bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis
Authors: Reichert Maximilian , Takano Shigetsugu , von Burstin Johannes , Kim Sang-Bae , Lee Ju-Seog , Ihida-Stansbury Kaori , Hahn Christopher , Heeg Steffen , Schneider Günter , Rhim Andrew D. , Stanger Ben Z. , Rustgi Anil K.
Published: January 2013

Pancreatic exocrine cell plasticity can be observed during development, pancreatitis with subsequent regeneration, and also transformation. For example, acinar–ductal metaplasia (ADM) occurs during acute pancreatitis and might be viewed as a prelude to pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC) development. To elucidate regulatory processes that overlap ductal development, ADM, and the progression of normal cells to PanIN lesions, we undertook a systematic approach to identify the Prrx1 paired homeodomain Prrx1 transcriptional factor as a highly regulated gene in these processes. Prrx1 annotates a subset of pancreatic ductal epithelial cells in Prrx1creERT2-IRES-GFP mice. Furthermore, sorted Prrx1+ cells have the capacity to self-renew and expand during chronic pancreatitis. The two isoforms, Prrx1a and Prrx1b, regulate migration and invasion, respectively, in pancreatic cancer cells. In addition, Prrx1b is enriched in circulating pancreatic cells (Pdx1cre;LSL-KrasG12D/+;p53fl/+;R26YFP). Intriguingly, the Prrx1b isoform, which is also induced in ADM, binds the Sox9 promoter and positively regulates Sox9 expression. This suggests a new hierarchical scheme whereby a Prrx1–Sox9 axis may influence the emergence of acinar–ductal metaplasia and regeneration. Furthermore, our data provide a possible explanation of why pancreatic cancer is skewed toward a ductal fate.
Lagging strand maturation factor Dna2 is a component of the replication checkpoint initiation machinery
Authors: Kumar Sandeep , Burgers Peter M.
Published: January 2013

Initiation of the DNA replication checkpoint in yeast is mainly mediated by Mec1 protein kinase, the ortholog of human ATR, while its homolog Tel1, the ortholog of human ATM, has a minor replication checkpoint function. Checkpoint initiation requires stimulation of Mec1 kinase activity by specific activators. Saccharomyces cerevisiae Dna2, a nuclease-helicase that is essential for Okazaki fragment maturation, is employed specifically during S phase to stimulate Mec1 kinase and initiate the replication checkpoint. Mutations (W128A and Y130A) in the unstructured N terminus of Dna2 abrogate its checkpoint function in vitro and in vivo. Dna2 shows partial redundancy for the replication checkpoint with checkpoint initiators 9-1-1 (S. cerevisiae Ddc1–Mec3–Rad17 and human Rad9–Rad1–Hus1) and Dpb11, the ortholog of human TopBP1. A triple mutant that eliminates the checkpoint functions of all three initiators abrogates the Mec1-dependent checkpoint.
Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes
Authors: Caravaca Juan Manuel , Donahue Greg , Becker Justin S. , He Ximiao , Vinson Charles , Zaret Kenneth S.
Published: January 2013

While most transcription factors exit the chromatin during mitosis and the genome becomes silent, a subset of factors remains and “bookmarks” genes for rapid reactivation as cells progress through the cell cycle. However, it is unknown whether such bookmarking factors bind to chromatin similarly in mitosis and how different binding capacities among them relate to function. We compared a diverse set of transcription factors involved in liver differentiation and found markedly different extents of mitotic chromosome binding. Among them, the pioneer factor FoxA1 exhibits the greatest extent of mitotic chromosome binding. Genomically, ∼15% of the FoxA1 interphase target sites are bound in mitosis, including at genes that are important for liver differentiation. Biophysical, genome mapping, and mutagenesis studies of FoxA1 reveals two different modes of binding to mitotic chromatin. Specific binding in mitosis occurs at sites that continue to be bound from interphase. Nonspecific binding in mitosis occurs across the chromosome due to the intrinsic chromatin affinity of FoxA1. Both specific and nonspecific binding contribute to timely reactivation of target genes post-mitosis. These studies reveal an unexpected diversity in the mechanisms by which transcription factors help retain cell identity during mitosis.
MORE SPIKELETS1Is Required for Spikelet Fate in the Inflorescence of Brachypodium
Authors: Derbyshire Paul , Byrne Mary E.
Published: January 2013

Grasses produce florets on a structure called a spikelet, and variation in the number and arrangement of both branches and spikelets contributes to the great diversity of grass inflorescence architecture. In Brachypodium (Brachypodium distachyon), the inflorescence is an unbranched spike with a terminal spikelet and a limited number of lateral spikelets. Spikelets are indeterminate and give rise to a variable number of florets. Here, we provide a detailed description of the stages of inflorescence development in Brachypodium. To gain insight into the genetic regulation of Brachypodium inflorescence development, we generated fast neutron mutant populations and screened for phenotypic mutants. Among the mutants identified, the more spikelets1 (mos1) mutant had an increased number of axillary meristems produced from inflorescence meristem compared with the wild type. These axillary meristems developed as branches with production of higher order spikelets. Using a candidate gene approach, mos1 was found to have a genomic rearrangement disrupting the expression of an ethylene response factor class of APETALA2 transcription factor related to the spikelet meristem identity genes branched silkless1 (bd1) in maize (Zea mays) and FRIZZY PANICLE (FZP) in rice (Oryza sativa). We propose MOS1 likely corresponds to the Brachypodium bd1 and FZP ortholog and that the function of this gene in determining spikelet meristem fate is conserved with distantly related grass species. However, MOS1 also appears to be involved in the timing of initiation of the terminal spikelet. As such, MOS1 may regulate the transition to terminal spikelet development in other closely related and agriculturally important species, particularly wheat (Triticum aestivum).
Rotation and generation of mental imagery in children with specific language impairment
Authors: Guarnera Maria , Commodari Elena , Peluso Cristina
Published: January 2013

Aim

To investigate the relationship between mental imagery and specific language impairment (SLI) and explore the assumption that children with SLI are less able to generate mental images and/or convert them, when compared to typical development (TD) children of the same age.

