bluuebunny/crossref_metadata_2025_split huggingface dataset:
High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease
Authors: Berentsen Sigbjørn , Randen Ulla , Vågan Anne Marita , Hjorth-Hansen Henrik , Vik Anders , Dalgaard Jakob , Jacobsen Eva-Marie , Thoresen Aud S. , Beiske Klaus , Tjønnfjord Geir E. 
Published: July 2010

AbstractMost patients diagnosed with primary chronic cold agglutinin disease (CAD) have a clonal lymphoproliferative bone marrow disorder. Treatment with rituximab is the only well-documented effective therapy, leading to 45%-60% partial responses (PR). Complete responses (CR) are rare, and median response duration is only 11 months. In a prospective multicenter trial, 29 patients received rituximab 375 mg/m2 on days 1, 29, 57 and 85; and fludarabine orally, 40 mg/m2 on days 1-5, 29-34, 57-61 and 85-89. Twenty-two patients (76%) responded, 6 (21%) achieving CR and 16 (55%) PR. Among 10 patients nonresponsive to rituximab monotherapy, 1 achieved CR and 6 PR. Median increase in hemoglobin level was 3.1 g/dL among the responders and 4.0 g/dL in those who achieved CR. Lower quartile of response duration was not reached after 33 months. Estimated median response duration was more than 66 months. Grade 3-4 hematologic toxicity occurred in 12 patients (41%). In conclusion, fludarabine and rituximab combination therapy is very efficient in patients with CAD. Toxicity may be a concern, and benefits should be carefully weighed against risks in very old and comorbid patients. It remains to be established whether the combination should be first-line or an efficient second-line therapy in CAD patients requiring treatment. This study is registered at http://www.clinicaltrials.gov as NCT00373594.
Biosynthesis of compatible solutes in rhizobial strains isolated from Phaseolus vulgaris nodules in Tunisian fields
Authors: Fernandez-Aunión Cristina , Hamouda Thouraya Ben , Iglesias-Guerra Fernando , Argandoña Montserrat , Reina-Bueno Mercedes , Nieto Joaquín J , Aouani M Elarbi , Vargas Carmen 
Published: July 2010

Abstract

Background
Associated with appropriate crop and soil management, inoculation of legumes with microbial biofertilizers can improve food legume yield and soil fertility and reduce pollution by inorganic fertilizers. Rhizospheric bacteria are subjected to osmotic stress imposed by drought and/or NaCl, two abiotic constraints frequently found in semi-arid lands. Osmostress response in bacteria involves the accumulation of small organic compounds called compatible solutes. Whereas most studies on rhizobial osmoadaptation have focussed on the model species Sinorhizobium meliloti, little is known on the osmoadaptive mechanisms used by native rhizobia, which are good sources of inoculants. In this work, we investigated the synthesis and accumulations of compatible solutes by four rhizobial strains isolated from root nodules of Phaseolus vulgaris in Tunisia, as well as by the reference strain Rhizobium tropici CIAT 899T.

Results
The most NaCl-tolerant strain was A. tumefaciens 10c2, followed (in decreasing order) by R. tropici CIAT 899, R. leguminosarum bv. phaseoli 31c3, R. etli 12a3 and R. gallicum bv. phaseoli 8a3. 13C- and 1H-NMR analyses showed that all Rhizobium strains synthesized trehalose whereas A. tumefaciens 10c2 synthesized mannosucrose. Glutamate synthesis was also observed in R. tropici CIAT 899, R. leguminosarum bv. phaseoli 31c3 and A. tumefaciens 10c2. When added as a carbon source, mannitol was also accumulated by all strains. Accumulation of trehalose in R. tropici CIAT 899 and of mannosucrose in A. tumefaciens 10c2 was osmoregulated, suggesting their involvement in osmotolerance. The phylogenetic analysis of the otsA gene, encoding the trehalose-6-phosphate synthase, suggested the existence of lateral transfer events. In vivo
13C labeling experiments together with genomic analysis led us to propose the uptake and conversion pathways of different carbon sources into trehalose. Collaterally, the β-1,2-cyclic glucan from R. tropici CIAT 899 was co-extracted with the cytoplasmic compatible solutes and its chemical structure was determined.

