bluuebunny/crossref_metadata_2025_split huggingface dataset:
N‐3 polyunsaturated fatty acid attenuates cholesterol gallstones by suppressing mucin production with a high cholesterol diet in mice
Authors: Kim Ja Kyung , Cho Soo Min , Kang So Hee , Kim Eunjung , Yi Hee , Yun Eun Sun , Lee Dong Goo , Cho Hee Jung , Paik Yong Han , Choi Yang Kyu , Haam Seung Joo , Shin Ho Chul , Lee Dong Ki 
Published: July 2012

AbstractBackground and AimThe increasing prevalence of cholesterol gallstone (CG) disease has become an economic burden to the healthcare system. Ursodeoxycholic acid (UDCA) is the only established medical agent used to dissolve gallstones. In investigating novel therapeutics for CG, we assessed the preventive effects of n‐3 polyunsaturated fatty acids (n‐3PUFA) on the formation of CG induced by feeding a lithogenic diet (LD) containing high cholesterol levels to mice.MethodsMice were divided into the following six groups: (A) regular diet (RD); (B) RD+n‐3PUFA; (C) LD; (D) LD+n‐3PUFA; (E) LD+UDCA; (F) LD+n‐3PUFA+UDCA. After RD/LD feeding for 2 weeks, n‐3PUFA or UDCA was administered orally and the diet maintained for 8 weeks. The levels of phospholipids and cholesterol in bile, CG formation, gallbladder wall thickness, MUC gene expression in gallbladder were analyzed.ResultsNo stone or sludge was evident in the RD groups (Groups A, B). Mice in the n‐3PUFA treatment (Groups D, F) showed significantly lower stone formation than the other LD groups (Groups C, E). The combination treatment of n‐3PUFA and UDCA suppressed stone formation more than mono‐therapy with n‐3PUFA or UDCA. Bile phospholipid levels were significantly elevated in the Group F. Hypertrophy of the gallbladder wall was evident in mice fed LD. MUC 2, 5AC, 5B and 6 mRNA expression levels were significantly elevated in the LD‐fed group, and this was suppressed by n‐3PUFA with or without UDCA.ConclusionsN‐3PUFA attenuated gallstone formation in mouse, through increasing the levels of bile phospholipids and suppressing bile mucin formation.
Potential for statins in the chemoprevention and management of hepatocellular carcinoma
Authors: Lonardo Amedeo , Loria Paola 
Published: July 2012

AbstractHepatocellular carcinoma (HCC) is a common, treatment‐resistant malignancy with a complex molecular pathogenesis. Statins are a widely used class of cholesterol‐lowering drugs with potential anticancer activity.We reviewed the evidence for a role of statins in primary and secondary chemoprevention of HCC and slowing the course of otherwise incurable primary or recurrent disease. A literature search (key words: Statins, hepatocellular carcinoma) conducted to this end, retrieved 119 references. Here we summarize the history, mechanism of action and cardiovascular use of statins and highlight that statins can affect several pathways implicated in the development of HCC. In vitro and animal studies provide strong evidence for a favorable effect of statins on HCC. However, evidence in humans is conflicting. We discuss in full detail the methodological strengths and pitfalls of published data including three cohort studies suggesting that the use of statins may protect from the development of HCC and of a single trial reporting increased survival in those with advanced HCC randomized to receive statins. A remarkably hepato‐safe class of drugs acting on both hepatocyte and endothelial cells, statins also have potentially beneficial effects in lowering portal hypertension. In conclusion, there is strong experimental evidence that statins are beneficial in chemopreventing and slowing the growth of HCC. However, randomized controlled trials are necessary in order to investigate the role of statins in the chemoprevention of HCC and in slowing the course of otherwise incurable disease in humans.
Investigation and management of hepatic incidentalomas
Authors: Fergusson James 
Published: July 2012

AbstractWith the widespread use of medical imaging has come the detection of incidental liver lesions that are, by and large, asymptomatic prior to their discovery. These lesions may become a source of anxiety and often require further investigation to reassure the patient of their usually benign nature. Use of contemporary hepatobiliary imaging and simple laboratory tests often allow a definite diagnosis to be made without resorting to exhaustive investigation or inappropriate surgery. The goal of this paper is to review the clinical features and imaging characteristics of common and important liver incidentalomas, their natural course, complications, and indications for surgical or other intervention.
Alteration of the timing of self‐initiated but not reactive saccades by electrical stimulation in the supplementary eye field
Authors: Kunimatsu Jun , Tanaka Masaki 
Published: July 2012

AbstractAlthough we can generate movements whenever we feel like doing so, the way in which neuronal signals regulate the timing of self‐initiated movements remains elusive. There is evidence that the dorsomedial frontal cortex, including the supplementary eye field (SEF), is involved in the self‐triggering of movements. Because the gradual evolution of cortical activity over the dorsomedial frontal cortex is known to reflect the temporal prediction of an upcoming event, we postulated that the timing of self‐initiated movements is regulated by the time course of neuronal activity in the SEF. To test the causal role, we applied electrical microstimulation to the SEF when monkeys prepared for memory‐guided saccades. Stimulation delayed the initiation of saccades when animals were required to make saccades 1200 ± 300 ms following the cue (self‐timed task), but not when they generated memory‐guided saccades in response to the offset of the fixation point (conventional task). As well as the increment in median saccade latencies, stimulation at ∼24% of sites also increased the occurrence of early erroneous saccades. Saccades facilitated by stimulation were always directed toward the cue, even when the cue was located away from the movement field. In contrast, stimulation to the frontal eye fields during saccade preparation exerted no effects in either task. These results suggest that the preparatory signals in the SEF may play a causal role in regulating the timing rather than the direction of self‐initiated saccades.
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

AbstractMotor 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

SummaryMethyloversatilis 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

AbstractAim  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

SummaryCynara 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

AbstractThe 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 PurposeThe 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 ApproachPAR2 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 ResultsPAR2 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 ImplicationsPAR2 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.
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.