Cutaneous melanoma with metastasis in a cynomolgus monkey (Macaca fascicularis)

Background  A 3.3-year-old-male cynomolgus macaque ( Macaca fascicularis ) showed a focally extensive soft, dark, discoid dermal mass, 0.5 cm in diameter, on the dorsal surface of the right hind foot, over the fourth and fifth metatarsal bones.
Methods and results  Microscopic examination revealed a cutaneous melanoma with local lymphatic invasion, characterized by neoplastic melanocytes within the subcapsular sinus of popliteal and inguinal lymph nodes. The diagnosis was confirmed by immunohistochemistry and transmission electron microscopy.
Conclusions  To our knowledge, this is the first documented case of melanoma in a cynomolgus monkey.     

An Attempt to Localize the Vaccinating Power of Klebsiella pneumoniae Ribosomal Preparations Using Saccharose-Gradient Ultracentrifugation

The study of the vaccinating power of ribosomal vaccines against Klebsiella pneumoniae led us to define the chemical nature which supports this protective activity. We tried to separate this support and the ribosomes by sucrose gradient ultracentrifugation. We isolated high protective membrane vesicles by this technique applied to salt-washed ribosomal preparations. When the ribosomal preparations were exposed to SDS, the protective activity was conserved all along the gradient, with no correlation with the ribosome concentration. The addition of bovine serum albumin to the ribosomal preparation focused the protective activity on the ribosomal peak. No correlation was observed between the response to capsular polysaccharide and the vaccinating power of the fractions.     

Should Malaria Treatment Be Guided by a Point of Care Rapid Test? A Threshold Approach to Malaria Management in Rural Burkina Faso

Background

In Burkina Faso, rapid diagnostic tests for malaria have been made recently available. Previously, malaria was managed clinically. This study aims at assessing which is the best management option of a febrile patient in a hyperendemic setting. Three alternatives are: treating presumptively, testing, or refraining from both test and treatment. The test threshold is the tradeoff between refraining and testing, the test-treatment threshold is the tradeoff between testing and treating. Only if the disease probability lies between the two should the test be used.

Methods and Findings

Data for this analysis was obtained from previous studies on malaria rapid tests, involving 5220 patients. The thresholds were calculated, based on disease risk, treatment risk and cost, test accuracy and cost. The thresholds were then matched against the disease probability. For a febrile child under 5 in the dry season, the pre-test probability of clinical malaria (3.2%), was just above the test/treatment threshold. In the rainy season, that probability was 63%, largely above the test/treatment threshold. For febrile children >5 years and adults in the dry season, the probability was 1.7%, below the test threshold, while in the rainy season it was higher (25.1%), and situated between the two thresholds (3% and 60.9%), only if costs were not considered. If they were, neither testing nor treating with artemisinin combination treatments (ACT) would be recommended.

Conclusions

A febrile child under 5 should be treated presumptively. In the dry season, the probability of clinical malaria in adults is so low, that neither testing nor treating with any regimen should be recommended. In the rainy season, if costs are considered, a febrile adult should not be tested, nor treated with ACT, but a possible alternative would be a presumptive treatment with amodiaquine plus sulfadoxine-pyrimethamine. If costs were not considered, testing would be recommended.     

In Vivo Characterization of Dynein-Driven nanovectors Using Drosophila Oocytes

Molecular motors transport various cargoes including vesicles, proteins and mRNAs, to distinct intracellular compartments. A significant challenge in the field of nanotechnology is to improve drug nuclear delivery by engineering nanocarriers transported by cytoskeletal motors. However, suitable in vivo models to assay transport and delivery efficiency remain very limited. Here, we develop a fast and genetically tractable assay to test the efficiency and dynamics of fluospheres (FS) using microinjection into Drosophila oocytes coupled with time-lapse microscopy. We designed dynein motor driven FS using a collection of dynein light chain 8 (LC8) peptide binding motifs as molecular linkers and characterized in real time the efficiency of the FS movement according to its linker’s sequence. Results show that the conserved LC8 binding motif allows fast perinuclear nanoparticle''s accumulation in a microtubule and dynein dependent mechanism. These data reveal the Drosophila oocyte as a new valuable tool for the design of motor driven nanovectors.     

