bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras
Authors: Xu Jin , Hedberg Christian , Dekker Frank J. , Li Qing , Haigis Kevin M. , Hwang Eugene , Waldmann Herbert , Shannon Kevin 
Published: December 2011

Abstract
The palmitoylation/depalmitoylation cycle of posttranslational processing is a potential therapeutic target for selectively inhibiting the growth of hematologic cancers with somatic NRAS mutations. To investigate this question at the single-cell level, we constructed murine stem cell virus vectors and assayed the growth of myeloid progenitors. Whereas cells expressing oncogenic N-RasG12D formed cytokine-independent colonies and were hypersensitive to GM-CSF, mutations within the N-Ras hypervariable region induced N-Ras mislocalization and attenuated aberrant progenitor growth. Exposing transduced hematopoietic cells and bone marrow from Nras and Kras mutant mice to the acyl protein thioesterase inhibitor palmostatin B had similar effects on protein localization and colony growth. Importantly, palmostatin B-mediated inhibition was selective for Nras mutant cells, and we mapped this activity to the hypervariable region. These data support the clinical development of depalmitoylation inhibitors as a novel class of rational therapeutics in hematologic malignancies with NRAS mutations.
Public health in the genomic era: will Public Health Genomics contribute to major changes in the prevention of common diseases?
Authors: Cleeren Evy , Van der Heyden Johan , Brand Angela , Van Oyen Herman 
Published: December 2011

Abstract
The completion of the Human Genome Project triggered a whole new field of genomic research which is likely to lead to new opportunities for the promotion of population health. As a result, the distinction between genetic and environmental diseases has faded. Presently, genomics and knowledge deriving from systems biology, epigenomics, integrative genomics or genome-environmental interactions give a better insight on the pathophysiology of common diseases. However, it is barely used in the prevention and management of diseases. Together with the boost in the amount of genetic association studies, this demands for appropriate public health actions. The field of Public Health Genomics analyses how genome-based knowledge and technologies can responsibly and effectively be integrated into health services and public policy for the benefit of population health. Environmental exposures interact with the genome to produce health information which may help explain inter-individual differences in health, or disease risk. However today, prospects for concrete applications remain distant. In addition, this information has not been translated into health practice yet. Therefore, evidence-based recommendations are few. The lack of population-based research hampers the evaluation of the impact of genomic applications. Public Health Genomics also evaluates the benefits and risks on a larger scale, including normative, legal, economic and social issues. These new developments are likely to affect all domains of public health and require rethinking the role of genomics in every condition of public health interest. This article aims at providing an introduction to the field of and the ideas behind Public Health Genomics.
On Friedrichs-type inequalities in domains rarely perforated along the boundary
Authors: Koroleva Yulia , Persson Lars-Erik , Wall Peter 
Published: December 2011

Abstract
This article is devoted to the Friedrichs inequality, where the domain is periodically perforated along the boundary. It is assumed that the functions satisfy homogeneous Neumann boundary conditions on the outer boundary and that they vanish on the perforation. In particular, it is proved that the best constant in the inequality converges to the best constant in a Friedrichs-type inequality as the size of the perforation goes to zero much faster than the period of perforation. The limit Friedrichs-type inequality is valid for functions in the Sobolev space H
1.

AMS 2010 Subject Classification: 39A10; 39A11; 39A70; 39B62; 41A44; 45A05.
Bifunctional TaqII restriction endonuclease: redefining the prototype DNA recognition site and establishing the Fidelity Index for partial cleaving
Authors: Żylicz-Stachula Agnieszka , Żołnierkiewicz Olga , Śliwińska Katarzyna , Jeżewska-Frąckowiak Joanna , Skowron Piotr M 
Published: December 2011

Abstract

Background
The TaqII enzyme is a member of the Thermus sp. enzyme family that we propounded previously within Type IIS restriction endonucleases, containing related thermophilic bifunctional endonucleases-methyltransferases from various Thermus sp.: TaqII, Tth111II, TthHB27I, TspGWI, TspDTI and TsoI. These enzymes show significant nucleotide and amino acid sequence similarities, a rare phenomenon among restriction endonucleases, along with similarities in biochemical properties, molecular size, DNA recognition sequences and cleavage sites. They also feature some characteristics of Types I and III.

