RNF17 blocks promiscuous activity of PIWI proteins in mouse testes

PIWI proteins and their associated piRNAs protect germ cells from the activity of mobile genetic elements. Two classes of piRNAs-primary and secondary-are defined by their mechanisms of biogenesis. Primary piRNAs are processed directly from transcripts of piRNA cluster loci, whereas secondary piRNAs are generated in an adaptive amplification loop, termed the ping-pong cycle. In mammals, piRNA populations are dynamic, shifting as male germ cells develop. Embryonic piRNAs consist of both primary and secondary species and are mainly directed toward transposons. In meiotic cells, the piRNA population is transposon-poor and largely restricted to primary piRNAs derived from pachytene piRNA clusters. The transition from the embryonic to the adult piRNA pathway is not well understood. Here we show that RNF17 shapes adult meiotic piRNA content by suppressing the production of secondary piRNAs. In the absence of RNF17, ping-pong occurs inappropriately in meiotic cells. Ping-pong initiates piRNA responses against not only transposons but also protein-coding genes and long noncoding RNAs, including genes essential for germ cell development. Thus, the sterility of Rnf17 mutants may be a manifestation of a small RNA-based autoimmune reaction

Comment on newly found Charge Density Waves in infinite layer Nickelates

Recent works[1-3] reported evidence for charge density waves (CDWs) in infinite layer nickelates (112 structure) based on resonant diffraction at the Ni $L_3$ edge measured at fixed scattering angle. We have found that a measurement with fixed momentum transfer, rather than scattering angle, does not show a resonance effect. We have also observed that a nearby structural Bragg peak from the substrate appears due to third harmonic content of the incident beam, and spreads intensity down to the region of the attributed CDW order. This was further confirmed by testing a bare substrate. We suggest procedures to confirm an effective resonant enhancement of a diffraction peak

Minotaur is critical for primary piRNA biogenesis

Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to silence transposon targets and, as such, form a molecular code that discriminates transposons from endogenous genes. Information ultimately carried by piRNAs is encoded within genomic loci, termed piRNA clusters. These give rise to long, single-stranded, primary transcripts that are processed into piRNAs. Despite the biological importance of this pathway, neither the characteristics that define a locus as a source of piRNAs nor the mechanisms that catalyze primary piRNA biogenesis are well understood. We searched an EMS-mutant collection annotated for fertility phenotypes for genes involved in the piRNA pathway. Twenty-seven homozygous sterile strains showed transposon-silencing defects. One of these, which strongly impacted primary piRNA biogenesis, harbored a causal mutation in CG5508, a member of the Drosophila glycerol-3-phosphate O-acetyltransferase (GPAT) family. These enzymes catalyze the first acylation step on the path to the production of phosphatidic acid (PA). Though this pointed strongly to a function for phospholipid signaling in the piRNA pathway, a mutant form of CG5508, which lacks the GPAT active site, still functions in piRNA biogenesis. We have named this new biogenesis factor Minotaur

Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas.

BACKGROUND: Adjuvant radiation therapy (RT) with temozolomide (TMZ) is standard of care for high grade gliomas (HGG) patients. RT is commonly started 3 to 5 weeks after surgery. The deformation of the tumor bed and brain from surgery to RT is poorly studied. This study examined the magnitude of volume change in the postoperative tumor bed and the potential impact of RT planning. METHOD AND MATERIALS: This study includes 24 patients with HGG who underwent craniotomy and adjuvant RT with TMZ at our institution. All patients had immediate postoperative MRI and repeat MRI during the day of RT simulation. Gross tumor volumes (GTV), clinical target volumes (CTV) of initial 46 Gy (CTV1) and boost to 60 Gy (CTV2) were contoured on both sets of MRIs according to RTOG (Radiation Therapy Oncology Group) guidelines. For patients who recurred after RT, the recurrence pattern was evaluated. RESULTS: An average of 17 days elapsed between immediate and delayed MRIs. GTV1 (FLAIR abnormality and tumor bed) decreased significantly on the delayed MRI as compared to immediate post-operative MRI (mean = 30.96cc, p = 0.0005), while GTV2 (contrast-enhanced T1 abnormality and tumor bed) underwent a non-significant increase (mean = 6.82cc, p = 0.07). Such changes lead to significant decrease of CTV1 (mean decrease is 113.9cc, p CONCLUSION: The postoperative tumor bed of HGGs undergoes substantial volumetric changes after surgery. Treatment planning based on delayed MRI significantly reduces the volume of treated brain tissue without local control detriment. The marked reduction of volume treated to 46 Gy based on delayed MRI scan, could result in increased sparing of organs at risk. There may be a small risk of inadequate radiation field design if radiation planning is based on immediate post-operative MRI

