Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular relationships of Helicobacter pylori strains in a family with gastroduodenal disease

Objective:Few studies have examined the genetic relationships of Helicobacter pylori strains affecting family members. Our aim was to do so.Methods:We characterized H. pylori isolates obtained from members of a single family presenting with various gastroduodenal diseases to examine H. pylori bacterial genetic similarity. Endoscopic evaluation with gastric mapping was performed on each individual to establish clinical and histological disease. Genomic DNA extracted from each H. pylori isolate was used to generate DNA fingerprints for each strain by REP-PCR. vacA genotypes and cagA presence were established by PCR.Results:Gastrointestinal diseases among the five members of this family included gastric adenocarcinoma in a 52-yr-old man (index patient), gastric MALT-lymphoma in the 73-yr-old mother; intestinal metaplasia (IV) and atrophic gastritis in the 48-yr-old brother; intestinal metaplasia (I-III) in the 47-yr-old brother, and a duodenal ulcer scar in the 42-yr-old sister. REP-PCR DNA fingerprints of H. pylori isolates from the index patient, his mother, and both of his brothers were identical or highly similar. By contrast, the H. pylori DNA fingerprint from the sister was markedly different from the H. pylori DNA fingerprints from the other family members. All isolates had the genotype cagA-positive and vacA slb/ml mosaic genotype.Conclusions:The DNA fingerprints of H. pylori strains obtained from members of this family with malignancy or premalignant histological disease were identical or highly similar and markedly different from the H. pylori DNA fingerprint from the sibling with duodenal ulcer disease. All H. pylori isolates within the family possessed genetic markers of enhanced virulence (presence of the cagA gene and vacA sl/ml mosaicism). In addition to host genetics and environmental factors, these findings suggest that infection with genetically similar H. pylori strains is a significant factor in determining the clinical outcome of an infection with H. pylori.
Clinical evaluation of integrated panel testing by next-generation sequencing for somatic mutations in neuroblastomas with MYCN unamplification

Neuroblastomas (NBs) exhibit heterogeneity and show clinically significant prognosis classified by genetic alterations. Among prognostic genes or genome factors, MYCN amplification (MNA) is the most established genomic marker of poor prognosis in patients with NB. However, the prognostic classification of more than 60% of patients without MNA has yet to be clarified. In this study, the application of target next-generation sequencing (NGS) was extended on the basis of a comprehensive panel of regions where copy number variations (CNVs) or point mutations occurred to improve the prognostic evaluation of these patients and obtain the sequence of 33 patients without MNA. A mean coverage depth of 887× was determined in the target regions in all of the samples, and the mapped read percentage was more than 99%. Somatic mutations in patients without MNA could be precisely defined on the basis of these findings, and 17 unique somatic aberrations, including 14 genes, were identified in 11 patients. Among these variations, most were CNVs with a number of 13. The 3-year event-free survival (EFS) of CNV(−) patients was 60.0% compared with the EFS (16.7%) of CNV(+) patients (P = 0.015, HR = 0.1344, 95%, CI = 0.027 to 0.678). CNVs were also associated with unfavorable histological characteristics (P = 0.003) and likely to occur in stage 4 (P = 0.041). These results might further indicate the role of CNVs in NB chemotherapy resistance (P = 0.059) and show CNVs as a therapeutic target. In multivariate analysis, the presence of CNVs was a clinically negative prognostic marker that impaired the outcome of patients without MNA and associated with poor prognosis in this tumor subset. Comprehensive genetic/genomic profiling instead of focusing on single genetic marker should be performed through in-depth NGS that could reveal prognostic information, improve NB target therapy, and provide a basis for investigations on NB pathogenesis.
In vivo gene transfer into the retina mediated by a novel liposome system.

PURPOSE To determine whether a reporter gene can be introduced into rat and mouse retinas in vivo using the authors' novel liposome system. METHODS Cytomegalovirus-promoted LacZ genes and nonhistone nuclear protein, high mobility group 1 (HMG1), were coencapsulated in liposomes by agitation and sonication. The liposomes were then coated with the envelope of inactivated hemagglutinating virus of Japan (HVJ; Sendai virus) by fusion (HVJ liposome). The HVJ liposome solution was injected into the vitreous cavity of adult Sprague-Dawley rats (n = 30) or the subretinal space of adult CD-1 mice (n = 42). LacZ expression was assessed by beta-galactosidase assay. RESULTS LacZ expression was demonstrated in the photoreceptors as long as 30 days after intravitreal and subretinal injections. beta-Gal activity was observed also in neurons and glial cells in the ganglion cell layer of the intravitreally injected rats and, although at lower intensity, in the retinal pigment epithelium of both animals. No inflammation or toxic effects secondary to the HVJ liposomes were detected on histologic examination. CONCLUSIONS In vivo transfer and expression of a reporter gene into adult mammalian retina can be achieved using HVJ liposomes. This method offers a promise as a nonviral system for in vivo gene transfer into adult mammalian neural retina.
Toxicity and dose-response studies of 1alpha-hydroxyvitamin D2 in a retinoblastoma xenograft model.