Results
Barker et al. reported the Type IIS/IIC restriction endonuclease TaqII as recognizing two distinct cognate site variants (5'-GACCGA-3' and 5'-CACCCA-3') while cleaving 11/9 nucleotides downstream. We used four independent methods, namely, shotgun cloning and sequencing, restriction pattern analysis, digestion of particular custom substrates and GeneScan analysis, to demonstrate that the recombinant enzyme recognizes only 5'-GACCGA-3' sites and cleaves 11/9 nucleotides downstream. We did not observe any 5'-CACCCA-3' cleavage under a variety of conditions and site arrangements tested. We also characterized the enzyme biochemically and established new digestion conditions optimal for practical enzyme applications. Finally, we developed and propose a new version of the Fidelity Index - the Fidelity Index for Partial Cleavage (FI-PC).

Conclusions
The DNA recognition sequence of the bifunctional prototype TaqII endonuclease-methyltransferase from Thermus aquaticus has been redefined as recognizing only 5'-GACCGA-3' cognate sites. The reaction conditions (pH and salt concentrations) were designed either to minimize (pH = 8.0 and 10 mM ammonium sulphate) or to enhance star activity (pH = 6.0 and no salt). Redefinition of the recognition site and reaction conditions makes this prototype endonuclease a useful tool for DNA manipulation; as yet, this enzyme has no practical applications. The extension of the Fidelity Index will be helpful for DNA manipulation with enzymes only partially cleaving DNA.
Factors associated with antenatal mental disorder in West Africa: A cross-sectional survey
Authors: Ola Bola , Crabb Jim , Tayo Adetokunbo , Gleadow Ware Selena H , Dhar Arup , Krishnadas Rajeev 
Published: December 2011

Abstract

Background
Maternal mental illness is likely to have a profound impact in less developed parts of the world. A mother experiencing mental illness in a low income setting is at risk of providing sub-optimal care for her offspring which can have grave consequences in an environment where poverty, overcrowding, poor sanitation, malnutrition, tropical diseases and a lack of appropriate medical services may be pronounced. Given the profound consequences of antenatal and postnatal mental illness on maternal mental health, foetal wellbeing and childhood growth and development the factors associated with mental illness in a Sub-Saharan setting merit clarification and investigation.

Methods
A prospective survey design was conducted in Lagos. Self reporting questionnaire 20 items - SRQ20 - assessed the presence of mental illness. The WHO Multi-country Study on Women's Health and Domestic Violence Questions assessed women's exposure to violence. Numerous variables potentially associated with mental illness including maternal socio-economic factors, maternal characteristics, obstetric variables and the characteristics of previous children were recorded. Direct logistic regression was performed to assess the impact of a number of variables on the likelihood of presence of mental disorder in the population.

Results
189 women were surveyed. 7% met the criteria for experiencing a common mental disorder according to their score on the SRQ-20. Of variables examined only the number of female children and the presence of inter personal violence predicted being a case of mental illness (OR = 3.400; 95%CI = 1.374 - 8.414 and OR = 5.676; 95%CI = 1.251 - 25.757 respectively).

Conclusions
Rates of mental disorder found in our study were lower than those previously observed internationally and in Africa, perhaps reflecting stigma about disclosing symptoms. The predictive nature of violence on mental disorder is in keeping with international evidence. Our study demonstrated that exposure to inter personal violence within the last 12 months and increasing numbers of female children predict the presence of mental illness in a sample of pregnant Nigerian women. Training and education for primary health care and obstetric health workers should highlight these areas.
Addressing risk factors for child abuse among high risk pregnant women: design of a randomised controlled trial of the nurse family partnership in Dutch preventive health care
Authors: Mejdoubi Jamila , van den Heijkant Silvia , Struijf Elle , van Leerdam Frank , HiraSing Remy , Crijnen Alfons 
Published: December 2011

