Important Clues (important + clue)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Cytologic feature by squash preparation of pineal parenchyma tumor of intermediate differentiation

DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008
Keiji Shimada M.D., Ph.D.
Abstract Pineal parenchyma tumor of intermediate differentiation (PPTID) is a very rare intracranial tumor, and pathological investigation limited to immunohistological and ultrastructural analyses have been published to date. Although intraoperative cytology is one of the important approaches for initial diagnosis in brain tumors, no or little studies on cellular morphology of PPTID have been demonstrated due to its rarity. We report here cytological features of PPTID obtained from stereotactic surgical specimens in a case of 27-year-old female manifested by dizziness and diplopia. Brain MRI revealed an unhomogeneously enhanced, large-sized tumor (56 × 52 × 60 mm) mainly located in the pineal region expanding from the midbrain to superior portion of the cerebellum and the fourth ventricle. Squash cytology showed increased nucleocytoplasmic ratio, hyperchromatic nuclei, and small rosette-like cell cluster but cellular pleomorphism was mild to moderate and necrotic background was not observed. Histology showed high cellularity, moderate nuclear atypia, and small rosette formation but neither bizarre tumor cells nor necrosis was present. Mitotic counts were very low (less than 1 per 10 high-power fields) and the MIB-1 labeling index was relatively high (10.1%). Tumor cells were immunohistochemically positive for neural markers such as synaptophysin, neurospecific enolase but not for glial fibrillary acidic protein or S-100. In some parts, cells were strongly reactive for neurofilament protein. Taken together, we made a final diagnosis of PPTID. This is the first presentation of cytological analysis by squash preparation that gives an important clue to accurate diagnosis of pineal parenchymal tumor and to understand its malignant potential. Diagn. Cytopathol. 2008;36:749,753. © 2008 Wiley-Liss, Inc. [source]


Coarctation of the Aorta: A Secondary Cause of Hypertension

JOURNAL OF CLINICAL HYPERTENSION, Issue 6 2004
L. Michael Prisant MD
Coarctation of the aorta is a constriction of the aorta located near the ligamentum arteriosum and the origins of the left subclavian artery. This condition may be associated with other congenital disease. The mean age of death for persons with this condition is 34 years if untreated, and is usually due to heart failure, aortic dissection or rupture, endocarditis, endarteritis, cerebral hemorrhage, ischemic heart disease, or concomitant aortic valve disease in uncomplicated cases. Symptoms may not be present in adults. Diminished and delayed pulses in the right femoral artery compared with the right radial or brachial artery are an important clue to the presence of a coarctation of the aorta, as are the presence of a systolic murmur over the anterior chest, bruits over the back, and visible notching of the posterior ribs on a chest x-ray. In many cases a diagnosis can be made with these findings. Two-dimensional echocardiography with Doppler interrogation is used to confirm the diagnosis. Surgical repair and percutaneous intervention are used to repair the coarctation; however, hypertension may not abate. Because late complications including recoarctation, hypertension, aortic aneurysm formation and rupture, sudden death, ischemic heart disease, heart failure, and cerebrovascular accidents may occur, careful follow-up is required. [source]


Colonic left-side increase of eosinophils: a clue to drug-related colitis in adults

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
G. CASELLA
Summary Background, The colon shows frequent eosinophilic infiltration in allergic proctocolitis of infants, whereas in adults, eosinophilic infiltration of the colon is less defined and may be found in different conditions including drug-induced colitis, even though the pathological findings are often inconsistent. Aim, To quantify eosinophils in the mucosa of normal controls and to compare them with those of patients with abdominal symptoms related to ,drug colitis'. Methods, Mucosal biopsies were obtained during colonoscopy in 15 controls and in 27 patients with abdominal symptoms, a history of probable ,drug-related colitis' and without obvious causes of eosinophilia. Results, The drugs related to the patient symptoms were nonsteroidal anti-inflammatory drugs (70%), antiplatelet agents (19%) and oestroprogestinic agents (11%). Colonoscopy was normal in 30% of patients and abnormal in 70%. Histology showed low content of inflammatory cells and normal crypt architecture in-patients with endoscopy similar to inflammatory bowel diseases. The eosinophil score was significantly higher in the left side of the colon in the patient group compared with controls. Conclusions, The finding of an increased eosinophil count limited to the left (descending and sigmoid) colon is an important clue towards a diagnosis of drug-related colitis [source]


