bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Toxicity With Gefitinib, Capecitabine, and Radiation Therapy in Pancreatic and Rectal Cancer: Phase I Trial Results
Authors: Czito Brian G. , Willett Christopher G. , Bendell Johanna C. , Morse Michael A. , Tyler Douglas S. , Fernando Nishan H. , Mantyh Christopher R. , Blobe Gerard C. , Honeycutt Wanda , Yu Daohai , Clary Bryan M. , Pappas Theodore N. , Ludwig Kirk A. , Hurwitz Herbert I. 
Published: January 2006

Purpose Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. Patients and Methods Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. Results Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. Conclusion The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.
Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Authors: Ajani Jaffer A. , Lee Fa-Chyi , Singh Deepti A. , Haller Daniel G. , Lenz Heinz-Josef , Benson Al B. , Yanagihara Ronald , Phan Alexandria T. , Yao James C. , Strumberg Dirk 
Published: January 2006

Purpose S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination. Methods Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of ≥ 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed. Results All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death. Conclusion S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.
The V-type H+ ATPase: molecular structure and function,physiological roles and regulation
Authors: Beyenbach Klaus W. , Wieczorek Helmut 
Published: January 2006

SUMMARYIt was nearly 30 years before the V-type H+ ATPase was admitted to the small circle of bona fide transport ATPases alongside F-type and P-type ATPases. The V-type H+ ATPase is an ATP-driven enzyme that transforms the energy of ATP hydrolysis to electrochemical potential differences of protons across diverse biological membranes via the primary active transport of H+. In turn, the transmembrane electrochemical potential of H+ is used to drive a variety of (i)secondary active transport systems via H+-dependent symporters and antiporters and (ii) channel-mediated transport systems. For example, expression of Cl- channels or transporters next to the V-type H+ ATPase in vacuoles of plants and fungi and in lysosomes of animals brings about the acidification of the endosomal compartment, and the expression of the H+/neurotransmitter antiporter next to the V-type H+ ATPase concentrates neurotransmitters in synaptic vesicles.First found in association with endosomal membranes, the V-type H+ ATPase is now also found in increasing examples of plasma membranes where the proton pump energizes transport across cell membranes and entire epithelia. The molecular details reveal up to 14 protein subunits arranged in (i) a cytoplasmic V1 complex, which mediates the hydrolysis of ATP, and (ii) a membrane-embedded V0 complex, which translocates H+ across the membrane. Clever experiments have revealed the V-type H+ ATPase as a molecular motor akin to F-type ATPases. The hydrolysis of ATP turns a rotor consisting largely of one copy of subunits D and F of the V1 complex and a ring of six or more copies of subunit c of the V0 complex. The rotation of the ring is thought to deliver H+ from the cytoplasmic to the endosomal or extracellular side of the membrane, probably via channels formed by subunit a. The reversible dissociation of V1 and V0complexes is one mechanism of physiological regulation that appears to be widely conserved from yeast to animal cells. Other mechanisms, such as subunit-subunit interactions or interactions of the V-type H+ATPase with other proteins that serve physiological regulation, remain to be explored. Some diseases can now be attributed to genetic alterations of specific subunits of the V-type H+ ATPase.
Effects of larval nutrition on the endocrinology of mosquito egg development
Authors: Telang Aparna , Li Yiping , Noriega Fernando G. , Brown Mark R. 
Published: January 2006

SUMMARY
Reproduction by female mosquitoes is dependent on energy resources but modulated by hormones. Our study focused on blood-meal-dependent, anautogenous Aedes aegypti and autogenous Ochlerotatus atropalpus that rely on larval-derived nutrient stores to develop eggs. To determine how larval nutrition affects the endocrinology of egg development in these females, we manipulated the quantity of larval food and measured in vitro production of juvenile hormone (JH) by corpora allata (CA) and ecdysteroids by ovaries. Newly emerged A. aegypti contain lower larval-derived protein reserves, and their CA produce high amounts of JH, in comparison with similarly staged Oc. atropalpus. Ecdysteroid production was initiated in newly emerged Oc. atropalpus females,which have higher protein reserves and which develop eggs without a blood meal, which is required by A. aegypti females to complete egg development.
Dynamics of the aerial maneuvers of spinner dolphins
Authors: Fish Frank E. , Nicastro Anthony J. , Weihs Daniel 
Published: January 2006

