bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering the flight autostabilizer of fruit flies by inducing aerial stumbles
Authors: Ristroph Leif , Bergou Attila J. , Ristroph Gunnar , Coumes Katherine , Berman Gordon J. , Guckenheimer John , Wang Z. Jane , Cohen Itai
Published: March 2010

Just as the Wright brothers implemented controls to achieve stable airplane flight, flying insects have evolved behavioral strategies that ensure recovery from flight disturbances. Pioneering studies performed on tethered and dissected insects demonstrate that the sensory, neurological, and musculoskeletal systems play important roles in flight control. Such studies, however, cannot produce an integrative model of insect flight stability because they do not incorporate the interaction of these systems with free-flight aerodynamics. We directly investigate control and stability through the application of torque impulses to freely flying fruit flies (
Drosophila melanogaster
) and measurement of their behavioral response. High-speed video and a new motion tracking method capture the aerial “stumble,” and we discover that flies respond to gentle disturbances by accurately returning to their original orientation. These insects take advantage of a stabilizing aerodynamic influence and active torque generation to recover their heading to within 2° in < 60 ms. To explain this recovery behavior, we form a feedback control model that includes the fly’s ability to sense body rotations, process this information, and actuate the wing motions that generate corrective aerodynamic torque. Thus, like early man-made aircraft and modern fighter jets, the fruit fly employs an automatic stabilization scheme that reacts to short time-scale disturbances.
Mutant

Ikzf1, Kras
G12D

, and
Notch1
cooperate in T lineage leukemogenesis and modulate responses to targeted agents
Authors: Dail Monique , Li Qing , McDaniel Andrew , Wong Jason , Akagi Keiko , Huang Ben , Kang Hio Chung , Kogan Scott C. , Shokat Kevan , Wolff Linda , Braun Benjamin S. , Shannon Kevin
Published: March 2010

Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in

Mx1-Cre, Kras
G12D

mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within
Ikzf1
is an early event in leukemogenesis that precedes

Kras
G12D

expression and later acquisition of somatic
Notch1
mutations. Importantly, biochemical analysis uncovered unexpected heterogeneity, which suggests that Ras signaling networks are remodeled during multistep tumorigenesis. We tested tumor-derived cell lines to identify biomarkers of therapeutic response to targeted inhibitors. Whereas all T-ALLs tested were sensitive to a dual-specificity phosphoinosityl 3-kinase/mammalian target of rapamycin inhibitor, biochemical evidence of Notch1 activation correlated with sensitivity to γ-secretase inhibition. In addition,

Kras
G12D

T-ALLs were more responsive to a MAP/ERK kinase inhibitor in vitro and in vivo. Together, these studies identify a genetic pathway involving

Ikzf1, Kras
G12D

, and
Notch1
in T lineage leukemogenesis, reveal unexpected diversity in Ras-regulated signaling networks, and define biomarkers of drug responses that may inform treatment strategies.
Pore architecture of the ORAI1 store-operated calcium channel
Authors: Zhou Yubin , Ramachandran Sweta , Oh-hora Masatsugu , Rao Anjana , Hogan Patrick G.
Published: March 2010

ORAI1 is the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, a store-operated channel that is central to Ca
2+
signaling in mammalian cells. Electrophysiological data have shown that the acidic residues E106 in transmembrane helix 1 (TM1) and E190 in TM3 contribute to the high selectivity of ORAI1 channels for Ca
2+
. We have examined the pore architecture of the ORAI1 channel using ORAI1 proteins engineered to contain either one or two cysteine residues. Disulfide cross-linking shows that ORAI1 assembles as a tetramer or a higher oligomer with TM1 centrally located. Cysteine side chains projecting from TM1 at position 88, 95, 102, or 106 cross-link efficiently to the corresponding side chain in a second ORAI1 monomer. Cysteine residues at position 190 or at surrounding positions in TM3 do not cross-link. We conclude that E106 residues in wild-type ORAI1 are positioned to form a Ca
2+
binding site in the channel pore and that E190 interacts less directly with ions traversing the pore. The cross-linking data further identify a relatively rigid segment of TM1 adjacent to E106 that is likely to contribute to the selectivity filter.
Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase
Authors: Beck Halfdan , Nähse Viola , Larsen Marie Sofie Yoo , Groth Petra , Clancy Trevor , Lees Michael , Jørgensen Mette , Helleday Thomas , Syljuåsen Randi G. , Sørensen Claus Storgaard
Published: March 2010

Maintenance of genome integrity is of critical importance to cells. To identify key regulators of genomic integrity, we screened a human cell line with a kinome small interfering RNA library. WEE1, a major regulator of mitotic entry, and CHK1 were among the genes identified. Both kinases are important negative regulators of CDK1 and -2. Strikingly, WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA, which was accompanied by a marked increase in single-stranded DNA. This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. Furthermore, the inferior proliferation of CHK1-depleted cells is improved substantially by codepletion of CDC25A. We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication.
The novel endosomal membrane protein Ema interacts with the class C Vps–HOPS complex to promote endosomal maturation
Authors: Kim Sungsu , Wairkar Yogesh P. , Daniels Richard W. , DiAntonio Aaron
Published: March 2010

