bluuebunny/crossref_metadata_2025 huggingface dataset:
Cocaine- and Amphetamine-Regulated Transcript Accelerates Termination of Follicle-Stimulating Hormone-Induced Extracellularly Regulated Kinase 1/2 and Akt Activation by Regulating the Expression and Degradation of Specific Mitogen-Activated Protein Kinase Phosphatases in Bovine Granulosa Cells
Authors: Sen Aritro , Lv Lihua , Bello Nora , Ireland James J. , Smith George W.
Published: September 2008

Pleiotropic actions of cocaine- and amphetamine-regulated transcript (CART) are well described in the central nervous system and periphery, but the intracellular mechanisms mediating biological actions of CART are poorly understood. Although CART is not expressed in mouse ovaries, we have previously established CART as a novel intracellular regulator of estradiol production in bovine granulosa cells. We demonstrated that inhibitory actions of CART on estradiol production are mediated through inhibition of FSH-induced cAMP accumulation, Ca2+ influx, and aromatase mRNA expression via a Go/i-dependent pathway. We also reported that FSH-induced estradiol production is dependent on Erk1/2 and Akt signaling, and CART may regulate other signaling proteins downstream of cAMP essential for estradiol production. Here, we demonstrate that CART is a potent inhibitor of FSH-stimulated Erk1/2 and Akt signaling and the mechanisms involved. Transient CART stimulation of bovine granulosa cells shortens the duration of FSH-induced Erk1/2 and Akt signaling whereas a prolonged (24 h) CART treatment blocks Erk1/2 and Akt activation in response to FSH. This CART-induced accelerated termination of Erk1/2 and Akt signaling is mediated both by induced expression and impaired ubiquitin-mediated proteasome degradation of dual specific phosphatase 5 (DUSP5) and protein phosphatase 2A. Results also support existence of a negative feedback loop in which CART via a Go/i-MAPK kinase dependent pathway activates Erk1/2, and the latter induces DUSP5 expression. Moreover, small interfering RNA mediated ablation of DUSP5 and/or protein phosphatase 2A prevents the CART-induced early termination of Erk1/2 and Akt signaling. Results provide novel insight into the intracellular mechanism of action of CART in regulation of FSH-induced MAPK signaling.
A Collector's Problem with Renewal Arrival Processes
Authors: Kella Offer , Stadje Wolfgang
Published: September 2008

We study a collector's problem with K renewal arrival processes for different type items, where the objective is to collect complete sets. In particular, we derive the asymptotic distribution of the sequence of interarrival times between set completions.
A Compact Framework for Hidden Markov Chains with Applications to Fractal Geometry
Authors: Ruiz Víctor
Published: September 2008

We introduce a class of stochastic processes in discrete time with finite state space by means of a simple matrix product. We show that this class coincides with that of the hidden Markov chains and provides a compact framework for it. We study a measure obtained by a projection on the real line of the uniform measure on the Sierpinski gasket, finding that the dimension of this measure fits with the Shannon entropy of an associated hidden Markov chain.
On the Relationships Between Lumpability and Filtering of Finite Stochastic Systems
Authors: Ledoux James , White Langford B. , Brushe Gary D.
Published: September 2008

The aim of this paper is to provide the conditions necessary to reduce the complexity of state filtering for finite stochastic systems (FSSs). A concept of lumpability for FSSs is introduced. In this paper we assert that the unnormalised filter for a lumped FSS has linear dynamics. Two sufficient conditions for such a lumpability property to hold are discussed. We show that the first condition is also necessary for the lumped FSS to have linear dynamics. Next, we prove that the second condition allows the filter of the original FSS to be obtained directly from the filter for the lumped FSS. Finally, we generalise an earlier published result for the approximation of a general FSS by a lumpable FSS.
Optimal Co-Adapted Coupling for the Symmetric Random Walk on the Hypercube
Authors: Connor Stephen , Jacka Saul
Published: September 2008

Let X and Y be two simple symmetric continuous-time random walks on the vertices of the n-dimensional hypercube, Z2n. We consider the class of co-adapted couplings of these processes, and describe an intuitive coupling which is shown to be the fastest in this class.
Asymptotics of Posteriors for Binary Branching Processes
Authors: Piau Didier
Published: September 2008

We compute the posterior distributions of the initial population and parameter of binary branching processes in the limit of a large number of generations. We compare this Bayesian procedure with a more naïve one, based on hitting times of some random walks. In both cases, central limit theorems are available, with explicit variances.
Pricing of Catastrophe Insurance Options Under Immediate Loss Reestimation
Authors: Biagini Francesca , Bregman Yuliya , Meyer-Brandis Thilo
Published: September 2008

We specify a model for a catastrophe loss index, where the initial estimate of each catastrophe loss is reestimated immediately by a positive martingale starting from the random time of loss occurrence. We consider the pricing of catastrophe insurance options written on the loss index and obtain option pricing formulae by applying Fourier transform techniques. An important advantage is that our methodology works for loss distributions with heavy tails, which is the appropriate tail behavior for catastrophe modeling. We also discuss the case when the reestimation factors are given by positive affine martingales and provide a characterization of positive affine local martingales.
Impact of Routeing on Correlation Strength in Stationary Queueing Network Processes
Authors: Daduna Hans , Szekli Ryszard
Published: September 2008