Potential of dendrochronology to assess annual rates of biomass productivity in savanna trees of West Africa

We examined the potential of dendrochronology to assess biomass productivity of individual savanna species from a semi-arid ecosystem in southern Senegal. The 9 tree species examined in this dendrochronologial study included: Acacia macrostachya, Acacia seyal, Balanites aegyptiaca, Combretum glutinosum, Cordyla pinnata, Pterocarpus erinaceus, Terminalia macroptera, Daniellia oliveri, and Combretum nigricans. Dendrochronologial analyses were applied on cross-sectional disks obtained from the tree stem to reconstruct past tree growth (diameter and biomass) histories. Despite challenges with discerning annual tree rings in these savanna species (associated with ring suppression, wedging, indistinct ring boundaries, and fires), tree species (A. macrostachya, A. seyal, and T. macroptera) with the highest dendrochronology potential produced a clear thin band of marginal parenchyma. A. macrostachya had rapid annual diameter and biomass growth increments in the juvenile years (ages 1–10), compared to T. macroptera which showed greater growth past this early juvenile period. Given the same species, generally wetter forests had lower annual and cumulative growth rates that were likely due to increased inter-tree and tree-grass competition for soil moisture in the wetter forests. We concluded that dendrochronology is well suited for retrospective annual biomass assessment in savanna trees of Senegal, West Africa.     

Poor Survival in Rheumatoid Arthritis Associated with Bronchiectasis: A Family-Based Cohort Study

Background

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.

Methods

We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.

Results

During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5–48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1–81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1–113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4–37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10⁻⁵).

Conclusion

DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.     

‘Ménage à trois’: a selfish genetic element uses a virus to propagate within Thermotogales

Prokaryotic viruses play a major role in the microbial ecology and evolution. However, the virosphere associated with deep‐sea hydrothermal ecosystems remains largely unexplored. Numerous instances of lateral gene transfer have contributed to the complex and incongruent evolutionary history of Thermotogales, an order well represented in deep‐sea hydrothermal vents. The presence of clustered regularly interspaced short palindromic repeats (CRISPR) loci has been reported in all Thermotogales genomes, suggesting that these bacteria have been exposed to viral infections that could have mediated gene exchange. In this study, we isolated and characterized the first virus infecting bacteria from the order Thermotogales, Marinitoga piezophila virus 1 (MPV1). The host, Marinitoga piezophila is a thermophilic, anaerobic and piezophilic bacterium isolated from a deep‐sea hydrothermal chimney. MPV1 is a temperate Siphoviridae‐like virus with a 43.7 kb genome. Surprisingly, we found that MPV1 virions carry not only the viral DNA but preferentially package a plasmid of 13.3 kb (pMP1) also carried by M. piezophila. This ‘ménage à trois’ highlights potential relevance of selfish genetic elements in facilitating lateral gene transfer in the deep‐sea biosphere.     

TpUB05, a Homologue of the Immunodominant Plasmodium falciparum Protein UB05, Is a Marker of Protective Immune Responses in Cattle Experimentally Vaccinated against East Coast Fever

Introduction

East Coast fever, a devastating disease of cattle, can be controlled partially by vaccination with live T. parva sporozoites. The antigens responsible for conferring immunity are not fully characterized. Recently it was shown that the P. falciparum immunodominant protein UB05 is highly conserved in T. parva, the causative agent of East Coast fever. The aim of the present investigation was to determine the role of the homologue TpUB05 in protective immunity to East Coast fever.

Methods

The cloning, sequencing and expression of TpUB05 were done according to standard protocols. Bioinformatics analysis of TpUB05 gene was carried out using algorithms found in the public domain. Polyclonal antiserum against recombinant TpUB05 were raised in rabbits and used for further analysis by Western blotting, ELISA, immunolocalization and in vitro infection neutralization assay. The ability of recombinant TpUB05 (r-TpUB05) to stimulate bovine PBMCs ex-vivo to produce IFN-γ or to proliferate was tested using ELISpot and [3H]-thymidine incorporation assays, respectively.

Results

All the 20 cattle immunised by the infection and treatment method (ITM) developed significantly higher levels of TpUB05 specific antibodies (p<0.0001) compared to the non-vaccinated ones. Similarly, r-TpUB05 highly stimulated bovine PMBCs from 8/12 (67%) of ITM-immunized cattle tested to produce IFN-γ and proliferate (p< 0.029) as compared to the 04 naїve cattle included as controls. Polyclonal TpUB05 antiserum raised against r-TpUB05 also marginally inhibited infection (p < 0.046) of bovine PBMCs by T. parva sporozoites. In further experiments RT-PCR showed that the TpUB05 gene is expressed by the parasite. This was confirmed by immunolocalization studies which revealed TpUB05 expression by schizonts and piroplasms. Bioinformatics analysis also revealed that this antigen possesses two transmembrane domains, a N-glycosylation site and several O-glycosylation sites.

Conclusion

It was concluded that TpUB05 is a potential marker of protective immunity in ECF worth investigating further.