Endosomal maturation is critical for accurate and efficient cargo transport through endosomal compartments. Here we identify a mutation of the novel Drosophila gene, ema (endosomal maturation defective) in a screen for abnormal synaptic overgrowth and defective protein trafficking. Ema is an endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. In the ema mutant, enlarged endosomal compartments accumulate as endosomal maturation fails, with early and late endosomes unable to progress into mature degradative late endosomes and lysosomes. Defective endosomal down-regulation of BMP signaling is responsible for the abnormal synaptic overgrowth. Ema binds to and genetically interacts with Vps16A, a component of the class C Vps–HOPS complex that promotes endosomal maturation. The human orthologue of ema, Clec16A, is a candidate susceptibility locus for autoimmune disorders, and its expression rescues the Drosophila mutant demonstrating conserved function. Characterizing this novel gene family identifies a new component of the endosomal pathway and provides insights into class C Vps–HOPS complex function.
Essential roles of sphingosine-1–phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema
Authors: Oskeritzian Carole A. , Price Megan M. , Hait Nitai C. , Kapitonov Dmitri , Falanga Yves T. , Morales Johanna K. , Ryan John J. , Milstien Sheldon , Spiegel Sarah
Published: March 2010

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1–phosphate (S1P), a ligand for a family of G protein–coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E–triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P2 antagonist JTE-013 and in S1P2-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P2 on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.
An Ergatis-based prokaryotic genome annotation web server
Authors: Hemmerich Chris , Buechlein Aaron , Podicheti Ram , Revanna Kashi V. , Dong Qunfeng
Published: March 2010

Summary: Ergatis is a flexible workflow management system for designing and executing complex bioinformatics pipelines. However, its complexity restricts its usage to only highly skilled bioinformaticians. We have developed a web-based prokaryotic genome annotation server, Integrative Services for Genomics Analysis (ISGA), which builds upon the Ergatis workflow system, integrates other dynamic analysis tools and provides intuitive web interfaces for biologists to customize and execute their own annotation pipelines. ISGA is designed to be installed at genomics core facilities and be used directly by biologists.

Availability: ISGA is accessible at http://isga.cgb.indiana.edu/ and the system is also freely available for local installation.

Contact:  qunfeng.dong@unt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Understanding changing patterns of survival and hospitalization for heart failure over two decades in New Zealand: utility of ‘days alive and out of hospital’ from epidemiological data
Authors: Wasywich Cara A. , Gamble Greg D. , Whalley Gillian A. , Doughty Robert N.
Published: March 2010

Aims

To describe changes in heart failure (HF) epidemiology in New Zealand between 1988 and 2008 using the number of days alive and out of hospital after a first hospitalization for HF, and to use these data to evaluate the overall impact of changing patterns of hospitalization and survival.

Methods and results

We performed a population analysis of all HF hospitalization and mortality data from 1 January 1988 to 31 December 2008 in New Zealand. The main outcome measures were: days alive and out of hospital, age standardized hospitalization rates, and mortality after an index hospitalization for HF. The number of days alive and out of hospital at 2 years increased by 2 months over the two decades of the study (from 448.8 to 511.3 days). Age standardized index HF hospitalization rates increased from 1988 to 1999, and declined thereafter, current rates are 106.9/100 000 for women and 174.3/100 000 for men. Patient age at index admission progressively increased, and hospital length of stay decreased. Mortality rates progressively decreased until 2000, but there has been no further decrease since then. Total hospital days have decreased up to 2008.

Conclusion

There have been major changes in the epidemiology of HF in New Zealand between 1988 and 2008, during which time there have been important changes in HF management. Despite increasing age, hospitalization rates are now declining and patients with HF are surviving longer out of hospital and with fewer hospital days. These results support the need for continued emphasis on delivery of effective community‐based care for patients with this long‐term condition.
The homeobox protein Prox1 is a negative modulator of ERRα/PGC-1α bioenergetic functions
Authors: Charest-Marcotte Alexis , Dufour Catherine R. , Wilson Brian J. , Tremblay Annie M. , Eichner Lillian J. , Arlow Daniel H. , Mootha Vamsi K. , Giguère Vincent
Published: March 2010

Estrogen-related receptor α (ERRα) and proliferator-activated receptor γ coactivator-1α (PGC-1α) play central roles in the transcriptional control of energy homeostasis, but little is known about factors regulating their activity. Here we identified the homeobox protein prospero-related homeobox 1 (Prox1) as one such factor. Prox1 interacts with ERRα and PGC-1α, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERRα/PGC-1α complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERRα and other factors. Importantly, ablation of Prox1 and ERRα have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis.
Expression of heme oxygenase‐1 in human leukemic cells and its regulation by transcriptional repressor Bach1
Authors: Miyazaki Takuya , Kirino Yohei , Takeno Mitsuhiro , Samukawa Sei , Hama Maasa , Tanaka Masatsugu , Yamaji Satoshi , Ueda Atsuhisa , Tomita Naoto , Fujita Hiroyuki , Ishigatsubo Yoshiaki
Published: March 2010