For exponential open and closed queueing networks, we investigate the internal dependence structure, compare the internal dependence for different networks, and discuss the relation of correlation formulae to the existence of spectral gaps and comparison of asymptotic variances. A central prerequisite for the derived theorems is stochastic monotonicity of the networks. The dependence structure of network processes is described by concordance order with respect to various classes of functions. Different networks with the same first-order characteristics are compared with respect to their second-order properties. If a network is perturbed by changing the routeing in a way which holds the routeing equilibrium fixed, the resulting perturbations of the network processes are evaluated.
Assessing a Linear Nanosystem's Limiting Reliability from its Components
Authors: Ebrahimi Nader
Published: September 2008

Nanosystems are devices that are in the size range of a billionth of a meter (1 x 10-9) and therefore are built necessarily from individual atoms. The one-dimensional nanosystems or linear nanosystems cover all the nanosized systems which possess one dimension that exceeds the other two dimensions, i.e. extension over one dimension is predominant over the other two dimensions. Here only two of the dimensions have to be on the nanoscale (less than 100 nanometers). In this paper we consider the structural relationship between a linear nanosystem and its atoms acting as components of the nanosystem. Using such information, we then assess the nanosystem's limiting reliability which is, of course, probabilistic in nature. We consider the linear nanosystem at a fixed moment of time, say the present moment, and we assume that the present state of the linear nanosystem depends only on the present states of its atoms.
The Number of Two Consecutive Successes in a Hoppe-Pólya Urn
Authors: Holst Lars
Published: September 2008

In a sequence of independent Bernoulli trials the probability of success in the kth trial is pk = a / (a + b + k − 1). An explicit formula for the binomial moments of the number of two consecutive successes in the first n trials is obtained and some consequences of it are derived.
Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitors in the ventral mesencephalon
Authors: Omodei Daniela , Acampora Dario , Mancuso Pietro , Prakash Nilima , Di Giovannantonio Luca Giovanni , Wurst Wolfgang , Simeone Antonio
Published: September 2008

Meso-diencephalic dopaminergic (mdDA) neurons control voluntary movement,cognition and the reward response, and their degeneration is associated with Parkinson's disease (PD). Prospective cell transplantation therapies for PD require full knowledge of the developmental pathways that control mdDA neurogenesis. We have previously shown that Otx2 is required for the establishment of the mesencephalic field and molecular code of the entire ventral mesencephalon (VM). Here, we investigate whether Otx2 is a specific determinant of mesencephalic dopaminergic (mesDA) neurogenesis by studying mouse mutants that conditionally overexpress or lack Otx2. Our data show that Otx2 overexpression in the VM causes a dose-dependent and selective increase in both mesDA progenitors and neurons, which correlates with a remarkable and specific enhancement in the proliferating activity of mesDA progenitors. Consistently, lack of Otx2 in the VM specifically affects the proliferation of Sox2+ mesDA progenitors and causes their premature post-mitotic transition. Analysis of the developmental pathway that controls the differentiation of mesDA neurons shows that, in the absence of Otx2, the expression of Lmx1a and Msx1, and the proneural genes Ngn2 and Mash1 is not activated in Sox2+ mesDA progenitors, which largely fail to differentiate into Nurr1+ mesDA precursors. Furthermore, proliferation and differentiation abnormalities exhibit increasing severity along the anterior-posterior (AP) axis of the VM. These findings demonstrate that Otx2, through an AP graded effect, is intrinsically required to control proliferation and differentiation of mesDA progenitors. Thus, our data provide new insights into the mechanism of mesDA neuron specification and suggest Otx2 as a potential target for cell replacement-based therapeutic approaches in PD.
Fine needle aspiration cytology in the investigation of breast lumps at the University Teaching Hospital in Lusaka, Zambia
Authors: Bowa Kasonde , Jewel Jim , Mudenda Victor
Published: September 2008

The study was undertaken to determine the value of fine needle aspiration cytology (FNAC) in the investigation of breast lumps at the University Teaching Hospital (UTH) in Lusaka, Zambia. This technique, which has been shown to be cheap, simple and accurate has not been in common use at this institution. FNAC and open biopsy (OB) were performed on 56 patients who presented with a breast lump and the results compared, in order to determine the accuracy of FNAC. FNAC was found to have a sensitivity of 72% and specificity of 100%. This level of accuracy compares favourably with the quality assurance criteria set for breast FNAC by the Royal College of Pathologists in the British National Health Service (NHS).
Clinical patterns and major causes of infertility among Sudanese couples
Authors: Elussein Elsir A , Magid Yagoub M , Omer Maha M , Adam Ishag
Published: September 2008

An understanding of the medical causes of infertility is crucial in order to reduce incidences of Infertility and for improving the clinical management of infertility. Although there were much data on infertility in other African countries, no data exist on infertility in Sudan. Seven hundred and ten Sudanese couples were investigated for the infertility in Khartoum Fertility Center, Sudan: 443 (62.4%) had primary infertility and 267 (37.6%) had secondary infertility. The mean (standard deviation) duration of the infertility was 5.2 (4.3) years. A positive male factor alone was found in 257 (36.2%) couples and a female factor in 350 (49.3%) couples: eleven (1.5%) couples had a combination of male and female factors: and the cause of infertility was unexplained in 92 (13.0%) couples. Oligozoospermia and asthenozoospermia were factors responsible for 16.8% and 17.5% of male infertility, respectively. Failure of ovulation (60.3%) was the most common cause of female infertility. The study revealed a high proportion of secondary infertility and a greater contribution of the female factors to infertility.
Fever of unknown origin in the elderly: nine years experience in China
Authors: Zheng Minghua , Lin Hailong , Luo Sheng , Xu Lihua , Zeng Yanjun , Chen Yongping
Published: September 2008

