bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-dimensional structure and ligand binding properties of trichosurin, a metatherian lipocalin from the milk whey of the common brushtail possum Trichosurus vulpecula
Authors: Watson Randall P. , Demmer Jerome , Baker Edward N. , Arcus Vickery L. 
Published: October 2007

Lipocalins are extracellular proteins (17–25 kDa) that bind and transport small lipophilic molecules. The three-dimensional structure of the first lipocalin from a metatherian has been determined at different values of pH both with and without bound ligands. Trichosurin, a protein from the milk whey of the common brushtail possum, Trichosurus vulpecula, has been recombinantly expressed in Escherichia coli, refolded from inclusion bodies, purified and crystallized at two different pH values. The three-dimensional structure of trichosurin was solved by X-ray crystallography in two different crystal forms to 1.9 Å (1 Å=0.1 nm) and 2.6 Å resolution, from crystals grown at low and high pH values respectively. Trichosurin has the typical lipocalin fold, an eight-stranded anti-parallel β-barrel but dimerizes in an orientation that has not been seen previously. The putative binding pocket in the centre of the β-barrel is well-defined in both high and low pH structures and is occupied by water molecules along with isopropanol molecules from the crystallization medium. Trichosurin was also co-crystallized with a number of small molecule ligands and structures were determined with 2-naphthol and 4-ethylphenol bound in the centre of the β-barrel. The binding of phenolic compounds by trichosurin provides clues to the function of this important marsupial milk protein, which is highly conserved across metatherians.
Comparative in vitro and ex vivo activities of selected inhibitors of transthyretin aggregation: relevance in drug design
Authors: Cardoso Isabel , Almeida Maria Rosário , Ferreira Nelson , Arsequell Gemma , Valencia Gregorio , Saraiva Maria João 
Published: October 2007

Destabilization of the tetrameric fold of TTR (transthyretin) is important for aggregation of the protein which culminates in amyloid fibril formation. Many TTR mutations interfere with tetramer stability, increasing the amyloidogenic potential of the protein. The vast majority of proposed TTR fibrillogenesis inhibitors are based on in vitro assays with isolated protein, limiting their future use in clinical assays. In the present study we investigated TTR fibrillogenesis inhibitors using a cellular system that produces TTR intermediates/aggregates in the medium. Plasmids carrying wild-type TTR, V30M or L55P cDNA were transfected into a rat Schwannoma cell line and TTR aggregates were investigated in the medium using a dot-blot filter assay followed by immunodetection. Results showed that, in 24 h, TTR L55P forms aggregates in the medium, whereas, up to 72 h, wild-type TTR and V30M do not. A series of 12 different compounds, described in the literature as in vitro TTR fibrillogenesis inhibitors, were tested for their ability to inhibit L55P aggregate formation; in this system, 2-[(3,5-dichlorophenyl) amino] benzoic acid, benzoxazole, 4-(3,5-difluorophenyl) benzoic acid and tri-iodophenol were the most effective inhibitors, as compared with the reference iododiflunisal, previously shown by ex vivo and in vitro procedures to stabilize TTR and inhibit fibrillogenesis. Among these drugs, 2-[(3,5-dichlorophenyl) amino] benzoic acid and tri-iodophenol stabilized TTR from heterozygotic carriers of V30M in the same ex vivo conditions as those used previously for iododiflunisal. The novel cellular-based test herein proposed for TTR fibrillogenesis inhibitor screens avoids not only lengthy and cumbersome large-scale protein isolation steps but also artefacts associated with most current in vitro first-line screening methods, such as those associated with acidic conditions and the absence of serum proteins.
Oxidative switches in functioning of mammalian copper chaperone Cox17
Authors: Voronova Anastassia , Meyer-Klaucke Wolfram , Meyer Thomas , Rompel Annette , Krebs Bernt , Kazantseva Jekaterina , Sillard Rannar , Palumaa Peep 
Published: October 2007