Heme oxygenase (HO)‐1 has anti‐oxidative, anti‐inflammatory, and anti‐apoptotic activities. However, little is known about the regulation of HO‐1 in human primary acute myeloid leukemia (AML) cells. Here we investigated the expression of HO‐1 in primary and established AML cells as well as other types of leukemic cells and normal monocytes, and its regulatory mechanism by the transcriptional repressor, BTB and CNC homology 1 (Bach1), and the activator, nuclear factor erythroid‐derived 2 related factor 2 (Nrf2). Leukemic cell lines such as U937 expressed little HO‐1, whereas most freshly isolated AML cells and monocytes expressed substantial amounts of HO‐1, along with Bach1 and Nrf2. When U937 cells were treated with phorbol myristate acetate (PHA) or γ‐interferon, they significantly expressed both HO‐1 and Bach1, like primary AML cells. Treatment with lipopolysaccharide (LPS) enhanced HO‐1 expression in U937 cells but suppressed it in primary monocytes and PMA‐treated U937 cells. In HO‐1‐expressing cells, Bach1 was localized in the cytoplasm, but Nrf2 was localized in the nuclei. Chromatin immunoprecipitation assay of these cells revealed the preferential binding of Nrf2 over Bach1 to Maf‐recognition elements, the enhancer regions of the HO‐1 gene. The downregulation of the HO‐1 gene with siRNA increased a cytotoxic effect of an anticancer drug on primary AML cells, whereas the downregulation of Bach1 increased HO‐1 expression, leading to enhanced survival. These and other results show that Bach1 plays a critical role in regulating HO‐1 gene expression in AML cells and its expression suppresses their survival by downregulating HO‐1 expression. Thus, functional upregulation of Bach1 is a potential strategy for antileukemic therapy. (Cancer Sci 2010)
Evidence for the effectiveness of sterile injecting equipment provision in preventing hepatitis C and human immunodeficiency virus transmission among injecting drug users: a review of reviews
Authors: Palmateer Norah , Kimber Jo , Hickman Matthew , Hutchinson Sharon , Rhodes Tim , Goldberg David
Published: March 2010

Aims  To review the evidence on the effectiveness of harm reduction interventions involving the provision of sterile injecting equipment in the prevention of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). The interventions assessed were needle and syringe programmes (NSP), alternative modes of needle/syringe provision (pharmacies, vending machines and outreach) and the provision of injecting equipment other than needles/syringes.

Methods  Systematic searches of the English language literature to March 2007 were undertaken to identify systematic, narrative or meta‐analytical reviews (also known as a review of reviews) of the impact of interventions on HCV transmission, HIV transmission or injecting risk behaviour (IRB). Critical appraisal criteria classified the reviews as either high quality (‘core’) or supplementary: a framework based on the quality of reviews, the reviewers' conclusions and the designs/findings of the primary studies was used to derive evidence statements.

Results  Three core and two supplementary reviews of injecting equipment interventions were identified. According to the proposed framework, this study found (a) insufficient evidence to conclude that any of the interventions are effective in preventing HCV transmission; (b) tentative evidence to support the effectiveness of NSP in preventing HIV transmission; (c) sufficient evidence to support the effectiveness of NSP (and tentative evidence of an additional impact of pharmacy NSP) in reducing self‐reported IRB; and (d) little to no evidence on vending machines, outreach or providing other injecting equipment in relation to any of the outcomes.

Conclusions  The evidence is weaker than given credit for in the literature. The lack of evidence for effectiveness of NSP vis‐à‐vis biological outcomes (HCV and HIV incidence/prevalence) reflects the limitations of studies that have been undertaken to investigate these associations. Particularly for HCV, low levels of IRB may be insufficient to reduce high levels of transmission. New studies are required to identify the intervention coverage necessary to achieve sustained changes in blood‐borne virus transmission.
The perspectives of young children in care about their circumstances and implications for social work practice
Authors: Winter Karen
Published: March 2010

Recent reviews of research regarding children in care have concluded that there remains little research which specifically focuses on young children. This paper presents the findings of research carried out with a sample of young children in care (aged 4–7 years) regarding their perspectives of their circumstances. The findings reveal that they have deeply held views regarding living with risk; removal from their families; unresolved feelings of guilt and loss; and not being listened to. This paper considers the implications of these findings for social work practice. It concludes by stressing the capacity of young children in care to express their perspectives, and the importance of practitioners seeking these views and incorporating them into assessment and decision‐making processes.
Someone to check in on me: social capital, social support and vulnerable parents with very young children in the Australian Capital Territory
Authors: Winkworth Gail , McArthur Morag , Layton Megan , Thompson Lorraine
Published: March 2010

