bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for MEIS1 in MLL-fusion gene leukemia
Authors: Kumar Ashish R. , Li Quanzhi , Hudson Wendy A. , Chen Weili , Sam Thien , Yao Qing , Lund Erik A. , Wu Baolin , Kowal Branden J. , Kersey John H. 
Published: December 2008

Abstract
Leukemias with MLL rearrangements are characterized by high expression of the homeobox gene MEIS1. In these studies, we knocked down Meis1 expression by shRNA lentivirus transduction in murine Mll-AF9 leukemia cells. Meis1 knockdown resulted in decreased proliferation and survival of murine Mll-AF9 leukemia cells. We also observed reduced clonogenic capacity and increased monocytic differentiation. The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown. Gene expression profiling of cells transduced with Meis1 shRNA showed reduced expression of genes associated with cell cycle entry and progression. shRNA-mediated knockdown of MEIS1 in human MLL-fusion gene leukemia cell lines resulted in reduced cell growth. These results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry. Targeting MEIS1 may have therapeutic potential for treating leukemias expressing this transcription factor.
The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation
Authors: Banno Fumiaki , Chauhan Anil K. , Kokame Koichi , Yang Jin , Miyata Shigeki , Wagner Denisa D. , Miyata Toshiyuki 
Published: December 2008

AbstractADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor (VWF). We previously identified 2 types of mouse Adamts13 gene: the 129/Sv-strain Adamts13 gene encodes the long-form ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain Adamts13 gene encodes the short-form ADAMTS13 lacking the distal C-terminal domains. To assess the physiologic significance of the distal C-terminal domains of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice (Adamts13S/S) that carry the short-form ADAMTS13. Similar to wild-type 129/Sv mice (Adamts13L/L), Adamts13S/S did not have ultralarge VWF multimers in plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice (Adamts13−/−). However, in vitro thrombogenesis under flow at a shear rate of 5000 s−1 was accelerated in Adamts13S/S compared with Adamts13L/L. Both in vivo thrombus formation in ferric chloride–injured arterioles and thrombocytopenia induced by collagen plus epinephrine challenge were more dramatic in Adamts13S/S than in Adamts13L/L but less than in Adamts13−/−. These results suggested that the C-terminally truncated ADAMTS13 exhibited decreased activity in the cleavage of VWF under high shear rate. Role of the C-terminal domains may become increasingly important under prothrombotic conditions.
Chaperoning erythropoiesis
Authors: Weiss Mitchell J. , dos Santos Camila O. 
Published: December 2008

AbstractMultisubunit complexes containing molecular chaperones regulate protein production, stability, and degradation in virtually every cell type. We are beginning to recognize how generalized and tissue-specific chaperones regulate specialized aspects of erythropoiesis. For example, chaperones intersect with erythropoietin signaling pathways to protect erythroid precursors against apoptosis. Molecular chaperones also participate in hemoglobin synthesis, both directly and indirectly. Current knowledge in these areas only scratches the surface of what is to be learned. Improved understanding of how molecular chaperones regulate erythropoietic development and hemoglobin homeostasis should identify biochemical pathways amenable to pharmacologic manipulation in a variety of red blood cell disorders including thalassemia and other anemias associated with hemoglobin instability.
Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families
Authors: Thangudu Ratna R , Manoharan Malini , Srinivasan N , Cadet Frédéric , Sowdhamini R , Offmann Bernard 
Published: December 2008

Abstract

Background
Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue.

Results
Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues.

Conclusion
We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function.
Straight walking and turning on a slippery surface
Authors: Gruhn Matthias , Zehl Lyuba , Büschges Ansgar 
Published: December 2008

SUMMARYIn stick insects, walking is the result of the co-action of different pattern generators for the single legs and coordinating inter-leg influences. We have used a slippery surface setup to understand the role the local neuronal processing in the thoracic ganglia plays in the ability of the animal to show turning movements. To achieve this, we removed the influence of mechanical coupling through the ground by using the slippery surface and removed sensory input by the successive amputation of neighboring legs. We analyzed the walking pattern of the front, middle and hind legs of tethered animals mounted above the surface and compared the kinematics of the straight walking legs with those of the curve walking inside and outside legs. The walking pattern was monitored both electrically through tarsal contact measurement and optically by using synchronized high-speed video. The vectors of leg movement are presented for the intact and a reduced preparation. Animals showed the ability to walk in a coordinated fashion on the slippery surface. Upon change from straight to curve walking, the stride length for the inside legs shortens and the vector of movement of the inner legs changes to pull the animal into the curve, while the outer legs act to pull and push it into the turn. In the reduced two-leg and in the single-leg preparation the behavior of the legs remained largely unchanged in the behavioral contexts of straight walking or turning with only small changes in the extreme positions. This suggests that the single stepping legs perform given motor programs on the slippery surface in a fashion that is highly independent not only of mechanical coupling between but also of the presence of the other legs.
Localization and regulation of a facilitative urea transporter in the kidney of the red-eared slider turtle (Trachemys scripta elegans)
Authors: Uchiyama Minoru , Kikuchi Ryosuke , Konno Norifumi , Wakasugi Tatsuya , Matsuda Kouhei 
Published: December 2008