This is a retrospective study of older patients admitted to the First and Second Affiliated Hospitals of Wenzhou Medical College, China, with a diagnosis of fever of unknown origin. The study took place from January 1998 to December 2006 among 102 patients who fulfilled the criteria. Infections were responsible for 50 cases (49.1%), followed by no diagnosis in 27 (26.5%), miscellaneous in nine (8.8%), neoplasms in eight (7.8%) and connective tissue disease in another eight (7.8%). Mycobacterium TB was the most frequent type of infection diagnosed.
The rise and fall of epidemic Neisseria meningitidis from a tertiary care hospital in Delhi, January 2005–June 2007
Authors: Kumar Surinder , Kashyap Bineeta , Bhalla Preena
Published: September 2008

Meningococcal meningitis is endemic in India. There has been a sudden surge of cases of meningococcal meningitis in 2005 in Delhi. Present study was undertaken to find out changing trends in incidence of this disease from a tertiary care hospital in New Delhi over a period of two and half years. All samples from suspected cases of meningococcal meningitis were subjected to Gram staining, culture and latex agglutination test for detection of Neisseria meningitidis ( N.meningitidis). Antimicrobial susceptibility of all isolates was performed using the disc diffusion test. 78.6%, 71.4% and 100% of the samples were positive for N.meningitidis by smear examination, culture and latex agglutination test respectively. Except for resistance to Penicillin and Erythromycin in 8.8% and 5.9%, the isolates were sensitive to the commonly used antibiotics. Using simple, rapid and reliable methods for diagnosis, defining risk factors and continuing surveillance remain important public health goals for the control of meningococcal disease.
Childhood epilepsy and school absence
Authors: Ibekwe Roland C , Ojinnaka Ngozi C
Published: September 2008

Epilepsy is one of the most common diseases encountered among school children. Its effect on school attendance and academic performance is a major cause of concern to both parents and clinicians. In this communication, the absence rate and academic performance of 50 school children with epilepsy attending normal schools was compared with that of their age- and sex-matched classmates using the class attendance register and overall score of the 2001/2002 academic year. The mean and standard deviation of the number of days an epileptic child was absent in the 2001/2002 session was 15.3 + 13.8 days while that of the controls was 9.4 + 9.6 days (x2 = 3.4,df = 49, p < 0.001). There was no significant relationship between the rate of absenteeism and overall score among both epileptic children (x2 = 6.34, df = 2, p = 0.18) and the controls (x2 = 1.43, df = 2, p = 0.49). School absenteeism was therefore more common among epileptic children, though there was no observed negative effect of this increased absence on academic performance.
Unforeseen difficulties faced by a hospital in dealing with mass disaster victims
Authors: Dhar Shabir Ahmed , Hamid Arshiya , Khan Shahzada Mohammed Salim , Butt Mohammed Farooq
Published: September 2008

Every major mass disaster challenges the health care services, especially in the third world. These challenges include the expected situations mainly pertaining to the overload of patients and the stretching of hospital facilities. We report our experiences about several unforseen challenges faced by our hospital in the 2005 earthquake that struck the Kashmir region.
Pattern of severe maternal morbidity in a tertiary hospital of Delhi, India: a pilot study
Authors: Chhabra Pragti , Guleria Kiran , Saini Narinder Kumar , Anjur Kannan Tupil , Vaid Neelam Bala
Published: September 2008

Severe maternal morbidity also known as ‘near miss’ may be a good indicator of the quality and effectiveness of obstetric care, as it may identify priorities in maternal care more rapidly than mortality alone. The objective of the study was to observe the pattern of severe maternal morbidity and its associated factors in a tertiary care hospital in Delhi. All patients admitted to the obstetrics and gynaecology department who fulfilled the definition of severe maternal morbidity conditions were included. A proforma was used to record sociodemographic, obstetric, antenatal care treatment and outcome details. A total of 63 women were included for analysis. The incidence of severe maternal morbidity was 3.3/100 deliveries. The mean age of the patients was 26.3 ± 5 years. More than half (55.5%) were uneducated: almost one-third (32%) were from outside Delhi – the median distance travelled was 10 km. The majority were antenatal admissions (68.3%). The proportion of postdelivery or abortion cases were greater among women who came from outside Delhi. Only 38.1% were registered during the antenatal period. The diagnoses were: eclampsia/pre-eclampsia (35%); haemorrhage (35%); sepsis (13%); obstructed labour (9.5%) and other medical conditions (11%). Severe anaemia was observed in 22% of cases. Only 43.5% were normal vaginal deliveries and 54.5% were delivered by caesarean section or with the use of instruments; 61.3% were live births. Hysterectomy was performed in 14.8%: the proportion of hysterectomy was higher in obstructed labour. Severe maternal morbidity cases constitute a significant burden on health resources.
Frequency and determinants of the metabolic syndrome in apparently healthy adult Nigerians
Authors: Wahab Kolawole Wasiu , Sani Mahmoud , Gbadamosi Maruf , Yandutse Mahmoud
Published: September 2008

