bluuebunny/crossref_metadata_2025 huggingface dataset:
Dictyostelium discoideum
Developmentally Regulated Genes Whose Expression Is Dependent on MADS Box Transcription Factor SrfA
Authors: Escalante Ricardo , Moreno Nicolas , Sastre Leandro
Published: December 2003

The MADS box transcription factor SrfA is required for spore differentiation in
Dictyostelium discoideum. srfA
null strains form rounded spores that do not resist adverse environmental conditions. Five genes whose expression is dependent on SrfA have been isolated by differential hybridization. One of these genes,
sigC
, is identical to
phg1b
, previously characterized in mutants with altered adhesive properties and found to encode a nine-transmembrane-domain protein. This gene is transcribed into two mRNAs as the result of alternative splicing of two internal exons. The slower-migrating mRNA codes for a shorter protein that lacks the first transmembrane fragment and is not expressed in
srfA
null strains. The other four genes (
sigA
,
sigB
,
sigD
, and
45D
) are expressed only during late developmental stages. In situ hybridization experiments showed that expression of
sigA
,
sigB
, and
sigD
is restricted to the sorus of developing structures.
sigA
codes for a homologue of malate dehydrogenase that converts pyruvate to malate to replenish the tricarboxylic acid cycle.
sigB
encodes a protein with significant similarity to the GP63 metalloproteinase of
Leishmania
, leishmanolysin. The sequence of SigD is highly similar to that of several spore coat proteins of
D. discoideum
, and it may play a role in that structure. The gene
45D
codes for an RNA-binding protein homologue whose expression is also dependent on the GATA transcription factor stalky (StkA). The expression of
sigB
is also dependent on both SrfA and StkA. The expression of
45D
, but not of
sigA
,
sigB
,
sigC
, and
sigD
, can be induced in
srfA
null cells by constitutive protein kinase A activation. Strains in which either
sigA
,
sigB
, or
sigD
is disrupted were isolated and found to form spores that are not detectably different from those of wild-type strains.
Cryptococcus neoformans
Gene Expression during Experimental Cryptococcal Meningitis
Authors: Steen B. R. , Zuyderduyn S. , Toffaletti D. L. , Marra M. , Jones S. J. M. , Perfect J. R. , Kronstad J.
Published: December 2003

Cryptococcus neoformans
, an encapsulated basidiomycete fungus of medical importance, is capable of crossing the blood-brain barrier and causing meningitis in both immunocompetent and immunocompromised individuals. To gain insight into the adaptation of the fungus to the host central nervous system (CNS), serial analysis of gene expression (SAGE) was used to characterize the gene expression profile of
C. neoformans
cells recovered from the CNS of infected rabbits. A SAGE library was constructed, and 49,048 tags were sequenced; 16,207 of these tags were found to represent unique sequences or tag families. Of the 304 most-abundant tags, 164 were assigned to a putative gene for subsequent functional grouping. The results (as determined according to the number of tags that identified genes encoding proteins required for these functions) indicated that the
C. neoformans
cells were actively engaged in protein synthesis, protein degradation, stress response, small-molecule transport, and signaling. In addition, a high level of energy requirement of the fungal cells was suggested by a large number of tags that matched putative genes for energy production. Taken together, these findings provide the first insight into the transcriptional adaptation of
C. neoformans
to the host environment and identify the set of fungal genes most highly expressed during cerebrospinal fluid infection.
MFα1
, the Gene Encoding the α Mating Pheromone of
Candida albicans
Authors: Panwar Sneh L. , Legrand Melanie , Dignard Daniel , Whiteway Malcolm , Magee Paul. T.
Published: December 2003

Candida albicans
, the single most frequently isolated human fungal pathogen, was thought to be asexual until the recent discovery of the mating-type-like locus (
MTL
). Homozygous
MTL
strains were constructed and shown to mate. Furthermore, it has been demonstrated that opaque-phase cells are more efficient in mating than white-phase cells. The similarity of the genes involved in the mating pathway in
Saccharomyces cerevisiae
and
C. albicans
includes at least one gene (
KEX2
) that is involved in the processing of the α mating pheromone in the two yeasts. Taking into account this similarity, we searched the
C. albicans
genome for sequences that would encode the α pheromone gene. Here we report the isolation and characterization of the gene
MFα1
, which codes for the precursor of the α mating pheromone in
C. albicans
. Two active α-peptides, 13 and 14 amino acids long, would be generated after the precursor molecule is processed in
C. albicans
. To examine the role of this gene in mating, we constructed an
mfα1
null mutant of
C. albicans
. The
mfα1
null mutant fails to mate as
MTLα
, while
MTL
a
mfα1
cells are still mating competent. Experiments performed with the synthetic α-peptides show that they are capable of inducing growth arrest, as demonstrated by halo tests, and also induce shmooing in
MTL
a cells of
C. albicans
. These peptides are also able to complement the mating defect of an
MTLα kex2
mutant strain when added exogenously, thereby confirming their roles as α mating pheromones.
Sporangium-Specific Gene Expression in theOomycete Phytopathogen
Phytophthorainfestans
Authors: Kim Kyoung Su , Judelson Howard S.
Published: December 2003