Salt glands in a Tithonian metriorhynchid crocodyliform and their physiological significance

LETHAIA, Issue 4 2000
Marta Fernández
Our knowledge of Mesozoic tetrapods is based mainly on osteological evidence. The discussion of the evolution of any homeostatic system is highly speculative because direct non-osteological evidence is uncommon. Here we report an extraordinarily well-preserved cast of a pair of lobulated protuberances in the skull of the marine metriorhynchid crocodiliform Geosaurus from the Tithonian (Jurassic) of Patagonia (Argentina). These protuberances are interpreted as representing salt glands. Based on their topology, these glands are identified as the nasals. Optimization of this character on a phylogenetic tree permits us to infer the ancestral condition for archosaurs. The relationship between salt gland and diet is also analysed. The presence of hypertrophied salt glands in the skull of Geosaurus suggests that as early as 140 million years ago, some Mesozoic marine reptiles had evolved an extra-renal osmoregulatory system. This achievement was an important clue in the successful colonization of marine environments. Salt glands preclude the risk of lethal dehydration and allow marine reptiles to include an important amount of invertebrates in their diet. [source]


Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis

ALLERGY, Issue 9 2010
P. Burney
To cite this article: Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010; 65: 1182,1188. Abstract Background:, Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods. Methods:, Sera from the ,random sample' of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix. Results:, Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country. Conclusions:, Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization. [source]


Are invasive plant species better competitors than native plant species?

OIKOS, Issue 2 2004
evidence from pair-wise experiments
Invasive plants often appear to be more competitive than native species, but there have been few tests of this hypothesis. We reviewed published pair-wise experiments between invading and native plant species. Although the designs that have been used allow only limited inferences, the available data suggest that the effect of invasive species on native species is usually stronger than vice versa. Furthermore, mixtures of invasive and native species are generally less productive than monocultures of the native species, but not less than monocultures of the invasive species. However, the selection of invaders and natives for study has not been random, and the data could be biased towards highly competitive invaders and natives that are weaker than average competitors. We attempt to clarify confusion surrounding the concept of competitive superiority in the context of plant invasions, and we discuss the limitations of the methods that have been used to investigate competition between invasive and native species. To rigorously test the generality of the hypothesis that invaders are better competitors than natives we need to compare the effects of closely related native and invasive species on each other. We suggest that the influence of an invading species on total plant community biomass is an important clue in understanding the role of competition in a plant invasion. The role of competition in the establishment and naturalization stages of the invasion process may be very different from its role in the "outbreak" stage. [source]


Actin mutations are one cause of congenital fibre type disproportion

ANNALS OF NEUROLOGY, Issue 5 2004
Nigel G. Laing PhD
We report three heterozygous missense mutations of the skeletal muscle alpha actin gene (ACTA1) in three unrelated cases of congenital fiber type disproportion (CFTD) from Japan and Australia. This represents the first genetic cause of CFTD to be identified and confirms that CFTD is genetically heterogeneous. The three mutations we have identified Leucine221Proline, Aspartate292Valine, and Proline332Serine are novel. They have not been found previously in any cases of nemaline, actin, intranuclear rod, or rod-core myopathy caused by mutations in ACTA1. It remains unclear why these mutations cause type 1 fiber hypotrophy but no nemaline bodies. The three mutations all lie on one face of the actin monomer on the surface swept by tropomyosin during muscle activity, which may suggest a common pathological mechanism. All three CFTD cases with ACTA1 mutations had severe congenital weakness and respiratory failure without ophthalmoplegia. There were no clinical features specific to CFTD cases with ACTA1 mutations, but the presence of normal eye movements in a severe CFTD patient may be an important clue for the presence of a mutation in ACTA1. Ann Neurol 2004 [source]


