bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular recognition and physicochemical properties in the discovery of selective antibacterial minor groove binders
Authors: Suckling Colin J. 
Published: February 2008

AbstractThe polyamide minor groove binders (MGBs), distamycin and netropsin, have been known for many years to have significant biological activities but high toxicity. Strategies are described for the development of more selective MGBs taking advantage of hydrophobic interactions with the minor groove of DNA. The introduction of branched alkyl side chain substituents, planar aromatic head groups and alkene isosteres of the amides have all been investigated. MGBs designed using these strategies and built from heterocyclic and aromatic amino acids with the ability to recognise short sequences of DNA have been found to be potent and selective antibacterial agents. Detailed structural and strength of binding investigations (NMR, capillary electrophoresis (CE), DNA footprinting, melting temperature measurement, ITC) show that their activity depends primarily upon molecular recognition in terms of both molecular shape and specific hydrogen bonding. However the lack of toxicity depends upon their basic tail group structure, the pKa of which has a major influence on access to bacterial and mammalian cells. Lead compounds are active in vivo at doses competitive with recently introduced antibacterial drugs. Copyright © 2008 John Wiley & Sons, Ltd.
SEREX, Proteomex, AMIDA, and beyond: Serological screening technologies for target identification
Authors: Rauch Jens , Gires Olivier 
Published: February 2008

AbstractDespite the great body of knowledge about the aetiology, pathogenesis, risk factors, and associated molecular processes, cancer remains a prime health concern. Over the past decades scientific and medical research focused on the identification of biomarkers and target molecules for the diagnosis and therapy of cancer. Such markers may allow for improved and early diagnosis, as well as for immunotherapeutic approaches for cancer treatment. A plethora of technologies dedicated to the identification of target molecules was developed including those relying on a humoral response against tumour‐associated antigens (TAA) in diseased individuals. As for other diseases, cancers elicit immune responses that result in the induction of T and B lymphocytes specific for tumour‐associated proteins, largely self‐antigens, but also those comprising viral and bacterial proteins. Cancer‐specific serum antibodies are of great use for the isolation and subsequent identification of their cognate antigens. The present review will concentrate on three major serological target identification methods,i.e.SEREX, Proteomex, and AMIDA, concluding with a summary of the milestones in the clinical advancement and applications of serological TAA.
Crystal structure of yeast hexokinase PI in complex with glucose: A classical “induced fit” example revised
Authors: Kuser Paula , Cupri Fabio , Bleicher Lucas , Polikarpov Igor 
Published: February 2008

AbstractHexokinase is the first enzyme in the glycolytic pathway that catalyzes the transfer of a phosphoryl group from ATP to glucose to form glucose‐6‐phosphate and ADP. Two yeast hexokinase isozymes are known, namely PI and PII. Here we redetermined the crystal structure of yeast hexokinase PI from Saccharomyces cerevisiae as a complex with its substrate, glucose, and refined it at 2.95 Å resolution. Comparison of the holo‐PI yeast hexokinase and apo‐hexokinase structures shows in detail the rigid body domain closure and specific loop movements as glucose binds and sheds more light on structural basis of the “induced fit” mechanism of reaction in the HK enzymatic action. We also performed statistical coupling analysis of the hexokinase family, which reveals two co‐evolved continuous clusters of amino acid residues and shows that the evolutionary coupled amino acid residues are mostly confined to the active site and the hinge region, further supporting the importance of these parts of the protein for the enzymatic catalysis. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Docking analysis of transient complexes: Interaction of ferredoxin‐NADP+ reductase with ferredoxin and flavodoxin
Authors: Medina Milagros , Abagyan Ruben , Gómez‐Moreno Carlos , Fernandez‐Recio Juan 
Published: February 2008

