bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab initio modeling of small proteins by iterative TASSER simulations
Authors: Wu Sitao , Skolnick Jeffrey , Zhang Yang
Published: May 2007

Background

Predicting 3-dimensional protein structures from amino-acid sequences is an important unsolved problem in computational structural biology. The problem becomes relatively easier if close homologous proteins have been solved, as high-resolution models can be built by aligning target sequences to the solved homologous structures. However, for sequences without similar folds in the Protein Data Bank (PDB) library, the models have to be predicted from scratch. Progress in the ab initio structure modeling is slow. The aim of this study was to extend the TASSER (threading/assembly/refinement) method for the ab initio modeling and examine systemically its ability to fold small single-domain proteins.

Results

We developed I-TASSER by iteratively implementing the TASSER method, which is used in the folding test of three benchmarks of small proteins. First, data on 16 small proteins (< 90 residues) were used to generate I-TASSER models, which had an average Cα-root mean square deviation (RMSD) of 3.8Å, with 6 of them having a Cα-RMSD < 2.5Å. The overall result was comparable with the all-atomic ROSETTA simulation, but the central processing unit (CPU) time by I-TASSER was much shorter (150 CPU days vs. 5 CPU hours). Second, data on 20 small proteins (< 120 residues) were used. I-TASSER folded four of them with a Cα-RMSD < 2.5Å. The average Cα-RMSD of the I-TASSER models was 3.9Å, whereas it was 5.9Å using TOUCHSTONE-II software. Finally, 20 non-homologous small proteins (< 120 residues) were taken from the PDB library. An average Cα-RMSD of 3.9Å was obtained for the third benchmark, with seven cases having a Cα-RMSD < 2.5Å.

Conclusion

Our simulation results show that I-TASSER can consistently predict the correct folds and sometimes high-resolution models for small single-domain proteins. Compared with other ab initio modeling methods such as ROSETTA and TOUCHSTONE II, the average performance of I-TASSER is either much better or is similar within a lower computational time. These data, together with the significant performance of automated I-TASSER server (the Zhang-Server) in the 'free modeling' section of the recent Critical Assessment of Structure Prediction (CASP)7 experiment, demonstrate new progresses in automated ab initio model generation. The I-TASSER server is freely available for academic users http://zhang.bioinformatics.ku.edu/I-TASSER.
Expression stability of commonly used reference genes in canine articular connective tissues
Authors: Ayers Duncan , Clements Dylan N , Salway Fiona , Day Philip JR
Published: May 2007

Background

The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS).

Results

The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were RPL13A and YWHAZ (M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were RPL13A and SDHA (M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were B2M and TBP (M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were SDHA and YWHAZ (K6) or SDHA and HMBS (DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression.

Conclusion

The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.
Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report
Authors: Lapadula Giuseppe , Izzo Ilaria , Costarelli Silvia , Cologni Giuliana , Bercich Luisa , Casari Salvatore , Gambarotti Marco , Torti Carlo
Published: May 2007

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage.
Prospective Multicentric Randomized Study Comparing Periareolar and Peritumoral Injection of Radiotracer and Blue Dye for the Detection of Sentinel Lymph Node in Breast Sparing Procedures: FRANSENODE Trial
Authors: Rodier Jean-François , Velten Michel , Wilt Marc , Martel Pierre , Ferron Gwanaël , Vaini-Elies Véronique , Mignotte Hervé , Brémond Alain , Classe Jean-Marc , Dravet François , Routiot Thierry , de Lara Christine Tunon , Avril Antoine , Lorimier Gérard , Fondrinier Eric , Houvenaeghel Gilles , Avigdor Sandrine
Published: May 2007

Purpose

To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer.

Patients and Methods

A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients.

Results

The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001).

Conclusion

This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.
Managing Older Patients With Colorectal Cancer
Authors: Sanoff Hanna Kelly , Bleiberg Harry , Goldberg Richard M.
Published: May 2007

Colorectal cancer (CRC) is predominantly a disease of older persons, and our population is aging. Physicians and their older patients commonly face the dilemma of whether or not to give/receive systemic chemotherapy for CRC. Evidence supports the safety and efficacy of systemic chemotherapy in fit older patients motivated enough to enroll onto clinical trials. Conversely, frail older patients are more likely to suffer adverse outcomes when faced with stressors and may not benefit from chemotherapy. However, the majority of patients are neither fit nor frail, and current evidence is insufficient to either quantify or qualify the benefit of chemotherapy for this intermediate group of patients. Thus, treatment decisions must be individualized based on each older person's physical state (eg, their function and degree of comorbidity) and values. Despite a growing body of data, a great deal of work is still needed to establish optimal strategies to care for patients diagnosed with cancer later in life.
Surgical Management of Oncogeriatric Patients
Authors: Audisio Riccardo A. , Zbar Andrew P. , Jaklitsch Michael T.
Published: May 2007