On the Chandra Detection of Diffuse X-Ray Emission from Sgr A*

ASTRONOMISCHE NACHRICHTEN, Issue S1 2003
M. E. Pessah
Abstract Kinematic studies of the stellar motions near Sgr A* have revealed the presence of several million solar masses of dark matter enclosed within 0.015 parsecs of the Galactic Center. However, it is not yet clear what fraction of this material is contained within a single point-like object, as opposed to an extended distribution of orbiting matter (e.g., in the form of neutron stars). Recent Chandra observations suggest that the X-ray emission from this source is partially diffuse. This result provides an important clue that can be used to set some constraints on the mass distribution surrounding the black hole. Here, we develop a simple model in which the diffuse emission is produced by a halo of neutron stars accreting from the gas falling toward the center. We discuss the various accretion mechanisms that are likely to contribute significantly to the X-ray flux, and show that a highly magnetized fraction of old neutron stars may account for the diffuse high-energy source. If this picture is correct, the upper bound to the mass of the central black hole is ,2.2 × 106M,. The core radius of the dark cluster must then be ,0.06 pc. We also discuss the sensitivity of our results to the various assumptions made in our calculations. [source]


Sedimentary Features and Their Implications of Microdigital Stromatolites from the Mesoproterozoic Wumishan Formation at the Jixian Section in North China

ACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 3 2010
Mingxiang MEI
Abstract: The Mesoproterozoic Wumishan Formation at the Jixian section in Tianjin is a set of more than 3000-m-thick stromatolitic carbonate succession. In this succession, several lithofacies units, that is, the subtidal stromatolitic biostrome, the thrombolitic bioherm, tidal-flat micritic dolomite and lagoon dolomitic shale, make up many meter-scale cycles of the peritidal carbonate type that have been nominated as the Wumishan cycles. Importantly, many microdigital stromatolites make up the stromatolitic biostrome unit of the Wumishan cycles in the lower part of the Wumishan Formation. These microdigital stromatolites have been grouped as a stromatolitic assemblage by paleontologists, that is, "Pseudogymnosolen mopanyuensis-Scuphus-Yangzhuang columnaris" assemblage. These microdigital stromatolites had also been interpreted as the aragonite (tufa) sea-floor precipitates by sedimentologists, and has further been thought as the special products of the transitional period from the sea-floor aragonite precipitates of the Archean to the clastic and muddy carbonates of the Neoproterozoic. Although there are some restrictions for the stratigraphic meaning of the concept of the stromatolitic assemblage, detailed studies on classification by paleontologists provide an important clue to understand the sedimentological meaning of the microdigital stromatolites. Furthermore, an important and obvious horizon for the end of the microdigital stromatolites was recorded in the Mesoproterozoic Wumishan Formation at the Jixian section, which provides useful information to understand the stromatolite decline occurred at c.1250 Ma and the evolving carbonate world of the Precambrian. [source]


Multiple forms of violence and other criminal activities as an indicator of severe child maltreatment

CHILD ABUSE REVIEW, Issue 4 2004
Janet Stanley
Abstract Child protection practice still appears to view child maltreatment as an event largely isolated from other family violence and criminal activities. Research undertaken by the authors suggests that children who have been subjected to the more severe forms of abuse are likely to have come from families who engage in several forms of criminal activity, inside and outside the family, which is often severe in nature. The child who has been maltreated may also become a participant in these activities. The authors recommend that these factors should be investigated in families who have maltreated a child, as the presence or absence of several forms of concurrent violence and other criminal activity may provide an important clue about the welfare of the child. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Using DNA sequencing electrophoresis compression artifacts as reporters of stable mRNA structures affecting gene expression

ELECTROPHORESIS, Issue 21 2007
Divya Kapoor
Abstract The formation of secondary structure in oligonucleotide DNA is known to lead to "compression" artifacts in electropherograms produced through DNA sequencing. Separately, the formation of secondary structure in mRNA is known to suppress translation; in particular, when such structures form in a region covered by the ribosome either during, or shortly after, initiation of translation. Here, we demonstrate how a DNA sequencing compression artifact provides important clues to the location(s) of translation-suppressing secondary structural elements in mRNA. Our study involves an engineered version of a gene sourced from Rhodothermus marinus encoding an enzyme called Cel12A. We introduced this gene into Escherichia coli with the intention of overexpressing it, but found that it expressed extremely poorly. Intriguingly, the gene displayed a remarkable compression artifact during DNA sequencing electrophoresis. Selected "designer" silent mutations destroyed the artifact. They also simultaneously greatly enhanced the expression of the cel12A gene, presumably by destroying stable mRNA structures that otherwise suppress translation. We propose that this method of finding problem mRNA sequences is superior to software-based analyses, especially if combined with low-temperature CE. [source]


Risk factors for epiploic foramen entrapment colic in a UK horse population: A prospective case-control study