Conclusions
The soil bacteria analyzed in this work accumulated mainly disaccharides in response to NaCl stress. We could not find a direct correlation between the trehalose content of the rhizobial strains and their osmotolerance, suggesting that additional osmoadaptive mechanism should be operating in the most NaCl-tolerant strain R. tropici CIAT 899.
Study of the nitric oxide system in the rat cerebellum during aging
Authors: Blanco Santos , Molina Francisco J , Castro Lourdes , Del Moral Maria L , Hernandez Raquel , Jimenez Ana , Rus Alma , Martinez-Lara Esther , Siles Eva , Peinado Maria A 
Published: July 2010

AbstractBackgroundThe cerebellum is the neural structure with the highest levels of nitric oxide, a neurotransmitter that has been proposed to play a key role in the brain aging, although knowledge concerning its contribution to cerebellar senescence is still unclear, due mainly to absence of integrative studies that jointly evaluate the main factors involved in its cell production and function. Consequently, in the present study, we investigate the expression, location, and activity of nitric oxide synthase isoenzymes; the protein nitration; and the production of nitric oxide in the cerebellum of adult and old rats.ResultsOur results show no variation in the expression of nitric oxide synthase isoforms with aging, although, we have detected some changes in the cellular distribution pattern of the inducible isoform particularly in the cerebellar nuclei. There is also an increase in nitric oxide synthase activity, as well as greater protein-nitration levels, and maintenance of nitrogen oxides (NOx) levels in the senescent cerebellum.ConclusionsThe nitric oxide/nitric oxide syntahses system suffers from a number of changes, mainly in the inducible nitric oxide synthase distribution and in overall nitric oxide synthases activity in the senescent cerebellum, which result in an increase of the protein nitration. These changes might be related to the oxidative damage detected with aging in the cerebellum.
Institutional review board challenges related to community-based participatory research on human exposure to environmental toxins: A case study
Authors: Brown Phil , Morello-Frosch Rachel , Brody J G , Altman Rebecca Gasior , Rudel Ruthann A , Senier Laura , Pérez Carla , Simpson Ruth 
Published: July 2010

Abstract

Background
We report on the challenges of obtaining Institutional Review Board (IRB) coverage for a community-based participatory research (CBPR) environmental justice project, which involved reporting biomonitoring and household exposure results to participants, and included lay participation in research.

Methods
We draw on our experiences guiding a multi-partner CBPR project through university and state Institutional Review Board reviews, and other CBPR colleagues' written accounts and conference presentations and discussions. We also interviewed academics involved in CBPR to learn of their challenges with Institutional Review Boards.

Results
We found that Institutional Review Boards are generally unfamiliar with CBPR, reluctant to oversee community partners, and resistant to ongoing researcher-participant interaction. Institutional Review Boards sometimes unintentionally violate the very principles of beneficence and justice which they are supposed to uphold. For example, some Institutional Review Boards refuse to allow report-back of individual data to participants, which contradicts the CBPR principles that guide a growing number of projects. This causes significant delays and may divert research and dissemination efforts. Our extensive education of our university Institutional Review Board convinced them to provide human subjects protection coverage for two community-based organizations in our partnership.

Conclusions
IRBs and funders should develop clear, routine review guidelines that respect the unique qualities of CBPR, while researchers and community partners can educate IRB staff and board members about the objectives, ethical frameworks, and research methods of CBPR. These strategies can better protect research participants from the harm of unnecessary delays and exclusion from the research process, while facilitating the ethical communication of study results to participants and communities.
Calorie restriction and endurance exercise share potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance in mice
Authors: Huang Ping , Li Shoufeng , Shao Mengle , Qi Qibin , Zhao Feng , You Jia , Mao Ting , Li Wenjun , Yan Zhen , Liu Yong 
Published: July 2010

Abstract

Background
Calorie restriction (CR) and endurance exercise are known to attenuate obesity and improve the metabolic syndrome. The aim of this study was to directly compare the effects of CR and endurance exercise in a mouse model of diet-induced obesity and insulin resistance.

Methods
Adult male C57BL/6N mice were randomly assigned and subjected to one of the six interventions for 8 weeks: low-fat diet (LC, 10% fat), low-fat diet with 30% calorie restriction (LR), high-fat diet (HC, 60% fat), high-fat diet with 30% calorie restriction (HR), high-fat diet with voluntary running exercise (HE), and high-fat diet with a combination of 30% calorie restriction and exercise (HRE). The impacts of the interventions were assessed by comprehensive metabolic analyses and pro-inflammatory cytokine gene expression.

