The Magellanic Corona as the key to the formation of the Magellanic Stream.

The dominant gaseous structure in the Galactic halo is the Magellanic Stream. This extended network of neutral and ionized filaments surrounds the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), the two most massive satellite galaxies of the Milky Way1-4. Recent observations indicate that the LMC and SMC are on their first passage around the Galaxy5, that the Magellanic Stream is made up of gas stripped from both clouds2,6,7 and that the majority of this gas is ionized8,9. Although it has long been suspected that tidal forces10,11 and ram-pressure stripping12,13 contributed to the formation of the Magellanic Stream, models have not been able to provide a full understanding of its origins3. Several recent developments-including the discovery of dwarf galaxies associated with the Magellanic group14-16, determination of the high mass of the LMC17, detection of highly ionized gas near stars in the LMC18,19 and predictions of cosmological simulations20,21-support the existence of a halo of warm (roughly 500,000 kelvin) ionized gas around the LMC (the 'Magellanic Corona'). Here we report that, by including this Magellanic Corona in hydrodynamic simulations of the Magellanic Clouds falling onto the Milky Way, we can reproduce the Magellanic Stream and its leading arm. Our simulations explain the filamentary structure, spatial extent, radial-velocity gradient and total ionized-gas mass of the Magellanic Stream. We predict that the Magellanic Corona will be unambiguously observable via high-ionization absorption lines in the ultraviolet spectra of background quasars lying near the LMC.

Survival in frontotemporal lobar degeneration and related disorders: latent class predictors and brain functional correlates.

BACKGROUND: Establishing survival rate in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Using the latent profile analysis (LPA) approach, we have previously suggested that FTLD patients can be grouped into specific phenotypes- "pseudomanic behavior" (LC1), "cognitive" (LC2), and "pseudodepressed behavior" (LC3)-on the basis of neuropsychological, functional, and behavioral data. OBJECTIVE: The aim of this study was to evaluate the rate of survival in FTLD, to identify predictors of survival, and to determine the likely usefulness of LPA in defining prognosis. METHODS: A total of 252 FTLD patients entered the study. A clinical evaluation and standardized assessment were carried out, as well as a brain imaging study. LPA on neuropsychological, functional, and behavioral data was performed. Each patient was followed up over a 5-year period, and institutionalization or death was considered. RESULTS: The survival rate was associated neither with demographic characteristics, co-morbidities, family history for dementia, nor clinical diagnosis. The presence of the three LC phenotypes was confirmed by LPA. A different survival rate was predicted by LCs, the worse prognosis being found in LC1 (hazard ratio [HR] = 15.7, 95% confidence interval [CI] = 7.2-34.9, p < 0.001, reference LC3). LC2 had a worse prognosis compared to LC3 (HR = 2.07, 95% CI = 0.98-4.37, p = 0.06). Greater hypoperfusion in the orbitomesial frontal cortex was specifically associated with LC1 compared with the other LCs. CONCLUSIONS: A data-driven approach regarding neuropsychological and behavioral assessment might be useful in clinical practice for defining a FTLD prognosis and hopefully will lead to the possibility of identifying patient groups for the evaluation of treatment response in future trials.

During infection of epithelial cells Salmonella enterica serovar Typhimurium undergoes a time-dependent transcriptional adaptation that results in simultaneous expression of three type 3 secretion systems.

The biogenesis of the Salmonella-containing vacuole within mammalian cells has been intensively studied over recent years. However, the ability of Salmonella to sense and adapt to the intracellular environment of different types of host cells has received much less attention. To address this issue, we report the transcriptome of Salmonella enterica serovar Typhimurium SL1344 within epithelial cells and show comparisons with Salmonella gene expression inside macrophages. We report that S. Typhimurium expresses a characteristic intracellular transcriptomic signature in response to the environments it encounters within different cell types. The signature involves the upregulation of the mgtBC, pstACS and iro genes for magnesium, phosphate and iron uptake, and Salmonella pathogenicity island 2 (SPI2). Surprisingly, in addition to SPI2, the invasion-associated SPI1 pathogenicity island and the genes involved in flagellar biosynthesis were expressed inside epithelial cells at later stages of the infection, while they were constantly downregulated in macrophage-like cells. To our knowledge, this is the first report of the simultaneous transcription of all three Type Three Secretion Systems (T3SS) within an intracellular Salmonella population. We discovered that S. Typhimurium strain SL1344 was strongly cytotoxic to epithelial cells after 6 h of infection and hypothesize that the time-dependent changes in Salmonella gene expression within epithelial cells reflects the bacterial response to host cells that have been injured by the infection process.