Major changes are taking place at a great pace in modern medicine, and surgical oncologists are at the forefront when new skills are to be tested and implemented. Perhaps the most significant change we are facing relates to the aging of our population, with most solid tumors presenting at age 70 years (± 5 years). The demographics and epidemiological details are covered in the appropriate sections of this special issue, but it is important to realize how such a shift influences our day-to-day practice. These principally are occurring in improved anesthetic care, minimally invasive surgery, nonoperative therapies, risk assessment, and quality-of-life estimates.
Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients
Authors: Estey Elihu
Published: May 2007

The median age of patients with acute myeloid leukemia (AML) is 65 to 70 years. The majority of older patients with AML probably do not receive specific treatment, and those who receive standard regimens have a median survival time of less than 1 year. This suggests that, in general, older patients should receive investigational therapy; however, factors other than age influence survival after administration of standard treatment and need to be accounted for when making treatment recommendations. In some cases where investigational therapy is unavailable, palliative care may be the best option. Like AML, myelodysplastic syndrome (MDS) is a disease of the elderly. It is divided into higher and lower risk groups. The natural history of high-risk MDS (eg, > 10% marrow blasts) bears more resemblance to that of AML than to that of an indolent disorder; accordingly, similar therapeutic considerations apply. The more benign natural history of lower risk MDS leads to consideration of reduction in transfusion needs and improvement in quality of life as primary goals of therapy. Lenalidomide, azacitidine, and decitabine, each recently approved by the US Food and Drug Administration, are useful in achieving these objectives.
A Practical Approach to Geriatric Assessment in Oncology
Authors: Rodin Miriam B. , Mohile Supriya G.
Published: May 2007

More than half of new cancers are diagnosed in elderly patients, but data from randomized clinical trials do not represent the elderly population. Comprehensive geriatric assessment (CGA) can contribute valuable information to oncologists for risk stratification of elderly cancer patients. Functional impairments, frailty markers, cognitive impairments, and physical disabilities increase the risk for adverse outcomes during cancer treatment. Evidence is accumulating that selected elderly cancer patients benefit from CGA and geriatric interventions. However, perceived barriers to CGA include time, familiarity, cost, and lack of a well-defined procedure to interpret and apply the information. We present a model for rapid selection of elderly who would benefit from CGA using screening tools such as the Vulnerable Elders-13 Survey. We also define important geriatric functional risk factors, including mobility limitation, frailty, and dementia, and demonstrate how brief screening tests can make use of data realistically available to clinical oncologists to determine a stage of aging. Summary tables and a decision tree demonstrate how these data can be compiled to determine the risk for toxicities and to anticipate ancillary support needs.
Lung Cancer in the Elderly
Authors: Gridelli Cesare , Langer Corey , Maione Paolo , Rossi Antonio , Schild Steven E.
Published: May 2007

Purpose

Elderly patients often have comorbidities and other characteristics that make the selection of treatment daunting.

Methods

We have reviewed the available evidence in the literature to gauge the results of therapy for elderly lung cancer patients.

Results

The beneficial results achieved with adjuvant chemotherapy in the general population with early non–small-cell lung cancer (NSCLC) cannot be automatically extrapolated to the elderly, who are at higher risk of toxicity. Retrospective analyses of combined chemoradiotherapy in locally advanced NSCLC patients suggest equivalent therapeutic benefit for younger and older patients, despite heightened toxicity. There have been no elderly-specific phase III trials for locally advanced NSCLC. For advanced NSCLC, on the basis of evidence-based data, single-agent chemotherapy remains the standard of care for nonselected elderly patients. However, retrospective analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with increased but acceptable toxicity for elderly patients. In limited-disease small-cell lung cancer (SCLC), sequential chemoradiotherapy is clearly less toxic compared with a standard concurrent approach, but our assessment of treatment is hindered by the absence of prospective elderly-specific trials. Although prophylactic cranial irradiation has emerged as a standard strategy, it should be omitted in patients with cognitive impairment. In extensive SCLC, etoposide in combination with either cisplatin or carboplatin has emerged as standard treatment; hematopoietic support may be necessary.

