bluuebunny/crossref_metadata_2025_split huggingface dataset:
WFIKKN1 and WFIKKN2 bind growth factors TGFβ1, BMP2 and BMP4 but do not inhibit their signalling activity
Authors: Szláma György , Kondás Katalin , Trexler Mária , Patthy László 
Published: October 2010

WFIKKN1 and WFIKKN2 are large extracellular multidomain proteins consisting of a WAP domain, a follistatin domain, an immunoglobulin domain, two Kunitz‐type protease inhibitor domains and an NTR domain. Recent experiments have shown that both proteins have high affinity for growth and differentiation factor (GDF)8 and GDF11. Here we study the interaction of WFIKKN proteins with several additional representatives of the transforming growth factor (TGF)β family using SPR measurements. Analyses of SPR sensorgrams suggested that, in addition to GDF8 and GDF11, both WFIKKN proteins bind TGFβ1, bone morphogenetic protein (BMP)2 and BMP4 with relatively high affinity (Kd ∼ 10−6 m). To assess the biological significance of these interactions we studied the effect of WFIKKN proteins on the activity of GDF8, GDF11, TGFβ1, BMP2 and BMP4 using reporter assays. These studies revealed that WFIKKN1 and WFIKKN2 inhibited the biological activity of GDF8 and GDF11 in the nanomolar range, whereas they did not inhibit the activities of TGFβ1, BMP2 and BMP4 even in the micromolar range. Our data indicate that WFIKKN proteins are antagonists of GDF8 and GDF11, but in the case of TGFβ1, BMP2 and BMP4 they function as growth factor binding proteins. It is suggested that the physical association of WFIKKN proteins with these growth factors may localize their action and thus help to establish growth factor gradients in the extracellular space.Structured digital abstract
A list of the large number of protein‐protein interactions described in this article is available via the MINT article MINT‐8044119
Restraints or alternatives: safety work in care of older persons
Authors: Ludwick Ruth , O’Toole Richard , Meehan Anita 
Published: October 2010

ludwick r., o’toole r. & meehan a. (2012) Restraints or alternatives: safety work in care of older persons.International Journal of Older People Nursing7, 11–19   doi: 10.1111/j.1748‐3743.2010.00244.xAim. To examine the factors and complexity that account for physical restraints use and their alternatives as nurses’ protect the safety of older adults.Background. Research on physical restraints has repeatedly shown the human, financial and work costs associated with their use, but their use continues to be a major quality issue across hospitals and across countries for older persons.Method. Interviews with medical surgical nurses in a Midwestern hospital in the United States were recorded and interpreted using grounded theory.Results. Using data that described the complexity of initiating, maintaining, or discontinuing restraints, we captured the density of these processes and showed how nurses made decisions about restraint use. The tasks carried out to protect the older person’s safety often involved using restraints or their alternatives and these tasks then set in motion a cascade of other types of tasks or work, e.g. diagnostic, comfort, articulation.Conclusions. The study extended the work on chronic illness trajectories and formulated a framework for understanding the complexity of the use of restraints and their alternatives. Using a tracing approach we were able to predict the types of situations that would most likely result in the initiation, maintenance and discontinuation of restraints or the use of alternative procedures.Relevance to practice. The study has identified a process of ‘safety work’ that identified the risk associated with the problem, the work to cope with the problem and risk, the conditions that influenced the process and the consequences or outcomes of the work strategies to maintain the older person’s safety.
Characterization of the ‘pristinamycin supercluster’ of Streptomyces pristinaespiralis
Authors: Mast Yvonne , Weber Tilmann , Gölz Melanie , Ort‐Winklbauer Regina , Gondran Anne , Wohlleben Wolfgang , Schinko Eva 
Published: October 2010

SummaryPristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and pristinamycin II. The semi‐synthetic derivatives of these compounds are used in human medicine as therapeutic agents against methicillin‐resistant Staphylococcus aureus strains. Only the partial sequence of the pristinamycin biosynthetic gene cluster has been previously reported. To complete the sequence, overlapping cosmids were isolated from a S. pristinaespiralis Pr11 gene library and sequenced. The boundaries of the cluster were deduced, limiting the cluster size to approximately 210 kb. In the central region of the cluster, previously unknown pristinamycin biosynthetic genes were identified. Combining the current and previously identified sequence information, we propose that all essential pristinamycin biosynthetic genes are included in the 210 kb region. A pristinamycin biosynthetic pathway was established. Furthermore, the pristinamycin gene cluster was found to be interspersed by a cryptic secondary metabolite cluster, which probably codes for a glycosylated aromatic polyketide. Gene inactivation experiments revealed that this cluster has no influence on pristinamycin production. Overall, this work provides new insights into pristinamycin biosynthesis and the unique genetic organization of the pristinamycin gene region, which is the largest antibiotic ‘supercluster’ known so far.
Electroacupuncture Protected Pyramidal Cells in Hippocampal CA1 Region of Vascular Dementia Rats by Inhibiting the Expression of P53 and Noxa
Authors: Zhu Yanzhen , Zeng Yanjun 
Published: October 2010

SUMMARYAim: Clinically electroacupuncture (EA) is proved an effective therapy for vascular dementia (VD), but their mechanisms remain uncertain. The aim of this study was to determine whether EA protects pyramidal cells from apoptosis in hippocampus of a VD rat model by inhibiting the expression of p53 and Noxa. Methods: One month after a VD animal model was established by bilateral occlusion of common carotid arteries, EA treatment was given at “Baihui” (DU20), “Dazhui” (DU14), and “Shenshu” (BL23). The learning and memory ability was assessed by Morris water maze. Neuronal apoptosis in hippocampus was evaluated with hematoxylin–eosin (HE) staining, and the expression of p53 and Noxa was analyzed by confocal laser scanning microscope with immunofluorescence staining. Results: Expressions of p53 and Noxa in the EA group and sham‐operated group were less than in the VD model group (P < 0.01), and the expression of p53 was positively correlated to expression of Noxa in hippocampus of VD rats (r = 0.918, P < 0.01). EA treatment could reduce the amount of apoptotic neurons in hippocampal CA1 area of rats with VD. The average latency in the Morris water maze test was significantly shorter, and escape strategies improved from edge and random searches to more linear swim pathway in the EA group compared with the VD model group (P < 0.01). Conclusions: The increasing expressions of p53 and Noxa play important roles in the pathogenesis of VD. EA improves learning and memory ability and protects pyramidal cells from apoptosis by blocking expression of p53 and Noxa in the hippocampal CA1 region of VD rats. These results suggest a novel mechanism of EA treatment to VD.
Melatonin Receptor Agonists: New Options for Insomnia and Depression Treatment
Authors: Spadoni Gilberto , Bedini Annalida , Rivara Silvia , Mor Marco 
Published: October 2010

SUMMARYThe circadian nature of melatonin (MLT) secretion, coupled with the localization of MLT receptors to the suprachiasmatic nucleus, has led to numerous studies of the role of MLT in modulation of the sleep‐wake cycle and circadian rhythms in humans. Although much more needs to be understood about the various functions exerted by MLT and its mechanisms of action, three therapeutic agents (ramelteon, prolonged‐release MLT, and agomelatine) are already in use, and MLT receptor agonists are now appearing as new promising treatment options for sleep and circadian‐rhythm related disorders. In this review, emphasis has been placed on medicinal chemistry strategies leading to MLT receptor agonists, and on the evidence supporting therapeutic efficacy of compounds undergoing clinical evaluation. A wide range of clinical trials demonstrated that ramelteon, prolonged‐release MLT and tasimelteon have sleep‐promoting effects, providing an important treatment option for insomnia and transient insomnia, even if the improvements of sleep maintenance appear moderate. Well‐documented effects of agomelatine suggest that this MLT agonist offers an attractive alternative for the treatment of depression, combining efficacy with a favorable side effect profile. Despite a large number of high affinity nonselective MLT receptor agonists, only limited data on MT1or MT2subtype‐selective compounds are available up to now. Administration of the MT2‐selective agonistIIK7to rats has proved to decrease NREM sleep onset latency, suggesting that MT2receptor subtype is involved in the acute sleep‐promoting action of MLT; rigorous clinical studies are needed to demonstrate this hypothesis. Further clinical candidates based on selective activation of MT1or MT2receptors are expected in coming years.
Lacosamide and Epilepsy
Authors: Harris Jacklyn A. , Murphy Julie A. 
Published: October 2010