BACKGROUND Although calcitriol (1,25-dihydroxycholecalciferol) and vitamin D(2) inhibit retinoblastoma growth in the athymic (nude) mouse xenograft (Y-79 cell line) model of retinoblastoma, they can cause severe toxicity. OBJECTIVE To examine the toxicity of and dose-dependent response for the inhibition of tumor growth for 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), an analogue with reduced systemic toxicity, in the athymic Y-79 mouse model. METHODS Mice were randomized into treatment and control groups for 5-week toxicity and dose-response studies. Treatment was via oral gavage 5 times per week. Dose-response studies measured tumor inhibition and drug serum levels. Tumor size and body weight were measured weekly together with various criteria for toxicity. Animals were euthanized at the end of the treatment period. Tumors and kidneys were harvested, and serum was analyzed for calcium and drug levels. RESULTS Doses of 0.1 to 1.2 microg/d were selected on the basis of toxicity studies for the dose-response trial. Tumor weight and volume in the 0.2-microg and 0.3-microg doses were significantly lower than in controls. Mortality rates and kidney calcification in mice treated with doses of 0.1 to 0.3 microg were lower than those observed in studies of calcitriol and vitamin D(2). CONCLUSION A vitamin D analogue, 1alpha-OH-D(2), inhibits tumor growth in this xenograft model of retinoblastoma with less toxicity than calcitriol and vitamin D(2).
Interactions between Intrinsic and Stimulus-Evoked Activity in Recurrent Neural Networks

Trial-to-trial variability is an essential feature of neural responses, but its source is a subject of active debate. Response variability (Mast and Victor, 1991; Arieli et al., 1995 & 1996; Anderson et al., 2000 & 2001; Kenet et al., 2003; Petersen et al., 2003a & b; Fiser, Chiu and Weliky, 2004; MacLean et al., 2005; Yuste et al., 2005; Vincent et al., 2007) is often treated as random noise, generated either by other brain areas, or by stochastic processes within the circuitry being studied. We call such sources of variability external to stress the independence of this form of noise from activity driven by the stimulus. Variability can also be generated internally by the same network dynamics that generates responses to a stimulus. How can we distinguish between external and internal sources of response variability? Here we show that internal sources of variability interact nonlinearly with stimulus-induced activity, and this interaction yields a suppression of noise in the evoked state. This provides a theoretical basis and potential mechanism for the experimental observation that, in many brain areas, stimuli cause significant suppression of neuronal variability (Werner and Mountcastle, 1963; Fortier, Smith and Kalaska, 1993; Anderson et al., 2000; Friedrich and Laurent, 2004; Churchland et al., 2006; Finn, Priebe and Ferster, 2007; Mitchell, Sundberg and Reynolds, 2007; Churchland et al., 2009). The combined theoretical and experimental results suggest that internally generated activity is a significant contributor to response variability in neural circuits.
Unsolved Problems in Comparing Brain Sizes in Homo Sapiens

When brain size is compared across taxonomic levels, there is a clear relation between body parameters and brain size. It is generally stated that the correlation between brain size and body parameters becomes very small at the species level (Aboitiz, 1996), but this is not the case for Homo sapiens where there is a strong correlation between brain size and body size across racial groups that differ in body size. The control for body size across racial groups (and sexes) is rendered difficult because bodies do not just differ only in height and weight. Within groups different studies show weak and inconsistent brain size/body height correlations. A better understanding of brain size/body height relations must await better quality data and a better understanding of how exactly body parameters should be scaled between groups and sexes. We attribute the clear between-group and weak within-group correlations to the large variety of body sizes and body types in our species, a variety which is only equalled in selectively bred species of animals. At present, there is no meaningful basis for the comparison of brain sizes within and between racial groups and sexes.
Developmental potential of defined neural progenitors derived from mouse embryonic stem cells

