bluuebunny/crossref_metadata_2025 huggingface dataset:
Thulium:yttrium‐aluminium‐garnet laser prostatectomy in men with refractory urinary retention
Authors: Bach Thorsten , Herrmann Thomas R.W. , Haecker Axel , Michel Maurice S. , Gross Andreas
Published: February 2009

OBJECTIVE

To evaluate the feasibility and efficacy of thulium:yttrium‐aluminium‐garnet (YAG) laser prostatectomy in patients with an indwelling transurethral catheter due to recurrent urinary retention secondary to benign prostatic obstruction.

PATIENTS AND METHODS

Preoperative data and postoperative outcome, as well as complications, were recorded in 65 patients with a history of recurrent urinary retention before surgery (group A), who were compared with a group of 143 men with no recurrent urinary retention (group B).

RESULTS

The mean (sd) volume of the prostate was 45.6 (22.5) and 43.1 (24.5) mL in groups A and B, respectively. The respective preoperative prostate‐specific antigen levels were 3.6 (7.8) and 2.8 (6.4) ng/mL, the surgical duration 72.4 (28.9) and 65.6 (28.6) min, the mean laser time and energy 32.5 (11.8) min/140.7 (42.1) kJ and 29.4 (11.6) min/117.6 (11.6) kJ, the maximum urinary flow rate after surgery 19.6 (11.2) and 19.1 (9.6) mL/s, and the postvoid residual urine volume 26.7 (36.3) and 20.6 (27.3) mL. Recorded complications were: bleeding, at 3% in group A and 1.4% in group B; urinary tract infection 15.4% and 4.2%; and a second procedure, 3% and 2.3%. Overall, complications were more frequent in group A (P = 0.02).

CONCLUSION

Thulium:YAG prostatectomy is feasible and effective, even in patients with potentially impaired detrusor function. The long‐term durability of these promising results has yet to be confirmed.
Food and eating as social practice – understanding eating patterns as social phenomena and implications for public health
Authors: Delormier Treena , Frohlich Katherine L. , Potvin Louise
Published: February 2009

Globally, public health agencies recognise obesity trends among populations as a priority. Explanations for population obesity patterns are linked to obesogenic environments and societal trends which encourage patterns of overeating and little physical activity. However, obesity prevention and nutrition intervention focus predominantly on changing individual level eating behaviours. Disappointingly, behaviour‐based nutrition education approaches to changing population eating patterns have met with limited success. Sociological perspectives propose that underlying social relations can help explain collective food and eating patterns, and suggest an analysis of the sociocultural context for understanding population eating patterns. We propose a theoretical framework for the examination of eating patterns as social phenomena. Giddens’ structuration theory, in particular his concept of social practices understood as an interplay of ‘agency’ and ‘social structure’ (rules and resources), is used to study food choice patterns. We discuss the application of these concepts for understanding routine food choice practices of families, elaborating how rules and resources configure the enabling or constraining conditions under which actors make food choices. The framework assists in characterising how social structural properties are integral to food choice practices, and could direct attention to these when considering nutrition interventions aimed at changing population eating patterns.
‘So forget how old I am!’ Examining age identities in the face of chronic conditions
Authors: Rozario Philip A. , Derienzis Daniel
Published: February 2009

This study examines the construction of age identity among older people with chronic conditions. Semi‐structured interviews were conducted with 45 participants from two senior centres. Applying symbolic interactionism and the concept of stigma to participants’ narratives, we identified three categories of age identities: definitely old; definitely not old; and ambivalent about their age identity. Further, we examined the metaphors of agelessness and the mask of ageing, the relationship between chronological age and age identity as well as the age‐related stereotypes that older people offered in their narratives of their experience of old age. Ideas about the meaning of old age itself varied, with some focusing on predominantly negative descriptors, while others saw it positively, i.e. as a time allowing for more freedom and self‐exploration. The influence of chronic conditions on older adults’ age identities is more complex and nuanced than the characterisations promoted by ageist stereotypes.
Reversible MRI Abnormalities in a Patient with Recurrent Status Migrainosus
Authors: Gentile S , Rainero I , Daniele D , Binello E , Valfrè W , Pinessi L
Published: February 2009

Status migrainosus is a condition characterized by a migraine attack causing disability, with or without aura, lasting for > 72 h. The pathophysiological mechanisms underlying this complication of migraine remain a matter of debate. We describe a migraine without aura patient who presented two episodes of status migrainosus associated with recurrent and reversible brain magnetic resonance imaging abnormalities. These abnormalities, confirmed also by positron emission tomography, suggest that status migrainosus can be associated with a condition of vasogenic cerebral oedema.
Recurrent Limb Pain and Migraine: Case Reports and A Clinical Review
Authors: Prakash S , Shah ND , Dholakia SY
Published: February 2009