SUMMARYThe spinner dolphin (Stenella longirostris) performs spectacular leaps from the water while rotating around its longitudinal axis up to seven times. Although twisting of the body while airborne has been proposed as the mechanism to effect the spin, the morphology of the dolphin precludes this mechanism for the spinning maneuver. A mathematical model was developed that demonstrates that angular momentum to induce the spin was generated underwater, prior to the leap. Subsurface corkscrewing motion represents a balance between drive torques generated by the flukes and by hydrodynamic forces at the pectoral fins, and resistive torques, induced by the drag forces acting on the rotating control surfaces. As the dolphin leaps clear of the water, this balance is no longer maintained as the density of the air is essentially negligible, and a net drive torque remains, which permits the dolphin's rotation speed to increase by as much as a factor of three for a typical specimen. The model indicates that the high rotation rates and orientation of the dolphin's body during re-entry into the water could produce enough force to hydrodynamically dislodge unwanted remoras.
Temperature sensitivities of cytosolic malate dehydrogenases from native and invasive species of marine mussels (genusMytilus):sequence-function linkages and correlations with biogeographic distribution
Authors: Fields Peter A. , Rudomin Emily L. , Somero George N. 
Published: January 2006

SUMMARYThe blue mussel Mytilus galloprovincialis, a native of the Mediterranean Sea, has invaded the west coast of North America in the past century, displacing the native blue mussel, Mytilus trossulus, from most of its former habitats in central and southern California. The invasive success of M. galloprovincialis is conjectured to be due, in part, to physiological adaptations that enable it to outperform M. trossulusat high temperatures. We have examined the structure and function of the enzyme cytosolic malate dehydrogenase (cMDH) from these species, as well as from the more distantly related ribbed mussel, Mytilus californianus,to characterize the effects of temperature on kinetic properties thought to exhibit thermal adaptation. The M. trossulus cMDH ortholog differs from the other cMDHs in a direction consistent with cold adaptation, as evidenced by a higher and more temperature-sensitive Michaelis-Menten constant for the cofactor NADH (KmNADH). This difference results from minor changes in sequence: the M. trossulus ortholog differs from the M. galloprovincialis ortholog by only two substitutions in the 334 amino acid monomer, and the M. californianusand M. trossulus orthologs differ by five substitutions. In each case, only one of these substitutions is non-conservative. To test the effects of individual substitutions on kinetic properties, we used site-directed mutagenesis to create recombinant cMDHs. Recombinant wild-type M. trossulus cMDH (rWT) has high KmNADHcompared with mutants incorporating the non-conservative substitutions found in M. californianus and M. galloprovincialis - V114H and V114N, respectively - demonstrating that these mutations are responsible for the differences found in substrate affinity. Turnover number(kcat) is also higher in rWT compared with the two mutants, consistent with cold adaptation in the M. trossulusortholog. Conversely, rWT and V114H appear more thermostable than V114N. Based on a comparison of KmNADH and kcat values among the orthologs, we propose that immersion temperatures are of greater selective importance in adapting kinetic properties than the more extreme temperatures that occur during emersion. The relative warm adaptation of M. galloprovincialis cMDH may be one of a suite of physiological characters that enhance the competitive ability of this invasive species in warm habitats.
Perturbation of the activity of a single identified neuron affects long-term memory formation in a molluscan semi-intact preparation
Authors: Lowe M. R. , Spencer G. E. 
Published: January 2006

SUMMARYThe aim of this study was to investigate the neural basis of operant conditioning in a semi-intact preparation of the pond snail, Lymnaea stagnalis. Lymnaea learns, via operant conditioning, to reduce its aerial respiratory behaviour in response to an aversive tactile stimulus to its open pneumostome. Here we report the successful conditioning of naïve semi-intact preparations to show `learning in the dish' and long-term memory that persists for at least 18 h. The neurons that generate this behaviour are readily identifiable and, for the first time, we have recorded from a neuron during a training paradigm that leads to long-term memory formation in the same preparation. Specifically, we recorded from the respiratory neuron Right Pedal Dorsal 1 (RPeD1), which is part of the respiratory central pattern generator and initiates the aerial respiratory behaviour. Previous studies have shown that long-term memory of this behaviour results in reduced RPeD1 activity. In the present study, we demonstrate that preventing RPeD1 impulse activity between training sessions reduces the number of sessions needed to produce long-term memory in our semi-intact preparation.
Microtubule-dependent relocation of branchial V-H+-ATPase to the basolateral membrane in the Pacific spiny dogfish (Squalus acanthias): a role in base secretion
Authors: Tresguerres Martin , Parks Scott K. , Katoh Fumi , Goss Greg G. 
Published: January 2006