SUMMARYWe will review all available studies on the use of lacosamide in the treatment of partial‐onset seizures. The available evidence includes two open‐label studies and three randomized controlled trials evaluating the safety and efficacy of oral lacosamide. One open‐label study and one randomized controlled trial evaluating the safety and tolerability of intravenous lacosamide was also identified. Lacosamide was found to be efficacious with significant reduction in seizure frequency dosed 400–600 mg daily. Moreover, its adverse drug effects were mild and infrequently reported in the literature. Findings suggest that lacosamide is an effective agent for adjunctive treatment of refractory partial‐onset seizures.
Role of Spinal Neurotransmitter Receptors in Itch: New Insights into Therapies and Drug Development
Authors: Cevikbas Ferda , Steinhoff Martin , Ikoma Akihiko 
Published: October 2010

SUMMARYTargets for antipruritic therapies are now expanding from the skin to the central nervous system. Recent studies demonstrate that various neuronal receptors in the spinal cord are involved in pruritus. The spinal opioid receptor is one of the best‐known examples. Spinal administration of morphine is frequently accompanied by segmental pruritus. In addition to μ‐opioid receptor antagonists, κ‐opioid receptor agonists have recently come into usage as novel antipruritic drugs, and are expected to suppress certain subtypes of itch such as hemodialysis‐ and cholestasis‐associated itch that are difficult to treat with antihistamines. The gastrin‐releasing peptide receptor in the superficial dorsal horn of the spinal cord has also received recent attention as a novel pathway of itch‐selective neural transmission. The NMDA glutamate receptor appears to be another potential target for the treatment of itch, especially in terms of central sensitization. The development of NMDA receptor antagonists with less undesirable side effects on the central nervous system might be beneficial for antipruritic therapies. Drugs suppressing presynaptic glutamate‐release such as gabapentin and pregabalin also reportedly inhibit certain subtypes of itch such as brachioradial pruritus. Spinal receptors of other neuromediators such as bradykinin, substance P, serotonin, and histamine may also be potential targets for antipruritic therapies, given that most of these molecules interfere not only with pain, but also with itch transmission or regulation. Thus, the identification of itch‐specific receptors and understanding itch‐related circuits in the spinal cord may be innovative strategies for the development of novel antipruritic drugs.
The effect of pyridine treatment on phase Q: Orgueil and Allende
Authors: MATSUDA Jun‐ichi , AMARI Sachiko , MORISHITA Kazuhiko , NAGASHIMA Kana , NARA Masayuki 
Published: October 2010

Abstract– Marrocchi et al. (2005) reported that low‐temperature fractions of heavy noble gases were largely removed upon pyridine treatment of the Orgueil CI meteorite. As pyridine is known to induce the swelling of the macromolecular network of organic matter, they concluded that the low‐temperature phase Q is macromolecular organic carbon. However, Busemann et al. (2008) showed that pyridine had no significant effect on the noble gas contents for other very primitive meteorites, such as CM and CR. Therefore, we prepared an HF–HCl residue and the pyridine‐treated residue of Orgueil, and re‐examined the results of Marrocchi et al. (2005) by analyzing all noble gases. We confirmed that heavy noble gases are surely removed by the pyridine treatment, but the degree of the loss of heavy noble gases is generally small, and is even smaller for the lighter noble gases. Furthermore, we could not observe the evidence of Xe isotopic ratios by removing only phase Q after the pyridine treatment. We further prepared the HF–HCl residue and the pyridine‐treated residue of the Allende CV3 meteorite and performed noble gas analyses. For Allende, there is no significant change in the elemental abundances after the pyridine treatment. These results suggest that only Orgueil is special, and it is likely that the gas loss of the Orgueil residue is due to the loss of some kind of organic matter that was formed and that adsorbed the fractionated Q and HL gases during the aqueous alteration within the parent body of Orgueil.
NGOs' Strategies and the Challenge of Development and Democracy in Bangladesh
Authors: Kabeer Naila , Mahmud Simeen , Isaza Castro Jairo Guillermo 
Published: October 2010