Although knowledge of how social support can mediate stress is now well known, finding ways to enable isolated parents to access social resources that could make a positive difference for children during their critical early years remains difficult. This paper reported on the findings of a telephone survey aimed at understanding levels of social capital and social support experienced by isolated parents raising young children on their own in Canberra, Australia. Specifically, it discussed a successful methodology for reaching isolated parents, those whom services find hard to reach. The survey found that despite the relative affluence of Canberra's population, there is a significant group of parents who are isolated from both formal and informal support and the social capital that can help them cope with the stresses and demands of raising young children. These parents were unsure where to get parenting information and had a strong sense that they were judged by their local communities and services. We identified lost opportunities by general practitioners and other widely used systems such as public housing and security to take more proactive roles and connect parents to formal service support systems. Flexible, affordable child care was identified as an unmet need for these parents, not only as a source of relief from extreme isolation but also to enable them to work or prepare for work through study.
ADHD and its comorbidity: an example of gene–environment interaction and its implications for child and family social work
Authors: Howe David
Published: March 2010

In many of their cases, child and family social workers, particularly those involved with abuse and neglect, will find themselves also working with children who have been diagnosed with attention deficit hyperactivity disorder (ADHD). The paper reviews current understandings and debates about the nature and causes of ADHD. Although modern evidence suggests the neurobiological basis of the condition and the effectiveness of medication in treating the behaviour, it is also recognized that the quality of the child's caregiving and social environment plays a significant role in the aetiology, maintenance and treatment of ADHD. Recognizing the part that psychosocial elements play in understanding the condition, child and family social workers can be valued members of multidisciplinary teams treating ADHD in which they offer support to parents, helping them to understand and manage their ADHD‐diagnosed child.
Ex vivo evaluation of the accuracy and coefficient of repeatability of three electronic apex locators using a simple mounting model: a preliminary report
Authors: D’Assunção F. L. C. , Albuquerque D. S. , Salazar‐Silva J. R. , Dos Santos V. C. , Sousa J. C. N.
Published: March 2010

D’Assunção FLC, Albuquerque DS, Salazar‐Silva JR, Dos Santos VC, Sousa JCN.
Ex vivo evaluation of the accuracy and coefficient of repeatability of three electronic apex locators using a simple mounting model: a preliminary report. International Endodontic Journal, 43, 269–274, 2010.

Aim  To compare ex vivo the accuracy and coefficient of repeatability of three electronic apex locators in locating the apical constriction.

Methodology  Thirty‐one single‐rooted teeth were used. The teeth were sectioned at the cement–‐enamel junction. A mounting model was used for the measurement of electronic length (EL). The Root ZX‐II, the Mini Apex Locator and the Novapex were used for electronic measurements. Each electronic measurement was obtained and repeated. After the last measurement, the file was cemented in place, and the apical 4 mm of each root canal was exposed. The distance from the tip of the file to the apical constriction was determined by three investigators and compared with the corresponding ELs.

Results  The coefficient of repeatability of all devices was acceptable: Root ZX‐II, 0.04 mm; Mini Apex Locator, 0.10 mm; and Novapex, 0.08 mm. There was little variation in inter‐examiner agreement; the ρC (Lin) correlation coefficient was 0.83 for examiners 1 and 2, 0.88 for examiners 1 and 3 and 0.99 for examiners 2 and 3. Using the Root ZX‐II, 13 of 31 electronic measurements were located at the apical constriction (42%). Otherwise, the tip of the file was not located at the apical constriction in any of the electronic measurements with the other two devices. The Wilcoxon signed rank test did not reveal any statistical difference between the Root ZX‐II measurements and the actual length (P = 0.628), but there was a statistical difference between the Mini Apex Locator and Novapex measurements and the actual length position (P < 0.05).

Conclusions  The devices tested in this study had a high coefficient of repeatability. The Root ZX‐II was accurate, but the Mini Apex Locator and Novapex were not accurate in locating the apical constriction.
Endodontists experience using ultrasonics for removal of intra‐canal fractured instruments
Authors: Madarati A. A. , Qualtrough A. J. E. , Watts D. C.
Published: March 2010

Madarati AA, Qualtrough AJE, Watts DC. Endodontists experience using ultrasonics for removal of intra‐canal fractured instruments. International Endodontic Journal 43, 301–305, 2010.

Aim  To investigate the experience of UK endodontists with aspects of ultrasonic use for removal of intra‐canal fractured instruments.

Methodology  A questionnaire form comprising both close‐ended and partially close‐ended questions with a covering letter explaining the aims of the study and indicating that all information would remain confidential and anonymous were sent to 180 endodontists working in the UK. Non respondents received a reminder with a differently worded covering letter. After collecting the responses, data were entered into SPSS software through which frequencies were determined and the chi‐square test at the 0.05 level of significance, when required, was applied.

