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Der Bericht der Melo-Kommission über die politischen Morde in den Philippinen lag über einen Monat unter Verschluss. Erst die Untersuchungsmissionen des UN Sonderbeauftragen für außergerichtliche Hinrichtungen Philip Aiston, sowie des Generaldirektors für Außenbeziehungen der EU-Kommission Eneko Landaburu führten zur Veröffentlichung des Berichts am 22. Februar. Der Artikel erschien kurz vor der Herausgabe des Melo-Berichts.

This work was supported by the Spanish Ministry of Economy and Competitiveness grant BIO2017-83035-R (AEI/FEDER, EU) awarded to I.L. and a Tenovus Scotland project grant S16/12 awarded to A.F.H. A.F.H. is supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program awarded to J.R.P. (grant agreement ERC-ADG-2014 proposal no. 670932 Dut-signal from EU). V.D.C. was supported by the Medical Research Council (MRC grant MC_UU_12016) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy (Boehringer Ingelheim, GlaxoSmithKline, and Merck KGaA). ; In bacteria, adaptation to changes in the environment is mainly controlled through two-component signal transduction systems (TCSs). Most bacteria contain dozens of TCSs, each of them responsible for sensing a different range of signals and controlling the expression of a repertoire of target genes (regulon). Over the years, identification of the regulon controlled by each individual TCS in different bacteria has been a recurrent question. However, limitations associated with the classical approaches used have left our knowledge far from complete. In this report, using a pioneering approach in which a strain devoid of the complete nonessential TCS network was systematically complemented with the constitutively active form of each response regulator, we have reconstituted the regulon of each TCS of S. aureus in the absence of interference between members of the family. Transcriptome sequencing (RNA-Seq) and proteomics allowed us to determine the size, complexity, and insulation of each regulon and to identify the genes regulated exclusively by one or many TCSs. This gain-of-function strategy provides the first description of the complete TCS regulon in a living cell, which we expect will be useful to understand the pathobiology of this important pathogen. ; Publisher PDF ; Peer reviewed

To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC). We systematically characterized consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c, and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines. Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%), and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%), and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use. DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings. This article is protected by copyright. All rights reserved.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation. ; We would like to thank Ernest Terribes for his advice and help in qPCR design andanalysisaswellasAlbaGarcíaandJes ús-María Hernández-Rivas for providing some DNA samples. We are grateful to Isabel Granada for her helpful advice regarding cytogenetic and FISH analyses. This project was supported by the Asociación Española C ontra el Cáncer, AECC (project ref.: GC16173697BIGA), by CERCA Program/Generalitat de Catalunya, the Catalan Government: 2014-SGR225 (GRE), Obra Social " La Caixa " and by Celgene Spain. E. Genescà is the recipient of agrant from the Spanish Health Ministry (ISCIII, CA12/00468) and an unrestricted grant from Gilead.A. Gonzalez-Perez is supported by a Ramon y Cajal fellowship (RYC-2013-14554) of the Educational Ministry (Madrid, Spain). This work was also partially supported by FEDER funds from the ...