The
oomycete genus
Phytophthora
includes many of the world's
most destructive plant pathogens, which are generally disseminated by
asexual sporangia. To identify factors relevant to the biology of these
propagules, genes induced in sporangia of the potato late blight
pathogen
Phytophthora infestans
were isolated using
cDNA macroarrays. Of ∼1,900 genes known to be expressed in
sporangia, 61 were up-regulated >5-fold in sporangia versus
hyphae based on the arrays, including 17 that were induced>
100-fold. A subset were also activated by starvation and in a
nonsporulating mutant. mRNAs of some genes declined in abundance after
germination, while others persisted through the germinated zoospore
cyst stage. Functions were predicted for about three-quarters of the
genes, including potential regulators (protein kinases and
phosphatases, transcription factors, and G-protein subunits),
transporters, and metabolic enzymes. Predominant among the last were
several dehydrogenases, especially a highly expressed sorbitol
dehydrogenase that accounted for 3% of the mRNA. Sorbitol
dehydrogenase activity also rose during sporulation and several stress
treatments, paralleling the expression of the gene. Another interesting
metabolic enzyme resembled creatine kinases, which previously were
reported only in animals and trypanosomes. These results provide
insight into the transcriptional and cellular processes occurring in
sporangia and identify potential targets for crop protection
strategies.
COEXISTENCE OF SUPERCONDUCTIVITY AND FERROMAGNETISM IN UGe2
Authors: KOO JE HUAN , CHO GUANGSUP
Published: December 2003

We investigate the coexistence of ferromagnetism and superconductivity in UGe 2 and Sr 2 RuO 4 in analogy with our previous model3 for high transition temperature superconductivity (HTSC). The Coulomb interaction for triplet electron pairs is reduced by a difference of the exchange interaction. If the electron–electron interaction Usf for UGe 2 and Usd for Sr 2 RuO 4 are larger than the reduced Coulomb interaction, superconductivity must happen. Under the same conditions, the coexistence of superconductivity and ferromagnetism is impossible in the case of our scheme, but changing phonons by pressures makes the coexistence possible for UGe 2.
Knowledge Management Education and Curriculum Development
Authors: Lau Cher Loon , Al-Hawamdeh Suliman
Published: December 2003

Given the emerging nature of the knowledge management (KM) profession and the differing schools of thought on KM by academics and practitioners, designing a curriculum in KM poses substantial challenges. One of these challenges is to be able to determine the optimal mix of subjects from the various disciplines that best meets the objective of developing the requisite professional competencies of knowledge professional. A two-pronged methodology was adopted for this study comprising a survey research to gather perceptions on KM and KM education as well as an investigation of relevant web sites on the Internet for existing postgraduate programs. The latter was used to support a comparative review of the courses' objectives and curriculum, where available. The study established that the adoption of KM in Singapore was most significant in large organizations and the public sector. However, there were differing perceptions as to who in an organization should be responsible for KM and what full-time KM roles should be in-scaled. Nonetheless, the findings did suggest that there is a potential market for knowledge professionals and reinforced the fact that KM is indeed interdisciplinary and drew upon the theories and practices of a number of disciplines such as information technology, information science, communication, business, and management.
Retaining Organizational Knowledge: A Case Study of an Australian Construction Company
Authors: Land Lesley Pek Wee , Land Malcolm , Handzic Meliha
Published: December 2003

Few would refute the importance of harnessing organizational knowledge — for reuse, learning, and process improvement. Once retained in a concrete form, knowledge becomes less fragmented and more easily accessible and useable. Such a knowledge management system indeed becomes a source of competitive advantage for an organization. The key to achieving this is by retaining the existing organizational knowledge so that we do not have to rely solely on available expertise. A number of knowledge management frameworks exist which help us to classify and structure knowledge. No single framework dominates, because different organizations have different needs depending on factors such as culture and business processes. At the same time, there is a lack of case studies on how organizations create or operate such a knowledge management system. In this paper, we present a case study of a knowledge management system used in a specific context — an Australian construction company. The study shows that, at least in this particular context, a knowledge management system can operate only where it does not interfere with the existing workflow of the organization. Furthermore, the importance of retaining valuable tacit knowledge is emphasized. We also discuss the implications for future research and practice.
Formal Knowledge Engineering Methods for Knowledge Discovery
Authors: Ramachandran Satheesh
Published: December 2003

This paper presents a framework for the integrated use of formal knowledge engineering methods and data mining based knowledge discovery methods. Knowledge is a key enterprise asset, and organizations are adopting both knowledge engineering and knowledge discovery paradigms for better knowledge management and enhanced decision support capability. Although there exists a useful interdependence between these endeavors, not much effort has been focused on using the full potential of one for the other. This paper presents a framework for the integrated use of established formal knowledge engineering methods and knowledge discovery processes with the ultimate intent of better managing the enterprise knowledge life cycle. It provides a brief overview of the knowledge discovery processes, and introduces a class of formal knowledge engineering methods and the perceived role of these methods in supporting the integration between the two worlds of knowledge discovery and knowledge engineering.
Powder X-ray diffraction analysis of the ferroelectric liquid crystal with a 2-methylbutoxypropionate unit as a function of temperature
Authors: Dobiášová L. , Šíchová H. , Valvoda V.
Published: December 2003

