Showing papers by "University of Würzburg published in 2005"
World Health Organization1, University of Otago2, Columbia University3, American Foundation for Suicide Prevention4, Ludwig Maximilian University of Munich5, National Institute for Health and Welfare6, University College Dublin7, University of Oslo8, Uppsala University9, University of Würzburg10, National Defense Medical College11, Karolinska Institutet12, University of Hong Kong13
TL;DR: Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates, and other interventions need more evidence of efficacy.
Abstract: ContextIn 2002, an estimated 877 000 lives were lost worldwide through
suicide. Some developed nations have implemented national suicide prevention
plans. Although these plans generally propose multiple interventions, their
effectiveness is rarely evaluated.ObjectivesTo examine evidence for the effectiveness of specific suicide-preventive
interventions and to make recommendations for future prevention programs and
research.Data Sources and Study SelectionRelevant publications were identified via electronic searches of MEDLINE,
the Cochrane Library, and PsychINFO databases using multiple search terms
related to suicide prevention. Studies, published between 1966 and June 2005,
included those that evaluated preventative interventions in major domains;
education and awareness for the general public and for professionals; screening
tools for at-risk individuals; treatment of psychiatric disorders; restricting
access to lethal means; and responsible media reporting of suicide.Data ExtractionData were extracted on primary outcomes of interest: suicidal behavior
(completion, attempt, ideation), intermediary or secondary outcomes (treatment
seeking, identification of at-risk individuals, antidepressant prescription/use
rates, referrals), or both. Experts from 15 countries reviewed all studies.
Included articles were those that reported on completed and attempted suicide
and suicidal ideation; or, where applicable, intermediate outcomes, including
help-seeking behavior, identification of at-risk individuals, entry into treatment,
and antidepressant prescription rates. We included 3 major types of studies
for which the research question was clearly defined: systematic reviews and
meta-analyses (n = 10); quantitative studies, either randomized
controlled trials (n = 18) or cohort studies (n = 24);
and ecological, or population- based studies (n = 41). Heterogeneity
of study populations and methodology did not permit formal meta-analysis;
thus, a narrative synthesis is presented.Data SynthesisEducation of physicians and restricting access to lethal means were
found to prevent suicide. Other methods including public education, screening
programs, and media education need more testing.ConclusionsPhysician education in depression recognition and treatment and restricting
access to lethal methods reduce suicide rates. Other interventions need more
evidence of efficacy. Ascertaining which components of suicide prevention
programs are effective in reducing rates of suicide and suicide attempt is
essential in order to optimize use of limited resources.
2,649 citations
TL;DR: A multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo found the median level of low-density lipoprotein cholesterol was reduced.
Abstract: Background Statins reduce the incidence of cardiovascular events in persons with type 2 diabetes mellitus. However, the benefit of statins in such patients receiving hemodialysis, who are at high risk for cardiovascular disease and death, has not been examined. Methods We conducted a multicenter, randomized, double-blind, prospective study of 1255 subjects with type 2 diabetes mellitus receiving maintenance hemodialysis who were randomly assigned to receive 20 mg of atorvastatin per day or matching placebo. The primary end point was a composite of death from cardiac causes, nonfatal myocardial infarction, and stroke. Secondary end points included death from all causes and all cardiac and cerebrovascular events combined. Results After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 ...
2,340 citations
TL;DR: These data definitively implicate perturbation of TGFβ signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.
Abstract: We report heterozygous mutations in the genes encoding either type I or type II transforming growth factor β receptor in ten families with a newly described human phenotype that includes widespread perturbations in cardiovascular, craniofacial, neurocognitive and skeletal development. Despite evidence that receptors derived from selected mutated alleles cannot support TGFβ signal propagation, cells derived from individuals heterozygous with respect to these mutations did not show altered kinetics of the acute phase response to administered ligand. Furthermore, tissues derived from affected individuals showed increased expression of both collagen and connective tissue growth factor, as well as nuclear enrichment of phosphorylated Smad2, indicative of increased TGFβ signaling. These data definitively implicate perturbation of TGFβ signaling in many common human phenotypes, including craniosynostosis, cleft palate, arterial aneurysms, congenital heart disease and mental retardation, and suggest that comprehensive mechanistic insight will require consideration of both primary and compensatory events.
1,564 citations
TL;DR: This review summarizes empirical research on the management of virtual teams, i.e., distributed work teams whose members predominantly communicate and coordinate their work via electronic media through electronic media, guided by a lifecycle model.
