Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution in bioinformatic resources: 2009 update on the Bioinformatics Links Directory

All of the life science research web servers published in this and previous issues of Nucleic Acids Research, together with other useful tools, databases and resources for bioinformatics and molecular biology research are freely accessible online through the Bioinformatics Links Directory, http://bioinformatics.ca/links_directory/. Entirely dependent on user feedback and community input, the Bioinformatics Links Directory exemplifies an open access research tool and resource. With 112 websites featured in the July 2009 Web Server Issue of Nucleic Acids Research, the 2009 update brings the total number of servers listed in the Bioinformatics Links Directory close to an impressive 1400 links. A complete list of all links listed in this Nucleic Acids Research 2009 Web Server Issue can be accessed online at http://bioinfomatics.ca/links_directory/narweb2009/. The 2009 update of the Bioinformatics Links Directory, which includes the Web Server list and summaries, is also available online at the Nucleic Acids Research website, http://nar.oxfordjournals. org/.
Behavioural and pharmacological relevance of stroke-prone spontaneously hypertensive rats as an animal model of a developmental disorder

The present study evaluates juvenile stroke-prone spontaneously hypertensive rats (SHRSP) as an animal model of a developmental disorder, which is diagnosed according to hyperactivity-impulsivity and/or inattention. To characterize behavioural alterations, we studied motor activity, as well as emotional and cognitive behaviours in juvenile SHRSP, with and without methylphenidate, a psychostimulant. Ambulatory and rearing activities in the open-field environment were significantly higher in SHRSP than in Wistar–Kyoto rats (WKY). In the elevated plus maze task, the entries into open arms, as an index of impulsivity, were significantly increased in SHRSP. In the Y-maze task, spontaneous alternation behaviour, as an index of attention, was significantly lowered in the male SHRSP, but not in the female SHRSP, indicating that spontaneous alternation deficit is gender specific. Methylphenidate (0.01–1 mg/kg, i.p.) significantly attenuated locomotor hyperactivity at low doses and dose-dependently improved the spontaneous alternation deficit in SHRSP. Our findings reveal that juvenile SHRSP manifest problematic behaviours resembling a developmental disorder, attention-deficit/hyperactivity disorder (ADHD), namely hyperactivity-impulsivity and/or inattention. Methylphenidate alleviated the behavioural symptoms of hyperactivity and inattention. We propose that juvenile SHRSP are an appropriate animal model of a developmental disorder resembling ADHD, from behavioural and pharmacological perspectives.
Effects of estradiol-17beta and bisphenol A administered chronically to mice throughout pregnancy and lactation on the male pups' reproductive system.

AIM To assess the effect of estradiol-17beta (E(2)) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice. METHODS Female mice were implanted with a tube filled with 10 ng, 500 ng, 1 microg, or 10 microg of E(2), or 100 microg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E(2) was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 microg/day. RESULTS Most of the mice given 1 microg and 10 microg of E(2) did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights (testes, epididymides and accessory reproductive glands) in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E(2) and 5 mg of BPA than that in the control. CONCLUSION Chronic exposure to E(2) and BPA might disrupt spermatogenesis in male pups.
Convergence accelerators in the computation of molecular integrals over Slater-type basis functions in the two-range one-center expansion method.

The so-called nonlinear transformations may be of substantial help in many practical problems including the so-called multicenter integrals. In this work Wynn's epsilon algorithm and the Levin's [ital u] transformation have been used to improve the convergence of the series representation of three-center two-electron integrals obtained via the so-called two-range one-center expansion method.
Connectivity of the human periventricular-periaqueductal gray region.

OBJECT The periventricular gray (PVG) zone and its continuation, the periaqueductal gray (PAG) substance, have been targets for deep brain stimulation (DBS) in the alleviation of intractable pain for longer than two decades. Nevertheless, the anatomical connectivity of this region has been fairly poorly defined. The effects of DBS in this region are probably related to the release of endogenous endorphins, but until the connectivity of this region is better understood the mechanisms will remain unclear. METHODS Diffusion tractography was used to trace the pathways of the PVG-PAG region in seven healthy human volunteers. Images were acquired with the aid of a 1.5-tesla magnetic resonance imaging system. The region of interest was located just lateral to the posterior commissure and extended caudally to the level of the superior colliculus. Probabilistic diffusion tractography was performed from each voxel in each patient's PVG-PAG region. The PVG-PAG region was found to yield descending projections to the spinal cord and cerebellum. Ascending projections to the thalamus and frontal lobes were also observed. CONCLUSIONS These findings suggest that the PVG-PAG region may modulate pain by two mechanisms: one involving the antinociceptive system in the spinal cord and the other involving influences on the central pain network.
Sensitivity analysis of the material properties of different soft-tissues: implications for a subject-specific knee arthroplasty.