Recurrent limb pain (RLP) is a well-known entity in childhood. It is considered a precursor of migraine. The temporal relationship of RLP with headache in childhood is lacking in the literature. However, there are many cases with limb pain in a close temporal relationship with migraine headache in adults. We report six female patients with RLP and migraine and delineate the temporal relationship between the two. Three patients had a history of RLP in childhood and developed migraine headache after many years. Conversely, two patients had a long history of migraine headache and later developed RLP. One patient developed RLP and migraine headache at the same age. Isolated limb pain was frequent in all six patients. It was mild to severe, for a few minutes to a few days, and predominantly located in the upper extremities. Only one patient reported allodynia. The patients showed response to preventive measures (all six patients) and abortive therapies (four patients), even in those attacks of RLP that were not associated with headache episodes. We also review the clinical profiles of the patients in whom RLP and migraine were related to each other, and speculate on the possible mechanisms for RLP in the patients with migraine.
Medical students’ experience of vaginal examinations of anaesthetised women
Authors: Broadmore J , Hutton JD , Langdana F
Published: February 2009

Medical students usually initially learn vaginal examination (VE) by examining consenting anaesthetised women. To assess their experience of this practice, a questionnaire was distributed to all 66 fifth‐year students at the Wellington School of Medicine in 2005—53 students responded. Although 184 women were available to approach for consent, only 141 were approached—students claimed insufficient time as their major difficulty. All male students discussed consent with women only in the 2 hours preoperatively, whereas nine (28%) of the female students sought consent earlier on the day or the day before. Of the 114 women asked, 97 gave written consent, but the VE was conducted in only 76 women mostly because the supervising gynaecologist claimed time constraints or was uninterested. Four other women were examined when consent was uncertain and two without consent. All but one of the students considered the experience educationally valuable. Eleven responding students did not perform a VE, and if the 13 nonresponders also did not, more than one‐third of students lack this educational opportunity prior to their final year. In conclusion, some students require more commitment to seeking consent, and some gynaecologists may need to better facilitate this learning opportunity so that the consent agreed with the woman and student is more often respected.
Risk factors in pregnancy for post‐traumatic stress and depression after childbirth
Authors: Söderquist J , Wijma B , Thorbert G , Wijma K
Published: February 2009

Objective The objective of this study was to find risk factors in pregnancy for post‐traumatic stress and depression 1 month after childbirth. Furthermore, the relation between post‐traumatic stress and depression was explored.

Design A prospective longitudinal study.

Setting Pregnant women in Linköping and Kalmar, Sweden.

Population A total of 1224 women were assessed in pregnancy, week 12–20 and 32, as well as 1 month postpartum.

Methods Post‐traumatic stress and depression after delivery were assessed 1 month postpartum. Potential risk factors were assessed in early and late pregnancy. Variables measured during pregnancy were trait anxiety, depression, fear of childbirth, childbirth‐related traumatic stress, stress coping capacity, social support, parity, educational level, age, gestation week, parity, educational level, civil status, previous psychological/psychiatric counselling, and previous experience of any traumatic events. Delivery mode was assessed from the medical records.

Main outcome measures Prevalence of post‐traumatic stress (criteria A, B, C, D, E, and F according to DSM‐IV) and depression (Beck’s depression inventory).

Results One month postpartum, 12 (1.3%) women had post‐traumatic stress (met symptom criteria B, C, and D for post‐traumatic stress disorder according to Diagnostic and statistical manual of mental disorders, 4th edition [DSM‐IV]). The most important risk factors in pregnancy were depression in early pregnancy (OR = 16.3), severe fear of childbirth (OR = 6.2), and ‘pre’‐traumatic stress (in view of the forthcoming delivery) in late pregnancy (OR = 12.5). The prevalence of depression was 5.6%. Post‐traumatic stress and depression were positively related 1 month postpartum and were predicted by mainly the same factors.

Conclusions Risk factors for post‐traumatic stress and depression after childbirth can be assessed in early pregnancy. Post‐traumatic stress and depression also seem to share the same underlying vulnerability factors.
The effect of urinary incontinence status during pregnancy and delivery mode on incontinence postpartum. A cohort study*
Authors: Wesnes SL , Hunskaar S , Bo K , Rortveit G
Published: February 2009

Objective  The objectives of this study were to investigate prevalence of urinary incontinence at 6 months postpartum and to study how continence status during pregnancy and mode of delivery influence urinary incontinence at 6 months postpartum in primiparous women.

Design  Cohort study.

Setting  Pregnant women attending routine ultrasound examination were recruited to the Norwegian Mother and Child Cohort Study (MoBa).

Population  A total of 12 679 primigravidas who were continent before pregnancy.

Methods  Data are from MoBa, conducted by the Norwegian Institute of Public Health. Data are based on questionnaires answered at week 15 and 30 of pregnancy and 6 months postpartum.

Main outcome measures  Urinary incontinence 6 months postpartum is presented as proportions, odds ratios and relative risks (RRs).

Results  Urinary incontinence was reported by 31% of the women 6 months after delivery. Compared with women who were continent during pregnancy, incontinence was more prevalent 6 months after delivery among women who experienced incontinence during pregnancy (adjusted RR 2.3, 95% CI 2.2–2.4). Adjusted RR for incontinence after spontaneous vaginal delivery compared with elective caesarean section was 3.2 (95% CI 2.2–4.7) among women who were continent and 2.9 (95% CI 2.3–3.4) among women who were incontinent in pregnancy.