SUMMARY
We have previously shown that continuous intravenous infusion of NaHCO3 for 24 h (∼1000 μmol kg-1 h-1)results in the relocation of V-H+-ATPase from the cytoplasm to the basolateral membrane in the gills of the Pacific dogfish. To further investigate this putative base-secretive process we performed similar experiments with the addition of colchicine, an inhibitor of cytoskeleton-dependent cellular trafficking processes. Blood pH and plasma total CO2 were significantly higher in the colchicines-treated,HCO3--infused fish compared with fish infused with HCO3- alone. The effect of colchicine was highest after 24 h of infusion (8.33±0.06 vs 8.02±0.03 pH units,15.72±3.29 vs 6.74±1.34 mmol CO2l-1, N=5). Immunohistochemistry and western blotting confirmed that colchicine blocked the transit of V-H+-ATPase to the basolateral membrane. Furthermore, western blotting analyses from whole gill and cell membrane samples suggest that the short-term (6 h) response to alkaline stress consists of relocation of V-H+-ATPases already present in the cell to the basolateral membrane, while in the longer term (24 h) there is both relocation of preexistent enzyme and upregulation in the synthesis of new units. Our results strongly suggest that cellular relocation of V-H+-ATPase is necessary for enhanced HCO3- secretion across the gills of the Pacific dogfish.
Effects of limb mass distribution on mechanical power outputs during quadrupedalism
Authors: Raichlen David A. 
Published: January 2006

SUMMARYMany researchers have suggested that cursorial mammals concentrate limb muscle mass proximally to reduce energy costs during locomotion. Although supported by experiments where mass is added to an individual's limbs, mammals with naturally occurring distally heavy limbs such as primates have similar energy costs compared with other mammals. This study presents a new hypothesis to explain how animals with distally heavy limbs maintain low energy costs. Since distal mass should increase energy costs due to higher amounts of muscular power outputs, this hypothesis is based on the divergent effects of stride frequency on internal and external power outputs (the power output to move the limbs and the body center of mass, respectively). The use of low stride frequencies reduces limb velocities and therefore decreases internal power, while associated long strides increase the vertical displacement of the body center of mass and therefore increase external power. Total power (the sum of internal and external power) may therefore not differ among mammals with different limb mass distributions. To test this hypothesis, I examined a sample of infant baboons (Papio cynocephalus) during ontogeny and compared them with more cursorial mammals. Limb mass distribution changes with age (from distal to more proximally concentrated) in baboons, and the infants used shorter strides and higher stride frequencies when limb mass was most proximally concentrated. Compared with non-primates who have more proximally concentrated limb mass, the infants used longer strides and lower stride frequencies. Relatively low internal power was associated with low stride frequencies in both the intra- and inter-specific samples. However, only in the inter-specific comparison were relatively long strides associated with high external power outputs. In both the intra-specific and the inter-specific samples, total power did not differ between groups who differed in limb mass distribution. The results of this study suggest that a trade-off mechanism is available to quadrupeds with distally heavy limbs allowing them to maintain similar total power outputs (and likely similar energy costs) compared with mammals with more proximally concentrated limb mass.
The relationship between 3-D kinematics and gliding performance in the southern flying squirrel,Glaucomys volans
Authors: Bishop Kristin L. 
Published: January 2006