AbstractBackgroundLow socio-economic status combined with other risk factors affects a person's physical and psychosocial health from childhood to adulthood. The societal impact of these problems is huge, and the consequences carry on into the next generation(s). Although several studies show these consequences, only a few actually intervene on these issues. In the United States, the Nurse Family Partnership focuses on high risk pregnant women and their children. The main goal of this program is primary prevention of child abuse. The Netherlands is the first country outside the United States allowed to translate and culturally adapt the Nurse Family Partnership into VoorZorg. The aim of the present study is to assess whether VoorZorg is as effective in the Netherland as in the United States.MethodsThe study consists of three partly overlapping phases. Phase 1 was the translation and cultural adaptation of Nurse Family Partnership and the design of a two-stage selection procedure. Phase 2 was a pilot study to examine the conditions for implementation. Phase 3 is the randomized controlled trial of VoorZorg compared to the care as usual. Primary outcome measures were smoking cessation during pregnancy and after birth, birth outcomes, child development, child abuse and domestic violence. The secondary outcome measure was the number of risk factors present.DiscussionThis study shows that the Nurse Family Partnership was successfully translated and culturally adapted into the Dutch health care system and that this program fulfills the needs of high-risk pregnant women. We hypothesize that this program will be effective in addressing risk factors that operate during pregnancy and childhood and compromise fetal and child development.Trial registrationCurrent Controlled TrialsISRCTN16131117
Intimate partner violence among women with HIV infection in rural Uganda: critical implications for policy and practice
Authors: Osinde Michael O , Kaye Dan K , Kakaire Othman 
Published: December 2011

Abstract

Background
Intimate partner violence (IPV) is a major public health problem in Africa and worldwide. HIV infected women face increased IPV risk. We assessed the prevalence and factors associated with IPV among HIV infected women attending HIV care in Kabale hospital, Uganda.

Methods
This cross-sectional study was conducted among 317 HIV infected women attending Kabale regional hospital HIV treatment centre, from March to December 2010. Participants were interviewed using an interviewer-administered questionnaire. Data was collected on socio-demographic variables, social habits, and IPV (using the abuse assessment screen and the Severity of Violence against Women Scale to identify physical, sexual and psychological violence). Characteristics of the participants who reported IPV were compared with those who did not. Multivariate logistic-regression analysis was conducted to analyze factors that were independently associated with IPV.

Results
The mean age of 317 respondents was 29.7 years. Twenty two (6.9%) were adolescents and 233 (73.5%) were married or cohabiting. The mean age of the spouse was 33.0 years.
One hundred and eleven (35.0%) were currently on antiretroviral therapy. Lifetime prevalence of IPV (physical or sexual) was 36.6%. In the preceding 12 months, IPV (any type) was reported by 93 respondents (29.3%). This was physical for 55 (17.6%), and sexual /psychological for 38 (12.1%). On multivariate multinomial logistic regression analysis, there was a significant but inverse association between education level and physical partner violence (adjusted relative risk (ARR) 0.50, confidence limits (95% CI) 0.31-0.82, p-value = 0.007). There was a significant but inverse association between education level of respondent and sexual/psychological violence (ARR 0.47 95%CI (0.25-0.87), p-value = 0.017) Likewise, there was a significant inverse association between the education level of the spouse and psychological/sexual violence (ARR 0.57, 95% CI 0.25-0.90, p-value = 0.018). Use of antiretroviral therapy was associated with increased prevalence of any type of violence (physical, sexual or psychological) with ARR 3.04 (95%CI 1.15-8.45, p-value = 0.032).

Conclusion
Almost one in three women living with HIV had suffered intimate partner violence in the preceding 12 months. Nearly one in five HIV patients reported physical violence, and about one in every seven HIV patients reported sexual/psychological violence. Likewise, women who were taking antiretroviral drugs for HIV treatment were more likely to report any type of intimate partner violence (physical, sexual or psychological). The implication of these findings is that women living with HIV especially those on antiretroviral drugs should be routinely screened for intimate partner violence.
A thermostable GH45 endoglucanase from yeast: impact of its atypical multimodularity on activity
Authors: Couturier Marie , Feliu Julia , Haon Mireille , Navarro David , Lesage-Meessen Laurence , Coutinho Pedro M , Berrin Jean-Guy 
Published: December 2011