Conclusion  Urinary incontinence was prevalent 6 months postpartum. The association between incontinence postpartum and mode of delivery was not substantially influenced by incontinence status in pregnancy. Prediction of a group with high risk of incontinence according to mode of delivery cannot be based on continence status in pregnancy.
Regulation of the Ras‐GTPase activating protein neurofibromin by C‐tail phosphorylation: implications for protein kinase C/Ras/extracellular signal‐regulated kinase 1/2 pathway signaling and neuronal differentiation
Authors: Leondaritis George , Petrikkos Loizos , Mangoura Dimitra
Published: February 2009

PKC, Ras, and ERK1/2 signaling is pivotal to differentiation along the neuronal cell lineage. One crucial protein that may play a central role in this signaling pathway is the Ras GTPase‐activating protein, neurofibromin, a PKC substrate that may exert a positive role in neuronal differentiation. In this report, we studied the dynamics of PKC/Ras/ERK pathway signaling, during differentiation of SH‐SY5Y neuroblastoma cells upon treatment with the PKC agonist, phorbol ester 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Surprisingly, we observed that, among other PKC‐dependent signaling events, TPA induced a rapid and sustained decrease of neurofibromin immunoreactivity which was not due to proteolysis. Instead, we identified a specific phosphorylation event at the C‐tail of neurofibromin. This phosphorylation was acute and correlated perfectly with the signaling dynamics of the Ras/ERK pathway. Moreover, it persisted throughout prolonged treatment and TPA‐induced differentiation of SH‐SY5Y cells, concurrently with sustained activation of ERK1/2. Most importantly, C‐tail phosphorylation of neurofibromin correlated with a shift of neurofibromin localization from the nucleus to the cytosol. We propose that PKC‐dependent, sustained C‐tail phosphorylation is a requirement for prolonged recruitment of neurofibromin from the nucleus to the cytosol in order for a fine regulation of Ras/ERK pathway activity to be achieved during differentiation.
An IRBIT homologue lacks binding activity to inositol 1,4,5‐trisphosphate receptor due to the unique N‐terminal appendage
Authors: Ando Hideaki , Mizutani Akihiro , Mikoshiba Katsuhiko
Published: February 2009

IRBIT is an inositol 1,4,5‐trisphosphate (IP3) receptor (IP3R)‐binding protein that inhibits the activation of IP3R by competing with IP3 for the common binding site on IP3R. In this study, we characterize an IRBIT homologue, termed Long‐IRBIT. Long‐IRBIT is highly homologous to IRBIT (∼88%) and heteromerizes with IRBIT. In spite of complete conservation of critical amino acids required for the interaction with IP3R and comparable phosphorylations on critical four Ser residues for IP3R‐binding, Long‐IRBIT retains little ability to interact with IP3R. Deletion mutagenesis analysis revealed that this low affinity to IP3R is attributable to an inhibitory effect of the Long‐IRBIT specific N‐terminal appendage (LISN domain). Immunohistochemical analysis revealed the distinct distribution of Long‐IRBIT and IRBIT in mouse cerebellar cortex, that is, Long‐IRBIT is mainly expressed in interneurons such as basket cells, while IRBIT is mainly expressed in glial cells. Furthermore, Long‐IRBIT, but not IRBIT, underwent phosphorylation during neuronal differentiation in neuroblastoma cells and this phosphorylation was dependent on the LISN domain. These results suggest that Long‐IRBIT has a different function from IRBIT.
The transferability of distribution models across regions: an amphibian case study
Authors: Zanini Flavio , Pellet Jérôme , Schmidt Benedikt R.
Published: February 2009

Aim Predicting species distribution is of fundamental importance for ecology and conservation. However, distribution models are usually established for only one region and it is unknown whether they can be transferred to other geographical regions. We studied the distribution of six amphibian species in five regions to address the question of whether the effect of landscape variables varied among regions. We analysed the effect of 10 variables extracted in six concentric buffers (from 100 m to 3 km) describing landscape composition around breeding ponds at different spatial scales. We used data on the occurrence of amphibian species in a total of 655 breeding ponds. We accounted for proximity to neighbouring populations by including a connectivity index to our models. We used logistic regression and information‐theoretic model selection to evaluate candidate models for each species.

Location Switzerland.

Results The explained deviance of each species’ best models varied between 5% and 32%. Models that included interactions between a region and a landscape variable were always included in the most parsimonious models. For all species, models including region‐by‐landscape interactions had similar support (Akaike weights) as models that did not include interaction terms. The spatial scale at which landscape variables affected species distribution varied from 100 m to 1000 m, which was in agreement with several recent studies suggesting that land use far away from the ponds can affect pond occupancy.

