Transforming growth factor: beta signaling is essential for limb regeneration in axolotls

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-beta). In the present study, the full length sequence of the axolotl TGF-beta1 cDNA was isolated. The spatio-temporal expression pattern of TGF-beta1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-beta signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-beta type I receptor, SB-431542, we show that TGF-beta signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-beta signaling are down-regulated. These data directly implicate TGF-beta signaling in the initiation and control of the regeneration process in axolotls.     

Geographic distribution of the invasive cattle tick Rhipicephalus microplus, a country-wide survey in Benin

The cattle tick Rhipicephalus microplus is currently invading the West African region, and little information is available on the spread of this exotic tick in this region. We set out a country-wide field survey to determine its current distribution in Benin. Ticks were collected on cattle from 106 farms selected by random sampling covering all regions of the country. Rhipicephalus annulatus was found on 70?% of all farms, R. decoloratus on 42?%, R. geigyi on 58?%, and R. microplus on 49?%. There is a clear geographic separation between the indigenous Rhipicephalus species and R. microplus. Rhipicephalus annulatus occurs mainly in the northern departments, but it was also observed in lower numbers in locations in the south. The presence of R. decoloratus is limited to the northern region, and in most locations, this tick makes up a small proportion of the collected ticks. The tick R. geigyi tends to be dominant, but occurs only in the four northern departments. The observations concerning R. microplus are entirely different, this species occurs in the southern and central region. The results of this survey confirm the invasive character and displacement properties of R. microplus, since in less than a decade it has colonized more than half of the country and has displaced indigenous ticks of the same genus in many of the sampled locations.     

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β). In the present study, the full length sequence of the axolotl TGF-β1 cDNA was isolated. The spatio-temporal expression pattern of TGF-β1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-β type I receptor, SB-431542, we show that TGF-β signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-β signaling are down-regulated. These data directly implicate TGF-β signaling in the initiation and control of the regeneration process in axolotls.     

New foci of <Emphasis Type="Italic">Rhipicephalus microplus</Emphasis> in West Africa

The invasive character of Rhipicephalus microplus was observed in Benin, the second West-African country from which this ticks species has been collected after the initial confirmed record in Ivory Coast in 2007. A cross-sectional study was carried out in the Department of Mono to examine the presence of the tick R. microplus. The survey covered 9 herds (villages) in an agro-ecological zone inhabited by agro-pastoralists, including the State Farm of Kpinnou that imported Girolando cattle from Brazil. Almost 800 ticks were sampled from 36 cattle, on average four cattle per village. The morphological identification revealed ticks of two different genera: Rhipicephalus and Amblyomma. Rhipicephalus microplus was the only representative of the species previously known as Boophilus or blue ticks. Its taxonomic identity was confirmed molecularly by PCR–RFLP. A comparison was made with the situation of R. microplus in Brazil.     

Monitoring HIV Drug Resistance Early Warning Indicators in Cameroon: A Study Following the Revised World Health Organization Recommendations

Background

The majority (>95%) of new HIV infection occurs in resource-limited settings, and Cameroon is still experiencing a generalized epidemic with ~122,638 patients receiving antiretroviral therapy (ART). A detrimental outcome in scaling-up ART is the emergence HIV drug resistance (HIVDR), suggesting the need for pragmatic approaches in sustaining a successful ART performance.

Methods

A survey was conducted in 15 ART sites of the Centre and Littoral regions of Cameroon in 2013 (10 urban versus 05 rural settings; 8 at tertiary/secondary versus 7 at primary healthcare levels), evaluating HIVDR-early warning indicators (EWIs) as-per the 2012 revised World Health Organization’s guidelines: EWI₁ (on-time pill pick-up), EWI₂ (retention in care), EWI₃ (no pharmacy stock-outs), EWI₄ (dispensing practices), EWI₅ (virological suppression). Poor performance was interpreted as potential HIVDR.

Results

Only 33.3% (4/12) of sites reached the desirable performance for “on-time pill pick-up” (57.1% urban versus 0% rural; p<0.0001) besides 25% (3/12) with fair performance. 69.2% (9/13) reached the desirable performance for “retention in care” (77.8% urban versus 50% rural; p=0.01) beside 7.7% (1/13) with fair performance. Only 14.4% (2/13) reached the desirable performance of “no pharmacy stock-outs” (11.1% urban versus 25% rural; p=0.02). All 15 sites reached the desirable performance of 0% “dispensing mono- or dual-therapy”. Data were unavailable to evaluate “virological suppression” due to limited access to viral load testing (min-max: <1%-15%). Potential HIVDR was higher in rural (57.9%) compared to urban (27.8%) settings, p=0.02; and at primary (57.9%) compared to secondary/tertiary (33.3%) healthcare levels, p=0.09.

Conclusions

Delayed pill pick-up and pharmacy stock-outs are major factors favoring HIVDR emergence, with higher risks in rural settings and at primary healthcare. Retention in care appears acceptable in general while ART dispensing practices are standard. There is need to support patient-adherence to pharmacy appointments while reinforcing the national drug supply system.     

Combined effects of Gm or Km immunoglobulin allotypes and age on antibody responses to Plasmodium falciparum VarO rosetting variant in Benin

Clinical protection of Beninese children against Plasmodium falciparum malaria was shown to be influenced by immunoglobulin (IG) Gm and Km allotypes, and related to seroreactivity with the rosette-forming VarO-antigenic variant. IgG to the VarO-infected erythrocyte surface, IgG1 and IgG3 to PfEMP1-NTS-DBL1α(1)-VarO were higher in the under 4-year-old children carrying the Gm 5,6,13,14;1,17 phenotype. In contrast, surface-reactive IgG, total IgG, IgG1 and IgG3 to NTS-DBL1α(1)- and DBL2βC2-VarO domains were lower in the above 4-year-old children harbouring the Km1 allotype. These data outline an age-related association of antibodies against malaria antigens and IG allotype distribution.