Introduction While developing a subject-specific knee model, different kinds of data-inputs are required. If information about geometries can be definitely obtained from images, more effort is necessary for the in vivo properties. Consequently, such information are recruited from the literature as common habit. However, the effects of the combined sources still need to be evaluated. Methods This work aims at developing an intact native subject-specific knee model for performing a sensitivity analysis on soft-tissues. The impacts on the biomechanical outputs were analysed during a daily activity for which articular knee kinetics and kinematics were compared among the different configurations. Prior to the sensitivity analysis, experimental and literature data were checked for the model reliability. Results Average values of mixed sources allowed the agreement with experimental data for personalized outputs. From the sensitivity analysis, knee kinematics did not significantly change in the selected ranges of properties for the soft-tissues (in rotation less than 0.5°), while contact stresses were greatly affected, especially for the articular cartilage (with differences in the results more than 100%). Conclusion In conclusion, during the development of a personalized knee model, the selection of the correct material properties is fundamental because wrong values could highly affect the numerical results. Level of evidence III a.
Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways

Rho GTPases and their downstream effectors regulate changes in the actin cytoskeleton that underlie cell motility and adhesion. They also participate, with RhoA, in the regulation of gene transcription by activating serum response factor (SRF)-mediated transcription from the serum response element (SRE). SRF-mediated transcription is also promoted by several proteins that regulate the polymerization or stability of actin. We have previously identified a family of PP2C phosphatases, POPXs, which can dephosphorylate the CDC42/RAC-activated kinase PAK and downregulate its enzymatic and actin cytoskeletal activity. We now report that POPX2 interacts with the formin protein mDia1 (DIAPH1). This interaction is enhanced when mDia1 is activated by RhoA. The binding of POPX2 to mDia1 or to an mDia-containing complex greatly decreases the ability of mDia1 to activate transcription from the SRE. We propose that the interaction between mDia1 and POPX2 (PPM1F) serves to regulate both the actin cytoskeleton and SRF-mediated transcription, and to link the CDC42/RAC1 pathways with those of RhoA.
First Use of a Mineral Liquid Crystal for Measurement of Residual Dipolar Couplings of a Nonlabeled Biomolecule.

Superimposing the two 13 C,1 H correlation maps of an unlabeled pentasaccharide acquired in D2 O (upper doublet) and in a magnetically aligned mineral liquid crystal, a colloidal suspension of V2 O5 (lower doublet), reveals that, in the second case, D components appear in addition to the usual splittings J. This is a result of the partial alignment of the biomolecule, and provides long-range structural NMR data.
Transcriptional Profiling of Arabidopsis Tissues Reveals the Unique Characteristics of the Pollen Transcriptome1[w]

Pollen tubes are a good model for the study of cell growth and morphogenesis because of their extreme elongation without cell division. Yet, knowledge about the genetic basis of pollen germination and tube growth is still lagging behind advances in pollen physiology and biochemistry. In an effort to reduce this gap, we have developed a new method to obtain highly purified, hydrated pollen grains of Arabidopsis through flowcytometric sorting, and we used GeneChips (Affymetrix, Santa Clara, CA; representing approximately 8,200 genes) to compare the transcriptional profile of sorted pollen with those of four vegetative tissues (seedlings, leaves, roots, and siliques). We present a new graphical tool allowing genomic scale visualization of the unique transcriptional profile of pollen. The 1,584 genes expressed in pollen showed a 90% overlap with genes expressed in these vegetative tissues, whereas one-third of the genes constitutively expressed in the vegetative tissues were not expressed in pollen. Among the 469 genes enriched in pollen, 162 were selectively expressed, and most of these had not been associated previously with pollen. Their functional classification reveals several new candidate genes, mainly in the categories of signal transduction and cell wall biosynthesis and regulation. Thus, the results presented improve our knowledge of the molecular mechanisms underlying pollen germination and tube growth and provide new directions for deciphering their genetic basis. Because pollen expresses about one-third of the number of genes expressed on average in other organs, it may constitute an ideal system to study fundamental mechanisms of cell biology and, by omission, of cell division.
Genome-wide analysis of day/night DNA methylation differences in Populus nigra

DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understood. In this study, we detected global methylation patterns in leaves of the black poplar Populus nigra ‘N46’ at 8:00 and 24:00 by methylated DNA immunoprecipitation sequencing (MeDIP-seq). We found 10,027 and 10,242 genes to be methylated in the 8:00 and 24:00 samples, respectively. The methylated genes appeared to be involved in multiple biological processes, molecular functions, and cellular components, suggesting important roles for DNA methylation in poplar cells. Comparing the 8:00 and 24:00 samples, only 440 differentially methylated regions (DMRs) overlapped with genic regions, including 193 hyper- and 247 hypo-methylated DMRs, and may influence the expression of 137 downstream genes. Most hyper-methylated genes were associated with transferase activity, kinase activity, and phosphotransferase activity, whereas most hypo-methylated genes were associated with protein binding, ATP binding, and adenyl ribonucleotide binding, suggesting that different biological processes were activated during the day and night. Our results indicated that methylated genes were prevalent in the poplar genome, but that only a few of these participated in diurnal gene expression regulation.
Afferent and Efferent Connections of the Dorsocentral Telencephalon in an Electrosensory Teleost, Gymnotus carapo

