Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity

Antigenic variation is an immune evasion strategy that has evolved in viral, bacterial and protistan pathogens. In the African trypanosome this involves stochastic switches in the composition of a variant surface glycoprotein (VSG) coat, using a massive archive of silent VSG genes to change the identity of the single VSG expressed at a time. VSG switching is driven primarily by recombination reactions that move silent VSGs into specialized expression sites, though transcription-based switching can also occur. Here we discuss what is being revealed about the machinery that underlies these switching mechanisms, including what parallels can be drawn with other pathogens. In addition, we discuss how such switching reactions act in a hierarchy and contribute to pathogen survival in the face of immune attack, including the establishment and maintenance of chronic infections, leading to host-host transmission

Visitor and firm taxes versus environmental options in a dynamical context

The main objective of the paper is to analyze the effects on economic agents’ behavior deriving from the introduction of financial activities aimed to environmental protection. The environmental protection mechanism we study should permit exchange of financial activities among citizens, firms, and Public Administration. Such a particular “financial market” is regulated by the Public Administration, but mainly fuelled by the interest of two classes of involved agents: firms and dwelling citizens. We assume that the adoption process of financial decisions is described by a two-population evolutionary game and we study the basic features of the resulting dynamics.Environmental options; environment preserving technologies; evolutionary games; tourism

Visitor and firm taxes versus environmental options in a dynamical context

The main objective of the paper is to analyze the effects on economic agents' behavior deriving from the introduction of financial activities aimed to environmental protection. The environmental protection mechanism we study should permit exchange of financial activities among citizens, firms, and Public Administration. Such a particular “financial market” is regulated by the Public Administration, but mainly fuelled by the interest of two classes of involved agents: firms and dwelling citizens. We assume that the adoption process of financial decisions is described by a two-population evolutionary game and we study the basic features of the resulting dynamics

A bioinformatics and molecular analysis of antigenic variation in African trypanosomes

The aim of this thesis was to further our knowledge about the contribution of silent alleles on megabase chromosomes to the late stages of trypanosome infection and test the hypothesis that this contribution takes shape in a hierarchy of expression due to differences between alleles in terms both of flanking regions and coding sequence. This was achieved through a combination of bioinformatics and molecular studies. The initial approach was to undertake an extensive manual curation of the available VSG archive; this endeavour resulted in establishment of a fertile collaboration with the Trypanosoma brucei genome sequencing project, and in creation, with the aid of P. Ward and S. Menon, of a dedicated web-based tool to handle and query curated VSG genes. Out of an updated estimate of ~1600 VSG genes, 940 (between half and three quarters) were annotated and shown to be arranged in subtelomeric arrays and to be largely present as pseudogenes (~90%). By considering separately the hypervariable N-terminal domain (three types, A, B and C) and the more conserved C-terminal domain (types 1 to 4, with two additional types identified in this study), it appeared that most of the degeneracy lay in the C-terminal domain. This suggested that N-terminal domains (one third of them being intact) would be utilised by a process of segmental gene conversion yielding hybrid genes, by recombination with functional C-terminal ends resident at the expression site. Under the assumption that “order” within the genome (the presence of patterns within the VSG archive) helps inform “order” in VSG expression (a hierarchy based on different activation probabilities), it was somewhat surprising to detect little evidence of clear substructuring within the archive: no “classes” of VSGs could be identified, based on coding sequence and flanking sequence features. In keeping with the observed high level of divergence within the VSG archive, clear orthologue groups (here defined as alleles sharing >60% amino acid sequence identity) were found not to include more than three to four members and to be scattered at random across the arrays. Putative functional genes could not be separated into groups based on expected differences in activation probabilities, such as a different number of upstream 70-bp repeats, shown to be involved in copying silent alleles to the expression site

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying

Energy Recovery from Low Temperature Heat Produced During Aerobic Biological Treatment

