bluuebunny/crossref_metadata_2025 huggingface dataset:
Do nonribosomal peptide synthetases occur in higher Eukaryotes?
Authors: Tiburzi Federica , Visca Paolo , Imperi Francesco
Published: October 2007

Is 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

Hemopexin (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

Recent 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
Medium-Contention Based Energy-Efficient Distributed Clustering (MEDIC) for Wireless Sensor Networks
Authors: Zhao Liang , Liang Qilian
Published: October 2007

In this paper, we utilize clustering to organize wireless sensors into an energy-efficient hierarchy. We propose a Medium-contention based Energy-efficient DIstributed Clustering (MEDIC) scheme, through which sensors self-organize themselves into energy-efficient clusters by bidding for cluster headship. This scheme is based on a new criterion that can be used by each sensor node to make a distributed decision on whether electing to be a cluster head or a non-head member, which is a fully distributed approach. Although MEDIC uses only local information, it achieves better performance in terms of effective lifetime and its Data/Energy Ratio is 25% higher than native LEACH (Low-Energy Adaptive Clustering Hierarchy), which relies on other routing algorithms to access global information. A complementary exponential data correlation model is also introduced to simulate different data aggregation effect.
Are metacaspases caspases?
Authors: Vercammen Dominique , Declercq Wim , Vandenabeele Peter , Van Breusegem Frank
Published: October 2007

The identification of caspases as major regulators of apoptotic cell death in animals initiated a quest for homologous peptidases in other kingdoms. With the discovery of metacaspases in plants, fungi, and protozoa, this search had apparently reached its goal. However, there is compelling evidence that metacaspases lack caspase activity and that they are not responsible for the caspaselike activities detected during plant and fungal cell death. In this paper, we attempt to broaden the discussion of these peptidases to biological functions beyond apoptosis and cell death. We further suggest that metacaspases and paracaspases, although sharing structural and mechanistic features with the metazoan caspases, form a distinct family of clan CD cysteine peptidases.
The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal
Authors: Maekawa Hiromi , Priest Claire , Lechner Johannes , Pereira Gislene , Schiebel Elmar
Published: October 2007

The spindle orientation checkpoint (SPOC) of budding yeast delays mitotic exit when cytoplasmic microtubules (MTs) are defective, causing the spindle to become misaligned. Delay is achieved by maintaining the activity of the Bfa1–Bub2 guanosine triphosphatase–activating protein complex, an inhibitor of mitotic exit. In this study, we show that the spindle pole body (SPB) component Spc72, a transforming acidic coiled coil–like molecule that interacts with the γ-tubulin complex, recruits Kin4 kinase to both SPBs when cytoplasmic MTs are defective. This allows Kin4 to phosphorylate the SPB-associated Bfa1, rendering it resistant to inactivation by Cdc5 polo kinase. Consistently, forced targeting of Kin4 to both SPBs delays mitotic exit even when the anaphase spindle is correctly aligned. Moreover, we present evidence that Spc72 has an additional function in SPOC regulation that is independent of the recruitment of Kin4. Thus, Spc72 provides a missing link between cytoplasmic MT function and components of the SPOC.
Skin and bones: the bacterial cytoskeleton, cell wall, and cell morphogenesis
Authors: Cabeen Matthew T. , Jacobs-Wagner Christine
Published: October 2007

The bacterial world is full of varying cell shapes and sizes, and individual species perpetuate a defined morphology generation after generation. We review recent findings and ideas about how bacteria use the cytoskeleton and other strategies to regulate cell growth in time and space to produce different shapes and sizes.
Microtubules are involved in anterior-posterior axis formation in C. elegans embryos
Authors: Tsai Miao-Chih , Ahringer Julie
Published: October 2007

