Micro-RNA Expression and Function in Lymphomas

The recent discovery of microRNAs (miRNAs) has introduced a new layer of complexity to the process of gene regulation. MiRNAs are essential for cellular function, and their dysregulation often results in disease. Study of miRNA expression and function in animal models and human lymphomas has improved our knowledge of the pathogenesis of this heterogeneous disease. In this paper, we attempt to describe the expression of miRNAs and their function in lymphomas and discuss potential miRNA-based therapies in the diagnosis and treatment of lymphomas

Studying the accretion geometry of EXO 2030+375 at luminosities close to the propeller regime

The Be X-ray binary EXO 2030+375 was in an extended low luminosity state during most of 2016. We observed this state with NuSTAR and Swift, supported by INTEGRAL observations as well as optical spectroscopy with the NOT. We present a comprehensive spectral and timing analysis of these data here to study the accretion geometry and investigate a possible onset of the propeller effect. The H-alpha data show that the circumstellar disk of the Be-star is still present. We measure equivalent widths similar to values found during more active phases in the past, indicating that the low-luminosity state is not simply triggered by a smaller Be disk. The NuSTAR data, taken at a 3-78 keV luminosity of ~6.8e35 erg/s (for a distance of 7.1 kpc), are well described by standard accreting pulsar models, such as an absorbed power-law with a high-energy cutoff. We find that pulsations are still clearly visible at these luminosities, indicating that accretion is continuing despite the very low mass transfer rate. In phase-resolved spectroscopy we find a peculiar variation of the photon index from ~1.5 to ~2.5 over only about 3% of the rotational period. This variation is similar to that observed with XMM-Newton at much higher luminosities. It may be connected to the accretion column passing through our line of sight. With Swift/XRT we observe luminosities as low as 1e34 erg/s during which the data quality did not allow us to search for pulsations, but the spectrum is much softer and well described by either a blackbody or soft power-law continuum. This softer spectrum might be due to the fact that accretion has been stopped by the propeller effect and we only observe the neutron star surface cooling.Comment: 11 pages, 6 figures, accepted for publication in A&A (v2 including language edits

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

A major star formation region in the receding tip of the stellar Galactic bar. II. Supplementary information and evidence that the bar is not the same structure as the triaxial bulge previouly reported

This paper is the second part of Garzon et al. (1997: ApJ 491, L31) in which we presented an outline of the analysis of 60 spectra from a follow-up program to the Two Micron Galactic Survey (TMGS) project in the l=27 deg., b=0 deg. area. In this second part, we present a more detailed explanation of the analysis as well a library of the spectra for more complete information for each of the 60 stars, and further discussions on the implications for the structure of the Galaxy. This region contains a prominent excess in the flux distribution and star counts previously observed in several spectral ranges, notably in the TMGS. More than 50% of the spectra of the stars detected with m_K<5.0 mag, within a very high confidence level, correspond to stars of luminosity class I, and a significant proportion of the remainder are very late giants which must also be rapidly evolving. We make the case, using all the available evidence, that we are observing a region at the nearer end of the Galactic bar, where the Scutum spiral arm breaks away, and that this is powerful evidence for the presence of the bar. Alternative explanations do not give nearly such a satisfactory account of the observations. The space localization of one and, a fortiori, of both ends of the bar allows us to infer a position angle for the bar of around 75 deg. with respect to the Sun-Galactic centre line. The angle is different from that given by other authors for the bar and this, we think, is because they refer to the triaxial bulge and not to the bar as detected here.Comment: 21 pages, 1 table, 9 figures, accepted in A

Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease