bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic sequence analysis of inherited bleeding diseases
Authors: Peyvandi Flora , Kunicki Tom , Lillicrap David 
Published: October 2013

Abstract
The genes encoding the coagulation factor proteins were among the first human genes to be characterized over 25 years ago. Since then, significant progress has been made in the translational application of this information for the 2 commonest severe inherited bleeding disorders, hemophilia A and B. For these X-linked disorders, genetic characterization of the disease-causing mutations is now incorporated into the standard of care and genetic information is used for risk stratification of treatment complications. With electronic databases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensively characterized inherited diseases in humans. Experience with the genetics of the rare bleeding disorders is, as expected, less well advanced. However, here again, electronic mutation databases have been developed and provide excellent guidance for the application of genetic analysis as a confirmatory approach to diagnosis. Most recently, progress has also been made in identifying the mutant loci in a variety of inherited platelet disorders, and these findings are beginning to be applied to the genetic diagnosis of these conditions. Investigation of patients with bleeding phenotypes without a diagnosis, using genome-wide strategies, may identify novel genes not previously recognized as playing a role in hemostasis.
Integrating microRNA and mRNA expression profiling in Symbiodinium microadriaticum, a dinoflagellate symbiont of reef-building corals
Authors: Baumgarten Sebastian , Bayer Till , Aranda Manuel , Liew Yi Jin , Carr Adrian , Micklem Gos , Voolstra Christian R 
Published: October 2013

Abstract

Background
Animal and plant genomes produce numerous small RNAs (smRNAs) that regulate gene expression post-transcriptionally affecting metabolism, development, and epigenetic inheritance. In order to characterize the repertoire of endogenous smRNAs and potential gene targets in dinoflagellates, we conducted smRNA and mRNA expression profiling over 9 experimental treatments of cultures from Symbiodinium microadriaticum, a photosynthetic symbiont of scleractinian corals.

Results
We identified a set of 21 novel smRNAs that share stringent key features with functional microRNAs from other model organisms. smRNAs were predicted independently over all 9 treatments and their putative gene targets were identified. We found 1,720 animal-like target sites in the 3'UTRs of 12,858 mRNAs and 19 plant-like target sites in 51,917 genes. We assembled a transcriptome of 58,649 genes and determined differentially expressed genes (DEGs) between treatments. Heat stress was found to produce a much larger number of DEGs than other treatments that yielded only few DEGs. Analysis of DEGs also revealed that minicircle-encoded photosynthesis proteins seem to be common targets of transcriptional regulation. Furthermore, we identified the core RNAi protein machinery in Symbiodinium.

Conclusions
Integration of smRNA and mRNA expression profiling identified a variety of processes that could be under microRNA control, e.g. protein modification, signaling, gene expression, and response to DNA damage. Given that Symbiodinium seems to have a paucity of transcription factors and differentially expressed genes, identification and characterization of its smRNA repertoire establishes the possibility of a range of gene regulatory mechanisms in dinoflagellates acting post-transcriptionally.
Perceptual organization of auditory streaming-task relies on neural entrainment of the stimulus-presentation rate: MEG evidence
Authors: Chakalov Ivan , Draganova Rossitza , Wollbrink Andreas , Preissl Hubert , Pantev Christo 
Published: October 2013

Abstract

Background
Humans are able to extract regularities from complex auditory scenes in order to form perceptually meaningful elements. It has been shown previously that this process depends critically on both the temporal integration of the sensory input over time and the degree of frequency separation between concurrent sound sources. Our goal was to examine the relationship between these two aspects by means of magnetoencephalography (MEG). To achieve this aim, we combined time-frequency analysis on a sensor space level with source analysis. Our paradigm consisted of asymmetric ABA-tone triplets wherein the B-tones were presented temporally closer to the first A-tones, providing different tempi within the same sequence. Participants attended to the slowest B-rhythm whilst the frequency separation between tones was manipulated (0-, 2-, 4- and 10-semitones).

Results
The results revealed that the asymmetric ABA-triplets spontaneously elicited periodic-sustained responses corresponding to the temporal distribution of the A-B and B-A tone intervals in all conditions. Moreover, when attending to the B-tones, the neural representations of the A- and B-streams were both detectable in the scenarios which allow perceptual streaming (2-, 4- and 10-semitones). Alongside this, the steady-state responses tuned to the presentation of the B-tones enhanced significantly with increase of the frequency separation between tones. However, the strength of the B-tones related steady-state responses dominated the strength of the A-tones responses in the 10-semitones condition. Conversely, the representation of the A-tones dominated the B-tones in the cases of 2- and 4-semitones conditions, in which a greater effort was required for completing the task. Additionally, the P1 evoked fields’ component following the B-tones increased in magnitude with the increase of inter-tonal frequency difference.