989 citations
TL;DR: This Review classifies strategies in the asymmetric synthesis of axially chiral biaryl compounds according to their underlying concepts and critically evaluates their scope and limitations with reference to selected model reactions and applications.
Abstract: A rotationally hindered and thus stereogenic biaryl axis is the structurally and stereochemically decisive element of a steadily growing number of natural products, chiral auxiliaries, and catalysts. Thus, it is not surprising that significant advances have been made in the asymmetric synthesis of axially chiral biaryl compounds over the past decade. In addition to the classic approach (direct stereoselective aryl-aryl coupling), innovative concepts have been developed in which the asymmetric information is introduced into a preformed, but achiral-that is, symmetric or configurationally labile-biaryl compound, or in which an aryl--C single bond is stereoselectively transformed into an axis. This Review classifies these strategies according to their underlying concepts and critically evaluates their scope and limitations with reference to selected model reactions and applications. Furthermore, the preconditions required for the existence of axial chirality in biaryl compounds are discussed.
985 citations
TL;DR: This study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.
Abstract: Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissuechewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and F. occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant’s defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.
944 citations
TL;DR: This work analyzed 93 single nucleotide polymorphisms for allelic association with AMD in two independent case-control cohorts of German origin and found the strongest association centered over a frequent coding polymorphism, Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of AMD.
Abstract: Age-related macular degeneration (AMD) is a multifactorial disease and a prevalent cause of visual impairment in developed countries. Risk factors include environmental components and genetic determinants. The complement factor H (CFH) has been the first major susceptibility gene for AMD identified within 1q32. Here, we focused on a second region of interest in 10q26 where a recent meta-analysis revealed strongest evidence for linkage to AMD at a genome-wide significance level. Within an interval of 22 Mb, we have analyzed 93 single nucleotide polymorphisms for allelic association with AMD in two independent case-control cohorts of German origin (AMD(combined) n=1166; controls(combined) n=945). Significant association was found across a 60 kb region of high linkage disequilibrium harboring two genes PLEKHA1 and hypothetical LOC387715. The strongest association (P=10(-34)) centered over a frequent coding polymorphism, Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of AMD. Besides abundant expression in placenta, we demonstrate weak expression of LOC387715 in the human retina. At present, however, there is no functional information on this gene, which appears to have evolved recently within the primate lineage. The joint contribution of the common risk allele at LOC387715, Ala69Ser, and at CFH, Tyr402His, was assessed in our case-control population, which suggests an additive model indicating an independent contribution of the two gene loci to disease risk. Our data show a disease odds ratio of 57.6 (95% CI: 37.2, 89.0) conferred by homozygosity for risk alleles at both CFH and LOC387715 when compared with the baseline non-risk genotype.
781 citations
TL;DR: In this article, the authors provided genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFAT-1 − / − hematopoietic stem cells to osteocallast-deficient Fos −/− mice, and by Fos−/− blastocyst complementation.
Abstract: NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1 − / − hematopoietic stem cells to osteoclast-deficient Fos − / − mice, and by Fos − / − blastocyst complementation, thus avoiding the embryonic lethality of NFATc1 − / − mice. However, in vitro osteoclastogenesis in NFATc1 -deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.
718 citations
TL;DR: These unexpected findings change the long-standing concept that the FXII-induced intrinsic coagulation pathway is not important for clotting in vivo and identify FXII as a novel target for antithrombotic therapy.
Abstract: Blood coagulation is thought to be initiated by plasma protease factor VIIa in complex with the membrane protein tissue factor. In contrast, coagulation factor XII (FXII)–mediated fibrin formation is not believed to play an important role for coagulation in vivo. We used FXII-deficient mice to study the contributions of FXII to thrombus formation in vivo. Intravital fluorescence microscopy and blood flow measurements in three distinct arterial beds revealed a severe defect in the formation and stabilization of platelet-rich occlusive thrombi. Although FXII-deficient mice do not experience spontaneous or excessive injury-related bleeding, they are protected against collagen- and epinephrine-induced thromboembolism. Infusion of human FXII into FXII-null mice restored injury-induced thrombus formation. These unexpected findings change the long-standing concept that the FXII-induced intrinsic coagulation pathway is not important for clotting in vivo. The results establish FXII as essential for thrombus formation, and identify FXII as a novel target for antithrombotic therapy.
692 citations
TL;DR: Postoperative chemotherapy alone is a promising treatment for medulloblastoma in young children without metastases in children who have complete resection, residual tumor, and macroscopic metastases.