The determinants of hotels' marketing managers' green marketing behaviour

Little is known about the factors underlying the pro-environmental behaviour of marketing managers. This paper explores the determinants of green marketing practices in the Red Sea hotel sector in Egypt. The research model assesses green marketing practices against the personal and organisational values of the marketing managers, together with a range of organisational and demographic variables expected to influence hotels' environmental behaviour. From a valid sample of 89 marketing managers responsible for 194 hotels, it was found that organisational contextual variables, and in particular targeting Western tourists, being affiliated to an international hotel chain and the marketers' own demographics, including age, academic subject studied and gender, were the best predictors of more proactive green marketing. Personal environmental values did not explain the pro-environmental behaviour of marketers, and the organisational environmental values that had explained part of their ethical behaviour had resulted from voluntarism rather than utilitarian or conformance-based values. Government policies also appeared to be ineffective determinants. The implications for green marketing practices are also discussed. © 2010 Taylor & Francis

An atlas of chromatoid body components

The genome of male germ cells is actively transcribed during spermatogenesis to produce phase-specific protein-coding mRNAs and a considerable amount of different noncoding RNAs. Ribonucleoprotein (RNP) granule-mediated RNA regulation provides a powerful means to secure the quality and correct expression of the requisite transcripts. Haploid spermatids are characterized by a unique, unusually large cytoplasmic granule, the chromatoid body (CB), which emerges during the switch between the meiotic and post-meiotic phases of spermatogenesis. To better understand the role of the CB in male germ cell differentiation, we isolated CBs from mouse testes and revealed its full RNA and protein composition. We showed that the CB is mainly composed of RNA-binding proteins and other proteins involved RNA regulation. The CB was loaded with RNA, including pachytene piRNAs, a diverse set of mRNAs, and a number of uncharacterized long noncoding transcripts. The CB was demonstrated to accumulate nascent RNA during all the steps of round spermatid differentiation. Our results revealed the CB as a large germ cell-specific RNP platform that is involved in the control of the highly complex transcriptome of haploid male germ cells

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA

Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma

Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL). However, it remains only partially understood how Jak3/STAT activation promotes lymphomagenesis. Recently, non-coding microRNAs (miRNAs) have been implicated in the pathogenesis of this malignancy. Here, we show that (i) malignant T cells display a decreased expression of a tumor suppressor miRNA, miR-22, when compared to non-malignant T cells, (ii) STAT5 binds the promoter of the miR-22 host gene, and (iii) inhibition of Jak3, STAT3, and STAT5 triggers increased expression of pri-miR-22 and miR-22. Curcumin, a nutrient with anti-Jak3 activity and histone deacetylase inhibitors (HDACi) also trigger increased expression of pri-miR-22 and miR-22. Transfection of malignant T cells with recombinant miR-22 inhibits the expression of validated miR-22 targets including NCoA1, a transcriptional co-activator in others cancers, as well as HDAC6, MAX, MYCBP, PTEN, and CDK2, which have all been implicated in CTCL pathogenesis. In conclusion, we provide the first evidence that de-regulated Jak3/STAT3/STAT5 signalling in CTCL cells represses the expression of the gene encoding miR-22, a novel tumor suppressor miRNA