Results  Overall, 97% of endodontists reported the use of ultrasonics for removal of fractured instruments. The majority of them (78%) used ultrasonics with a coolant at least some of the time. Forty‐seven per cent of users activated tips at medium to maximum power settings. The greatest proportion (53%) activated the tips for approximately 10 s.

Conclusions  Endodontists reported different techniques when using ultrasonics for removal of fractured instruments.
Investigation of the interactions between neutrophils and endodontic isolates of Enterococcus faecalis
Authors: Sairafi R. , Ready D. , Gulabivala K. , Nair S.P.
Published: March 2010

Aim  The primary aim of this study was to investigate the effect of phagocytosis by neutrophils on the antimicrobial sensitivity of Enterococcus faecalis strains. A secondary aim was to determine whether carriage of a plasmid encoding aggregation substance (AS), which has been reported to increase the survival of some strains inside neutrophils, affected the antimicrobial susceptibility of E. faecalis after phagocytosis by neutrophils.

Methodology  An assay was carried out to identify isolates of E. faecalis which demonstrated pheromone‐responsive clumping caused by the production of aggregation substance (AS). Four E. faecalis strains grown to both logarithmic and stationary phases were exposed to sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX) to determine the minimum inhibitory concentrations of these two agents. The antimicrobial susceptibility tests were repeated with E. faecalis strains which survived phagocytosis by neutrophils for 18 h.

Results  As expected a laboratory strain of E. faecalis OG1RF which was AS negative became AS positive after introduction of the pheromone responsive plasmid pCF10 into the bacterium to give strain OG1RF(pCF10). These two strains and two endodontic isolates, E08‐584 which demonstrated pheromone‐responsive clumping and E08‐398 which did not, were selected for further study All the test E. faecalis strains were inhibited by low concentrations of sodium hypochlorite (MIC range 0.02–0.3%) and chlorhexidine gluconate (MIC range 0.0004–0.004%). Bacteria recovered from inside neutrophils after 18 h following phagocytosis were susceptible to both ¼MIC and MIC of CHX and NaOCl.

Conclusions  Aggregation substance did not appear to affect the antimicrobial susceptibility of any of the strains to CHX or NaOCl. All of the E. faecalis strains examined were capable of survival for 18 h inside the neutrophils following phagocytosis; regardless of their capacity to produce aggregation substance. In addition, all strains of E. faecalis had enhanced susceptibilities to the antimicrobial agents after residence inside neutrophils for 18 h.
The probability of and factors influencing tooth survival following non‐surgical root canal treatment – a prospective study
Authors: Ng Y.‐L. , Mann V. , Gulabivala K.
Published: March 2010

Aim  To investigate the probability of and factors influencing tooth survival following primary or secondary root canal treatment.

Methodology  This prospective study involved annual follow‐up of up to 4 years of primary (759 teeth, 572 patients) or secondary (858 teeth, 642 patients) root canal treatment in an Eastman cohort. Informed consent was obtained from the patients. Pre‐, intra‐ and post‐operative data were collected prospectively on customised proforma. Information about extraction of the root treated tooth was reported by the patient, the referring dentist or extracted from the patient's hospital medical records. The timing and reasons for extraction were recorded. Tooth survival was estimated and prognostic factors investigated using Cox regression. Clustering effects within patients were adjusted in all models using robust standard error.

Results  The 4‐year tooth survival after primary root canal treatment (95.4%) or secondary root canal treatment (95.3%) were similar. Fourteen prognostic factors were identified. Significant patient factors included: History of diabetes and systemic steroid therapy. Significant pre‐operative factors included: narrow periodontal probing depth; pain; discharging sinus; cervical root resorption; and iatrogenic perforation (for retreatment cases only). Significant intra‐operative factors included: iatrogenic perforation; patency at apical terminus; and extrusion of root fillings. Significant post‐operative restorative factors included: Presence of cast restoration or temporary restoration; presence of cast post & core; proximal contacts with both mesial and distal adjacent teeth; and terminal location of the tooth. The presence of pre‐operative pain had a profound effect on tooth loss within the first 22 months after treatment (HR = 3.1; P = 0.001) with a lesser effect beyond 22 months (HR = 2.4; P = 0.01). Patency at the apical terminus reduced tooth loss (HR = 0.3; P < 0.01) within the first 22 months after treatment but had no significant effect on tooth survival beyond 22 months. Extrusion of gutta‐percha root filling did not have any effect on tooth survival (HR = 1.1; P = 0.2) within the first 22 months but significantly increased the hazard of tooth loss beyond 22 months (HR = 3.0; P = 0.003).

Conclusions  The 4‐year tooth survival following primary or secondary root canal treatment was 95%; with fourteen prognostic factors common to both.
A comparison of enterococcal genotypes from the human mouth and cheese
Authors: Williams S.C. , Wade W.G.
Published: March 2010

Aim  The aim of this study was to investigate the prevalence of enterococci in saliva, from within infected root treated teeth, and in British‐produced cheeses. An additional aim was to determine if similar enterococcal genotypes were found within these three groups.