SUMMARYUrea is the major excretory end product of nitrogen metabolism in most chelonian reptiles. In the present study, we report the isolation of a 1632 base pair cDNA from turtle kidney with one open reading frame putatively encoding a 403-residue protein, the turtle urea transporter (turtle UT). The first cloned reptilian UT has high homology with UTs (facilitated urea transporters) cloned from vertebrates, and most closely resembles the UT-A subfamily. Injection of turtle UT cRNA into Xenopus oocytes induced a 6-fold increase in [14C]urea uptake that was inhibited by phloretin. The turtle UT mRNA expression and tissue distribution were examined by RT-PCR with total RNA from various tissues. Expression of turtle UT mRNA was restricted to the kidney, and no signal was detected in the other tissues,such as brain, heart, alimentary tract and urinary bladder. An approximately 58 kDa protein band was detected in membrane fractions of the kidney by western blot using an affinity-purified antibody that recognized turtle UT expressed in Xenopus oocytes. In an immunohistochemical study using the anti-turtle UT antibody, UT-immunopositive cells were observed along the distal tubule but not in the collecting duct. In turtles under dry conditions,plasma osmolality and urea concentration increased, and using semi-quantitative RT-PCR the UT mRNA expression level in the kidney was found to increase 2-fold compared with control. The present results, taken together,suggest that the turtle UT probably contributes to urea transport in the distal tubule segments of the kidney in response to hyperosmotic stress under dry conditions.
Caudal fin shape modulation and control during acceleration, braking and backing maneuvers in bluegill sunfish,Lepomis macrochirus
Authors: Flammang B. E. , Lauder G. V. 
Published: December 2008

SUMMARYEvolutionary patterns of intrinsic caudal musculature in ray-finned fishes show that fine control of the dorsal lobe of the tail evolved first, followed by the ability to control the ventral lobe. This progression of increasing differentiation of musculature suggests specialization of caudal muscle roles. Fine control of fin elements is probably responsible for the range of fin conformations observed during different maneuvering behaviors. Here, we examine the kinematics of the caudal fin and the motor activity of the intrinsic caudal musculature during kick-and-glide, braking and backing maneuvers, and compare these data with our previous work on the function of the caudal fin during steady swimming. Kick-and-glide maneuvers consisted of large-amplitude, rapid lateral excursion of the tail fin, followed by forward movement of the fish with the caudal fin rays adducted to reduce surface area and with the tail held in line with the body. Just before the kick, the flexors dorsalis and ventralis, hypochordal longitudinalis, infracarinalis and supracarinalis showed strong activity. During braking, the dorsal and ventral lobes of the tail moved in opposite directions, forming an `S'-shape,accompanied by strong activity in the interradialis muscles. During backing up, the ventral lobe initiated a dorsally directed wave along the distal edge of the caudal fin. The relative timing of the intrinsic caudal muscles varied between maneuvers, and their activation was independent of the activity of the red muscle of the axial myomeres in the caudal region. There was no coupling of muscle activity duration and electromyographic burst intensity in the intrinsic caudal muscles during maneuvers, as was observed in previous work on steady swimming. Principal-component analysis produced four components that cumulatively explained 73.6% of the variance and segregated kick-and-glide,braking and backing maneuvers from each other and from steady swimming. The activity patterns of the intrinsic caudal muscles during maneuvering suggest motor control independent from myotomal musculature, and specialization of individual muscles for specific kinematic roles.
Regional variation in parvalbumin isoform expression correlates with muscle performance in common carp (Cyprinus carpio)
Authors: Brownridge Philip , de Mello Luciane Vieira , Peters Mary , McLean Lynn , Claydon Amy , Cossins Andrew R. , Whitfield Phillip D. , Young Iain S. 
Published: December 2008