Revisiting brain reserve hypothesis in frontotemporal dementia: evidence from a brain perfusion study.

BACKGROUND: Literature data on Alzheimer's disease suggest that years of schooling and occupational level are associated with a reserve mechanism. No data on patients with behavioral variant frontotemporal dementia (bvFTD) are available yet. OBJECTIVE: To evaluate the impact of education, occupation, and midlife leisure activities on brain reserve in bvFTD. METHODS: Fifty-four bvFTD patients entered the study and underwent neuropsychological and behavioral assessment, including the FTD-modified Clinical Dementia Rating for FTD (FTD-modified CDR), and SPECT imaging. We tested for the linear correlation of educational and occupational level, and midlife leisure activities with regional cerebral blood flow (rCBF), controlling for demographic variables (age and gender) and for cognitive performance (FTD-modified CDR) (statistical parametric mapping). RESULTS: A significant relationship between higher educational and occupational attainments and lower rCBF in medial frontal cortex and dorsolateral frontal cortex, bilaterally, was found (p < 0.005). When midlife leisure activities were considered, no correlation was found. The correlation between a reserve index, accounting for both educational and occupational level, and rCBF showed the same pattern of hypoperfusion. CONCLUSIONS: This study suggests that education and occupation act as proxies for reserve capacity in bvFTD. These lifestyle attainments may counteract the onset of this genetic-based disease in at-risk individuals.

It's easy to build your own microarrayer!

DNA microarrays are becoming the tool of choice for microbial gene-expression profiling and genotypic analysis. The construction of a gridding robot for the 'in-house' production of microarrays is a choice worth considering, and offers distinct advantages over other options in terms of cost effectiveness and scale. Having built our own robot, we want to dispel some of the myths that might be associated with such a project, as well as provide practical advice for potential builders in the UK and Europe.

Extra-ribosomal spacer sequences in Triturus.

We show that, in Triturus vulgaris meridionalis, sequences homologous to the rDNA "non-transcribed" spacer (NTS) are clustered at chromosomal loci where they are not associated with 18 S or 28 S rDNA genes: these sequences are referred to as the extra-ribosomal spacer sequences. Genomic clones containing such extra-ribosomal spacer sequences have been isolated. As shown by restriction mapping, these clones appear to consist mostly of repetitive BamHI fragments that are, in turn, internally repetitious and highly homologous to each other. The structure of the clones was confirmed by nucleotide sequence analysis, which also demonstrates the high degree of conservation between the BamHI elements and the homologous NTS sequences. An intriguing 12 base-pair homology between the extra-ribosomal spacer sequences and a Xenopus NTS enhancer sequence is reported. The possibility that a repetitive octanucleotide motif found within the BamHI elements could act as a recombination hotspot by virtue of its similarity with the Escherichia coli chi sequence is discussed.

Molecular organization of ribosomal RNA genes clustered at variable chromosomal sites in Triturus vulgaris meridionalis (Amphibia, Urodela).

The ribosomal RNA genes of Triturus vulgaris meridionalis (Amphibia, Urodela) show the peculiar feature of being clustered not only at the nucleolar organizer, present in the species at a definite chromosome location, but also at "additional ribosomal sites" which are highly variable in number and chromosomal distribution among individuals. The additional ribosomal sites are most often found at specific chromosome regions, such as telomeres, C-bands and centromeres, in virtually all the chromosomes. With increasing numbers of additional clusters, the genomic dosages of ribosomal RNA genes are found to increase over a tenfold range, though not linearly. At a molecular level, the ribosomal DNA repeats differ in size because of discrete variations in the length of the non-transcribed spacers. However, the resulting length heterogeneity of the gene family is rather limited within a single genome as well as within the species. Many of the ribosomal loci appear to be internally homogeneous with respect to the repeat length. Moreover, separate clusters from distant genomic regions can share the same size class of ribosomal repeats even in the same specimen. The nucleolar organizer is mostly endowed with "shorter" ribosomal repeating units, ranging in size from 13.7 X 10(3) to 15.2 X 10(3) base-pairs. The additional ribosomal sites are characterized by the occurrence of "longer" repeats, ranging in size from 16.2 X 10(3) to 19.7 X 10(3) base-pairs. The "shorter" class of ribosomal repeats is always detected in the amplified ribosomal DNA, suggesting that the nucleolar organizer locus is involved in the amplification process in most oocytes. "Longer" ribosomal repeats are also detectable in the amplified ribosomal DNA of a few females.