Methods

Twenty‐four children, aged six to eight, took part in two tests to see how well they generated and rotated mental images. The participants were 12 SLI children (six boys and six girls) and 12 TD children (six boys and six girls), matched by age and gender.

Results

The statistical analysis showed a significant difference between the two groups when it came to generating mental imagery. However, there were no significant differences with regard to rotating mental imagery.

Conclusion

The results suggest imagery deficit in language‐impaired children is not caused by mental rotation, but by other aspects of image processing, such as generation, maintenance and interpretation of visual images.
Sulfated Small Molecules Targeting EBV in Burkitt Lymphoma: From In Silico Screening to the Evidence of In Vitro Effect on Viral Episomal DNA
Authors: Lima Raquel T. , Seca Hugo , Palmeira Andreia , Fernandes Miguel X. , Castro Felipe , Correia‐da‐Silva Marta , Nascimento Maria S. J. , Sousa Emília , Pinto Madalena , Vasconcelos M. Helena
Published: January 2013

Epstein–Barr virus (EBV) infects more than 90% of the world population. Following primary infection, Epstein–Barr virus persists in an asymptomatic latent state. Occasionally, it may switch to lytic infection. Latent EBV infection has been associated with several diseases, such as Burkitt lymphoma (BL). To date, there are no available drugs to target latent EBV, and the existing broad‐spectrum antiviral drugs are mainly active against lytic viral infection. Thus, using computational molecular docking, a virtual screen of a library of small molecules, including xanthones and flavonoids (described with potential for antiviral activity against EBV), was carried out targeting EBV proteins. The more interesting molecules were selected for further computational analysis, and sub‐sequently, the compounds were tested in the Raji (BL) cell line, to evaluate their activity against latent EBV. This work identified three novel sulfated small molecules capable of decreasing EBV levels in a BL. Therefore, the in silico screening presents a good approach for the development of new anti‐EBV agents.
Chiral Bicyclic Tetramates as Non‐Planar Templates for Chemical Library Synthesis
Authors: Anwar Muhammad , Moloney Mark G.
Published: January 2013

Chemoselective Dieckmann cyclization reactions may be used on oxazolidine and thiazolidine templates derived from various aldehydes to access bicyclic tetramates, which have potential as templates for chemical library construction. Bioassay against Staphylococcus aureus and Escherichia coli showed that these systems have little or no intrinsic antibacterial bioactivity.
A Novel Approach to Active Compounds Identification Based on Support Vector Regression Model and Mean Impact Value
Authors: Jiang Jian‐Lan , Su Xin , Zhang Huan , Zhang Xiao‐Hang , Yuan Ying‐Jin
Published: January 2013

Traditionally, active compounds were discovered from natural product extracts by bioassay‐guided fractionation, which was with high cost and low efficiency. A well‐trained support vector regression model based on mean impact value was used to identify lead active compounds on inhibiting the proliferation of the HeLa cells in curcuminoids from Curcuma longa L. Eight constituents possessing the high absolute mean impact value were identified to have significant cytotoxicity, and the cytotoxic effect of these constituents was partly confirmed by subsequent MTT (3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays and previous reports. In the dosage range of 0.2–211.2, 0.1–140.2, 0.2–149.9 μm, 50% inhibiting concentrations (IC50) of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were 26.99 ± 1.11, 19.90 ± 1.22, and 35.51 ± 7.29 μm, respectively. It was demonstrated that our method could successfully identify lead active compounds in curcuminoids from Curcuma longa L. prior to bioassay‐guided separation. The use of a support vector regression model combined with mean impact value analysis could provide an efficient and economical approach for drug discovery from natural products.
Health‐related quality of life in colorectal cancer
Authors: Färkkilä N. , Sintonen H. , Saarto T. , Järvinen H. , Hänninen J. , Taari K. , Roine R. P.
Published: January 2013

Aim

As a consequence of the improved survival of patients and of cost‐effectiveness requirements for new treatments, health‐related quality of life (HRQoL) issues have gained increasing attention in colorectal cancer (CRC). This cross‐sectional study assesses HRQoL in several health states of CRC and explores factors influencing HRQoL.

Method

Five hundred and eight Finnish CRC patients (aged 26–96 years; colon cancer 56%; women 47%) assessed their HRQoL using generic 15D and EQ‐5D and cancer‐specific EORTC QLQ‐C30 questionnaires. Patients were divided into five groups: primary treatment, rehabilitation, remission, metastatic disease and palliative care. The patients' HRQoL was compared with population reference values. Multivariate modelling was used to find factors associated with HRQoL scores.