EQUINE VETERINARY JOURNAL, Issue 4 2008
D. C. ARCHER
Summary Reasons for performing study: Epiploic foramen entrapment (EFE) is a common cause of small intestinal strangulation in the horse and its epidemiology requires further investigation. Objectives: To identify horse- and management-level risk factors for EFE and to explore reasons for the apparent seasonality of this condition. Hypothesis: Horses exhibiting certain behaviours and those exposed to particular management practices that vary seasonally are at increased risk of EFE. Methods: A prospective unmatched, multicentre case-control study was conducted over 24 months in the UK. Data on 77 cases and 216 control horses were obtained from 9 collaborating clinics and logistic regression was used to identify associations between horse and management variables and the likelihood of EFE. Results: In a final multivariable model crib-biting/ windsucking behaviour was associated with the largest increase in likelihood of EFE. A history of colic in the previous 12 months, increased stabling in the previous 28 days and height of the horse also increased the likelihood of EFE. Horses with access to a mineral/salt lick, those easily frightened and horses not fed at the same time as others were at reduced risk of EFE. Conclusions: Horses exhibiting certain behaviours, those with a previous history of colic and horses of greater height appear to be at inherently greater risk of EFE. The increase in likelihood of EFE with increased duration of stabling may explain the apparent seasonality of this condition. Potential relevance: These findings assist identification of horses at high-risk of EFE and provide information on management strategies that may reduce this risk. If the observed associations are causal, avoiding sudden increases in duration of stabling, not feeding horses in the same group at the same time and providing a mineral/salt lick may reduce the likelihood of EFE. The risk factors identified in this study provide important clues to the aetiology of EFE. [source]


Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function

FEBS JOURNAL, Issue 24 2002
Jesús Sánchez Más
The ,-melanocyte-stimulating hormone (,MSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of ,MSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent ,MSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships. [source]


Ribosomal RNA gene fragments from fossilized cyanobacteria identified in primary gypsum from the late Miocene, Italy

GEOBIOLOGY, Issue 2 2010
G. PANIERI
Earth scientists have searched for signs of microscopic life in ancient samples of permafrost, ice, deep-sea sediments, amber, salt and chert. Until now, evidence of cyanobacteria has not been reported in any studies of ancient DNA older than a few thousand years. Here, we investigate morphologically, biochemically and genetically primary evaporites deposited in situ during the late Miocene (Messinian) Salinity Crisis from the north-eastern Apennines of Italy. The evaporites contain fossilized bacterial structures having identical morphological forms as modern microbes. We successfully extracted and amplified genetic material belonging to ancient cyanobacteria from gypsum crystals dating back to 5.910,5.816 Ma, when the Mediterranean became a giant hypersaline brine pool. This finding represents the oldest ancient cyanobacterial DNA to date. Our clone library and its phylogenetic comparison with present cyanobacterial populations point to a marine origin for the depositional basin. This investigation opens the possibility of including fossil cyanobacterial DNA into the palaeo-reconstruction of various environments and could also be used to quantify the ecological importance of cyanobacteria through geological time. These genetic markers serve as biosignatures providing important clues about ancient life and begin a new discussion concerning the debate on the origin of late Miocene evaporites in the Mediterranean. [source]


Differentiation of morphology, genetics and electric signals in a region of sympatry between sister species of African electric fish (Mormyridae)

JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2008
S. LAVOUÉ
Abstract Mormyrid fishes produce and sense weak electric organ discharges (EODs) for object detection and communication, and they have been increasingly recognized as useful model organisms for studying signal evolution and speciation. EOD waveform variation can provide important clues to sympatric species boundaries between otherwise similar or morphologically cryptic forms. Endemic to the watersheds of Gabon (Central Africa), Ivindomyrus marchei and Ivindomyrus opdenboschi are morphologically similar to one another. Using morphometric, electrophysiological and molecular characters [cytochrome b sequences and amplified fragment length polymorphism (AFLP) genotypes], we investigated to what extent these nominal mormyrid species have diverged into biological species. Our sampling covered the known distribution of each species with a focus on the Ivindo River, where the two taxa co-occur. An overall pattern of congruence among datasets suggests that I. opdenboschi and I. marchei are mostly distinct. Electric signal analysis showed that EODs of I. opdenboschi tend to have a smaller initial head-positive peak than those of I. marchei, and they often possess a small third waveform peak that is typically absent in EODs of I. marchei. Analysis of sympatric I. opdenboschi and I. marchei populations revealed slight, but significant, genetic partitioning between populations based on AFLP data (FST , 0.04). Taken separately, however, none of the characters we evaluated allowed us to discriminate two completely distinct or monophyletic groups. Lack of robust separation on the basis of any single character set may be a consequence of incomplete lineage sorting due to recent ancestry and/or introgressive hybridization. Incongruence between genetic datasets in one individual, which exhibited a mitochondrial haplotype characteristic of I. marchei but nevertheless fell within a genetic cluster of I. opdenboschi based on AFLP genotypes, suggests that a low level of recent hybridization may also be contributing to patterns of character variation in sympatry. Nevertheless, despite less than perfect separability based on any one dataset and inconclusive evidence for complete reproductive isolation between them in the Ivindo River, we find sufficient evidence to support the existence of two distinctive species, I. opdenboschi and I. marchei, even if not ,biological species' in the Mayrian sense. [source]