Cox17, a copper chaperone for cytochrome-c oxidase, is an essential and highly conserved protein in eukaryotic organisms. Yeast and mammalian Cox17 share six conserved cysteine residues, which are involved in complex redox reactions as well as in metal binding and transfer. Mammalian Cox17 exists in three oxidative states, each characterized by distinct metal-binding properties: fully reduced mammalian Cox170S–S binds co-operatively to four Cu+; Cox172S–S, with two disulfide bridges, binds to one of either Cu+ or Zn2+; and Cox173S–S, with three disulfide bridges, does not bind to any metal ions. The Em (midpoint redox potential) values for two redox couples of Cox17, Cox173S–S↔Cox172S–S (Em1) and Cox172S–S↔Cox170S–S (Em2), were determined to be −197 mV and −340 mV respectively. The data indicate that an equilibrium exists in the cytosol between Cox170S-S and Cox172S–S, which is slightly shifted towards Cox170S-S. In the IMS (mitochondrial intermembrane space), the equilibrium is shifted towards Cox172S–S, enabling retention of Cox172S–S in the IMS and leading to the formation of a biologically competent form of the Cox17 protein, Cox172S–S, capable of copper transfer to the copper chaperone Sco1. XAS (X-ray absorption spectroscopy) determined that Cu4Cox17 contains a Cu4S6-type copper–thiolate cluster, which may provide safe storage of an excess of copper ions.
Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption?
Authors: Dixit Sayali S. , Sleat David E. , Stock Ann M. , Lobel Peter 
Published: October 2007

NPC1L1 (Niemann–Pick C1-like 1), the pharmacological target of the cholesterol-uptake inhibitor ezetimibe, is a transporter localized on the brush border of enterocytes. Although this protein plays a key role in intestinal uptake of sterols, multiple molecular events that underlie intestinal cholesterol absorption have not been fully characterized. Two proteins that might be involved in this process are NPC1 and NPC2 (Niemann–Pick disease type C proteins 1 and 2), which function in the endosomal/lysosomal cholesterol egress pathway and whose deficiency results in NPC (Niemann–Pick type C) disease. The involvement of these proteins in intestinal cholesterol absorption was examined in mutant mice lacking either NPC1 or NPC2. Our data indicate that deficiencies in either protein do not have an effect on cholesterol uptake or absorption. This contrasts with recent results obtained for the fruitfly Drosophila melanogaster, which indicate that a deficiency of NPC1 (dNPC1a being its Drosophila homologue) leads to activation of an NPC1L1 (Drosophila homologue dNPC1b)-independent cholesterol uptake pathway, underscoring fundamental differences in mammalian and non-mammalian cholesterol metabolism.
Do nonribosomal peptide synthetases occur in higher Eukaryotes?
Authors: Tiburzi Federica , Visca Paolo , Imperi Francesco 
Published: October 2007

AbstractIs There An Answer? is intended to serve as a forum in which readers to IUBMB Life may pose questions of the type that intrigue biochemists but for which there may be no obvious answer or one may be available but not widely known or easily accessible.Readers are invited to e‐mail ascenzi@uniroma3.it if they have questions to contribute or if they can provide answers to questions that are provided here from time to time. In the latter case, instructions will be sent to interested readers. Answers should be, whenever possible, evidence‐based and provide relevant references.Paolo Ascenzi
Heme‐hemopexin: A ‘Chronosteric’ heme‐protein
Authors: Ascenzi Paolo , Fasano Mauro 
Published: October 2007