The ferroelectric liquid crystal material [4-[(4-methyloxyfenyl) carbonyloxyl] bifenyl-4′-yl]-(S)-2-methylbutoxypropionate containing a lateral methyl group on the aromatic ring of the alkoxybenzoate unit and two chiral carbons has been investigated by X-ray powder diffraction analysis at the 28 °C–105 °C temperature range. On cooling through the SmC temperature range, the layer spacing decreases from 28.3 to 27.7 Å with a small variation of average intermolecular distances. Lattice parameters of tetragonal and monoclinic crystalline phases occurring at lower temperatures have been determined.
Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology
Authors: Laithier Véronique , Grill Jacques , Le Deley Marie-Cécile , Ruchoux Marie-Madeleine , Couanet Dominique , Doz François , Pichon Fabienne , Rubie Hervé , Frappaz Didier , Vannier Jean-Paul , Babin-Boilletot Annie , Sariban Eric , Chastagner Pascal , Zerah Michel , Raquin Marie-Anne , Hartmann Olivier , Kalifa Chantal
Published: December 2003

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months.

Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy.

Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR.

Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.
Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia
Authors: Cheson Bruce D. , Bennett John M. , Kopecky Kenneth J. , Büchner Thomas , Willman Cheryl L. , Estey Elihu H. , Schiffer Charles A. , Doehner Hartmut , Tallman Martin S. , Lister T. Andrew , Lo-Coco Francesco , Willemze Roel , Biondi Andrea , Hiddemann Wolfgang , Larson Richard A. , Löwenberg Bob , Sanz Miguel A. , Head David R. , Ohno Ryuzo , Bloomfield Clara D.
Published: December 2003

An International Working Group met to revise the diagnostic and response criteria for acute myelogenous leukemia originally published in 1990, as well as to provide definitions of outcomes and reporting standards to improve interpretability of data and comparisons among trials. Since the original publication, there have been major advances in our understanding of the biology and molecular genetics of acute leukemia that are clinically relevant and warrant incorporation into response definitions. Differences from the 1990 recommendations included a category of leukemia-free state, new criteria for complete remission, including cytogenetic and molecular remissions and remission duration. Storage of viable blasts for correlative studies is important for future progress in the therapy of these disorders.
Analysis of Factors Associated With Outcome in Patients With Malignant Peritoneal Mesothelioma Undergoing Surgical Debulking and Intraperitoneal Chemotherapy
Authors: Feldman Andrew L. , Libutti Steven K. , Pingpank James F. , Bartlett David L. , Beresnev Tatiana H. , Mavroukakis Sharon M. , Steinberg Seth M. , Liewehr David J. , Kleiner David E. , Alexander H. Richard
Published: December 2003

Purpose: Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy.

Patients and Methods: Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed.

Results: At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only).

Conclusion: Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.
Consultation With a Medical Oncologist Before Surgery and Type of Surgery Among Elderly Women With Early-Stage Breast Cancer
Authors: Keating Nancy L. , Landrum Mary Beth , Ayanian John Z. , Winer Eric P. , Guadagnoli Edward
Published: December 2003

Purpose: Prior studies have documented variation in breast cancer treatment and care that does not follow guideline recommendations, particularly for elderly women. We assessed whether consultation with a medical oncologist before surgery was associated with use of definitive surgery, axillary node dissection, and type of surgery.

Methods: We conducted a retrospective cohort study of a population-based sample of 9,630 women aged ≥ 66 years diagnosed with breast cancer during 1995 to 1996. We measured the adjusted proportion visiting a medical oncologist before surgery, identified factors associated with such visits, and assessed the association between visits with a medical oncologist and use of definitive surgery (mastectomy or breast-conserving surgery with radiation v breast-conserving surgery without radiation); axillary dissection; and breast-conserving surgery versus mastectomy among women undergoing definitive surgery.

Results: Nineteen percent of women visited a medical oncologist before surgery; these women were younger, more often had larger or more poorly differentiated cancers, had more comorbid illnesses, and were treated more often at a teaching hospital (all P < .05). Women who saw a medical oncologist before surgery were more likely than others to undergo definitive surgery (adjusted odds ratio [OR], 1.28; 95% CI, 1.05 to 1.56) and axillary dissection (adjusted OR, 1.44; 95% CI, 1.19 to 1.73), but less likely to undergo breast-conserving surgery among women undergoing definitive surgery (OR, 0.84; 95% CI, 0.75 to 0.95).

Conclusion: Elderly women who consulted with a medical oncologist before surgery were more likely to receive guideline-recommended care. Additional research is needed allow a better understanding of the quality and content of discussions that elderly women have with various providers about breast-conserving surgery and mastectomy.
Top-down regression of the avian oviduct during late oviposition in a small passerine bird
Authors: Williams T. D. , Ames C. E.
Published: December 2003

Egg production in oviparous vertebrates is assumed to be costly but the physiological basis of any costs remains unknown. The avian oviduct is a highly differentiated linear organ, with five functionally specific regions. Here we show that the oviduct regresses rapidly `from the top down' as soon as the more proximal regions have completed their function but while the distal regions still retain an oviductal egg. In zebra finches Taeniopygia guttata, oviduct mass did not differ between early laying birds at the 1-egg stage compared with late-laying birds (with one remaining yolky follicle; dry mass, 151-167 mg). However, in birds with no remaining yolky follicles but with an oviductal egg, oviduct mass decreased to 94 mg (44%). Regression occurred unequally among different regions of the oviduct, with significant decreases in the proximal infundibulum/magnum and isthmus regions(59% and 40%, respectively), but no change in distal shell gland/vagina mass. The shell gland did not regress until after the last oviposition. Thus, the avian oviduct has a highly regulated size-function relationship consistent with a high maintenance energy cost for this organ. We suggest that oviduct function is a significant contributor to the physiological costs of egg production and might mediate individual variation in maternal effects associated with non-yolk components of egg quality (e.g. immunoglobulins,lysozyme).
Postprandial response of gastric pH in leopard sharks (Triakis semifasciata)and its use to study foraging ecology
Authors: Papastamatiou Yannis P. , Lowe Christopher G.
Published: December 2003

Changes in gastric pH of leopard sharks Triakis semifasciata were quantified as an indicator of feeding frequency and ration size. Continuous in situ measurements of gastric pH were made in captive adult leopard sharks using an autonomous pH/temperature probe for periods ranging from 5-16 days. Instrumented sharks were fed meals of squid at different ration sizes. Gastric fluid samples were also taken from non-instrumented juvenile leopard sharks at different time intervals after feeding, and the pH measured to quantify effects of the pH probe in the stomach. Continuous in situmeasurements of pH show that empty stomachs have a low pH of 1.54±1.42(mean ± s.d.) and that feeding causes a rapid increase in pH to 3.11±0.71, followed by a gradual decrease back down to baseline levels. There was a positive relationship between changes in pH and meal size(r2=0.72, P=0.001). There were no significant differences in pH between continuous in situ and laboratory serial sample measurements. Together these findings indicate that gastric acid secretion may be continuous in leopard sharks, and that changes in gastric pH may be used to estimate feeding chronology, frequency and ration size of leopard sharks in the field.
Are melanized feather barbs stronger?
Authors: Butler Michael , Johnson Amy S.
Published: December 2003

Melanin has been associated with increased resistance to abrasion,decreased wear and lowered barb breakage in feathers. But, this association was inferred without considering barb position along the rachis as a potentially confounding variable. We examined the cross-sectional area,breaking force, breaking stress, breaking strain and toughness of melanized and unmelanized barbs along the entire rachis of a primary feather from an osprey (Pandion haliaetus). Although breaking force was higher for melanized barbs, breaking stress (force divided by cross-sectional area) was greater for unmelanized barbs. But when position was considered, all mechanical differences between melanized and unmelanized barbs disappeared. Barb breaking stress, breaking strain and toughness decreased, and breaking stiffness increased, distally along the rachis. These proximal-distal material property changes are small and seem unlikely to affect flight performance of barbs. Our observations of barb bending, breaking and morphology, however,lead us to propose a design principle for barbs. We propose that, by being thicker-walled dorso-ventrally, the barb's flexural stiffness is increased during flight; but, by allowing for twisting when loaded with dangerously high forces, barbs firstly avoid failure by bending and secondly avoid complete failure by buckling rather than rupturing.
Adaptive function of soil consumption: anin vitrostudy modeling the human stomach and small intestine
Authors: Dominy Nathaniel J. , Davoust Estelle , Minekus Mans
Published: December 2003

Despite occurring in a wide variety of taxa, deliberate soil consumption(geophagy) is a poorly understood behavior. In humans, geophagy is sometimes considered aberrant or a sign of metabolic dysfunction. However, geophagy is normally assigned an adaptive function in nonhuman primates and various other organisms. One hypothesis submits that clay-rich soil adsorbs intestinal insults, namely plant metabolites or diarrhoea-causing enterotoxins. Here we test the capacity of kaolin, a commonly ingested clay, to adsorb quinine (an alkaloid) and two types of tannin (digestion-inhibitors). Trials were conducted in vitro using the TNO Intestinal Model, a device that closely simulates digestion by the human stomach and small intestine. Kaolin reduced the bioavailability of each compound by ≤30%. However, because we could not replicate clay-epithelial adhesion and reduced motility, these results may underestimate adsorption in vivo. We also show that kaolin fails to render calcium oxalate soluble. We conclude that gastrointestinal adsorption is the most plausible function of human geophagy. Adaptive advantages include greater exploitation of marginal plant foods and reduced energetic costs of diarrhoea, factors that could account for the high frequency of geophagy in children and pregnant women across the tropics.
Ontogeny of osmoregulatory structures and functions in the green crabCarcinus maenas(Crustacea, Decapoda)
Authors: Cieluch Ude , Anger Klaus , Aujoulat Fabien , Buchholz Friedrich , Charmantier-Daures Mireille , Charmantie Guy
Published: December 2003