Conclusion

With the exception of advanced NSCLC, prospective elderly-specific studies are lacking. Available data suggest that outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally worse.
Senescence As an Anticancer Mechanism
Authors: Hornsby Peter J.
Published: May 2007

Senescence was originally described as a terminal nondividing state of normal human cells reached after many cell divisions in culture. The cause was shown to be shortening of telomeres, leading to telomere dysfunction and cell cycle arrest. Subsequently, a more rapid, nontelomere-dependent form of senescence, often termed stress-induced premature senescence, was described. Mostly importantly, it occurs in response to activated oncogene products. Oncogene-induced senescence has been shown to play a role in tumor suppression in vivo; it does not seem to involve changes in telomeres. A second phenomenon that plays a role in tumor suppression, which does involve progressive telomere shortening, is crisis, the state that cells reach when cell cycle checkpoints are impaired and cells can no longer respond to telomere shortening or oncogene activation by entering senescence. These two processes, oncogene-induced senescence and telomere-based crisis, exert powerful anticancer effects.
Multidisciplinary Approach to the Geriatric Oncology Patient
Authors: Terret Catherine , Zulian Gilbert B. , Naiem Arash , Albrand Gilles
Published: May 2007

Given the dramatic demographic shift observed in developed countries, the medical community, especially oncologists, geriatricians, and primary care providers, are confronted with the expanding challenge of the management of elderly people with cancer. Ageing is associated with the accumulation of multiple and various medical and social problems. With a prevalence comparable to that of other chronic conditions in this age group, such as diabetes or dementia, cancer holds a prominent place among diseases of the elderly. The care of elderly cancer patients is fundamentally interdisciplinary. Communication and collaboration between geriatricians/primary care providers and oncologists represent key features of effective care in geriatric oncology. The combination of the disease-oriented approach of oncologists and the patient-oriented approach of geriatricians is the most powerful way to better serve this specific population. The medical approach of elderly cancer patients should ideally be under the lead of geriatricians or primary care providers sensitive to geriatric issues. Oncologists should manage the biologic consequences of the interplay between cancer and ageing. Close collaboration between clinicians will help promote active dedicated clinical research and the development of guidelines on the management of elderly people with cancer.
Lymphoma in Older Patients
Authors: Thieblemont Catherine , Coiffier Bertrand
Published: May 2007

One half of patients newly diagnosed with lymphoma are older than 60 years and a significant proportion of them older than 80 years. Older patients treated for lymphoma may not tolerate the high-dose therapies used in younger patients, usually because of the presence of concomitant diseases. Diffuse large B-cell lymphoma represents more than 60% of all lymphomas seen in older patients. Clinical presentation and prognostic parameters are identical to those described in young patients. However, response rate is usually lower in elderly patients compared with young patients, even if the patients are treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. Therefore, event-free and overall survival rates are shorter in elderly patients, even if disease-free survival rates are not really shorter than in young patients. Rituximab added to the CHOP regimen has recently been shown to dramatically improve the survival of these older patients without increasing the toxicity of the treatment. Patients older than 80 years may also be treated with rituximab plus CHOP, except for those having severe organ failure secondary to other diseases. Very few of these older patients may benefit from a salvage treatment after relapse.
The Cancer Aging Interface: A Research Agenda
Authors: Cohen Harvey Jay
Published: May 2007

There are substantial knowledge gaps in our understanding of the relationships between cancer and aging. These include areas of basic biology, societal aspects, and clinical aspects. Recommendations for research agendas in each of these areas are offered. In addition, the need for training investigators to work at this interface is addressed.
Science of Cancer and Aging
Authors: Irminger-Finger Irmgard
Published: May 2007

This review provides an overview of a selection of the most pertinent molecular pathways that link cancer and aging and focuses on those where recent advances were most important. When organizing the bulk of information on this subject, I became aware of the fact that the most evident partition, namely, mechanisms that influence aging and mechanisms that influence cancer occurrence, is difficult to apply. Most mechanisms explaining the aging process are also those that influence carcinogenesis. Mechanisms that are described in tumor suppressor pathways are also contributors to the aging process. From an intuitive point of view, there are phenomena that have traditionally been contributed to aging others to cancer-inducing factors and they are presented herein.
Sailing the skies: the improbable aeronautical success of the pterosaurs
Authors: Wilkinson Matthew T.
Published: May 2007

