The Metabolite Transporters of the Plastid Envelope: An Update

The engulfment of a photoautotrophic cyanobacterium by a primitive mitochondria-bearing eukaryote traces back to more than 1.2 billion years ago. This single endosymbiotic event not only provided the early petroalgae with the metabolic capacity to perform oxygenic photosynthesis, but also introduced a plethora of other metabolic routes ranging from fatty acids and amino acids biosynthesis, nitrogen and sulfur assimilation to secondary compounds synthesis. This implicated the integration and coordination of the newly acquired metabolic entity with the host metabolism. The interface between the host cytosol and the plastidic stroma became of crucial importance in sorting precursors and products between the plastid and other cellular compartments. The plastid envelope membranes fulfill different tasks: they perform important metabolic functions, as they are involved in the synthesis of carotenoids, chlorophylls, and galactolipids. In addition, since most genes of cyanobacterial origin have been transferred to the nucleus, plastidial proteins encoded by nuclear genes are post-translationally transported across the envelopes through the TIC–TOC import machinery. Most importantly, chloroplasts supply the photoautotrophic cell with photosynthates in form of reduced carbon. The innermost bilayer of the plastidic envelope represents the permeability barrier for the metabolites involved in the carbon cycle and is literally stuffed with transporter proteins facilitating their transfer. The intracellular metabolite transporters consist of polytopic proteins containing membrane spans usually in the number of four or more α-helices. Phylogenetic analyses revealed that connecting the plastid with the host metabolism was mainly a process driven by the host cell. In Arabidopsis, 58% of the metabolite transporters are of host origin, whereas only 12% are attributable to the cyanobacterial endosymbiont. This review focuses on the metabolite transporters of the inner envelope membrane of plastids, in particular the electrochemical potential-driven class of transporters. Recent advances in elucidating the plastidial complement of metabolite transporters are provided, with an update on phylogenetic relationship of selected proteins

Dati VIIRS-Nightfire per il monitoraggio del gas flaring in Amazzonia: il caso Yasun\ued

L\u2019estrazione di combustibili fossili \ue8 un\u2019attivit\ue0 che ha ormai raggiunto aree remote ad alta diversit\ue0 biologica e culturale, tra le quali desta gran preoccupazione l\u2019espansione della frontiera petrolifera in Amazzonia occidentale, specialmente nella Riserva della Biosfera Yasun\uec (YBR), uno dei luoghi pi\uf9 biodiversi del pianeta e casa ancestrale degli indigeni Waorani. In prossimit\ue0 di questa zona, gli impatti socio-ambientali diretti e indiretti delle varie fasi dell\u2019estrazione petrolifera sono ampiamente documentati. Tra queste attivit\ue0, la distribuzione spaziale e gli impatti ambientali del gas flaring non sono stati ancora investigati a fondo, anche a causa della mancanza di un sistema di monitoraggio e documentazione delle posizioni dei flare e dei volumi di gas bruciato. Negli ultimi anni si sta assistendo per\uf2 a un\u2019inversione di tendenza, grazie allo sviluppo di vari metodi di monitoraggio da remoto, attraverso l\u2019analisi multispettrale da satellite. Lo scopo di questo studio \ue8 mappare l\u2019attivit\ue0 di gas flaring nell\u2019area dello YBR, analizzando diacronicamente e valutando gli impatti potenziali sia sulla biodiversit\ue0 che sulle comunit\ue0 locali. I dati giornalieri prodotti dalla NOAA da gennaio 2017 a marzo 2018, basate sull\u2019elaborazione di immagini dal sensore \u201cVisible Infrared Imaging Radiometric Suite\u201d del satellite Suomi-SNPP per il monitoraggio delle attivit\ue0 di gas flaring, sono stati analizzati e geoprocessati con dati sulle aree protette e comunit\ue0 indigene. Per il corretto posizionamento dei flare, quando possibile, \ue8 stato fatto riferimento ai dataset annuali della NOAA, per i nuovi flare \ue8 stato usato il centroide delle rilevazioni. I risultati preliminari mostrano la presenza di un nuovo sito di flare nel campo petrolifero Tiputini vicino all\u2019 \u201cArea Nucleo\u201d della YBR; tre flare sono stati rilevati nella zona buffer e 19 nella zona di transizione della YBR. spaziale ha inoltre identificato 6 comunit\ue0 indigene in un raggio di 6 Km dai flare. Questo studio rivela l\u2019enorme potenziale degli open data come Nightfire della NOAA per il monitoraggio di aree remote ad elevata importanza per la conservazione della biodiversit\ue0 e dei territori indigeni

Development of a Semi-Field System for Contained Field Trials With Aedes Aegypti in Southern Mexico

Development of new genetic approaches to either interfere with the ability of mosquitoes to transmit dengue virus or to reduce vector population density requires progressive evaluation from the laboratory to contained field trials, before open field release. Trials in contained outdoor facilities are an important part of this process because they can be used to evaluate the effectiveness and reliability of modified strains in settings that include natural environmental variations without releasing mosquitoes into the open field. We describe a simple and cost-effective semi-field system designed to study Aedes aegypti carrying a dominant lethal gene (fsRIDL) in semi-field conditions. We provide a protocol for establishing, maintaining, and monitoring stable Ae. aegypti population densities inside field cages