SummaryRecent research Bangladesh has come to embody an interesting paradox. On the one hand, it has experienced rising rates of growth, a slow but steady decline in poverty and impressive progress in terms of social development, outperforming some of its richer neighbours on a number of Millennium Development Goals. On the other hand, it has an abysmal record on governance and was ranked as the world's most corrupt country for five consecutive years by Transparency International. There is an emerging view that the country's extremely active development NGO sector has contributed to some of the more positive achievements. The question that this paper sets out to address is why these organisations have not made an equivalent contribution on the governance front. The paper argues that while Bangladesh is reported to have more NGOs per capita than other developing countries, those organisations have gradually abandoned social mobilising and collective action strategies for a narrower focus on service delivery and microcredit provision. Our research with the members of six organisations that straddle the continuum between microfinance and social mobilisation suggests that the specific developmental strategies of these membership‐based groups do indeed have consequences for both development and democracy in the country.
Adaptive Social Protection: Mapping the Evidence and Policy Context in the Agriculture Sector in South Asia
Authors: Arnall Alex , Oswald Katy , Davies Mark , Mitchell Tom , Coirolo Cristina 
Published: October 2010

SummaryAn aim of government and the international community is to respond to global processes and crises through a range of policy and practical approaches that help limit damage from shocks and stresses. Three approaches to vulnerability reduction that have become particularly prominent in recent years are social protection (SP), disaster risk reduction (DRR) and climate change adaptation (CCA). Although these approaches have much in common, they have developed separately over the last two decades. However, given the increasingly complex and interlinked array of risks that poor and vulnerable people face, it is likely that they will not be sufficient in the long run if they continue to be applied in isolation from one another.In recognition of this challenge, the concept of Adaptive Social Protection (ASP) has been developed. ASP refers to a series of measures which aims to build resilience of the poorest and most vulnerable people to climate change by combining elements of SP, DRR and CCA in programmes and projects. The aim of this paper is to provide an initial assessment of the ways in which these elements are being brought together in development policy and practice. It does this by conducting a meta‐analysis of 124 agricultural programmes implemented in five countries in south Asia. These are Afghanistan, Bangladesh, India, Nepal and Pakistan.The findings show that full integration of SP, DRR and CCA is relatively limited in south Asia, although there has been significant progress in combining SP and DRR in the last ten years. Projects that combine elements of SP, DRR and CCA tend to emphasise broad poverty and vulnerability reduction goals relative to those that do not. Such approaches can provide valuable lessons and insights for the promotion of climate resilient livelihoods amongst policymakers and practitioners.
Limited lymph-node recovery based on lymph-node localisation is sufficient for accurate staging: Table 1
Authors: Cserni Gábor , Bori Rita , Sejben István 
Published: October 2010

AimsTo assess the reliability of nodal staging in colorectal carcinomas (CRCs) when only lymph nodes close to the tumour are recovered and examined histologically.MethodsLymph nodes from CRC resection specimens were recovered into two fractions: one from around the tumour and the 3 cm sidelong bowel segment associated with it in the proximal and distal directions, and another from the remaining part of the resection specimen.ResultsOf the 762 CRCs (239 right colon, 251 left colon, 257 rectum, 15 unspecified localisation) there were 393 node-negative and 369 node-positive cases. The median number of LNs examined was 18. The assessment of the LNs located in the close fraction (median 13) yielded an adequate qualitative nodal status in 756 patients (99.2%). In four cases (two rectal and two right colic), no LN metastases could be identified in the close-fraction lymph nodes, but nodes from the distant fraction contained metastases. Of the node-positive carcinomas which had at least one positive lymph node in the close fraction, 203 belonged to the pN1 category and 162 to the pN2 category of the Tumour Node Metastasis staging system. Only 14 cases (10 rectal, two right and two left colic tumours) were misclassified as pN1 (on the basis of lymph nodes recovered from the close fraction) although they were of the pN2 category.ConclusionsIn general, nodal status of CRCs may be adequately assessed by examining the lymph nodes from the close fraction around the tumour and the 3 cm sidelong bowel segment in both directions.
Lymphatic vessel density and its prognostic value in stage I colorectal carcinoma
Authors: Barresi V , Reggiani-Bonetti L , Di Gregorio C , Ponz De Leon M , Barresi G 
Published: October 2010