Pterosaur wings bore a striking resemblance to sails, having a bony spar at the leading edge, formed by the forelimb and one enormously elongated digit,and an elastic wing membrane. Such simple wings would be expected to have performed badly due to excessive deformation, membrane flutter and poor control characteristics. Here I discuss how certain anatomical features,specifically a forewing membrane in the inner part of the wing and a system of fibres embedded in the distal part, may have countered these shortcomings. The forewing, supported by the unique pteroid bone, would have reduced the wings'geometric twist, and has been shown in wind tunnel tests to improve membrane stability at low angles of attack and dramatically increase the maximum lift coefficient at high angles of attack. The function of the fibres is poorly understood, but it is suggested that they improved membrane stability and optimised twist nearer the wingtips.
Aerodynamics of wing-assisted incline running in birds
Authors: Tobalske Bret W. , Dial Kenneth P.
Published: May 2007

Wing-assisted incline running (WAIR) is a form of locomotion in which a bird flaps its wings to aid its hindlimbs in climbing a slope. WAIR is used for escape in ground birds, and the ontogeny of this behavior in precocial birds has been suggested to represent a model analogous to transitional adaptive states during the evolution of powered avian flight. To begin to reveal the aerodynamics of flap-running, we used digital particle image velocimetry (DPIV) and measured air velocity, vorticity, circulation and added mass in the wake of chukar partridge Alectoris chukar as they engaged in WAIR (incline 65–85°; N=7 birds) and ascending flight(85°, N=2). To estimate lift and impulse, we coupled our DPIV data with three-dimensional wing kinematics from a companion study. The ontogeny of lift production was evaluated using three age classes: baby birds incapable of flight [6–8 days post hatching (d.p.h.)] and volant juveniles (25–28 days) and adults (45+ days). All three age classes of birds, including baby birds with partially emerged, symmetrical wing feathers,generated circulation with their wings and exhibited a wake structure that consisted of discrete vortex rings shed once per downstroke. Impulse of the vortex rings during WAIR was directed 45±5° relative to horizontal and 21±4° relative to the substrate. Absolute values of circulation in vortex cores and induced velocity increased with increasing age. Normalized circulation was similar among all ages in WAIR but 67% greater in adults during flight compared with flap-running. Estimated lift during WAIR was 6.6%of body weight in babies and between 63 and 86% of body weight in juveniles and adults. During flight, average lift was 110% of body weight. Our results reveal for the first time that lift from the wings, rather than wing inertia or profile drag, is primarily responsible for accelerating the body toward the substrate during WAIR, and that partially developed wings, not yet capable of flight, can produce useful lift during WAIR. We predict that neuromuscular control or power output, rather than external wing morphology, constrain the onset of flight ability during development in birds.
The scent of danger: arginine as an olfactory cue of reduced predation risk
Authors: Ferrer Ryan P. , Zimmer Richard K.
Published: May 2007

Animal perception of chemosensory cues is a function of ecological context. Larvae of the California newt (Taricha torosa), for example, exhibit predator-avoidance behavior in response to a chemical from cannibalistic adults. The poison tetrodotoxin (TTX), well known as an adult chemical defense, stimulates larval escape to refuges. Although they are cannibals,adult newts feed preferentially on worms (Eisenia rosea) over conspecific young. Hence, larval avoidance reactions to TTX are suppressed in the presence of odor from these alternative prey. The free amino acid,arginine, is abundant in fluids emitted by injured worms. Here, we demonstrate that arginine is a natural suppressant of TTX-stimulated larval escape behavior. Compared to a tapwater control, larvae initiated vigorous swimming in response to 10–7 mol l–1 TTX. This excitatory response was eliminated when larval nasal cavities were blocked with an inert gel, but not when gel was placed on the forehead (control). In additional trials, a binary mixture of arginine and 10–7 mol l–1 TTX failed to induce larval swimming. The inhibitory effect of arginine was, however, dose dependent. An arginine concentration as low as 0.3-times that of TTX was significantly suppressant. Further analysis showed that suppression by arginine of TTX-stimulated behavior was eliminated by altering the positively-charged guanidinium moiety, but not by modifying the carbon chain, carboxyl group, or amine group. These results are best explained by a mechanism of competitive inhibition between arginine and TTX for common, olfactory receptor binding sites. Although arginine alone has no impact on larval behavior, it nevertheless signals active adult predation on alternative prey, and hence, reduced cannibalism risk.
Larval programming of post-hatch muscle growth and activity in Atlantic salmon (Salmo salar)
Authors: Albokhadaim Ibrahim , Hammond Chrissy L. , Ashton Clare , Simbi Bigboy H. , Bayol Stephanie , Farrington Samantha , Stickland Neil
Published: May 2007

Larval muscle development in Atlantic salmon is known to be affected by temperature; however, the long term effects and possible mechanisms involved are less well understood. Therefore, the aim of this study was to evaluate the influence of egg incubation temperature on post-hatch muscle growth and fish activity.