Non-communicable disease conditions such as the metabolic syndrome further strain the already insufficient health resources in Africa, where communicable diseases such as malaria and HIV/AIDS are still causing significant morbidity and mortality. We studied the frequency and determinants of the syndrome in apparently healthy Nigerian volunteers in order to provide a basis for the establishment of a prevention programme.
Conservative management of splenic injury in the tropics
Authors: Kuzma Jerzy , Atua Vincent
Published: September 2008

We undertook this study in order to determine whether the conservative management of splenic injuries is a safe practice in a low-volume tropical hospital. We evaluated 69 consecutive patients with splenic injury prospectively. The outcome measures were morbidity and mortality rates, overall hospital stay and blood transfusion requirements. Spleen preservation was achieved in 85% (59) of cases. Of the 16 patients who underwent splenic surgery, six had splenorraphy (38%). The overall mortality was 4.3% (3) and the deaths were not related to the conservative management. Our findings suggest that not only is the conservative management of splenic injuries safe, but also that the repair of an enlarged spleen (splenorrhaphy) is safe and feasible in tropical hospital settings. The findings in this study provide further evidence that the conservative management of splenic injury in a tropical hospital without computed tomography scan is a safe practice.
The mental health consequences of intimate partner violence against women in Agaro Town, southwest Ethiopia
Authors: Tadegge Amare Deribew
Published: September 2008

There are very few population-based studies on the mental health consequences of intimate partner violence (IPV) from Ethiopia. This study was conducted among 510 ‘ever partnered’ women in Agaro Town in February 2007. Mental distress and depression were measured using self-reporting questionnaires and Kessler's Scales. All types of IPV (physical, sexual and emotional abuses) were significantly associated with mental distress and depression. Women who suffered from physical, sexual and emotional abuses were more likely to have mental distress. We recommend using information education communications to educate the community and thereby preventing IPV and the mental health consequences.
A structured training module using an inexpensive endotrainer for improving the performance of trainee surgeons
Authors: Mir Iqbal Saleem , Mohsin Mir , Malik Anjum , Shah Abdul Qayoom , Majid Tafazul
Published: September 2008

Training in minimal access surgery has always been difficult in developing countries with limited resources, non availability of formal animal labs, inaffordability of conventional endotrainers and lack of trained endosurgeons to help the amateurs. It is always difficult to start a new procedure in such places where not only the patients but the orthodox surgical fraternity are reluctant to accept new ideas and newer trends in surgery. After thorough discussions with senior surgeons, the author (who was the only trained endosurgeon to begin with) developed a training policy to train the surgeons over a period of time through various exercises before allowing them to assist him in the actual surgeries. A homemade, inexpensive endotrainer was designed for these exercises. Audio-visual seminars were held in between the training sessions. This training module can be employed by other rural hospitals to improve the skills of surgeons who are new to the art of endosurgery.
Incidence of skeletal deformities in endemic fluorosis
Authors: A Shashi , M Kumar , M Bhardwaj
Published: September 2008

An investigation was undertaken in three endemic fluorotic areas of Punjab State, India, to assess the prevalence of skeletal deformities. The concentration of fluoride in drinking water varies from 2.3 to 22.5 mg/L. The patients affected with skeletal fluorosis revealed joint pain in both upper and lower limbs, numbing and tingling of the extremities, back pains and knock-knees. Prevalence of skeletal fluorosis was found to be 29% of grade-I, 51% of grade-II and 20% of grade-III and was higher in males (63%) compared with females (37%).
High-risk behaviours and associated factors among HIV-positive individuals in clinical care in southwest Ethiopia
Authors: Deribe Kebede , Woldemichael Kifle , Wondafrash Mekitie , Haile Amaha , Amberbir Alemayehu
Published: September 2008

A hospital-based cross-sectional survey was conducted among 705 HIV-positive individuals. The result showed that 24% of the participants reported unprotected intercourse in their most recent sexual episode. Nine percent of these events were with partners perceived to be HIV-negative and 39% with those of unknown HIV status. Protected sex at recent episode was independently associated with knowing a partner's HIV status, disclosing HIV status to a partner, receipt of antiretroviral treatment and perceiving HIV as less stigmatizing. This highlights the need for interventions among HIV-positive individuals that will assist them in attaining and maintaining safer sex practices.
Crimean Congo hemorrhagic fever and diffuse alveolar haemorrhage
Authors: Doganci Levent , Ceyhan Meltem , Tasdeler Nuriye Fisgin , Sarikayalar Hanife , Tulek Necla
Published: September 2008

Although the pathology of Crimean Congo haemorrhagic fever (CCHF) is mainly related to a haemorrhagic process with secondary cytokine storm, there have been no published reports of this fatal disease being a cause of diffuse alveolar haemorrhage (DAH). There are many aetiological factors emphasizing the direct role of endothelial injury on DAH. We present the case of a young adult Turkish man with diffuse bilateral alveolar haemorrhage without an episode of gross haemoptysis caused by the CCHF virus. Successful clinical results and a rapid clinical and radiological clearance were obtained within few days after starting daily oral ribavirin treatment. This fatal infection should be considered to exist in any patient presenting with DAH, and should rapidly be treated with ribavirin. Another very important factor which should always be borne in mind is the contagious character of the CCHF virus. It is one of the most dangerous microorganisms transmitted from person to person. Even the bronchoscopes contaminated with patient blood carry a high risk for nosocomial spread to medical staff and other patients.
Childhood cancer in Sudan: 1999–2007
Authors: Abuidris Dafalla O , Ahmed Mohamed E , Elgaili Elgaili M , Arora Ramandeep S
Published: September 2008