The case for sequencing the genome of the electric eel Electrophorus electricus

JOURNAL OF FISH BIOLOGY, Issue 2 2008
J. S. Albert
A substantial international community of biologists have proposed the electric eel Electrophorus electricus (Teleostei: Gymnotiformes) as an important candidate for genome sequencing. In this study, the authors outline the unique advantages that a genome sequencing project of this species would offer society for developing new ways of producing and storing electricity. Over tens of millions of years, electric fish have evolved an exceptional capacity to generate a weak (millivolt) electric field in the water near their body from specialized muscle-derived electric organs, and simultaneously, to sense changes in this field that occur when it interacts with foreign objects. This electric sense is used both to navigate and orient in murky tropical waters and to communicate with other members of the same species. Some species, such as the electric eel, have also evolved a strong voltage organ as a means of stunning prey. This organism, and a handful of others scattered worldwide, convert chemical energy from food directly into workable electric energy and could provide important clues on how this process could be manipulated for human benefit. Electric fishes have been used as models for the study of basic biological and behavioural mechanisms for more than 40 years by a large and growing research community. These fishes represent a rich source of experimental material in the areas of excitable membranes, neurochemistry, cellular differentiation, spinal cord regeneration, animal behaviour and the evolution of novel sensory and motor organs. Studies on electric fishes also have tremendous potential as a model for the study of developmental or disease processes, such as muscular dystrophy and spinal cord regeneration. Access to the genome sequence of E. electricus will provide society with a whole new set of molecular tools for understanding the biophysical control of electromotive molecules, excitable membranes and the cellular production of weak and strong electric fields. Understanding the regulation of ion channel genes will be central for efforts to induce the differentiation of electrogenic cells in other tissues and organisms and to control the intrinsic electric behaviours of these cells. Dense genomic sequence information of E. electricus will also help elucidate the genetic basis for the origin and adaptive diversification of a novel vertebrate tissue. The value of existing resources within the community of electric fish research will be greatly enhanced across a broad range of physiological and environmental sciences by having a draft genome sequence of the electric eel. [source]


Autoimmune and inflammatory disorders and risk of malignant lymphomas , an update

JOURNAL OF INTERNAL MEDICINE, Issue 6 2008
K. E. Smedby
Abstract. As specific autoimmune disorders now constitute established risk factors for malignant lymphomas, we describe this association. We review reported risk levels, risk determinants, lymphoma subtypes and biological mechanisms in autoimmunity/inflammation, emphasizing on recent findings. Whilst numerous reports describe average lymphoma risks in large patient groups, there's a recent shift of focus to risk determinants and the role of inflammatory activity. Studies highlight associations with diffuse large B-cell lymphoma, apart from lymphoma development in target organs of inflammation. Future studies of high-risk patient subsets using detailed assessments of autoimmunity/inflammation and lymphoma may give important clues to lymphomagenesis. [source]


Two serine residues distinctly regulate the rescue function of Humanin, an inhibiting factor of Alzheimer's disease-related neurotoxicity: functional potentiation by isomerization and dimerization