Salmon eggs were incubated at either 10°C or 5°C from fertilization until hatching, then subsequently both groups were reared at 5°C. Fish from both groups were sampled at the eyed stage, 6 and 21 weeks after first feeding, for muscle cellularity analysis and immunocytochemistry. In addition,to try to establish a mechanism for altered growth, the activity of the fish was measured at 3, 6 and 21 weeks after first feeding.

Our results demonstrate that whereas fish incubated at 10°C grow faster, the fish incubated at 5°C show a more sustained period of muscle growth and by 21 weeks are significantly longer, heavier and have more muscle fibres than those fish incubated at a higher temperature. We also demonstrate that fish raised at 5°C show increased food seeking activity throughout development and that this may explain their sustained growth and muscle development.

These results taken together, demonstrate that egg incubation temperature up to hatching in salmon is critical for longer term muscle growth, twinned with increased activity. This is of interest to the aquaculture industry in term of the production of good quality fish protein.
Fightversusflight: physiological basis for temperature-dependent behavioral shifts in lizards
Authors: Herrel A. , James R. S. , Van Damme R.
Published: May 2007

Previous studies have demonstrated that a behavioral shift from flight to aggressive behavior occurs at low temperatures in some lizards. Our data for the agamid lizard Trapelus pallida demonstrate how the effect of temperature on whole organism performance traits such as sprint speed (much lower performance at lower temperature) and bite force (largely independent of temperature) may explain the shift from flight to fight behavior with decreasing temperature. Moreover, our data hint at the physiological basis for this effect as isolated muscle power output, twitch and tetanus time traits,relevant to sprinting, appear to be strongly temperature-dependent muscle properties. Maximal muscle force production, on the other hand, appears largely independent of temperature. Unexpectedly, differences in the physiological properties of jaw versus limb muscle were observed that enhance the ability of the jaw muscle to generate maximal force at all temperatures tested. Thus our data show how behavioral responses may be determined by the limitations set by temperature on physiological processes.
Molecular characterization of an epithelial Ca2+ channel-like gene from crayfishProcambarus clarkii
Authors: Gao Yongping , Wheatly Michele G.
Published: May 2007

This study describes the cloning, sequencing and functional characterization of an epithelial Ca2+ channel (ECaC)-like gene isolated from antennal gland (kidney) of the freshwater crayfish Procambarus clarkii. The full-length cDNA consisted of 2687 bp with an open reading frame of 2169 bp encoding a protein of 722 amino acids with a predicted molecular mass of 81.7 kDa. Crayfish ECaC had 76–78% identity at the mRNA level (80–82% amino acid identity) with published fish sequences and 56–62% identity at the mRNA level (52–60% amino acid identity) with mammalian ECaCs. Secondary structure of the crayfish ECaC closely resembled that of cloned ECaCs. Postmolt ECaC expression was exclusively restricted to epithelia associated with Ca2+ influx and was virtually undetectable in non-epithelial tissues (eggs, muscle). Compared with expression levels in hepatopancreas, expression in gill was 10-fold greater and expression was highest in antennal gland (15-fold greater than in hepatopancreas). Compared with baseline expression levels in intermolt stage,expression of ECaC in antennal gland increased 7.4- and 23.8-fold,respectively, in pre- and postmolt stages of the molting cycle. This increase was localized primarily in the labyrinth and nephridial canal, regions of the antennal gland associated with renal Ca2+ reabsorption. The ECaC in crayfish appears to be expressed in epithelia associated with unidirectional Ca2+ influx and relative expression is correlated with rate of Ca2+ influx.
Homing strategies of the Australian desert ant Melophorus bagotiI. Proportional path-integration takes the ant half-way home
Authors: Narendra Ajay
Published: May 2007

Highly evolved eusocial insects such as ants return from a food source to their nest by the shortest possible distance. This form of navigation, called path-integration, involves keeping track of the distance travelled and the angles steered on the outbound journey, which then aids in the computation of the shortest return distance. In featureless terrain, ants rely on the path integrator to travel the entire distance to return to the nest, whereas in landmark-rich habitats ants are guided by visual cues and in the absence of the visual cues homing ants rely on the path integrator to travel only an initial 10–60 cm of the homebound distance. The functioning of the path integrator in a habitat of intermediate landmark density is unknown. The findings reported here show that when the outward journey is on a familiar foraging area, and the inward journey is on an unfamiliar area, the Australian route-following desert ant Melophorus bagoti relies on the path integrator and consistently travels half the distance of the outward trip. However, when both the outward and inward trips are performed in plain and featureless channels, which blocks the distinct terrestrial visual cues, ants travel the entire distance accurately. A similar half-way abbreviation of the home vector occurs when the ant's outward trip is in an L-shaped channel and the homeward trip is over an open and unfamiliar region. The ecological significance of these new findings is discussed.
Homing strategies of the Australian desert antMelophorus bagotiII. Interaction of the path integrator with visual cue information
Authors: Narendra Ajay
Published: May 2007