There is paucity of information on childhood cancer from Sudan with the last studies published more than 20 years ago. This study aims to provide a current picture of childhood cancer in Sudan. Data was obtained from the hospital registry for the period May 1999 to June 2007 on all paediatric patients presenting to the Institute of Nuclear Medicine and Oncology, University of Gezira, Wad Madani, Sudan. There were 322 children with cancer during this time period with a male:female ratio of 1.6:1. Lymphomas (111, 35%), leukaemia (83, 26%) and Wilms' tumour (43, 13%) were the three most common groups of tumours. Thirty percent of all lymphomas were Burkitt's lymphoma; 3.4% of all childhood cancer cases were nasopharyngeal carcinomas.
Osteomyelitis of the ribs: a strategy for prompt diagnosis and effective management
Authors: Mohanty Debajyoti , Agrawal Vivek , Jain Bhupendra Kumar , Gupta Richa , Rathi Vinita , Gupta Arun
Published: September 2008

Seven patients were treated for osteomyelitis rib (OR). Discharging sinuses and painful swellings were the presenting symptoms. An initial chest X-ray was unremarkable in all patients. Fine needle aspiration cytology and microscopy of pus did not reveal acid-fast bacillus in any patient. Computerized tomography (CT) of thorax was consistent with the diagnosis of OR in five patients. The patients underwent a subperiosteal excision of the affected part of the ribs or an excision biopsy of the unhealthy granulation tissue. Histopathological diagnosis was consistent with the diagnosis of tuberculosis (TB) OR in six patients. The patients received anti-TB drugs or appropriate antibiotics following surgery. All responded to treatment except one with a non-TB OR, who required further excision of the unhealthy rib ends. Inclusion of a CT of the thorax and an excision biopsy in the diagnostic process facilitates prompt diagnosis and effective management of OR.
Risk of hepatitis B virus in the slaughter house
Authors: Ola S O , Otegbayo J A , Yakubu A , Odaibo G N , Olaleye D O
Published: September 2008

The study involved 180 Nigerian butchers and 180 traders (controls) selected by multistage stratified sampling who had their sera assayed for HBsAg (hepatitis B surface antigen) by enzyme-linked immunosorbent assay method. The butchers and the controls had an HBsAg sero-prevalence rate of 9.4% and 3.3%, respectively. Various risky practices were more common among the butchers but their hepatitis B antigenaemia was not related to the duration of their occupational exposure. The study shows that the butchers constitute a high risk occupation for hepatitis B viral infection.
Pyomyositis mimicking leptospirosis: two cases in a Brazilian tertiary care hospital in a non-tropical area
Authors: Luz Letícia Perondi , Dora José Miguel , Goldani Luciano Zubaran
Published: September 2008

Pyomyositis is a subacute, deep suppurative bacterial infection of skeletal muscle not arising from contiguous infection. It is presumably haematogenous in origin, and characterized by muscle pain and swelling. We report on two patients who presented with pyomyositis in a tertiary care hospital in temperate region located in southern Brazil with a clinical presentation, which was initially suggestive of leptospirosis. This report discusses the pathogenesis, clinical presentation, diagnosis and management of pyomyositis. Physicians living in non-tropical areas should note that pyomyositis might occur in those areas, and its initial clinical presentation may be similar to leptospirosis
Primary amoebic meningoencephalitis: a new case from Venezuela
Authors: Caruzo Giusseppe , Cardozo José
Published: September 2008

Primary amoebic meningoencephalitis (PAM) is not often seen. To date, less than 300 cases have been communicated to the medical literature since the disease was first discovered in 1965. Six of these reports originated in Venezuela. The authors describe a new spontaneous case of PAM in a 33-year-old previously healthy Western-Venezuelan man.
Long-distance placement of substrate RNA by H/ACA proteins
Authors: Liang Bo , Kahen Elliot J. , Calvin Kate , Zhou Jing , Blanco Mario , Li Hong
Published: September 2008

The structural basis for accurate placement of substrate RNA by H/ACA proteins is studied using a nonintrusive fluorescence assay. A model substrate RNA containing 2-aminopurine immediately 3′ of the uridine targeted for modification produces distinct fluorescence signals that report the substrate's docking status within the enzyme active site. We combined substrate RNA with complete and subcomplexes of H/ACA ribonucleoprotein particles and monitored changes in the substrate conformation. Our results show that each of the three accessory proteins, as well as an active site residue, have distinct effects on substrate conformations, presumably as docking occurs. Interestingly, in some cases these effects are exerted far from the active site. Application of our data to an available structural model of the holoenzyme, enables the functional role of each accessory protein in substrate placement to come into view.
A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae
Authors: Huang Bo , Lu Jian , Byström Anders S.
Published: September 2008

