MIR205HG/LEADR Long Noncoding RNA Binds to Primed Proximal Regulatory Regions in Prostate Basal Cells Through a Triplex- and Alu-Mediated Mechanism

Aside serving as host gene for miR-205, MIR205HG transcribes for a chromatin-associated long noncoding RNA (lncRNA) able to restrain the differentiation of prostate basal cells, thus being reannotated as LEADR (Long Epithelial Alu-interacting Differentiation-related RNA). We previously showed the presence of Alu sequences in the promoters of genes modulated upon MIR205HG/LEADR manipulation. Notably, an Alu element also spans the first and second exons of MIR205HG/LEADR, suggesting its possible involvement in target selection/binding. Here, we performed ChIRP-seq to map MIR205HG/LEADR chromatin occupancy at genome-wide level in prostate basal cells. Our results confirmed preferential binding to regions proximal to gene transcription start site (TSS). Moreover, enrichment of triplex-forming sequences was found upstream of MIR205HG/LEADR-bound genes, peaking at −1,500/−500 bp from TSS. Triplexes formed with one or two putative DNA binding sites within MIR205HG/LEADR sequence, located just upstream of the Alu element. Notably, triplex-forming regions of bound genes were themselves enriched in Alu elements. These data suggest, from one side, that triplex formation may be the prevalent mechanism by which MIR205HG/LEADR selects and physically interacts with target DNA, from the other that direct or protein-mediated Alu (RNA)/Alu (DNA) interaction may represent a further functional requirement. We also found that triplex-forming regions were enriched in specific histone modifications, including H3K4me1 in the absence of H3K27ac, H3K4me3 and H3K27me3, indicating that in prostate basal cells MIR205HG/LEADR may preferentially bind to primed proximal regulatory elements. This may underscore the need for basal cells to keep MIR205HG/LEADR target genes repressed but, at the same time, responsive to differentiation cues

Growth in glucose-based medium and exposure to subinhibitory concentrations of imipenem induce biofilm formation in a multidrug-resistant clinical isolate of Acinetobacter baumannii

<p>Abstract</p> <p>Background</p> <p><it>Acinetobacter baumannii </it>is emerging as an important nosocomial pathogen. Multidrug resistance, as well as ability to withstand environmental stresses, makes eradication of <it>A. baumannii </it>difficult, particularly from hospital settings.</p> <p>Results</p> <p>Over a six-year period, 73 isolates of <it>A. baumannii </it>were collected from infected patients in two hospitals in Italy. While 69 out of the 73 isolates displayed identical multidrug antibiotic resistance pattern, they were susceptible to carbapenems. Genetic profiles of these 69 isolates, determined by Pulsed Field Gel Electrophoresis (PFGE), indicated that they were genetically related and could be clustered in a specific clone, called SMAL. We tested the ability of the SMAL clone to form biofilm, an important determinant for bacterial colonization of the human host and for persistence in the hospital environment. Biofilm formation by <it>A. baumannii </it>SMAL, measured as surface adhesion to polystyrene, is strongly affected by growth conditions, being impaired in rich growth media such as LB, while being favoured in glucose-based medium. Surface adhesion in glucose-based media is inhibited by treatment with cellulase, suggesting that it depends on production of cellulose or of a chemically related extracellular polysaccharide. Exposure of <it>A. baumannii </it>SMAL to subinhibitory concentrations of imipenem resulted in biofilm stimulation and increased production of iron uptake proteins. Growth in iron-supplemented medium also stimulated surface adhesion, thus suggesting that increased intracellular iron concentrations might act as an environmental signal for biofilm formation in <it>A. baumannii </it>SMAL.</p> <p>Conclusions</p> <p>Our results indicate that exposure to subinhibitory concentrations of imipenem can stimulate biofilm formation and induce iron uptake in a pathogenic strain of <it>A. baumannii</it>, with potential implications on antibiotic susceptibility and ability to persist in the human host.</p

An unusual case of venous thoracic outlet syndrome in relation to the anatomical position of the subclavian vein valves in a young athlete