JOURNAL OF NEUROCHEMISTRY, Issue 6 2003
Kenzo Terashita
Abstract The 24-residue peptide Humanin (HN), containing two Ser residues at positions 7 and 14, protects neuronal cells from insults of various Alzheimer's disease (AD) genes and A,. It was not known why the rescue function of (S14G)HN is more potent than HN by two to three orders of magnitude. Investigating the possibility that the post-translational modification of Ser14 might play a role, we found that HN with d -Ser at position 14 exerts neuroprotection more potently than HN by two to three orders of magnitude, whereas d -Ser7 substitution does not affect the rescue function of HN. On the other hand, S7A substitution nullified the HN function. Multiple series of experiments indicated that Ser7 is necessary for self-dimerization of HN, which is essential for neuroprotection by this factor. These findings indicate that the rescue function of HN is quantitatively modulated by d -isomerization of Ser14 and Ser7-relevant dimerization, allowing for the construction of a very potent HN derivative that was fully neuroprotective at 10 pm against 25 µm A,1,43. This study provides important clues to the understanding of the neuroprotective mechanism of HN, as well as to the development of novel AD therapeutics. [source]


Competence profiles of recently registered nurses working in intensive and emergency settings

JOURNAL OF NURSING MANAGEMENT, Issue 8 2007
ANNE H. SALONEN MNSc
Background, Preceptorship is an essential method of supporting nurse competence, guaranteeing high quality care and increasing job satisfaction. Aim, To describe recently registered nurses' perceptions of their competence level, and to identify factors influencing these perceptions. Method, The survey was conducted by using Meretoja's Nurse Competence Scale. The sample comprised 235 registered nurses working in intensive and emergency settings. The data were analysed by using statistical methods. Results, Nurses' self-assessed competence level ranged from moderate to good. A statistically significant association was seen between competence level and age, length of current work experience and the frequency of using competencies. Conclusions, The results shed useful light on the educational needs of nurses and provide important clues for the development of preceptorship programmes. The Nurse Competence Scale proved to be a reliable and valid instrument in assessing the competence of recently registered nurses. Implications for nursing management, We recommend that management strategies be developed to enhance and support positive learning environments for competence development. We recommend preceptorship programmes based on systematic competence assessments made by nurses themselves, their preceptors and managers. [source]


Neurovascular Alignment in Adult Mouse Skeletal Muscles

MICROCIRCULATION, Issue 2 2005
SHAWN E. BEARDEN
ABSTRACT Objective: Muscle blood flow increases with motor unit recruitment. The physical relationships between somatic motor nerves, which control muscle fiber contraction, and arterioles, which control microvascular perfusion, are unexplored. The authors tested the hypothesis that motor axons align with arterioles in adult skeletal muscle. Methods: Transgenic mice (C57BL/6 background, n = 5; 10 months of age) expressing yellow fluorescent protein in all motor nerves underwent vascular casting (Microfil). Excised epitrochlearis, gracilis, gluteus maximus, and spinotrapezius muscles were imaged at 380× and 760× and a computer-integrated tracing system (Neurolucida) was used to acquire 3-dimensional digital renderings of entire arteriolar and neural networks within each muscle. Results: Arteriolar networks were typically ,3-fold longer than neural networks. Nerves coursed with arterioles until terminating at motor endplates. Across muscles, proximity analyses revealed that , 75% of total nerve length (9.8,48.8 mm) lay within 200 ,m of the nearest arteriole (diameters of 15,60 , m). Conclusions: Somatic motor nerves and arterioles align closely within adult mammalian skeletal muscle. Understanding the signals governing neurovascular alignment may hold important clues for the advancement of tissue engineering and regeneration. [source]


Distinctiveness in the face of gene flow: hybridization between specialist and generalist gartersnakes

MOLECULAR ECOLOGY, Issue 18 2008
BENJAMIN M. FITZPATRICK
Abstract Patterns of divergence and polymorphism across hybrid zones can provide important clues as to their origin and maintenance. Unimodal hybrid zones or hybrid swarms are composed predominantly of recombinant individuals whose genomes are patchworks of alleles derived from each parental lineage. In contrast, bimodal hybrid zones contain few identifiable hybrids; most individuals fall within distinct genetic clusters. Distinguishing between hybrid swarms and bimodal hybrid zones can be important for taxonomic and conservation decisions regarding the status and value of hybrid populations. In addition, the causes of bimodality are important in understanding the generation and maintenance of biological diversity. For example, are distinct clusters mostly reproductively isolated and co-adapted gene complexes, or can distinctiveness be maintained by a few ,genomic islands' despite rampant gene flow across much of the genome? Here we focus on three patterns of distinctiveness in the face of gene flow between gartersnake taxa in the Great Lakes region of North America. Bimodality, the persistence of distinct clusters of genotypes, requires strong barriers to gene flow and supports recognition of distinct specialist (Thamnophis butleri) and generalist (Thamnophis radix) taxa. Concordance of DNA-based clusters with morphometrics supports the hypothesis that trophic morphology is a key component of divergence. Finally, disparity in the level of differentiation across molecular markers (amplified fragment length polymorphisms) indicates that distinctiveness is maintained by strong selection on a few traits despite high gene flow currently or in the recent past. [source]