Microtubules deliver positional signals and are required for establishing polarity in many different organisms and cell types. In Caenorhabditis elegans embryos, posterior polarity is induced by an unknown centrosome-dependent signal. Whether microtubules are involved in this signaling process has been the subject of controversy. Although early studies supported such an involvement (O'Connell, K.F., K.N. Maxwell, and J.G. White. 2000. Dev. Biol. 222:55–70; Wallenfang, M.R., and G. Seydoux. 2000. Nature. 408:89–92; Hamill, D.R., A.F. Severson, J.C. Carter, and B. Bowerman. 2002. Dev. Cell. 3:673–684), recent work involving RNA interference knockdown of tubulin led to the conclusion that centrosomes induce polarity independently of microtubules (Cowan, C.R., and A.A. Hyman. 2004. Nature. 431:92–96; Sonneville, R., and P. Gonczy. 2004. Development. 131: 3527–3543). In this study, we investigate the consequences of tubulin knockdown on polarity signaling. We find that tubulin depletion delays polarity induction relative to wild type and that polarity only occurs when a small, late-growing microtubule aster is visible at the centrosome. We also show that the process of a normal meiosis produces a microtubule-dependent polarity signal and that the relative levels of anterior and posterior PAR (partitioning defective) polarity proteins influence the response to polarity signaling. Our results support a role for microtubules in the induction of embryonic polarity in C. elegans.
Hormonal control of the renal immune response and antibacterial host defense by arginine vasopressin
Authors: Chassin Cécilia , Hornef Mathias W. , Bens Marcelle , Lotz Michael , Goujon Jean-Michel , Vimont Sophie , Arlet Guillaume , Hertig Alexandre , Rondeau Eric , Vandewalle Alain
Published: October 2007

Ascending urinary tract infection (UTI) and pyelonephritis caused by uropathogenic Escherichia coli (UPEC) are very common infections that can cause severe kidney damage. Collecting duct cells, the site of hormonally regulated ion transport and water absorption controlled by vasopressin, are the preferential intrarenal site of bacterial adhesion and initiation of inflammatory response. We investigated the effect of the potent V2 receptor (V2R) agonist deamino-8-D-arginine vasopressin (dDAVP) on the activation of the innate immune response using established and primary cultured collecting duct cells and an experimental model of ascending UTI. dDAVP inhibited Toll-like receptor 4–mediated nuclear factor κB activation and chemokine secretion in a V2R-specific manner. The dDAVP-mediated suppression involved activation of protein phosphatase 2A and required an intact cystic fibrosis transmembrane conductance regulator Cl− channel. In vivo infusion of dDAVP induced a marked fall in proinflammatory mediators and neutrophil recruitment, and a dramatic rise in the renal bacterial burden in mice inoculated with UPECs. Conversely, administration of the V2R antagonist SR121463B to UPEC-infected mice stimulated both the local innate response and the antibacterial host defense. These findings evidenced a novel hormonal regulation of innate immune cellular activation and demonstrate that dDAVP is a potent modulator of microbial-induced inflammation in the kidney.
Between‐Groups Study Designs Demand Between‐Groups Analyses: A Response to Hernandez‐Reif, Shor‐Posner, Baez, Soto, Mendoza, Castillo, Quintero, Perez, and Zhang
Authors: Moyer Christopher A.
Published: October 2007

The most recent massage therapy (MT) study by Hernandez‐Reif et al. displays flaws persistent in this area of research that are attributable to MT researchers’ frequent mistake of using within‐group analyses of dependent variables in studies that are purported to be randomized control trials. This practise violates the logic of using randomization to create treatment and control groups, and thereby fails to control for the validity threats of spontaneous remission, placebo effects, and statistical regression. The result is that a clear understanding of what MT can and cannot do is seriously hampered.
Hochuekkito, a Kampo (Traditional Japanese Herbal) Medicine, Enhances Mucosal IgA Antibody Response in Mice Immunized with Antigen‐Entrapped Biodegradable Microparticles
Authors: Matsumoto Tsukasa , Noguchi Masaaki , Hayashi Osamu , Makino Kimiko , Yamada Haruki
Published: October 2007

The effect of oral administration of Hochuekkito (HET; Bu‐Zhong‐Yi‐Qi‐Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen‐specific antibodies in mucosal site, ovalbumin (OVA)‐entrapped biodegradable microparticles (OVA‐microparticles) were used as an antigen. Mice were orally immunized with OVA‐microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA‐specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payer′s patches were investigated for cytokines production, it was found that the IFN‐γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyer′s patch cells revealed enhanced expression of L‐selectin gene. The increase of L‐selectin positive cells in B lymphocytes fraction was observed in Peyer′s patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN‐γ secretion and increased population of L‐selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine.
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

The 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

Premature 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

Title.  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

Title.  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

Title.  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.
The meaning of care dependency as shared by care givers and care recipients: a concept analysis
Authors: Boggatz Thomas , Dijkstra Ate , Lohrmann Christa , Dassen Theo
Published: October 2007

Title. The meaning of care dependency as shared by care givers and care recipients: a concept analysis

Aim. This paper is a report of a concept analysis to identify a meaning of care dependency that can be shared by both care givers and care recipients.