The ontogeny of osmoregulation, the development of branchial transporting epithelia and the expression of the enzyme Na+/K+-ATPase were studied in Carcinus maenas (L.) obtained from the North Sea,Germany. Laboratory-reared zoea larvae, megalopae and young crabs were exposed to a wide range of salinities, and hemolymph osmolality was measured after 24 h exposure time (72 h in juveniles). Zoea I larvae slightly hyper-regulated in dilute media (10.2‰ and 17.0‰) and osmoconformed at>17‰. All later zoeal stages (II-IV) osmoconformed in salinities from 10.2‰ to 44.3‰. The megalopa hyper-regulated at salinities from 10.2 to 25.5‰. Young crabs hyperregulated at salinities from 5.3‰ to 25.5‰, showing an increase in their osmoregulatory capacity. The development of transporting epithelia and the expression of Na+/K+-ATPase were investigated by means of transmission electron microscopy and immunofluorescence microscopy. In the zoea IV, only a very light fluorescence staining was observed in gill buds. Epithelial cells were rather undifferentiated, without showing any features of ionocytes. Gills were present in the megalopa, where Na+/K+-ATPase was located in basal filaments of the posterior gills. In crab I juveniles and adults, Na+/K+-ATPase was noted in the three most posterior pairs of gills, but lacking in anterior gills. Ionocytes could first be recognized in filaments of megalopal posterior gills, persisting through subsequent stages at the same location. Thus, the development of the gills and the expression of Na+/K+-ATPase are closely correlated with the ontogeny of osmoregulatory abilities. The morphological two-step metamorphosis of C. maenas can also be regarded as an osmo-physiological metamorphosis, (i) from the osmoconforming zoeal stages to the weakly regulating megalopa, and (ii) to the effectively hyper-regulating juvenile and adult crabs.
Cold-acclimation inPeromyscus: temporal effects and individual variation in maximum metabolism and ventilatory traits
Authors: Rezende Enrico L. , Chappell Mark A. , Hammond Kimberly A.
Published: December 2003

Thermal acclimation in small endotherms provides an excellent model for the study of physiological plasticity, as energy requirements can be easily manipulated and the results are relevant for natural conditions. Nevertheless,how physiology changes throughout acclimation, and how individuals vary in their response to acclimation, remain poorly understood. Here we describe a high temporal-resolution study of cold acclimation in the deer mouse Peromyscus maniculatus. The experimental design was based on repeated measures at short intervals throughout cold acclimation, with controls(maintained at constant temperature) for measurement artifacts. We monitored body mass, maximum metabolic rate in cold exposure and ventilatory traits(respiratory frequency, tidal and minute volume and oxygen extraction) for 3 weeks at 23°C. Then, half of the individuals were held for 7 weeks at 5°C. Body mass was differently affected by cold acclimation depending on sex. Maximal metabolism(V̇O2max)increased significantly during the first week of cold acclimation, `overshot'after 5 weeks and dropped to a plateau about 34% above control values at week 7. Similarly, ventilatory traits increased during cold acclimation, though responses were different in their kinetics and magnitude. Body mass, maximum metabolism, and most ventilatory traits were repeatable after 7 weeks in control and cold-acclimated animals. However, repeatability tended to be lower in the cold-acclimated group, especially while animals were still acclimating. Our results show that acclimation effects may be under- and/or overestimated,depending on when trials are performed, and that different traits respond differently, and at different rates, to acclimation. Hence, future studies should be designed to ensure that animals have attained steady-state values in acclimation experiments.
Locomotion of lizards on inclines and perches: hindlimb kinematics of an arboreal specialist and a terrestrial generalist
Authors: Higham Timothy E. , Jayne Bruce C.
Published: December 2003

Arboreal animals, especially lizards, often traverse three-dimensional networks of narrow perches with variable and steep inclines, but the effects of both incline and narrow surfaces on the locomotor movement and function of limbs are poorly understood. Thus, we quantified the three-dimensional hindlimb kinematics of a specialized arboreal lizard, Chamaeleo calyptratus, moving horizontally, and up and down a 30° incline on a narrow (2.4 cm) perch and a flat surface. We compared the flat-surface data of C. calyptratus with those of an anatomically generalized terrestrial lizard, Dipsosaurus dorsalis. Inclines had significant main effects for relatively few kinematic variables of C. calyptratus (11%)compared to D. dorsalis (73%). For C. calyptratus, the main effects of locomotor surface were nearly three times more widespread than those of incline. The foot of C. calyptratus was markedly anterior to the hip at footfall, primarily as a result of an unusually extended knee for a lizard. A large amount of knee flexion during early stance may be used by C. calyptratus to actively pull the body forward in a manner not found in D. dorsalis. Unexpectedly, the pelvic rotation of C. calyptratus greatly exceeded that of D. dorsalis and, unlike D. dorsalis, was not affected by incline. The more medial location of the foot of C. calyptratus on the narrow perch during stance was primarily a result of knee flexion rather than femur depression. Unlike previous qualitative descriptions of chameleons, our data for the hindlimb posture of C. calyptratus during stance indicate that the limb was not particularly erect.
Dynamics of leg muscle function in tammar wallabies (M. eugenii)during levelversusincline hopping
Authors: Biewener A. A. , McGowan C. , Card G. M. , Baudinette R. V.
Published: December 2003