Individually foraging ants are known to return to their nest by using path-integration and recording visual information present in the environment. The interaction between the path integrator and the information provided by the visual cues in an Australian desert ant are reported here. Ants were trained to travel in a 1-m wide and 20-m long corridor of cylinders. Homeward paths of trained ants were recorded in the presence and absence of vector information and route cues in both the familiar training field and in an unfamiliar test field. Homing ants used route cue information only in a familiar context. The route cues were not essential but served to reduce the deviation of the homing trajectory from the nest–feeder line. When displaced locally, homebound ants initially oriented towards the nest using distant cues and then headed in a direction intermediate between that dictated by the path integrator and the distant cues. If in the course of travel ants encountered the familiar path they adhered to it. If not, they travelled on average half the distance of the outbound journey and initiated a search directed towards the nest. Following the search, ants headed in a direction intermediate between that dictated by the route cues and the distant cues. In an unfamiliar context neither vector nor route cue information could steer a homing ant towards the nest. The dominance of distant cues, the importance of familiar context and the interaction between different navigation strategies are discussed here.
Tribute to P. L. Lutz: a message from the heart – why hypoxic bradycardia in fishes?
Authors: Farrell A. P.
Published: May 2007

The sensing and processing of hypoxic signals, the responses to these signals and the modulation of these responses by other physical and physiological factors are an immense topic filled with numerous novel and exciting discoveries. Nestled among these discoveries, and in contrast to mammals, is the unusual cardiac response of many fish to environmental hypoxia– a reflex slowing of heart rate. The afferent and efferent arms of this reflex have been characterised, but the benefits of the hypoxic bradycardia remain enigmatic since equivocal results have emerged from experiments examining the benefit to oxygen transfer across the gills. The main thesis developed here is that hypoxic bradycardia could afford a number of direct benefits to the fish heart, largely because the oxygen supply to the spongy myocardium is precarious (i.e. it is determined primarily by the partial pressure of oxygen in venous blood, PvO2) and,secondarily, because the fish heart has an unusual ability to produce large increases in cardiac stroke volume (VSH) that allow cardiac output to be maintained during hypoxic bradycardia. Among the putative benefits of hypoxic bradycardia is an increase in the diastolic residence time of blood in the lumen of the heart, which offers an advantage of increased time for diffusion, and improved cardiac contractility through the negative force–frequency effect. The increase in VSH will stretch the cardiac chambers, potentially reducing the diffusion distance for oxygen. Hypoxic bradycardia could also reduce cardiac oxygen demand by reducing cardiac dP/dt and cardiac power output, something that could be masked at cold temperature because of a reduced myocardial work load. While the presence of a coronary circulation in certain fishes decreases the reliance of the heart on PvO2, hypoxic bradycardia could still benefit oxygen delivery via an extended diastolic period during which peak coronary blood flow occurs. The notable absence of hypoxic bradycardia among fishes that breathe air during aquatic hypoxia and thereby raise their PvO2, opens the possibility that that the evolutionary loss of hypoxic bradycardia may have coincided with some forms of air breathing in fishes. Experiments are needed to test some of these possibilities. Ultimately, any potential benefit of hypoxic bradycardia must be placed in the proper context of myocardial oxygen supply and demand, and must consider the ability of the fish heart to support its routine cardiac power output through glycolysis.
Noninvasive Optical Detection of Bone Mineral
Authors: Kozloff Kenneth M , Weissleder Ralph , Mahmood Umar
Published: May 2007

FRFP binds to mineral at osteoblastic, osteoclastic, and quiescent surfaces, with accumulation likely modulated by vascular delivery. In vivo visualization and quantification of binding can be accomplished noninvasively in animal models through optical tomographic imaging.

Introduction: The development of near-infrared optical markers as reporters of bone metabolism will be useful for early diagnosis of disease. Bisphosphonates bind differentially to osteoblastic and osteoclastic surfaces depending on choice of side-chain and dose, and fluorescently tagged bisphosphonates provide a convenient way to visualize these sites. This study examines the ability of a fluorescently labeled pamidronate imaging probe to bind to regions of bone formation and resorption in vivo.