Conclusions
The enhancement of the evoked fields in the source space, along with the B-tones related activity of the time-frequency results, likely reflect the selective enhancement of the attended B-stream. The results also suggested a dissimilar efficiency of the temporal integration of separate streams depending on the degree of frequency separation between the sounds. Overall, the present findings suggest that the neural effects of auditory streaming could be directly captured in the time-frequency spectrum at the sensor-space level.
A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe abdominal Aortic calcification in stage 3 and 4 kidney disease patients
Authors: Craver Lourdes , Dusso Adriana , Martinez-Alonso Montserrat , Sarro Felipe , Valdivielso José M , Fernández Elvira 
Published: October 2013

Abstract

Background
Vascular calcification (VC) contributes to high mortality rates in chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired phosphaturic response to FGF23 may affect VC. Therefore, their relative contribution to abdominal aortic calcification (AAC) was examined in patients CKD stages 3–4.

Methods
Potential risk factors for AAC, measured by the Kauppila Index (KI), were studied in 178 patients.

Results
In multivariate linear analysis, AAC associated positively with age, male gender, CKD-stage, presence of carotid plaques (CP) and also with FGF23, but negatively with fractional excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes with elevations in PTH, with reductions in GFR, and also with elevations in FGF23 but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic and zero-inflated analysis confirmed the independent association of age, CKD stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23 ratio of 1/3.9, below which the chances for a patient of presenting severe AAC increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios decreased from 1/1 to 1/3.9 but markedly increased in parallel with further reductions in FEP/FGF23 < 1/3.9.

Conclusions
In CKD 3–4, an impaired phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC independently of age, gender or CP.
Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small cell lung cancer: results of a prospective single-center study
Authors: Su Sheng-Fa , Hu Yin-Xiang , Ouyang Wei-Wei , Lu Bing , Ma Zhu , Li Qing-Song , Li Hui-Qin , Geng Yi-Chao 
Published: October 2013

Abstract

Background
The role of chemotherapy given concurrently with thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not well defined. We performed this study to investigate overall survival and toxicity in patients with stage IV NSCLC treated with this modality.

Methods
From 2003 to 2010, 201 patients were enrolled in this study. All patients received chemotherapy with concurrent thoracic three-dimensional radiotherapy. The study endpoints were the assessment of overall survival (OS) and acute toxicity.

Results
For all patients, the median survival time (MST) was 10.0 months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%, respectively. The MST was 14.0 months for patients who received a total radiation dose ≥63 Gy to the primary tumor, whereas it was 8.0 months for patients who received a total dose <63 Gy (P = 0.000). On multivariate analysis, a total dose ≥63 Gy, a single site of metastatic disease, and undergoing ≥4 cycles of chemotherapy were independent prognostic factors for better OS (P = 0.007, P = 0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was a marginally significant prognostic factor (P = 0.063). When the whole group was subdivided into patients with metastasis at a single site and multiple sites, a higher radiation dose to the primary tumor remained a significant prognostic factor for improved OS. For patients who received ≥4 cycles of chemotherapy, high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the subgroup that received <4 chemotherapy cycles, the radiation dose was of marginal statistical significance regarding OS (P = 0.063). Treatment-related toxicity was found to be acceptable.

Conclusions
Radiation dose to primary tumor, the number of metastatic sites, and the number of chemotherapy cycles were independent prognostic factors for OS in stage IV NSCLC patients treated with concurrent chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic radiotherapy was shown to play an important role in improving OS.

Trial registration
Registered on (ChiCTR-TNC-10001026)
Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients - a randomized double-blind placebo-controlled pilot study
Authors: Sharafedtinov Khaider K , Plotnikova Oksana A , Alexeeva Ravilay I , Sentsova Tatjana B , Songisepp Epp , Stsepetova Jelena , Smidt Imbi , Mikelsaar Marika 
Published: October 2013

Abstract

Background
Gut lactobacilli can affect the metabolic functions of healthy humans. We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA (Deutsche Sammlung für Mikroorganismen, DSM 21380) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension.

Methods
In this 3-week, randomized, double-blind, placebo-controlled, parallel pilot study, 25 subjects ingested probiotic cheese and 15 ingested control cheese. Fifty grams of each cheese provided 175 kcal of energy. Blood pressure (BP), anthropometric characteristics, markers of liver and kidney function, metabolic indices (plasma glucose, lipids, and cholesterol), and urine polyamines were measured. Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods. The data were analyzed by t-test for independent samples and Spearman’s partial correlation analysis.