Background. Care dependency can be perceived from the care recipient’s and the care giver’s perspective. To allow for comparisons, both sides should share the same understanding of the concept. The current research about care dependency has focused on external assessment by nurses and suffers from a tendency to use the concept with different meanings. As a consequence, research on dependency may capture different phenomena.

Method. Walker and Avant’s method for concept analysis served as the guideline for this study. The Medline, CINAHL and Cochrane databases were searched for the period 1996–2006 using the terms dependence, dependency, care dependence and care dependency.

Results. Care dependency can be defined as a subjective, secondary need for support in the domain of care to compensate a self‐care deficit. Functional limitations are a necessary antecedent and unmet needs are a possible consequence of care dependency. The conceptual difference between care dependency, functional limitations and unmet needs may be meaningless for study participants. They may better understand these differences if they are asked about all three phenomena in the same investigation.

Conclusion. Care givers and care recipients can agree on the suggested attributes of care dependency but may judge them in different ways. Self‐assessed care dependency has the potential to challenge preconceptions of care givers about care dependency.
Strong size evolution of the most massive galaxies since z ∼ 2
Authors: Trujillo Ignacio , Conselice C. J. , Bundy Kevin , Cooper M. C. , Eisenhardt P. , Ellis Richard S.
Published: October 2007

Using the combined capabilities of the large near-infrared Palomar/DEEP-2 survey, and the superb resolution of the Advanced Camera for Surveys HST camera, we explore the size evolution of 831 very massive galaxies (M⋆≥ 1011h−270 M⊙) since z∼ 2. We split our sample according to their light concentration using the Sérsic index n. At a given stellar mass, both low (n < 2.5) and high (n > 2.5) concentrated objects were much smaller in the past than their local massive counterparts. This evolution is particularly strong for the highly concentrated (spheroid like) objects. At z∼ 1.5, massive spheroid-like objects were a factor of 4 (±0.4) smaller (i.e. almost two orders of magnitudes denser) than those we see today. These small sized, high-mass galaxies do not exist in the nearby Universe, suggesting that this population merged with other galaxies over several billion years to form the largest galaxies we see today.
The neuropathology of autism: where do we stand?
Authors: Schmitz C. , Rezaie P.
Published: October 2007

The neurobiology and neuropathology of the autism spectrum disorders (ASD) remain poorly defined. Brain imaging studies suggest that the deficits in social cognition, language, communication and stereotypical patterns of behaviour that are manifest in individuals with ASD, are related to functional disturbance and ‘disconnectivity’, affecting multiple brain regions. These impairments are considered to arise as a consequence of abnormal pre‐ and postnatal development of a distributed neural network. Examination of the brain post mortem continues to provide fundamental information concerning the cellular and subcellular alterations that take place in the brain of autistic individuals. Neuropathological observations that have emerged over the past decade also point towards early pre‐ and postnatal developmental abnormalities that involve multiple regions of the brain, including the cerebral cortex, cortical white matter, amygdala, brainstem and cerebellum. However, the neuropathology of autism is yet to be clearly defined, and there are several areas that remain open to further investigation. In this respect, more concerted efforts are required to examine the various aspects of cellular pathology affecting the brain in autism. This paper briefly highlights four key areas that warrant further evaluation.
Spinocerebellar ataxia type 7 (SCA7): widespread brain damage in an adult‐onset patient with progressive visual impairments in comparison with an adult‐onset patient without visual impairments
Authors: Rüb U. , Brunt E. R. , Seidel K. , Gierga K. , Mooy C. M. , Kettner M. , Van Broeckhoven C. , Bechmann I. , La Spada A. R. , Schöls L. , Den Dunnen W. , De Vos R. A. I. , Deller T.
Published: October 2007

