Reversible switch from hemoglobin A to C in sheep and recovery from anemia following experimental infection with Anaplasma ovis

Anemia causes a change in the type of circulating hemoglobin (Hb) in sheep carrying the βA-globin haplotype, where the Hb A is replaced with Hb C, unlike Hb B. The effect of the substitution of Hb A with Hb C on the recovery from anemia was investigated by comparing the hematological picture of sheep, following experimental infection with Anaplasma ovis. The blood values were obtained from 3 AB and 3 BB Hb sheep after the development of the disease where anemia is a pathognomonic symptom. The expression of the silent gene encoding for Hb C was detected by isoelectric focusing and quantified by high performance liquid chromatography. Both Hb AB genotype and Hb C occurrence were involved in the lower recovery from anemia in the trial

La paratubercolosi negli ovini e caprini I: prolegomeni allo studio delle cause predisponenti a questa malattia

La paratubercolosi, o enterite paratubercolare (conosciuta anche come malattia di Johne), è una patologia infettiva ad andamento cronico sostenuta da Mycobacterium avium subsp. paratuberculosis (MAP). È diffusa ovunque si pratichi l’allevamento ovino e caprino, rappresentando una delle malattie infettive più importanti per i danni arrecati agli allevamenti. Alla diffusione del MAP hanno contribuito specifici fattori gestionali, ma soprattutto la commercializzazione incontrollata di animali, con conseguente aumento dell’incidenza della malattia e prevalenza di allevamenti infetti ormai variabile tra il 7 ed il 60% su scala mondiale. In questo quadro si colloca il progetto PON “EpiSud-Programma per lo sviluppo di metodologie per l’identificazione ed il controllo di infezioni micobatteriche animali”, che vede il Parco Tecnologico Padano come proponente e l’Istituto Zooprofilattico della Sicilia nonché l’Università degli Studi di Bari Aldo Moro (DETO-Sez. Cliniche veterinarie e Produzioni Animali) in qualità di partner. L’Università di Bari, in particolare, sta conducendo un’indagine epidemiologica in Puglia su allevamenti estensivi ovini e caprini al fine di studiare la prevalenza della malattia ed i fattori di rischio scatenanti l’infezione in relazione alle pratiche gestionali adottate dagli allevatori. L’indagine è ancora in fieri ed è prematuro trarre conclusioni circa i dati epidemiologici; è tuttavia possibile, ancorché su dati parziali, avanzare ipotesi circa i fattori di rischio. Data la natura complessa di detti fattori, per l’analisi è stato scelto un approccio multivariato, cosicché nel presente lavoro si riportano i risultati dei primi dati raccolti mediante la somministrazione agli allevatori di un’apposita scheda aziendale, redatta al fine di reperire una serie di informazioni di carattere strutturale, igienico-sanitario e gestionale

Pre-operative radiochemotherapy with raltitrexed for resectable locally-advanced rectal cancer : a phase II study

Background: The aim of the study was to evaluate the response to and toxicity of pre-operative radiochemotherapy containing raltitrexed (Tomudex) for resectable rectal adenocarcinoma. Patients and Methods: From November 2000 to June 2002, 18 consecutive patients staged T3 N0/N+ were treated with pre-operative chemotherapy (3 mg/m 2 of raltitrexed on days 1, 19, 38) and concurrent radiotherapy (RT) (50.4 Gy) in 6 weeks, followed by radical surgery within 8 weeks. Results: The treatment compliance was high. No major acute toxicity was reported. Concerning late toxicity, genitourinary adverse effects were prevalent. A complete response was observed in one patient (6%), partial response in eight (47%), stable disease in seven (41%) and progression in one case. Three-year actuarial disease-free and overall survival rates were 37% and 87.5%, respectively. Conclusion: Raltitrexed did not increase the pathological response rate compared with the rates obtained with use of preoperative RT alone and reported in the literature. Acute morbidity was low and acceptable, while late toxicity was considerable, prevalently concerning sexual dysfunction and urinary complications

A human genome editing-based MLL::AF4 B-cell ALL model recapitulates key cellular and molecular leukemogenic features

The cellular ontogeny and location of the MLL-breakpoint influence the capacity of MLL-edited CD34+ HSPCs to initiate pro-B-ALL, and recapitulate the molecular features of MLL-AF4+ infant B-ALL patients. We provide key insights into the cellular-molecular leukemogenic determinants of MLL-AF4+ infant B-ALL

Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia

B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicted by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to its leukemogenesis. Here, we have integrated genome-wide DNA methylome and transcriptome data from 69 patients with de novo MLL-rearranged leukemia (MLLr) and non-MLLr iB-ALL leukemia uniformly treated according to the Interfant-99/06 protocol. iB-ALL methylome signatures display a plethora of common and specific alterations associated with chromatin states related to enhancer and transcriptional control in normal hematopoietic cells. DNA methylation, gene expression, and gene coexpression network analyses segregated MLLr away from non-MLLr iB-ALL and identified a coordinated and enriched expression of the AP-1 complex members FOS and JUN and RUNX factors in MLLr iB-ALL, consistent with the significant enrichment of hypomethylated CpGs in these genes. Integrative methylome-transcriptome analysis identified consistent cancer cell vulnerabilities, revealed a robust iB-ALL–specific gene expression–correlating dmCpG signature, and confirmed an epigenetic control of AP-1 and RUNX members in reshaping the molecular network of MLLr iB-ALL. Finally, pharmacological inhibition or functional ablation of AP-1 dramatically impaired MLLr-leukemic growth in vitro and in vivo using MLLr-iB-ALL patient–derived xenografts, providing rationale for new therapeutic avenues in MLLr-iB-ALL.We thank CERCA/Generalitat de Catalunya (SGR180) and Fundació Josep Carreras-Obra Social la Caixa for their institutional support. Financial support for this work was obtained from the European Research Council (CoG-2014-646903 and PoC-2018-811220 to PM), the Spanish Ministry of Economy and Competitiveness (SAF-2019-108160-R and SAF2016-76758-R to PM and IV, respectively), the Spanish Association against cancer (AECC-CI-2015 and PROYE18061FERN to CB and MFF), the Fundación Uno entre Cienmil (to PM), the Health Institute Carlos III (ISCIII/FEDER, PI17/01028, PI15/00892, PI18/01527 to CB and AFF/MFF, respectively). We also acknowledge the Plan de Ciencia, Tecnología e Innovación from the Asturias Government cofunding 2018–2022/FEDER (IDI/2018/146to MFF). MFF also acknowledges funding from Fundación General CSIC (0348_CIE_6_E). PM also acknowledges financial support from Fundación Leo Messi. JRT and MV are supported by Juan de la Cierva fellowships by the Spanish Ministry of Science and Innovation (FJCI-2015-26965, IJC2018-36825-I, IJCI-2017-3317) and IUOPA-ISPA-FINBA (The IUOPA is supported by the Obra Social Cajastur-Liberbank, Spain). RTR is supported by a fellowship from the AECC scientific foundation. RFP and PSO are supported by the Severo Ochoa program (BP17-114 and BP17-165, respectively).Peer reviewe