Results
Endurance exercise significantly attenuated high-fat diet-induced obesity. CR dramatically prevented high-fat diet-induced metabolic abnormalities. A combination of CR and endurance exercise further reduced obesity and insulin resistance under the condition of high-fat diet. CR and endurance exercise each potently suppressed the expression of inflammatory cytokines in white adipose tissues with additive effects when combined, but the effects of diet and exercise interventions in the liver were moderate to minimal.

Conclusions
CR and endurance exercise share a potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance.
Increased hypolipidemic benefits of cis-9, trans-11 conjugated linoleic acid in combination with trans-11 vaccenic acid in a rodent model of the metabolic syndrome, the JCR:LA-cp rat
Authors: Jacome-Sosa M Miriam , Lu Jing , Wang Ye , Ruth Megan R , Wright David C , Reaney Martin J , Shen Jianheng , Field Catherine J , Vine Donna F , Proctor Spencer D 
Published: July 2010

Abstract

Background
Conjugated linoleic acid (cis-9, trans-11 CLA) and trans-11 vaccenic acid (VA) are found naturally in ruminant-derived foods. CLA has been shown to have numerous potential health related effects and has been extensively investigated. More recently, we have shown that VA has lipid-lowering properties associated with reduced hepatic lipidogenesis and chylomicron secretion in the JCR:LA-cp rat. The aim of this study was to evaluate potential additional hypolipidemic effects of purified forms of CLA and VA in an animal model of the metabolic syndrome (the JCR:LA-cp rat).

Methods
Twenty four obese JCR:LA-cp rats were randomized and assigned to one of three nutritionally adequate iso-caloric diets containing 1% w/w cholesterol and 15% w/w fat for 16 wk: 1) control diet (CD), 2) 1.0% w/w cis-9, trans-11 CLA (CLA), 3) 1.0% w/w VA and 1% w/w cis-9, trans-11 CLA (VA+CLA). Lean rats were fed the CD to represent normolipidemic conditions.

Results
Fasting plasma triglyceride (TG), total cholesterol and LDL-cholesterol concentrations were reduced in obese rats fed either the CLA diet or the VA+CLA diet as compared to the obese control group (p < 0.05, p < 0.001; p < 0.001, p < 0.01; p < 0.01, p < 0.001, respectively). The VA+CLA diet reduced plasma TG and LDL-cholesterol to the level of the normolipidemic lean rats and further decreased nonesterified fatty acids compared to the CLA diet alone. Interestingly, rats fed the VA+CLA diet had a higher food intake but lower body weight than the CLA fed group (P < 0.05). Liver weight and TG content were lower in rats fed either CLA (p < 0.05) or VA+CLA diets (p < 0.001) compared to obese control, consistent with a decreased relative protein abundance of hepatic acetyl-CoA carboxylase in both treatment groups (P < 0.01). The activity of citrate synthase was increased in liver and adipose tissue of rats fed, CLA and VA+CLA diets (p < 0.001) compared to obese control, suggesting increased mitochondrial fatty acid oxidative capacity.

Conclusion
We demonstrate that the hypolipidemic effects of chronic cis-9, trans-11 CLA supplementation on circulating dyslipidemia and hepatic steatosis are enhanced by the addition of VA in the JCR:LA-cp rat.
Different SNP Combinations in the GCH1 Gene and Use of Labor Analgesia
Authors: Dabo Fatimah , Grönbladh Alfhild , Nyberg Fred , Sundström-Poromaa Inger , Åkerud Helena 
Published: July 2010

Background: The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject. Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used. Results: Homozygous carriers of the pain-protective SNP combination of GCH1 arrived to the delivery ward with a more advanced stage of cervical dilation compared to heterozygous carriers and non-carriers. However, homozygous carriers more often used second line labor analgesia compared to the others. Conclusion: The pain-protective SNP combination of GCH1 may be of importance in the limited number of homozygous carriers during the initial dilation of cervix but upon arrival at the delivery unit these women are more inclined to use second line labor analgesia.
An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies
Authors: Mazin Pavel V , Gelfand Mikhail S , Mironov Andrey A , Rakhmaninova Aleksandra B , Rubinov Anatoly R , Russell Robert B , Kalinina Olga V 
Published: July 2010

Abstract

Background
Recent progress in sequencing and 3 D structure determination techniques stimulated development of approaches aimed at more precise annotation of proteins, that is, prediction of exact specificity to a ligand or, more broadly, to a binding partner of any kind.