Spinocerebellar ataxia type 7 (SCA7) represents a rare and severe autosomal dominantly inherited ataxic disorder and is among the known CAG‐repeat, or polyglutamine, diseases. In contrast to other currently known autosomal dominantly inherited ataxic disorders, SCA7 may manifest itself with different clinical courses. Because the degenerative changes evolving during these different clinical courses are not well known, many neurological disease symptoms still are unexplained. We performed an initial pathoanatomical study on unconventional thick tissue sections of the brain of a clinically diagnosed and genetically confirmed adult‐onset SCA7 patient with progressive visual impairments. In this patient we observed loss of myelinated fibres in distinct central nervous fibre tracts, and widespread degeneration of the cerebellum, telencephalon, diencephalon and lower brainstem. These degenerative changes offer appropriate explanations for a variety of less‐understood neurological symptoms in adult‐onset SCA7 patients with visual impairments: gait, stance and limb ataxia, falls, dysarthria, dysphagia, pyramidal signs, Parkinsonian features, writing problems, impairments of saccades and smooth pursuits, altered pupillary functions, somatosensory deficits, auditory deficits and mental impairments.
MMP‐2, ‐3 and ‐9 levels and activity are not related to Aβ load in the frontal cortex in Alzheimer's disease
Authors: Baig S. , Kehoe P. G. , Love S.
Published: October 2007

Matrix metalloproteinases (MMPs) ‐2, ‐3 and ‐9 are up‐regulated in several cell types on exposure to amyloid β peptide (Aβ) and have Aβ‐degrading activity in vitro. The aims of this study were to determine (i) the distribution of MMP‐2, ‐3 and ‐9 in the cerebral cortex in Alzheimer's disease (AD) and control brains; (ii) whether the levels and activity of these proteases are increased in AD; and (iii) whether their activity is related to Aβ load. In addition, we examined whether promoter polymorphisms in the MMP‐3 and ‐9 genes are associated with AD in the study cohort. Paraffin sections of frontal lobe from AD and control cases were immunostained for MMP‐2, ‐3 and ‐9 and tissue homogenates used for MMP activity assays. DNA from these cases was genotyped for the MMP‐3 5A/6A (‐1171) and MMP‐9 C‐1562T promoter polymorphisms. Immunohistochemistry revealed MMP‐3 in plaques and both MMP‐3 and ‐9 around scattered neurones. The levels and activity of all three MMPs were similar in AD and control brains and bore no relationship to Aβ load. Analysis of MMP‐3 ‐1171 5A/6A allele frequencies showed that the 6A allele (with reduced promoter activity) was associated with AD; the MMP‐9 C‐1562T polymorphism was not. The levels and activities of MMP‐2, ‐3 and ‐9 are not increased in the frontal cortex in AD and are not related to Aβ load. Our findings suggest that altered expression of these proteases does not make a significant contribution to the accumulation of Aβ in AD.
Tidal and seasonal controls in the formation of Late Miocene inclined heterolithic stratification deposits, western Amazonian foreland basin
Authors: HOVIKOSKI JUSSI , RÄSÄNEN MATTI , GINGRAS MURRAY , RANZI ALCEU , MELO JANIRA
Published: October 2007