Taking shape: control of bacterial cell wall biosynthesis

MOLECULAR MICROBIOLOGY, Issue 5 2005
George C. Stewart
Summary The characteristic shape of a bacterial cell is a function of the three dimensional architectures of the cell envelope and is determined by the balance between lateral wall extension and synthesis of peptidoglycan at the division septum. The three dimensional patterns of cell wall synthesis in the bacterium Bacillus subtilis is influenced by actin-like proteins that form helical coils in the cell and by the MreCD membrane proteins that link the cytoskeletal elements with the penicillin-binding proteins that carry out peptidoglycan synthesis. Recent genetic studies have provided important clues as to how these proteins are arranged in the cell and how they function to regulate cell shape. [source]


An analysis of the factory model for chromosome replication and segregation in bacteria

MOLECULAR MICROBIOLOGY, Issue 4 2001
James Sawitzke
Recent advances in microscopy have given us important clues as to the nature of chromosome segregation in bacteria. Most current observations favour the view that the process is co-replicational: DNA replication forks are anchored at the cell centre, and the newly replicated DNA is moved towards the cell poles. This scheme can account for orderly segregation even at high growth rates where multiple replication cycles overlap. We argue that there are five distinct activities directly involved in co-replicational segregation dynamics. These we refer to as Push, Direct, Condense, Hold and Clear. We attempt to assign one of these roles to each protein implicated in chromosome segregation. The proposed process is very different from mitosis in eukaryotic cells and perhaps more closely resembles the formation of separate sister chromatids during DNA replication. [source]


Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2007
J. M. Woulfe
Neurodegenerative diseases are characterized pathologically by the abnormal accumulation of pathogenic protein species within the cell. Several neurodegenerative diseases feature intranuclear protein aggregation in the form of intranclear inclusion bodies. Studies of these intranuclear inclusions are providing important clues regarding the cellular pathophysiology of these diseases, as exemplified by recent progress in defining the genetic basis of a subset of frontotemporal dementia cases. The precise role of intranuclear inclusion bodies in disease pathogenesis is currently a focus of debate. The present review provides an overview of the diverse family of neurodegenerative diseases in which nuclear inclusions form part of the neuropathological spectrum. In addition, current pathogenetic concepts relevant to these diseases will be reviewed and arguments for and against a protective role for intranuclear inclusions will be presented. The relationship of pathological intranuclear inclusions to functional intranuclear bodies will also be discussed. Finally, by analogy with pathological intranuclear inclusions, I will speculate on the possibility that intranuclear protein aggregation may represent a constitutive cellular protective mechanism occurring in neurons under physiological conditions. [source]


Apoptosis in amyotrophic lateral sclerosis: a review of the evidence

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2001
S. Sathasivam
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting the upper and lower motor neurones of the central nervous system. Recently, a lot of interest has been generated by the possibility that a mechanism of programmed cell death, termed apoptosis, is responsible for the motor neurone degeneration in this condition. Apoptosis is regulated through a variety of different pathways which interact and eventually lead to controlled cell death. Apart from genetic regulation, factors involved in the control of apoptosis include death receptors, caspases, Bcl-2 family of oncoproteins, inhibitor of apoptosis proteins (IAPs), inhibitors of IAPs, the p53 tumour suppressor protein and apoptosis-related molecules. The first part of this article will give an overview of the current knowledge of apoptosis. In the second part of this review, we will examine in detail the evidence for and against the contribution of apoptosis in motor neurone cell death in ALS, looking at cellular-, animal- and human post-mortem tissue-based models. In a chronic neurodegenerative disease such as ALS, conclusive evidence of apoptosis is likely to be difficult to detect, given the rapidity of the apoptotic cell death process in relation to the relatively slow time course of the disease. Although a complete picture of motor neurone death in ALS has not been fully elucidated, there is good and compelling evidence that a programmed cell death pathway operates in this disorder. The strongest body of evidence supporting this comes from the findings that, in ALS, changes in the levels of members of the Bcl-2 family of oncoproteins results in a predisposition towards apoptosis, there is increased expression or activation of caspases-1 and -3, and the dying motor neurones in human cases exhibit morphological features reminiscent of apoptosis. Further supporting evidence comes from the detection of apoptosis-related molecules and anti-Fas receptor antibodies in human cases of ALS. However, the role of the p53 protein in cell death in ALS is at present unclear. An understanding of the mechanism of programmed cell death in ALS may provide important clues for areas of potential therapeutic intervention for neuroprotection in this devastating condition. [source]