We recently showed that the γ-subunit of Kluyveromyces lactis killer toxin (γ-toxin) is a tRNA endonuclease that cleaves , , and 3′ of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U). The 5-methoxycarbonylmethyl (mcm5) side chain was important for efficient cleavage by γ-toxin, and defects in mcm5 side-chain synthesis correlated with resistance to γ-toxin. Based on this correlation, a genome-wide screen was performed to identify gene products involved in the formation of the mcm5 side chain. From a collection of 4826 homozygous diploid Saccharomyces cerevisiae strains, each with one nonessential gene deleted, 63 mutants resistant to Kluyveromyces lactis killer toxin were identified. Among these, eight were earlier identified to have a defect in formation of the mcm5 side chain. Analysis of the remaining mutants and other known γ-toxin resistant mutants revealed that sit4, kti14, and KTI5 mutants also have a defect in the formation of mcm5. A mutant lacking two of the Sit4-associated proteins, Sap185 and Sap190, displays the same modification defect as a sit4-null mutant. Interestingly, several mutants were found to be defective in the synthesis of the 2-thio (s2) group of the mcm5s2U nucleoside. In addition to earlier described mutants, formation of the s2 group was also abolished in urm1, uba4, and ncs2 mutants and decreased in the yor251c mutant. Like the absence of the mcm5 side chain, the lack of the s2 group renders less sensitive to γ-toxin, reinforcing the importance of the wobble nucleoside mcm5s2U for tRNA cleavage by γ-toxin.
Identification of pseudouridine methyltransferase in Escherichia coli
Authors: Ero Rya , Peil Lauri , Liiv Aivar , Remme Jaanus
Published: September 2008

In ribosomal RNA, modified nucleosides are found in functionally important regions, but their function is obscure. Stem–loop 69 of Escherichia coli 23S rRNA contains three modified nucleosides: pseudouridines at positions 1911 and 1917, and N3 methyl-pseudouridine (m3Ψ) at position 1915. The gene for pseudouridine methyltransferase was previously not known. We identified E. coli protein YbeA as the methyltransferase methylating Ψ1915 in 23S rRNA. The E. coli ybeA gene deletion strain lacks the N3 methylation at position 1915 of 23S rRNA as revealed by primer extension and nucleoside analysis by HPLC. Methylation at position 1915 is restored in the ybeA deletion strain when recombinant YbeA protein is expressed from a plasmid. In addition, we show that purified YbeA protein is able to methylate pseudouridine in vitro using 70S ribosomes but not 50S subunits from the ybeA deletion strain as substrate. Pseudouridine is the preferred substrate as revealed by the inability of YbeA to methylate uridine at position 1915. This shows that YbeA is acting at the final stage during ribosome assembly, probably during translation initiation. Hereby, we propose to rename the YbeA protein to RlmH according to uniform nomenclature of RNA methyltransferases. RlmH belongs to the SPOUT superfamily of methyltransferases. RlmH was found to be well conserved in bacteria, and the gene is present in plant and in several archaeal genomes. RlmH is the first pseudouridine specific methyltransferase identified so far and is likely to be the only one existing in bacteria, as m3Ψ1915 is the only methylated pseudouridine in bacteria described to date.
YbeA is the m3Ψ methyltransferase RlmH that targets nucleotide 1915 in 23S rRNA
Authors: Purta Elzbieta , Kaminska Katarzyna H. , Kasprzak Joanna M. , Bujnicki Janusz M. , Douthwaite Stephen
Published: September 2008

Pseudouridines in the stable RNAs of Bacteria are seldom subjected to further modification. There are 11 pseudouridine (Ψ) sites inEscherichia colirRNA, and further modification is found only at Ψ1915 in 23S rRNA, where the N-3 position of the base becomes methylated. Here, we report the identity of theE. colimethyltransferase that specifically catalyzes methyl group addition to form m3Ψ1915. Analyses ofE. colirRNAs using MALDI mass spectrometry showed that inactivation of theybeAgene leads to loss of methylation at nucleotide Ψ1915. Methylation is restored by complementing the knockout strain with a plasmid-encoded copy ofybeA. Homologs of theybeAgene, and thus presumably the ensuing methylation at nucleotide m3Ψ1915, are present in most bacterial lineages but are essentially absent in the Archaea and Eukaryota. Loss ofybeAfunction inE. colicauses a slight slowing of the growth rate. Phylogenetically,ybeAand its homologs are grouped with other putative S-adenosylmethionine-dependent, SPOUT methyltransferase genes in the Cluster of Orthologous Genes COG1576;ybeAis the first member to be functionally characterized. The YbeA methyltransferase is active as a homodimer and docks comfortably into the ribosomal A site without encroaching into the P site. YbeA makes extensive interface contacts with both the 30S and 50S subunits to align its active site cofactor adjacent to nucleotide Ψ1915. Methylation by YbeA (redesignated RlmH forrRNAlarge subunitmethyltransferaseH) possibly functions as a stamp of approval signifying that the 50S subunit has engaged in translational initiation.
The sarcin–ricin loop of 23S rRNA is essential for assembly of the functional core of the 50S ribosomal subunit
Authors: Lancaster Laura , Lambert Nicole J. , Maklan Eric J. , Horan Lucas H. , Noller Harry F.
Published: September 2008