The developmental potential of a uniform population of neural progenitors was tested by implanting them into chick embryos. These cells were generated from retinoic acid-treated mouse embryonic stem (ES) cells, and were used to replace a segment of the neural tube. At the time of implantation, the progenitors expressed markers defining them as Pax6-positive radial glial (RG) cells, which have recently been shown to generate most pyramidal neurons in the developing cerebral cortex. Six days after implantation, the progenitors generated large numbers of neurons in the spinal cord, and differentiated into interneurons and motoneurons at appropriate locations. They also colonized the host dorsal root ganglia (DRG) and differentiated into neurons, but, unlike stem cell-derived motoneurons, they failed to elongate axons out of the DRG. In addition, they neither expressed the DRG marker Brn3a nor the Trk neurotrophin receptors. Control experiments with untreated ES cells indicated that when colonizing the DRG, these cells did elongate axons and expressed Brn3a, as well as Trk receptors. Our results thus indicate that ES cell-derived progenitors with RG characteristics generate neurons in the spinal cord and the DRG. They are able to respond appropriately to local cues in the spinal cord, but not in the DRG, indicating that they are restricted in their developmental potential.
Compensatory climbing fiber innervation after unilateral pedunculotomy in the newborn rat: Origin and topographic organization

In neonatal rats the unilateral transaction of the cerebellar peduncles causes a fast and complete degeneration of the contralateral inferior olive. Axons from the remaining olive recross the cerebellar midline and partially innervate the deprived hemicortex. Analysis of the topographic organization of this compensatory projection studied with the axonal tracing method provided the following results.
The Influence of the Integrity of Posterolateral Structures on Tibiofemoral Orientation When an Anterior Cruciate Ligament Graft is Tensioned *

Background The effect of injury to the posterolateral structures of the knee on the success of an anterior cruciate ligament reconstruction is not well known. Hypothesis Increasing graft tension increases the amount of external rotation of the tibia if the posterolateral structures are deficient. Study Design Laboratory study. Methods Eight cadaveric knees underwent techniques similar to a clinical reconstruction except that the distal fixation on the tibia was an external tensioning device used to apply a traction force on the graft. The knee was secured in a joint-testing machine and an instrumented spatial linkage was used to measure the motion of the tibia with respect to the femur. Measurements were taken with forces increasing from 0 to 100 N. The fibular collateral ligament, popliteofibular ligament, and the popliteus tendon were individually cut sequentially, and differences in the relative position of the tibia with respect to the femur were compared with the intact baseline. Results External rotation increased significantly when all of the posterolateral structures were cut and 60, 80, or 100 N of distal traction was applied. Conclusions Deficiency of posterolateral structures of the knee significantly affected the relative external rotation of the tibia. Clinical Relevance Injured posterolateral structures should be repaired before fixation of anterior cruciate ligament grafts.
Relationship between post-exercise plasma CK elevation and muscle mass involved in the exercise.

The purpose of this study was to investigate whether a larger post-exercise increase in plasma creatine kinase (CK) activity would be produced when a larger amount of muscle is damaged by eccentric exercise. Twenty-two non-weight trained females were placed into two groups; Group A (n = 12) and Group B (n = 10). Both groups performed 24 maximal eccentric actions of the forearm flexors on each bout. The right and left arm were exercised on the same day for Group A (24 eccentric actions per arm, a total of 48 actions). In contrast, Group B performed 24 actions with either the right or the left arm on the first bout and performed 24 eccentric actions with the opposite arm on the second bout 3-5 weeks later. Blood samples were taken before and for 5 days after each exercise and plasma CK activity was determined. Forearm flexion isometric force (ISO), range of motion evaluated by relaxed elbow joint angle (RANG) and flexed elbow joint angle (FANG), and perceived muscle soreness (SOR) were also examined to indirectly assess muscle damage. All of the muscle damage indicators changed significantly over time (p < 0.01) for both groups, but changes were not significantly different between arms or between groups. Because it seemed that both arms were equally "damaged" for each group, it was expected that Group A (two arms were exercised on the same day) should show an approximate two-fold increase in plasma CK compared to Group B when one arm was exercised on each bout. (ABSTRACT TRUNCATED AT 250 WORDS)
Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro

Current evidence indicates that the physiological functions of inflammatory cells are highly sensitive to their microenvironment, which is partially determined by the inflammatory cells and their potential targets. In the present investigation, interactions between neutrophils, macrophages and muscle cells that may influence muscle cell death are examined. Findings show that in the absence of macrophages, neutrophils kill muscle cells in vitro by superoxide‐dependent mechanisms, and that low concentrations of nitric oxide (NO) protect against neutrophil‐mediated killing. In the absence of neutrophils, macrophages kill muscle cells through a NO‐dependent mechanism, and the presence of target muscle cells causes a three‐fold increase in NO production by macrophages, with no change in the concentration of inducible nitric oxide synthase. Muscle cells that are co‐cultured with both neutrophils and macrophages in proportions that are observed in injured muscle show cytotoxicity through a NO‐dependent, superoxide‐independent mechanism. Furthermore, the concentration of myeloid cells that is necessary for muscle killing is greatly reduced in assays that use mixed myeloid cell populations, rather than uniform populations of neutrophils or macrophages. These findings collectively show that the magnitude and mechanism of muscle cell killing by myeloid cells are modified by interactions between muscle cells and neutrophils, between muscle cells and macrophages and between macrophages and neutrophils.
Methionine in proteins defends against oxidative stress

