BBB integrity, colistin brain uptake, and plasma proinflammatory cytokines were measured following the administration of
Salmonella enterica
lipopolysaccharide (LPS), an agent known to induce BBB disruption. Despite LPS inducing a 4-fold increase in colistin brain uptake and a significant (
P
< 0.05) 1.2-fold increase in [
14
C]sucrose BBB penetration, plasma cytokine levels were lower with LPS treatment relative to those obtained with bacterial infection with
P. aeruginosa
. This study demonstrates that the brain uptake of colistin is not increased in mice during
P. aeruginosa
-induced systemic bacteremia despite a significant increase in plasma levels of three proinflammatory cytokines.
A Mutation in the PP2C Phosphatase Gene in a Staphylococcus aureus USA300 Clinical Isolate with Reduced Susceptibility to Vancomycin and Daptomycin
Authors: Passalacqua Karla D. , Satola Sarah W. , Crispell Emily K. , Read Timothy D.
Published: July 2012

Methicillin-resistant
Staphylococcus aureus
(MRSA) strains with reduced susceptibility to vancomycin (MIC of 4 to 8 μg/ml) are referred to as vancomycin-intermediate
S. aureus
(VISA). In this study, we characterized two isogenic USA300
S. aureus
isolates collected sequentially from a single patient with endocarditis where the
S. aureus
isolate changed from being susceptible to vancomycin (VSSA) (1 μg/ml) to VISA (8 μg/ml). In addition, the VISA isolate lost beta-lactamase activity and showed increased resistance to daptomycin and linezolid. The two strains did not differ in growth rate, but the VISA isolate had a thickened cell wall and was less autolytic. Transcriptome sequencing (RNA-seq) analysis comparing the two isolates grown to late exponential phase showed significant differences in transcription of cell surface protein genes (
spa
, SBI [second immunoglobulin-binding protein of
S. aureus
], and fibrinogen-binding proteins), regulatory genes (
agrBCA
, RNAIII,
sarT
, and
saeRS
), and others. Using whole-genome shotgun resequencing, we identified 6 insertion/deletion mutations between the VSSA and VISA isolates. A protein phosphatase 2C (PP2C) family phosphatase had a 6-bp (nonframeshift) insertion mutation in a highly conserved metal binding domain. Complementation of the clinical VISA isolate with a wild-type copy of the PP2C gene reduced the vancomycin and daptomycin MICs and increased autolytic activity, suggesting that this gene contributed to the reduced vancomycin susceptibility phenotype acquired
in vivo
. Creation of
de novo
mutants from the VSSA strain resulted in different mutations, demonstrating that reduced susceptibility to vancomycin in USA300 strains can occur via multiple routes, highlighting the complex nature of the VISA phenotype.
Enterococcus faecalis Enhances Cell Proliferation through Hydrogen Peroxide-Mediated Epidermal Growth Factor Receptor Activation
Authors: Boonanantanasarn Kanitsak , Gill Ann Lindley , Yap YoonSing , Jayaprakash Vijayvel , Sullivan Maureen A. , Gill Steven R.
Published: July 2012

Enterococcus faecalis
is a member of the intestinal and oral microbiota that may affect the etiology of colorectal and oral cancers. The mechanisms by which
E. faecalis
may contribute to the initiation and progression of these cancers remain uncertain. Epidermal growth factor receptor (EGFR) signaling is postulated to play a crucial role in oral carcinogenesis. A link between
E. faecalis
and EGFR signaling in oral cancer has not been elucidated. The present study aimed to evaluate the association between
E. faecalis
and oral cancer and to determine the underlying mechanisms that link
E. faecalis
to EGFR signaling. We report the high frequency of
E. faecalis
infection in oral tumors and the clinical association with EGFR activation. Using human oral cancer cells, we support the clinical findings and demonstrate that
E. faecalis
can induce EGFR activation and cell proliferation.
E. faecalis
activates EGFR through production of H
2
O
2
, a signaling molecule that activates several signaling pathways. Inhibitors of H
2
O
2
(catalase) and EGFR (gefitinib) significantly blocked
E. faecalis
-induced EGFR activation and cell proliferation. Therefore,
E. faecalis
infection of oral tumor tissues suggests a possible association between
E. faecalis
infection and oral carcinogenesis. Interaction of
E. faecalis
with host cells and production of H
2
O
2
increase EGFR activation, thereby contributing to cell proliferation.
Identification of Critical Host Mitochondrion-Associated Genes during Ehrlichia chaffeensis Infections
Authors: Von Ohlen Tonia , Luce-Fedrow Alison , Ortega M. Teresa , Ganta Roman R. , Chapes Stephen K.
Published: July 2012

Ehrlichia chaffeensis
is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on
Drosophila melanogaster
S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for
E. chaffeensis
growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to support
Ehrlichia
replication. Three additional
D. melanogaster
fly lines with putative mutations in pyrimidine metabolism were also tested. Ten fly lines carrying mutations in the genes
CG6479
,
separation anxiety
,
chitinase 11
,
CG6364
(
Uck2
),
CG6543
(
Echs1
),
withered
(
whd
),
CG15881
(
Ccdc58
),
CG14806
(
Apop1
),
CG11875
(
Nup37
), and
dumpy
(
dp
) had increased resistance to infection with
Ehrlichia
. Analysis of RNA by quantitative real-time reverse transcription-PCR (qRT-PCR) confirmed that the bacterial load was decreased in these mutant flies compared to wild-type infected control flies. Seven of these genes (
san
,
Cht11
,
Uck2
,
Echs1
,
whd
, C
cdc58
, and
Apop1
) encoded proteins that had mitochondrial functions or could be associated with proteins with mitochondrial functions. Treatment of THP-1 cells with double-stranded RNA to silence the human
UCK2
gene indicates that the disruption of the uridine-cytidine kinase affects
E. chaffeensis
replication in human macrophages. Experiments with cyclopentenyl cytosine (CPEC), a CTP synthetase inhibitor and cytosine, suggest that the nucleotide salvage pathway is essential for
E. chaffeensis
replication and that it may be important for the provision of CTP, uridine, and cytidine nucleotides.