SUMMARYGliding is the simplest form of flight, yet relatively little is known about its mechanics in animals. The goal of this study was to describe the body position and performance of a gliding mammal and to identify correlates between kinematics and aerodynamic performance. To do this, I used a pair of high-speed digital cameras to record a portion of the middle of glides by southern flying squirrels, Glaucomys volans. The squirrels launched from a height of 4 m and landed on a vertical pole. Reflective markers were applied to anatomical landmarks and the 3-D coordinates of these points were computed to describe the kinematics of the glides. From these data I estimated the lift and drag generated during the glide, and correlated these variables with gliding performance as measured by glide angle, glide speed and stability. In the majority of the glide sequences the squirrels accelerated in the downward direction and accelerated horizontally forward as they moved through the calibrated volume in the middle of the glide trajectory, rather than exhibiting a steady glide in which the body weight is balanced by the resultant aerodynamic force. Compared to human engineered airfoils, the angles of attack used by the squirrels were unexpectedly high, ranging from 35.4°to 53.5°, far above the angle of attack at which an aircraft wing would typically stall. As expected based on aerodynamic theory, there was a negative correlation between angle of attack and lift coefficient, indicating that the wings are stalled, and a positive correlation between angle of attack and drag coefficient. Also as expected, there was a negative correlation between lift-to-drag ratio and angle of attack, as increasing angle of attack produced both less lift and more drag. Within glides, there was a strong correlation between nose-down pitching rotations and limb movements that tended to increase the angle of attack of the wing membrane, suggesting that the animals actively control their pitch by moving their limbs. The squirrels used much steeper glide angles than those reported for other gliding animals, ranging from 40.4° to 57.4°. It is likely that this is because they did not launch from a great enough height to reach their minimum glide angle. In some trials the glide angle increased over the captured portion of the glide,whereas in others it decreased, and the magnitude of the changes varied substantially, rendering it difficult to ascertain which portion of the glide trajectory was represented. Decreases in glide angle were strongly correlated with increases in lift coefficient, but were uncorrelated with drag coefficient.
Hagfish slime ecomechanics: testing the gill-clogging hypothesis
Authors: Lim Jeanette , Fudge Douglas S. , Levy Nimrod , Gosline John M. 
Published: January 2006

SUMMARY
Hagfish are able to produce substantial amounts of slime when harassed, but the precise ecological function of the slime is unclear. One possibility is that the slime acts as a defence against gill-breathing predators, whose gills may become entangled with the slime's mixture of mucins and fibrous threads during an attack. We previously demonstrated that hagfish slime does not bind water tightly, but instead behaves like a fine sieve that slows water down via viscous entrainment. These properties are consistent with the gill-clogging hypothesis, which we tested here by quantifying the effects of hagfish slime on water flow through an artificial gill model and real fish gills. Our results indicate that the slime is capable of clogging gills and increasing the resistance that they present to the flow of water. We also characterized the behaviour of slime release from live hagfish and the effect of convective mixing on the formation of slime in vitro. Our observations show that exudate is locally released from the slime glands as a coherent jet and that hagfish do not appear to use their slime as a protective envelope. We found that convective mixing between the exudate and seawater is necessary for proper slime formation, but excessive mixing leads to the slime's collapse. We suggest that the loose binding of water by the slime may be an optimal solution to the problem of delivering an expanding jet of flow-inhibiting material to the gills of would-be predators.
Use of RNA Fluorescence In Situ Hybridization in the Prenatal Molecular Diagnosis of Myotonic Dystrophy Type I
Authors: Bonifazi Emanuela , Gullotta Francesca , Vallo Laura , Iraci Raniero , Nardone Anna Maria , Brunetti Ercole , Botta Annalisa , Novelli Giuseppe 
Published: January 2006

Abstract
Background: Myotonic dystrophy type 1 (DM1; OMIM #160900) is an autosomal-dominant genetic disorder with multisystemic clinical features associated with a CTG expansion in the 3′ untranslated region of the DMPK gene on chromosome 19q13.3. A long-PCR protocol to detect the DM1 expansion is rapid, sensitive, and accurate, but interpretative limitations can occur when the expansion size exceeds the PCR amplification range and in cases of somatic mosaicism.
Methods: To overcome these problems, we used RNA fluorescence in situ hybridization (RNA-FISH) to study cultured cells derived from chorionic villus samples (CVS) with the DM1 mutation. The RNA-FISH method is designed to detect the distinctive DM1 cellular phenotype, characterized by the presence of nuclei with focal ribonuclear inclusions (foci) containing the DMPK expanded transcripts. We analyzed 6 CVS from DM1-predicted pregnancies and 6 CVS from DM1-negative pregnancies.
Results: In 4 DM1-predicted fetuses with a CTG expansion &gt;200 CTG, varying numbers of ribonuclear inclusions were clearly visible in all cells. One case with a somatic mosaicism for the DMPK mutation showed 15% of cells with no nuclear foci. No nuclear signals were detected in all controls examined (n = 6) and in 1 DM1-positive sample with a CTG expansion &lt;100 copies.
Conclusion: Nuclear foci, and therefore the DM1 mutation they are caused by, can be detected efficiently on interphase nuclei of trophoblast cells with RNA-FISH when the CTG expansion is &gt;200 copies.