Materials and Methods: In vitro binding of a far-red fluorescent pamidronate (FRFP) to mineral was assessed using intact and demineralized dentine slices. In vivo, FRFP binding was studied in three models: developing neonatal mouse, bone healing after injury, and metastasis-induced osteolysis and fracture. 3D fluorescence molecular tomographic (FMT) imaging was used to visualize signal deep within the body.

Results: FRFP binding to bone depends on the quantity of mineral present and can be liberated from the bone during decalcification. In vivo, FRFP binds to surfaces of actively forming bone, as assessed by alkaline phosphatase staining, surfaces undergoing active resorption, as noted by scalloped bone border and presence of osteoclasts, and to quiescent surfaces not involved in formation or resorption. Binding is likely modulated by vascular delivery of the imaging agent to the exposed mineral surface and total quantity of surface exposed. FMT imaging is capable of visualizing regions of bone formation because of a large volume of labeled surface, but like radiolabeled bone scans, cannot discriminate pure osteolysis caused by metastasis.

Conclusions: FRFP may function as a local biomarker of bisphosphonate deposition to assess interplay between drug and cellular environment or may be combined with other imaging agents or fluorescent cells for the noninvasive assessment of local bone metabolism in vivo.
Aging Impairs IGF-I Receptor Activation and Induces Skeletal Resistance to IGF-I
Authors: Cao Jay J , Kurimoto Pamela , Boudignon Benjamin , Rosen Clifford , Lima Florence , Halloran Bernard P
Published: May 2007

IGF-I plays an important anabolic role in stimulating bone formation and maintaining bone mass. We show that the pro-proliferative, anti-apoptotic, and functional responses to IGF-I in bone and BMSCs decrease with aging. These changes are associated with impaired receptor activation and signal transduction through the MAPK and PI3K pathways.

Introduction: IGF-I is a potent anabolic agent having effects across diverse tissues and cell types. With aging, bone becomes resistant to the anabolic actions of IGF-I. To examine the effects of aging on bone responsiveness to IGF-I, we measured the pro-proliferative, anti-apoptotic, and functional responses of bone and bone marrow stromal cells (BMSCs) to IGF-I and evaluated IGF-I signal transduction in young, adult, and old mice.

Materials and Methods: Male C57BL/6 mice 6 wk (young), 6 mo (adult), and 24 mo (old) were treated with IGF-I for 2 wk using osmotic minipumps, and osteoblast proliferation (BrdU labeling) in vivo, and osteoprogenitor number (BMSC culture and calcium nodule formation) were measured. Proliferation, apoptosis, and expression of key osteoblast factors (alkaline phosphatase, collagen, osteocalcin, RANKL, osteoprotegerin (OPG), macrophage-colony stimulating factor [M-CSF]) and IGF-I signaling elements and their activation in IGF-I—treated cells were studied using QRT-PCR and Western blot analysis. Data were analyzed using ANOVA.

Results: Aging decreased the basal and IGF-I—stimulated number of BrdU-labeled osteoblasts and reduced the ability of IGF-I to stimulate osteoprogenitor formation (calcium nodule number) by 50%. The pro-proliferative and anti-apoptotic actions of IGF-I were blunted in cells from old animals. These changes were accompanied by age-related alterations in the ability of IGF-I to regulate alkaline phosphatase, collagen, osteocalcin, RANKL, OPG, and M-CSF expression. IGF-I binding was normal, but IGF-I receptor mRNA and protein expression was increased in aged animals by 2- and 10-fold, respectively. The age-related changes in proliferation, apoptosis, and function were accompanied by loss of IGF-I—induced signaling at the receptor level and at key regulatory sites along the MAPK (ERK1/2) and PI3K (AKT) pathways.

Conclusions: Our data show that aging is accompanied by loss of bone and BMSC/osteoblast responsiveness to IGF-I and that these changes are associated with resistance to IGF-I signaling that involve receptor activation and downstream signaling events.
Age-Related Changes in Trabecular Architecture Differ in Female and Male C57BL/6J Mice
Authors: Glatt Vaida , Canalis Ernesto , Stadmeyer Lisa , Bouxsein Mary L
Published: May 2007

We used μCT and histomorphometry to assess age-related changes in bone architecture in male and female C57BL/6J mice. Deterioration in vertebral and femoral trabecular microarchitecture begins early, continues throughout life, is more pronounced at the femoral metaphysis than in the vertebrae, and is greater in females than males.

Introduction: Despite widespread use of mice in the study of musculoskeletal disease, the age-related changes in murine bone structure and the relationship to whole body BMD changes are not well characterized. Thus, we assessed age-related changes in body composition, whole body BMD, and trabecular and cortical microarchitecture at axial and appendicular sites in mice.