The goal of our study was to examine whether the in vivoforce-length behavior, work and elastic energy savings of distal muscle-tendon units in the legs of tammar wallabies (Macropus eugenii) change during level versus incline hopping. To address this question, we obtained measurements of muscle activation (via electromyography),fascicle strain (via sonomicrometry) and muscle-tendon force(via tendon buckles) from the lateral gastrocnemius (LG) and plantaris (PL) muscles of tammar wallabies trained to hop on a level and an inclined (10°, 17.4% grade) treadmill at two speeds (3.3 m s-1and 4.2 m s-1). Similar patterns of muscle activation, force and fascicle strain were observed under both level and incline conditions. This also corresponded to similar patterns of limb timing and movement (duty factor, limb contact time and hopping frequency). During both level and incline hopping, the LG and PL exhibited patterns of fascicle stretch and shortening that yielded low levels of net fascicle strain [LG: level,-1.0±4.6% (mean ± s.e.m.) vs incline,0.6±4.5%; PL: level, 0.1±1.0% vs incline,0.4±1.6%] and muscle work (LG: level, -8.4±8.4 J kg-1muscle vs incline, -6.8±7.5 J kg-1 muscle; PL:level, -2.0±0.6 J kg-1 muscle vs incline,-1.4±0.7 J kg-1 muscle). Consequently, neither muscle significantly altered its contractile dynamics to do more work during incline hopping. Whereas electromyographic (EMG) phase, duration and intensity did not differ for the LG, the PL exhibited shorter but more intense periods of activation, together with reduced EMG phase (P<0.01), during incline versus level hopping. Our results indicate that design for spring-like tendon energy savings and economical muscle force generation is key for these two distal muscle-tendon units of the tammar wallaby, and the need to accommodate changes in work associated with level versusincline locomotion is achieved by more proximal muscles of the limb.
Prognostic Value of Combination of Cardiac Troponin T and B-Type Natriuretic Peptide after Initiation of Treatment in Patients with Chronic Heart Failure
Authors: Ishii Junnichi , Cui Wei , Kitagawa Fumihiko , Kuno Takahiro , Nakamura Yuu , Naruse Hiroyuki , Mori Yoshihisa , Ishikawa Takashi , Nagamura Youichi , Kondo Takeshi , Oshima Hisaji , Nomura Masanori , Ezaki Kouji , Hishida Hitoshi
Published: December 2003

Background: Recent studies have suggested that cardiac troponin T (cTnT) and troponin I may detect ongoing myocardial damage involved in the progression of chronic heart failure (CHF). This study was prospectively designed to examine whether the combination of cTnT, a marker for ongoing myocardial damage, and B-type natriuretic peptide (BNP), a marker for left ventricular overload, would effectively stratify patients with CHF after initiation of treatment.

Methods: We measured serum cTnT, plasma BNP, and left ventricular ejection fraction (LVEF) on admission for worsening CHF [New York Heart Association (NYHA) functional class III to IV] and 2 months after initiation of treatment to stabilize CHF (n = 100; mean age, 68 years).

Results: Mean (SD) concentrations of cTnT [0.023 (0.066) vs 0.063 (0.20) μg/L] and BNP [249 (276) vs 753 (598) ng/L], percentage increased cTnT (>0.01 μg/L; 35% vs 60%), NYHA functional class [2.5 (0.6) vs 3.5 (5)], and LVEF [43 (13)% vs 36 (12)%] were significantly (P <0.01) improved 2 months after treatment compared with admission. During a mean follow-up of 391 days, there were 44 cardiac events, including 12 cardiac deaths and 32 readmissions for worsening CHF. On a stepwise Cox regression analysis, increased cTnT and BNP were independent predictors of cardiac events (P <0.001). cTnT >0.01 μg/L and/or BNP >160 ng/L 2 months after initiation of treatment were associated with increased cardiac mortality and morbidity rates.

Conclusion: The combination of cTnT and BNP measurements after initiation of treatment may be highly effective for risk stratification in patients with CHF.
Amino-Terminal Form of Parathyroid Hormone (PTH) with Immunologic Similarities to hPTH(1–84) Is Overproduced in Primary and Secondary Hyperparathyroidism
Authors: D’Amour Pierre , Brossard Jean-Hugues , Rousseau Louise , Roy Louise , Gao Ping , Cantor Tom
Published: December 2003

Background: To separate non-(1–84)parathyroid hormone [non-(1–84)PTH] from PTH(1–84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1–84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure.