A Xenopus multifinger protein, Xfin, is expressed in specialized cell types and is localized in the cytoplasm.

Xfin is a member of a large family of Krüppel-type transcripts stored in the Xenopus egg, whose function is unknown. By using polyclonal antibodies raised against fusion proteins containing different portions of Xfin, we have identified the Xfin gene product and established its pattern of expression in some adult tissues and during oogenesis and embryogenesis. The corresponding mRNA localization has been studied by in situ hybridization on ovary and testis sections. The Xfin product is found in the cytoplasm, both during oogenesis and adulthood; in adult tissues, it is differentially expressed in a cell-type specific fashion. The expression of the protein in specialized cell types and its cytoplasmic localization may favour the hypothesis that it could be involved in cell differentiation events through protein-RNA interactions.

A Zn-finger protein, Xfin, is expressed during cone differentiation in the retina of the frog Xenopus laevis.

Xfin is a member of a Zn-finger multigene family that shares homology with the Drosophila segmentation gene, Krüppel. This paper reports on our identification and cellular localization, through the utilization of specific antibodies, of the expression product of Xfin in the Xenopus laevis retina, and its pattern of expression during the retinal developmental stages. By immunostaining sections of the retina, we show that the major staining is localized in the cytoplasm of the cones. The protein appears at an early differentiation stage of the cones, when they can not be univocally identified by morphological criteria, and is maintained up to the adult retina. The same antigenicity pattern is detectable in the retina of the anuran genus Bufo. The immunostaining data are confirmed by Western blot analysis on Xenopus eye protein extracts. Because of its cytoplasmic localization, and because of the ability of Zn-finger proteins to bind nucleic acids, we think that Xfin may be involved in the terminal differentiation of the cones through RNA-protein interactions.

Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli.

BACKGROUND: Alverine citrate is commonly used in the treatment of painful affections of the colon. AIM: To determine whether alverine citrate acts on the vagal sensory endings. METHODS: Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied. RESULTS: The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5-10 microg/kg), substance P (5-10 microg/kg) or phenylbiguanide (5-10 microg/kg), a 5-HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present. CONCLUSIONS: Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti-spasmodic effects.

The serotonin 5-HT2B receptor from the puffer fish Tetraodon fluviatilis: cDNA cloning, genomic organization and alternatively spliced variants.

We cloned the 5-HT2B serotonin receptor from the puffer fish Tetraodon fluviatilis. Two cDNAs differing in length because of the use of alternative polyadenylation sites were isolated. We partly characterized the genomic organization of the 5-HT2B gene and we found two introns conserved in position between the puffer fish and mammals. In addition, four splice variants which would generate truncated forms of the receptor were detected.

Prevention of neuronal cell damage induced by oxidative stress in-vitro: effect of different Ginkgo biloba extracts.

The effect of two different Ginkgo biloba extracts (GB1 and GB4) was studied in-vitro on cultured neurons exposed to oxidative stress caused by H2O2(50 micromol L(-1)) and FeSO4(100 micromol L(-1)). Only about 50% of the neurons were still viable at the end of the experiment (8 h) in control conditions, while the two extracts dose dependently increased the number of viable cells, in the concentration range 10-200 microg mL(-1). The two Ginkgo biloba extracts differed in their effect on hydroxyl-radical-scavenging capacity: GB1 and GB4 had an IC50 (50% inhibiting concentration) value of 78 microg mL(-1) and 186 microg mL(-1), respectively. However, both extracts inhibited apoptosis in cortical neurons after oxidative stress in-vitro. These observations make one suppose that different preparations of Ginkgo biloba have quantitatively different actions and outline the importance of the contribution of apoptosis prevention toward their neuroprotective action.

[3 cases of diverticulum of the 4th duodenal segment]. / Considerazioni su 3 casi di diverticolo della quarta porzione duodenale.

Three cases of diverticulum of the IV duodenal portion are presented. The Authors, after having summarized the general features of the duodenal diverticula, remembered the rareness of the ones of its fourth portion, describe the clinical cases and conclude synthetizing the main indications to this type of surgery: complicated diverticula, certainly symptomatic diverticula, of great size diverticula.

¹³¹I treatment of toxic nodular goiter under combined thyrostatic-thyromimetic medication is at low risk of late hypothyroidism.