AbstractFerredoxin (Fd) interacts with ferredoxin‐NADP+ reductase (FNR) to transfer two electrons to the latter, one by one, which will finally be used to reduce NADP+ to NADPH. The formation of a transient complex between Fd and FNR is required for the electron transfer (ET), and extensive mutational and crystallographic studies have been reported to characterize such protein–protein interaction. However, some aspects of the association mechanism still remain unclear. Moreover, in spite of their structural differences, flavodoxin (Fld) can replace Fd in its function and interact with FNR to transfer electrons with only slightly lower efficiency. Although crystallographic structures for the FNR:Fd association have been reported, experimental structural data for the FNR:Fld interaction are highly elusive. We have modeled here the interactions between FNR and both of its protein partners, Fd and Fld, using surface energy analysis, computational rigid‐body docking simulations, and interface side‐chain refinement. The results, consistent with previous experimental data, suggest the existence of alternative binding modes in these ET proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Video‐Assisted Thyroidectomy Significantly Reduces the Risk of Early Postthyroidectomy Voice and Swallowing Symptoms
Authors: Lombardi Celestino P. , Raffaelli Marco , D’alatri Lucia , De Crea Carmela , Marchese Maria Raffaella , Maccora Daria , Paludetti Gaetano , Bellantone Rocco 
Published: February 2008

AbstractBackgroundVoice and swallowing symptoms are frequently reported after thyroidectomy even in absence of objective voice alterations. We evaluated the influence of the video‐assisted approach on voice and swallowing outcome of thyroidectomy.MethodsSixty‐five patients undergoing total thyroidectomy (TT) were recruited. Eligibility criteria were: nodule size ≤30 mm, thyroid volume ≤30 ml, no previous neck surgery. Exclusion criteria were: younger than aged 18 years and older than aged 75 years, vocal fold paralysis, history of voice, laryngeal or pulmonary diseases, malignancy other than papillary thyroid carcinoma. Patients were randomized for video‐assisted (VAT) or conventional (CT) thyroidectomy. Videostrobolaryngoscopy (VSL), acoustic voice analysis (AVA), and maximum phonation time (MPT) evaluation were performed preoperatively and 3 months after TT. Subjective evaluation of voice (voice impairment score = VIS) and swallowing (swallowing impairment score = SIS) were obtained preoperatively, 1 week, 1 month, and 3 months after TT.ResultsFifty‐three patients completed the postoperative evaluation: 29 in the VAT group, and 24 in the CT group. No laryngeal nerves injury was shown at postoperative VSL. Mean postoperative MPT, F0, Flow, Fhigh, and the number of semitones were significantly reduced in the CT group but not in the VAT group. Mean VIS 3 months after surgery was significantly higher than preoperatively in CT group but not in the VAT group. Mean SIS was significantly decreased 1 and 3 months after VAT but not after CT.ConclusionsThe incidence and the severity of early voice and swallowing postthyroidectomy symptoms are significantly reduced in patients who undergo VAT compared with conventional surgery.
Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation
Authors: Annambhotla Suman , Bourgeois Sebastian , Wang Xinwen , Lin Peter H. , Yao Qizhi , Chen Changyi 
Published: February 2008

AbstractAbdominal aortic aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remain poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advances in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation, including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics, and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA.
Taste preferences, liking and other factors related to fruit and vegetable intakes among schoolchildren: results from observational studies
Authors: Brug Johannes , Tak Nannah I. , te Velde Saskia J. , Bere Elling , de Bourdeaudhuij Ilse 
Published: February 2008

The present paper explores the relative importance of liking and taste preferences as correlates of fruit and vegetable (FV) intakes among schoolchildren in Europe. The paper first provides an overview of potential determinants of food choice among children and subsequently summarizes the results of two recent observational studies on determinants of FV intakes among school-aged children. It is proposed that taste preferences and liking are important for children's food choices as part of a broader spectrum of nutrition behaviour determinants. Taste preferences and liking are important for motivation to eat certain foods, but social-cultural and physical environmental factors that determine availability and accessibility of foods, as well as nutrition knowledge and abilities should also be considered.Study 1 shows that children with a positive liking for FV have a greater likelihood to eat fruits (odds ratio (OR) = 1·97) or vegetables (OR = 1·60) every day, while ability and opportunity related factors such as knowledge, self-efficacy, parental influences and accessibility of FV were also associated with likelihood of daily intakes (ORs between 1·16 and 2·75). These results were consistent across different countries in Europe. Study 2 shows that taste prerences were the stongest mediator of gender differences in FV intakes among children; the fact that girls eat more could for a large extend be explained by there stronger taste preferences.
Influence of parental attitudes in the development of children eating behaviour
Authors: Scaglioni Silvia , Salvioni Michela , Galimberti Cinzia 
Published: February 2008