Upper Miocene strata in the Acre sub‐basin, Brazil, consist dominantly of various types of inclined heterolithic stratification and pedogenic horizons. These strata were sedimentologically and ichnologically described to: (i) study different temporal controls responsible for inclined heterolithic stratification generation and their variation in a distal–proximal trend; and (ii) delineate the depositional setting. For this purpose, nine representative outcrops were sedimentologically and ichnologically studied, and their facies associations described. Thickness variations of the heterolithic strata of various orders (lamina, lamina bundles and beds) were analysed by statistical methods (Fourier transform). The deposits were interpreted as tidally and seasonally influenced estuarine or delta‐related and continental strata. The inclined heterolithic stratification deposits represented vastly different settings ranging from tidally dominated, brackish‐water ichnofossils‐bearing channels to seasonally controlled, articulatedPurussaurus(a freshwater alligator) fossil‐bearing channels. Several time cycles were distinguished in the strata, including semi‐diurnal, fortnightly and seasonal. Tidal imprint was best observed in low‐energy brackish‐water settings, whereas seasonal rhythmicity was distinguishable throughout the depositional system. However, the latter was most apparent in riverine channels proximal to the inferred fluvio‐tidal transition. The different temporal controls commonly had distinguishable impact on sedimentological and ichnological properties in the studied sediments. The differing properties included: (i) the degree and nature of lateral variability with respect to lithology and bedforms in inclined heterolithic stratification; (ii) the lateral continuity of inclined heterolithic stratification; (iii) the nature of sedimentary contacts between the inclined heterolithic stratification members; (iv) thickness variation of inclined heterolithic stratification members within a set; (v) the cyclicities observed in inclined heterolithic stratification series; (vi) the degree of bioturbation; (vii) the types of trace fossils observed; and (viii) the distribution of bioturbation in adjacent inclined heterolithic stratification members.
In vivo analysis of the lumenal binding protein (BiP) reveals multiple functions of its ATPase domain
Authors: Snowden Christopher James , Leborgne‐Castel Nathalie , Wootton Lucie Jan , Hadlington Jane Louise , Denecke Jurgen
Published: October 2007

The endoplasmic reticulum (ER) chaperone binding protein (BiP) binds exposed hydrophobic regions of misfolded proteins. Cycles of ATP hydrolysis and nucleotide exchange on the ATPase domain were shown to regulate the function of the ligand‐binding domain in vitro. Here we show that ATPase mutants of BiP with defective ATP‐hydrolysis (T46G) or ATP‐binding (G235D) caused permanent association with a model ligand, but also interfered with the production of secretory, but not cytosolic, proteins in vivo. Furthermore, the negative effect of BiP(T46G) on secretory protein synthesis was rescued by increased levels of wild‐type BiP, whereas the G235D mutation was dominant. Unexpectedly, expression of a mutant BiP with impaired ligand binding also interfered with secretory protein production. Although mutant BiP lacking its ATPase domain had no detrimental effect on ER function, expression of an isolated ATPase domain interfered with secretory protein synthesis. Interestingly, the inhibitory effect of the isolated ATPase was alleviated by the T46G mutation and aggravated by the G235D mutation. We propose that in addition to its role in ligand release, the ATPase domain can interact with other components of the protein translocation and folding machinery to influence secretory protein synthesis.
High‐throughput quantitative luminescence assay of the growth in planta of Pseudomonas syringae chromosomally tagged with Photorhabdus luminescens luxCDABE
Authors: Fan Jun , Crooks Casey , Lamb Chris
Published: October 2007

Bioluminescent strains of the Arabidopsis thaliana pathogens Pseudomonas syringae pathovar (pv.) tomato and pv. maculicola were made by insertion of the luxCDABE operon from Photorhabdus luminescens into the P. syringae chromosome under the control of a constitutive promoter. Stable integration of luxCDABE did not affect bacterial fitness, growth in planta or disease outcome. Luminescence accurately and reliably reported bacterial growth in infected Arabidopsis leaves both with a fixed inoculum followed over time and with varying inocula assayed at a single time point. Furthermore, the bioluminescence assay could detect a small (1.3‐fold) difference in bacterial growth between different plant genotypes with a precision comparable to that of the standard plate assay. Luminescence of luxCDABE‐tagged P. syringae allows rapid and convenient quantification of bacterial growth without the tissue extraction, serial dilution, plating and manual scoring involved in standard assays of bacterial growth by colony formation in plate culture of samples from infected tissue. The utility of the bioluminescence assay was illustrated by surveying the 500‐fold variation in growth of the universally virulent P. syringae pv. maculicola ES4326 among more than 100 Arabidopsis ecotypes and identification of two quantitative trait loci accounting for 48% and 16%, respectively, of the variance of basal resistance to P. syringae pv. tomato DC3000 in the Col‐0 × Fl‐1 F2 population. Luminescence assay of bacteria chromosomally tagged with luxCDABE should greatly facilitate the genetic dissection of quantitative differences in gene‐for‐gene, basal and acquired disease resistance and other aspects of plant interactions with bacterial pathogens requiring high‐throughput assays or large‐scale quantitative screens.
The association of asthma, atopy and lung function with hormone replacement therapy and surgical cessation of menstruation in a population‐based sample of English women
Authors: Jarvis D. , Leynaert B.
Published: October 2007

Background:  Gynaecological surgery that may lead to cessation of menstruation is a major indication for the use of hormone replacement therapy (HRT) which in turn has been associated with asthma.