Abstract: Background The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone. Methods After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate. Treatment was terminated if a complete remission was achieved. Leukoencephalopathy and cognitive deficits were evaluated. Results Forty-three children were treated according to protocol. In children who had complete resection (17 patients), residual tumor (14), and macroscopic metastases (12), the five-year progression-free and overall survival rates (±SE) were 82±9 percent and 93±6 percent, 50±13 percent and 56±14 percent, and 33±14 percent and 38±15 percent, respectively. The rates in 31 patients without macroscopic metastases were 68±8 percent and 77±8 percent. Desmoplastic histology, ...
612 citations
TL;DR: Comparison of data generated by current and future genome projects as well as complementary studies in other species will allow one to approach the molecular and evolutionary mechanisms underlying genome diversity in fish, and will certainly significantly contribute to the understanding of gene evolution and function in humans and other vertebrates.
Abstract: Teleost fish, which roughly make up half of the extant vertebrate species, exhibit an amazing level of biodiversity affecting their morphology, ecology and behaviour as well as many other aspects of their biology. This huge variability makes fish extremely attractive for the study of many biological questions, particularly of those related to evolution. New insights gained from different teleost species and sequencing projects have recently revealed several peculiar features of fish genomes that might have played a role in fish evolution and speciation. There is now substantial evidence that a round of tetraploidization/rediploidization has taken place during the early evolution of the ray-finned fish lineage, and that hundreds of duplicate pairs generated by this event have been maintained over hundreds of millions of years of evolution. Differential loss or subfunction partitioning of such gene duplicates might have been involved in the generation of fish variability. In contrast to mammalian genomes, teleost genomes also contain multiple families of active transposable elements, which might have played a role in speciation by affecting hybrid sterility and viability. Finally, the amazing diversity of sex determination systems and the plasticity of sex chromosomes observed in teleost might have been involved in both pre- and postmating reproductive isolation. Comparison of data generated by current and future genome projects as well as complementary studies in other species will allow one to approach the molecular and evolutionary mechanisms underlying genome diversity in fish, and will certainly significantly contribute to our understanding of gene evolution and function in humans and other vertebrates.
TL;DR: A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV Mpros, potent antiviral activity, and extremely low cellular toxicity in cell-based assays.
Abstract: The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (Mpros), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of Mpro-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV Mpros, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases.
TL;DR: A new approach termed “controlled aliasing in parallel imaging results in higher acceleration” (CAIPIRINHA) is presented, which modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure.
Abstract: In all current parallel imaging techniques, aliasing artifacts resulting from an undersampled acquisition are removed by means of a specialized image reconstruction algorithm. In this study a new approach termed "controlled aliasing in parallel imaging results in higher acceleration" (CAIPIRINHA) is presented. This technique modifies the appearance of aliasing artifacts during the acquisition to improve the subsequent parallel image reconstruction procedure. This new parallel multi-slice technique is more efficient compared to other multi-slice parallel imaging concepts that use only a pure postprocessing approach. In this new approach, multiple slices of arbitrary thickness and distance are excited simultaneously with the use of multi-band radiofrequency (RF) pulses similar to Hadamard pulses. These data are then undersampled, yielding superimposed slices that appear shifted with respect to each other. The shift of the aliased slices is controlled by modulating the phase of the individual slices in the multi-band excitation pulse from echo to echo. We show that the reconstruction quality of the aliased slices is better using this shift. This may potentially allow one to use higher acceleration factors than are used in techniques without this excitation scheme. Additionally, slices that have essentially the same coil sensitivity profiles can be separated with this technique.
Malmö University1, Imperial College London2, French Institute of Health and Medical Research3, Leiden University Medical Center4, Technische Universität München5, University of Amsterdam6, Hull and East Yorkshire Hospitals NHS Trust7, International Atomic Energy Agency8, University of Würzburg9, Lund University10, Aberdeen Royal Infirmary11, Mayo Clinic12, University College London13
TL;DR: The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, and positron emission tomography.
Abstract: The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.
TL;DR: FRET from CFP to FlAsH reports GPCR activation in living cells without disturbing receptor function and shows that the small size of the tetracysteine-biarsenical tag can be decisively advantageous.