Results
We present a method, SDPclust, for identification of protein functional subfamilies coupled with prediction of specificity-determining positions (SDPs). SDPclust predicts specificity in a phylogeny-independent stochastic manner, which allows for the correct identification of the specificity for proteins that are separated on a phylogenetic tree, but still bind the same ligand. SDPclust is implemented as a Web-server http://bioinf.fbb.msu.ru/SDPfoxWeb/ and a stand-alone Java application available from the website.

Conclusions
SDPclust performs a simultaneous identification of specificity determinants and specificity groups in a statistically robust and phylogeny-independent manner.
Turning crocodilian hearts into bird hearts: growth rates are similar for alligators with and without right-to-left cardiac shunt
Authors: Eme John , Gwalthney June , Owerkowicz Tomasz , Blank Jason M. , Hicks James W. 
Published: July 2010

SUMMARYThe functional and possible adaptive significance of non-avian reptiles' dual aortic arch system and the ability of all non-avian reptiles to perform central vascular cardiac shunts have been of great interest to comparative physiologists. The unique cardiac anatomy of crocodilians – a four-chambered heart with the dual aortic arch system – allows for only right-to-left (R–L; pulmonary bypass) cardiac shunt and for surgical elimination of this shunt. Surgical removal of the R–L shunt, by occluding the left aorta (LAo) upstream and downstream of the foramen of Panizza, results in a crocodilian with an obligatory, avian/mammalian central circulation. In this study, R–L cardiac shunt was eliminated in age-matched, female American alligators (Alligator mississippiensis; 5–7 months of age). We tested the hypothesis that surgical elimination of R–L cardiac shunt would impair growth (a readily measured proxy for fitness) compared with sham-operated, age-matched controls, especially in animals subjected to exhaustive exercise. While regular exercise caused a decrease in size (snout-to-vent length, head length and body mass), elimination of the capacity for R–L cardiac shunt did not greatly reduce animal growth, despite a chronic ventricular enlargement in surgically altered juvenile alligators. We speculate that, despite being slightly smaller, alligators with an occluded LAo would have reached sexual maturity in the same breeding season as control alligators. This study suggests that crocodilian R–L cardiac shunt does not provide an adaptive advantage for juvenile alligator growth and supports the logic that cardiac shunts persist in crocodilians because they have not been selected against.
Developmental plasticity of shell morphology of quagga mussels from shallow and deep-water habitats of the Great Lakes
Authors: Peyer Suzanne M. , Hermanson John C. , Lee Carol Eunmi 
Published: July 2010

SUMMARY
The invasive zebra mussel (Dreissena polymorpha) has quickly colonized shallow-water habitats in the North American Great Lakes since the 1980s but the quagga mussel (Dreissena bugensis) is becoming dominant in both shallow and deep-water habitats. While quagga mussel shell morphology differs between shallow and deep habitats, functional causes and consequences of such difference are unknown. We examined whether quagga mussel shell morphology could be induced by three environmental variables through developmental plasticity. We predicted that shallow-water conditions (high temperature, food quantity, water motion) would yield a morphotype typical of wild quagga mussels from shallow habitats, while deep-water conditions (low temperature, food quantity, water motion) would yield a morphotype present in deep habitats. We tested this prediction by examining shell morphology and growth rate of quagga mussels collected from shallow and deep habitats and reared under common-garden treatments that manipulated the three variables. Shell morphology was quantified using the polar moment of inertia. Of the variables tested, temperature had the greatest effect on shell morphology. Higher temperature (∼18–20°C) yielded a morphotype typical of wild shallow mussels regardless of the levels of food quantity or water motion. In contrast, lower temperature (∼6–8°C) yielded a morphotype approaching that of wild deep mussels. If shell morphology has functional consequences in particular habitats, a plastic response might confer quagga mussels with a greater ability than zebra mussels to colonize a wider range of habitats within the Great Lakes.
Genetic differences in hemoglobin function between highland and lowland deer mice
Authors: Storz Jay F. , Runck Amy M. , Moriyama Hideaki , Weber Roy E. , Fago Angela 
Published: July 2010