Results
The probiotic L. plantarum TENSIA was present in variable amounts (529.6 ± 232.5 gene copies) in 16/25 (64%) study subjects. Body mass index (BMI) was significantly reduced (p = 0.031) in the probiotic cheese group versus the control cheese group. The changes in BMI were closely associated with the water content of the body (r = 0.570, p = 0.0007) when adjusted for sex and age. Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI (r = 0.383, p = 0.0305) and urinary putrescine content (r = 0.475, p = 0.006). In patients simultaneously treated with BP-lowering drugs, similar reductions of BP were observed in both groups. A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP (r = 0.617, p = 0.0248) and a trend toward lower values of morning systolic BP (r = −0.527, p = 0.0640) at the end of the study after adjusting for BMI, age, and sex.

Conclusion
In a pilot study of obese hypertensive patients, a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values, recognized symptoms of metabolic syndrome.

Trial registration
Current Controlled Trials ISRCTN76271778
The addition of whole soy flour to cafeteria diet reduces metabolic risk markers in wistar rats
Authors: Andrade Gláucia Ferreira , de Almeida Crislaine das Graças , Espeschit Ana Cristina Rocha , Dantas Maria Inês de Souza , Benjamin Laércio dos Anjos , Ribeiro Sonia Machado Rocha , Martino Hércia Stampini Duarte 
Published: October 2013

Abstract

Background
Soybean is termed a functional food because it contains bioactive compounds. However, its effects are not well known under unbalanced diet conditions. This work is aimed at evaluating the effect of adding whole soy flour to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity markers in rats.

Methods
In this study, 30 male adult Wistar rats were used, distributed among three groups (n = 10): AIN-93 M diet, cafeteria diet (CAF) and cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were measured: food intake; weight gain; serum concentrations of triglycerides, total cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS); humidity and lipid fecal content; weight and fat of the liver. The villous height, the crypt depth and the thickness of the duodenal and ileal circular and longitudinal muscle layers of the animals were also measured.

Results
There was a significant reduction in the food intake in the CAF group. The CAFS showed lower serum concentrations of triglycerides and serum TBARS and a lower percentage of hepatic fat, with a corresponding increase in thickness of the intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c and villous height. The addition of soy did not promote any change in these parameters.

Conclusions
The inclusion of whole soy flour in a high-fat diet may be helpful in reducing some markers of metabolic risk; however, more studies are required to clarify its effects on unbalanced diets.
Inhibition of protein kinase CK2 with the clinical-grade small ATP-competitive compound CX-4945 or by RNA interference unveils its role in acute myeloid leukemia cell survival, p53-dependent apoptosis and daunorubicin-induced cytotoxicity
Authors: Quotti Tubi Laura , Gurrieri Carmela , Brancalion Alessandra , Bonaldi Laura , Bertorelle Roberta , Manni Sabrina , Pavan Laura , Lessi Federica , Zambello Renato , Trentin Livio , Adami Fausto , Ruzzene Maria , Pinna Lorenzo A , Semenzato Gianpietro , Piazza Francesco 
Published: October 2013

Abstract

Background
The involvement of protein kinase CK2 in sustaining cancer cell survival could have implications also in the resistance to conventional and unconventional therapies. Moreover, CK2 role in blood tumors is rapidly emerging and this kinase has been recognized as a potential therapeutic target. Phase I clinical trials with the oral small ATP-competitive CK2 inhibitor CX-4945 are currently ongoing in solid tumors and multiple myeloma.

Methods
We have analyzed the expression of CK2 in acute myeloid leukemia and its function in cell growth and in the response to the chemotherapeutic agent daunorubicin We employed acute myeloid leukemia cell lines and primary blasts from patients grouped according to the European LeukemiaNet risk classification. Cell survival, apoptosis and sensitivity to daunorubicin were assessed by different means. p53-dependent CK2-inhibition-induced apoptosis was investigated in p53 wild-type and mutant cells.

Results
CK2α was found highly expressed in the majority of samples across the different acute myeloid leukemia prognostic subgroups as compared to normal CD34+ hematopoietic and bone marrow cells. Inhibition of CK2 with CX-4945, K27 or siRNAs caused a p53-dependent acute myeloid leukemia cell apoptosis. CK2 inhibition was associated with a synergistic increase of the cytotoxic effects of daunorubicin. Baseline and daunorubicin-induced STAT3 activation was hampered upon CK2 blockade.

