Plasma and PBMC miRNA profile in sexually HIV-1 exposed seronegative individuals

Background: MicroRNAs (miRNAs) are small 20- to 24-nt non-coding RNAs involved in the post-transcriptional regulation of gene expression which play important defensive roles in several viral infections. Global expression profiles of cellular miRNAs have identified alterations of specific miRNAs post-HIV-1 infection both in vitro and in different patient cohorts suggesting potential roles for miRNA in pathogenesis and disease progression. We therefore decided to verify if natural resistance to HIV-1 infection observed in seronegative individuals repeatedly exposed to HIV-1 (HESN) through unprotected sexual intercourse could be secondary to a different expression of their miRNA profile. Methods: Expression levels of 25 miRNAs selected according to their proven anti-HIV-1 properties were analyzed in plasma, basal PBMC and in in vitro HIV-1 infected macrophages isolated from 30 HESN, 30 HIV seropositive subjects (HIV + ) and 30 healthy controls (HC).Results: In plasma the expression of mir-155, mir-382, mir-28 and mir-198 was significantly augmented in both HIV + and HESN compared to HC probably as a consequence of viral exposure. Conversely the expression of mir-223 and mir-150 in plasma was significantly increased only in HESN and this result was also confirmed in basal PBMC suggesting a protective effect for these miRNAs in resistance to HIV-1 infection. Furthermore, the expression of mir-150 was significantly increased in HESN macrophages following HIV-1 infection. Conclusions: mir-223 and mir-150 can target the 3\ua2UTR of HIV-1 transcripts, and they have already been identified as anti-HIV-1 miRNAs. The higher expression of these miRNA in HESN samples could therefore represent a key protection mechanism against HIV infection

Cellular preservation of musculoskeletal specializations in the Cretaceous bird Confuciusornis

The hindlimb of theropod dinosaurs changed appreciably in the lineage leading to extant birds, becoming more ‘crouched’ in association with changes to body shape and gait dynamics. This postural evolution included anatomical changes of the foot and ankle, altering the moment arms and control of the muscles that manipulated the tarsometatarsus and digits, but the timing of these changes is unknown. Here, we report cellular-level preservation of tendon- and cartilage-like tissues from the lower hindlimb of Early Cretaceous Confuciusornis. The digital flexor tendons passed through cartilages, cartilaginous cristae and ridges on the plantar side of the distal tibiotarsus and proximal tarsometatarsus, as in extant birds. In particular, fibrocartilaginous and cartilaginous structures on the plantar surface of the ankle joint of Confuciusornis may indicate a more crouched hindlimb posture. Recognition of these specialized soft tissues in Confuciusornis is enabled by our combination of imaging and chemical analyses applied to an exceptionally preserved fossil

Disaster relief operations: past, present and future

The aim of the preface is to introduce the scope of this special issue (SI). We explain our editorial approach and summarise our findings based on articles included in this SI. Finally, we outline future research questions which stemmed out of the discussions of this SI

Pareto based optimization of flotation cells configuration using an oriented genetic algorithm

It is customary to use more than one stage of flotation to obtain an acceptable level of separation of valuables. Flotation circuit design is usually accomplished by applying empirical rules or by using expertise of practitioners which may result in operations not working at their optimum conditions. Given the capabilities of genetic algorithms (GA) in finding an optimum solution in very disturbed search spaces, they can be used to obtain the desired flotation circuit configuration. In flotation circuit configuration optimization problem, a combination of metallurgical parameters such as yield and concentrate ash content could be used as the fitness function for the genetic algorithm. The multi-objective nature of the problem justified the use of the Pareto method to arrive at a set of solutions. The appropriate configuration based on technical or economic considerations could then be chosen. To obtain the fitness function for any given configuration, it is necessary to model every flotation stage. The proposed method was used to find the optimum circuit configuration for a coal washing plant. The objective was to arrive at the highest yield while producing a concentrate with a certain ash content (11.2%). The feed to the flotation circuit was characterized based on the size fractions and their flotation rate constants. Results showed that with a 95% confidence the absolute difference between the modeled and measured values were 2.9-5.5% for yield and 0.4-1.1% for concentrate ash content. When the proposed GA-based circuit configuration was implemented in the plant, the yield increased from the original value of 57.6% to 64.3% while producing concentrate ash content (10.9%) within acceptable limits. By adding one stage to the current three-stage circuit, it was predicted that the yield could be further increased by 3.8% while keeping the quality of the concentrate within the appropriate level

Pareto based optimization of flotation cells configuration using oriented genetic algorithm

It is customary to use more than one stage of flotation to obtain an acceptable level of separation of valuables. Flotation circuit design is usually accomplished by applying empirical rules which usually results in operations not working at their optimum conditions. Given the capabilities of genetic algorithms (GA) in finding an optimum solution in a very disturbed search spaces, they can be used to obtain the desired flotation circuit configuration. In flotation circuit configuration and optimization problem, a combination of metallurgical parameters such as yield and concentrate ash content could be used as the fitness function for the genetic algorithm. The multi-objective nature of the problem justified to use Pareto method to arrive at a set of solutions. The appropriate configuration based on technical or economical considerations could then be chosen. To obtain the fitness function for any given configuration, it is necessary to model every flotation stage. The proposed method was used to find the optimum circuit configuration for a coal washing plant. The objective was to arrive at the highest yield while producing a concentrate with a certain ash content (< 11 %). The feed to the flotation circuit was characterized based on the size fractions and their flotation rate constants. Results showed that with a 95% confidence, the absolute difference between the modeled and measured values were 2.9-5.5% for yield and 0.4-1.1% for concentrate ash content. When the proposed GAbased circuit configuration was implemented in the plant, the yield increased from the original value of 57.6% to 65.7% while producing concentrate ash content (1 0.9%) within acceptable limits. By adding one stage to the current three-stage circuit, it was predicted that the yield could further increase by 3.8% while keeping the quality of the concentrate within the appropriate level