Main conclusions Different species are affected by different landscape variables at different spatial scales and these effects may vary geographically, resulting in a generally low transferability of distribution models across regions. We also found that connectivity seems generally more important than landscape variables. This suggests that metapopulation processes may play a more important role in species distribution than habitat characteristics.
Perturbation‐resilient block‐iterative projection methods with application to image reconstruction from projections
Authors: Davidi R. , Herman G.T. , Censor Y.
Published: February 2009

A block‐iterative projection algorithm for solving the consistent convex feasibility problem in a finite‐dimensional Euclidean space that is resilient to bounded and summable perturbations (in the sense that convergence to a feasible point is retained even if such perturbations are introduced in each iterative step of the algorithm) is proposed. This resilience can be used to steer the iterative process towards a feasible point that is superior in the sense of some functional on the points in the Euclidean space having a small value. The potential usefulness of this is illustrated in image reconstruction from projections, using both total variation and negative entropy as the functional.
Unintended Consequences of Granting Small Firms Exemptions from Securities Regulation: Evidence from the Sarbanes‐Oxley Act
Authors: GAO FENG , WU JOANNA SHUANG , ZIMMERMAN JEROLD
Published: February 2009

This paper provides evidence about the unintended consequences arising when small companies are exempted from costly regulations—these firms have incentives to stay small. Between 2003 and 2008, the SEC postponed compliance with Section 404 of the Sarbanes‐Oxley Act of 2002 (SOX) for “non‐accelerated filers” (firms with public float less than $75 million). We hypothesize and find that some of these firms had an incentive to remain below this bright line threshold. Moreover, we document that these firms remained small by undertaking less investment, making more cash payouts to shareholders, reducing the number of shares held by non‐affiliates, making more bad news disclosures, and reporting lower earnings than control firms. Finally, there is no evidence that firms remaining small are doing so to maintain insiders' private control benefits. These findings have implications beyond SOX because numerous federal and state regulations exempt small firms via bright line size thresholds.
A Lobbying Approach to Evaluating the Sarbanes‐Oxley Act of 2002
Authors: HOCHBERG YAEL V. , SAPIENZA PAOLA , VISSING‐JØRGENSEN ANNETTE
Published: February 2009

We evaluate the impact of the Sarbanes‐Oxley Act (SOX) on shareholders by studying the lobbying behavior of investors and corporate insiders in order to affect the final implemented rules under SOX. Investors lobbied overwhelmingly in favor of strict implementation of SOX, while corporate insiders and business groups lobbied against strict implementation. We identify firms most affected by the law as those whose insiders lobbied against strict implementation. Such firms appear to be characterized by agency problems, rather than motivated by concerns over compliance costs. Cumulative stock returns during the five and a half months leading up to SOX passage were approximately 7% higher for corporations whose insiders lobbied against SOX disclosure‐related provisions than for similar non‐lobbying firms, consistent with an expectation that SOX would reduce agency problems. Analysis of returns in the post‐passage implementation period suggests that investors' positive expectations with regards to the effects of these provisions were warranted.
Financial Globalization, Governance, and the Evolution of the Home Bias
Authors: KHO BONG‐CHAN , STULZ RENÉ M. , WARNOCK FRANCIS E.
Published: February 2009

We merge portfolio theories of home bias with corporate finance theories of insider ownership to create the optimal corporate ownership theory of the home bias. The theory has two components: (1) foreign portfolio investors exhibit a large home bias against countries with poor governance because their investment is limited by high optimal ownership by insiders (the “direct effect” of poor governance) and domestic monitoring shareholders (the “indirect effect”) in response to the governance and (2) foreign direct investors from “good governance” countries have a comparative advantage as insider monitors in “poor governance” countries, so that the relative importance of foreign direct investment is negatively related to the quality of governance. Using both country‐level data on U.S. investors' foreign investment allocations and Korean firm‐level data, we find empirical evidence supporting our optimal corporate ownership theory of the home bias.
Migrainous Vertigo: Results of Caloric Testing and Stabilometric Findings
Authors: Teggi Roberto , Colombo Bruno , Bernasconi Luca , Bellini Chiara , Comi Giancarlo , Bussi Mario
Published: February 2009

Background.— Association between migraine and vertigo has been widely studied during the last years. A central or peripheral vestibular damage may occur in patients with migrainous vertigo. Despite much evidence, at present the International Headache Society classification does not include a specific category for migrainous vertigo.

Objectives.— To assess the prevalence of central and peripheral vestibular disorders and postural abnormalities in patients diagnosed as affected by definite migrainous vertigo according to Neuhauser.

Methods.— Thirty patients with migraine and acute vertigo lasting from minutes to hours underwent a full otoneurological screening for spontaneous, positional, and positioning nystagmus with head‐shaking and head‐thrust (Halmagyi) tests, an audiometric examination, and videonystagmography with bithermal stimulation according to Freyss. Videonystagmographic findings were compared with those of 15 migraineurs without lifetime vertigo (group M). Next day, a static posturography was performed; posturographic results have been compared with those of a second control group of 30 healthy patients matched for age and sex (group C).

Results.— In total, 14 subjects with migrainous vertigo showed otovestibular disorders; 6 subjects showed impaired vestibulo‐oculomotor reflexes (20%). Five more patients had bilateral increased responses (16.6%). Five patients showed signs of central brainstem or cerebellar disorders for altered pursuit or saccades or positional direction changing nystagmus. Stabilometric results returned higher values of Length and Surface above all when testing was performed in eyes closed conditions compared with the normal control group. The subgroup of 14 subjects with migrainous vertigo and vestibular abnormalities performed poorly in stabilometric exams and seemed to rely more on visual cues in balance control than the subgroup of 16 subjects with migrainous vertigo but without abnormalities.