AbstractHemopexin (HPX) serves as scavenger and transporter of toxic plasma heme to the liver. HPX is formed by two four‐bladed β‐propeller domains, resembling two thick disks that lock together at a 90° angle. The heme is bound between the two β‐propeller domains in a pocket formed by the interdomain linker peptide. Residues His213 and His266 coordinate the heme iron atom giving a stable bis‐histidyl complex. The HPX‐heme geometry is reminiscent of heme‐proteins endowed with ligand binding and (pseudo‐)enzymatic properties. HPX‐heme binds reversibly CO, •NO, and cyanide by detaching His213; however, O2 induces HPX‐heme(II) oxidation. Furthermore, HPX‐heme(II) facilitates •NO/O2 and •NO/peroxynitrite scavenging. Heme sequestering by HPX prevents heme‐mediated activation of oxidants which induce the low‐density lipoprotein oxidation. Here, ligand binding and (pseudo‐)enzymatic properties of HPX‐heme are reviewed. HPX, acting not only as a heme carrier but also displaying transient heme‐based ligand binding and (pseudo‐)enzymatic properties, could be considered a ‘chronosteric’ heme‐protein. IUBMB Life, 59: 700‐708, 2007
Focal adhesion kinase: An essential kinase in the regulation of cardiovascular functions
Authors: Vadali Kavita , Cai Xinming , Schaller Michael D. 
Published: October 2007

AbstractRecent studies using animal models have demonstrated an important role for FAK in the cardiovascular system. In particular, FAK is essential for angiogenesis in the embryo, functions in heart development and modulates the response of cardiomyocytes to pressure overload in adult mice. FAK function at the cellular level is discussed to provide insight into the mechanisms regulating these biological events and the role of FAK in controlling endothelial junctions and responses to mechanical stimulation are discussed. IUBMB Life, 59: 709‐716, 2007
B‐cell chronic lymphocytic leukaemia cells show specific changes in membrane protein expression during different stages of cell cycle
Authors: Bennett Fiona , Rawstron Andy , Plummer Marieth , Tute Ruth de , Moreton Paul , Jack Andrew , Hillmen Peter 
Published: October 2007

SummaryThe proliferating component in chronic lymphocytic leukaemia (CLL) is usually small (<1%) and restricted to a specific micro‐environmental niche. To characterize the proliferating component, CLL cells from bone marrow or lymph nodes of 23 patients were assessed for expression of up to 66 surface antigens in combination with nuclear Ki‐67/MCM6. Ki‐67 expression was associated with step‐wise increases in CD23/CD95/CD86/CD39/CD27 and decreases in CD24/CD69/CXCR4/CXCR5. Ki‐67+ cells showed increased CD38 expression, but with considerable inter‐patient variability: in some cases Ki‐67 expression was only detectable in CD38− CLL cells. The results suggest continuous re‐entry into the cell cycle as no distinct stem cell pool was detectable.
Primary ovarian insufficiency: a more accurate term for premature ovarian failure
Authors: Welt Corrine K. 
Published: October 2007

SummaryPremature ovarian failure (POF) is a disorder with a complicated clinical presentation and course that is poorly defined by its name. A more scientifically accurate term for the disorder is primary ovarian insufficiency (POI), a term that can be appropriately modified to describe the state of ovarian function. In recent years, the known aetiologies of POI have expanded, although the cause of POI in a majority of clinical cases remains undefined. The most common aetiologies should be ruled out clinically including chromosomal abnormalities, fragile X premutations and autoimmune causes. Management should be directed at symptom resolution and bone protection, but most importantly should include psychosocial support for women facing this devastating diagnosis.
Environmental features influencing Carabid beetle (Coleoptera) assemblages along a recently deglaciated area in the Alpine region
Authors: GOBBI MAURO , ROSSARO BRUNO , VATER AMBER , DE BERNARDI FIORENZA , PELFINI MANUELA , BRANDMAYR PIETRO 
Published: October 2007