AbstractBackgroundThe gene encoding an atypical multi-modular glycoside hydrolase family 45 endoglucanase bearing five different family 1 carbohydrate binding modules (CBM1), designatedPpCel45A, was identified in thePichia pastorisGS115 genome.ResultsPpCel45A (full-length open reading frame), and three derived constructs comprising (i) the catalytic module with its proximal CBM1, (ii) the catalytic module only, and (iii) the five CBM1 modules without catalytic module, were successfully expressed to high yields (up to 2 grams per litre of culture) inP. pastorisX33. Although the constructs containing the catalytic module displayed similar activities towards a range of glucans, comparison of their biochemical characteristics revealed striking differences. We observed a high thermostability ofPpCel45A (Half life time of 6 h at 80°C), which decreased with the removal of CBMs and glycosylated linkers. However, both binding to crystalline cellulose and hydrolysis of crystalline cellulose and cellohexaose were substantially boosted by the presence of one CBM rather than five.ConclusionsThe present study has revealed the specific features of the first characterized endo β-1,4 glucanase from yeast, whose thermostability is promising for biotechnological applications related to the saccharification of lignocellulosic biomass such as consolidated bioprocessing.
The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma
Authors: Nishimura Akinobu , Matsumine Akihiko , Asanuma Kunihiro , Matsubara Takao , Nakamura Tomoki , Uchida Atsumasa , Kato Ko , Sudo Akihiro 
Published: December 2011

Abstract

Background
Malignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions.

Methods
We retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas.

Results
The most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05).

Conclusions
Unplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.
New Methods with Perturbations for Non-Expansive Mappings in Hilbert Spaces
Authors: Yao Yonghong , Shahzad Naseer 
Published: December 2011

AbstractIn this paper, we suggest and analyze two iterative algorithms with perturbations for non-expansive mappings in Hilbert spaces. We prove that the proposed iterative algorithms converge strongly to a fixed point of some non-expansive mapping.2000 Mathematics Subject Classification 47H09, 47H10.
Some certain properties of the generalized hypercubical functions
Authors: Letić Duško , Cakić Nenad , Davidović Branko , Berković Ivana , Desnica Eleonora 
Published: December 2011

Abstract
In this article, the results of theoretical research of the generalized hypercube function by generalizing two known functions referring to the cube hypervolume and hypersurface and the recurrent relation between them have been presented. By introducing two degrees of freedom k and n (and the third half-edge r), we are able to develop the derivative functions for all three arguments and discuss the possibilities of their use. The symbolic evaluation, numerical experiment, and graphic presentation of the functions are realized using Mathcad Professional and Mathematica.

MSC 2010: 33E30; 33E50; 33E99; 52B11.
Calcitonin Gene-Related Peptide Promotes Cellular Changes in Trigeminal Neurons and Glia Implicated in Peripheral and Central Sensitization
Authors: Cady Ryan J , Glenn Joseph R , Smith Kael M , Durham Paul L 
Published: December 2011

Background: Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results: Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions: Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.
Safety and efficacy of tinea pedis and onychomycosis treatment in people with diabetes: a systematic review
Authors: Matricciani Lisa , Talbot Kerwin , Jones Sara 
Published: December 2011

AbstractBackgroundEffective treatment of tinea pedis and onychomycosis is crucial for patients with diabetes as these infections may lead to foot ulcers and secondary bacterial infections resulting in eventual lower limb amputation. Although numerous studies have assessed the effectiveness of antifungal drug and treatment regimens, most exclude patients with diabetes and examine otherwise healthy individuals. While these studies are useful, results cannot necessarily be extrapolated to patients with diabetes. The purpose of this study was to therefore identify the best evidence‐based treatment interventions for tinea pedis or onychomycosis in people with diabetes.MethodsThe question for this systemic review was: ‘what evidence is there for the safety and/or efficacy of all treatment interventions for adults with tinea pedis and/or onychomycosis in people with diabetes’? A systematic literature search of four electronic databases (Scopus, EbscoHost, Ovid, Web of Science) was undertaken (6/1/11). The primary outcome measure for safety was self‐reported adverse events likely to be drug‐related, while the primary outcome measures assessed for ‘efficacy’ were mycological, clinical and complete cure.ResultsThe systematic review identified six studies that examined the safety and/or efficacy of treatment interventions for onychomycosis in people with diabetes. No studies were identified that examined treatment for tinea pedis. Of the studies identified, two were randomised controlled trials (RCTs) and four were case series. Based on the best available evidence identified, it can be suggested that oral terbinafine is as safe and effective as oral itraconazole therapy for the treatment of onychomycosis in people with diabetes. However, efficacy results were found to be poor.ConclusionsThis review indicates that there is good evidence (Level II) to suggest oral terbinafine is as safe and effective as itraconazole therapy for the treatment of onychomycosis in people with diabetes. Further research is needed to establish the evidence for other treatment modalities and treatment for tinea pedis for people with diabetes. Future efforts are needed to improve the efficacy of treatment intervention.