Abstract The possibility of recovering the heat ejected with the exhaust air arising from the aerobic conversion of organic waste for feeding a micro organic Rankine cycle (ORC) was investigated. This heat was upgraded by the combustion of a given amount of solid recovered fuel (SRF). The exhaust air rate ejected by the aerobic process ranged from 40 to 95 kg/day per each tonne/day of waste processed and the temperature ranged, respectively, from 340 K to 330 K. Calculations refer to a typical aerobic treatment facility able to process 20,000 tonnes of organic waste per year. Maximum efficiency in the utilization of the heat produced by the combustion of SRF, ranging from 14% to 22%, was achieved for ORC operating at a compression ratio from 1.5 to 2.5 and exhaust air temperatures from about 340 to 350 K. Operating the ORC with compression ratios higher than 3.5 and exhaust air temperatures of about 510 K, the power output ranged from about 9 to 12 kW. In these conditions, for the size of the facility investigated, the efficiency of the utilization of the heat generated by the combustion of SRF was from 4% to 7% higher than the ORC thermodynamic efficiency

The Rieti Land Reclamation Authority relevance in the management of surface waters for the irrigation purposes of the Rieti Plain (Central Italy)

The Rieti Plain is crowned by calcareous-marly reliefs (Rieti and Sabini Mountains) and represents an intra-Apennine Plio- Quaternary alluvial and fluvial-lacustrine basin formed after multistage extensional tectonic processes. This territory presents huge amounts of water resources (Velino and Turano rivers; several springs; Lungo and Ripasottile lakes, relics of ancient Lacus Velinus). The aquifers occurring in the reliefs often have hydraulic continuity with the Rieti plain groundwater (detected at about 1-4 m below ground surface), which has general flow directions converging from the reliefs to the lake sector. Hydraulic exchanges between groundwater and surface waters are variable in space and time and play a relevant role for groundwater resource distribution. The Rieti Land Reclamation Authority was instituted in 1929 by Royal Decree N. 34171-3835, and integrates eight former authorities, dating the end of 1800s. It contributes to maintain the reclamation actions in the Rieti Plain, which started with the realization of the Salto and Turano artificial reservoirs, along two left tributaries of Velino River. The hydroelectric energy production purposes struggle with the reclamation and flood mitigation activities in the plain. The Land Reclamation Authority actuated the Integrated Reclamation General Project through the realization of pumping stations, connection and drainage canals, forestry-hydraulic works, rural roads, movable dams along Velino River and irrigation ditches. The irrigation activities, granted by the derivation of 5 m3/s from the Velino River, are carried out through 194,000 hectares within the territory of 42 municipalities of the Rieti Province. The Rieti Land Reclamation Authority contributes to the irrigation needs and to the environmental and hydrogeological protection and monitoring

The Coexistence of asthma and Chronic Ostructive Pulmonary Disease (COPD): prevalence and risk factors in young, middle-aged and elderly people from the general population

Background: The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors. Methods: A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20–44 (n = 5163) 45–64 (n = 2167) and 65–84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Results: A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged &lt;65 and 65–84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%–2.0%), 2.1% (1.5%–2.8%) and 4.5% (3.2%–5.9%) in the 20–44, 45–64 and 65–84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p&lt;0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions. Conclusion: Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.</br

Multiple facets in the control of acromegaly

Q2Q1Aims The current article provides a brief overview of the criteria for defining disease control in acromegaly. Methods This was a retrospective, narrative review of previously published evidence chosen at the author’s discretion along with an illustrative case study from Latin America. Findings and ConclusionsIn the strictest sense, “cure” in acromegaly is defined as complete restoration of normal pulsatile growth hormone secretion, although this is rarely achieved. Rather than “cure”, as such, it is more appropriate to refer to disease control and remission, which is defined mainly in terms of specific biochemical targets (for growth hormone and insulin-like growth factor-1) that predict or correlate with symptoms, comorbidities and mortality. However, optimal management of acromegaly goes beyond biochemical control to include control of tumour growth (which may be independent of biochemical control) and comprehensive management of the symptoms and comorbidities typically associated with the disease, as these may not be adequately managed with acromegaly-specific therapy alone.https://orcid.org/0000-0002-8433-5435N/

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech

Aphasia in one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute troke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening tes