AIM: Treatment of toxic nodular goiter with ¹³¹I is a first-line therapy for hyperthyroidism. To avoid a thyrotoxic storm, ¹³¹I is usually administered after pretreatment with antithyroid drugs, with thyroid-stimulating hormone (TSH) increase and functional recruitment of inhibited normal tissue. Therefore, both autonomous nodule(s) and normal tissue are irradiated. This may be a reason for late hypothyroidism occurring in 15-25% of patients. This study aimed at assessing different pretreatment modalities with combined methymazole and triiodothyronine, achieving euthyroidism with suppressed TSH. METHODS: After diagnosis of autonomously functioning toxic nodule, patients were subjected to thyrostatic medication. Two months later, TSH was checked; if >0.5 mU/L triiodothyronine treatment was associated. After 2 more months, if the TSH level was suppressed, patients received ¹³¹I-therapy. A total of 149 patients were consecutively enrolled, 41 of whom with uninodular and 108 with multinodular goiter. They were evaluated at diagnosis, pretreatment, 3 and 6 months after therapy and at late follow-up (6.8+/-4.2 years; range: 1-22 years). RESULTS: Administered activity was calculated according to ¹³¹I uptake and gland weight. Methymazole was discontinued 6 days before treatment and T3 was maintained until administration of ¹³¹I-therapy. Euthyroidism was achieved in 88% of patients. At late follow-up, subclinical hypothyroidism was observed in 10 patients (6.7%) and overt hypothyroidism in 5 patients (3.3%). No pathological consequences or side effects of ¹³¹I-therapy were found during the 6.8+/-4.2 year follow-up period. CONCLUSION: Treatment of toxic nodular goiter with ¹³¹I-therapy, under combined thyrostatic-thyromimetic treatment is a simple, safe, well-tolerated, and effective procedure.

The lactic acid-induced acid tolerance response in Salmonella enterica serovar Typhimurium induces sensitivity to hydrogen peroxide.

Transcriptome analyses of Salmonella enterica serovar Typhimurium revealed that 15 genes were significantly up-regulated after 2 h of adaptation with lactic acid. cadB was the most highly up-regulated gene and was shown to be an essential component. Lactic acid-adapted cells exhibited sensitivity to hydrogen peroxide, likely due to down-regulation of the OxyR regulon.

Current data and ideas on digestive sensitivity.

Remarkable advances have recently been made in the study of visceral sensitivity. Both electrophysiological and histological data emphasize the richness and the complexity of information elicited in the visceral area including the digestive tract. In addition these afferents are largely involved in physiological mechanisms which are not only restricted to the visceral area. The current knowledge of visceral sensitivity leads us to reconsider the classical ideas and concepts previously accepted in this field and raises questions to help gain a better comprehension of sensory physiology in general.

Broad-range bacteriophage resistance in Streptococcus thermophilus by insertional mutagenesis.

Streptococcus thermophilus is a lactic acid bacterium used in industrial milk fermentation. To obtain phage-resistant starters, S. thermophilus strain Sfi1 was submitted to mutagenesis with the thermolabile insertional vector pG(+)host9:ISS1 followed by a challenge with the lytic S. thermophilus phage Sfi19. Vector insertions into four distinct sites led to a phage-resistance phenotype. Three mutants were characterized further. They were protected against the homologous challenging phage and 14 heterologous phages. All three mutants adsorbed phages. No intracellular phage DNA synthesis was observed in mutants R7 and R71, while mutant R24 showed a delayed and diminished phage DNA synthesis compared to the parental Sfi1 strain. In mutant R7 a short deletion occurred next to the insertion site which removed the upstream sequences and the 15 initial codons from orf 394, encoding a likely transmembrane protein. Analogy with other phage systems suggests an involvement of this protein in the phage DNA injection process. In mutant R24 the vector was inserted into orf 269 predicting an oxido-reductase. When the vector sequence was removed via homologous recombination across the duplicated insertion elements, mutant R24 returned to the phage susceptibility of the parental strain. This observation suggested that inactivation of orf 269 was not crucial for the resistance phenotype. A gene encoding a likely restriction subunit of a type I restriction-modification system was located directly downstream of the insertion site in mutant R24. hsdM and hsdS genes encoding the modification and specificity subunits of a type I R-M system and biological evidence for an active R-M system were detected in strain Sfi1, suggesting involvement of a type I R-M system in the resistance phenotype of R24.