AimsThe assessment of lymphatic vessel density (LVD) has been suggested as a tool to determine the metastatic risk of neoplasias. On this premise, the authors aimed to verify whether progression risk of stage I colorectal cancer may be related to LVD. The authors also evaluated and correlated vascular endothelial growth factor (VEGF)-A expression with LVD revealed in the same cases in order to investigate its potential lymphangiogenic role in the early stage colorectal cancer.MethodsLVD and VEGF immunoexpression were analysed and compared in series of 29 stage I surgically resected colorectal carcinomas obtained from patients showing disease progression and in a cohort of 23 stage I colorectal cancers from patients with no evidence of disease progression. The prognostic value of LVD and of VEGF expression on the progression-free survival to colorectal cancer was investigated.ResultsA high density of peritumoural lymphatics (P-LVD) was significantly associated with high VEGF expression and disease progression. Moreover, high P-LVD and high VEGF expression were significant negative prognostic parameters associated with a shorter disease-free interval in stage I colorectal cancer.ConclusionsIf our findings are further confirmed in other studies, the assessment of P-LVD on surgical specimens might be used as a tool to identify patients with stage I colorectal cancer at higher risk of progression in order to submit them to adjuvant therapies. Since P-LVD seems to show a VEGF-A mediated regulation in stage I colorectal cancer, therapies targeting this factor might be exploited to reduce lymphangiogenesis and the progression risk of this neoplasia.
European field study of the efficacy and safety of the novel anthelmintic monepantel in sheep
Authors: Jones M. D. , Hunter R. P. , Dobson D. P. , Reymond N. , Strehlau G. A. , Kubacki P. , Tranchard E. S. N. , Walters M. E. 
Published: October 2010

During 2007, a large‐scale controlled, multicentre, blinded and randomised field study was conducted in Scotland, England and France to assess the efficacy and safety of monepantel, the first molecule to be developed from the recently discovered amino‐acetonitrile derivatives class of anthelmintics, in sheep. Monepantel was administered orally, at a minimum dose of 2.5 mg/kg bodyweight, for the control of gastrointestinal nematodes in sheep maintained at pasture in a range of commercial production systems. Efficacy was measured by faecal egg count (FEC) reduction tests seven days after treatment and was demonstrated to be over 98 per cent against mixed‐genus infections. The reduction in FEC of monepantel‐treated sheep was statistically significantly greater than in untreated control sheep (P<0.0001). The efficacy of monepantel against mixed‐genus natural field infections of the major gastrointestinal nematodes was in agreement with similar studies conducted in Australia and New Zealand. There were no treatment‐related adverse events during the study, which included the use of a range of concomitant treatments.
Diagnosis of feline polycystic kidney disease by a combination of ultrasonographic examination and PKD1 gene analysis
Authors: Lee Y‐J. , Chen H‐Y. , Hsu W‐L. , Ou C‐M. , Wong M‐L. 
Published: October 2010

Persian‐related and non‐Persian‐related cats were examined by ultrasonography and/or molecular testing to determine the prevalence of feline polycystic kidney disease (PKD) and the presence of a PKD1 gene mutation. PCR was used to amplify exon 29 of the PKD1 gene using genomic DNA extracted from blood samples, and the PCR products were analysed by direct DNA sequencing. Among the 111 cats included in the study, 54 were examined by both ultrasonography and gene testing for a point mutation in exon 29 of the PKD1 gene. The prevalence of PKD diagnosed by ultrasonography was 25.9 per cent in all the cats and 24.2 per cent in Persian‐related cats. The prevalence of the transversion mutation in exon 29 of the PKD1 gene was 13.5 per cent in all cats and 15.7 per cent in Persian‐related cats. Three cats that were diagnosed with PKD by ultrasonography did not have the mutation within exon 29. Nucleotide analysis of exon 29 indicated that male cats had a higher point mutation rate than female cats.