Discussion.— Our results indicate that vestibular functional damage may occur in all vestibular pathways; central and peripheral signs are equally represented. Our data are not inconsistent with the hypothesis that a vestibulo‐spinal dysfunction is the causal factor for the posturographic results. Moreover, the Visual Romberg Index is significant for increased visual cue dependence in migraineurs.
Serotonin Depletion Increases Nociception‐Evoked Trigeminal NMDA Receptor Phosphorylation
Authors: Maneepak Montree , Le Grand Supang , Srikiatkhachorn Anan
Published: February 2009

Objective.— To investigate the effect of serotonin depletion on phosphorylation and expression of NR1 subunit of N‐methyl‐D‐aspartate (NMDA) receptor in trigeminal nucleus caudalis (TNC), and on trigeminal nociception evoked by dural inflammation.

Background.— Migraine is associated with low serotonin condition and an increased neuronal excitability. NMDA receptor is implicated in central plasticity change that leads to neural sensitization. Alteration in NMDA receptor phosphorylation or expression in TNC may be responsible for increased trigeminal nociception in serotonin‐depleted state.

Methods.— Adult male Wistar rats were separated into normal and low serotonin groups. Serotonin was depleted by intraperitoneal injection with para‐chlorophenylalanine 3 days before the experiment. Trigeminal nociception was induced by applying inflammatory soup on exposed dura. Two hours after induction, phosphorylated NR1, NR1, and Fos expressions were studied in TNC by immunohistochemistry.

Results.— Dural application of inflammatory soup led to the activation of trigeminal nociceptive system as well as the phosphorylation of NR1, which were further enhanced in the low serotonin condition. There was a strong relationship between NR1 phosphorylation and trigeminal nociception. However, neither meningeal inflammation nor serotonin depletion altered NR1 expression.

Conclusions.— Low serotonin condition facilitates dural inflammation‐induced NR1 phosphorylation and trigeminal nociception. It is suggested that the mechanism of nociceptive facilitation in serotonin‐depleted state may involve the increase in NR1 phosphorylation rather than the upregulation of NR1 subunit of NMDA receptor.
An Unusual Suicide Inside a Grave with Two Gunshot Wounds to the Head—The Psychological Approach
Authors: Kastanaki Anastasia E. , Kranioti Elena F. , Theodorakis Pavlos N. , Michalodimitrakis Manolis
Published: February 2009

Abstract:  In this report, the authors present a case of suicide committed by a 66‐year‐old man, inside a grave at the local cemetery, with two gunshot wounds to the head. A multiple‐paged, handwritten suicide note was found in an army type bag inside the victim’s car, while a second one was found in his house. Medicolegal examination of the body revealed two typical contact gunshot entrance wounds and one exit wound to the head. Toxicological analysis of the femoral blood was negative for alcohol and drugs. The history, scene and autopsy findings, along with further police investigation, indicated an obvious case of suicide. The literature is reviewed and discussed. We report this case as the place of suicide is extremely uncommon and as there is no mention of a gunshot suicide inside a grave in the current literature.
The mitochondrial death pathway: a promising therapeutic target in diseases
Authors: Gupta Sanjeev , Kass George E.N. , Szegezdi Eva , Joseph Bertrand
Published: February 2009

Introduction

Mitochondria and cell death

Mitochondrial outer membrane permeabilization (MOMP): point of no return

Mitochondrial IMS: poison cabinet

Mitochondrial pathway of cell death and disease pathogenesis

Therapeutic strategies that promote MOMP and cell death

Therapeutic strategies that inhibit MOMP and cell death

Conclusion and future directions

The mitochondrial pathway to apoptosis is a major pathway of physiological cell death in vertebrates. The mitochondrial cell death pathway commences when apoptogenic molecules present between the outer and inner mitochondrial membranes are released into the cytosol by mitochondrial outer membrane permeabilization (MOMP). BCL‐2 family members are the sentinels of MOMP in the mitochondrial apoptotic pathway; the pro‐apoptotic B cell lymphoma (BCL)‐2 proteins, BCL‐2 associated x protein and BCL‐2 antagonist killer 1 induce MOMP whereas the anti‐apoptotic BCL‐2 proteins, BCL‐2, BCL‐xl and myeloid cell leukaemia 1 prevent MOMP from occurring. The release of pro‐apoptotic factors such as cytochrome c from mitochondria leads to formation of a multimeric complex known as the apoptosome and initiates caspase activation cascades. These pathways are important for normal cellular homeostasis and play key roles in the pathogenesis of many diseases. In this review, we will provide a brief overview of the mitochondrial death pathway and focus on a selection of diseases whose pathogenesis involves the mitochondrial death pathway and we will examine the various pharmacological approaches that target this pathway.
Early healing of implants placed into fresh extraction sockets: an experimental study in the beagle dog. De novo bone formation
Authors: Vignoletti Fabio , Johansson Carina , Albrektsson Tomas , De Sanctis Massimo , San Roman Fidel , Sanz Mariano
Published: February 2009

Objectives: Describe the early phases of tissue integration in implants placed into fresh extraction sockets and test whether a new implant surface nano‐topography (DCD nano‐particles, Nanotite™) promotes early osseointegration when compared with minimally rough surface implants (DAE, Osseotite®).

Material and Methods: Sixteen beagle dogs received 64 test and control implants randomly installed into the distal socket of 3P3 and 4P4. Histomorphometric analysis of bone to implant contact (BIC) and bone area was performed at 4 h, 1, 2, 4 and 8 weeks.