Venous Thoracic Outlet Syndrome (vTOS) consists of upper extremities oedema, sometimes with varicose dilation of the superficial veins of the arm in consequence of compression and/or thrombosis of the subclavian vein. More specific factors, such as muscle hypertrophy, have additionally been registered in athletes. The case focuses on a 20-year-old male student in medicine, with an intense training activity in body building. The subject has presented symptoms of upper limbs oedema he has also reported heaviness and paresthesia in the left arm and hand. Varicose dilation of a superficial vein close to the axillary fossa was visible at naked eye. Both Doppler ultrasound evaluation and Angio TC were negative for venous thrombosis and/or complete obstruction from external compression. These reports depict an uncommon clinical scenario, which correlate an intense upper body training activity with the presence of a second valve distally of the first valve into the subclavian vein

Excessive Unbalanced Meat Consumption in the First Year of Life Increases Asthma Risk in the PASTURE and LUKAS2 Birth Cohorts

A higher diversity of food items introduced in the first year of life has been inversely related to subsequent development of asthma. In the current analysis, we applied latent class analysis (LCA) to systematically assess feeding patterns and to relate them to asthma risk at school age. PASTURE (N=1133) and LUKAS2 (N=228) are prospective birth cohort studies designed to evaluate protective and risk factors for atopic diseases, including dietary patterns. Feeding practices were reported by parents in monthly diaries between the 4(th) and 12(th) month of life. For 17 common food items parents indicated frequency of feeding during the last 4 weeks in 4 categories. The resulting 153 ordinal variables were entered in a LCA. The intestinal microbiome was assessed at the age of 12 months by 16S rRNA sequencing. Data on feeding practice with at least one reported time point was available in 1042 of the 1133 recruited children. Best LCA model fit was achieved by the 4-class solution. One class showed an elevated risk of asthma at age 6 as compared to the other classes (adjusted odds ratio (aOR): 8.47, 95% CI 2.52-28.56, p = 0.001) and was characterized by daily meat consumption and rare consumption of milk and yoghurt. A refined LCA restricted to meat, milk, and yoghurt confirmed the asthma risk effect of a particular class in PASTURE and independently in LUKAS2, which we thus termed unbalanced meat consumption (UMC). The effect of UMC was particularly strong for non-atopic asthma and asthma irrespectively of early bronchitis (aOR: 17.0, 95% CI 5.2-56.1, p < 0.001). UMC fostered growth of iron scavenging bacteria such as Acinetobacter (aOR: 1.28, 95% CI 1.00-1.63, p = 0.048), which was also related to asthma (aOR: 1.55, 95% CI 1.18-2.03, p = 0.001). When reconstructing bacterial metabolic pathways from 16S rRNA sequencing data, biosynthesis of siderophore group nonribosomal peptides emerged as top hit (aOR: 1.58, 95% CI 1.13-2.19, p = 0.007). By a data-driven approach we found a pattern of overly meat consumption at the expense of other protein sources to confer risk of asthma. Microbiome analysis of fecal samples pointed towards overgrowth of iron-dependent bacteria and bacterial iron metabolism as a potential explanation.Peer reviewe