Plasma and PBMC miRNA Profile in sexually HIV-1 exposed seronegative individuals

background: MicroRNAs (miRNAs) are small 20- to 24-nt non-coding RNAs involved in the post-transcriptional regulation of gene expression which play important roles in several viral infections. Global expression profiles of cellular miRNAs identified alterations of specific miRNAs post-HIV infection both in vitro and in different patient cohorts; these data suggest a potential role for miRNA in pathogenesis and disease progression. We verified if natural resistance to HIV infection in seronegative individuals repeatedly exposed to HIV (HESN) could be secondary to a peculiar miRNA signature. Methods: expression levels of 84 miRNAs, selected according to their proven anti-HIV properties were analyzed by a specific miRNA array and results were confirmed by individual RT- qPCR in plasma, unstimulated PBMC and in in vitro HIV infected PBMC isolated from 40 HESN, 40 HIV seropositive subjects (HIV+) and 40 healthy controls (HC). Results: Results showed that: 1) whereas the basal PBMC miRNA profile from HESN was similar to the one observed in HC and was characterized by an increased expression of miR-138, miR-150 and miR-190, mir29a and miR223 expression was significantly upregulated in HESN alone; 2) miR-28, miR-29a, miR-150 and miR223 expression was significantly downregulated in HIV-stimulated PBMC of HESN alone; 3) miR-28, miR-29a, miR-29b, miR-29c, miR125b, miR-146, miR-150, miR-155, miR-190 and miR-382 were increased in plasma of both HESN and HIV+ compared to HC; 4) of miR-138 and miR-223 plasmatic levels are exclusively increased in HESN compared to both HIV-1+ patients and HC. conclusions: HIV exposure modifies miRNA expression even in the absence of overt infection. Because the miRNAs that are increased in HESN, i.e. miR-29a, miR-138 and miR-223 were shown to play important role in reducing HIV replication via their ability to bind the 3\u2019 UTR of viral mRNA, the modulation of these miRNAs could represents a key protection mechanism against HIV infection

Identification of a Specific miRNA Profile in HIV-Exposed Seronegative Individuals

Objective: MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. Methods: Expression level of 84 miRNAs was analyzed by RT-qPCR in plasma and unstimulated peripheral blood mononuclear cell (PBMC) of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+), and 30 healthy controls (HC). Results were confirmed by individual RT-qPCR in in vitro HIV-1-infected PBMC and in their cell culture medium. Dicer and Drosha expression was analyzed in basal PBMC. Results: Whereas Dicer and Drosha expression was comparable in HESN, HIV+ and HC, several miRNAs were upregulated both in HESN and HIV+ compared with HC. Furthermore, miRNA-29a and miR-223 were upregulated in both unstimulated PBMC and plasma of HESN alone; their expression was reduced upon in vitro HIV-1 infection of HESN PBMC indicating that, upon infection, they are secreted in the extracellular milieu. These results were confirmed by individual qPCR. Conclusions: Our studies demonstrate that HIV-1 exposure modifies miRNAs expression even in the absence of productive infection. Because those miRNAs that are specifically increased only in HESN have been known to reduce HIV-1 replication, their modulation could represent an important mechanism in resistance to HIV-1 infection

Plasma and PBMC miRNA profile in sexually HIV- exposed seronegative individuals

Background: MicroRNAs (miRNAs) are small 20- to 24-nt non-coding RNAs involved in the post-transcriptional regulation of gene expression which play important defensive roles in several viral infections. Global expression profiles of cellular miRNAs have identified alterations of specific miRNAs post-HIV-1 infection both in vitro and in different patient cohorts suggesting potential roles for miRNA in pathogenesis and disease progression. We therefore decided to verify if natural resistance to HIV-1 infection observed in seronegative individuals repeatedly exposed to HIV-1 (HESN) through unprotected sexual intercourse could be secondary to a different expression of their miRNA profile. Method: expression levels of 25 miRNAs selected according to their proven anti-HIV-1 properties were analyzed in plasma, basal PBMC and in in vitro HIV-1 infected macrophages isolated from 30 HESN, 30 HIV seropositive subjects (HIV+) and 30 healthy controls (HC). Result: In plasma the expression of mir-155, mir-382, mir-28 and mir-198 was significantly augmented in both HIV+ and HESN compared to HC probably as a consequence of viral exposure. Conversely the expression of mir-223 and mir-150 in plasma was significantly increased only in HESN and this result was also confirmed in basal PBMC suggesting a protective effect for these miRNAs in resistance to HIV-1 infection. Furthermore, the expression of mir-150 was significantly increased in HESN macrophages following HIV-1 infection. Conclusion: mir-223 and mir-150 can target the 3\u2019UTR of HIV-1 transcripts, and they have already been identified as anti-HIV-1 miRNAs. The higher expression of these miRNA in HESN samples could therefore represents a key protection mechanism against HIV infection