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Deregulation of the miR-15a/16-1 cluster has a key role in the pathogenesis of chronic lymphocytic leukemia (CLL), a clinically heterogeneous disease with indolent and aggressive forms. The miR-15a/16-1 locus is located at 13q14, the most frequently deleted region in CLL. Starting from functional investigations of a rare SNP upstream the miR cluster, we identified a novel allele-specific mechanism that exploits a cryptic activator region to recruit the RNA polymerase III for miR-15a/16-1 transcription. This regulation of the miR-15a/16- locus is independent of the DLEU2 host gene, which is often transcribed monoallellically by RPII. We found that normally one allele of miR-15a/16-1 is transcribed by RNAPII, the other one by RNAPIII. In our subset of CLL patients harboring 13q14 deletions, exclusive RNA polymerase III (RPIII)-driven transcription of the miR-15a/16-1 was the consequence of loss of the RPII-regulated allele and correlated with high expression of the poor prognostic marker ZAP70 (P=0.019). Thus, our findings point to a novel biological process, characterized by double allele-specific transcriptional regulation of the miR-15a/16-1 locus by alternative mechanisms. Differential usage of these mechanisms may distinguish at onset aggressive from indolent forms of CLL. This provides a basis for the clinical heterogeneity of the CLL patients carrying 13q14 deletions.

Maria Adele Giamberardino,1,* Giannapia Affaitati,1,* Raffaele Costantini,2 Francesco Cipollone,3,* Paolo Martelletti4,* 1Department of Medicine and Science of Aging, Headache Center, Geriatrics Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 2Department of Medical, Oral and Biotechnological Sciences, Institute of Surgical Pathology, “G. D’Annunzio” University of Chieti, Chieti, Italy; 3Department of Medicine and Science of Aging, Medical Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 4Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy *These authors contributed equally to this work Abstract: Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP) plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs) against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4–14 monthly migraine days): one Phase II and two Phase III trials (completed) and one Phase III trial (ongoing). Monthly subcutaneous administration (70 mg or 140 mg) of erenumab vs placebo for 3–6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (P

Giamberardino MA, Affaitati G, Costantini R, et al. J Pain Res. 2017;10:2751–2760.On page 2756, left column, lines 7 and 8: “Patients who previously had failed two preventative medications were excluded.” should have been: “Patients who previously had failed more than two preventive medications were excluded.”On page 2756, right column, lines 41–43: “There was a difference of −1.1 days in the main change in monthly migraine days between 70 mg erenumab group and placebo.” should have been: “There was a difference of −2.5 days in the mean change in monthly migraine days between 70 mg erenumab group and placebo.”Read the original article

The technological interest in MoTe2 as a phase engineered material is related to the possibility of triggering the 2H–1T′ phase transition by optical excitation, potentially allowing for an accurate patterning of metallic areas into a semiconducting canvas via laser irradiation. In this paper, we investigate the photo-induced modifications of a bulk 2H-MoTe2 crystal by means of time-resolved X-ray photoemission spectroscopy. We observe that in the microsecond timescale, the core levels shift to higher kinetic energies due to surface photovoltage fields, while in the sub-nanosecond range, the photoemission peaks shift in the opposite direction. With the support of DFT calculations, we ascribe the latter effect to the deformation of the lattice in the out-of-plane direction, which is along the pathway for the 2H–1T′ phase transition. Our data indicate an intermediate lattice excitation state with a measured lifetime in the order of 600 ps, in which the displacement of Mo and Te atoms causes the Te 4d electrons to shift towards higher binding energies. [ABSTRACT FROM AUTHOR]