Methods:  Information on asthma‐like symptoms, lung function and immunoglobulin E (IgE) sensitization to house dust mite (HDM) and on menstrual status and use of HRT was collected from 3724 women aged between 35 and 64 years living in England. Association of health outcomes with use of HRT and with surgery resulting in cessation of menstruation was examined in multivariable models.

Results:  Over a third of women who had ever used HRT had undergone surgery resulting in cessation of menstruation. Current use of HRT was associated with frequent wheeze, particularly in lean women [body mass index (BMI) < 25; odds ratio (OR) 1.90; 95% confidence interval (CI) 1.17–3.05; BMI 25+; OR 1.02; 95% CI 0.69–1.51]. Wheeze was associated with the reporting of menstrual cessation that was due to surgery even if women denied ever using HRT (OR 1.55; 95% CI 1.09–2.20). There was some evidence that HRT use was associated with airway obstruction in leaner women but little evidence that it was associated with IgE sensitization to HDM.

Conclusions:  In this cross‐sectional study use of HRT was associated with asthma‐like symptoms, particularly in those who have lower BMI. A substantial proportion of women whose periods have stopped because of surgery use HRT but this does not fully explain their increased morbidity.
Frequency of insertion/deletion polymorphism in exon 8 of HLA‐G and kidney allograft outcome
Authors: Crispim J. C. O. , Mendes‐Junior C. T. , Wastowski I. J. , Costa R. , Castelli E. C. , Saber L. T. , Donadi E. A.
Published: October 2007

Human leukocyte antigen‐G (HLA‐G) is a non‐classical major histocompatibility complex (MHC) class Ib molecule predominantly expressed in cytotrophoblasts, where it acts as a specific immunosuppressor. Literature data have shown that grafts in some settings, such as cardiac and liver/kidney‐associated transplantations, express HLA‐G and this expression is associated with less severe rejection and also reduces the incidence of rejection. Fourteen‐base pair deletion/insertion polymorphism has been reported in exon 8 of the 3′‐untranslated region of HLA‐G. This polymorphism within exon 8 of the HLA‐G gene might influence transcription activity, which in turn may influence the stability of HLA‐G transcripts. This influences the stability of the HLA‐G protein and therefore is of potential functional relevance. In order to determine a possible correlation between the 14‐bp insertion/deletion polymorphism and kidney allograft outcome, we isolated genomic DNA from 83 patients who had received isolated kidney allografts, and we classified the 83 specimens into two groups, grafts presenting Banff features of rejection group and a non‐rejection group, and compared them with a control group of 97 healthy subjects. The 14‐bp polymorphism at exon 8 was genotyped in all groups. There was no significant difference in allelic frequencies of 14‐bp insertion/deletion polymorphism between normal controls and kidney transplant patients. In the RG, the homozygous genotype +14/+14 bp (P = 0.0238) was significantly increased in the group with acute rejection compared with the healthy control group. Analysis of other HLA‐G polymorphisms and functional studies on immune regulation are essential to elucidate the role of HLA‐G in kidney allografts.
Chronic rejection with sclerosing peritonitis following pediatric intestinal transplantation
Authors: Ramos Esther , Molina Manuel , Sarría Jesús , Pérez‐Moneo Begoña , Burgos Emilio , López‐Santamaría Manuel , Prieto Gerardo
Published: October 2007