Methodology  Seventy four samples were collected from the three groups and cultured on Chromocult® enterococci agar. The cultured bacteria were then identified using the Rapid ID 32 Strep kit (bioMerieux). DNA was then extracted from the enterococcal isolates, and genotyping performed by means of repetitive extragenic palindromic (REP) PCR with REP1R‐DT and REP‐2DT primers. Strains were assigned to clonal types by means of the GelCompar software analysis of REP‐PCR profiles.

Results  Enterococci were isolated from 8 of 50 saliva samples, and from 4 of 15 root canal samples, and from seven of nine cheese samples. Sixteen isolates were identified as E. faecalis, one isolate was identified as E. faecium, one isolate was identified as E. durans, and one isolate identified as E. avium. REP‐PCR revealed nine clonal types within E. faecalis. The same clonal types were found in samples from saliva, from the root canal, and from British‐produced cheeses.

Conclusions  The prevalence of enterococci in the oral cavity was found to be 12%. The prevalence in the infected previously treated root canal was 27%. Enterococci was isolated from seven out of nine British cheeses investigated. The same clonal types of E. faecalis were recovered from saliva, from in the previously treated infected root canal and from British‐produced cheese's. It would be of interest to investigate the prevalence of E. faecalis in the oral cavity from people that do not eat cheese due to the fact of medical reasons or through choice, to see if there is any difference in the prevalence found.
Apical fit of initial K‐files in maxillary molars assessed by micro‐computed tomography
Authors: Paqué F. , Zehnder M. , Marending M.
Published: March 2010

Paqué F, Zehnder M, Marending M. Apical fit of initial K‐files in maxillary molars assessed by micro‐computed tomography. International Endodontic Journal, 43, 328–335, 2010.

Aim  To two‐ and three‐dimensionally assess the fit of the first K‐file binding at working length after a crown‐down canal procedure.

Methodology  Twelve maxillary molars with fully developed roots and four separate root canals were selected. Canals were pre‐flared using ProFile 0.04 instruments to three quarters of estimated working length (WL). WL was electronically determined using an ISO 06 K‐file. Progressively larger K‐files were inserted passively to WL. The first binding file was termed initial apical file (IAF). On micro‐computed tomography (μCT) scans, cross‐sectional areas of IAFs and canals and the largest and smallest root canal diameters were measured 1 mm from instrument tips. Volumes of the apical 2 mm of the instruments and corresponding root canal sections were calculated, and file binding was assessed.

Results  IAF sizes ranged from ISO‐size 0.08–0.30 and were lowest in second mesiobuccal and highest in palatal canals. Files bound in the apical 2 mm in 96% of the canals. The mean canal area filled by the instruments 1 mm from the tip was below 40% in all canal types, the filled volume below 50% (anova, P > 0.05). The mean ratio (±SD) between largest and smallest canal diameter was 3.0 ± 2.6 for first mesiobuccal, 3.3 ± 2.6 for second mesiobuccal, 4.1 ± 3.5 for distobuccal and 1.6 ± 0.4 for palatal canals, indicating oval to flattened cross‐sections.

Conclusions  Two‐ and three‐dimensional analysis of μCT scans revealed that whilst IAFs bound in the apical area, their fit was poor, because their shape does not correspond to maxillary molar canal anatomy.
Pattern of antibiotic prescription in the management of endodontic infections amongst Spanish oral surgeons
Authors: Segura‐Egea J. J. , Velasco‐Ortega E. , Torres‐Lagares D. , Velasco‐Ponferrada M. C. , Monsalve‐Guil L. , Llamas‐Carreras J. M.
Published: March 2010

Segura‐Egea JJ, Velasco‐Ortega E, Torres‐Lagares D, Velasco‐Ponferrada MC, Monsalve‐Guil L, Llamas‐Carreras JM. Pattern of antibiotic prescription in the management of endodontic infections amongst Spanish oral surgeons. International Endodontic Journal, 43, 342–350, 2010.

Aim  To identify antibiotic prescription practices in the treatment of endodontic infections amongst Spanish oral surgeons.

Methodology  Members of the Spanish Oral Surgery Society (SECIB) were surveyed on antibiotic prescription on six different pulpal and periapical diagnoses. A total of 200 questionnaires were delivered with 127 returned (64%).

Results  The average duration of antibiotic therapy was 7.0 ± 1.0 days. Ninety five percent of respondents selected amoxicillin as the first choice antibiotic in patients with no medical allergies, alone (34%) or associated to clavulanate (61%). The first drug of choice for patients with an allergy to penicillins was clindamycin 300 mg (65%), followed by azithromycin (15%) and metronidazole‐spiramycin (13%). For cases of irreversible pulpitis, 86% of respondents prescribed antibiotics. For the scenario of a necrotic pulp, acute apical periodontitis and no swelling, 71% prescribed antibiotics. Almost 60% of respondents prescribed antibiotics for necrotic pulps with chronic apical periodontitis and a sinus tract; in this clinical situation, odontologists prescribed more frequently antibiotics compared to stomatologists (P = 0.0080; odds ratio = 8.0; C. I. 95% = 1.7–37.1).