SUMMARYThe mechanical properties of the axial muscles vary along the length of a fish's body. This variation in performance correlates with the expression of certain muscle proteins. Parvalbumin (PARV) is an important calcium binding protein that helps modulate intracellular calcium levels which set the size and shape of the muscle calcium transient. It therefore has a central role in determining the functional properties of the muscle. Transcript data revealed eight specific isoforms of PARV in common carp (Cyprinus carpio)skeletal muscle which we classified as α1 and β1–7. This study is the first to show expression of all eight skeletal muscle PARV isoforms in carp at the protein level and relate regional differences in expression to performance. All of the PARV isoforms were characterised at the protein level using 2D-PAGE and tandem mass spectrometry. Comparison of carp muscle from different regions of the fish revealed a higher level of expression of PARV isoforms β4 and β5 in the anterior region, which was accompanied by an increase in the rate of relaxation. We postulate that changes in specific PARV isoform expression are an important part of the adaptive change in muscle mechanical properties in response to varying functional demands and environmental change.
Peak energy turnover in lactating European hares: the role of fat reserves
Authors: Valencak T. G. , Tataruch F. , Ruf T. 
Published: December 2008

SUMMARYEuropean hares (Lepus europaeus) in central Europe have high energetic costs of reproduction, mainly due to precocial, rapidly growing young that rely largely on energy-rich milk. Thus, hares in this climate build up large fat stores during winter that are then gradually depleted during the spring-to-autumn breeding season. We hypothesized that the diminishing fat stores of females over the breeding season might affect resource allocation,peak energy assimilation during lactation or the total investment in offspring. Therefore, we measured energy intake, milk quality and milk production throughout lactation in spring, summer and autumn in females raising (size-manipulated) litters with three young each, under a natural photoperiod but at buffered ambient temperatures inside our facility. Over the course of the breeding season, the amount of milk production remained constant, but the fat content of the milk decreased. Hence, total energy transfer to young decreased significantly in autumn. By using undecanoic acid as a tracer of body fat mobilization, we were able to show that milk fat partially originated from maternal fat stores, particularly in spring. The peak sustained energy assimilation rates of lactating females were significantly higher in autumn, due to increased rates of food intake. We conclude that fat stores allow female hares to downregulate energy intake and expenditure early in the breeding season, whereas late breeding forces them to reach peak energy intake levels. Accordingly, we suggest that in hares, peak energy turnover during lactation varies with the availability of fat reserves. Limits to the sustained metabolic rate serve as variable constraints on reproductive investment. Thus, there might be a trade-off in energetic costs to mothers rearing early versus late litters in the year.
Occludin and hydromineral balance inXenopus laevis
Authors: Chasiotis Helen , Kelly Scott P. 
Published: December 2008

SUMMARYTo investigate the response of the tight junction (TJ) protein occludin to environmental change in an anuran amphibian, we examined occludin tissue distribution, immunolocalization and alterations in mRNA expression in African clawed frogs (Xenopus laevis) acclimated to brackish water (BW)conditions (from freshwater to 2‰, 5‰ or 10‰ salt water). Occludin mRNA is widely expressed in Xenopus and is abundant in tissues involved in regulating salt and water balance, such as the gastrointestinal (GI) tract, kidney and urinary bladder. Immunohistochemical analyses revealed strong occludin immunolabelling in the apicolateral region of epithelia lining the GI tract and mRNA expression increased along the longitudinal axis of the gut. In kidney tissue, occludin was differentially expressed on the luminal side of the nephron tubule, appearing in the distal tubules and collecting ducts only. In response to BW acclimation, Xenopus exhibited a significant loss of tissue water as well as salinity-dependent elevations in serum osmolality as a result of increased urea levels followed by elevated serum Na+ and Cl–levels. Tissue-specific alterations in the ionomotive enzyme Na+,K+-ATPase were also observed in Xenopus in response to BW acclimation. Most notably, Na+,K+-ATPase activity in the rectum increased in response to elevated environmental salt concentrations while renal activity decreased. Furthermore, acclimation to BW caused tissue-specific and salinity-dependent alterations in occludin mRNA expression within select Xenopus osmoregulatory organs. Taken together, these studies suggest that alterations in occludin, in conjunction with active transport processes, may contribute to amphibian hydromineral homeostasis during environmental change.
Temperature adaptation of cytosolic malate dehydrogenases of limpets(genusLottia): differences in stability and function due to minor changes in sequence correlate with biogeographic and vertical distributions
Authors: Dong Yunwei , Somero George N. 
Published: December 2008