Methods: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15–20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65–84) structure requirement were used to measure basal and fractionated PTH values.

Results: T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13 (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients [47 (35.1) vs 33.4 (26.1) pmol/L; P <0.01]. By contrast, CA-PTH concentrations were similar to or higher than T-PTH in three of five patients with primary hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA-PTH assay reacted with the hPTH(1–84) peak and with a minor peak different from the non-(1–84) peak recognized by the T-PTH assay. This minor peak was not recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25 (23)% in patients with primary hyperparathyroidism, and 22 (7)% in renal failure patients, assuming equimolar reactivity to hPTH(1–84) in the CA-PTH assay. It was not oxidized hPTH(1–84), which migrated differently on HPLC and reacted similarly in the CA and T-PTH assays.

Conclusions: This new molecular form of PTH has structural integrity of the (1–4) region but presumably is modified in the region (15–20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined.
Simultaneous Determination of Tocotrienols, Tocopherols, Retinol, and Major Carotenoids in Human Plasma
Authors: Lee Bee-Lan , New Ai-Li , Ong Choon-Nam
Published: December 2003

Background: Epidemiologic evidence suggests that the concentrations of antioxidant vitamins in human plasma may play an important role in numerous chronic diseases, such as cancer and cardiovascular disease. However, methods for simultaneous measurement of these antioxidants are scarce. We developed and validated a new HPLC method for simultaneous determination of these vitamers in human plasma that uses a novel column-switching approach.

Methods: The new method uses liquid–liquid extraction and isocratic separation with two monomeric C18 columns maintained at 35 and 4 °C coupled with ultraviolet–visible and fluorometric detection. This method could separate 14 vitamers and 3 internal standards within 27 min. No additional modifier was required; the mobile phase was acetonitrile–methanol (65:35 by volume), and the flow rate was 1 mL/min.

Results: For photodiode array detection, the detection limits (signal-to-noise ratio >3) were 0.02 mg/L for β-carotene, lutein, zeaxanthin, and canthaxanthin; 0.01 mg/L for all-trans-retinol, β-cryptoxanthin, α-carotene, and lycopene; and 0.1 mg/L for all tocopherols and tocotrienols. The detection limit was at least 25-fold lower (0.004 mg/L) when fluorometry was used for measurement of δ-, γ-, and α-tocotrienol and δ-tocopherol compared with ultraviolet detection. The recovery and imprecision of the assay were generally >90% and <10%, respectively.

Conclusions: This new method separates a wide range of fat-soluble antioxidant vitamins in human plasma, including six carotenoids, three isoforms of tocotrienols and tocopherols (δ-, γ-, and α-), and all-trans-retinol. The overall findings suggest that our method is faster, more sensitive, and more comprehensive than existing methods.
Identification of New Mutations of the HFE, Hepcidin, and Transferrin Receptor 2 Genes by Denaturing HPLC Analysis of Individuals with Biochemical Indications of Iron Overload
Authors: Biasiotto Giorgio , Belloli Silvana , Ruggeri Giuseppina , Zanella Isabella , Gerardi Gianmario , Corrado Marcella , Gobbi Elena , Albertini Alberto , Arosio Paolo
Published: December 2003

Background: Hereditary hemochromatosis is a recessive disorder characterized by iron accumulation in parenchymal cells, followed by organ damage and failure. The disorder is mainly attributable to the C282Y and H63D mutations in the HFE gene, but additional mutations in the HFE, transferrin receptor 2 (TfR2), and hepcidin genes have been reported. The copresence of mutations in different genes may explain the phenotypic heterogeneity of the disorder and its variable penetrance.

Methods: We used denaturing HPLC (DHPLC) for rapid DNA scanning of the HFE (exons 2, 3, and 4), hepcidin, and TfR2 (exons 2, 4 and 6) genes in a cohort of 657 individuals with altered indicators of iron status.

Results: DHPLC identification of C282Y and H63D HFE alleles was in perfect agreement with the restriction endonuclease assay. Fourteen DNA samples were heterozygous for the HFE S65C mutation. In addition, we found novel mutations: two in HFE (R66C in exon 2 and R224G in exon 4), one in the hepcidin gene (G71D), and one in TfR2 (V22I), plus several intronic or silent substitutions. Six of the seven individuals with hepcidin or TfR2 coding mutations carried also HFE C282Y or S65C mutations.

Conclusion: DHPLC is an efficient method for mutational screening for the genes involved in hereditary hemochromatosis and for the study of their copresence.
Effects of LDL, Cholesterol, and Their Oxidized Forms on the Precipitation Kinetics of Calcium Phosphates
Authors: Wang He-Ping , Feng Xiao-Jing , Gou Bao-Di , Zhang Tian-Lan , Xu Shan-Jin , Wang Kui
Published: December 2003

Background: LDL, cholesterol, and their oxidized forms are known cardiovascular risk factors and are often found in atherosclerotic lesions of various stages. Little is known, however, about whether they are directly involved in the formation of calcium phosphate compounds.