The sarcin–ricin loop (SRL) of 23S rRNA in the large ribosomal subunit is a factor-binding site that is essential for GTP-catalyzed steps in translation, but its precise functional role is thus far unknown. Here, we replaced the 15-nucleotide SRL with a GAAA tetraloop and affinity purified the mutant 50S subunits for functional and structural analysis in vitro. The SRL deletion caused defects in elongation-factor-dependent steps of translation and, unexpectedly, loss of EF-Tu-independent A-site tRNA binding. Detailed chemical probing analysis showed disruption of a network of rRNA tertiary interactions that hold together the 23S rRNA elements of the functional core of the 50S subunit, accompanied by loss of ribosomal protein L16. Our results reveal an influence of the SRL on the higher-order structure of the 50S subunit, with implications for its role in translation.
The C-terminal region of Ge-1 presents conserved structural features required for P-body localization
Authors: Jinek Martin , Eulalio Ana , Lingel Andreas , Helms Sigrun , Conti Elena , Izaurralde Elisa
Published: September 2008

The removal of the 5′ cap structure by the DCP1–DCP2 decapping complex irreversibly commits eukaryotic mRNAs to degradation. In human cells, the interaction between DCP1 and DCP2 is bridged by the Ge-1 protein. Ge-1 contains an N-terminal WD40-repeat domain connected by a low-complexity region to a conserved C-terminal domain. It was reported that the C-terminal domain interacts with DCP2 and mediates Ge-1 oligomerization and P-body localization. To understand the molecular basis for these functions, we determined the three-dimensional crystal structure of the most conserved region of the Drosophila melanogaster Ge-1 C-terminal domain. The region adopts an all α-helical fold related to ARM- and HEAT-repeat proteins. Using structure-based mutants we identified an invariant surface residue affecting P-body localization. The conservation of critical surface and structural residues suggests that the C-terminal region adopts a similar fold with conserved functions in all members of the Ge-1 protein family.
Factors Influencing the Career Aspirations and Preferred Modes of Working in Recent Dental Graduates in Wales
Authors: Davies Luke , Thomas David R , Sandham Sandra J , Treasure Elizabeth T , Chestnutt Ivor G
Published: September 2008

Introduction

In England and Wales, National Health Service (NHS) primary dental care services are now commissioned on a local basis. In planning for the future, it is important that commissioning authorities have a clear understanding of the perspectives of recent dental graduates: vocational dental practitioners (VDPs).

Objectives

This study investigated the career aspirations and preferred modes of working of VDPs in Wales.

Methodology

Data were collected via a postal questionnaire, comprising 37 closed and open questions, mailed to all 59 VDPs in Wales.

Results

A total of 53 (90%) VDPs participated, of whom 47 saw their future in general dental practice: 5, 35, and 7 indicating a preference to work in the NHS, mixed (NHS and private), and private sector, respectively. None selected the Community Dental Service as their preferred vocation. More than half of all respondents intended to undertake a postgraduate qualification within the next five years and 22 wished to specialise. Of the 53 VDPs, 44 were concerned that lack of NHS contracts would limit where they could practise, and agreed that family and other social commitments were a significant influence on choice of practice location. Access to high-quality premises and continuing professional development were agreed as important by 41 VDPs. A majority (37) agreed that private dentistry was an attractive alternative to NHS dentistry. Of the respondents, 38 (22 females, 16 males) expected to work part-time at some point in the future and 14 said they would consider a career outside dentistry. Only nine VDPs agreed that they would be happy working in a single-handed practice and even fewer (six) indicated they would be happy working for a corporate body.

Conclusions

Numerous factors impact on the career aspirations of VDPs. These factors have been quantified in this study, and healthcare-commissioning bodies need to be aware of them when planning future dental care provision in Wales.
An Audit of Dentine Hypersensitivity Treatments in Six General Dental Practices in Scotland
Authors: Chadwick R Graham , Mason Andrew G
Published: September 2008

Aims

This investigation sought to: (a) determine the agents used by nine dentists to treat dentine hypersensitivity and measure their effectiveness; (b) evaluate the adoptive ease and apparent success of the most effective treatment when used by all nine dentists; and (c) validate a novel categorical ranking score for dentine hypersensitivity.

Methods

A clinical audit methodology was used in the setting of general dental practice. In the initial data-collection round, patients presenting with dentine hypersensitivity were treated using the dentist's favoured regimen. Evaluation of agent effectiveness was made by patient completion of a pre- and post-treatment visual analogue scale (VAS) for the frequency (f) and severity (s) of hypersensitivity. A four-point categorical ranking scale (CRS) was also used to assess the impact of hypersensitivity upon lifestyle (L) (1= No sensitivity/effect on what I eat/drink; 2 = Sometimes sensitive, rarely interfering with what I eat/drink; 3 = Sometimes sensitive, occasionally interfering with what I eat/drink; 4 = Always sensitive, always interfering with what I eat/drink). The most successful treatment was determined and used by all participating dentists. Its effectiveness was then assessed using the same criteria.

Results

Four agents were routinely used to treat hypersensitivity: (Duraphat (D) (Colgate), Duraphat & Sensodyne (DS) (GlaxoSmithKline), Sensodyne (S) (GlaxoSmithKline), Seal & Protect (SP) (De Trey, Dentsply). All produced statistically significant ( P<0.001) reductions in VAS (Tukey) and CRS (Kruskal-Wallis) scores, except for DS and S. Of these, the greatest percentage reduction was seen for SP (f=72.01%, s=71.19%, L=45.98%). When SP was applied by all dentists, similar percentage reductions were seen (f=68.74%, s=75.85%, L=38.33%). The CRS, in both data-collection rounds, correlated well with the corresponding VAS scores (Spearman R for f=0.77 ( P<0.001) and for s=0.80 ( P<0.001).