Conclusions  The majority of the members of the SECIB were selecting the appropriate antibiotic for use in endodontic infections, but there are still many who are prescribing antibiotics inappropriately. The use of antibiotics for minor infections, or in some cases in patients without infections, could be a major contributor to the world problem of antimicrobial resistance.
Habitats of relict terrestrial snails in southern Siberia: lessons for the reconstruction of palaeoenvironments of full‐glacial Europe
Authors: Horsák Michal , Chytrý Milan , Pokryszko Beata M. , Danihelka Jiří , Ermakov Nikolai , Hájek Michal , Hájková Petra , Kintrová Kateřina , Kočí Martin , Kubešová Svatava , Lustyk Pavel , Otýpková Zdenka , Pelánková Barbora , Valachovič Milan
Published: March 2010

Aim Shells of fossil molluscs are important for palaeoecological reconstructions. However, the habitat requirements of snail species typical of central European full‐glacial loess sediments are poorly known because most of them became very rare or extinct in Europe. The recent discovery of an almost complete extant assemblage of such species in mountainous regions of central Asia enables more precise characterization of their habitats, which may significantly improve reconstructions of Pleistocene environments.

Location Altai Mountains, Russia.

Methods Terrestrial snail assemblages, vegetation composition and selected environmental variables were recorded at 118 sites along a gradient of climatic continentality in the Russian Altai. Habitat characteristics of sites where species typical of the full‐glacial period occurred were described using a classification tree.

Results Seven of the eight species that are typical of central European full‐glacial loess sediments were found in the study area. They were confined to cool areas with January mean temperatures below −17 °C, but occurred mainly in sheltered habitats with a warmer microclimate, such as scrub or open woodland.Pupilla loessicaandVallonia tenuilabrishad the broadest habitat range, occurring from woodland to dry steppe. Unexpectedly,Columella columella,Pupilla alpicola,Vertigo genesii,V. parcedentataandV. pseudosubstriatawere found mainly in wooded fens and shrubby tundra rather than in open steppe. Most of these seven species were recorded in base‐rich wooded fens. Very dry open steppe habitats usually supported no snails.

Main conclusions Habitat ranges of the studied snails in the Altai indicate that the full‐glacial landscapes of central European lowlands that harboured these species were not completely dominated by open and dry loess steppe. Most probably they contained a significant component of shrubby vegetation, patches of wet habitats, and probably also areas of woodland at sites with a favourable mesoclimate.
Species associations in an old‐growth temperate forest in north‐eastern China
Authors: Wang Xugao , Wiegand Thorsten , Hao Zhanqing , Li Buhang , Ye Ji , Lin Fei
Published: March 2010

1. Studying the spatial pattern of plants may provide significant insights into processes and mechanisms that maintain species richness. We used data from a fully mapped 25‐ha temperate forest plot at Changbaishan (CBS), north‐eastern China, to conduct a community‐wide assessment of the type and frequency of intra‐ and interspecific spatial association patterns. We analysed complex scale effects in the patterning of large trees of 15 common species. First, we tested for overall spatial patterning at 6, 30 and 50 m neighbourhoods and classified the types of bivariate association patterns at these spatial scales (analysis 1). We then explored small‐scale (0–20 m) association patterns conditioning on the larger‐scale pattern (analysis 2) and tested for positive large‐scale (50–250 m) association patterns (analysis 3).

2. Analysis 1 provided ample evidence for non‐random spatial patterning, and the type and frequency of spatial association patterns changed with scale. Trees of most species pairs co‐occurred less than expected by chance and positive associations were rare in local neighbourhoods. Analysis 2 revealed a separation of scales in which significant small‐scale interactions faded away at distances of 10–15 m. One third of all species pairs showed significant and mostly negative bivariate small‐scale association, which occurred more often than expected by chance between species sharing attributes such as family, fruit type and habitat association. This suggests the occurrence of competitive interactions. Analysis 3 showed that only 8% of all species pairs co‐occurred at large scales.

3. Comparison of our results with an analogous study conducted in the species‐rich tropical forest at Sinharaja, Sri Lanka, revealed several structural similarities including the dominance of segregation and partial overlap in the overall patterning (analysis 1) and the separation of scales (analysis 2). However, species pairs at CBS showed considerably more significant negative small‐scale associations (31% vs. 6% at Sinharaja).

4. Synthesis. The techniques presented here allow for a detailed analysis of the complex spatial associations in species‐rich forests and have the potential to reveal indicative patterns that may allow researchers to discriminate among competing hypotheses of community assemblage and dynamics. However, this will require comparative studies involving a large number of plots.
Competition increases with abiotic stress and regulates the diversity of biological soil crusts
Authors: Bowker Matthew A. , Soliveres Santiago , Maestre Fernando T.
Published: March 2010

1. The stress‐gradient hypothesis (SGH) predicts that the frequency of facilitative and competitive interactions will vary inversely across abiotic stress gradients, with facilitation being more common when abiotic stress is high. The effect of competition intensity on species richness is generally thought to be negative, but tests along true stress gradients are lacking. This body of research has primarily focused on vascular plants and could be well informed by broadening to other communities.