Biotinylated dextran amine was injected unilaterally into dorsal regions of the telencephalon of the weakly electric fish Gymnotus carapo in order to study the afferent and efferent connections of specific dorsal regions with ventral regions of the telencephalon and with other regions of the central nervous system. Efferent pathways from the dorsolateral area of the telencephalon project ipsilaterally to the anterior hypothalamic nucleus, the ventral thalamus and magnocellular tegmental nucleus, whose axons reach the spinal cord. Anterograde labeling showed that the central division of the dorsal telencephalon sends efferent projections through the lateral forebrain bundle towards the ipsilateral lateral and medial preglomerular nucleus, the pretectal nucleus, the optic tectum and the dorsal torus semicircularis, regions that are all involved in the processing of electrosensory and/or multisensory information. In addition, when biotinylated dextran amine was injected into the dorsal torus semicircularis, retrogradely labeled neurons were observed in the dorsocentral area of the telencephalon. The dorsocentral area is also a target of the extra-telencephalic afferents originating from rostral, lateral and medial regions of preglomerular complex. Within the telencephalon, neurons of many ventral subdivisions project ipsilaterally to the dorsocentral area. The dorsocentral, dorsolateral and dorsomedial areas are connected ipsilaterally and reciprocally. The dorsocentral area is reciprocally connected with its contralateral homologue through the anterior commissure.
A new approach to cooperative pathfinding

In the multi-agent pathfinding problem, groups of agents need to plan paths between their respective start and goal locations in a given environment, usually a two-dimensional map. Existing approaches to this problem include using static or dynamic information to help coordination. However, the resulting behaviour is not always desirable, in that too much information is hand-coded into the problem, agents take paths which look unintelligent, or because the agents collide and must re-plan frequently. We present a distributed approach in which agents share information about the direction in which they traveled when passing through each location. This information is then used to encourage agents passing through the same location to travel in the same direction as previous agents. In addition to this new approach, we present performance metrics for multi-agent path planning as well as experimental results for the new approach. These results indicate that the number of collisions between agents is reduced and that the visual fidelity is improved.
Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl‐CoA dehydrogenase deficiencies, with special focus on genotype–phenotype relationship

Mutation analysis of metabolic disorders, such as the fatty acid oxidation defects, offers an additional, and often superior, tool for specific diagnosis compared to traditional enzymatic assays. With the advancement of the structural part of the Human Genome Project and the creation of mutation databases, procedures for convenient and reliable genetic analyses are being developed. The most straightforward application of mutation analysis is to specific diagnoses in suspected patients, particularly in the context of family studies and for prenatal/preimplantation analysis. In addition, from these practical uses emerges the possibility to study genotype–phenotype relationships and investigate the molecular pathogenesis resulting from specific mutations or groups of mutations. In the present review we summarize current knowledge regarding genotype–phenotype relationships in three disorders of mitochondrial fatty acid oxidation: very‐long chain acyl‐CoA dehydrogenase (VLCAD, also ACADVL), medium‐chain acyl‐CoA dehydrogenase (MCAD, also ACADM), and short‐chain acyl‐CoA dehydrogenase (SCAD, also ACADS) deficiencies. On the basis of this knowledge we discuss current understanding of the structural implications of mutation type, as well as the modulating effect of the mitochondrial protein quality control systems, composed of molecular chaperones and intracellular proteases. We propose that the unraveling of the genetic and cellular determinants of the modulating effects of protein quality control systems may help to assess the balance between genetic and environmental factors in the clinical expression of a given mutation. The realization that the effect of the monogene, such as disease‐causing mutations in the VLCAD, MCAD, and SCAD genes, may be modified by variations in other genes presages the need for profile analyses of additional genetic variations. The rapid development of mutation detection systems, such as the chip technologies, makes such profile analyses feasible. However, it remains to be seen to what extent mutation analysis will be used for diagnosis of fatty acid oxidation defects and other metabolic disorders. Hum Mutat 18:169–189, 2001. © 2001 Wiley‐Liss, Inc.
Rosiglitazone decreases bone mass and bone marrow fat.