Abstract: Fluorescence resonance energy transfer (FRET) from cyan to yellow fluorescent proteins (CFP/YFP) is a well-established method to monitor protein-protein interactions or conformational changes of individual proteins. But protein functions can be perturbed by fusion of large tags such as CFP and YFP. Here we use G protein-coupled receptor (GPCR) activation in living cells as a model system to compare YFP with the small, membrane-permeant fluorescein derivative with two arsen-(III) substituents (fluorescein arsenical hairpin binder; FlAsH) targeted to a short tetracysteine sequence. Insertion of CFP and YFP into human adenosine A(2A) receptors allowed us to use FRET to monitor receptor activation but eliminated coupling to adenylyl cyclase. The CFP/FlAsH-tetracysteine system gave fivefold greater agonist-induced FRET signals, similar kinetics (time constant of 66-88 ms) and perfectly normal downstream signaling. Similar results were obtained for the mouse alpha(2A)-adrenergic receptor. Thus, FRET from CFP to FlAsH reports GPCR activation in living cells without disturbing receptor function and shows that the small size of the tetracysteine-biarsenical tag can be decisively advantageous.
TL;DR: Punch skin biopsy is a safe and reliable technique andConfocal microscopy may be particularly useful to investigate myelinated nerve fibres, dermal receptors and dermal annex innervation and to assess the potential usefulness of skin biopsies as an outcome measure in peripheral neuropathy trials.
Abstract: immunostaining, intraepidermal, nerve fibres, painful neuropathy, peripheral neuropathy, skin biopsy, small fibre neuropathy
TL;DR: Guard cells provide an excellent system to study cross-talk, as multiple signaling pathways induce both short- and long-term responses in these sensory cells, and are related to ion transport at the plasma membrane and vacuolar membrane.
Abstract: Stomata can be regarded as hydraulically driven valves in the leaf surface, which open to allow CO2 uptake and close to prevent excessive loss of water. Movement of these 'Watergates' is regulated by environmental conditions, such as light, CO2 and humidity. Guard cells can sense environmental conditions and function as motor cells within the stomatal complex. Stomatal movement results from the transport of K+ salts across the guard cell membranes. In this review, we discuss the biophysical principles and mechanisms of stomatal movement and relate these to ion transport at the plasma membrane and vacuolar membrane. Studies with isolated guard cells, combined with recordings on single guard cells in intact plants, revealed that light stimulates stomatal opening via blue light-specific and photosynthetic-active radiation-dependent pathways. In addition, guard cells sense changes in air humidity and the water status of distant tissues via the stress hormone abscisic acid (ABA). Guard cells thus provide an excellent system to study cross-talk, as multiple signaling pathways induce both short- and long-term responses in these sensory cells.
TL;DR: The role of IL-17 is crucially involved in the cytokine network as an effector cytokine in EAE and neutralization ofIL-17 with a monoclonal antibody also ameliorated the disease course.
TL;DR: The goal of the present document is to review the most recent achievements in the field and to analyze future directions in research and development.
TL;DR: It is demonstrated that uptake of cis-platin is mediated by hOCT2 in renal proximal tubules, explaining its organ-specific toxicity.
Abstract: Cis- platin is an effective anti-neoplastic agent, but it is also highly nephrotoxic. Here, we clearly identify the human organic cation transporter 2 (hOCT2) as the critical transporter for cis- platin nephrotoxicity in isolated human proximal tubules and offer a potential mechanism for reducing nephrotoxicity in clinical practice. Interaction of cis- platin with hOCT2 in kidney or hOCT1 in liver was investigated with the fluorescent cation 4-[4-(dimethyl-amino)styril]-methylpyridinium in stably transfected HEK293 cells and for the first time in tissues physiologically expressing these transporters, human proximal tubules, and human hepatocyte couplets. Cis- platin (100 μmol/L) inhibited transport via hOCT2-HEK293 but not hOCT1-HEK293. In human proximal tubules cis- platin competed with basolateral organic cation transport, whereas it had no effect in tubules from a diabetic kidney or in hepatocytes. In hOCT2-HEK293 cells treated for 15 hours, incubation with cis- platin induced apoptosis, which was completely suppressed by contemporaneous incubation with the hOCT2 substrate cimetidine (100 μmol/L). These findings demonstrate that uptake of cis- platin is mediated by hOCT2 in renal proximal tubules, explaining its organ-specific toxicity. A combination of cis- platin with other substrates that compete for hOCT2 offers an effective option to decrease nephrotoxicity in the clinical setting.
TL;DR: The authors found that goal-related accessibility and post-fulfillment inhibition were proportional to the goal's expectancy, the goal value, and their interaction, and these effects are proportional to strength of the motivation.