Results: Wound healing initiated with a coagulum that was substituted by a provisional matrix at 1 week. Bone formation started concomitant to a marked bone resorption. At 2 weeks, woven bone formation was evident and gradually remodelled into lamellar bone at 4 and 8 weeks. BIC increased similarly throughout the study in both groups with a tendency to higher percentages for the test devices at 2 and 4 weeks. The influence of the DCD nano‐particles was more evident at the fourth premolar site.

Conclusion: Osseointegration occurred similarly at both implant groups, although the socket dimension appeared to influence bone healing. It is suggested that the enhanced nano‐topography has a limited effect in the immediate implant surgical protocol.
Gastrointestinal stromal tumors in a baboon, a spider monkey, and a chimpanzee and a review of the literature
Authors: Bommineni Y.R. , Dick, Jr E.J. , Hubbard G.B.
Published: February 2009

Background  Gastrointestinal stromal tumors (GISTs) are believed to originate from the intestinal pacemaker cells (interstitial cells of Cajal) or their progenitor cells. Spontaneous tumors have been reported in dogs, horses, rhesus, and a chimpanzee and they have been produced experimentally in mice and rats. GISTs represent a diagnostic challenge because they cannot be differentiated from non‐lymphoid mesenchymal tumors without using human c‐kit (CD117) immunohistochemistry.

Methods  Three neoplasms were incidental findings at necropsy in the stomachs of a baboon and a spider monkey and in the rectum of a chimpanzee.

Results  The GISTs were initially diagnosed grossly and histologically with hematoxylin and eosin as leiomyomas. Immunohistochemical analysis revealed that all three were c‐kit (CD117) positive.

Conclusions  These are the first reports of GISTs in the baboon and spider monkey and the second in a chimpanzee. The occurrence of GISTs in non‐human primates may provide a unique opportunity to study these tumors.
A Single Conserved Leucine Residue on the First Intracellular Loop Regulates ER Export of G Protein‐Coupled Receptors
Authors: Duvernay Matthew T. , Dong Chunmin , Zhang Xiaoping , Robitaille Mélanie , Hébert Terence E. , Wu Guangyu
Published: February 2009

The intrinsic structural determinants for export trafficking of G protein‐coupled receptors (GPCRs) have been mainly identified in the termini of the receptors. In this report, we determined the role of the first intracellular loop (ICL1) in the transport from the endoplasmic reticulum (ER) to the cell surface of GPCRs. The α2B‐adrenergic receptor (AR) mutant lacking the ICL1 is unable to traffic to the cell surface and to initiate signaling measured as ERK1/2 activation. Mutagenesis studies identify a single Leu48 residue in the ICL1 modulates α2B‐AR export from the ER. The ER export function of the Leu48 residue can be substituted by Phe, but not Ile, Val, Tyr and Trp, and is unlikely involved in correct folding or dimerization of α2B‐AR in the ER. Importantly, the isolated Leu residue is remarkably conserved in the center of the ICL1s among the family A GPCRs and is also required for the export to the cell surface of β2‐AR, α1B‐AR and angiotensin II type 1 receptor. These data indicate a crucial role for a single Leu residue within the ICL1 in ER export of GPCRs.
Identification of the Novel TRAPP Associated Protein Tca17
Authors: Montpetit Ben , Conibear Elizabeth
Published: February 2009

Vesicle tethers are long coiled–coil proteins or multisubunit complexes that provide specificity to the membrane fusion process by linking cargo‐containing vesicles to target membranes. Transport protein particle (TRAPP) is a well‐characterized multisubunit tethering complex that acts as a GTP exchange factor and is present in two cellular forms: a 7 subunit TRAPP I complex required for ER‐to‐Golgi transport, and a 10 subunit TRAPP II complex that mediates post‐Golgi trafficking. In this work, we have identified Tca17, which is encoded by the non‐essential ORF YEL048c, as a novel binding partner of the TRAPP complex. Loss of Tca17 or any of the non‐essential TRAPP subunits (Trs33, Trs65 and Trs85) leads to defects in the Golgi‐endosomal recycling of Snc1. We show that Tca17, a Sedlin_N family member similar to the TRAPP subunit Trs20, interacts with the TRAPP complex in a Trs33‐ and Trs65‐dependent manner. Mutation of TCA17 or TRS33 perturbs the association of Trs65 with the rest of the TRAPP complex and alters the localization of the Rab GTPase Ypt31. These data support a model in which Tca17 acts with Trs33 and Trs65 to promote the assembly and/or stability of the TRAPP complex and regulate its activity in post‐Golgi trafficking events.
14‐3‐3 Ligand Prevents Nuclear Import of c‐ABL Protein in Chronic Myeloid Leukemia
Authors: Mancini Manuela , Veljkovic Nevena , Corradi Valentina , Zuffa Elisa , Corrado Patrizia , Pagnotta Eleonora , Martinelli Giovanni , Barbieri Enza , Santucci Maria Alessandra
Published: February 2009