SUMMARYWe characterized functional and structural properties of cytoplasmic malate dehydrogenases (cMDHs) from six limpets of the genus Lottia that have different vertical and latitudinal distributions. Particular attention was given to the cryptic species pair Lottia digitalis (northern occurring) and L. austrodigitalis (southern occurring) because of recent contraction in the southern range of L. digitalis and a northward range extension of L. austrodigitalis. As an index of adaptation of function, we measured the effects of temperature on the apparent Michaelis–Menten constant (Km) of the cofactor NADH(KmNADH). KmNADHvalues of cMDHs from the mid- to high-intertidal, low-latitude species L. scabra and L. gigantea were less sensitive to high temperature than those of cMDHs from the low- and mid-intertidal, high-latitude species L. scutum and L. pelta. cMDH of L. digitalis was more sensitive to high temperatures than the cMDH ortholog of L. austrodigitalis. Thermal stability (rate of loss of activity at 42.5°C) showed a similar pattern of interspecific variation. Comparison of the deduced amino acid sequences showed that interspecific differences ranged from one to as many as 17 residues. Differences in KmNADH and thermal stability between orthologs of L. digitalis and L. austrodigitalis result from a single amino acid substitution. At position 291, the glycine residue in cMDH of L. digitalis is replaced by a serine in cMDH of L. austrodigitalis, a change that favors additional hydrogen bonding and reduced conformational entropy. This difference between closely related congeners demonstrates the role of minor alterations in protein sequence in temperature adaptation and suggests that such variation is important in governing shifts in biogeographic range in response to climate change.
Effects of cocaine on honey bee dance behaviour
Authors: Barron Andrew B. , Maleszka Ryszard , Helliwell Paul G. , Robinson Gene E. 
Published: December 2008

SUMMARYThe role of cocaine as an addictive drug of abuse in human society is hard to reconcile with its ecological role as a natural insecticide and plant-protective compound, preventing herbivory of coca plants(Erythroxylum spp.). This paradox is often explained by proposing a fundamental difference in mammalian and invertebrate responses to cocaine, but here we show effects of cocaine on honey bees (Apis mellifera L.)that parallel human responses. Forager honey bees perform symbolic dances to advertise the location and value of floral resources to their nest mates. Treatment with a low dose of cocaine increased the likelihood and rate of bees dancing after foraging but did not otherwise increase locomotor activity. This is consistent with cocaine causing forager bees to overestimate the value of the floral resources they collected. Further, cessation of chronic cocaine treatment caused a withdrawal-like response. These similarities likely occur because in both insects and mammals the biogenic amine neuromodulator systems disrupted by cocaine perform similar roles as modulators of reward and motor systems. Given these analogous responses to cocaine in insects and mammals, we propose an alternative solution to the paradox of cocaine reinforcement. Ecologically, cocaine is an effective plant defence compound viadisruption of herbivore motor control but, because the neurochemical systems targeted by cocaine also modulate reward processing, the reinforcing properties of cocaine occur as a `side effect'.
High Treatment Success Rates When Switching to Once Daily Nevirapine Containing Antiretroviral Therapy
Authors: Benzie Andrew , Marett Brett , Mackie Nicola E , Winston Alan 
Published: December 2008

IntroductionTwo recent studies have highlighted low rates of virological response to once daily nevirapine containing combination antiretroviral therapy (CART) in treatment naïve HIV-1 infected subjects.AimWe assessed factors associated with treatment responses in a cohort of HIV-1 infected, therapy naïve individuals, commencing nevirapine CART with two nucleoside reverse transcriptase inhibitors (NRTI) containing either lamivudine or emtricitabine.ResultsBetween January 2002 and 2006, 173 subjects (80 female) met the study inclusion criteria. All subjects initially commenced on twice daily nevirapine with six different NRTI backbones. Mean follow up was 802 days. 49 (28%) subjects switched to once daily nevirapine, 23 (13%) within the first year. After 48 weeks of therapy, HIV RNA was < 50 copies/mL in 154/173 subjects (89%). A trend was observed towards improved virological outcome (HIV RNA < 50 copies/mL) and switching to once daily nevirapine during the first year of therapy (p=0.051).ConclusionWhilst awaiting the results of prospective studies assessing once daily nevirapine, our data describe high treatment success rates and good safety responses when switching to once daily nevirapine.