TL;DR: This study illustrates for the first time the phenotypic variation of the polysaccharide capsule in the initial phase of pneumococcal infections using a modified fixation method that allowed monitoring of the state of capsule expression of pathogens during the infectious process.
Abstract: The capsular polysaccharide of Streptococcus pneumoniae represents an important virulence factor and protects against phagocytosis. In this study the amount of capsular polysaccharide present on the bacterial surface during the infection process was illustrated by electron microscopic studies. After infection of A549 cells (type II pneumocytes) and HEp-2 epithelial cells a modified fixation method was used that allowed visualization of the state of capsule expression. This modified fixation procedure did not require the use of capsule-specific antibodies. Visualization of pneumococci in intimate contact and invading cells demonstrated that pneumococci were devoid of capsular polysaccharide. Pneumococci not in contact with the cells did not show alterations in capsular polysaccharide. After infection of the cells, invasive pneumococci of different strains and serotypes were recovered. Single colonies of these recovered pneumococci exhibited an up-to-105-fold-enhanced capacity to adhere and an up-to-104-fold-enhanced capacity to invade epithelial cells. Electron microscopic studies using a lysine-ruthenium red (LRR) fixation procedure or cryo-field emission scanning electron microscopy revealed a reduction in capsular material, as determined in detail for a serotype 3 pneumococcal strain. The amount of polysaccharide in the serotype 3 capsule was also determined after intranasal infection of mice. This study illustrates for the first time the phenotypic variation of the polysaccharide capsule in the initial phase of pneumococcal infections. The modified LRR fixation allowed monitoring of the state of capsule expression of pathogens during the infectious process.
TL;DR: This is the first report on the cultivation of bacteria in insect antennae and the first case of a symbiosis involving bacteria of the important antibiotic-producing genus Streptomyces, which might play an important role in other insects as well.
TL;DR: In this article, the authors used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1.
Abstract: Mirror neurons discharge with both action observation and action execution. It has been proposed that the mirror neuron system is instrumental in motor learning. The human primary motor cortex (M1) displays mirror activity in response to movement observation, is capable of forming motor memories, and is involved in motor learning. However, it is not known whether movement observation can lead directly to the formation of motor memories in the M1, which is considered a likely physiological step in motor learning. Here, we used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1. An extended period of observation of thumb movements that were oriented oppositely to the previously determined habitual directional bias increased the probability of TMS-evoked thumb movements to fall within the observed direction. Furthermore, the acceleration of TMS-evoked thumb movements along the principal movement axis and the balance of excitability of muscle representations active in the observed movements were altered in favor of the observed movement direction. These findings support a role for the mirror neuron system in memory formation and possibly human motor learning.
TL;DR: Using genetic mapping, mutation identification and western-blot data, it is identified the defective protein in FA-J cells as BRIP1, a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.
Abstract: Seven Fanconi anemia-associated proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core complex that activates the monoubiquitination of FANCD2, targeting FANCD2 to BRCA1-containing nuclear foci. Cells from individuals with Fanconi anemia of complementation groups D1 and J (FA-D1 and FA-J) have normal FANCD2 ubiquitination. Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1.
TL;DR: A large-scale analysis of more than 54,000 currently known ITS2 sequences shows that the previously described core structure can be found for more than 5000 sequences in a wide variety of taxa within the eukaryotes, indicating that the core secondary structure is indeed conserved.
Abstract: The ongoing characterization of novel species creates the need for a molecular marker which can be used for species- and, simultaneously, for mega-systematics. Recently, the use of the internal transcribed spacer 2 (ITS2) sequence was suggested, as it shows a high divergence in sequence with an assumed conservation in structure. This hypothesis was mainly based on small-scale analyses, comparing a limited number of sequences. Here, we report a large-scale analysis of more than 54,000 currently known ITS2 sequences with the goal to evaluate the hypothesis of a conserved structural core and to assess its use for automated large-scale phylogenetics. Structure prediction revealed that the previously described core structure can be found for more than 5000 sequences in a wide variety of taxa within the eukaryotes, indicating that the core secondary structure is indeed conserved. This conserved structure allowed an automated alignment of extremely divergent sequences as exemplified for the ITS2 sequences of a ctenophorean eumetazoon and a volvocalean green alga. All classified sequences, together with their structures can be accessed at http://www.biozentrum.uni-wuerzburg.de/bioinformatik/projects/ITS2.html. Furthermore, we found that, although sample sequences are known for most major taxa, there exists a profound divergence in coverage, which might become a hindrance for general usage. In summary, our analysis strengthens the potential of ITS2 as a general phylogenetic marker and provides a data source for further ITS2-based analyses.