AVANÇOS EM BIOTECNOLOGIA PARA A REGENERAÇÃO CELULAR E TECIDUAL: DESAFIOS E PERSPECTIVAS NO TRATAMENTO DE DOENÇAS HUMANAS

Biotechnology constitutes a realm of inquiry that extends its benefits across diverse domains of knowledge, ranging from agricultural sciences to clinical applications. This field leverages technology to address challenges frequently entailing living organisms. Of current significance is the endeavor to elucidate the process of animal regeneration, particularly within the human species, given its burgeoning potential as an ally in the treatment and cure of various maladies. Recognizing the societal importance of this subject, the present article seeks to expound upon contemporary biotechnological advancements facilitating the exploration of cellular and tissue regeneration for the treatment of human diseases. To this end, a comprehensive review of articles delineating the current landscape was conducted, involving a comparative analysis of regenerative activity across species, with a specific focus on humans. Evidentially, the use of biomaterials in tissue regeneration assumes paramount importance, albeit not without the formidable challenge posed by the inflammatory process. Stem cells, conversely, present themselves as promising entities in the realm of regeneration. However, their interaction within the host organism necessitates further scrutiny to attain a more nuanced understanding. Despite strides made in the field of regenerative medicine, the lack of comprehensive comprehension regarding the properties of biomaterials and their responses within the human body constrains their clinical applicability. Nevertheless, an auspicious future is envisioned, marked by advancements in biomaterials and a heightened understanding of interactions within the human body, thereby fostering the development of more efficacious treatments for a myriad of diseases.La biotecnología es un campo de investigación que beneficia diversas áreas del conocimiento,desde las ciencias agrarias hasta las aplicaciones clínicas, utilizando tecnologías para abordarproblemas que a menudo involucran organismos vivos. Un gran interés en este campo en laactualidad es dilucidar el proceso de regeneración animal, especialmente en los humanos, ya quese ha convertido en un aliado potencial en la cura y tratamiento de diversas enfermedades. Dadala importancia de este tema para la sociedad, este artículo tiene como objetivo discutir los avancesbiotecnológicos actuales que ayudan a aprovechar el potencial de la regeneración celular y tisularen el tratamiento de enfermedades humanas. Con este fin, se realizó una compilación de artículosque describen el escenario actual, analizando comparativamente la actividad regenerativa entreespecies y humanos. A partir de la exposición, fue posible constatar que el uso de biomateriales enla regeneración tisular es crucial, pero el proceso inflamatorio representa un gran desafío. Lascélulas madre, por otro lado, parecen ser prometedoras en el campo de la regeneración; sinembargo, su interacción en el organismo huésped necesita un estudio más profundo para unamejor comprensión. A pesar del progreso en la medicina regenerativa, la falta de comprensiónsobre las propiedades de los biomateriales y sus respuestas en el cuerpo limitan su aplicaciónclínica. No obstante, se espera un futuro prometedor con avances en biomateriales y unacomprensión más profunda de las interacciones en el cuerpo humano, promoviendo tratamientosmás efectivos para diversas enfermedades.Biotechnology constitutes a realm of inquiry that extends its benefits across diverse domains of knowledge, ranging from agricultural sciences to clinical applications. This field leverages technology to address challenges frequently entailing living organisms. Of current significance is the endeavor to elucidate the process of animal regeneration, particularly within the human species, given its burgeoning potential as an ally in the treatment and cure of various maladies. Recognizing the societal importance of this subject, the present article seeks to expound upon contemporary biotechnological advancements facilitating the exploration of cellular and tissue regeneration for the treatment of human diseases. To this end, a comprehensive review of articles delineating the current landscape was conducted, involving a comparative analysis of regenerative activity across species, with a specific focus on humans. Evidentially, the use of biomaterials in tissue regeneration assumes paramount importance, albeit not without the formidable challenge posed by the inflammatory process. Stem cells, conversely, present themselves as promising entities in the realm of regeneration. However, their interaction within the host organism necessitates further scrutiny to attain a more nuanced understanding. Despite strides made in the field of regenerative medicine, the lack of comprehensive comprehension regarding the properties of biomaterials and their responses within the human body constrains their clinical applicability. Nevertheless, an auspicious future is envisioned, marked by advancements in biomaterials and a heightened understanding of interactions within the human body, thereby fostering the development of more efficacious treatments for a myriad of diseases.A biotecnologia é um campo de pesquisa que beneficia várias áreas de conhecimento, desde as ciências agrárias até ao uso clínico, recorrendo a tecnologias para resolver problemas que, muitas vezes, envolvem organismos vivos. Um grande interesse deste ramo, atualmente, é esclarecer o processo de regeneração animal, especialmente na espécie humana, uma vez que se tornou um aliado potencial na cura e no tratamento de várias doenças. Dada a importância deste assunto para a sociedade, o presente artigo procura abordar os atuais avanços biotecnológicos que ajudam na busca por utilizar a potencialidade da regeneração celular e tecidual no tratamento de doenças humanas. Para esse efeito, foi realizada uma revisão de artigos que descrevessem o cenário atual, analisando comparativamente a atividade regenerativa entre espécies e seres humanos. A partir do exposto, foi possível verificar que a utilização de biomateriais na regeneração tecidual é crucial, porém o processo inflamatório é um grande desafio. Já as células-tronco mostram ser uma promessa na área de regeneração, no entanto, a sua interação no organismo hospedeiro precisa ser mais bem estudada para se obter um melhor entendimento. Apesar do progresso na medicina regenerativa, a falta de compreensão sobre as propriedades dos biomateriais e suas respostas no corpo limitam a sua aplicação clínica. Ainda assim, espera-se um futuro promissor com avanços nos biomateriais e uma compreensão mais profunda das interações no corpo humano, promovendo tratamentos mais eficazes para diversas doenças