The present paper is a review of available data on effects of parental feeding attitudes and styles on child nutritional behaviour. Food preferences develop from genetically determined predispositions to like sweet and salty flavours and to dislike bitter and sour tastes. There is evidence for existence of some innate, automatic mechanism that regulate appetite. However, from birth genetic predispositions are modified by experience. There are mechanisms of taste development: mere exposure, medicine effect, flavour learning, flavour nutrient learning. Parents play a pivotal role in the development of their child's food preferences and energy intake, with research indicating that certain child feeding practices, such as exerting excessive control over what and how much children eat, may contribute to childhood overweight. Mothers are of particular interest on children's eating behaviour, as they have been shown to spend significantly more time than fathers in direct interactions with their children across several familial situations.A recent paper describes two primary aspects of control:restriction, which involves restricting children's access to junk foods and restricting the total amount of food, andpressure, which involves pressuring children to eat healthy foods (usually fruits and vegetables) and pressuring to eat more in general.The results showed significant correlations between parent and child for reported nutritional behaviour like food intake, eating motivations, and body dis- and satisfaction. Parents create environments for children that may foster the development of healthy eating behaviours and weight, or that may promote overweight and aspects of disordered eating. In conclusion positive parental role model may be a better method for improving a child's diet than attempts at dietary control.
Survey of Neodohrniphora spp. (Diptera: Phoridae) at colonies of Atta sexdens rubropilosa (FOREL) and specificity of attack behaviour in relation to their hosts
Authors: Silva V.S.G. , Bailez O. , Viana-Bailez A.M. , Tonhasca A. , Castro Della Lucia T.M. 
Published: February 2008

AbstractAtta sexdens rubropilosa is a leaf-cutting ant that is a significant agricultural and forestry pest in the Neotropical region. This ant is parasitized by flies from the genera Neodohrniphora spp., Apocephalus spp. and Myrmosicarius spp. This study was carried out to determine which species of Neodohrniphora spp. are found near foraging trails of Atta sexdens rubropilosa and to evaluate the specificity of attack behaviour of these parasitoids. From May 2002 to April 2004, we sampled Neodohrniphora spp. hovering over foraging trails of Atta sexdens rubropilosa between 8:00 and 11:00 h and between 15:00 and 18:00 h. To investigate the attacking behaviour against the ants, flies were released individually inside an observation chamber containing a single leaf-cutting ant worker. Each parasitoid was confronted successively with a worker ant of A. sexdens rubropilosa, Atta laevigata Smith, Acromyrmex crassispinus Forel and Acromyrmex subterraneus molestans Santschi. Phorids of three species were identified: Neodohrniphora elongata Brown, Neodohrniphora declinata Borgmeier and Neodohrniphora tonhascai Brown. The three phorid species were active throughout the year and often along the same foraging trails, but N. elongata was the most frequent species. In the laboratory assay, N. elongata, N. declinata and N. tonhascai attacked workers of A. sexdens rubropilosa, A. laevigata and A. crassispinus, but not of A. subterraneus molestans.
Positive association between resistance to Bacillus thuringiensis and overwintering survival of cabbage loopers, Trichoplusia ni (Lepidoptera: Noctuidae)
Authors: Caron V. , Myers J.H. 
Published: February 2008