TL;DR: Current knowledge about the physical and chemical properties of plant cuticles and their role in interactions with microorganisms, phytophagous insects, and their antagonists are summarized.
Abstract: The surface of the primary aerial parts of terrestrial plants is covered by a cuticle, which has crucial autecological functions, but also serves as an important interface in trophic interactions. The chemical and physical properties of this layer contribute to these functions. The cuticle is composed of the cuticular layer and the cuticle proper, which is covered by epicuticular waxes. Whereas the cutin fraction is a polyester-type biopolymer composed of hydroxyl and hydroxyepoxy fatty acids, the cuticular waxes are a complex mixture of long-chain aliphatic and cyclic compounds. These highly lipophilic compounds determine the hydrophobic quality of the plant surface and, together with the microstructure of the waxes, vary in a species-specific manner. The physicochemical characteristics contribute to certain optical features, limit transpiration, and influence adhesion of particles and organisms. In chemical ecology, where interactions between organisms and the underlying (allelo-) chemical principles are studied, it is important to determine what is present at this interface between the plant and the environment. Several useful equations can allow estimation of the dissolution of a given organic molecule in the cuticle and its transport properties. The implementation of these equations is exemplified by examining glucosinolates, which play an important role in interactions of plants with other organisms. An accurate characterization of physicochemical properties of the plant surface is needed to understand its ecological significance. Here, we summarize current knowledge about the physical and chemical properties of plant cuticles and their role in interactions with microorganisms, phytophagous insects, and their antagonists.
TL;DR: Although many molecular details of the coronavirus life cycle remain to be investigated, the available information suggests that these viruses and their distant nidovirus relatives employ a unique collection of enzymatic activities and other protein functions to synthesize a set of 5′-leader-containing subgenomic mRNAs and to replicate the largest RNA virus genomes currently known.
Abstract: Coronavirus genome replication and transcription take place at cytoplasmic membranes and involve coordinated processes of both continuous and discontinuous RNA synthesis that are mediated by the viral replicase, a huge protein complex encoded by the 20-kb replicase gene. The replicase complex is believed to be comprised of up to 16 viral subunits and a number of cellular proteins. Besides RNA-dependent RNA polymerase, RNA helicase, and protease activities, which are common to RNA viruses, the coronavirus replicase was recently predicted to employ a variety of RNA processing enzymes that are not (or extremely rarely) found in other RNA viruses and include putative sequence-specific endoribonuclease, 3′-to-5′ exoribonuclease, 2′-O-ribose methyltransferase, ADP ribose 1′-phosphatase and, in a subset of group 2 coronaviruses, cyclic phosphodiesterase activities. This chapter reviews (1) the organization of the coronavirus replicase gene, (2) the proteolytic processing of the replicase by viral proteases, (3) the available functional and structural information on individual subunits of the replicase, such as proteases, RNA helicase, and the RNA-dependent RNA polymerase, and (4) the subcellular localization of coronavirus proteins involved in RNA synthesis. Although many molecular details of the coronavirus life cycle remain to be investigated, the available information suggests that these viruses and their distant nidovirus relatives employ a unique collection of enzymatic activities and other protein functions to synthesize a set of 5′-leader-containing subgenomic mRNAs and to replicate the largest RNA virus genomes currently known.
TL;DR: Drosophila protein Spire represents a third class of actin nucleation factor that nucleates new filaments at a rate similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament.
Abstract: The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor. In vitro, Spire nucleates new filaments at a rate that is similar to that of the formin family of proteins but slower than in the activated Arp2/3 complex, and it remains associated with the slow-growing pointed end of the new filament. Spire contains a cluster of four WASP homology 2 (WH2) domains, each of which binds an actin monomer. Maximal nucleation activity requires all four WH2 domains along with an additional actin-binding motif, conserved among Spire proteins. Spire itself is conserved among metazoans and, together with the formin Cappuccino, is required for axis specification in oocytes and embryos, suggesting that multiple actin nucleation factors collaborate to construct essential cytoskeletal structures.
TL;DR: A neural feedback mechanism is described; newly born neurons produce cardiotrophin-1, which instructs multipotent cortical precursors to generate astrocytes, thereby ensuring that gliogenesis does not occur until neurogenesis is largely complete.