Results

The HRQoL of CRC patients is fairly good and comparable with that of the standardized general population except for those under palliative care. The mean 15D score of patients in the primary treatment group was 0.889 (95% CI 0.869–0.914), in rehabilitation 0.877 (0.855–0.907), in remission 0.886 (0.875–0.903), in metastatic disease 0.860 (0.844–0.878) and in palliative care 0.758 (0.716–0.808). The respective EQ‐5D scores were 0.760 (0.699–0.823), 0.835 (0.777–0.881), 0.850 (0.828–0.882), 0.820 (0.783–0.858) and 0.643 (0.546–0.747). Multivariate analysis showed that fatigue, pain, age and financial difficulties had a marked negative impact on HRQoL.

Conclusion

The mean HRQoL scores of CRC patients varied considerably depending on the HRQoL instrument used, but remained surprisingly good up to the palliative stage. In addition to age‐ and cancer‐related symptoms, financial difficulties also had a clear negative impact on HRQoL, which needs to be taken into consideration when supporting patient HRQoL.
Autophagy and hypoxia in colonic adenomas related to aggressive features
Authors: Giatromanolaki A. , Koukourakis M. I. , Koutsopoulos A. V. , Harris A. L. , Gatter K. C. , Sivridis E.
Published: January 2013

Aim

The study investigated whether autophagic activity and hypoxia parallel the adenoma–carcinoma sequence.

Method

The study comprised 120 tubular adenomas with high‐grade dysplasia, including 22 with questionable evidence of invasion, 37 with definite stromal invasion and 29 with severely dysplastic adenoma, 10 traditional serrated adenomas and 22 classical tubular adenomas lacking aggressive features. The samples were stained immunohistochemically for autophagy (LC3A and Beclin‐1) and hypoxia‐inducible factor1‐alpha (HIF1α) markers.

Results

LC3A was detected as diffuse cytoplasmic staining and as dense “stone‐like” structures (SLS) within cytoplasmic vacuoles. Beclin‐1 reactivity was purely cytoplasmic, whereas that of HIF1α was both cytoplasmic and nuclear. SLS counts in noninvasive, nontransformed areas of tubular adenomas were consistently low (median SLS = 0.5; 200× magnification), whereas a progressive increase was noted from areas of equivocal invasion (median SLS = 1.3; 200× magnification) and intramucosal carcinoma (median SLS = 1.4; 200× magnification) to unequivocal invasive foci (median SLS = 2.1; 200× magnification) (P < 0.0001). A similar association was shown for Beclin‐1 and HIF1α expression (P < 0.05). Traditional serrated adenomas yielded low SLS counts and weak HIF1α reactivity, but high cytoplasmic LC3A and Beclin‐1 expression (P < 0.01).

Conclusion

A hypoxia‐driven autophagy in adenomatous polyps, when particularly intense and localized, is commonly associated with early invasion or severely dysplastic adenoma.
Local recurrence after prone vs supine abdominoperineal excision for low rectal cancer
Authors: Anderin C. , Granath F. , Martling A. , Holm T.
Published: January 2013

Aim

Tumour‐involved circumferential resection margins (CRMs) and intra‐operative perforation (IOP) are well known risk factors for local recurrence after surgery for low rectal cancer. In conventional abdominoperineal excision (APE) the patient remains in the supine position for the perineal part of the procedure. However, turning the patient to the prone position may improve visualization which potentially might reduce the risk of involved CRMs and IOP and thus improve local control. The study was carried out to assess local recurrence rates after APE in relation to the positioning of the patient during the perineal part of the procedure.

Method

This cohort study includes 466 patients having APE for low rectal cancer between 2001 and December 2010. Data were retrieved from the regional rectal cancer registry in Stockholm and from a retrospective review of patient files.

Results

An incomplete resection was reported in 12.4% after APE in the supine position and in 6.8% after APE in the prone position (P = 0.038). Corresponding figures for IOP were 12.4% and 4.0% (P < 0.001). Prone APE was associated with a 39% relative reduction in local recurrence events compared with APE in the supine position, although the difference was not statistically significant (hazard ratio 0.61, 95% CI 0.27–1.37).

Conclusion

APE in the prone position reduced the incidence of incomplete resection and IOP, but the study did not find a statistically significant difference in local failure rates related to the position of the patient.
Survival of patients with Stage III colon cancer is improved in hereditary non‐polyposis colorectal cancer compared with sporadic cases. A Danish registry based study
Authors: Brixen L. M. , Bernstein I. T. , Bülow S. , Ehrnrooth E.
Published: January 2013

Aim

Patients with hereditary non‐polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colorectal cancer (CRC). The aim was to compare survival after Stage III CC in patients with HNPCC with those having sporadic CC.

Method

A total of 230 patients with hereditary cancer from the Danish HNPCC Register and 3557 patients with sporadic CC from the Danish Colorectal Cancer Database, diagnosed during May 2001–December 2008, were included. HNPCC patients were classified according to mismatch repair mutation status and family pedigree. Sporadic cases had no known family history of cancer. Patient characteristics, geographical differences and survival data were analysed.

Results

The overall survival (OS) was better in HNPCC patients compared with sporadic CC after stratification for sex and age (P = 0.02; CI 1.04–1.7). The 5‐year survival was 70% in HNPCC patients compared with 56% in sporadic CC (P < 0.001). No survival difference was found between HNPCC subgroups but a tendency to better OS was seen in patients with Lynch syndrome. No geographical differences in OS were found. The median follow‐up was 3.9 (0–9.5) years for HNPCC vs 3.2 (0–9.6) years for sporadic CC.