Abstract:  Intestinal transplantation is considered the usual treatment for patients with permanent intestinal failure when parenteral nutrition has failed. Chronic rejection is a complication difficult to diagnose because of the scarcity and lack of specificity in the symptoms and the characteristics of typical histological findings. We report the case of a four‐yr‐old patient who received an isolated intestinal transplant. After developing a chronic rejection he presented an intestinal obstruction secondary to a sclerosing peritonitis that required the surgical removal of the graft.
Acyclovir‐resistant herpes simplex virus pneumonia post‐unrelated stem cell transplantation: A word of caution
Authors: Frangoul Haydar , Wills Marcia , Crossno Christine , Engel Michael , Domm Jennifer
Published: October 2007

Abstract:  HSV causes serious complications in immunocompromised patients, especially SCT recipients. Although ACV is an effective antiviral prophylaxis, the emergence of ACV resistance is a growing problem. The authors describe two cases of fatal ACV‐resistant HSV in two pediatric patients following unrelated donor SCT. Despite the in vitro sensitivity of the HSV isolates to foscarnet, both patients failed to respond to foscarnet therapy. Other antiviral therapies should be considered in those patients who fail to show rapid clinical improvement.
Invasive aspergillosis in a paediatric haematology department: a 15‐year review
Authors: Crassard Nicolas , Hadden Hélène , Piens Marie‐Antoinette , Pondarré Corinne , Hadden Richard , Galambrun Claire , Pracros Jean‐Pierre , Souillet Gérard , Basset Thierry , Berthier Jean‐Claude , Philippe Noel , Bertrand Yves
Published: October 2007

Invasive aspergillosis (IA) is an increasingly common and often fatal fungal infection in children with haematological disorders. To describe the epidemiology, diagnosis, treatment and outcome of IA in children, retrospective review of the medical records of proven and probable IA between January 1986 and December 2000 was used. Twenty‐four patients with IA were identified (10 proven and 14 probable) with a median age of 8.5 years. The incidence of IA was particularly high in acute myeloblastic leukaemia (5.35%) and leukaemia relapse (4%). Twenty‐two patients presented with lung involvement. Broncho‐alveolar lavage led to a diagnosis in 11 cases, but diagnosis was difficult and repeated invasive explorations were required. Antifungal therapy mainly consisted of amphotericin B. Eight patients underwent open‐thorax surgery without any complication. Nine patients (37.5%) were cured of IA and three are still alive. The mortality was 87.5%. Three patients died of massive haemoptysis, including two before neutropenia recovery. Four patients presented with IA recurrence and three were cured again. Despite significant progress having been made in the treatment and diagnosis of IA, it is still a devastating complication in children with haematological disorders. New antifungal therapies and strategies are promising, but objective data are still lacking.
Disseminated histoplasmosis in acquired immunodeficiency syndrome patients in Uberaba, MG, Brazil
Authors: Mora Delio José , Barbosa dos Santos Celso Tadeu , Silva‐Vergara Mario León
Published: October 2007

Histoplasmosis occurs in approximately 5% of acquired immunodeficiency syndrome (AIDS) patients in endemic areas and often evolves to a disseminated picture if diagnosis is delayed and/or CD4 count falls below 150 cells × mm3 without high active antiretroviral therapy (HAART). This report presents clinical features of patients with histoplasmosis admitted from 1992 to 2005. Of the 57 individuals, 45 (79%) were male, aged 20–40 years; 30 (52.6%) presented histoplasmosis together with HIV diagnosis and 35 (61.4%) referred illness course up to 4 weeks. Fever, hepatomegaly and/or splenomegaly, dyspnea and skin lesions were noticed in 50 (87.7%), 38 (66.7%), 30 (52.6%) and 25 (43.9%) patients respectively. High levels of lactic acid dehydrogenase, X‐ray lung interstitial pattern, pancytopenia and CD4 count <100 cells × mm3 were observed in 48 (84.2%), 35 (66%), 34 (59.6%) and 33 (94%) patients respectively. Mycological diagnosis was performed by one or more methods in all patients. Thirty nine (68.4%) received amphotericin B and/or itraconazole. A cure rate was observed in 76.9% and nine (23.1%) died early during therapy. Otherwise death occurred in 18 (31.6%) before diagnosis was completed. Despite free HAART disposal in public Brazilian health services, histoplasmosis still occurs as the first AIDS baseline condition in patients without antiretroviral therapy, many of whom are not receiving any medical care for HIV infection.