Abstract1. The spatio‐temporal approach was used to evaluate the environmental features influencing carabid beetle assemblages along a chronosequence of an Italian Alpine glacier foreland. The influence of environmental variables on species richness, morphology (wing and body length), and distribution along the chronosequence was tested.2. Species richness was found to be a poor indicator of habitat due to weak influences by environmental variables. It seems that the neighbouring habitats of a glacier foreland are not able to determine significant changes in carabid species richness.3. Instead it appears that history (age since deglaciation) and habitat architecture of a glacier foreland are strongly correlated to species adaptive morphological traits, such as wing morphology and body length. Assemblages characterised by species with reduced wing size are linked to the older stages of the chronosequence, where habitat is more structured. Assemblages characterised by the largest species are linked to the younger sites near the glacier. These morphological differentiations are explained in detail.4. Habitat age can therefore be considered the main force determining assemblage composition. On the basis of the relationship between morphological traits and environmental variables, it seems likely that age since deglaciation is the main variable influencing habitat structure (primary effect) on the Forni foreland. The strong relationship between carabid assemblages and habitat type indicates that site age has but a secondary effect on carabid assemblages. This may be utilised to interpret potential changes in assemblages linked to future glacier retreat.
Colonisation of Heliconia caribaea by aquatic invertebrates: resource and microsite characteristics
Authors: YEE DONALD A. , WILLIG MICHAEL R. 
Published: October 2007

Abstract 1. Colonisation of ephemeral aquatic habitats via oviposition by invertebrates may be influenced by a variety of factors, such as the quality of aquatic habitat and the characteristics of the surrounding terrestrial environment. The water‐holding bracts of Heliconia caribaea, a subtropical herb that produces ephemeral aquatic habitats, are colonised by a variety of aquatic invertebrates. To date, no experiments have been conducted to identify the cues that affect colonisation patterns via oviposition selection in Heliconia.2. Artificial bracts were used to assess the influence of two types of resources found in bracts (plant produced carbohydrates and terrestrial snail faeces) on oviposition site‐selection by invertebrate taxa via a replicated factorial design at four locations in the Luquillo Experimental Forest of Puerto Rico, U.S.A. Eleven microsite characteristics thought to affect oviposition were measured for each experimental container.3. Most taxa responded in a minor way to microsite characteristics, whereas site selection by the most numerically dominant groups (e.g. Syrphidae) were influenced principally by resources within artificial bracts. Overall, the greatest response by particular taxa was to the presence of snail faeces. At the community level, total abundance, richness, and evenness of invertebrates increased with increasing biomass of faeces. Variation in sugar produced a more complex response.4. In general, the terrestrial matrix surrounding these aquatic habitats was only a secondary determinant of population and community attributes; the principal factor affecting site selection was the quality of the aquatic habitat.
Untreated dental caries in children with cerebral palsy in the Brazilian context
Authors: DE CAMARGO MARCELA APARECIDA FERREIRA , ANTUNES JOSÉ LEOPOLDO FERREIRA 
Published: October 2007

Objectives.  To assess the prevalence of untreated dental caries in children with cerebral palsy and to assess socio‐demographic, behavioural, and clinical covariates.Design.  Cross‐sectional assessment of 200 children and adolescents with cerebral palsy (2–17 years old) enrolled in a specialized healthcare unit in São Paulo, Brazil. The dental examination followed the World Health Organization's guidelines for oral health surveys; familial caretakers informed on socio‐economic status and behaviour; the patient's medical record informed their clinical status.Results.  The proportion of children that presented at least one tooth affected by untreated caries was 49.5%. Poor socio‐economic standings and a higher frequency of sugar consumption associated with a worse profile of dental health; different types of cerebral palsy (spastic, tetraparesis) did not. The prevalence of untreated caries was higher than reference values assessed for the overall population of the same age range.Conclusions.  The high burden of untreated dental caries on cerebral palsy patients reinforces the importance of the dentist in the interdisciplinary healthcare team attending these children. Factors associated with this outcome are the same for the general population; these findings underscore the necessity of implementing effective caries prevention in this population of cerebral palsy children.
Vulnerable and strong – lesbian women encountering maternity care
Authors: Spidsberg Bente Dahl 
Published: October 2007