Conclusion

HNPCC patients with Stage III CC have a better OS compared with sporadic CC. No significant difference in OS was found within HNPCC subgroups.
Effect of preoperative two‐dimensional animation information on perioperative anxiety and knowledge retention in patients undergoing bowel surgery: a randomized pilot study
Authors: Tou S. , Tou W. , Mah D. , Karatassas A. , Hewett P.
Published: January 2013

Aim

The use of multimedia information provided preoperatively can potentially reduce anxiety in patients and improve the hospital experience. However, the use of two‐dimensional (2D) animation (cartoon) to provide information to patients undergoing colorectal surgery has not been investigated. This study investigated the effect of preoperative 2D information on anxiety and knowledge retention in patients undergoing bowel surgery.

Method

Patients were randomized to one of two groups; the video group watched a 13‐min cartoon animation whereas the nonvideo group did not. Anxiety levels were measured at the preadmission clinic, postvideo, on the day of admission for surgery, within 24‐h after surgery and before discharge using the Spielberger state‐trait anxiety inventory and visual analogue scale. Both groups completed a knowledge retention questionnaire and the video group completed a feedback questionnaire about the animation.

Results

Thirty‐one patients (16 video, 15 nonvideo) participated in the study. There was no significant difference in baseline anxiety score between two groups. An immediate reduction (P = 0.03) in anxiety score was observed in the video group after watching the video compared with baseline. There was a significant reduction in anxiety score in the video group at discharge compared with the nonvideo group (P = 0.03). There was no significant difference in knowledge retention between two groups. Eighty‐eight per cent of patients who watched the video found it beneficial.

Conclusion

2D animation is an effective medium for delivering information to patients undergoing bowel surgery and can potentially reduce anxiety related to surgery and improve the hospital experience.
Determining in‐patient diabetes treatment satisfaction in the UK—the DIPSat study
Authors: Rutter C. L. , Jones C. , Dhatariya K. K. , James J. , Irvine L. , Wilson E. C. F. , Singh H. , Walden E. , Holland R. , Harvey I. , Bradley C. , Sampson M. J.
Published: January 2013

Aims

To measure in‐patient diabetes treatment satisfaction and its relationship to in‐patient diabetes care.

Methods

In a cross‐sectional study, diabetes in‐patient specialist nurses at 58 UK hospitals asked insulin‐treated in‐patients with diabetes to complete the recently updated Diabetes Treatment Satisfaction Questionnaire for In‐patients and a general questionnaire; 1319 in‐patients completed these questionnaires.

Results

Satisfaction with the general diabetes treatment items in the Diabetes Treatment Satisfaction Questionnaire for In‐patients was high, but there were high levels of extreme dissatisfaction with meal choices, meal quality and lack of similarity of hospital meals to normal domestic choices—23% would never or rarely have made similar meal choices at home. Hyperglycaemia or hypoglycaemia was reported for much of the in‐patient stay (20% and 7%, respectively) and 26% reported at least one severe hypoglycaemic episode; these groups had lower satisfaction with the timing of medication in relation to meals (P < 0.003). More frequent in‐patient hyperglycaemia or hypoglycaemia were associated with significantly poorer overall satisfaction scores and negative well‐being scores (both P < 0.0001). Previous experience of a multiple daily insulin injection regimen was associated with more dissatisfaction than other regimens (P < 0.01). Multiple regression models explained 36% of variability in overall treatment satisfaction, with most (22.4%) accounted for by satisfaction with time spent with a diabetes in‐patient specialist nurse (P < 0.0001). Self‐administration of insulin was independently associated with higher treatment satisfaction (P < 0.006) in this model.

Conclusions

The DIPSat programme describes the complex relationships between diabetes in‐patient treatment satisfaction and in‐patient diabetes care.
Clinical predictors of risk of hypoglycaemia during addition and titration of insulin glargine for type 2 diabetes mellitus
Authors: Karl D. M. , Gill J. , Zhou R. , Riddle M. C.
Published: January 2013

Aim

Addition and titration of basal insulin is usually effective in improving glycaemic control in type 2 diabetes, but fear of hypoglycaemia remains a barrier. Ability to predict which patients might be at greatest risk of hypoglycaemia might facilitate individualization of treatment and improve safety. The aim of this study was to obtain information about clinical characteristics which might predict risk of hypoglycaemia during initiation of basal insulin.

Methods

Patient‐level data from 2251 participants in 11 studies in which insulin glargine was started and titrated using similar treat‐to‐target methods was pooled and analysed with logistic regression models.

Results

Participants had mean age 58 years, diabetes duration 8.9 years, body mass index 31.0 and baseline A1c 8.8%. They attained mean A1c 7.1% during 6 months of treatment with final mean glargine dosage 0.44 units/kg. Symptomatic hypoglycaemia occurred in 52%, glucose‐confirmed hypoglycaemia (blood glucose <50 mg/dl) in 17%, repeated glucose‐confirmed events in 7% and severe hypoglycaemia in 1.5%. Independent predictors of glucose‐confirmed hypoglycaemia were younger age, lower body mass index, use of a sulphonylurea in addition to metformin, lower attained A1c and lower dosage of glargine.