Here we demonstrated that the ‘loss of function’ of not‐rearranged c‐ABL in chronic myeloid leukemia (CML) is promoted by its cytoplasmic compartmentalization bound to 14‐3‐3 sigma scaffolding protein. In particular, constitutive tyrosine kinase (TK) activity of p210 BCR‐ABL blocks c‐Jun N‐terminal kinase (JNK) phosphorylation leading to 14‐3‐3 sigma phosphorylation at a critical residue (Ser186) for c‐ABL binding in response to DNA damage. Moreover, it is associated with 14‐3‐3 sigma over‐expression arising from epigenetic mechanisms (promoter hyper‐acetylation). Accordingly, p210 BCR‐ABL TK inhibition by the TK inhibitor Imatinib mesylate (IM) evokes multiple events, including JNK phosphorylation at Thr183, p38 mitogen‐activated protein kinase (MAPK) phosphorylation at Thr180, c‐ABL de‐phosphorylation at Ser residues involved in 14‐3‐3 binding and reduction of 14‐3‐3 sigma expression, that let c‐ABL release from 14‐3‐3 sigma and nuclear import, and address BCR‐ABL‐expressing cells towards apoptotic death. Informational spectrum method (ISM), a virtual spectroscopy method for analysis of protein interactions based on their structure, and mathematical filtering in cross spectrum (CS) analysis identified 14‐3‐3 sigma/c‐ABL binding sites. Further investigation on CS profiles of c‐ABL‐ and p210 BCR‐ABL‐containing complexes revealed the mechanism likely involved 14‐3‐3 precluded phosphorylation in CML cells.
The presence of Merkel cells and CD10‐ and CD34‐positive stromal cells compared in benign and malignant oral tumors
Authors: Gao HW , Ho JY , Lee HS , Yu CP
Published: February 2009

Background:  To describe sequential changes in Merkel cells (MC), and CD10+ and CD34+ stromal cells (SC) during the transition from benign to malignant oral lesions and correlate with clinicopathologic parameters.

Materials and methods:  Changes in cytokeratin 20‐positive (CK20+) Merkel cells, CD10+ and CD34+ SC were immunohistochemically examined in specimens of 28 oral verrucous carcinomas (VC), 32 squamous cell carcinomas (SCC) and 36 benign squamous lesions (BSL). Immunoreactivity and localized inflammation were measured quantitatively and/or semiquantitatively, and between‐group results were statistically compared.

Results:  The mean number of CD34+ SC was significantly lower in VC (57.36) and SCC (33.81) than BSL (351.56, P < 0.001). However, the three tumor types had similar staining level and number of CD10+ SC. We found a significant difference in the density of MC between BSL and VC (P < 0.001) or SCC (P < 0.001). The number of CK20+ MC was significantly lower in highly inflamed specimens than mildly inflamed specimens (P = 0.001).

Conclusion:  CD34+ SC and to a lesser extent MC, but not CD10+ SC, reveal statistically different density during the transition from benign to malignant oral lesions. The correlations between the CD34+ SC expression and squamous lesions may be associated with epithelial dysplasia and/or tumor invasion.
Progesterone modulation of α5 nAChR subunits influences anxiety‐related behavior during estrus cycle
Authors: Gangitano D. , Salas R. , Teng Y. , Perez E. , De Biasi M.
Published: February 2009

Smokers often report an anxiolytic effect of cigarettes. In addition, stress‐related disorders such as anxiety, post‐traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the α5 nicotinic acetylcholine receptor subunit in anxiety‐related responses, control and α5 subunit null mice (α5−/−) were subjected to the open field activity (OFA), light–dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, α5−/−behaved like wild‐type controls. In the EPM, female α5−/−mice displayed an anxiolytic‐like phenotype, while male α5−/−mice were undistinguishable from littermate controls. We studied the hypothalamus–pituitary–adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin‐releasing factor. Consistent with an anxiolytic‐like phenotype, female α5−/−mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of α5, we treated cultured NTera 2 cells with progesterone and found that α5 protein levels were upregulated. In addition, brain levels of α5 mRNA increased upon progesterone injection into ovariectomized wild‐type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic‐like in wild‐type mice, but no cycle‐dependent fluctuations in anxiety levels were found in α5−/−females. Thus, α5‐containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone‐dependent modulation of α5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.
Passage through the Golgi is necessary for Shiga toxin B subunit to reach the endoplasmic reticulum
Authors: McKenzie Jenna , Johannes Ludger , Taguchi Tomohiko , Sheff David
Published: February 2009

Both Shiga holotoxin and the isolated B subunit, navigate a retrograde pathway from the plasma membrane to the endoplasmic reticulum (ER) of mammalian cells to deliver catalytic A subunits into the cytosol. This route passes through early/recycling endosomes and then through the Golgi. Although passage through the endosomes takes only 30 min, passage through the Golgi is much slower, taking hours. This suggests that Golgi passage is a key step in retrograde traffic. However, there is no empirical data demonstrating that Golgi passage is required for the toxins to enter the ER. In fact, an alternate pathway bypassing the Golgi is utilized by SV40 virus. Here we find that blocking Shiga toxin B access to the entire Golgi with AlF4− treatment, temperature block or subcellular surgery prevented Shiga toxin B from reaching the ER. This suggests that there is no direct endosome to ER route available for retrograde traffic. Curiously, when Shiga toxin B was trapped in endosomes, it entered the cytosol directly from the endosomal compartment. Our results suggest that trafficking through the Golgi apparatus is required for Shiga toxin B to reach the ER and that diversion into the Golgi may prevent toxin escape from endosomes into the cytosol.
Talin 2 is a large and complex gene encoding multiple transcripts and protein isoforms
Authors: Debrand Emmanuel , El Jai Yasmine , Spence Lorraine , Bate Neil , Praekelt Uta , Pritchard Catrin A. , Monkley Susan J. , Critchley David R.
Published: February 2009

