Chromospheric impact of an exploding solar granule

Observations of multi-wavelength and therefore height-dependent information following events throughout the solar atmosphere and unambiguously assigning a relation between these rapidly evolving layers are rare and difficult to obtain. Yet, they are crucial for our understanding of the physical processes that couple the different regimes in the solar atmosphere. We characterize the exploding granule event with simultaneous observations of Hinode spectroplarimetric data in the solar photosphere and Hinode broadband CaIIH images combined with Interface Region Imaging Spectrograph (IRIS) slit spectra. We follow the evolution of an exploding granule and its connectivity throughout the atmosphere and analyze the dynamics of a magnetic element that has been affected by the abnormal granule. In addition to magnetic flux maps we use a local correlation tracking method to infer the horizontal velocity flows in the photosphere and apply a wavelet analysis on several IRIS chromospheric emission features such as MgIIk2v and MgIIk3 to detect oscillatory phenomena indicating wave propagation. During the vigorous expansion of the abnormal granule we detect radially outward horizontal flows, causing, together with the horizontal flows from the surrounding granules, the magnetic elements in the bordering intergranular lanes to be squeezed and elongated. In reaction to the squeezing, we detect a chromospheric intensity and velocity oscillation pulse which we identify as an upward traveling hot shock front propagating clearly through the IRIS spectral line diagnostics of MgIIh&k. Conclusion: Exploding granules can trigger upward-propagating shock fronts that dissipate in the chromosphere.Comment: 5 pages (3 figures)+1 page movie snapshots(2 figures), accepted in A&A letters, movies can be found at http://www.science-media.org/216 and http://www.science-media.org/21

Tubulin is actively exported from the nucleus through the Exportin1/CRM1 pathway

Microtubules of all eukaryotic cells are formed by α- and β-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and β-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase

Pharmacovigilance pregnancy data in a large population of patients with chronic inflammatory disease exposed to certolizumab pegol.

Introduction Chronic inflammatory diseases (CIDs), including rheumatic diseases and other inflammatory conditions, often affect women of reproductive age. Tumor necrosis factor inhibitors (TNFi) are widely used to treat CID, but there is limited information on outcomes of TNFi-exposed pregnancies. We evaluated pregnancy outcomes from 1392 prospectively reported pregnancies exposed to certolizumab pegol (CZP), a PEGylated, Fc-free TNFi with no to minimal placental transfer. Methods CZP-exposed pregnancies in patients with CID from the UCB Pharmacovigilance global safety database were reviewed from the start of CZP clinical development (July 2001) to 1 November 2020. To limit bias, the analysis focused on prospectively reported cases with known pregnancy outcomes. Results In total, 1392 prospective pregnancies with maternal CZP exposure and known pregnancy outcomes (n = 1425) were reported; 1021 had at least first-trimester CZP exposure. Live birth was reported in 1259/1425 (88.4%) of all prospective outcomes. There were 150/1425 (10.5%) pregnancy losses before 20 weeks (miscarriage/induced abortion), 11/1425 (0.8%) stillbirths, and 5/1392 (0.4%) ectopic pregnancies. Congenital malformations were present in 30/1259 (2.4%) live-born infants, of which 26 (2.1%) were considered major according to the Metropolitan Atlanta Congenital Defects Program criteria. There was no pattern of congenital malformations. Discussion and conclusion No signal for adverse pregnancy outcomes or congenital malformations was observed in CZP-exposed pregnancies. Although the limitations of data collected through this methodology (including underreporting, missing information, and absence of a comparator group) should be considered, these data provide reassurance for women with CID who require CZP treatment during pregnancy, and their treating physicians

The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilumwith Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium\u27s growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al