Conclusions

These findings confirm low rates of clinically important hypoglycaemia using this method, and suggest that higher risk of hypoglycaemia may be suspected when patients needing insulin are younger, less obese and taking metformin and a sulphonylurea, and especially when A1c levels ≤7.0% are attained with glargine dosage ≤0.4 units/kg.
Transglial transmission at the dorsal root ganglion sandwich synapse: glial cell to postsynaptic neuron communication
Authors: Rozanski Gabriela M. , Li Qi , Stanley Elise F.
Published: January 2013

The dorsal root ganglion (DRG) contains a subset of closely‐apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS–glial cell–NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long‐lasting response in its NS pair via a transglial signaling pathway that we term a ‘sandwich synapse’ (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS‐to‐SGC leg of the two‐synapse pathway is purinergic via P2Y2 receptors but the second SGC‐to‐NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic postsynaptic receptor. Selective block by D‐2‐amino‐5‐phosphonopentanoate (AP5) implicated glutamatergic transmission via N‐methyl‐d‐aspartate receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N‐methyl‐d‐aspartate receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 receptor. Isolated DRG cell clusters exhibited daisy‐chain and branching NS–glial cell–NS contacts, suggestive of a network organization within the ganglion. The identification of the glial‐to‐neuron transmitter and receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway.
Dichotomy of decorin activity on the insulin‐like growth factor‐I system
Authors: Morrione Andrea , Neill Thomas , Iozzo Renato V.
Published: January 2013

The stromal‐specific proteoglycan decorin has emerged in recent years as a critical regulator of tumor initiation and progression. Decorin regulates the biology of various types of cancer by modulating the activity of several receptor tyrosine kinases coordinating growth, survival, migration, and angiogenesis. Decorin binds to surface receptors for epidermal growth factor and hepatocyte growth factor with high affinity, and negatively regulates their activity and signaling via robust internalization and eventual degradation. The insulin‐like growth factor (IGF)‐I system plays a critical role in the regulation of cell growth both in vivo and in vitro. The IGF‐I receptor (IGF‐IR) is also essential for cellular transformation, owing to its ability to enhance cell proliferation and protect cancer cells from apoptosis. Recent data have pointed to a role of decorin in regulating the IGF‐I system in both nontransformed and transformed cells. Significantly, there is a surprising dichotomy in the mechanism of decorin action on IGF‐IR signaling, which differs considerably between physiological and pathological cellular models. In this review, we summarize the current knowledge on decorin regulation of the IGF‐I system in normal and transformed cells, and discuss possible decorin‐based therapeutic approaches to target IGF‐IR‐driven tumors.
The influence of simulated clinical use on the flexibility of rotary ProTaper Universal, K3 and EndoSequence nickel–titanium instruments
Authors: Viana A. C. D. , Pereira E. S. J. , Bahia M. G. A. , Buono V. T. L.
Published: January 2013

Aim

To investigate the influence of cyclic flexural and torsional loading on the flexibility of ProTaper Universal, K3 and EndoSequence nickel–titanium instruments, in view of the hypothesis that these types of loading would decrease the flexibility of the selected NiTi rotary files.

Methodology

The instruments evaluated were S2 and F1 ProTaper Universal, sizes 20 and 25, .06 taper K3, and sizes 20 and 25, .06 taper EndoSequence. Flexibility was determined by 45° bending tests according to ISO 3630‐1 specification. Values of the bending moment (MB) obtained with new instruments were considered as the control group (CG). Bending tests were then conducted in instruments previously fatigued to one‐fourth and three‐fourths of their average fatigue life (fatigue groups, FG¼ and FG¾), as well as after cyclic torsional loading (torsional group, TG). Fatigue tests were carried out in a bench device that allowed the files to rotate freely inside an artificial canal with an angle of curvature of 45° and a radius of 5 mm. Cyclic torsional loading tests were performed that entailed rotating the instrument from zero angular deflection to 180° and then returning to zero applied torque in 20 cycles. Data were analysed using one‐way analysis of variance at a significance level of 5%.

Results

Simulated clinical use by means of flexural fatigue tests did not affect the flexibility of the instruments, except for a significant increase in flexibility observed in a few instruments (P < 0.05). In addition, comparative statistical analyses between the values of MB measured in new instruments and after cyclic torsional loading showed no significant differences between them (P > 0.05).

Conclusions

The flexibility of rotary ProTaper Universal, K3 and EndoSequence NiTi instruments, measured in bending tests, was not adversely affected by simulated clinical use in curved root canals.
Diabetes mellitus and inflammatory pulpal and periapical disease: a review
Authors: Lima S. M. F. , Grisi D. C. , Kogawa E. M. , Franco O. L. , Peixoto V. C. , Gonçalves‐Júnior J. F. , Arruda M. P. , Rezende T. M. B.
Published: January 2013