A variety of reactive oxygen species react readily with methionine residues in proteins to form methionine sulfoxide, thus scavenging the reactive species. Most cells contain methionine sulfoxide reduc‐tases, which catalyze a thioredoxin‐dependent reduction of methionine sulfoxide back to methionine. Thus, methionine residues may act as catalytic antioxidants, protecting both the protein where they are located and other macromolecules. To test this hypothesis directly, we replaced 40% of the methionine residues in Escherichia coli with norleucine, the carbon‐containing analog, in which the sulfur of methionine is substituted by a methylene group (‐CH2‐). The intracellular free methionine and S‐adenosylmethionine pools were not altered, nor was the specific activity of the key enzyme, glutamine synthetase. When unstressed, both control and norleucine‐substituted cells survived equally well at stationary phase for at least 32 h. However, oxidative stress was more damaging to the norleucine‐substituted cells. They died more rapidly than control cells when challenged by hypochlorite, hydrogen peroxide, or ionizing radiation. One of the most abundant proteins in the cell, elongation factor Tu, was found to be more oxidatively modified in norleucine‐substituted cells, consistent with loss of the antioxidant defense provided by methionine residues. The results of these studies support the hypothesis that methionine in protein acts as an endogenous antioxidant in cells. —Luo, S. , Levine, R. L. Methionine in proteins defends against oxidative stress. FASEB J. 23, 464‐472 (2009)
A Novel Embedding Method for Information Diffusion Prediction in Social Network Big Data

With the increase of social networking websites and the interaction frequency among users, the prediction of information diffusion is required to support effective generalization and efficient inference in the context of social big data era. However, the existing models either rely on expensive probabilistic modeling of information diffusion based on partially known network structures, or discover the implicit structures of diffusion from users’ behaviors without considering the impacts of different diffused contents. To address the issues, in this paper, we propose a novel information-dependent embedding-based diffusion prediction (IEDP) model to map the users in observed diffusion process into a latent embedding space, then the temporal order of users with the timestamps in the cascade can be preserved by the embedding distance of users. Our proposed model further learns the propagation probability of information in the cascade as a function of the relative positions of information-specific user embeddings in the information-dependent subspace. Then, the problem of temporal propagation prediction can be converted into the task of spatial probability learning in the embedding space. Moreover, we present an efficient margin-based optimization algorithm with a fast computation to make the inference of the information diffusion in the latent embedding space. When applying our proposed method to several social network datasets, the experimental results show the effectiveness of our proposed approach for the information diffusion prediction and the efficiency with respect to the inference speed compared with the state-of-the-art methods.
Diversityofaquatic prokaryotic communities in theCuatro Cienegasbasin

The Cuatro Cienegas basin (Coahuila, México) is a composite of different water systems in the middle of the desert with unusually high levels of endemism and diversity in different taxa. Although the diversity of macrobiota has been well described, little is known about the diversity and distribution of microorganisms in the oligotrophic ponds. Here we describe the extent and distribution of diversity found in aquatic prokaryotic communities by analysis of terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes and phylogenetic analysis of cloned genes. Twelve locations within the basin were sampled. Among all the samples, we found a total of 117 operational taxonomic units (OTUs) using T-RFLPs, which ranged in any single sample from four to 49. OTU richness and Shannon diversity indices for different sites varied, but none were particularly high. 16S rRNA gene sequence data showed 68 different phylotypes among 198 clones. The most abundant phylotypes were Gammaand Betaproteobacteria, and extreme halophiles. The differences among sites were significant; 45 TRFs were found only once, and 37% of the total diversity was represented by differences between sites, suggesting high b-diversity. Further studies are needed to test whether this is a direct consequence of environmental heterogeneity in the basin.
The effects of L2 proficiency level on the processing of wh-questions among Dutch second language speakers of English

Abstract Using a self-paced reading task, the present study explores how Dutch-English L2 speakers parse English wh-subject-extractions and wh-object-extractions. Results suggest that English native speakers and highly-proficient Dutch–English L2 speakers do not always exhibit measurable signs of on-line reanalysis when reading subject-versus object-extractions in English. However, less-proficient Dutch-English L2 speakers exhibit greater processing costs on subject-extractions relative to object-extractions, similar to previously reported findings (e.g., Dussias and Piñar, Second Language Research 26: 443–472, 2010; Juffs, Second Language Research 21: 121–151, 2005; Juffs and Harrington, Studies in Second Language Acquisition 17: 482–516, 1995). These findings are discussed in light of relevant research surrounding on-line processing among L2 speakers and their ability to adopt native-like processing patterns in the L2.