AbstractTitle.  Vulnerable and strong – lesbian women encountering maternity care Aim.  This paper is a report of a study to describe the maternity care experiences narrated by a sample of lesbian couples.Background.  Pregnant and labouring women are dependent on the professional skill and caring ability of the healthcare provider. Studies show that lesbian women who reveal their sexual identity are exposed to homophobic prejudice and discrimination in midwifery care.Method.  A phenomenological hermeneutical study inspired by the French philosopher Paul Ricoeur was conducted. Six lesbian couples were recruited in Norway by a snowball method, reporting a total of eight children conceived by donor insemination. Joint interviews were performed in January 2006, and the participants were encouraged to share narratives about important events in their maternity care experiences.Findings.  The fundamental life conditions of vulnerability, responsibility and caring permeated the narratives, and were related with the couples’ decisions to be open about their sexual identity. Being exposed, they experienced under‐ and over‐focusing on sexuality. They felt responsible for having the right attitude in interactions, which meant being open, but not over‐assertive. They described genuinely caring situations as well as being content with less genuine care, and demonstrated that in addition to receiving care, they provided care in the encounters.Conclusion.  Lesbian women are a vulnerable group when encountering maternity care. They took responsibility in caring situations because of healthcare providers’ uncertainty and anxiety. Existential needs, such as being seen, being cared for and communicated with, should be considered equally important for lesbian women and heterosexual women in labour.
Methodological issues in online data collection
Authors: Cantrell Mary Ann , Lupinacci Paul 
Published: October 2007

AbstractTitle.  Methodological issues in online data collection Aim.  This paper is a report of a study to evaluate the use of an online data collection method to survey early survivors of childhood cancer about their physical and psychosocial characteristics and health‐related quality of life.Background.  A major advantage in conducting web‐based nursing research is the ability to involve participants who are challenging to study because of their small numbers or inaccessibility because of geographic location. As paediatric oncology patients and early survivors of childhood cancer are often not easily accessible because of their small numbers at single institutions, web‐based research methods have been proposed as a potentially effective approach to collect data in studies involving these clinical populations.Method.  Guided by published literature on using the Internet for data collection, an online protocol was developed; this included construction of a website, development of a homepage and interactive HyperText Markup Language pages and the posting of the study link on various websites. Data collection occurred over a 6‐month period between December 2005 and May 2006.Findings.  Despite using strategies in conducting online research cited in published literature, the recruitment of subjects was very prolonged and the volume of missing data among many respondents excluded them from the study and created bias within the study’s results.Conclusion.  Web‐based, online data collection methods create opportunities to conduct research globally, especially among difficult to access populations. However, web‐based research requires careful consideration of how the study will be advertized and how data will be collected to ensure high quality data and validity of the findings.
New midwifery? A qualitative analysis of midwives’ decision‐making strategies
Authors: Porter Sam , Crozier Kenda , Sinclair Marlene , Kernohan W. George 
Published: October 2007

AbstractTitle.  New midwifery? A qualitative analysis of midwives’ decision‐making strategies Aim.  This paper is a report of a study to explore the reasons why midwives decided to adopt observed decision‐making strategies relating to the use of technology.Background.  Literature on the development of midwifery and nursing has suggested that they are developing more egalitarian relationships with clients in decision‐making processes.Methods.  A qualitative approach was adopted, using participant observation with a convenience sample of midwives (n = 16), and a focus group of midwives (n = 8). Data collection took place over 9 months in 2004.Findings.  The dominant mode of decision‐making was bureaucratic decision‐making, which involved adherence to written policies and procedures. The least frequently used was ‘new professional’ decision‐making, which involved collaboration with clients. The reasons for midwives’ approaches could be categorized under three main headings: first, context, including possible litigation, management strategies, workload pressures, and medical dominance; second, midwives’ characteristics, including both lack of experience and the reliance on tradition of some experienced midwives; and third, women’s perceived characteristics, some of whom were seen by midwives as either unwilling or unable to participate in decision‐making. There was also implicit evidence that some midwives were uncomfortable with the new professional rebalancing of power relations between professionals and the laity.Conclusion.  Managers need to question whether the strategies they adopt hinder or support clinicians in their efforts to involve women in decisions. Clinicians need to consider whether they wish to be selective or universal in their use of new professional strategies.