Talins are large adaptor proteins that link the integrin family of adhesion molecules to F‐actin. In vertebrates, there are two talin genes. Talin 1 is essential for integrin‐mediated cell adhesion; the role of talin 2 is unclear. Here we report a detailed analysis of mammalian talin 2. This reveals the existence of a previously unrecognized promoter associated with a CpG island, and separated from the first coding exon by numerous alternatively spliced noncoding exons spanning > 200 kb. Analysis of a mouse gene trap line shows that this promoter accounts for most of the talin 2 expression in adult tissues. We also demonstrate that testis and kidney express truncated talin 2 isoforms that lack the N‐terminal half of the protein, and provide evidence for the developmentally regulated expression of the short testis‐specific talin 2 isoform in elongating spermatids. Finally, we identify four tissue‐specific alternative splicing events within the coding region of talin 2.
What's posterity ever done for me? On strategy in government
Authors: Mulgan Geoff
Published: February 2009

Geoff Mulgan examines what is known about public strategy and the criticisms that have been levelled at attempts to be more strategic. What explains the successes and the failures and what can make strategy work?
The case for care
Authors: Narey Martin
Published: February 2009

Martin Narey, Chief Executive of Barnardo's, says that we might need to take more children into care – and more of them into residential care
The road to progressive taxation
Authors: Murphy Richard
Published: February 2009

Richard Murphy examines the recent increase in the rate of tax for high income earners in the UK and argues that this should be the beginning of a journey whose destination is a wholly progressive taxation system.
Methylation of α‐Amino Acids and Derivatives Using Trimethylsilyldiazomethane
Authors: Leggio Antonella , Liguori Angelo , Perri Francesca , Siciliano Carlo , Viscomi Maria Caterina
Published: February 2009

A study of the methylation of N‐nosyl‐α‐amino acids and derivatives with trimethylsilyldiazomethane is here reported. Trimethylsilyldiazomethane allows the chemo‐specific methylation of the carboxyl function of N‐nosyl‐α‐amino acids in high yields and purity. This method provides a practical route to N‐methyl‐α‐amino acids avoiding the use of the more toxic and explosive diazomethane. This simple and safe methylation methodology of α‐amino acids and derivatives is not limited to organic synthesis and involves the use of a commercially available reagent as well.
Histone Deacetylase Inhibition Activity and Molecular Docking of (E )‐Resveratrol: Its Therapeutic Potential in Spinal Muscular Atrophy
Authors: Dayangaç‐Erden Didem , Bora Gamze , Ayhan Peruze , Kocaefe Çetin , Dalkara Sevim , Yelekçi Kemal , Demir Ayhan S. , Erdem‐Yurter Hayat
Published: February 2009

Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy, SMN2. The disease severity correlates inversely with increased SMN2 copy. Currently, the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. Among our candidate prodrug library, we found that (E )‐resveratrol, which is one of the polyphenolic compounds, inhibited histone deacetylase activity in a concentration‐dependent manner and half‐maximum inhibition was observed at 650 μm. Molecular docking studies showed that (E )‐resveratrol had more favorable free energy of binding (−9.09 kcal/mol) and inhibition constant values (0.219 μm) than known inhibitors. To evaluate the effect of (E )‐resveratrol on SMN2 expression, spinal muscular atrophy type I fibroblast cell lines was treated with (E )‐resveratrol. The level of full‐length SMN2 mRNA and protein showed 1.2‐ to 1.3‐fold increase after treatment with 100 μm (E )‐resveratrol in only one cell line. These results indicate that response to (E )‐resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of (E )‐resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy.
Methods for Computer‐Aided Chemical Biology. Part 4: Selectivity Searching for Ion Channel Ligands and Mapping of Molecular Fragments as Selectivity Markers
Authors: Ahmed Hany E. A. , Geppert Hanna , Stumpfe Dagmar , Lounkine Eugen , Bajorath Jürgen
Published: February 2009

For the computational exploration of structure–selectivity relationships, a compound selectivity system consisting of 243 antagonists of ionotropic glutamate ligand‐gated ion channels was designed. Selected antagonists were organized in nine different selectivity sets. In systematic selectivity search calculations utilizing these data sets, structural fingerprints produced a significant enrichment of selective compounds over non‐selective molecules and database decoys. The molecular basis of these findings was explored in detail. Fingerprint bit settings characteristic of antagonists with different selectivity profiles were identified and the corresponding structural features were correlated with sets of molecular fragments derived from selective and non‐selective antagonists following a hierarchical fragmentation strategy separating aromatic and aliphatic core structure elements and substituents. This analysis rationalized the selectivity search performance of structural fingerprints and revealed structural motifs that are selectivity markers for different types of ion channel antagonists.