Materials and Methods: Peripheral DXA was used to assess body composition and whole body BMD in vivo, and μCT and histomorphometry were used to measure trabecular and cortical architecture in excised femora, tibia, and vertebrae in male and female C57BL/6J mice at eight time-points between 1 and 20 mo of age (n = 6–9/group).

Results: Body weight and total body BMD increased with age in male and female, with a marked increase in body fat between 6 and 12 mo of age. In contrast, trabecular bone volume (BV/TV) was greatest at 6–8 wk of age and declined steadily thereafter, particularly in the metaphyseal region of long bones. Age-related declines in BV/TV were greater in female than male. Trabecular bone loss was characterized by a rapid decrease in trabecular number between 2 and 6 mo of age, and a more gradual decline thereafter, whereas trabecular thickness increased slowly over life. Cortical thickness increased markedly from 1 to 3 mo of age and was maintained or slightly decreased thereafter.

Conclusions: In C57BL/6J mice, despite increasing body weight and total body BMD, age-related declines in vertebral and distal femoral trabecular bone volume occur early and continue throughout life and are more pronounced in females than males. Awareness of these age-related changed in bone morphology are critical for interpreting the skeletal response to pharmacologic interventions or genetic manipulation in mice.
Determination of Twin Zygosity: A Comparison of DNA with Various Questionnaire Indices
Authors: Jackson Robert W. , Snieder Harold , Davis Harry , Treiber Frank A.
Published: May 2007

This study examined cross-validation and test-retest reliability of questions and questionnaire indices commonly used for twin zygosity classification. Mothers of 58 monozygotic (MZ) and 52 dizygotic (DZ) same sex twin pairs were interviewed by telephone to answer questions regarding the similarity of their twins (mean age = 14.6 ± 2.8 years). A logistic regression equation correctly classified 91% of both MZ and DZ twin pairs in our sample using 7 of the 12 zygosity questions. The internal consistency for the total questionnaire (Cronbach's alpha) was 0.88. The median two month temporal stability estimate for the individual questions was r = .56 and r = .79 for the test total. For the cross-validation, zygosity classification indices taken from 9 previous studies were applied to our sample and compared to classification according to DNA microsatellite analyses (agreement range = 44 to 100%). The accuracy of the classification indices was significantly lower than the original studies for 62% of the comparisons. If zygosity determination with DNA markers or blood group typing for all subjects is not feasible, rather than using classification indices based on other studies, an optimal classification scheme can be achieved by using a zygosity questionnaire of which the reliability and validity of the questions is established in a random subsample of the same twin cohort.
Height Discordance in Monozygotic Females is not Attributable to Discordant Inactivation of X-linked Stature Determining Genes
Authors: Healey S.C. , Kirk K.M. , Hyland V.J. , Munns C.F. , Henders A.K. , Batch J.A. , Heath A.C. , Martin N.G. , Glass I.A.
Published: May 2007

We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.
Twins, Chorionicity and Zygosity
Authors: Derom Robert , Bryan Elizabeth , Derom Catherine , Keith Louis , Vlietinck Robert
Published: May 2007

Accurate determination of zygosity and chorionicity is essential in all multiple maternities. The parents and the multiples themselves ask it. It is of medical importance and now considered as a prerequisite in several domains of twin research, especially when perinatal data are analysed. It helps the multiples and their parents and teachers to ascertain identity. The methods are briefly described and a plea is made to obstetricians and paediatricians to use them systematically at the time of birth.
Induction of Labour and Scheduled Cesarean Deliveries in Twin Pregnancies at the Port-Royal Maternity Hospital in Paris France
Authors: Papiernik Emile , Hessabi Madieh , Dubourdieu Corinne , Zeitlin Jennifer
Published: May 2007

The study is a critical analysis of the decisions to induce labour or schedule cesareans in the practice of a third level referral centre, with as outcome criterion the reduction of fetal death. 783 women pregnant with twins were included from 1.1.1993 to 31.12.1998, in three groups:originally booked, referred for care during pregnancy, or transferred from another institution. The results show that an important proportion of preterm deliveries result from a medical decision to induce labour or from a scheduled cesarean in the originally booked group with even higher proportions in groups of referred and transferred women. These results are discussed in relation to fetal death rates and causes. Deaths related to fetal growth restriction were not observed in women originally booked for care. The hospital bias has been discussed. The conclusion is that decisions to minimize fetal deaths in twin pregnancies increased preterm deliveries by medical decision.