Conclusion

For the dentists in this audit, the use of SP was found to be reliable and predictable. The CRS provided a simple and reliable measure of dentine hypersensitivity. Subject to validation in a larger study, this could be used in a future audit as an alternative to multiple VAS scores.
Mentoring. A Quality Assurance Tool for Dentists Part 1: The Need for Mentoring in Dental Practice
Authors: Holt Vernon P , Ladwa Russ
Published: September 2008

This paper introduces the concept of mentoring and its use in dental practice. It explains how there has been a drive for quality in all areas of healthcare in the United Kingdom (UK), and that clinical audit and clinical governance are two of the quality assurance tools that have been developed. It suggests that the most important factor in the provision of quality care is the dentist and that it is therefore essential that dentists are given support and encouragement by their peers, together with recognition of good performance. The next section of the paper considers factors that hinder a dentist's quality of performance. It explains that there are multiple stresses in dental practice and, if they are not managed and controlled, that they can lead to professional burnout, anxiety and depression. One of the most important stressors that can impact on the quality of patient care is the constraint of time, which can frequently result from pressure from third parties such as managers and administrators. Dentists often feel isolated. The final section of the paper describes how dentists may be supported. Techniques include developing special interests within oral healthcare, career development, good human resource management, peer review and study groups, and coaching and mentoring. The nature of these last two techniques is discussed and the authors conclude that the best tool for supporting the quality of performance of dentists is mentoring.
Central Giant Cell Granuloma in Palate Associated with Orthodontic Treatment
Authors: Wong Yiu-Kai , Cheng Jason Chi-Fung
Published: September 2008

A case report of a central giant cell granuloma in the palate, which arose after orthodontic treatment, is presented with a review of relevant literature. Treatment options and clinical implications are also discussed.
The social organization of representations of history: The textual accomplishment of coming to terms with the past
Authors: Tileagă Cristian
Published: September 2008

This paper is concerned with the social organization of collective memory and representations of history in the context of how post‐communist democracies reckon with former regimes. It specifically centres on the textual accomplishment of coming to terms with the past in the ‘Tismăneanu Report’ condemning Communism in Romania. The focus is on how the Report displays and shapes the ideological contours of coming to terms with the past around a particular ‘social representation’ of history. Several constitutive features of the Report that facilitate bringing off a particular ‘representation of history’ are identified: (a) the construction of a practical framework for the inquiry as a matter of public concern and attention; (b) the production of ‘Communism’ as an empirical category with uniquely bound features; and (c) the structuring of time by bringing together a political agenda and national identity. The present argument tries to place representations of history (and coming to terms with the past) as something in need of constitution rather than simply relied on. It is suggested that a conception of coming to terms with the past as a textual accomplishment may lead to a fuller appreciation of the structure, function and salience of representations of history as integral part of moral/political/legal courses of action.
Second nature
Authors: Corcoran Tim
Published: September 2008

Are ontological meanings somehow sacrosanct in arguments concerning psychology – particularly those scored by discursive accounts of human being? Or is the purposeful deferment of ontological concerns in discursive psychology (DP) another instance of method‐fetishism (Koch, 1981)? Shotter's (1995) understanding of joint action and Chouliaraki's (2002) critical realist account of social action combine to support an alternate position to the predominant discursive psychological approach informed by epistemological constructionism (DPEC). The DPEC position is here contrasted with a discursive psychological approach informed by ontological constructionism (DPOC). Via this distinction, a path for future discursive psychological studies is charted, one which values understanding the kinds of practical‐moral knowledges (Shotter, 1993) available to people in accounting for themselves and their actions as psychosocial agents. Contrary to claims that the DPEC/DPOC distinction is supercilious (Edley, 2001) or oxymoronic (Drewery, 2000), the importance of debating what ontology can mean for psychology is herein seen as central to the pursuit of personal, relational and collective wellness in contemporary life.
Narrowband biphoton generation near atomic resonance
Authors: Du Shengwang , Wen Jianming , Rubin Morton H.
Published: September 2008

Generating nonclassical light offers a benchmark tool for fundamental research and potential applications in quantum optics. Conventionally, it has become a standard technique to produce nonclassical light through the nonlinear optical processes occurring in nonlinear crystals. We describe this process using cold atomic-gas media to generate such nonclassical light, especially focusing on narrowband biphoton generation. Compared with the standard procedure the new biphoton source has such properties as long coherence time, long coherence length, high spectral brightness, and high conversion efficiency. Although there exist two methodologies describing the physical process, we concentrate on the theoretical aspect of the entangled two-photon state produced from the four-wave mixing in a multilevel atomic ensemble using perturbation theory. We show that both linear and nonlinear optical responses to the generated fields play an important role in determining the biphoton waveform and, consequently, on the two-photon temporal correlation. There are two characteristic regimes determined by whether the linear or nonlinear coherence time is dominant. In addition, our model provides a clear physical picture that brings insight into understanding biphoton optics with this new source. We apply our model to recent work on generating narrowband (and even subnatural linewidth) paired photons using the technique of electromagnetically induced transparency and slow-light effect in cold atoms and find good agreement with experimental results.