AbstractDevelopment of resistance to insecticides has generally been associated with fitness costs that may be magnified under challenging conditions. Lepidopterans which are resistant to the biopesticide Bacillus thuringiensis subsp. kurstaki (Btk) have been shown to have reduced fitness, such as lower survival when subjected to overwintering stress. Recently, resistance to Btk has been found in some populations of Trichoplusia ni Hübner in greenhouses in British Columbia. This situation provides an opportunity to investigate potential trade-offs between overwintering survival and insecticide resistance in a major pest species. Here, we assess the survival and eventual fecundity of Btk resistant and susceptible T. ni pupae exposed to cool temperatures. Contrary to our expectations, resistant T. ni had higher overwintering survival than susceptible individuals. This is the first account of a potential advantage associated with Btk resistance. Resistant and susceptible moths had reduced fecundity and smaller progeny after cold exposure compared to controls, and this may counteract the survival advantage. Nevertheless, it seems unlikely that this is sufficient to select out the resistant phenotype in the presence of strong selection for resistance and in the absence of immigration of susceptible moths. The appearance of resistance without evidence of a trade-off in overwintering survival presents a major challenge to management in production greenhouses.
Complex trauma of war captivity: a prospective study of attachment and post-traumatic stress disorder
Authors: Solomon Z. , Dekel R. , Mikulincer M. 
Published: February 2008

BackgroundVictims of war captivity sometimes suffer from complex post-traumatic stress disorder (PTSD), a unique form of PTSD that entails various alterations in personality. These alterations may involve changes in attachment orientation.MethodThe sample comprised two groups of veterans from the 1973 Yom Kippur War: 103 ex-prisoners of war (ex-POWs) and 106 comparable control veterans. They were assessed at two points in time, 18 years and 30 years after the war.ResultsEx-POWs suffered from more post-traumatic symptoms than controls at both measurements points and these symptoms increased only among ex-POWs from Time 1 to Time 2. In addition, both attachment anxiety and attachment avoidance increased with time among ex-POWs, whereas they decreased slightly or remained stable among controls. Finally, the increases in attachment anxiety and avoidance were positively associated with the increase in post-traumatic symptoms among both study groups. Further analyses indicated that early PTSD symptoms predicted later attachment better than early attachment predicted later PTSD symptoms.ConclusionsThe results suggest that: (1) complex traumas are implicated in attachment orientations and PTSD symptoms even many years after captivity; (2) there is an increase in attachment insecurities (anxiety, avoidance) and an increase in PTSD symptoms decades after the captivity; (3) and post-traumatic stress symptoms predict attachment orientations better than attachment orientations predict an increase in PTSD symptoms.
Results of the Clinical Testing of a New Drug “Metronidazole” in the Treatment of Chronic Alcoholism*
Authors: BONFIGLIO G. , DONADIO G. 
Published: February 2008

Résumé L'utilisation du “Metronidazole” dans les vaginites et les uréthrites a étée, pendant des années, le sujet de recherches et expériences et seulement récemment et presque par chance il a été découvert que ce remède pourrait être un auxiliaire utile dans le traitement de l'alcoolisme chronique. Cet article est limitéà la description du traitement d'un seul cas d'alcoolisme chronique et conclut avec la théorie que l'administration de la drogue a provoqué chez ce malade une aversion progressive pour l'alcool quand, pendant le traitement, le patient buvait des breuvages alcooliques; la réaction à l'alcool était du type rencontré chez les patients traités avec Disulfiran.ZusammenfassungDie Verwendung von “Metronidazol” bei Scheiden‐ und Harnröhrenentzündung bildete seit Jahren einen Gegenstand zur Forschung und für Experimente, doch erst kürzlich und beinahe durch Zufall wurde entdeckt, dass dieser Heilstoff ein nützliches therapeutischen Mittel für chronischen Alkoholismus sein könnte. Diese Abhandlung beschränkt sich auf die Beschreibung der Behandlung eines Einzelfalles von chronischem Alkoholismus und schliesst mit der Theorie, dass die Verabreichung von Drogen bei dem betreffenden Patienten eine fortschreitende Abneigung gegen Alkohol hervorbrachte und dass, wenn der Patient während der Behandlung alkoholische Getränke einnahm, Alkoholreaktionen der Art, wie sie bei mit Disulfiram behandelten Patienten beobachtet wurden, auftraten.
The Rush to Combine: Sociological Dissimilarities of Alcoholism and Drug Abuse*
Authors: PITTMAN DAVID J. 
Published: February 2008