2. We report the first regional‐scale test of the SGH using biological soil crusts dominated by mosses and lichens, a key multi‐functional community of arid and semi‐arid ecosystems worldwide. We examined the intensity of facilitative or competitive interactions at the level of the community and among species pairs along an aridity gradient. Along this gradient we also examined the relationship between competition intensity and species richness.

3. All evidence strongly suggested that negative species interactions are prevalent in this study system and much more common than expected by chance. At the community scale, we found that abiotic stress associated with aridity was positively related to and explained 6–56% of the variance in indicators of facilitation or competition, dependent on the index and algorithm used. Despite this intriguing contradiction of the SGH at the whole community scale, we found scant dependency of species‐level interactions upon abiotic stress. However, the sign and intensity of these interactions proved to be species‐specific. We also found that the relationship between competition and species richness, usually negatively affected by competition, was positively related to richness at low abiotic stress, and negatively related to richness at high abiotic stress.

4. Synthesis. We propose that the response of species interactions to stress gradients may partially depend upon the particular modes of facilitation and competition, in addition to type of stressor and life‐history strategies of species involved. We also hypothesize that because stress can act as a filter, a greater number of species interactions are possible under low stress conditions. We believe that this may render intransitivity dominant over niche segregation and expansion, potentially resulting in positive effects of competition on species richness in low stress situations.
Serum and Cerebrospinal Fluid Prolactin levels in Male and Female Patients with Clinically‐Isolated Syndrome or Relapsing‐Remitting Multiple Sclerosis
Authors: Markianos M. , Koutsis G. , Evangelopoulos M. E. , Mandellos D. , Sfagos C.
Published: March 2010

There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug‐free male and female patients with clinically‐isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing‐remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17–61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women.
Both p110α and p110β Isoforms of Phosphatidylinositol 3‐OH‐Kinase are Required for Insulin Signalling in the Hypothalamus
Authors: Tups A. , Anderson G. M. , Rizwan M. , Augustine R. A. , Chaussade C. , Shepherd P. R. , Grattan D. R.
Published: March 2010

Both insulin and leptin action in the brain are considered to involve activation of phosphoinositide 3‐kinase (PI3K), although the roles of different PI3K isoforms in insulin signalling in the hypothalamus are unknown. In the present study, we characterised the roles of these isoforms in hypothalamic insulin and leptin signalling and investigated the cross‐talk of both hormones. To evaluate PI3K levels in the hypothalamus, PI3K was immunoprecipitated using an antibody directed against the p85 subunit, and then total PI3K activity was measured in the presence of novel isoform‐selective pharmacological inhibitors of each isoform of PI3K. Subsequently, these inhibitors were administered into the lateral ventricle of male Sprague‐Dawley rats, followed by vehicle, insulin, leptin or both hormones 45 min later. PI3K activity was determined by immunohistochemical detection of phosphorylated AKT (S473). In a separate study, the effects of the inhibitors on the anorexigenic action of insulin and leptin were determined. Hypothalamic insulin signalling was specifically mediated by the combined actions of the class Ia isoforms p110α and p110β. Total hypothalamic PI3K activity was inhibited 65% by a p110α inhibitor, and 35% by a p110β inhibitor, with a combination of inhibitors being equally effective as the broad‐spectrum PI3K inhibitor wortmannin. Individual i.c.v. administration of p110α and p110β inhibitors partly prevented insulin‐induced phosphorylated AKT (S473) in the arcuate nucleus, whereas simultaneous application completely blocked insulin action. Unlike insulin, leptin did not induce phosphorylated AKT in the hypothalamus, as detected by immunohistochemistry, and the anorectic effects of leptin were not affected by pre‐treatment with a combination of p110α and p110β inhibitors. The enhanced anorectic effect of a combined i.c.v. application of both insulin and leptin could be prevented by pre‐treatment with the combination of p110α and p110β inhibitors. The data suggest that p110α and p110β isoforms of PI3K are necessary to mediate insulin action in the hypothalamus. The role of PI3K in leptin action is less clear, but it may be involved by means of an insulin‐dependent sensitisation of leptin action.
HDAC7: a viable target in the treatment of cystic fibrosis
Authors: Franciosi S
Published: March 2010

Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis Hutt et al. (2009)

Nature Chemical Biology 6(1): 25–33
De novo nonsense mutations in the sodium channel gene, SCN2A, in sporadic intractable epilepsy
Authors: Franciosi S
Published: March 2010

De novo mutations of voltage‐gated sodium channel αII gene SCN2A in intractable epilepsies Ogiwara et al. (2009)

Neurology 73(13): 1046–1053