Paratransgenesis to control malaria vectors: a semi-field pilot study

BACKGROUND: Malaria still remains a serious health burden in developing countries, causing more than 1 million deaths annually. Given the lack of an effective vaccine against its major etiological agent, Plasmodium falciparum, and the growing resistance of this parasite to the currently available drugs repertoire and of Anopheles mosquitoes to insecticides, the development of innovative control measures is an imperative to reduce malaria transmission. Paratransgenesis, the modification of symbiotic organisms to deliver anti-pathogen effector molecules, represents a novel strategy against Plasmodium development in mosquito vectors, showing the potential to reduce parasite development. However, the field application of laboratory-based evidence of paratransgenesis imposes the use of more realistic confined semi-field environments. METHODS: Large cages were used to evaluate the ability of bacteria of the genus Asaia expressing green fluorescent protein (Asaia (gfp)), to diffuse in Anopheles stephensi and Anopheles gambiae target mosquito populations. Asaia (gfp) was introduced in large cages through the release of paratransgenic males or by sugar feeding stations. Recombinant bacteria transmission was directly detected by fluorescent microscopy, and further assessed by molecular analysis. RESULTS: Here we show the first known trial in semi-field condition on paratransgenic anophelines. Modified bacteria were able to spread at high rate in different populations of An. stephensi and An. gambiae, dominant malaria vectors, exploring horizontal ways and successfully colonising mosquito midguts. Moreover, in An. gambiae, vertical and trans-stadial diffusion mechanisms were demonstrated. CONCLUSIONS: Our results demonstrate the considerable ability of modified Asaia to colonise different populations of malaria vectors, including pecies where its association is not primary, in large environments. The data support the potential to employ transgenic Asaia as a tool for malaria control, disclosing promising perspective for its field application with suitable effector molecules

Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib

Blood smear, a key diagnostic tool in hematology: Lessons from two cases of acute hemolysis in previously undiagnosed g6pd deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common worldwide distributed hereditary red cells enzymatic defect. The most common life-threatening clinical presentation of G6PD deficiency is acute hemolytic crisis triggered by exposition to oxidative agents such as fava beans, drugs, or infections. Management of acute hemolytic crisis in patients with no previous history of hereditary red cell disorders is particularly challenging for hematologists and emergency department (ED) physicians. We report two cases of acute hemolytic crisis in patients with previously unknown G6PD deficiency, where blood smear analysis played a key role in decision-making process. The trigger of acute hemolytic crisis was in both cases the recent intake of large amount of fava beans. Although Case 1 typically involved a male subject with unknown G6PD deficiency, Case 2 is of particular interest since the patient is a female with previously unknown G6PD deficiency. A recent study highlights the possible appearance of clinical signs for G6PD deficiency with aging in elder female population. Thus, hematologists should always take into account the possible lyonization effect on G6PD activity for G6PD deficiency inherited red cell disorder in the presence of unexplained acute hemolytic crisis in women with circulating hemi-ghosts

Mapping Aedes aegypti indoor resting behavior reveals a preference vulnerable to householder-led vector control

Many mosquito vectors rest inside human habitations, a behavioral trait that is exploited for vector control by indoor residual spraying (IRS) of interior walls with insecticide. Although IRS and its refined version targeted IRS are very effective against Aedes aegypti, they are expensive and logistically challenging to deliver in densely populated urban areas where outbreaks of dengue and other arboviruses are the greatest challenge. In experiments in Recife, Brazil, we set out to quantify the indoor resting behavior of Ae. aegypti at a level beyond that previously reported. We found that significantly more Ae. aegypti males, unfed and fed females visited the base of walls (height 0–20 cm, corresponding to 12.3% of the total wall surface) more frequently than upper wall areas, with the difference more pronounced at higher temperatures. When the lowest 20 cm of the walls was treated with an appropriate insecticide and colored black, we recorded up to 85% cumulative mortality after 24-h exposure in the experimental room. The findings are significant because feasibly, householders could treat this small and accessible target zone manually, without the need for visits by costly IRS teams or equipment, reducing insecticide use and enabling communities to actively protect their own indoor environment

High Incidence of Invasive Fungal Diseases in Patients with FLT3-Mutated AML Treated with Midostaurin: Results of a Multicenter Observational SEIFEM Study

The potential drug-drug interactions of midostaurin may impact the choice of antifungal (AF) prophylaxis in FLT3-positive acute myeloid leukemia (AML) patients. To evaluate the incidence of invasive fungal diseases (IFD) during the treatment of FLT3-mutated AML patients and to correlate it to the different AF prophylaxis strategies, we planned a multicenter observational study involving 15 SEIFEM centers. One hundred fourteen patients treated with chemotherapy + midostaurin as induction/reinduction, consolidation or both were enrolled. During induction, the incidence of probable/proven and possible IFD was 10.5% and 9.7%, respectively; no statistically significant difference was observed according to the different AF strategy adopted. The median duration of neutropenia was similar in patients with or without IFD. Proven/probable and possible IFD incidence was 2.4% and 1.8%, respectively, during consolidation. Age was the only risk factor for IFD (OR, 95% CI, 1.10 [1.03–1.19]) and complete remission achievement after first induction the only one for survival (OR, 95% CI, 5.12 [1.93–13.60]). The rate of midostaurin discontinuation was similar across different AF strategies. The IFD attributable mortality during induction was 8.3%. In conclusion, the 20.2% overall incidence of IFD occurring in FLT3-mutated AML during induction with chemotherapy + midostaurin, regardless of AF strategy type, was noteworthy, and merits further study, particularly in elderly patients