Diabetes mellitus (DM) is one of the most common metabolic disorders. DM is characterized by hyperglycaemia, resulting in wound healing difficulties and systemic and oral manifestations, which have a direct effect on dental pulp integrity. Experimental and clinical studies have demonstrated a higher prevalence of periapical lesions in patients with uncontrolled diabetes. The influence of DM on periapical bone resorption and its impact on dental intervention of such patients are reviewed, and its aetiology and pathogenesis are analysed at molecular level. Pulps from patients with diabetes have the tendency to present limited dental collateral circulation, impaired immune response, increased risk of acquiring pulp infection (especially anaerobic ones) or necrosis, besides toothache and occasional tendency towards pulp necrosis caused by ischaemia. In regard to molecular pathology, hyperglycaemia is a stimulus for bone resorption, inhibiting osteoblastic differentiation and reducing bone recovery. The relationship between poorly controlled diabetes and bone metabolism is not clearly understood. Molecular knowledge about pulp alterations in patients with diabetes could offer new therapeutic directions. Knowledge about how diabetes affects systemic and oral health has an enduring importance, because it may imply not only systemic complications but also a higher risk of oral diseases with a significant effect on pulp and periapical tissue.
Molecular analysis of Malassezia species isolated from Israeli patients with pityriasis versicolor
Authors: Lyakhovitsky Anna , Shemer Avner , Amichai Boaz
Published: January 2013

Background  Pityriasis versicolor (PV) is a common superficial fungal infection of the skin caused by Malassezia species. The clinical significance of each of these species is not fully understood. M. furfur has long been identified as the causative agent of PV. Several recent studies suggest that M. globosa is most frequently associated with PV.

Objectives  The aim of this study was to examine the prevalence of Malassezia species in affected and unaffected skin in Israeli patients with PV using a polymerase chain reaction (PCR)‐based culture‐independent method.

Methods  Samples were taken from affected skin of 75 patients with PV (35 females and 40 males, age range 18–65 years) who visited our outpatient clinic and from unaffected skin in 26 patients for direct microscopy and detection of Malassezia species using a PCR‐based method.

Results  The major Malassezia species in PV was M. globosa, found in 97.3% (73 of 75) of samples from affected skin and 80.8% (21 of 26) samples of unaffected skin. M. restricta was associated with M. globosa in 1.3% (one of 75) of patients. No cases of M. furfur were detected in this study. There was no difference in the distribution of Malassezia species between affected and unaffected skin.

Conclusion  Based on the PCR test, we have shown that M. globosa is probably most frequently associated with PV.
Interrogating participatory catchment organisations: cases from Canada, New Zealand, Scotland and the Scottish–English Borderlands
Authors: Cook B R , Atkinson M , Chalmers H , Comins L , Cooksley S , Deans N , Fazey I , Fenemor A , Kesby M , Litke S , Marshall D , Spray C
Published: January 2013

Catchment management in the developed world is undergoing a fundamental reconfiguration in which top‐down governance is being challenged by local organisations promoting collaborative decisionmaking. Local, participation‐based organisations are emerging as mediators of relations between governments and publics. These organisations, defined here as participatory catchment organisations (PCOs), are emergent at a time when developed world catchment management is itself undergoing substantial change. Through in‐depth engagement with four PCOs, and using six case studies, we identify the principles associated with successful problem resolution. The findings illustrate the importance of PCOs as two‐way bridges between publics and governments. We identify three principles shared by these organisations (i.e. trust brokers, collaborative decisionmaking and win‐wins) that show how, through participatory approaches founded on trust, complex problems can be resolved in ways that do not unduly punish groups or individuals. In conclusion, we identify four questions that highlight the need to consider the practicality of evolving relations amongst governments, publics, and the organisations that have come to mediate catchment management.
Genistein Excitation of Gonadotrophin‐Releasing Hormone Neurones in Juvenile Female Mice
Authors: Bhattarai J. P. , Ábrahám I. M. , Han S. K.
Published: January 2013

We investigated the effects of the phytoestrogen genistein on gonadotrophin‐releasing hormone (GnRH) neurones using single‐cell electrophysiology on GnRH‐green fluorescent protein (GFP) transgenic juvenile female mice. Perforated patch‐clamp recordings from GnRH‐GFP neurones showed that approximately 83% of GnRH neurones responded to 30 μm genistein with a markedly prolonged membrane depolarisation. This effect not only persisted in the presence of tetrodotoxin, but also in the presence of amino acid receptor antagonists, indicating the direct site of action on postsynaptic GnRH neurones. Using a voltage clamp technique, we found that 30 μm genistein increased the frequency of synaptic current of GnRH neurones clamped at −60 mV in the presence of glutamate receptor blocker but not GABAA receptor blocker. Pre‐incubation of GnRH neurones with 30 μm genistein enhanced kisspeptin‐induced membrane depolarisation and firing. GnRH neurones of juvenile mice injected with genistein in vivo showed an enhanced kisspeptin response compared to vehicle‐injected controls. The transient receptor potential channel (TRPC) blocker 2‐aminoethoxydiphenyl borate (75 μm) blocked the genistein‐mediated response on GnRH neurones. These results demonstrate that genistein acts on GnRH neurones in juvenile female mice to induce excitation via GABA neurotransmission and TRPCs to enhance kisspeptin‐induced activation.
Environmental controls on the Late Holocene carbonate sedimentation of a karstic lake in the Middle‐Atlas Mountains (Lake Afourgagh, Morocco)
Authors: Détriché Sébastien , Bréhéret Jean‐Gabriel , Karrat L'houcine , Hinschberger Florent , Macaire Jean‐Jacques
Published: January 2013