CONTEXT Activation of peroxisome proliferator-activated receptor-γ is believed to promote adipocyte development from mesenchymal stem cells in the bone marrow at the expense of osteoblasts, leading to decreased bone mineral density (BMD) and increased marrow fat. OBJECTIVE The objective of the study was to examine the effect of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, on BMD assessed by dual-energy x-ray absorptiometry in 53 healthy postmenopausal women and spine bone marrow fat assessed by magnetic resonance imaging proton spectroscopy. DESIGN This was a 14-wk prospective, double-blind, randomized, placebo-controlled trial. SETTING The study was conducted in the general community. PATIENTS Fifty-three healthy postmenopausal women participated in the study. INTERVENTION Intervention included rosiglitazone tablets of 8 mg/d. MAIN OUTCOME MEASURES The primary end point was a change in BMD. RESULTS At the femoral neck, BMD decreased by 1.34 ± 0.60% (mean ± sem) in the rosiglitazone group, whereas BMD increased by 0.28 ± 0.56% in the placebo group (P = 0.055). At the lumbar spine, BMD decreased by 1.03 ± 0.34% in the rosiglitazone group and 0.42 ± 0.35% in the placebo group (P = 0.22). The bone resorption marker carboxy-terminal telopeptide increased by 20.4 ± 7.7% (mean ± sem) in the rosiglitazone group and decreased by 7.1 ± 4.7% in the placebo group (P = 0.003). Spine fat decreased by 13.5 ± 5.5% (mean ± sem) in the rosiglitazone group and increased by 6.8 ± 7.4% in the placebo group (P = 0.056). CONCLUSIONS Contrary to what was expected, spine fat decreased during rosiglitazone treatment. Furthermore, rosiglitazone treatment resulted in uncoupling of bone resorption and formation leading to bone loss. Our data suggest that the bone marrow osteoblast-adipocyte relationship is more complex than was assumed and that the two cell types can be independently affected.
Similarities and differences in the effects of verapamil, diltiazem and nifedipine on arterial baroreflexes of anesthetized cats.

The effects of verapamil, diltiazem and nifedipine on baroreflex sensitivity (BS) were investigated in anesthetized cats at equihypotensive doses of 100, 100 and 10 micrograms/kg, respectively. The gain in BS (ms/mmHg) was calculated from the ratio delta heart period/delta systolic pressure following evoked rises and falls in arterial pressure. Verapamil and diltiazem significantly augmented BS while nifedipine depressed BS during evoked rises in arterial pressure. By contrast, BS was significantly depressed by diltiazem and nifedipine in response to depressor challenges with nitroprusside, while it was unaffected by verapamil. The augmentatory action of verapamil on BS after pressor challenges, was abolished by bilateral vagotomy while the inhibitory action of nifedipine was still evident after vagotomy, suggesting a vagal augmentatory action for verapamil and an involvement of the cardiac sympathetic nerves in the inhibitory action of nifedipine on BS. The differences between the actions of the 3 drugs on BS are not readily explainable by our data but they cannot be attributed to alterations of cardiac autonomic function since at the doses employed none of the drugs affected the cardiac responses to carotid occlusion, i.v. isoproterenol or electrical stimulation of the right vagus. It is concluded that BS is affected differently by the 3 chemically unrelated calcium channel blockers in a way which could either be contributory or deleterious to the antihypertensive effectiveness of these drugs.
Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis.

BACKGROUND Borrelia burgdorferi is difficult to detect in synovial fluid, which limits our understanding of the pathogenesis of Lyme arthritis, particularly when arthritis persists despite antibiotic therapy. METHODS Using the polymerase chain reaction (PCR), we attempted to detect B. burgdorferi DNA in joint-fluid samples obtained over a 17-year period. The samples were tested in two separate laboratories with four sets of primers and probes, three of which target plasmid DNA that encodes outer-surface protein A (OspA). RESULTS B. burgdorferi DNA was detected in 75 of 88 patients with Lyme arthritis (85 percent) and in none of 64 control patients. Each of the three OspA primer-probe sets was sensitive, and the results were moderately concordant in the two laboratories (kappa = 0.54 to 0.73). Of 73 patients with Lyme arthritis that was untreated or treated with only short courses of oral antibiotics, 70 (96 percent) had positive PCR results. In contrast, of 19 patients who received either parenteral antibiotics or long courses of oral antibiotics (> or = 1 month), only 7 (37 percent) had positive tests (P < 0.001). None of these seven patients had received more than two months of oral antibiotic treatment or more than three weeks of intravenous antibiotic treatment. Of 10 patients with chronic arthritis (continuous joint inflammation for one year or more) despite multiple courses of antibiotics, 7 had consistently negative tests in samples obtained three months to two years after treatment. CONCLUSIONS PCR testing can detect B. burgdorferi DNA in synovial fluid. This test may be able to show whether Lyme arthritis that persists after antibiotic treatment is due to persistence of the spirochete.