Methods: We used the pH-stat technique to follow the kinetics of calcium phosphate precipitation at pH 7.4, 37 °C, and ionic strength 0.150 mol/L, in the presence or absence of LDL, oxidized LDL, cholesterol, cholestane-3β,5α,6β-triol, and cholesteryl linoleate. The precipitates were characterized by x-ray diffraction, scanning and transmission electronic microscopy coupled with energy-dispersion x-ray analysis, and inductively coupled plasma atomic emission spectroscopy.

Results: Under the experimental conditions, LDL (14.8 and 43.1 mg/L protein) had no significant effect on the precipitation kinetics. Oxidized LDL (14.8 and 43.1 mg/L protein) prolonged the nucleation phase and diminished the amount of total precipitate, and both the extent of oxidation and the concentration of the protein affected the kinetics. Cholesterol microcrystals (71.4 and 143 mg/L) made the nucleation phase shorter (300 min vs 390 min for the control), and the precipitated particles had an organic core and a shell composed of calcium phosphates. l-α-Phosphatidylcholine vesicles (143 mg/L), cholesterol (71.4 mg/L)/phospholipid (143 mg/L) mixed vesicles, cholesteryl linoleate (143 mg/L), and cholestane-3β,5α,6β-triol (71.4 mg/L) prolonged the nucleation phase.

Conclusions: LDL is not involved directly in the precipitation of calcium phosphates. Oxidized LDL inhibits both nucleation and crystal growth, possibly by attracting calcium ions in the solution and thus reducing supersaturation. Cholesterol microcrystals serve as seeds for the precipitation of hydroxyapatite, whereas l-α-phosphatidylcholine, cholesteryl linoleate, and cholestane-3β,5α,6β-triol exhibit inhibitive effects on the nucleation of calcium phosphates.
Alcohol Use Disorders and Risk Factor Interactions for Adolescent Suicidal Ideation and Attempts
Authors: Kelly Thomas M. , Lynch Kevin G. , Donovan John E. , Clark Duncan B.
Published: December 2003

Four hundred eighty‐two adolescents who were diagnosed with at least one mental disorder were studied to determine the predictors of suicidal ideation and suicide attempts. Major depression was predictive of suicidal ideation and suicide attempts for both genders. Chronic stress was found predictive of male suicidal ideation, while low self‐esteem and high family dysfunction were found to be predictive of suicidal ideation in females. Statistical trends suggest that females with comorbid alcohol use/conduct disorder were approximately three times more likely to have attempted suicide than those with only one of these conditions. Clinicians working with adolescents should be aware that, while depression remains the number one clinical risk for suicidal behavior, risk factors for suicidal ideation may be different than those for attempted suicide and may vary by gender.
Risk Factors Associated with Overdose Among Bahraini Youth
Authors: Al Ansari Ahmed M. , Hamadeh Randah R. , Matar Ali M. , Marhoon Huda , Buzaboon Bana Y. , Raees Ahmed G.
Published: December 2003

The aim of this study was to identify the risk factors of overdose among Bahraini youth (15–24 years). These factors included psychiatric disorders, family pathology, and psychosocial stress. All suicide attempters in the country during an 18‐month period (N = 100) were identified prospectively. One hospital‐matched control was selected for each case. Both cases and controls underwent a semistructured personal interview in the two state general hospitals. A matched pair analysis was done, as well as computation of McNemar's continuity corrected chi‐square test, odds ratio, and the 95% confidence interval of the odds ratio. The overdose attempter was more likely than the control to be unemployed, a member of a non‐intact family, having a mother whose education was high school or above, not having a friend, involved in a boy/girlfriend relationship, and a cigarette smoker. More students among attempters had failed an examination in the past year than matched controls. Father's education, social class, death of father, recent row with a friend, use of drugs and alcohol, relationship with teachers, recent mobility, financial difficulties, and legal problems were similar in both groups. Stresses generated from living in a non‐intact family, interpersonal relationships mainly with the opposite sex, unemployment, and school performance came out as the main risk factors. The association of previously identified risk factors such as depression, aggressive behavior, and use of drug and alcohol was low among attempters. While the results of this study are consistent with the present view that suicidal behaviors are multifactorial in origin, the magnitude and effect of each factor are culturally determined.
Differences in Nonfatal Suicide Behaviors among Mexican and European American Middle School Children
Authors: Tortolero Susan R. , Roberts Robert E.
Published: December 2003

This report describes ethnic and gender differences in suicide ideation among two large samples of middle school students in New Mexico (n= 2,140) and Texas (n= 1,302). Students completed a self‐administered questionnaire on suicide ideation and psychosocial risk factors. Mexican Americans in both samples reported significantly higher prevalence of suicide ideation than did their European American counterparts. Mexican Americans were 1.8 times more likely to have high suicide ideation than European Americans. The suicide ideation risk for Mexican Americans remained unchanged in both samples after adjusting for gender, age, family structure, depression, low social support, and self‐esteem. This study indicates that ethnicity plays an important role in suicidal ideation, but the mechanism remains unclear.