Conclusions
These results suggest that CK2 is over expressed across the different acute myeloid leukemia subsets and acts as an important regulator of acute myeloid leukemia cell survival. CK2 negative regulation of the protein levels of tumor suppressor p53 and activation of the STAT3 anti-apoptotic pathway might antagonize apoptosis and could be involved in acute myeloid leukemia cell resistance to daunorubicin.
Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength
Authors: Lee Sang-il , Hida Akiko , Tsujimura Sei-ichi , Morita Takeshi , Mishima Kazuo , Higuchi Shigekazu 
Published: October 2013

Abstract

Background
Our aim was to determine the association between melanopsin gene polymorphism and pupillary light reflex under diverse photic conditions, including different intensities and wavelengths.

Methods
A total of 195 visually corrected subjects volunteered for investigation of the melanopsin gene of single nucleotide polymorphism (SNP) of rs1079610 (I394T). The genotype groups were TT (n = 126), TC (n = 55), and CC (n = 8), and 75 of the subjects, including subjects with TT (n = 34), TC (n = 33), and CC (n = 8) participated in our experiment. Three monochromatic lights with peak wavelengths of 465 nm (blue), 536 nm (green), and 632 nm (red) were prepared, and each light was projected to the subjects with five intensities, 12, 13, 14, 14.5 and 15 log photons/(cm2 s), for one minute. The pupil size of the left eye was measured under each light condition after a 1-minute adaptation.

Results
The pupils of the TC + CC genotypes (n = 38) were significantly smaller than those of the TT genotype (n = 31) under a blue (463 nm) light condition with 15 log photons/(cm2 s) (P < 0.05). In contrast, there were no significant differences under green (536 nm) and red (632 nm) light conditions. Conversely, relative pupil constrictions of the TC + CC genotypes were greater than those of the TT genotype under both blue and green conditions with high intensities (14.5 and 15 log photons/(cm2 s)). In contrast, there were no significant differences between genotype groups in pupil size and relative pupilloconstriction under the red light conditions.

Conclusions
Our findings suggest that the melanopsin gene polymorphism (I394T) functionally interacts with pupillary light reflex, depending on light intensity and, particularly, wavelength, and that under a light condition fulfilling both high intensity and short wavelength, the pupillary light response of subjects with the C allele (TC + CC) is more sensitive to light than that of subjects with the TT genotype.
Adhesion-promoting receptors on phagocytes
Authors: Wright Samuel D. , Detmers Patricia A. 
Published: October 2013

ABSTRACT
Phagocytes express a family of structurally related receptors, LFA-1, CR3, and p150,95, that mediate adhesion of leukocytes to a variety of cells and surfaces. LFA-1 mediates the binding of killer T cells to targets, CR3 mediates binding of phagocytes to iC3b-coated surfaces and to endothelial cells, and LFA-1, CR3, and p150,95 each mediate the binding of bacterial lipopolysaccharide. Here we review the structure and function of each of these receptors and present evidence that they are related to a larger class of adhesion-promoting receptors called integrins. Of particular emphasis are observations that the capacity of these receptors to promote adhesion is strongly and reversibly modulated by both soluble and surface-bound stimuli. We review this form of regulation and present evidence that changes in the binding activity of adhesion-promoting receptors is accomplished by changes in the two-dimensional distribution of receptors in the plane of the membrane. Inactive receptors are randomly distributed in the membrane, and their ability to bind a ligand-coated surface is enabled by a ligand-independent movement into small clusters. The implications of these structural features are discussed.
The structure of the macrophage actin skeleton
Authors: Yin H. L. , Hartwig J. H. 
Published: October 2013

ABSTRACT
The actin skeleton of the macrophage consists of a three-dimensional network of actin filaments and associated proteins. The organization of this multiprotein structure is regulated at several levels in cells. Receptor stimulation induces a massive actin polymerization at the cell cortex, changes in cell shape and active cellular movements. Gelsolin may have a pivotal role in restructuring the actin skeleton in response to agonist stimulation, as the activity of this potent actin-modulating protein is regulated by both Ca2+ and polyphosphoinositides. Micromolar concentrations of Ca2+ activate gelsolin to bind to the sides of actin filaments, sever, and cap the filament end. Polyphosphoinositides, in particular PIP and PIP2, release gelsolin from the filament ends. A structure-function analysis of gelsolin indicates that its N-terminal half is primarily responsible for severing actin filaments, and elucidates mechanisms by which Ca2+ and phospholipid may regulate gelsolin functions. The ultrastructure of actin filaments in the macrophage cortical cytoplasm is regulated, to a large extent, by the actin cross-linking protein, actin-binding protein (ABP) which defines filament orthogonality.