SUMMARY
In high-altitude vertebrates, adaptive changes in blood–O2 affinity may be mediated by modifications of hemoglobin (Hb) structure that affect intrinsic O2 affinity and/or responsiveness to allosteric effectors that modulate Hb–O2 affinity. This mode of genotypic specialization is considered typical of mammalian species that are high-altitude natives. Here we investigated genetically based differences in Hb–O2 affinity between highland and lowland populations of the deer mouse (Peromyscus maniculatus), a generalist species that has the broadest altitudinal distribution of any North American mammal. The results of a combined genetic and proteomic analysis revealed that deer mice harbor a high level of Hb isoform diversity that is attributable to allelic polymorphism at two tandemly duplicated α-globin genes and two tandemly duplicated β-globin genes. This high level of isoHb diversity translates into a correspondingly high level of interindividual variation in Hb functional properties. O2 equilibrium experiments revealed that the Hbs of highland mice exhibit slightly higher intrinsic O2 affinities and significantly lower Cl– sensitivities relative to the Hbs of lowland mice. The experiments also revealed distinct biochemical properties of deer mouse Hb related to the anion-dependent allosteric regulation of O2 affinity. In conjunction with previous findings, our results demonstrate that modifications of Hb structure that alter allosteric anion sensitivity play an important role in the adaptive fine-tuning of blood–O2 affinity.
Harbor seal vibrissa morphology suppresses vortex-induced vibrations
Authors: Hanke Wolf , Witte Matthias , Miersch Lars , Brede Martin , Oeffner Johannes , Michael Mark , Hanke Frederike , Leder Alfred , Dehnhardt Guido 
Published: July 2010

SUMMARYHarbor seals (Phoca vitulina) often live in dark and turbid waters, where their mystacial vibrissae, or whiskers, play an important role in orientation. Besides detecting and discriminating objects by direct touch, harbor seals use their whiskers to analyze water movements, for example those generated by prey fish or by conspecifics. Even the weak water movements left behind by objects that have passed by earlier can be sensed and followed accurately (hydrodynamic trail following). While scanning the water for these hydrodynamic signals at a swimming speed in the order of meters per second, the seal keeps its long and flexible whiskers in an abducted position, largely perpendicular to the swimming direction. Remarkably, the whiskers of harbor seals possess a specialized undulated surface structure, the function of which was, up to now, unknown. Here, we show that this structure effectively changes the vortex street behind the whiskers and reduces the vibrations that would otherwise be induced by the shedding of vortices from the whiskers (vortex-induced vibrations). Using force measurements, flow measurements and numerical simulations, we find that the dynamic forces on harbor seal whiskers are, by at least an order of magnitude, lower than those on sea lion (Zalophus californianus) whiskers, which do not share the undulated structure. The results are discussed in the light of pinniped sensory biology and potential biomimetic applications.
Opsin co-expression in Limulus photoreceptors: differential regulation by light and a circadian clock
Authors: Katti C. , Kempler K. , Porter M. L. , Legg A. , Gonzalez R. , Garcia-Rivera E. , Dugger D. , Battelle B.-A. 
Published: July 2010

SUMMARY
A long-standing concept in vision science has held that a single photoreceptor expresses a single type of opsin, the protein component of visual pigment. However, the number of examples in the literature of photoreceptors from vertebrates and invertebrates that break this rule is increasing. Here, we describe a newly discovered Limulus opsin, Limulus opsin5, which is significantly different from previously characterized Limulus opsins, opsins1 and 2. We show that opsin5 is co-expressed with opsins1 and 2 in Limulus lateral and ventral eye photoreceptors and provide the first evidence that the expression of co-expressed opsins can be differentially regulated. We show that the relative levels of opsin5 and opsin1 and 2 in the rhabdom change with a diurnal rhythm and that their relative levels are also influenced by the animal's central circadian clock. An analysis of the sequence of opsin5 suggests it is sensitive to visible light (400–700 nm) but that its spectral properties may be different from that of opsins1 and 2. Changes in the relative levels of these opsins may underlie some of the dramatic day–night changes in Limulus photoreceptor function and may produce a diurnal change in their spectral sensitivity.