The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal rearrangements in its 5' noncoding region in '30% of diffuse large-cell lymphoma (DLCL). We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10-3-1.6 x 10-2 per bp), often biallelic, mutations clustering in its 5' noncoding region. These mutations are of somatic origin and are found in cases displaying either normal or rearranged BCL6 alleles indicating their independence from chromosomal rearrangements and linkage to immunoglobulin genes. These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression. Sequencing Procedures. PCR products E1.10, E1.11, and E1.12 were subjected to direct sequence analysis as described (21). In addition, a unique PCR product encompassing the same genomic region (nucleotides +413 to + 1141), amplified by primers E1.21C (upstream; 5'-ATGCTTTGGCTCCAA-GTT-3') and E1.26 (downstream; 5'-CACGATACTTCA-TCTCATC-3'), annealing temperature = 54°C, was subcloned into the pGEM-T vector (Promega), and DNA minipreps (Wizard DNA purification system, Promega) were sequenced using forward and reverse primers with the ABI373A DNA sequencer (Perkin-Elmer, Applied Biosystems Division).

Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PL(pro)) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PL(pro) inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PL(pro). Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PL(pro) and these can now be used as lead compounds for further antiviral drug development.

Inverted planar heterojunction (PHJ) perovskite solar cells have attracted great attention due to their advantages of low-temperature fabrication on flexible substrates by solution processing with high efficiency. Poly(3,4ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) is the most widely used hole transport layer (HTL)in inverted PHJ perovskite solar cells; however, the acidic and hygroscopic nature of PEDOT: PSS can cause degradation and reduce the device stability. In this work, we demonstrated that low-cost solution-processed hydrophobic copper iodide (CuI) can serve as a HTL to replace PEDOT: PSS in inverted PHJ perovskite solar cells with high performance and enhanced device stability. Power conversion efficiency (PCE) of 13.58% was achieved by employing CuI as a HTL, slightly exceeding PEDOT: PSS based device with PCE of 13.28% under the same experimental conditions. Furthermore, the CuI based devices exhibited better air stability than that of PEDOT: PSS based devices. The results indicate that low-cost solution-processed CuI is a promising alternative to PEDOT: PSS HTL and could be widely used in inverted PHJ perovskite solar cells.

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Highlights d CerS1 and derived C 18:0 ceramide are increased in skeletal muscle of obese mice d Conventional and muscle-specific CerS1 deficiency protects from insulin resistance d CerS1 deletion in muscle improves glucose metabolism via increased muscle-derived Fgf21 d CerS1 inhibition in muscle might provide an approach to treat insulin resistance