The Lake Afourgagh sediment record and facies successions provide an outstanding example of environmentally controlled carbonate sedimentation. Afourgagh is a small, shallow permanent lake located in the Middle‐Atlas Mountains in Morocco in a karstic context. It is fed by ground waters that are relatively enriched in Mg resulting from the leaching of the Jurassic dolomitic bedrock of the catchment. This eutrophic lake is episodically restricted and characterized by alkaline waters with a fluctuating high Mg/Ca ratio. The maximum extension of the Holocene shoreline coincides with evidence of a lake stabilization level corresponding to the outflow of the lake through a wadi. Lakeshore terrace sediments deposited on an alluvial fan siltstone during the past ca 2500 cal yr bp comprise four main facies: a littoral crust, palaeosols, palustrine silts and charophyte tufas, which reflect different environments from the shoreline toward the deeper water. In the more distal parts, the charophyte tufas display a well‐expressed lamination punctuated by the development of microstromatolites on algae thalli. The mineralogical composition of the carbonates is linked to the facies. While the charophyte tufas are characterized by a relatively high content in aragonite, in addition to low‐Mg calcite, the littoral crust is mainly composed of magnesite. This pattern is related to the evolving chemistry of water due to the influence of charophyte proliferation during dry summers. Calcium‐carbonate precipitation on algae thalli (both bioinduced and microbially mediated) progressively induces an increase in the Mg/Ca ratio of the lake water, while the capillary evaporation of shallow ground waters causes precipitation of a magnesite precursor on the shoreline, producing magnesite during early diagenesis. This effect is characteristic of two episodes: part of the Roman Warm Period and the beginning of the Dark Age Cold Period. The carbonate mineralogy of the different depositional sequences at Afourgagh indicates lake‐level and water‐chemistry fluctuations under a climatic influence. Therefore, among other regional records, the Lake Afourgagh sedimentary record provides useful evidence for reconstructing these environmental changes.
Deep hypothermia protects against acute hypoxia in vivo in rats: a mechanism related to the attenuation of oxidative stress
Authors: Alva Norma , Azuara Daniel , Palomeque Jesús , Carbonell Teresa
Published: January 2013

New Findings

What is the central question of this study?

Hypoxia generates extreme physiological stress. This stress leads to the formation of oxidants. The effects of hypothermia in oxidative stress are less well known, but hypothermia has recently been used to protect against ischaemic lesions. The mechanisms of such protection are, to date, unknown.

What is the main finding and its importance?

We have used extreme conditions of hypoxia (10% oxygen) and hypothermia (22°C) to analyse the oxidant–antioxidant balance in rats. Our experimental findings suggest that hypothermia plays a protective role against lipid peroxidation in vivo through the preservation of reduced/oxidized glutathione, providing new insights into the use of hypothermia.

There is growing interest in using hypothermia to prevent hypoxic damage in clinical and experimental models, although the mechanisms regulated by hypothermia are still unclear. As reactive oxygen and nitrogen species are the main factors causing cellular damage, our objective was to study the scope of hypothermia in preventing hypoxia‐induced oxidative damage. We analysed systemic and hepatic indicators of oxidative stress after an acute hypoxic insult (10% oxygen in breathing air) in normothermic (37°C body temperature) and hypothermic conditions (22°C) in rats. Exposure to hypoxia resulted in tissue damage (aspartate aminotransferase increased from 54.6 ± 6.9 U l−1 in control animals to 116 ± 1.9 U l−1 in hypoxia, and alanine aminotransferase increased from 19 ± 0.8 to 34 ± 2.9 U l−1), oxidative stress (nitric oxide metabolites increased from 10.8 ± 0.4 μm in control rats to 23 ± 2.7 μm in hypoxia, and thiobarbituric reactive substances increased from 3.3 ± 0.2 to 5.9 ± 0.4 nm) and antioxidant consumption (reduced/oxidized glutathione ratio changed from 9.8 ± 0.3 to 6.8 ± 0.3). In contrast, when hypothermia was applied prior to hypoxia, the situation was reversed, with a reduction in aspartate aminotransferase (from 116 ± 1.9 in hypoxic animals to 63 ± 7.8 U l−1 in animals exposed to hypothermia followed by hypoxia), alanine aminotransferase (from 34 ± 2.9 to 19 ± 0.9 U l−1), oxidative stress (nitric oxide metabolites decreased from 23 ± 2.7 to 17.8 ± 1.9 μm and thiobarbituric acid‐reactive substances decreased from 5.9 ± 0.4 to 4.3 ± 0.2 nm) and antioxidant preservation (reduced/oxidized glutathione ratio changed from 6.8 ± 0.3 to 11.1 ± 0.1). Hypoxia induced a decrease in liver enzymatic antioxidant activities even during hypothermia. Both treatments, hypoxia and hypothermia, produced a similar increase in hepatic caspase‐3 activity. In conclusion, hypothermia prevented the tissue damage and oxidative stress elicited by hypoxia. Our results provide new evidence concerning the protective mechanism of hypothermia in vivo.
Genetic Tools To Enhance the Study of Gene Function and Regulation in Staphylococcus aureus
Authors: Bose Jeffrey L. , Fey Paul D. , Bayles Kenneth W.
Published: January 2013

The
bursa aurealis
transposon has been used to create transposon insertion libraries of
Bacillus anthracis
and
Staphylococcus aureus
. To provide a set of genetic tools to enhance the utility of these libraries, we generated an allelic-exchange system that allows for the replacement of the transposon with useful genetic markers and fluorescent reporter genes. These tools were tested in the Nebraska Transposon Mutant Library (NTML), containing defined transposon insertions in 1,952 nonessential
S. aureus
genes. First, we generated a plasmid that allows researchers to replace the genes encoding green fluorescent protein (GFP) and erythromycin resistance in the transposon with a noncoding DNA fragment, leaving a markerless mutation within the chromosome. Second, we produced allelic-exchange plasmids to replace the transposon with alternate antibiotic resistance cassettes encoding tetracycline, kanamycin, and spectinomycin resistance, allowing for the simultaneous selection of multiple chromosomal mutations. Third, we generated a series of fluorescent reporter constructs that, after allelic exchange, generate transcriptional reporters encoding codon-optimized enhanced cyan fluorescent protein (ECFP), enhanced yellow fluorescent protein (EYFP), DsRed.T3(DNT), and eqFP650, as well as superfolder green fluorescent protein (sGFP). Overall, combining the NTML with this allelic-exchange system provides an unparalleled resource for the study of
S. aureus
.
Genetic Diversity of Cryptosporidium spp. within a Remote Population of Soay Sheep on St. Kilda Islands, Scotland
Authors: Connelly L. , Craig B. H. , Jones B. , Alexander C. L.
Published: January 2013

This is the first report to characterize the genotypes and subtypes of
Cryptosporidium
species infecting a geographically isolated population of feral Soay sheep (
Ovis aries
) on Hirta, St. Kilda, Scotland, during two distinct periods: (i) prior to a population crash and (ii) as host numbers increased.
Cryptosporidium
DNA was extracted by freeze-thawing of immunomagnetically separated (IMS) bead-oocyst complexes, and species were identified following nested-PCR-restriction fragment length polymorphism (RFLP)/PCR sequencing at two
Cryptosporidium
18S rRNA loci. Two hundred fifty-five samples were analyzed, and the prevalent
Cryptosporidium
species in single infections were identified as
C. hominis
(11.4% of all samples tested),
C. parvum
(9%),
C. xiaoi
(12.5%), and
C. ubiquitum
(6.7%).
Cryptosporidium parvum
was also present with other
Cryptosporidium
species in 27.1% of all samples tested.
Cryptosporidium parvum
- and
C. hominis
-positive isolates were genotyped using two nested-PCR assays that amplify the
Cryptosporidium
glycoprotein 60 gene (
GP60
).
GP60
gene analysis showed the presence of two
Cryptosporidium
genotypes, namely,
C. parvum
IIaA19G1R1 and
C. hominis
IbA10G2. This study reveals a higher diversity of
Cryptosporidium
species/genotypes than was previously expected. We suggest reasons for the high diversity of
Cryptosporidium
parasites within this isolated population and discuss the implications for our understanding of cryptosporidiosis.
Symbiont-Mediated Protection against Fungal Pathogens in Pea Aphids: a Role for Pathogen Specificity?
Authors: Parker Benjamin J. , Spragg Chelsea J. , Altincicek Boran , Gerardo Nicole M.
Published: January 2013

Here we show that a bacterial endosymbiont,
Regiella insecticola
, protects pea aphids (
Acyrthosiphon pisum
) from the aphid-specific fungal entomopathogen
Zoophthora occidentalis
but not from the generalist insect fungal pathogen
Beauveria bassiana
. This finding highlights the complex influence of fungi on the dynamics of this economically important agricultural pest.
Recent Evolutionary Radiation and Host Plant Specialization in the Xylella fastidiosa Subspecies Native to the United States
Authors: Nunney Leonard , Vickerman Danel B. , Bromley Robin E. , Russell Stephanie A. , Hartman John R. , Morano Lisa D. , Stouthamer Richard
Published: January 2013

The bacterial pathogen,
Xylella fastidiosa
, infects many plant species in the Americas, making it a good model for investigating the genetics of host adaptation. We used multilocus sequence typing (MLST) to identify isolates of the native U.S. subsp.
multiplex
that were largely unaffected by intersubspecific homologous recombination (IHR) and to investigate how their evolutionary history influences plant host specialization. We identified 110 “non-IHR” isolates, 2 minimally recombinant “intermediate” ones (including the subspecific type), and 31 with extensive IHR. The non-IHR and intermediate isolates defined 23 sequence types (STs) which we used to identify 22 plant hosts (73% trees) characteristic of the subspecies. Except for almond, subsp.
multiplex
showed no host overlap with the introduced subspecies (subspecies
fastidiosa
and
sandyi
). MLST sequences revealed that subsp.
multiplex
underwent recent radiation (<25% of subspecies age) which included only limited intrasubspecific recombination (ρ/θ = 0.02); only one isolated lineage (ST50 from ash) was older. A total of 20 of the STs grouped into three loose phylogenetic clusters distinguished by nonoverlapping hosts (excepting purple leaf plum): “almond,” “peach,” and “oak” types. These host differences were not geographical, since all three types also occurred in California. ST designation was a good indicator of host specialization. ST09, widespread in the southeastern United States, only infected oak species, and all peach isolates were ST10 (from California, Florida, and Georgia). Only ST23 had a broad host range. Hosts of related genotypes were sometimes related, but often host groupings crossed plant family or even order, suggesting that phylogenetically plastic features of hosts affect bacterial pathogenicity.