Viral infections in the mouth

ORAL DISEASES, Issue 2002
CG Teo
Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein,Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via non-glossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis. [source]


Pathological and molecular biological aspects of the renal epithelial neoplasms, up-to-date

PATHOLOGY INTERNATIONAL, Issue 6 2004
Yoji Nagashima
Renal neoplasms are not necessarily high in frequency, but they are characteristic in their heterogeneity and occasional association with systemic familial tumor syndromes and phacomatoses (e.g. clear cell renal cell carcinoma and von Hippel-Lindau disease, Wilms tumor and aniridia, genitourinary malformation and mental retardation (so-called, WAGR syndrome), and angiomyolipoma and tuberous sclerosis). Physicians and pathologists should take note of these syndromes and associated renal neoplasms because they have provided important clues to elucidate the mechanism of tumorigenesis concerning cancer-suppressor genes. This review aims to present recent classification of renal parenchymal neoplasms based on their molecular biological characteristics, and future problems yet to be clarified. [source]


Update on skin repigmentation therapies in vitiligo

PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2009
Rafael Falabella
Summary Treatment for vitiligo is difficult and prolonged. Nevertheless, at present considerable knowledge accumulated during several decades on the pathogenic mechanisms, revealed important clues for designing new strategies to improve vitiligo depigmentation. With available medical therapies, high repigmentation percentages mostly on facial and neck lesions are achieved, although they are less effective on trunk and limbs and poor on the acral parts of the extremities. Narrow band UVB and psoralens and UVA are the two most important treatments for generalized vitiligo affecting more than 10,20% of the cutaneous surface, and topical corticosteroids, or calcineurin inhibitors are the most valuable treatments for localized vitiligo. Persistence of achieved regimentation is variable and an undefined percentage of patients may have variable recurrence. When vitiligo becomes refractory, surgical methods may improve depigmentation as effectively as with medical therapy; in segmental (unilateral) or long standing, non-segmental (bilateral) stable vitiligo, repigmentation with surgical methods is usually permanent. [source]


Production of Melanocyte-Specific Antibodies to Human Melanosomal Proteins: Expression Patterns in Normal Human Skin and in Cutaneous Pigmented Lesions

PIGMENT CELL & MELANOMA RESEARCH, Issue 4 2001
Victoria Virador
Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein 1 (TYRP1), Dopachrome tautomerase (DCT) and Pmel17 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation. [source]


Pollination Biology of Distylous Rubiaceae in the Atlantic Rain Forest, SE Brazil

PLANT BIOLOGY, Issue 5 2002
C. C. de Castro
Abstract: Data on pollination biology constitute important clues for the comprehension of pollen flow and genetic differentiation in plant populations. Pollinator type, availability and behaviour may modify morphological and mating patterns in populations of typically distylous species. This study investigates the pollination biology of four distylous species of Rubiaceae in the Atlantic rain forest, SE Brazil. Data on flowering phenology, floral lifespan, stigmatic receptivity, pollen availability, nectar volume and concentration, and pollinator activity were collected. The species studied flower sequentially throughout the wet season, and produce terminal inflorescences which bear small, tubular, diurnal, nectariferous flowers. Despite these similarities, some of the species studied are pollinated by different groups of pollinators, probably due to their distribution, availability of flowers and corolla length. On the other hand, pollinator specificity does not seem to be so important for distylous species. Long mouthparts, like those of most of the recorded pollinators, may reach lower sexual organs and, together with the self- and intramorph-incompatibilities observed, be sufficient to perform legitimate pollination and maintain levels of intermorph mating. [source]