ZusammenfassungIn dieser Abhandlung besprachen wir die hauptsächlichsten Unterschiede zwischen Rauschgiftsucht und Alkoholismus vom sozial‐kulturellen Gesichtspunkt aus gesehen. Meiner Ansicht nach ist es erfahrungsgemäss unklug, Studien über alle Suchtabarten zu vereinen, da die sozialen Definitionen dieser Zustände, die ihnen von der menschlischen Gemeinschaft beigemessenen Werte und die sozialen Reaktionen gegenüber den verschiedenen Suchtarten äussserst unterschiedlich sind.
Gene therapy for haemophilia
Authors: Murphy Samuel L. , High Katherine A. 
Published: February 2008

SummaryThe ultimate goal of gene therapy is the replacement of a defective gene sequence with a corrected version to eliminate disease for the lifetime of the patient. This challenging task is not yet accomplished, however significant progress is evident. An initial spate of clinical trials attempting the treatment of haemophilia with gene transfer primarily resulted in the demonstration of good safety profiles, but without efficacy. Subsequent reengineering of vector plasmids and delivery systems resulted in markedly improved outcomes in animal models of the disease. The most recent clinical trial for the treatment of haemophilia B with gene transfer showed transient achievement of efficacy in the highest dose cohort tested, but also exposed a previously hidden barrier to the future success of these treatments. The progress and problems of gene therapies for haemorrhagic disorders will be discussed. This review will concentrate on approaches in or near clinical application.
Schizophrenia sufferers and their carers: a survery of understanding of the condition and its treatment, and of satisfaction with services
Authors: WRAY S. J. 
Published: February 2008

This paper reports a simple random survey of all identifiable schizophrenia sufferers, not in long‐term residential or hospital care in one Health Board area. The survey was carried out (1) to assess service users' and carers' understanding of the illness, and (2) to assess perceptions of services by people with schizophrenia and their carers.A response rate of 55.6% from a sample of 142 was achieved; 79 service users and 22 carers were interviewed.In general service users reported a limited understanding of the condition of schizophrenia and its treatment. Many reported an understanding that was either neutral or negative, as assessed by the Knowledge about Schizophrenia Interview. Carers generally had a more positive understanding of the condition than the user group, but considerable scope for improvement by educational intervention remained.It was found that people with schizophrenia generally perceived the service in a positive light, but had specific dissatisfaction with regard to medication, vocational training and hospitalization.Both service users and carers were dissatisfied with information and advice from professionals and identified these as areas that require improvement. On the whole carers expressed less satisfaction with services than did people with schizophrenia.
Assessing the side‐effects of antipsychotic drugs: a survey of CPN practice
Authors: BENNETT J. , DONE J. , HUNT B. 
Published: February 2008

Assessing the side‐effects of antipsychotic drugs: a survey of CPN practiceThe provision of community‐based care for people with serious and enduring mental health problems requires an approach that combines drug therapy, psychological interventions and skills training. Mental health nurses are being required to place more emphasis on their work with this client group. It has been suggested that community psychiatric nurses (CPNs) will require training in appropriate skills to work with the seriously mentally ill. While the training of CPNs to use psychological intervention strategies has received limited attention, the area of medication management, including the detection of side‐effects, is relatively unexplored. Community psychiatric nurses' practice with clients on antipsychotic medication was investigated. This paper reports selected findings on the assessment of medication side‐effects and CPNs' attitude to this aspect of their role. Fifty CPNs in three health districts completed a self‐administered questionnaire. The results showed that the CPNs were supervising the medication of large numbers of clients. They reported that their training had adequately prepared them to assess clients for medication side‐effects and that this was being done frequently. They also felt that their reports of side‐effects influence the pre‐scribers' decisions on medication when clients are reviewed. However, the data also suggested that CPNs were only monitoring their clients for three to four side‐effects and that they held an unfavourable attitude towards their involvement with medication.